
1: Mil Med. 2008 Oct;173(10):1044-7.

A 31-year-old Army specialist presenting with acute oligoarthritis.

Keith MP, Roebuck JD.

Department of Rheumatology, National Naval Medical Center, Bethesda, MD 20889,
USA.

A 31-year-old Army specialist was evaluated at Walter Reed Army Medical Center
for an acute attack of arthritis in the left hand. After an initial evaluation,
the patient was referred to the rheumatology service, and gout was diagnosed on
the basis of synovial fluid analysis. This case demonstrates an uncommon
presentation of a common disorder in an active duty soldier. The discussions
presented following the clinical data are meant to expand diagnostic
considerations for patients with similar symptoms, to address risk factors for
gout relevant to the military, and to clarify the management of gout.

Publication Types: 
    Case Reports

PMID: 19160628 [PubMed - indexed for MEDLINE]

2: Cell Cycle. 2009 Jan 1;8(1):27-30. Epub 2009 Jan 31.

NALP3 inflammasome functional polymorphisms and gout susceptibility.

Miao ZM, Zhao SH, Yan SL, Li CG, Wang YG, Meng DM, Zhou L, Mi QS.

Department of Medicine, the Affiliated Hospital of Qingdao Medical College,
Qingdao University, Qingdao, P.R. China. miaozm@qdumh.qd.sd.cn

Gout is the most common autoinflammatory arthritis characterized by elevated
serum urate and recurrent attacks of intra-articular crystal deposition of
monosodium urate (MSU). Although the pathogenesis of gout is still unclear,
accumulated studies indicate that genetic factors trigger gout development,
including some susceptibility genes that control the production and clearance of 
urate and lead to hyperuricemia. However, the epidemiological evidence suggests
that only less than 10% of hyperuricemia patients develop gout, indicating that
other genes unrelated to the urate metabolism may also contribute to the diseases
susceptibility. Accumulated evidences have implied that MSU crystal-induced
inflammation is a paradigm of innate immunity and that NALP3 inflammasome, an
innate immune complex containing NALP3, ASC and CARD-8, is involved in gout
development. Recent studies suggest that NALP3 and CARD-8 functional mutations
contribute to the development of autoinflammatory diseases including hereditary
periodic fever syndrome, arthritis as well as hypertension susceptibility. Taking
into account these genetic findings, here we would like to propose a novel
hypothesis that functional mutations in NALP3 inflammasome may make NALP3
inflammasome as attractive susceptibility candidates and genetic markers for
gout. Further clinical genetic studies need to be performed to confirm the role
of NALP3 inflammasome in the etiology of gout.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 19106604 [PubMed - indexed for MEDLINE]

3: N Z Med J. 2008 Nov 7;121(1285):73-81.

Cardiovascular disease risk factor assessment and management in gout: an analysis
using guideline-based electronic clinical decision support.

Colvine K, Kerr AJ, McLachlan A, Gow P, Kumar S, Ly J, Wiltshire C, Robinson E,
Dalbeth N.

Department of Medicine, North Shore Hospital, Shakespeare Road, Private Bag
93-503, Takapuna, Auckland, New Zealand. keith.colvine@waitematadhb.govt.nz

AIM: To assess the need for cardiovascular disease (CVD) risk management in
patients with gout. METHODS: We studied 100 consecutive patients referred to the 
rheumatology service for management of gout. CVD risk factor and management data 
were collected. PREDICT CVD decision support software was used to calculate
Framingham 5-year CVD risk, and to analyse therapeutic targets. RESULTS:
Fifty-nine (59%) patients had a high (>15%) or very high (> or = 20%) 5-year CVD 
risk. For those at high risk of CVD, target systolic blood pressure was achieved 
in 34%; target LDL-cholesterol in 49%, target HDL-cholesterol in 56%; and 81% did
not smoke. For patients with diabetes, target HbA1c was reached in 40%. For
high-risk individuals only 50% of eligible patients were on aspirin, 64% on
beta-blockers, 53% statins, and 65% ACE inhibitors. There were no significant
differences in duration of gout, presence of tophaceous disease, use of
urate-lowering therapy or C-reactive protein between patients at high risk of
CVD, and those with lower risk. CONCLUSIONS: Patients with gout referred to
secondary care are at high risk for CVD, and have a large burden of modifiable
risk factors. Implementation of CVD screening and management programs in these
patients should have high therapeutic yield.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 19079439 [PubMed - indexed for MEDLINE]

4: Transplantation. 2008 Dec 15;86(11):1543-7.

Gout in renal allograft recipients according to the pretransplant hyperuricemic
status.

Hernández-Molina G, Cachafeiro-Vilar A, Villa AR, Alberú J, Rull-Gabayet M.

Immunology and Rheumatology Department, Instituto Nacional de Ciencias Médicas y 
Nutrición Salvador Zubirán, Mexico City, Mexico.

BACKGROUND: Studies to date regarding hyperuricemia and gout in the postrenal
transplant (RT) setting do not distinguish neither if patients with gout after
the allograft had or did not have hyperuricemia before been transplanted nor if
data concerning to hyperuricemia correspond to prevalent or incident cases. Among
RT patients, we assessed (1) the incidence of gout in recipients with and without
hyperuricemia pre-RT and (2) the incidence of hyperuricemia during the follow-up.
METHODS: We selected from our RT registry (1989-2003) 236 subjects who were
transplanted in our institution, with at least 1 year follow-up, without gout
pre-RT, with at least one measurement of serum uric acid pre-RT and two post-RT. 
Immunosuppressants, demographic, and clinical features were registered. Survival 
curves for hyperuricemia and gout were derived using the Kaplan-Meier method and 
were statistically tested by log rank test. RESULTS: The median follow-up was 4.8
years (1.0-14.9), 43% were women, with a mean body mass index of 22.7+/-3.7 kg/m2
and a mean age at the moment of transplant of 32.4+/-11 years. The incidence of
hyperuricemia was 315.2 x 1000 patient-years. Hyperuricemia was diagnosed in half
of the subjects during the first year of follow-up. The incidence of gout was
19.7 x 1000 and 2.67 x 1000 patient-years in the groups with and without
hyperuricemia pretransplant, respectively (Log rank 9.44, P<0.002). The group
with hyperuricemia pre-RT also had earlier and more aggressive gout. CONCLUSIONS:
Hyperuricemia was a common complication among RT recipients. However, gout
incidence varied according to the pretransplant hyperuricemic status.

PMID: 19077887 [PubMed - indexed for MEDLINE]

5: Clin Exp Rheumatol. 2008 Sep-Oct;26(5 Suppl 51):S115-9.

Gout and mortality.

Kim SY, De Vera MA, Choi HK.

Division of Rheumatology, Department of Medicine, University of Pennsylvania, PA,
USA.

This review provides an update on the most recent data on mortality in people
with gout. A large prospective study among men found that those with gout have a 
higher risk of death from all causes. Among men who did not have pre-existing
coronary heart disease, the increased mortality risk is due primarily to an
elevated risk of cardiovascular death, particularly from coronary heart disease. 
Also, an extension study of a large clinical trial among men with above-average
risk for coronary heart disease found that a diagnosis of gout accompanied by an 
elevated uric acid level is associated with increased long-term (approximately 17
years) risk of all-cause mortality that arises largely from an increased risk of 
cardiovascular disease (CVD) mortality. Although limited, these emerging data
suggest that men with gout have a higher risk of death from all causes and the
increased mortality risk is primarily due to an elevated risk of CVD death. These
findings would provide support for the aggressive management of cardiovascular
risk factors in men with gout. More data that adjust comprehensively for various 
associated CVD markers are needed to reinforce this concept. Furthermore, given
apparent potential sex differences in gout epidemiology and its risk factors,
prospective studies specifically among women would be valuable.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 19026153 [PubMed - indexed for MEDLINE]

6: Nat Clin Pract Rheumatol. 2008 Dec;4(12):675-9. Epub 2008 Nov 11.

Painful knee locking caused by gouty tophi successfully treated with allopurinol.

Chatterjee S, Ilaslan H.

Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, OH
44195, USA. chattes@ccf.org

BACKGROUND: A 67-year-old man presented to a rheumatology clinic with a 1-week
history of severe pain and swelling of his right knee. He had been receiving
allopurinol for about 5 months for the treatment of chronic gouty arthropathy of 
more than 30 years' duration. On examination, his right knee was warm and
swollen. The aspirated fluid contained intracellular and extracellular monosodium
urate crystals, but Gram staining and culture were negative. The affected knee
was injected with triamcinolone, but the patient continued to experience severe
pain and complained of locking of the knee 3 weeks after the onset of his initial
symptoms. Physical examination at this time showed no sign of inflammation, but
the knee had a very limited range of motion. INVESTIGATIONS: Physical
examination; routine laboratory investigations, including CBC, complete metabolic
panel, measurement of serum uric acid levels, and synovial fluid analysis;
radiological investigations, including radiography of the right knee and CT of
the right knee with intra-articular contrast. DIAGNOSIS: CT showed no internal
derangement, but revealed extensive intra-articular and extra-articular amorphous
soft tissue calcifications, compatible with gouty tophi. MANAGEMENT: The patient 
declined an arthroscopic procedure to remove the gouty tophi. Treatment consisted
of continuous allopurinol therapy and narcotics for symptomatic pain relief. Over
the next 12 months, the patient's serum uric acid levels, and presumably his
total-body urate pool, were substantially reduced. The knee unlocked and the pain
subsided. Follow-up CT about 3 years after the initial examination showed
complete resolution of the calcified intra-articular and extra-articular tophi.

Publication Types: 
    Case Reports

PMID: 19002128 [PubMed - indexed for MEDLINE]

7: Arthritis Rheum. 2008 Nov 15;59(11):1540-8.

Comment in:
    Arthritis Rheum. 2008 Nov 15;59(11):1535-7.

Effects of febuxostat versus allopurinol and placebo in reducing serum urate in
subjects with hyperuricemia and gout: a 28-week, phase III, randomized,
double-blind, parallel-group trial.

Schumacher HR Jr, Becker MA, Wortmann RL, Macdonald PA, Hunt B, Streit J,
Lademacher C, Joseph-Ridge N.

University of Pennsylvania and VA Medical Center, Philadelphia, PA 19104, USA.
schumacr@mail.med.upenn.edu

OBJECTIVE: To compare the urate-lowering efficacy and safety of febuxostat,
allopurinol, and placebo in a large group of subjects with hyperuricemia and
gout, including persons with impaired renal function. METHODS: Subjects (n =
1,072) with hyperuricemia (serum urate level > or = 8.0 mg/dl) and gout with
normal or impaired (serum creatinine level >1.5 to < or = 2.0 mg/dl) renal
function were randomized to receive once-daily febuxostat (80 mg, 120 mg, or 240 
mg), allopurinol (300 or 100 mg, based on renal function), or placebo for 28
weeks. RESULTS: Significantly (P < or = 0.05) higher percentages of subjects
treated with febuxostat 80 mg (48%), 120 mg (65%), and 240 mg (69%) attained the 
primary end point of last 3 monthly serum urate levels <6.0 mg/dl compared with
allopurinol (22%) and placebo (0%). A significantly (P < 0.05) higher percentage 
of subjects with impaired renal function treated with febuxostat 80 mg (4 [44%]
of 9), 120 mg (5 [45%] of 11), and 240 mg (3 [60%] of 5) achieved the primary end
point compared with those treated with 100 mg of allopurinol (0 [0%] of 10).
Proportions of subjects experiencing any adverse event or serious adverse event
were similar across groups, although diarrhea and dizziness were more frequent in
the febuxostat 240 mg group. The primary reasons for withdrawal were similar
across groups except for gout flares, which were more frequent with febuxostat
than with allopurinol. CONCLUSION: At all doses studied, febuxostat more
effectively lowered and maintained serum urate levels <6.0 mg/dl than did
allopurinol (300 or 100 mg) or placebo in subjects with hyperuricemia and gout,
including those with mild to moderately impaired renal function.

Publication Types: 
    Clinical Trial, Phase III
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18975369 [PubMed - indexed for MEDLINE]

8: Arthritis Rheum. 2008 Nov 15;59(11):1549-54.

Gout and the risk of Parkinson's disease: a cohort study.

De Vera M, Rahman MM, Rankin J, Kopec J, Gao X, Choi H.

Arthritis Research Centre of Canada and University of British Columbia,
Vancouver, British Columbia, Canada.

OBJECTIVE: Several studies have suggested that higher serum uric acid levels lead
to a lower risk of Parkinson's disease (PD) because uric acid exerts antioxidant 
effects on neurons. Our objective was to examine the relationship between gout
and the risk of PD in persons age > or = 65 years. METHODS: We conducted a
population-based cohort study using the British Columbia Linked Health Database
and PharmaCare data (i.e., prescription drug data for those age > or = 65 years).
We compared incidence rates of PD between 11,258 gout patients and 56,199
controls matched on age, sex, date of gout diagnosis, and length of medical
record. Cox proportional hazards models were used to estimate the relative risk
(RR) of PD, adjusting for age, sex, prior comorbid conditions, and use of
diuretics and nonsteroidal antiinflammatory drugs. RESULTS: Over an 8-year median
followup, we identified 1,182 new cases of PD. Compared with individuals without 
gout, the multivariate RR of PD among those with gout was 0.70 (95% confidence
interval [95% CI] 0.59-0.83). In subgroup analyses, the inverse association was
similarly present in both sexes and was evident among those who did not use
diuretics (RR 0.66, 95% CI 0.54-0.81), but not among diuretic users (RR 0.80, 95%
CI 0.58-1.10, P for interaction 0.35). CONCLUSION: Our population-based data
provide evidence for a protective effect of gout on the risk of PD and support
the purported protective role of uric acid.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18975349 [PubMed - indexed for MEDLINE]

9: Arthritis Res Ther. 2008;10(5):221. Epub 2008 Oct 10.

Developments in the scientific and clinical understanding of gout.

So A.

Service de Rhumatologie, Departement de Médecine, CHU Vaudois, University of
Lausanne, Ave Pierre Decker, 1011 Lausanne, Switzerland.
alexanderkai-lik.so@chuv.ch

Gout is the most common form of inflammatory arthritis in the elderly. In the
last two decades, both hyperuricemia and gout have increased markedly and similar
trends in the epidemiology of the metabolic syndrome have been observed. Recent
studies provide new insights into the transporters that handle uric acid in the
kidney as well as possible links between these transporters, hyperuricemia, and
hypertension. The treatment of established hyperuricemia has also seen new
developments. Febuxostat and PEG-uricase are two novel treatments that have been 
evaluated and shown to be highly effective in the management of hyperuricemia,
thus enlarging the therapeutic options available to lower uric acid levels.
Monosodium urate (MSU) crystals are potent inducers of inflammation. Within the
joint, they trigger a local inflammatory reaction, neutrophil recruitment, and
the production of pro-inflammatory cytokines as well as other inflammatory
mediators. Experimentally, the uptake of MSU crystals by monocytes involves
interactions with components of the innate immune system, namely Toll-like
receptor (TLR)-2, TLR-4, and CD14. Intracellularly, MSU crystals activate
multiple processes that lead to the formation of the NALP-3 (NACHT, LRR, and
pyrin domain-containing-3) inflammasome complex that in turn processes
pro-interleukin (IL)-1 to yield mature IL-1 beta, which is then secreted. The
inflammatory effects of MSU are IL-1-dependent and can be blocked by IL-1
inhibitors. These advances in the understanding of hyperuricemia and gout provide
new therapeutic targets for the future.

Publication Types: 
    Review

PMID: 18947374 [PubMed - indexed for MEDLINE]

10: Bull NYU Hosp Jt Dis. 2008;66(3):231-9.

Update on the management of hyperuricemia and gout.

Pillinger MH, Keenan RT.

New York Universuty School of Medicine, New York, NY, USA.
michael.pillinger@med.nyu.edu

Gout is the most common inflammatory arthritis in the United States, with more
than three million sufferers. Management of gout has changed relatively little in
the past 50 years, despite the fact that many gout patients have
contraindications to one or more currently available gout therapies. However,
recent insights into gout pathophysiology suggest that time is ripe for a change.
This article reviews recent updates in the management of gout, including new
insights into dietary management that may permit better control of
hyuperuricemia. Also reviewed are the biological and clinical data behind
newly-developed drugs for gout that are likely to receive serious consideration
for FDA approval, and clinical use, in the foreseeable future.

Publication Types: 
    Review

PMID: 18937638 [PubMed - indexed for MEDLINE]

11: J Clin Rheumatol. 2008 Oct;14(5 Suppl):S47-54.

Gout: what primary care physicians want to know.

Dore RK.

Division of Rheumatology, David Geffen School of Medicine, University of
California at Los Angeles, Los Angeles, CA 90095-1720, USA. rkdmail@sbcglobal.net

Gout is an inflammatory arthritis that has been recognized since ancient times.
It is the most common type of inflammatory arthritis in men. Despite these facts,
no new advances have been made in the diagnosis and treatment of gout for over 50
years. Since there have been no new advances and the condition has been
recognized for so many centuries, the diagnosis and treatment of gout has not
elicited interest in learning more about the disease. Thus, managing gout is a
challenge for the clinician caring for the gout patient. Rheumatologists should
be the educators of primary care physicians (PCPs) about the diagnosis and
optimal treatment of gout. A recent educational meeting was held, the
Hyperuricemia and Gout Summit, in which a panel of leading rheumatologists
educated PCPs about gout management through didactic presentations and breakout
sessions focused on case studies. At this meeting, the PCPs discussed some of
their key challenges in managing gout in their practice. This article reviews
current recommendations for the diagnosis and treatment of gout, using
educational examples from the Hyperuricemia and Gout Summit. It also highlights
the importance of providing practical recommendations to PCPs to improve the
standard of care for gout in the primary care setting.

Publication Types: 
    Review

PMID: 18830091 [PubMed - indexed for MEDLINE]

12: N Z Med J. 2008 Oct 3;121(1283):43-50.

High prevalence of gout in patients with Type 2 diabetes: male sex, renal
impairment, and diuretic use are major risk factors.

Suppiah R, Dissanayake A, Dalbeth N.

Department of Rheumatology, Middlemore Hospital, Counties Manukau District Health
Board, Private Bag 93311, Otahuhu, Auckland, New Zealand.
RSuppiah@middlemore.co.nz

AIMS: Gout and hyperuricaemia are recognised features of the metabolic syndrome. 
The objective of this study was to determine the prevalence of gout in patients
with diabetes. METHODS: We studied 292 consecutive outpatients attending diabetes
clinics between August and September 2005. A self-reported history of gout was
obtained, and was confirmed by clinical chart review. Information regarding
associated comorbidities was also recorded. Current treatments were compared with
published EULAR guidelines for the management of gout. RESULTS: Gout was
confirmed in 0/27 (0%) patients with Type 1 diabetes and 59/265 (22%) of patients
with Type 2 diabetes (p<0.01). Prevalence rates varied depending on age and sex, 
and were highest (41%) in men with type 2 diabetes over the age of 65 years.
Multivariate analysis showed that the following variables were independent
predictors for gout in patients with Type 2 diabetes: male sex (adjusted OR 4.4, 
95%CI 2.1-9.6), impaired renal function (adjusted OR 1.2 for every 10 ml/min
reduction in GFR, 95%CI 1.1-1.4), diuretic use (adjusted OR 3.2, 95%CI 1.6-6.6), 
and high triglycerides (adjusted OR 2.2, 95%CI 1.0-4.7) Only 28/59 (47%) of
patients with gout were on urate-lowering therapy. A further 24/59 (41%) met
recommended criteria for urate-lowering therapy but were not receiving this
medication. CONCLUSION: This study has demonstrated a high prevalence of gout in 
patients with Type 2 diabetes. Improved recognition of those at high risk of gout
is needed to ensure optimal management of these patients.

PMID: 18841184 [PubMed - indexed for MEDLINE]

13: Bioorg Med Chem. 2008 Nov 1;16(21):9432-42. Epub 2008 Sep 20.

Synthesis and anti-inflammatory structure-activity relationships of
thiazine-quinoline-quinones: inhibitors of the neutrophil respiratory burst in a 
model of acute gouty arthritis.

Chia EW, Pearce AN, Berridge MV, Larsen L, Perry NB, Sansom CE, Godfrey CA,
Hanton LR, Lu GL, Walton M, Denny WA, Webb VL, Copp BR, Harper JL.

Malaghan Institute of Medical Research, PO Box 7060, Wellington South, New
Zealand.

Sixteen new thiazine-quinoline-quinones have been synthesised, plus one bicyclic 
analogue. These compounds inhibited neutrophil superoxide production in vitro
with IC(50)s as low 60 nM. Compounds with high in vitro anti-inflammatory
activity were also tested in a mouse model of acute inflammation. The most active
compounds inhibited both neutrophil infiltration and superoxide production at
doses 2.5 micromol/kg, highlighting their potential for development as novel
NSAIDs.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18835721 [PubMed - indexed for MEDLINE]

14: Lancet. 2008 Dec 6;372(9654):1953-61. Epub 2008 Oct 1.

Comment in:
    Lancet. 2008 Dec 6;372(9654):1929-30.

Association of three genetic loci with uric acid concentration and risk of gout: 
a genome-wide association study.

Dehghan A, Köttgen A, Yang Q, Hwang SJ, Kao WL, Rivadeneira F, Boerwinkle E, Levy
D, Hofman A, Astor BC, Benjamin EJ, van Duijn CM, Witteman JC, Coresh J, Fox CS.

Department of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands.

BACKGROUND: Hyperuricaemia, a highly heritable trait, is a key risk factor for
gout. We aimed to identify novel genes associated with serum uric acid
concentration and gout. METHODS: Genome-wide association studies were done for
serum uric acid in 7699 participants in the Framingham cohort and in 4148
participants in the Rotterdam cohort. Genome-wide significant single nucleotide
polymorphisms (SNPs) were replicated in white (n=11 024) and black (n=3843)
individuals who took part in the study of Atherosclerosis Risk in Communities
(ARIC). The SNPs that reached genome-wide significant association with uric acid 
in either the Framingham cohort (p<5.0 x 10(-8)) or the Rotterdam cohort (p<1.0 x
10(-7)) were evaluated with gout. The results obtained in white participants were
combined using meta-analysis. FINDINGS: Three loci in the Framingham cohort and
two in the Rotterdam cohort showed genome-wide association with uric acid. Top
SNPs in each locus were: missense rs16890979 in SLC2A9 (p=7.0 x 10(-168) and 2.9 
x 10(-18) for white and black participants, respectively); missense rs2231142 in 
ABCG2 (p=2.5 x 10(-60) and 9.8 x 10(-4)), and rs1165205 in SLC17A3 (p=3.3 x
10(-26) and 0.33). All SNPs were direction-consistent with gout in white
participants: rs16890979 (OR 0.59 per T allele, 95% CI 0.52-0.68, p=7.0 x
10(-14)), rs2231142 (1.74, 1.51-1.99, p=3.3 x 10(-15)), and rs1165205 (0.85,
0.77-0.94, p=0.002). In black participants of the ARIC study, rs2231142 was
direction-consistent with gout (1.71, 1.06-2.77, p=0.028). An additive genetic
risk score of high-risk alleles at the three loci showed graded associations with
uric acid (272-351 mumol/L in the Framingham cohort, 269-386 mumol/L in the
Rotterdam cohort, and 303-426 mumol/L in white participants of the ARIC study)
and gout (frequency 2-13% in the Framingham cohort, 2-8% in the Rotterdam cohort,
and 1-18% in white participants in the ARIC study). INTERPRETATION: We identified
three genetic loci associated with uric acid concentration and gout. A score
based on genes with a putative role in renal urate handling showed a substantial 
risk for gout.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18834626 [PubMed - indexed for MEDLINE]

15: Cleve Clin J Med. 2008 Jul;75 Suppl 5:S17-21.

The gout diagnosis.

Dore RK.

Division of Rheumatology, David Geffen School of Medicine, University of
California at Los Angeles, 92780, USA. rkdmail@sbcglobal.net

Synovial fluid aspiration and analysis is the gold standard for making the
diagnosis of gout but is not always performed when indicated in clinical
practice. In clinical situations when joint aspiration simply cannot be
performed, a presumptive (or clinical) diagnosis of gout may be made in
consultation with published recommendations and criteria from expert societies. A
thorough patient history and physical examination are critical to a presumptive
diagnosis of gout, as is serum urate measurement at the time of an acute attack
and at follow-up 2 weeks later.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18822471 [PubMed - indexed for MEDLINE]

16: Cleve Clin J Med. 2008 Jul;75 Suppl 5:S5-8.

Clinical manifestations of hyperuricemia and gout.

Mandell BF.

Department of Rheumatic and Immunologic Diseases, Center for Vasculitis Care and 
Research, Cleveland Clinic, Cleveland, OH 44195, USA. mandelb@ccf.org

Biologically significant hyperuricemia occurs when serum urate levels exceed
urate solubility, ie, at approximately 6.8 mg/dL. At serum urate levels above
this threshold, manifestations of chronic crystal deposition, including gouty
arthritis, may occur, although asymptomatic hyperuricemia often persists for many
years without progression. Intercritical asymptomatic periods follow the
resolution of acute gout flares, but crystals remain in the joint during these
intervals and further deposition may continue silently. Ultimately this may lead 
to persistent attacks, chronic pain, and, in some patients, joint damage.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18822469 [PubMed - indexed for MEDLINE]

17: Cleve Clin J Med. 2008 Jul;75 Suppl 5:S2-4.

The pathogenesis of gout.

Schumacher HR Jr.

University of Pennsylvania, Philadelphia, PA, USA. schumacr@mail.med.upenn.edu

An elevated serum urate level, together with local factors, can result in the
deposition of urate crystals into the joints. Once crystals are deposited into a 
joint, they can be released into the joint space and initiate an inflammatory
cascade causing acute gouty arthritis. These acute flares resolve, but the
crystals remain in the joint. The way to ultimately correct the underlying
metabolic problem of hyperuricemia and the crystal deposition is to lower the
serum urate level and dissolve the crystal deposits. This will stop both the
acute attacks and the progressive joint damage.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18822468 [PubMed - indexed for MEDLINE]

18: Cleve Clin J Med. 2008 Jul;75 Suppl 5:S22-5.

The practical management of gout.

Schumacher HR Jr, Chen LX.

University of Pennsylvania, Philadelphia, PA, USA. schumacr@mail.med.upenn.edu

Gout management requires a comprehensive strategy that considers both acute and
chronic aspects of the disease. Acute gout flares should be treated with
anti-inflammatory agents as rapidly as possible. The underlying hyperuricemia may
be treated with urate-lowering agents initiated at a time appropriate for the
individual patient. Successful urate lowering ultimately prevents flares and
disease progression and should be started immediately in patients with advanced
or tophaceous disease. When urate-lowering therapy is initiated,
anti-inflammatory prophylaxis should be used to reduce the risk of flares induced
by abrupt changes in urate levels. Regular monitoring of serum urate can ensure
therapeutic dosing of urate-lowering agents to achieve levels below 6 mg/dL,
which are associated with a reduction in flares and tophi.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18819330 [PubMed - indexed for MEDLINE]

19: Cleve Clin J Med. 2008 Jul;75 Suppl 5:S9-12.

Epidemiology of gout.

Weaver AL.

Department of Internal Medicine, Division of Rheumatology, University of Nebraska
Medical Center, Omaha, NE, USA. Weaver2aj@tds.net

The incidence and prevalence of gout are rising, likely as a result of a changing
pattern of risk factors. At-risk populations are growing, due to the fact that
people are living longer. Longevity and current dietary and lifestyle choices
have also contributed to increased rates of comorbidities associated with
hyperuricemia and gout. The use of medications to treat such comorbidities also
plays a role in some cases of gout. While dietary and lifestyle modification may 
be useful as adjunctive measures, such changes do not replace pharmacologic
treatments for gout or associated comorbidities.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18819329 [PubMed - indexed for MEDLINE]

20: Ophthal Plast Reconstr Surg. 2008 Sep-Oct;24(5):404-6.

Gouty tophus of the upper eyelid.

Yang CC, Vagefi MR, Davis D, Mamalis N, Anderson RL, McCann J.

Center for Facial Appearances, Salt Lake City, Utah, USA. ccluislin@gmail.com

A 64-year-old man with gout presented with history of an enlarging mass in the
left upper eyelid causing mechanical ptosis. The patient underwent excisional
biopsy. The histopathologic findings confirmed the diagnosis of gouty tophus of
the eyelid.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 18806665 [PubMed - indexed for MEDLINE]

21: Ophthal Plast Reconstr Surg. 2008 Sep-Oct;24(5):403-4.

Medial canthal tophus.

Jordan DR, Belliveau MJ, Brownstein S, McEachren T, Kyrollos M.

Department of Ophthalmology, University of Ottawa Eye Institute, Ottawa, Ontario,
Canada. jordan1897@rogers.com

A 68-year-old-man was seen in consultation for a suspicious medial canthal lesion
that developed over a 2-year period. The raised, nodular lesion was skin colored,
had a raised pearly border and a central depression with superficial crusting.
Basal cell carcinoma was suspected and an excisional biopsy was performed.
However, a granulomatous inflammatory process with features consistent with gout 
was identified. Further inquiry confirmed a history of gout including prior tophi
on each elbow. Gouty tophi are extremely rare in the periocular area but should
be considered in the differential diagnosis of basal cell carcinoma as they may
have a similar clinical appearance.

Publication Types: 
    Case Reports

PMID: 18806664 [PubMed - indexed for MEDLINE]

22: Clin Exp Rheumatol. 2008 Jul-Aug;26(4):620-6.

The Health Assessment Questionnaire Disability Index is a valid measure of
physical function in gout.

Taylor WJ, Colvine K, Gregory K, Collis J, McQueen FM, Dalbeth N.

Department of Medicine, University of Otago, Wellington, New Zealand.
will.taylor@otago.ac.nz

OBJECTIVE: There are no disability instruments that have specifically been
validated for gout. The aim of this study was to determine the construct validity
of the Health Assessment Questionnaire Disability Index (HAQ-DI) in gout and the 
internal validity using Rasch analysis. METHODS: An observational cohort study of
two groups of clinic patients with gout (n=20, n=53), in which clinical and
functional measures were correlated with HAQ-DI scores. Rasch analysis was used
to determine the internal validity of summated scores as a measure of physical
disability. RESULTS: The HAQ-DI items fitted a Rasch measurement model,
confirming internal validity of the scale, although there was evidence of
disordered thresholds and rescoring items as a 3-option response rather than a
4-option response improved model fit and resolved the disordered thresholds.
HAQ-DI scores showed a bimodal distribution and evidence of floor effects.
Clinical indices correlated highly with HAQ-DI scores in gout patients,
particularly other measures of physical function. A strong relationship between
days of sick leave and HAQ-DI was observed in gout patients (r2=0.44, p<0.001).
CONCLUSIONS: It is concluded that HAQ-DI has good construct and internal validity
in gout but a modified scoring approach better fits a Rasch model.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 18799093 [PubMed - indexed for MEDLINE]

23: Singapore Med J. 2008 Aug;49(8):e202-4.

Wrist gouty arthritis presenting as scaphoid erosions with scapholunate ligament 
disruption.

Lee YH, Tan HW, Lee HC.

Department of Orthopaedic Surgery, Changi General Hospital, 2 Simei Street 3,
Singapore 529889. davelyh@singnet.com.sg

We report a 43-year-old man who presented with features of acute wrist
inflammation with scapholunate dissociation. Radiologically, erosions were noted 
in the proximal pole of the scaphoid. The patient underwent wrist arthrotomy,
exploration and washout with intraoperative bacterial cultures and histology
specimens were obtained. Histological analysis revealed the diagnosis of gout. We
discuss the clinical presentation and literature review of this topic. This case 
illustrates that gout may mimic infection.

Publication Types: 
    Case Reports

PMID: 18756333 [PubMed - indexed for MEDLINE]

24: Drugs. 2008;68(13):1865-74.

Comment in:
    Drugs. 2008;68(13):1875-6.    Drugs. 2008;68(13):1875-6.    Drugs. 2008;68(13):1875-6.

Febuxostat.

Hair PI, McCormack PL, Keating GM.

Wolters Kluwer Health | Adis, Auckland, New Zealand.

*Febuxostat is an orally administered, non-purine, selective inhibitor of
xanthine oxidase approved for the management of chronic hyperuricaemia in
patients with gout. *In a randomized, double-blind, dose-ranging study in
patients with gout and hyperuricaemia, significantly more recipients of
febuxostat 40-120 mg/day than placebo had serum urate levels of < 6.0 mg/dL after
4 weeks of treatment. *Serum urate levels were reduced below 6.0 mg/dL at the
last three monthly observations in a significantly greater proportion of patients
with gout and hyperuricaemia receiving febuxostat 80 or 120 mg once daily than in
those receiving allopurinol 300 mg once daily in a 52-week, randomized,
double-blind trial (FACT). *Similarly, febuxostat 80, 120 or 240 mg once daily
showed significantly greater urate-lowering efficacy than allopurinol 100 or 300 
mg once daily in a 28-week, randomized, double-blind, placebo-controlled trial
(APEX) in patients with gout and hyperuricaemia. *Long-term treatment with
febuxostat for up to 4 years or more reduced the incidence of gout flares to (or 
close to) zero. *Febuxostat was generally well tolerated in clinical trials,
including extension studies lasting > or = 4 years, with most treatment-related
adverse events being mild to moderate in severity.

Publication Types: 
    Review

PMID: 18729537 [PubMed - indexed for MEDLINE]

25: Clin Podiatr Med Surg. 2008 Oct;25(4):755-62, xi.

Salvage of the first ray with concomitant septic and gouty arthritis by use of a 
bone block joint distraction arthrodesis and external fixation.

Stapleton JJ, Rodriguez RH, Jeffries LC, Zgonis T.

Foot and Ankle Surgery, VSAS Orthopaedics, Lehigh Valley Hospital, Cedar Crest
Campus, Allentown, PA, USA.

Gouty arthropathy about the first metatarsal-phalangeal joint with a superimposed
deep infection poses a great challenge to the foot and ankle surgeon. The
inflammatory nature of gout compromises the soft-tissue envelope and vasculature 
to the area. Acute gouty arthropathy is usually a contraindication to surgical
intervention secondary to wound-healing complications and possible vasospasm
leading to tissue necrosis. However, if deep infection is present this must be
managed with adequate surgical débridement followed by delayed soft-tissue and
osseous reconstruction to prevent amputation. The authors present an exceptional 
clinical manifestation of gouty arthropathy of the first metatarsal-phalangeal
joint concomitant with deep abscess and osteomyelitis and the surgical approach
taken to afford functional limb salvage.

Publication Types: 
    Review

PMID: 18722911 [PubMed - indexed for MEDLINE]

26: Rheumatology (Oxford). 2008 Oct;47(10):1567-70. Epub 2008 Aug 18.

Gout and the risk of type 2 diabetes among men with a high cardiovascular risk
profile.

Choi HK, De Vera MA, Krishnan E.

Department of Medicine, Division of Rheumatology, Vancouver General Hospital,
Canada. hchoi@partners.org

OBJECTIVE: Our objective was to evaluate the independent relation between a
history of gout and the future risk of type 2 diabetes among men with a high
cardiovascular risk profile. METHODS: We prospectively examined over a 6-yr
period the relation between gout and the risk of incident type 2 diabetes in 11
351 male participants from the Multiple Risk Factor Intervention Trial (MRFIT).
Incident diabetes was defined based on the American Diabetes Association (ADA)
criteria for epidemiological studies. Cox proportional hazards regression was
used to adjust for potential confounders. RESULTS: We documented 1215 new cases
of type 2 diabetes. After adjusting for age, BMI, smoking, family history of type
2 diabetes, alcohol intake, dietary factors and presence of individual components
of the metabolic syndrome, the multivariate relative risk (RR) for incident type 
2 diabetes among men with gout at baseline, as compared with men without gout,
was 1.34 (95% CI 1.09, 1.64). When we further adjusted for serum uric acid
levels, the association remained significant (RR 1.26; 95% CI 1.02, 1.54). When
we updated the status of gout annually during follow-up as a time-varying
covariate, the association remained similar. The association also remained
similar in our subgroup analyses by major covariates (P-values for interaction
>0.16). CONCLUSIONS: These findings from men with a high cardiovascular risk
profile suggest that men with gout are at a higher future risk of type 2 diabetes
independent of other known risk factors. These data expand on well-established,
cross-sectional associations between hyperuricaemia, gout and the metabolic
syndrome, and extend the link to the future risk of type 2 diabetes.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18710901 [PubMed - indexed for MEDLINE]

27: Chin J Integr Med. 2008 Jun;14(2):103-6. Epub 2008 Aug 6.

Clinical effect and action mechanism of Weicao Capsule in treating gout.

Song EF, Xiang Q, Ren KM, Hu JC, Wu F, Gong MF, Zhang H, Bi HM.

Department of Traditional Chinese Medicine, Renmin Hospital of Wuhan University, 
Wuhan, China. songef@126.com

OBJECTIVE: To study the therapeutic effect of Weicao Capsule (WCC) on gout.
METHODS: Two hundred gout patients were assigned to two groups. The treated group
was treated with WCC and the control group was treated with Tongfengding Capsule.
Both groups were given the respective treatments orally 3 times a day, 2 capsules
each time with 2 weeks as one course and all patients received 2 successive
courses of treatment. Changes of blood beta(2)-microglobulin (beta(2)-M),
hemoglobin (Hb), 24 h urinary protein (24 h UP), pH value of urine and blood uric
acid (BUA) as well as kidney function were observed. RESULTS: After treatment,
level of beta(2)-M got lowered significantly, Hb and 24 h UP, blood urea
nitrogen, serum creatinine and the clearance rate of creatinine, as well as blood
lipids all improved obviously in the treated group (all P<0.01), while these
parameters remained unchanged in the control group (P>0.05). The pH value of
urine was improved in both groups showing an insignificant difference between
them (P>0.05). BUA was decreased in both groups with a decrease to a larger
extent in the treated group (P<0.01). The total effective rate was 87% in the
treated group, which was superior to that in the control group (62%, P<0.05).
CONCLUSION: WCC has a favorable therapeutic effect on gout and its mechanism of
action for improving renal function and reducing urinary protein could be related
with the lowering of blood beta(2)-M, BUA and lipids.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18679600 [PubMed - indexed for MEDLINE]

28: Joint Bone Spine. 2008 Oct;75(5):610-2. Epub 2008 Jul 31.

Ultrasonography for diagnosing atypical gout. Two case reports.

Le Goff B, Berthelot JM, André V, Guillot P, Maugars Y.

CHU de Nantes, Service de rhumatologie, 1 place Alexis Ricordeau, 44093 Nantes
Cedex 1, France. benoit.legoff@chu-nantes.fr

Gout is characterized by the deposition of monosodium urate crystals on the
surface of the articular cartilage, within periarticular tissues, and within bone
and skin. The diagnosis rests on identification of the crystals in joint fluid or
a tophus. However, joint aspiration is not always feasible, and the presentation 
may be atypical. We describe two cases of chronic gouty arthritis misdiagnosed as
psoriatic arthritis. Ultrasonography of the bone and joints disclosed two
patterns recently described as highly suggestive of gout, namely, the
double-contour appearance of the cartilage and the snowstorm appearance of the
synovial membrane. In addition, ultrasonography was useful for guided aspiration 
of joint fluid or other material containing monosodium urate crystals. Thus,
ultrasonography may contribute to improve the diagnosis and treatment of gout.

Publication Types: 
    Case Reports

PMID: 18674948 [PubMed - indexed for MEDLINE]

29: Curr Rheumatol Rep. 2008 Jul;10(3):249-55.

Gout and coronary artery disease: epidemiologic clues.

Krishnan E.

S709 BST South, 3500 Terrace Street, Pittsburgh, PA 15215, USA.
arthritis.md@gmail.com

Gout is the leading cause of inflammatory arthritis, typically affecting men and 
characterized by intermittent, abrupt onset of intense inflammation. The
association between gout, atherosclerosis, and vascular disease has been noted in
medical literature since the end of the 19th century, yet it has not been well
studied. This review critically appraises the few epidemiologic studies that ask 
if gout is a risk factor for coronary artery disease. An exhaustive literature
search using search engines and cross-referencing found four major studies and
several smaller studies that have evaluated gout as a risk factor for coronary
artery disease. The available studies were too heterogeneous to permit formal
meta-analysis. Although there are gaps in evidence pointing to a causative
pathway, overall, evidence exists for a relationship between gouty arthritis and 
coronary artery disease independent of traditional risk factors.

Publication Types: 
    Review

PMID: 18638434 [PubMed - indexed for MEDLINE]

30: Curr Rheumatol Rep. 2008 Jul;10(3):235-48.

Non-crystalline and crystalline rheumatic disorders in chronic kidney disease.

Sarraf P, Kay J, Reginato AM.

US National Instituteof Arthritis and Musculoskeletal and Skin Diseases,
Bethesda, MD, USA.

Rheumatic syndromes are cause for morbidity in patients with end-stage renal
disease. Recent advances in understanding the role of tissue remodeling have
provided insight into the pathogenic mechanisms responsible for some of these
manifestations. Here, we survey recent and clinically relevant advances in
translational research that impact our understanding of rheumatic syndromes seen 
in patients with significant renal disease. The management of acute and chronic
crystalline arthropathies in chronic kidney disease and hemodialysis patients is 
discussed.

Publication Types: 
    Review

PMID: 18638433 [PubMed - indexed for MEDLINE]

31: Curr Rheumatol Rep. 2008 Jul;10(3):218-27.

Colchicine: its mechanism of action and efficacy in crystal-induced inflammation.

Nuki G.

University of Edinburgh, Osteoarticular Research Group, The Queen's Medical
Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland,
United Kingdom. g.nuki@ed.ac.uk

New light has been shed on the mechanisms of action of colchicine in
crystal-associated arthropathies. Colchicine, long used to treat gout, arrests
microtubule assembly and inhibits many cellular functions. At micromolar
concentrations, it suppresses monosodium urate crystal-induced
NACHT-LRR-PYD-containing protein-3 (NALP3) inflammasome-driven caspase-1
activation, IL-1beta processing and release, and L-selectin expression on
neutrophils. At nanomolar concentrations, colchicine blocks the release of a
crystal-derived chemotactic factor from neutrophil lysosomes, blocks neutrophil
adhesion to endothelium by modulating the distribution of adhesion molecules on
the endothelial cells, and inhibits monosodium urate crystal-induced production
of superoxide anions from neutrophils. Cyto-chrome P450 3A4, the multidrug
transporter P-glycoprotein, and the drugs that bind these proteins influence its 
pharmacokinetics and pharmacodynamics. Trial evidence supports its efficacy in
acute gout and in preventing gout flares, but it has narrow therapeutic index,
and overdosage is associated with gastrointestinal, hepatic, renal,
neuromuscular, and cerebral toxicity; bone marrow damage; and high mortality.

Publication Types: 
    Review

PMID: 18638431 [PubMed - indexed for MEDLINE]

32: Drug Saf. 2008;31(8):643-65.

A benefit-risk assessment of benzbromarone in the treatment of gout. Was its
withdrawal from the market in the best interest of patients?

Lee MH, Graham GG, Williams KM, Day RO.

Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital,
University of New South Wales, Sydney, New South Wales, Australia.

Benzbromarone, a potent uricosuric drug, was introduced in the 1970s and was
viewed as having few associated serious adverse reactions. It was registered in
about 20 countries throughout Asia, South America and Europe. In 2003, the drug
was withdrawn by Sanofi-Synthélabo, after reports of serious hepatotoxicity,
although it is still marketed in several countries by other drug companies. The
withdrawal has greatly limited its availability around the world, and increased
difficulty in accessing it in other countries where it has never been
available.The overall aim of this paper is to determine if the withdrawal of
benzbromarone was in the best interests of gouty patients and to present a
benefit-risk assessment of benzbromarone. To determine this, we examined (i) the 
clinical benefits associated with benzbromarone treatment and compared them with 
the success of alternative therapies such as allopurinol and probenecid,
particularly in patients with renal impairment; (ii) the attribution of the
reported cases of hepatotoxicity to treatment with benzbromarone; (iii) the
incidence of hepatotoxicity possibly due to benzbromarone; (iv) adverse reactions
to allopurinol and probenecid. From these analyses, we present recommendations on
the use of benzbromarone.Large reductions in plasma urate concentrations in
patients with hyperuricaemia are achieved with benzbromarone and most patients
normalize their plasma urate. The half-life of benzbromarone is generally short
(about 3 hours); however, a uricosuric metabolite, 6-hydroxybenzbromarone, has a 
much longer half-life (up to 30 hours) and is the major species responsible for
the uricosuric activity of benzbromarone, although its metabolism by cytochrome
P450 (CYP) 2C9 in the liver may vary between patients as a result of
polymorphisms in this enzyme. It is effective in patients with moderate renal
impairment. Standard dosages of benzbromarone (100 mg/day) tend to produce
greater hypouricaemic effects than standard doses of allopourinol (300 mg/day) or
probenecid (1000 mg/day).Adverse effects associated with benzbromarone are
relatively infrequent, but potentially severe. Four cases of
benzbromarone-induced hepatotoxicity were identified from the literature. Eleven 
cases have been reported by Sanofi-Synthélabo, but details are not available in
the public domain. Only one of the four published cases demonstrated a clear
relationship between the drug and liver injury as demonstrated by rechallenge.
The other three cases lacked incontrovertible evidence to support a diagnosis of 
benzbromarone-induced hepatotoxicity. If all the reported cases are assumed to be
due to benzbromarone, the estimated risk of hepatotoxicity in Europe was
approximately 1 in 17 000 patients but may be higher in Japan.Benzbromarone is
also an inhibitor of CYP2C9 and so may be involved in drug interactions with
drugs dependent on this enzyme for clearance, such as warfarin. Alternative drugs
to benzbromarone have significant adverse reactions. Allopurinol is associated
with rare life-threatening hypersensitivity syndromes; the risk of these
reactions is approximately 1 in 56 000. Rash occurs in approximately 2% of
patients taking allopurinol and usually leads to cessation of prescription of the
drug. Probenecid has also been associated with life-threatening reactions in a
very small number of case reports, but it frequently interacts with many renally 
excreted drugs. Febuxostat is a new xanthine oxidoreductase inhibitor, which is
still in clinical trials, but abnormal liver function is the most commonly
reported adverse reaction.Even assuming a causal relationship between
benzbromarone and hepatotoxicity in the identified cases, benefit-risk assessment
based on total exposure to the drug does not support the decision by the drug
company to withdraw benzbromarone from the market given the paucity of
alternative options. It is likely that the risks of hepatotoxicity could be
ameliorated by employing a graded dosage increase, together with regular
monitoring of liver function. Determination of CYP2C9 status and consideration of
potential interactions through inhibition of this enzyme should be considered.
The case for wider and easier availability of benzbromarone for treating selected
cases of gout is compelling, particularly for patients in whom allopurinol
produces insufficient response or toxicity.We conclude that the withdrawal of
benzbromarone was not in the best interest of patients with gout.

Publication Types: 
    Comparative Study
    Review

PMID: 18636784 [PubMed - indexed for MEDLINE]

33: J Rheumatol. 2008 Sep;35(9):1859-64. Epub 2008 Jul 15.

Comment in:
    J Rheumatol. 2008 Sep;35(9):1689-91.

Dietary and lifestyle changes associated with high prevalence of hyperuricemia
and gout in the Shandong coastal cities of Eastern China.

Miao Z, Li C, Chen Y, Zhao S, Wang Y, Wang Z, Chen X, Xu F, Wang F, Sun R, Hu J, 
Song W, Yan S, Wang CY.

Department of Endocrinology, Medical School Hospital of Qingdao University,
Qingdao, China.

OBJECTIVE: To demonstrate the prevalence of hyperuricemia and gout associated
with dietary and lifestyle changes and evaluate the implication of metabolic
disorders to the development of hyperuricemia. METHODS: Data collected from 5,003
subjects randomly recruited from 5 coastal cities (Qingdao, Rizhao, Yantai,
Weihai, and Dongying) of Shandong province in Eastern China were analyzed.
RESULTS: Overall, the prevalence for hyperuricemia and gout in the studied
populations was 13.19% and 1.14%, respectively. The prevalence was significantly 
higher in men as compared to women (18.32% vs 8.56% for hyperuricemia, 1.94% vs
0.42% for gout). Hyperuricemia was more common in men over age 30 and in women
over age 50. A significant steady increase for the prevalence was noted as
compared to the previous published data. Urban residents showed much higher
prevalence of hyperuricemia as compared to rural residents (14.9% vs 10.1%, p =
0.004). Similarly, higher prevalence was noted in the developed city compared to 
the less developed city (18.02 vs 5.3%). These discrepancies were highly
correlated with economic development as manifested by the increase of daily
consumption of meat and seafood. Additionally, alcohol, overweight or obesity,
hypertension, and abnormal triglycerides were highly associated with higher
prevalence of hyperuricemia. Moreover, hyperuricemia is likely a risk factor for 
the development of diabetes mellitus. CONCLUSION: There was a remarkable increase
for the prevalence of hyperuricemia and gout, which is highly correlated with the
development of the economy as manifested by dietary and lifestyle changes.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18634142 [PubMed - indexed for MEDLINE]

34: Prescrire Int. 2008 Jun;17(95):123.

Treatment of gout attacks.

[No authors listed]

Gout attacks resolve in 3 to 10 days without treatment. Treatment is mainly
empirical. Paracetamol and application of ice can be tried. If they fail, the
best options is a moderate dose of ibuprofen, and NSAID with well-documented
adverse effects.

PMID: 18630391 [PubMed - indexed for MEDLINE]

35: Ir Med J. 2008 May;101(5):147-9.

A survey of the management of gout in primary care.

Owens D, Whelan B, McCarthy G.

Department of Rheumatology, Mater Misericordiae Hospital, Dublin.
daowens@eircom.net

There is no information available regarding current practice and standards in
management of gout in Irish general practice. This study aims to assess current
practice in the context of the 2006 EULAR evidence based recommendations for
diagnosis and management of gout. A 20 point questionnaire was circulated to all 
170 general practitioners in the North Dublin GP Partnership assessing frequency 
of diagnostic and therapeutic interventions undertaken. 91% of practitioners
manage gout exclusively in primary care. 89% make a diagnosis on clinical grounds
and 77% routinely measure serum urate. Diagnostic joint aspiration is rarely
performed (3%). 86% routinely assess and manage risk factors for gout. 66%
initiate urate-lowering therapy. Only 32% routinely monitor urate levels in
patients receiving urate-lowering therapy. Thus, although management of gout in
primary care in Ireland is generally in line with the EULAR recommendations some 
aspects of care remain suboptimal.

PMID: 18624262 [PubMed - indexed for MEDLINE]

36: Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):604-7.

An unusual patient with hypothyroidism, tophaceous gout, and marked joint
destruction.

Montoya F, Torres RJ, Fraile JM, Puig JG.

Divisions of Internal Medicine, La Paz University Hospital, Madrid, Spain.

This report describes a 75-year-old Caucasian man with extensive urate deposits
and severe gouty arthropathy that confined him to a wheelchair. Since age 50, he 
suffered multiple acute gout flares and progressive deformities in his hands,
feet, knees, and elbows (tophi). Serum creatinine was 1.4 mg/dL and serum urate
9.4 mg/dL. Conditions known to increase uric acid production (psoriasis, chronic 
bronchitis) and to decrease uric acid excretion (hypothyroidism, metabolic
syndrome, and nephroangiosclerosis) may operate in a single patient, illustrating
the dramatic clinical course of untreated gout.

Publication Types: 
    Case Reports

PMID: 18600513 [PubMed - indexed for MEDLINE]

37: Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):585-91.

Determinants of the clinical outcomes of gout during the first year of
urate-lowering therapy.

Becker MA, MacDonald PA, Hunt BJ, Lademacher C, Joseph-Ridge N.

Rheumatology Section, Department of Medicine, University of Chicago Pritzker
School of Medicine, Chicago, Illinois, USA. mbecker@medicine.bsd.uchicago.edu

Clinical benefit early in urate-lowering treatment of gout is difficult to
document. We examined data from 1,832 gouty subjects treated with either
urate-lowering agents or placebo to identify determinants of gout flare incidence
and tophus size during year 1 of treatment. Reductions from pretreatment serum
urate levels influenced flare frequency and tophus size, but the effect of urate 
level on flare incidence was biphasic. Lower urate levels were associated with
higher flare incidence early in treatment but lower incidence by one year. The
complex relationship between urate-lowering and clinical outcome early in
treatment has implications for both clinical and investigative approaches to
urate-lowering management.

Publication Types: 
    Randomized Controlled Trial

PMID: 18600509 [PubMed - indexed for MEDLINE]

38: Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):570-4.

Molecular analysis of hypoxanthine guanine phosphoribosyltransferase (HPRT)
deficiencies: novel mutations and the spectrum of Japanese mutations.

Yamada Y, Nomura N, Yamada K, Wakamatsu N, Kaneko K, Fujimori S.

Department of Genetics, Institute for Developmental Research, Aichi Human Service
Center, Kasugai Aichi, Japan. yasyam@inst-hsc.jp

Inherited mutation of hypoxanthine guanine phosphoribosyltransferase, (HPRT)
gives rise to Lesch-Nyhan syndrome or HPRT-related gout. We have identified a
number of HPRT mutations in patients manifesting different clinical phenotypes,
by analyzing all nine exons of the HPRT gene (HPRT1) from genomic DNA and reverse
transcribed mRNA using the PCR technique coupled with direct sequencing.
Recently, we detected two novel mutations: a single nucleotide substitution (430C
> T) resulting in a nonsense mutation Q144X, and a deletion of HPRT1 exon 1
expressing no mRNA of HPRT. Furthermore, we summarized the spectrum of 56
Japanese HPRT mutations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18600506 [PubMed - indexed for MEDLINE]

39: Geriatrics. 2008 Jul;63(7):13-8, 20.

Therapeutic challenges in the management of gout in the elderly.

Singh H, Torralba KD.

Department of Geriatrics, University of Arkansas for Medical Sciences, Little
Rock, USA.

Gout is the most common inflammatory arthritis in the elderly population.
Management in the elderly requires special consideration. Physiologic changes
associated with aging and co-morbidities make the elderly prone to adverse
effects of drugs otherwise successfully used in younger counterparts. Use of
colchicine, non-steroidal anti-inflammatory drugs, and urate-lowering therapies
may be restricted in those with limited renal reserve. Corticosteroids are safe
alternatives for short-term use in acute gout. Elderly patients need laboratory
monitoring for side effects more frequently than usual. Non-pharmacologic
measures such as dietary modifications, regular exercise, and ice therapy should 
be considered vital adjunctive treatments. A brief review of future therapies is 
also discussed.

Publication Types: 
    Review

PMID: 18593209 [PubMed - indexed for MEDLINE]

40: Arthritis Res Ther. 2008;10(3):112. Epub 2008 Jun 6.

Comment on:
    Arthritis Res Ther. 2008;10(3):R64.

Gout in the spotlight.

So A.

Understanding how uric acid crystals provoke inflammation is crucial to improving
our management of acute gout. It is well known that urate crystals stimulate
monocytes and macrophages to elaborate inflammatory cytokines, but the tissue
response of the synovium is less well understood. Microarray analysis of mRNA
expression by these lining cells may help to delineate the genes that are
modulated. Employing a murine air-pouch model, a number of genes expressed by
innate immune cells were found to be rapidly upregulated by monosodium urate
crystals. These findings provide new research avenues to investigate the
physiopathology of gouty inflammation, and may eventually lead to new therapeutic
targets in acute gout.

Publication Types: 
    Comment
    Editorial

PMID: 18564404 [PubMed - indexed for MEDLINE]

41: Vesalius. 2007 Dec;13(2):60-7.

Drink, dames & disease: Erasmus Darwin on inheritance.

Wilson PK.

Kienle Center for Humanistic Medicine, Penn. State University College of
Medicine, Hershey, Pennsylvania 17033, USA.

Dr Erasmus Darwin (1731-1802) readily acknowledged that diseases including gout, 
consumption, scrofula, epilepsy, and insanity were hereditarily transferred. He
also viewed a particular interconnectedness between intemperance (alcoholism) and
other hereditary diseases. Darwin's view of 'hereditary' incorporated a malleable
admixture of nature and nurture causes. Consistent with his deistic beliefs that 
development on the Earth followed no fixed plan, Darwin argued that hereditary
diseases were not predestined. To overcome or prevent disease, Darwin argued that
one must learn how best to exert power over nature and to improve nurture.

Publication Types: 
    Biography
    Historical Article

Personal Name as Subject: 
    Darwin E

PMID: 18549074 [PubMed - indexed for MEDLINE]

42: N Z Med J. 2008 May 23;121(1274):79-85.

Debunking the myths to provide 21st Century management of gout.

Winnard D, Kake T, Gow P, Barratt-Boyes C, Harris V, Hall DA, Mason H, Merriman
T, Dalbeth N; Maaori Gout Action Group in Counties Manukau District Health Board.

Counties Manukau District Health Board, Private Bag 94052, South Auckland Mail
Centre, Manukau City, New Zealand. WinnarD@middlemore.co.nz

Epidemiologic and recent qualitative research suggests that the impact of
under-treated gout is far more significant than many health professionals
realise. The magnitude of this impact for Maaori and Pacific men of working age
has been identified as a particular concern by the recently formed Maaori Gout
Action Group in Counties Manukau District Health Board (South Auckland, New
Zealand). The Group has identified that to achieve modern management of gout,
those with gout need to be supported by primary care practitioners who are aware 
of the need for early intervention with allopurinol, as well as whaanau/families 
and communities who understand the impact and causes of gout and the lifestyle
changes that are needed alongside long-term allopurinol. The Group wishes to
support further research into the impact and causes of gout, particularly for
Maaori, and to develop strategic alliances to ensure that the treatment and
prevention of gout is advocated by those working with conditions such as diabetes
and cardiovascular disease where gout is a frequent comorbidity.

PMID: 18535649 [PubMed - indexed for MEDLINE]

43: Lancet. 2008 May 31;371(9627):1854-60.

Comment in:
    J Fam Pract. 2008 Oct;57(10):655-7.    J Fam Pract. 2008 Sep;57(9):576.    Lancet. 2008 Oct 11;372(9646):1301; author reply 1301-2.    Nat Clin Pract Rheumatol. 2009 Jan;5(1):12-3.

Use of oral prednisolone or naproxen for the treatment of gout arthritis: a
double-blind, randomised equivalence trial.

Janssens HJ, Janssen M, van de Lisdonk EH, van Riel PL, van Weel C.

Department of General Practice, Radboud University Nijmegen Medical Centre,
Nijmegen, Netherlands. h.janssens@hag.umcn.nl

BACKGROUND: Non-steroidal anti-inflammatory drugs and colchicine used to treat
gout arthritis have gastrointestinal, renal, and cardiovascular adverse effects. 
Systemic corticosteroids might be a beneficial alternative. We investigated
equivalence of naproxen and prednisolone in primary care. METHODS: We did a
randomised clinical trial to test equivalence of prednisolone and naproxen for
the treatment of monoarticular gout. Primary-care patients with gout confirmed by
presence of monosodium urate crystals were eligible. 120 patients were randomly
assigned with computer-generated randomisation to receive either prednisolone (35
mg once a day; n=60) or naproxen (500 mg twice a day; n=60), for 5 days.
Treatment was masked for both patients and physicians. The primary outcome was
pain measured on a 100 mm visual analogue scale and the a priori margin for
equivalence set at 10%. Analyses were done per protocol and by intention to
treat. This study is registered as an International Standard Randomised
Controlled Trial, number ISRCTN14648181. FINDINGS: Data were incomplete for one
patient in each treatment group, so per-protocol analyses included 59 patients in
each group. After 90 h the reduction in the pain score was 44.7 mm and 46.0 mm
for prednisolone and naproxen, respectively (difference 1.3 mm; 95% CI -9.8 to
7.1), suggesting equivalence. The difference in the size of change in pain was
1.57 mm (95% CI -8.65 to 11.78). Adverse effects were similar between groups,
minor, and resolved by 3 week follow-up. INTERPRETATION: Oral prednisolone and
naproxen are equally effective in the initial treatment of gout arthritis over 4 
days.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18514729 [PubMed - indexed for MEDLINE]

44: Arthritis Rheum. 2008 Jun;58(6):1854-65.

Enhanced osteoclastogenesis in patients with tophaceous gout: urate crystals
promote osteoclast development through interactions with stromal cells.

Dalbeth N, Smith T, Nicolson B, Clark B, Callon K, Naot D, Haskard DO, McQueen
FM, Reid IR, Cornish J.

University of Auckland, Grafton, Auckland, New Zealand. n.dalbeth@auckland.ac.nz

OBJECTIVE: To analyze cellular mechanisms of bone erosion in gout. METHODS:
Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells
(SFMCs) from patients with gout were analyzed for the presence of osteoclast
precursors. Fixed tophus and bone samples were analyzed by immunohistochemistry. 
Mechanisms of osteoclastogenesis were studied by culturing murine preosteoclast
RAW 264.7 cells, bone marrow stromal ST2 cells, and human synovial fibroblasts
with monosodium urate monohydrate (MSU) crystals. RESULTS: PBMCs from patients
with severe erosive gout had the preferential ability to form osteoclast-like
cells in culture with RANKL and monocyte colony-stimulating factor (M-CSF). The
number of PBMC-derived tartrate-resistant acid phosphatase (TRAP)-positive
multinucleated cells strongly correlated with the number of tophi (r = 0.6296, P 
= 0.630). Patients with severe erosive and tophaceous gout also had higher
circulating concentrations of RANKL and M-CSF. Furthermore, greater numbers of
TRAP-positive multinucleated cells were cultured from SFMCs derived from gouty
knee effusions than from paired PBMCs (P = 0.004). Immunohistochemical analysis
demonstrated numerous multinucleated cells expressing osteoclast markers within
tophi and at the interface between soft tissue and bone. MSU crystals did not
directly promote osteoclast formation from RAW 264.7 cells in vitro. However, MSU
crystals inhibited osteoprotegerin gene and protein expression in ST2 cells and
human synovial fibroblasts, without significantly altering RANKL gene expression.
Conditioned medium from ST2 cells cultured with MSU crystals promoted osteoclast 
formation from RAW 264.7 cells in the presence of RANKL. CONCLUSION: Chronic
tophaceous and erosive gout is characterized by enhanced osteoclast development. 
These data provide a rationale for the study of osteoclast-targeted therapies for
the prevention of bone damage in chronic gout.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18512794 [PubMed - indexed for MEDLINE]

45: J Am Soc Nephrol. 2008 Nov;19(11):2204-10. Epub 2008 May 28.

Association of incident gout and mortality in dialysis patients.

Cohen SD, Kimmel PL, Neff R, Agodoa L, Abbott KC.

Division of Renal Diseases, Department of Medicine, George Washington University 
Medical Center, Washington DC, USA

Previous studies have shown that gout is associated with an increased risk for
cardiovascular mortality in the general population, but this has not been well
studied in patients with ESRD. In this study, the incidence of gout and its
association with mortality was evaluated in 259,209 patients in the United States
Renal Data System. Overall, the incidence of gout in the first year of dialysis
was 5% and in the first 5 yr was 15.4%. Independent risk factors for gout in
adjusted analyses included black race, older age, female gender, hypertension,
ischemic heart disease, congestive heart failure, and alcohol use. Factors
associated with a lower risk for gout included a history of diabetes, smoking,
and peripheral vascular disease. Time-dependent Cox regression analysis suggested
that an episode of gout was independently associated with a 1.5-fold increase in 
mortality risk (adjusted hazard ratio 1.49; 95% confidence interval 1.43 to
1.55). The mechanisms underlying this association require further study.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18508965 [PubMed - indexed for MEDLINE]

46: Arch Intern Med. 2008 May 26;168(10):1104-10.

Long-term cardiovascular mortality among middle-aged men with gout.

Krishnan E, Svendsen K, Neaton JD, Grandits G, Kuller LH; MRFIT Research Group.

Division of Rheumatology, Department of Medicine, University of Pittsburgh School
of Medicine, Pittsburgh, Pennsylvania, USA. e.krishnan@stanford.edu

BACKGROUND: There are limited data available on the association of gouty
arthritis (gout) in middle age with long-term cardiovascular disease (CVD)
mortality. METHODS: We performed a 17-year follow-up study of 9105 men, aged 41
to 63 years and at above-average risk for coronary heart disease, who were
randomized to the Multiple Risk Factor Intervention Trial and who did not die or 
have clinical or electrocardiographic evidence of coronary artery disease during 
the 6-year trial. Risk of CVD death and other causes subsequent to the sixth
annual examination associated with gout was assessed by means of Cox proportional
hazards regressions. RESULTS: The unadjusted mortality rates from CVD among those
with and without gout were 10.3 per 1000 person-years and 8.0 per 1000
person-years, respectively, representing an approximately 30% greater risk. After
adjustment for traditional risk factors, use of diuretics and aspirin, and serum 
creatinine level, the hazard ratio (gout vs no gout) for coronary heart disease
mortality was 1.35 (95% confidence interval [CI], 1.06-1.72). The hazard ratio
for death from myocardial infarction was 1.35 (95% CI, 0.94-1.93); for death from
CVD overall, 1.21 (95% CI, 0.99-1.49); and for death from any cause, 1.09 (95%
CI, 1.00-1.19) (P = .04). The association between hyperuricemia and CVD was weak 
and did not persist when analysis was limited to men with hyperuricemia without a
diagnosis of gout. CONCLUSION: Among middle-aged men, a diagnosis of gout
accompanied by an elevated uric acid level imparts significant independent CVD
mortality risk. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000487.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18504339 [PubMed - indexed for MEDLINE]

47: Qual Life Res. 2008 Jun;17(5):815-22. Epub 2008 May 24.

The disutility of chronic gout.

Khanna D, Ahmed M, Yontz D, Ginsburg SS, Park GS, Leonard A, Tsevat J.

Division of Rheumatology, Department of Medicine, David Geffen School of
Medicine, University of California at Los Angeles, 1000 Veteran Avenue, Los
Angeles, CA 90095, USA. dkhanna@mednet.ucla.edu

INTRODUCTION: Gout is a chronic painful inflammatory arthritis. Data regarding
the impact of gout on health-related quality of life, however, are limited.
METHODS: We interviewed patients with chronic stable gout. Health status was
measured by using the Short Form 36 (SF-36) physical component summary (PCS) and 
physical component summary (MCS) and the Health Assessment
Questionnaire-Disability Index (HAQ-DI). Direct preference-based measures
included a health rating scale (RS), the time tradeoff (TTO), and standard gamble
(SG) for one's current health state with gout and current health state without
gout; indirect preference-based measures included the SF-6D and the EQ-5D.
Disutilities for gout were assessed by subtracting preference scores for current 
health states with gout from those for current health without gout and were
compared between patients ranking gout as their top health concern versus the
rest of the patients. RESULTS: Of the 80 interviewees, 72 (90%) were male, 55
(69%) were Caucasian, and the mean (SD) age was 60 (11) years. The mean SF-36 PCS
and MCS scores were 38.9 and 48.6, respectively. The mean (SD) SF-6D score was
0.68 (0.13) and the mean (SD) EQ-5D score was 0.73 (0.23). The mean (SD) RS
disutility for gout was 0.05 (0.12), the mean TTO disutility was 0.03 (0.12), and
the mean SG disutility was 0.02 (0.11). The RS disutilities of subject patients
who ranked gout as their top concern (n = 17) trended towards being statistically
significantly larger than those of the remaining patients, P = 0.06 but their TTO
and SG disutilities were similar to those of the remaining patients. CONCLUSION: 
Although physical functioning of patients with gout is often compromised,
patients with chronic stable gout do not assign a large disutility to gout per
se. Still, patients who rank their gout as their top health concern tend to
assign greater RS disutility to gout than do other patients.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18500578 [PubMed - indexed for MEDLINE]

48: Am J Clin Nutr. 2008 May;87(5):1480-7.

Effects of diet, physical activity and performance, and body weight on incident
gout in ostensibly healthy, vigorously active men.

Williams PT.

Donner Laboratory, Life Sciences Division, Ernest Orlando Lawrence Berkeley
National Laboratory, Berkeley, CA 94720, USA. ptwilliams@lbl.gov

BACKGROUND: Physical activity and cardiorespiratory fitness are not currently
recognized as factors related to preventing gout, nor are risk factors for gout
in physically active men well understood. OBJECTIVE: The objective was to
identify risk factors for gout in ostensibly healthy, vigorously active men.
DESIGN: Incident self-reported gout was compared with baseline diet, body mass
index (BMI; in kg/m(2)), physical activity (in km/d run), and cardiorespiratory
fitness (in m/s during 10-km footrace) prospectively in 28,990 male runners.
RESULTS: Men (n = 228; 0.79%) self-reported incident gout during 7.74 y of
follow-up. The risk of gout increased with higher alcohol intake [per 10 g/d;
relative risk (RR): 1.19; 95% CI: 1.12, 1.26; P < 0.0001], meat consumption (per 
servings/d; RR: 1.45; 95% CI: 1.06, 1.92; P = 0.002), and BMI (RR: 1.19; 95% CI: 
1.15, 1.23; P < 0.0001) and declined with greater fruit intake (per pieces/d; RR:
0.73; 95% CI: 0.62, 0.84; P < 0.0001), running distance (per km/d; RR: 0.92; 95% 
CI: 0.88, 0.97; P < 0.001), and fitness (per m/s; RR: 0.55; 95% CI: 0.41, 0.75; P
< 0.0001). The RR per 10 g alcohol/d consumed as wine (1.27; P = 0.002), beer
(1.19; P < 0.0001), and mixed drinks (1.13; P = 0.18) was not significantly
different from each other. Men who consumed > 15 g alcohol/d had 93% greater risk
than abstainers, and men who averaged > 2 pieces fruit/d had 50% less risk than
those who ate < 0.5 fruit/d. Risk of gout was 16-fold greater for BMI > 27.5 than
< 20. Compared with the least active or fit men, those who ran > or = 8 km/d or >
4.0 m/s had 50% and 65% lower risk of gout, respectively. Lower BMI contributed
to the risk reductions associated with distance run and fitness. CONCLUSION:
These findings, based on male runners, suggest that the risk of gout is lower in 
men who are more physically active, maintain ideal body weight, and consume diets
enriched in fruit and limited in meat and alcohol.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 18469274 [PubMed - indexed for MEDLINE]

49: J Hand Surg Eur Vol. 2008 Aug;33(4):528-9. Epub 2008 May 1.

Intra-tendinous gout in a repaired flexor digitorum profundus.

Sainsbury DC, Hidvegi N, Blair JW.

Department of Plastic Surgery, Queen Victoria Hospital, East Grinstead, West
Sussex, UK. sainsburydave@hotmail.com

A patient presented with decreased flexion and triggering following a zone IIc
flexor digitorum profundus repair 7 years previously. Chalky-white deposits,
confirmed histologically as gout, were present at the repair site.

Publication Types: 
    Case Reports

PMID: 18450796 [PubMed - indexed for MEDLINE]

50: Ortop Traumatol Rehabil. 2008 Mar-Apr;10(2):99-110.

Crystal-associated synovitis- ultrasonographic feature and clinical correlation.

Fodor D, Albu A, Gherman C.

2nd Internal Medicine and Rheumatology Department, Iuliu Hatieganu University of 
Medicine and Pharmacy, Cluj-Napoca, Romania.

The aim of this paper is to describe the ultrasonographic findings in
rheumatologic pathology due to crystal deposition. There are four main types of
crystals involved: monosodium urate, calcium pyrophosphate dihydrate, basic
calcium phosphate (hydroxyapatite), and calcium oxalate. In gout the joint fluid 
is anechoic only at the first gouty attack; afterwards the synovium begins to
proliferate. Double contuour sign, a focal or diffuse enhancement of the
superficial margin of the articular cartilage is a specific finding. Bursitis has
chronic features from the beginning. The ultrasonographic aspect of tophi depends
on their age and size (at first small, hypoechoic and homogenous nodules, then
echoic with hyperechoic edges and finally pseudotumoral, inhomogeneous). The
depositions in the superficial layer are hyperechoic, well delimited only in the 
absence of inflammatory reaction. The depositions at the entheseal level are
leading to the gouty enthesopathy. In knee involvement irregularities of the
anterior surface of patella are found. In chondrocalcinosis the most important
ultrasonographic signs are the thin hyperechoic band, parallel to the surface of 
the hyaline cartilage and the punctuated pattern of the fibrocartilage. In
hydroxyapatite associated disease, calcifications are frequent in the shoulder or
in the great trochanter of the hip, with aspects depending of the calcification
phase. Milwakee shoulder is an advanced form of this pathology, associated with
rotator cuff arthropathy. Oxalate crystal deposition disease is seen rarely, in
patients with primary hyperoxaluria and in patients with end-stage renal disease.
Therefore ultrasonography is useful in characterize the articular and
juxta-articular alterations in crystal related diseases.

Publication Types: 
    Review

PMID: 18449120 [PubMed - indexed for MEDLINE]

51: Arthritis Rheum. 2008 May 15;59(5):665-9.

Validation of the Health Assessment Questionnaire disability index in patients
with gout.

Alvarez-Hernández E, Peláez-Ballestas I, Vázquez-Mellado J, Terán-Estrada L,
Bernard-Medina AG, Espinoza J, Aceves-Avila FJ, Goycochea-Robles MV, Garza M,
Ventura L, Burgos-Vargas R; REUMAIMPACT.

Department of Rheumatology, Hospital General de México, México City, México.

OBJECTIVE: To assess the psychometric properties of the Health Assessment
Questionnaire (HAQ) disability index (DI) in patients with gout. METHODS: This
study was conducted in a multicenter cohort of patients with gout whose data were
collected at baseline (time 0) and 6 months later (time 6). Reliability was
assessed by test-retest reliability (intraclass correlation coefficient [ICC])
and internal consistency (Cronbach's alpha coefficient). Construct validity was
assessed with convergent validity (HAQ DI correlation with Short Form 36 [SF-36])
and discriminative validity (HAQ DI correlation with clinical features).
Sensitivity to change was determined by comparing HAQ DI time 0 versus HAQ DI
time 6 (percentage of change, effect size, smallest real difference [SRD], and
Guyatt's responsiveness index [GRI]). RESULTS: We included 206 patients (96.6%
men, mean +/- SD age and disease duration 56.3 +/- 12.4 years and 9.3 +/- 8.5
years, respectively). Of these, 52.4% had joint pain, 22.8% swelling, 32.5%
reduced joint mobility, and 36.9% tophi. The mean HAQ DI score was 0.59 +/- 0.77 
(95% confidence interval [95% CI] 0.49-0.70). ICC (n = 36, evaluations at
baseline and 5 days later) was 0.76. Cronbach's alphas were 0.91 (95% CI
0.88-0.92, P = 0.000) for the 20 HAQ DI items and 0.93 (95% CI 0.92-0.94, P =
0.000) for the 8 HAQ DI categories. The HAQ DI correlated in predictable ways
with SF-36 subscales and clinical variables, and discriminated between subgroups 
with and without any joint pain, swelling, and tophi. Concerning sensitivity to
change (n = 167), the difference between HAQ DI time 0 and HAQ DI time 6 was 0.31
+/- 0.58 (effect size 0.62, SRD 0.59, and GRI 1.91). DeltaHAQ DI correlated with 
Deltapain (r = 0.349, P = 0.000). CONCLUSION: The HAQ DI is a valid and reliable 
measure of functioning in patients with gout.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 18438898 [PubMed - indexed for MEDLINE]

52: Minerva Med. 2008 Apr;99(2):203-12.

Gout and related morbid conditions: pharmacological and SPA therapy.

Petraccia L, Fraioli A, Liberati G, Lopalco M, Grassi M.

Department of Clinics and Medical Therapy, Umberto I Hospital, University of
Rome, La Sapienza, Rome, Italy.

Gouty arthritis is estimated to be the most frequent manifestation of
inflammatory arthritis in men aged over 40. Hyperuricemia occurs because of both 
exogenous and genetic factors, which are particularly influential in some
populations such as Taiwan aborigines. Current understanding of the disease
etiopathogenesis, its clinical manifestations and the stages of its progression
are presented here. The criteria for a correct diagnosis of the disease are also 
reported, pointing out how to distinguish gout from clinical events of different 
origin but with a very similar symptomatology. A distinction is made between the 
agents used to relieve the acute attack (colchicine, nonsteroidal
anti-inflammatory drugs, corticosteroids) and those used with the purpose of
correcting hyperuricemia and preventing recurrences and complications
(allopurinol, uricosurics). Mecha-nisms of action, administration routes, doses, 
side effects and contraindications of every drug are described. Besides
pharmacological therapy, the importance and the efficacy of spa therapy is
underlined. Finally, perspectives opened by gene therapy are mentioned.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18431328 [PubMed - indexed for MEDLINE]

53: J Clin Rheumatol. 2008 Feb;14(1):41-4.

Theodore Roosevelt's inflammatory rheumatism.

Pinals RS.

Department of Medicine, Division of Rheumatology and Connective Tissue Research, 
UMDNJ-Robert Wood Johnson Medical School, P.O. Box 19, New Brunswick, NJ
08903-0019, USA. pinalsrs@umdnj.edu

Theodore Roosevelt's death at age 60 was probably caused by a pulmonary embolus, 
but it was preceded by a 2 1/2-month illness described as inflammatory
rheumatism. He had intermittent fever and acute arthritis in several joints
leading to hospitalization and enforced bed rest for 6 weeks. The details of his 
illness and its possible etiology are reviewed. Inflammatory rheumatism was a
descriptive term within which several modern diagnoses might be included.
Although it is not possible to identify Roosevelt's illness with any certainty,
it was most compatible with polyarticular gout, although reactive arthritis,
rheumatic fever, and several other diagnoses cannot be ruled out.

Publication Types: 
    Biography
    Case Reports
    Historical Article
    Portraits

Personal Name as Subject: 
    Roosevelt T

PMID: 18431099 [PubMed - indexed for MEDLINE]

54: J Clin Rheumatol. 2008 Feb;14(1):6-11.

Higher therapeutic plasma oxypurinol concentrations might be required for gouty
patients with chronic kidney disease.

Panomvana D, Sripradit S, Angthararak S.

Department of Pharmacy (Clinical), Faculty of Pharmaceutical Sciences,
Chulalongkorn University, Bangkok 10330, Thailand. duangchit.p@chula.ac.th

BACKGROUND: Lower dosages of allopurinol are recommended to avoid toxicity in
gout patients with impaired renal function. This often has resulted in inadequate
control of hyperuricemia. The optimum therapeutic range of plasma oxypurinol
concentrations in gout patients with chronic kidney disease has never been
investigated. This study was performed to examine the relationships between
plasma oxypurinol concentrations and the changes in serum urate level and renal
function after taking a standard dose of allopurinol, 300 mg daily, in gout
patients with renal insufficiency. PATIENTS AND METHODS: The study was conducted 
in 27 gout patients with renal insufficiency in a rheumatology clinic at the
Rajvithi Hospital, Bangkok. Both new and current patients, after they
discontinued allopurinol completely for 4 weeks, were treated with allopurinol
300 mg daily for 6 weeks. Blood samples were collected immediately before and 5
hours after the studied dose had been taken. Serum urate levels and renal
function were recorded before and after the 6 weeks of allopurinol treatments.
RESULTS: Most patients receiving allopurinol 300 mg/d had their plasma oxypurinol
concentrations higher than the proposed therapeutic range for patients with
normal renal function. There were significant relationships between changes in
serum urate level with both trough and fifth-hour oxypurinol concentrations (R = 
0.42, P = 0.002 and R = 0.27, P = 0.007, respectively). Higher plasma oxypurinol 
concentrations resulted in a higher percentage of patients who could meet the
therapeutic treatment goal. No serious side effect and no significantly change in
creatinine clearance were observed indicating that high levels of oxypurinol did 
not appear to relate to higher prevalence of adverse reaction. CONCLUSIONS:
Higher percentages of patients could meet the treatment goal when their plasma
oxypurinol concentrations were higher than the proposed therapeutic range for
patients with normal renal function.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18431090 [PubMed - indexed for MEDLINE]

55: Cochrane Database Syst Rev. 2008 Apr 16;(2):CD005521.

Systemic corticosteroids for acute gout.

Janssens HJ, Lucassen PL, Van de Laar FA, Janssen M, Van de Lisdonk EH.

Transeedijk 62, Lobith, Netherlands, 6915 XZ. h.janssens2@chello.nl

BACKGROUND: Gout is one of the most frequently occurring rheumatic diseases,
worldwide. Given the well-known drawbacks of the regular treatments for acute
gout (non-steroidal anti-inflammatory drugs (NSAIDs), colchicine), systemic
corticosteroids might be safe alternatives. OBJECTIVES: To assess the efficacy
and safety of systemic corticosteroids in the treatment of acute gout in
comparison with placebo, NSAIDs, colchicine, other active drugs, other therapies,
or no therapy. SEARCH STRATEGY: Searches were done in the following electronic
databases: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
Library 2007); MEDLINE (1966 to 2007) through PubMed; EMBASE (1974 to 2007); Web 
of Science (1975 to 2007); LILACS (1986 to 2007); and databases of ongoing trials
(up to April 2007). SELECTION CRITERIA: Randomized controlled trials and
controlled clinical trials investigating the use of systemic corticosteroids in
the treatment of acute gout were included. DATA COLLECTION AND ANALYSIS: Two
review authors decided independently which trials to include. The same review
authors also collected the data in a standardised form and assessed the
methodological quality of the trial using validated criteria. When possible,
continuous and dichotomous data were summarised statistically. MAIN RESULTS:
Three head to head trials involving 148 patients (74 systemic corticosteroids; 74
comparator drugs) were included. Placebo-controlled trials were not found. In the
studies, different kinds of systemic corticosteroids and different kinds of
control drugs were used, both administered in different routes. Intramuscular
triamcinolone acetonide was compared respectively to oral indomethacine, and
intramuscular adrenocorticotropic hormone (ACTH); oral prednisolone (together
with a single intramuscular diclophenac injection) was compared to oral
indomethacine (together with a single placebo injection). Outcome measurements
varied: average number of days until total relief of signs, mean decrease of pain
per unit of time in mm on a visual analogue scale (VAS) - during rest and
activity. In the triamcinolone-indomethacine trial the clinical joint status was 
used as an additional outcome. Clinically relevant differences between the
studied systemic corticosteroids and the comparator drugs were not found;
important safety problems attributable to the used corticosteroids were not
reported. The quality of the three studies was graded as very low to moderate.
Statistical pooling of results was not possible. AUTHORS' CONCLUSIONS: There is
inconclusive evidence for the efficacy and effectiveness of systemic
corticosteroids in the treatment of acute gout. Patients with gout did not report
serious adverse effects from systemic corticosteroids, when used short term.

Publication Types: 
    Meta-Analysis
    Review

PMID: 18425920 [PubMed - indexed for MEDLINE]

56: Intern Med J. 2008 Jun;38(6):388-95. Epub 2008 Apr 14.

Utilization of allopurinol in the Australian community.

Chung Y, Lu CY, Graham GG, Mant A, Day RO.

Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital,
Darlinghurst, NSW 2010, Australia.

BACKGROUND: International data suggest that suboptimal use of allopurinol is
common. Allopurinol dose should be lower in renal impairment, but higher when
gout is not controlled. The aim of the study was to examine trends in the usage
of allopurinol in the Australian community. METHODS: Community dispensing data on
the urate-lowering drugs allopurinol and probenecid were obtained from databases 
kept by Medicare Australia and the Drug Utilization Sub-Committee, for January
1992 to December 2005. RESULTS: Allopurinol comprised 98.4% of all prescriptions 
for urate-lowering drugs dispensed during 2005. Most prescriptions were for
allopurinol 300 mg, but there was a steady shift towards use of allopurinol 100
mg in all states and territories over the period of the study. There were marked 
variations in prescribing rates across the country. New South Wales had the
highest rate of subsidized prescribing for allopurinol 300 mg (39.3 per 1000
population). Tasmania had the highest rate for allopurinol 100 mg (14.3 per 1000 
population), which coincided with an educational programme to decrease
allopurinol dose in patients with renal impairment. Prescribing rates in the
Northern Territory were substantially lower than all other regions, at 10.8 and
3.3 prescriptions per 1000 population for allopurinol 300 and 100 mg,
respectively. CONCLUSION: The increased uptake of allopurinol 100 mg suggests
greater adherence to dosing guidelines and that there is value in educational
programmes to optimize drug usage. Variability in utilization rates across
regions indicates the need for research on factors responsible. Precise
understanding of dosing trends requires access to deidentified, individual dosing
data.

PMID: 18422564 [PubMed - indexed for MEDLINE]

57: J Clin Pharmacol. 2008 Jun;48(6):708-18. Epub 2008 Apr 16.

Population pharmacokinetic and pharmacodynamic analysis of pegloticase in
subjects with hyperuricemia and treatment-failure gout.

Yue CS, Huang W, Alton M, Maroli AN, Waltrip RW, Wright D, Marco MD.

Université de Montréal, Faculté de pharmacie, Pavillon Jean Coutu, 2940 Chemin de
la polytechnique, Montreal, Quebec, H3T 1J4 Canada. corinne.seng.yue@umontreal.ca

Pegloticase is designed to convert urate into the easily excretable allantoin to 
treat hyperuricemia in gout. The aim of this analysis was to describe the
pharmacokinetics and pharmacodynamics of pegloticase in 40 gout patients.
Pegloticase was administered as intravenous infusions every 2 weeks at 4- and
8-mg doses or every 4 weeks at 8- or 12-mg doses for 12 weeks. Serum pegloticase 
concentrations, plasma urate, and serum antibody response were determined.
Population pharmacokinetics and pharmacodynamics analyses were performed. Data
were modeled simultaneously, and covariates were investigated (age, gender, race,
body weight, ideal body weight, and antibody response). The dosing regimens to
maintain uric acid levels below the therapeutic target of 6 mg/dL were then
predicted by the model. The pharmacokinetics were best described by a
1-compartment linear model, while the pharmacodynamics model was fitted as a
direct effect of pegloticase on uric acid concentrations with a suppressive
maximum effect attributed to drug (E(max)) function. Pegloticase suppressed uric 
acid levels up to 83%. Weight only affected clearance and volume of distribution.
No covariates affected pharmacodynamics. Simulation suggests pegloticase
administered at 8 mg every 2 or 4 weeks as 2-hour intravenous infusions will
maintain uric acid levels well under 6 mg/dL.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 18420531 [PubMed - indexed for MEDLINE]

58: J Ethnopharmacol. 2008 May 22;117(3):478-82. Epub 2008 Mar 4.

Pharmacological basis for use of Pistacia integerrima leaves in hyperuricemia and
gout.

Ahmad NS, Farman M, Najmi MH, Mian KB, Hasan A.

College of Medical Sciences, National University of Sciences and Technology,
Rawalpindi 46000, Pakistan. naseemsaud@yahoo.com

ETHNOPHARMACOLOGICAL SIGNIFICANCE: Pistacia integerrima Stew ex. Brandis is an
important component of commonly dispensed traditional dosage forms. We wished to 
determine whether polyphenolic constituents of this plant could be useful in
oxidative stress and have potential to counter hyperuricemia. MATERIAL AND
METHODS: Radical scavenging activity was determined by
1,1-diphenyl-2-picrylhydrazyl (DPPH) and xanthine oxidase (XO) inhibitory
activity assay in vitro. Fructose (FRS) induced hyperuricemic animal model was
used to asses the serum uric acid (UA) lowering effect by plant products.
RESULTS: Ethyl acetate and n-BuOH fractions had the highest DPPH radical
scavenging activity. Fifty percent inhibitory concentration (IC(50)) was 6 and
7.6 microg/ml respectively. It was less than quercetin (IC(50) 0.95 microg/ml)
and ascorbic acid (IC(50) 1.76 microg/ml). Xanthine oxidase inhibitory activity
was comparable between n-BuOH and EtOAc (IC(50) 19 and 20 microg/ml) extracts but
less than quercetin (IC(50) 0.65 microg/ml) and allopurinol (IC(50) 0.10
microg/ml). The antioxidant activity as well as the inhibitory activity towards
the enzyme XO by quercetin-3-O-beta-d-glucopyranoside (5),
kaempferol-3-O-beta-d-glucopyranoside (6),
quercetin-3-O-(6''-O-syringyl)-beta-d-glucopyranoside (7),
kaempferol-3-O-(4''-O-galloyl)-alpha-l-arabinopyranoside (8), rutin (4) together 
with aglycons, quercetin (1), kaempferol (2) and apigenin (3) was promising to
continue in vivo hypouricemic studies. Ethyl acetate extract had dose dependent
UA lowering effect in hyperuricemic mice. This effect was comparable with
quercetin but less than allopurinol. CONCLUSIONS: These findings are encouraging 
to plan clinical studies in hyperuricemic patients.

PMID: 18420362 [PubMed - indexed for MEDLINE]

59: PLoS ONE. 2008 Apr 9;3(4):e1948.

Association of common polymorphisms in GLUT9 gene with gout but not with coronary
artery disease in a large case-control study.

Stark K, Reinhard W, Neureuther K, Wiedmann S, Sedlacek K, Baessler A, Fischer M,
Weber S, Kaess B, Erdmann J, Schunkert H, Hengstenberg C.

Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität Regensburg,
Regensburg, Germany.

BACKGROUND: Serum uric acid (UA) levels have recently been shown to be
genetically influenced by common polymorphisms in the GLUT9 gene in two
genome-wide association analyses of Italian and British populations. Elevated
serum UA levels are often found in conjunction with the metabolic syndrome.
Hyperuricemia is the major risk factor for gout and has been associated with
increased cardiovascular morbidity and mortality. The aim of the present study
was to further elucidate the association of polymorphisms in GLUT9 with gout and 
coronary artery disease (CAD) or myocardial infarction (MI). To test our
hypotheses, we performed two large case-control association analyses of
individuals from the German MI Family Study. METHODS AND FINDINGS: First, 665
patients with gout and 665 healthy controls, which were carefully matched for age
and gender, were genotyped for four single nucleotide polymorphisms (SNPs) within
or near the GLUT9 gene. All four SNPs demonstrated highly significant association
with gout. SNP rs6855911, located within intron 7 of GLUT9, showed the strongest 
signal with a protective effect of the minor allele with an allelic odds ratio of
0.62 (95% confidence interval 0.52-0.75; p = 3.2*10(-7)). Importantly, this
finding was not influenced by adjustment for components of the metabolic syndrome
or intake of diuretics. Secondly, 1,473 cases with severe CAD or MI and 1,241
healthy controls were tested for the same four GLUT9 SNPs. The analyses revealed,
however, no significant association with CAD or with MI. Additional screening of 
genome-wide association data sets showed no signal for CAD or MI within the GLUT9
gene region. CONCLUSION: Thus, our results provide compelling evidence that
common genetic variations within the GLUT9 gene strongly influence the risk for
gout but are unlikely to have a major effect on CAD or MI in a German population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18398472 [PubMed - indexed for MEDLINE]

60: Curr Opin Investig Drugs. 2008 Apr;9(4):422-9.

Pegloticase, a polyethylene glycol conjugate of uricase for the potential
intravenous treatment of gout.

Biggers K, Scheinfeld N.

West Virginia University School of Medicine, Robert C Byrd Health Sciences
Center, Morgantown, WV 26506-9100, USA.

Savient Pharmaceuticals Inc (formerly Bio-Technology General Corp), under license
from Duke University, is developing pegloticase, PEG conjugates of uricase (urate
oxidase), for the potential treatment of gout. The in-life portion of the phase
III trials have been completed.

Publication Types: 
    Review

PMID: 18393109 [PubMed - indexed for MEDLINE]

61: Rheumatology (Oxford). 2008 May;47(5):617-21. Epub 2008 Mar 19.

Associations between gout tophus and polymorphisms 869T/C and -509C/T in
transforming growth factor beta1 gene.

Chang SJ, Chen CJ, Tsai FC, Lai HM, Tsai PC, Tsai MH, Ko YC.

Department of Public Health, Faculty of Medicine, College of Medicine, Kaohsiung 
Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.
changsj@kmu.edu.tw

OBJECTIVES: To investigate the associations between gout tophus and polymorphisms
869T/C and -509C/T in TGF-beta1 gene. METHODS: The polymorphisms 869T/C and
-509C/T were determined in 73 gout patients and 114 healthy controls among male
Taiwanese using the PCR-restriction fragment length polymorphism method. Each
patient was matched with 1-2 controls by age within 1-2 yrs. The tophus number
was measured from all the patients' arms and legs. RESULTS: Neither 869T/C nor
-509C/T showed a significant association between patients and controls in the
proportions of genotypes, allele frequency or dominant and recessive models. The 
mean number of tophi for all patients was 1.53 +/- 3.44, showing a significant
difference in distribution among the genotypes at polymorphism 869T/C (P =
0.006), but not those in polymorphism -509C/T (P > 0.05). Those carrying genotype
CC at polymorphism 869T/C have a mean number of tophi 0.35 (+/- 1.11), which is
significantly lower than those carrying genotype TT (3.73 +/- 4.67; P < 0.05).
Those with genotype TT at polymorphism 869T/C also had 11.06 times the likelihood
of having at least one tophus compared with the genotype CC after adjustment of
hyperuricaemia (95% CI = 1.84, 66.36; P = 0.009). However, except for the tophus 
number, these two polymorphisms did not show any significant association with the
clinical characteristics or biochemical markers. CONCLUSIONS: The polymorphism
869T/C in TGF-beta1 gene has a significant association with the occurrence of
tophus in gout patients.

PMID: 18356176 [PubMed - indexed for MEDLINE]

62: Curr Opin Rheumatol. 2008 Mar;20(2):198-202.

Refractory gout: what is it and what to do about it?

Fels E, Sundy JS.

Departments of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.

PURPOSE OF REVIEW: The purpose of this review is to discuss the defining
characteristics of refractory gout and the pharmacological management of this
problem. RECENT FINDINGS: Refractory gout refers to those patients who have
ongoing symptoms of active disease and cannot maintain a target serum urate less 
than 6 mg/dl. Patients with refractory gout have reduced quality of life,
functional impairment, and joint destruction. Multiple factors contribute to
refractory gout, and they often relate to delayed or insufficient dosing with
allopurinol. Chronic kidney disease imparts a dose limitation on allopurinol that
further impairs the effectiveness of urate-lowering therapy. Febuxostat, a novel 
xanthine oxidase inhibitor, represents a potential alternative to allopurinol in 
refractory gout patients. Uricase, the enzyme that catalyzes conversion of uric
acid into allantoin, is showing promise with its ability to rapidly diminish
serum urate levels. The recently defined role of the NALP3 inflammasome in the
inflammatory phase of gout suggests a potential role for interleukin-1 inhibition
in urate crystal-induced inflammation. SUMMARY: Refractory gout occurs when urate
levels are not adequately controlled. Emerging therapies may improve the clinical
course of patients with recalcitrant disease.

Publication Types: 
    Review

PMID: 18349751 [PubMed - indexed for MEDLINE]

63: Curr Opin Rheumatol. 2008 Mar;20(2):192-7.

Control of renal uric acid excretion and gout.

Taniguchi A, Kamatani N.

Institute of Rneumatology, Tokyo Women's Medical University, 10-22 Kawada-cho,
Shinjuku-ku, Tokyo, Japan. amtanigu@ior.twmu.ac.jp

PURPOSE OF REVIEW: Impaired renal uric acid excretion is the major mechanism of
hyperuricemia in patients with primary gout. This review highlights recent
advances in the knowledge of normal mechanisms of renal uric acid handling and
derangement of these mechanisms in uric acid underexcretion. RECENT FINDINGS: The
discovery of URAT1 has facilitated identification of other molecules potentially 
involved in uric acid transport in the renal tubules. Some of these molecules
show gender differential expression in animal experiments. Sodium-dependent
monocarboxylate cotransporters have been shown to transport lactate and butyrate,
and may have roles in hyperuricemia associated with diabetic ketoacidosis and
alcohol ingestion. Certain polymorphisms in SLC22A12 may be associated with the
development of hyperuricemia or gout, although confirmation is needed. Mechanisms
of hyperuricemia associated with uric acid underexcretion in patients with
familial juvenile hyperuricemic nephropathy also remain to be clarified. Distal
tubular salt wasting and compensatory upregulation of the resorption of sodium
and uric acid in the proximal tubule may explain the hyperuricemia associated
with this disorder. SUMMARY: Much progress has been made in understanding the
mechanisms of renal uric acid handling. Elucidation of the mechanisms of
hyperuricemia in patients with familial juvenile hyperuricemic nephropathy will
shed light on the function of uromodulin, functional impairment of which
eventually results in diminished uric acid excretion.

Publication Types: 
    Review

PMID: 18349750 [PubMed - indexed for MEDLINE]

64: Curr Opin Rheumatol. 2008 Mar;20(2):187-91.

Hyperuricemia, gout and the metabolic syndrome.

Puig JG, Martínez MA.

Vascular Risk Unit, Division of Internal Medicine, La Paz University Hospital,
Paseo de la Castellana 261, Madrid, Spain. jgarciapuig@terra.es

PURPOSE OF REVIEW: The metabolic syndrome is defined by the clustering of a
number of cardiovascular risk factors and entails an increased risk for
cardiovascular disease and mortality from both cardiovascular disease and all
causes. In the present paper, we review the most recent evidence on the
association between hyperuricemia, metabolic syndrome, and cardiovascular
disease. RECENT FINDINGS: Serum urate is frequently elevated in patients with the
metabolic syndrome and increases with the number of components of this condition.
Hyperuricemia has been related to decreased renal uric acid excretion, which may 
be mediated by enhanced proximal tubular sodium reabsorption and
hyperinsulinemia. Recent epidemiologic studies have shed some light on the
prognosis of hyperuricemia. While hyperuricemia appears to show a benign
significance in low cardiovascular risk individuals, it clearly increases
cardiovascular mortality in patients at high cardiovascular disease risk.
SUMMARY: Clinicians should be aware of the presence of metabolic syndrome in
patients with hyperuricemia or gout in order to control its components (high
blood pressure, obesity, etc.) and hence reduce the risk for cardiovascular
disease. Long-term, randomized interventional clinical trials are needed to test 
the hypothesis that urate-lowering therapy can reduce cardiovascular risk in
these patients.

Publication Types: 
    Review

PMID: 18349749 [PubMed - indexed for MEDLINE]

65: Curr Opin Rheumatol. 2008 Mar;20(2):179-86.

Lifestyle and gout.

Hak AE, Choi HK.

Departments of Internal Medicine and Rheumatology, Erasmus MC University Medical 
Center, Rotterdam, The Netherlands.

PURPOSE OF REVIEW: This review summarizes recent epidemiologic research findings 
on gout, and attempts to put them into the context of clinical and public health 
decision-making aimed at prevention and improved management of gout. RECENT
FINDINGS: A large prospective study found that coffee consumption was inversely
associated with risk of gout and that consumption of sugar-sweetened soft drinks 
or fructose was strongly associated with an increased gout risk. Studies based on
the Third National Health and Nutrition Examination Survey (NHANES III) suggest
that these consumptions affect serum uric acid levels parallel to the direction
of gout risk. Furthermore, data from NHANES III show a remarkably high prevalence
of the metabolic syndrome among individuals with gout. Prospective studies found 
an increased risk of myocardial infarction and cardiovascular mortality in gout
patients. SUMMARY: Lifestyle and dietary recommendations for gout patients should
consider other health benefits, since gout is often associated with major chronic
disorders such as the metabolic syndrome and an increased risk for cardiovascular
disease and mortality. In addition to recent dietary recommendations, gout
patients should be advised to limit fructose intake. The inverse link between
coffee and the risk of gout suggests that coffee could be allowed among gout
patients.

Publication Types: 
    Review

PMID: 18349748 [PubMed - indexed for MEDLINE]

66: Curr Opin Rheumatol. 2008 Mar;20(2):173-8.

Establishing outcome domains for evaluating treatment of acute and chronic gout.

Grainger R, Taylor WJ.

Department of Medicine, Wellington School of Medicine & Health Sciences,
University of Otago, Wellington 6242, New Zealand.

PURPOSE OF REVIEW: Novel therapies for gout have recently been developed which
has prompted considerable efforts in defining the relevant outcomes for
measurement in intervention trials of gout. This review summarizes the consensus 
exercises refining domains for measurement and the work of individual groups in
assessment of the validity of measurement tools for these domains. RECENT
FINDINGS: Recent publications have focused on the consensus exercises and
validation studies of measurement tools, particularly in relation to tophus size 
and imaging. SUMMARY: Consensus on potential outcome domains has been achieved,
but measuring these domains requires further validation in observational studies 
and confirmation of relevance from people with gout. Further work is also
required in refining measurements of tophus size and imaging scores. The role of 
a response criteria measure is also yet to be defined, especially in relation to 
reduction in flare frequency, or whether composite criteria are necessary.

Publication Types: 
    Review

PMID: 18349747 [PubMed - indexed for MEDLINE]

67: Curr Opin Rheumatol. 2008 Mar;20(2):167-72.

We can make gout management more successful now.

Becker MA, Chohan S.

Rheumatology Section, Department of Medicine, University of Chicago Pritzker
School of Medicine, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
mbecker@medicine.bsd.uchicago.edu

PURPOSE OF REVIEW: The purpose of this editorial review is to identify and
comment on factors contributing to the current less-than-optimal state of gout
management and to emphasize immediate opportunities to improve management
practices affecting many patients with gout. RECENT FINDINGS: Numerous
publications document deficits in the current management and clinical outcomes of
gout despite detailed understanding of the pathogenesis and pathophysiology of
the disorder, the ability to establish the diagnosis with certainty, and the
likely effectiveness, for most patients, of available lifestyle and
pharmacological interventions. Among impediments to successful gout management
are diagnostic inaccuracy; a paucity of validated management recommendations to
guide care providers; incomplete patient education about gout and the aims and
modalities of management; suboptimal patient adherence, even to demonstrably
effective therapeutic recommendations; comorbidities and drug interferences that 
complicate treatment of gout; patient groups at special risk for progression to
chronic tophaceous gout; and limited urate-lowering alternatives. SUMMARY: Recent
publication of evidence-based recommendations for the diagnosis and management of
gout and the impending availability of new urate-lowering agents suggest that
this is an opportune time to initiate professional and patient education efforts 
toward improved management of this increasingly common disorder.

Publication Types: 
    Review

PMID: 18349746 [PubMed - indexed for MEDLINE]

68: Med Decis Making. 2008 Jul-Aug;28(4):606-13. Epub 2008 Mar 18.

Willingness to pay for a cure in patients with chronic gout.

Khanna D, Ahmed M, Yontz D, Ginsburg SS, Tsevat J.

Division of Immunology, Department of Internal Medicine, University of Cincinnati
College of Medicine, Cincinnati, OH, USA. dkhanna@mednet.ucla.edu

INTRODUCTION: Gout is a chronic painful inflammatory arthritis. The authors
interviewed patients with chronic stable gout to assess their hypothetical
willingness to pay (WTP) to be cured of their gout. Patients and METHODS:
Patients with gout were asked how much money they would be willing to pay every
month out of pocket or as a co-pay to cure their gout. To assess determinants of 
WTP amounts, the authors performed stepwise multivariable linear regression
analysis, controlling for demographics, health status, and relative concern about
gout. RESULTS: Of the 78 patients, 70 (90%) were male, 54 (69%) were Caucasian,
21 (27%) were African American, and 32 (41%) had annual incomes < $25,000. The
median WTP amount was $25 ($0, $75) per month, and the mean (s) was $52 ($74) per
month (range, $0-$350); 23 (30%) patients were unwilling to pay any amount.
Patients who rated their gout as their top health concern were willing to pay a
median of $63 ($25, $100) per month. In multivariable analysis, gout as the top
health concern, greater frequency of gouty attacks over the past 1 y, and younger
age were significantly associated with WTP amounts (R(2) =0:19 ). CONCLUSION:
Many patients with chronic gout would be willing to pay money every month in
perpetuity to be cured of their gout. Younger patients, patients whose main
health concern is gout, and patients with frequent attacks are willing to pay the
most.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18349436 [PubMed - indexed for MEDLINE]

69: J Manag Care Pharm. 2008 Mar;14(2):164-75.

Disease-related and all-cause health care costs of elderly patients with gout.

Wu EQ, Patel PA, Yu AP, Mody RR, Cahill KE, Tang J, Krishnan E.

Analysis Group, 111 Huntington Ave, 10th Fl., Boston, MA 02199,USA.
ewu@analysisgroup

BACKGROUND: Gout is a common cause of inflammatory arthritis in the United
States, and its prevalence has increased in recent decades, especially among
older adults. Older adults with gout are of particular interest because they tend
to experience higher rates of tophi, an advanced stage of gout, than do younger
patients. OBJECTIVE: For older adults with gout to (1) assess health care
utilization and costs from a third-party payer perspective; (2) evaluate health
care costs related to tophi; and (3) explore the relationship between elevated
serum uric acid (UA) level, an indicator of disease control, and health care
utilization. METHODS: Data were extracted from the Integrated Healthcare
Information Services (IHCIS) claims database (1999-2005), which includes
approximately 40 private health plans in the United States for approximately 13
million beneficiaries, about 4% of whom are aged 65 years or older. Patients were
included in the study if they: (1) had 2 diagnoses of gout (International
Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code
of 274.xx) on separate medical claims or 1 gout diagnosis plus at least 1
gout-related pharmacy claim (i.e., allopurinol, probenecid, colchicines, or
sulfinpyrazone); (2) were at least 65 years old at the first diagnosis date
(study index date); and (3) had 1 year of continuous eligibility both before and 
after the study index date. A comparison sample of elderly members without gout
was selected using a 1:1 match to gout patients based on age, gender, and
geographic region. Individuals in the comparison group also had 1 year of
continuous eligibility both before and after the study index date, defined as the
same index date as the respective matched gout patient. Patients with possible
tophi were identified from at least 1 medical claim with an ICD-9-CM code 274.8x 
(274.81=gouty tophi of the ear; 274.82 = gouty tophi of other sites except ear;
274.89 = gout with other specified manifestations) during the 12-month study
period following the study index date. Additionally, a subgroup of gout patients 
with at least 1 serum UA measure was selected. Patients were divided into 3
groups according to their serum UA level on the earliest test date (serum UA
index date): low (< 6 mg per dL), moderate-high (6-8.99 mg per dL), and very high
(> or = 9 mg per dL). Health care utilization was categorized into inpatient
services, outpatient services, emergency room services, other medical services,
and use of prescription drugs. Medical services were classified by the place of
service indicated in the claim. Medical services costs and pharmacy costs were
defined as the amount paid to the provider plus member cost share (e.g.,
deductible, copayment). Two types of costs were assessed in the analysis: total
all-cause health care costs and gout-related costs, defined as costs associated
with a claim with a primary or secondary diagnosis of gout (ICD-9-CM code
274.xx). Differences in total all-cause health care costs were calculated by
comparing (1) gout patients and gout-free members during the 12-month period
following the study index date; (2) gout patients with and without tophi during
the 12-month period following the study index date; and (3) gout patients across 
the 3 serum UA categories during the 12-month period following the serum UA index
date. Multivariate regression analyses were used to control for patients'
baseline demographics, prior comorbidities indicated by the Deyo-Charlson
Comorbidity Index, and number of medications used during the 12 months prior to
the study index date. RESULTS: Over the 7 years of claims data through 2005,
there were 11,935 gout patients aged 65 years or older. The sample had an average
age of 71.4 years and was predominantly male (73.5%). In the 12 months following 
the study index date, the mean unadjusted per-patient gout-related health care
cost was $876 (standard deviation $3,373) in 2005 dollars, 5.9% of the total
all-cause health care cost of $14,734 (SD $27,401) for gout patients. Unadjusted 
total 12-month all-cause health care cost for the gout-free members was $9,219
(SD $20,186). After statistical adjustment for comorbidities, the difference in
total 12-month all-cause health care costs between gout patients and gout-free
members was $3,038 (P < 0.001). A diagnosis suggesting possible tophi was found
in 2.0% (n = 240) of gout patients in the sample. After statistical adjustment
for comorbidities, the difference in total 12-month all-cause health care costs
between gout patients with and without tophi was $5,501 (P < 0.001), and the
difference in total adjusted 12-month gout-related costs between patients with
and without tophi was $1,710 (P < 0.001). Among the 2,237 (18.7%) patients with
at least 1 serum UA measure, 28.3% had a low serum UA level, 52.4% had a
moderate-high serum UA level, and 19.3% had a very high serum UA level. For
patients with low, moderate-high, and very high serum UA levels,
regression-adjusted gout-related costs in the 12 months following the serum UA
index date represented, respectively, 2.9%, 2.7%, and 3.9% of total
regression-adjusted health care costs. The group with a very high serum UA level 
had significantly higher regression-adjusted total 12-month all-cause health care
costs and gout-related costs compared with those with a low serum UA level
($3,103 and $276 higher, respectively). CONCLUSIONS: Elderly patients with a
diagnosis of gout have higher all-cause health care utilization and costs
compared with matched elderly patients without a diagnosis of gout. Gout-related 
costs represent about 6% of total health care costs in elderly patients with
gout. Very high serum UA levels (i.e., > or = 9 mg per dL) and diagnoses
suggesting possible tophi are associated with increased utilization and costs in 
elderly gout patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18331118 [PubMed - indexed for MEDLINE]

70: Nat Genet. 2008 Apr;40(4):437-42. Epub 2008 Mar 9.

SLC2A9 is a newly identified urate transporter influencing serum urate
concentration, urate excretion and gout.

Vitart V, Rudan I, Hayward C, Gray NK, Floyd J, Palmer CN, Knott SA, Kolcic I,
Polasek O, Graessler J, Wilson JF, Marinaki A, Riches PL, Shu X, Janicijevic B,
Smolej-Narancic N, Gorgoni B, Morgan J, Campbell S, Biloglav Z, Barac-Lauc L,
Pericic M, Klaric IM, Zgaga L, Skaric-Juric T, Wild SH, Richardson WA, Hohenstein
P, Kimber CH, Tenesa A, Donnelly LA, Fairbanks LD, Aringer M, McKeigue PM,
Ralston SH, Morris AD, Rudan P, Hastie ND, Campbell H, Wright AF.

MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK.

Uric acid is the end product of purine metabolism in humans and great apes, which
have lost hepatic uricase activity, leading to uniquely high serum uric acid
concentrations (200-500 microM) compared with other mammals (3-120 microM). About
70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human
population, impaired renal excretion leads to hyperuricemia. About 10% of people 
with hyperuricemia develop gout, an inflammatory arthritis that results from
deposition of monosodium urate crystals in the joint. We have identified genetic 
variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance
in serum uric acid concentrations, following a genome-wide association scan in a 
Croatian population sample. SLC2A9 variants were also associated with low
fractional excretion of uric acid and/or gout in UK, Croatian and German
population samples. SLC2A9 is a known fructose transporter, and we now show that 
it has strong uric acid transport activity in Xenopus laevis oocytes.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18327257 [PubMed - indexed for MEDLINE]

71: Nat Genet. 2008 Apr;40(4):430-6. Epub 2008 Mar 9.

SLC2A9 influences uric acid concentrations with pronounced sex-specific effects.

Döring A, Gieger C, Mehta D, Gohlke H, Prokisch H, Coassin S, Fischer G, Henke K,
Klopp N, Kronenberg F, Paulweber B, Pfeufer A, Rosskopf D, Völzke H, Illig T,
Meitinger T, Wichmann HE, Meisinger C.

Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for 
Environmental Health, 85764 Neuherberg, Germany.

Serum uric acid concentrations are correlated with gout and clinical entities
such as cardiovascular disease and diabetes. In the genome-wide association study
KORA (Kooperative Gesundheitsforschung in der Region Augsburg) F3 500K (n =
1,644), the most significant SNPs associated with uric acid concentrations mapped
within introns 4 and 6 of SLC2A9, a gene encoding a putative hexose transporter
(effects: -0.23 to -0.36 mg/dl per copy of the minor allele). We replicated these
findings in three independent samples from Germany (KORA S4 and SHIP (Study of
Health in Pomerania)) and Austria (SAPHIR; Salzburg Atherosclerosis Prevention
Program in Subjects at High Individual Risk), with P values ranging from 1.2 x
10(-8) to 1.0 x 10(-32). Analysis of whole blood RNA expression profiles from a
KORA F3 500K subgroup (n = 117) showed a significant association between the
SLC2A9 isoform 2 and urate concentrations. The SLC2A9 genotypes also showed
significant association with self-reported gout. The proportion of the variance
of serum uric acid concentrations explained by genotypes was about 1.2% in men
and 6% in women, and the percentage accounted for by expression levels was 3.5%
in men and 15% in women.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18327256 [PubMed - indexed for MEDLINE]

72: Drugs. 2008;68(4):407-15.

Overview of the management of acute gout and the role of adrenocorticotropic
hormone.

Schlesinger N.

Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, 
New Jersey 08903-0019, USA. schlesna@umdnj.edu

It is important to distinguish between therapy used to reduce acute inflammation 
in gout and therapy used to manage hyperuricaemia in patients with chronic gouty 
arthritis. This article discusses treatments for acute gout, emphasizing the use 
of corticotrophin (adrenocorticotropic hormone; ACTH) and the evidence on which
we base our treatment of acute gout. There are no formal guidelines for the
treatment of acute gout and only a few randomized controlled trials have been
conducted to evaluate the efficacy of the various treatments for acute gout. The 
options available for the treatment of acute attacks of gout are NSAIDs,
colchicine, corticosteroids, corticotropin and intra-articular corticosteroids.
Most rheumatologists practicing in the US use combination therapy to treat acute 
gout, a practice that merits study. In a patient without complications, NSAIDs
are the preferred therapy. The most important determinant of therapeutic success 
is not which NSAID is chosen, but rather how soon NSAID therapy is initiated.
Exciting new research shows that corticotropin acts peripherally by activation of
the melanocortin type 3 receptor, and this could be responsible, at least in
part, for its efficacy in acute gout. Hopefully, this will lead to renewed
interest in corticotropin as a treatment for acute gout.

Publication Types: 
    Review

PMID: 18318560 [PubMed - indexed for MEDLINE]

73: Minerva Med. 2007 Dec;98(6):759-67.

Diagnosis of gout.

Schlesinger N.

Division of Rheumatology, Department of Medicine, UMDNJ-Robert Wood Johnson
Medical School, One Robert Wood Johnson Pl., New Brunswick, NJ 08903-0019, USA
schlesna@umdnj.edu

Acute gouty arthritis typically presents with rapid development of severe joint
pain, swelling, and tenderness that reaches its maximum within just 6-12 h,
especially with overlying erythema, most classically in the first
metatarsophalangeal joint. Demonstrating the presence of monosodium urate (MSU)
crystals in the joint fluid or tophus has been the gold standard for the
diagnosis of gout. However, many physicians do not perform synovial fluid
analysis. In the absence of demonstrating the presence of MSU crystals in
aspirated joint fluid or tophus clinical, radiological and laboratory criteria
are helpful. This paper presents an overview of the various classification
criteria, clinical presentations, laboratory and radiological studies needed to
make the diagnosis of gout.

Publication Types: 
    Review

PMID: 18299687 [PubMed - indexed for MEDLINE]

74: N Z Med J. 2007 Nov 9;120(1265):U2808.

Colchicine prescribing and safety monitoring in patients with gout.

Ly J, Gow P, Dalbeth N.

Department of Rheumatology, Middlemore Hospital, Otahuhu, Auckland.
JasonLy@adhb.govt.nz

AIM: To assess current colchicine prescribing and safety monitoring in patients
with gout. METHODS: Colchicine dosing was analysed by chart review of 50
consecutive patients presenting to Middlemore Hospital (South Auckland, New
Zealand) with acute gout. The dose of colchicine was compared with the New
Zealand Rheumatology Association (NZRA) consensus statement on colchicine use for
acute gout. Safety monitoring was analysed by chart review of a separate group of
50 patients attending rheumatology clinics on long-term prophylactic colchicine
and with renal impairment (creatinine > or = 0.17 mmol/L or creatinine clearance 
< or =0.83 ml/sec). Monitoring of creatine kinase (CK) and full blood count (FBC)
was compared with published quality of care indicators regarding safety
monitoring of colchicine. Risk factors for colchicine toxicity were recorded; age
>75 years, statin use, renal transplant, haemodialysis, and renal impairment.
RESULTS: Forty-eight (96%) patients treated for acute gout received colchicine at
doses < or =2.5 mg/24 hours, in accordance with the NZRA statement. In this
group, 60% had at least one risk factor for colchicine toxicity. For the
long-term prophylactic colchicine treatment group, 76% had CK and FBC monitoring 
in accordance with the quality of care indicator. Additional risk factors for
colchicine toxicity were present in 58% of patients on long-term colchicine.
Laboratory monitoring identified colchicine-related adverse drug reaction in one 
patient. CONCLUSIONS: Current prescribing of colchicine for acute gout is in
accordance with the NZRA consensus statement. For long-term colchicine use, there
is reasonable adherence to the quality of care indicator for safety monitoring.
These patients are at high risk for toxicity, and safety monitoring has an
acceptable yield.

PMID: 18264188 [PubMed - indexed for MEDLINE]

75: Br J Pharmacol. 2008 Mar;153(6):1288-95. Epub 2008 Feb 11.

Colchicine suppresses neutrophil superoxide production in a murine model of gouty
arthritis: a rationale for use of low-dose colchicine.

Chia EW, Grainger R, Harper JL.

Malaghan Institute of Medical Research, Wellington, New Zealand.

BACKGROUND AND PURPOSE: When used to treat gouty arthritis, colchicine is
believed to work by inhibiting microtubule-dependent cell infiltration. However, 
in vitro, colchicine also reduces monosodium urate (MSU)-induced superoxide
production by neutrophils. Our study aimed to compare the effects of colchicine
on neutrophil superoxide production and infiltration in an in vivo model of acute
gouty inflammation. EXPERIMENTAL APPROACH: In vitro: Human and murine peritoneal 
neutrophils were incubated with MSU with and without colchicine, and superoxide
production was measured. In vivo: Mice were treated with colchicine followed by
an intraperitoneal injection of MSU to induce acute inflammation. After 4h, the
peritoneal cells were recovered to measure superoxide production and neutrophil
infiltration. Sera were tested for liver and renal toxicity. KEY RESULTS:
Colchicine dose-dependently inhibited MSU-induced superoxide production by both
human and murine neutrophils in vitro. Oral colchicine inhibited MSU-induced
superoxide production by neutrophils in vivo at doses 100 times lower than those 
required to inhibit neutrophil infiltration and without acute liver or renal
toxicity. Neutrophils treated with colchicine in vivo still produced superoxide
in response to another stimulus, 4-beta-phorbol-12-myristate-13-acetate.
CONCLUSIONS AND IMPLICATIONS: These results show a beneficial effect of
colchicine for the treatment of MSU-induced superoxide production in vivo at
sub-toxic doses without compromising superoxide production by other physiological
processes. This is the first in vivo data to provide a biological rationale that 
supports the implementation of low dose, non-toxic, colchicine therapy for the
treatment of gouty arthritis.

Publication Types: 
    Comparative Study
    In Vitro
    Research Support, Non-U.S. Gov't

PMID: 18264123 [PubMed - indexed for MEDLINE]

76: J Rheumatol. 2008 Mar;35(3):498-501. Epub 2008 Feb 1.

Gout in ambulatory care settings in the United States.

Krishnan E, Lienesch D, Kwoh CK.

Division of Rheumatology, Department of Medicine, University of Pittsburgh School
of Medicine, Pittsburgh, Pennsylvania 15261, USA. Arthritis.MD@gmail.com

OBJECTIVE: To describe the ambulatory care utilization by patients with gouty
arthritis (gout) in the United States using a nationally representative sample.
METHODS: A cross-sectional survey design based on the ambulatory care data from
the 2002 US National Ambulatory Medical Care Survey and National Hospital
Ambulatory Medical Care Survey was used to examine the ambulatory care burden for
gout, the characteristics of gout patients, the types of providers who see gout
patients, and prescribing patterns associated with the management of gout.
Weighted analyses were performed to estimate the effect of age, sex, and
ethnicity on the association with gout and prescription of allopurinol. RESULTS: 
Of the 973 million ambulatory care visits in the United States, 3.9 million were 
for gout. The majority of visits were for men. The average age for men with gout 
was lower than that for women with gout (65 vs 70 years of age). Over two-thirds 
of these gout visits were attended to by primary care providers, whereas visits
to rheumatologists constituted only a very small proportion of these visits
(1.3%). There were 2.8 million prescriptions for allopurinol, 700,000
prescriptions for nonsteroidal antiinflammatory drugs, 381,000 prescriptions for 
colchicine, and 341,000 prescriptions for prednisone. After adjusting for age and
sex, Asians were 2.7 times more likely than Caucasians to have a gout visit. Yet 
these patients had lower probability of receiving allopurinol (odds ratio 0.04,
95% confidence interval 0.01-0.27). CONCLUSION: The majority of patients with
gout are seen by generalist physicians. Asian ethnicity is associated with higher
number of visits for gout, but a lower frequency of allopurinol treatment.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18260174 [PubMed - indexed for MEDLINE]

77: Ann Rheum Dis. 2009 Jan;68(1):51-6. Epub 2008 Feb 4.

Efficacy and tolerability of urate-lowering drugs in gout: a randomised
controlled trial of benzbromarone versus probenecid after failure of allopurinol.

Reinders MK, van Roon EN, Jansen TL, Delsing J, Griep EN, Hoekstra M, van de Laar
MA, Brouwers JR.

Department of Clinical Pharmacy and Pharmacology, Medisch Centrum Leeuwarden,
Leeuwarden, The Netherlands. m.reinders@atriummc.nl

OBJECTIVES: To investigate the efficacy and tolerability of allopurinol as the
first-choice antihyperuricaemic treatment for gout, and compare the efficacy and 
tolerability of benzbromarone and probenecid as second-choice treatment. METHODS:
Prospective, multicentre, open-label, two-stage randomised controlled trial in
gout patients with normal renal function. Enrolled patients were given 300 mg
allopurinol for 2 months (stage 1). Those patients who could not tolerate
allopurinol or who did not attain the target serum urate concentration (sUr) <
or=0.30 mmol/l (5.0 mg/dl), which was defined as successful, were randomised to
benzbromarone 200 mg/day or probenecid 2 g/day for another 2 months (stage 2).
RESULTS: 96 patients were enrolled in stage 1. 82 patients (85%) were eligible
for the analysis at the end of stage 1: there was a mean (SD) decrease in sUr
concentration of 35 (11)% from baseline; 20 patients (24%) attained target sUr < 
or=0.30 mmol/l; and 9 patients (11%) stopped allopurinol because of adverse drug 
reactions. 62 patients were enrolled in stage 2. 27 patients received
benzbromarone (3 patients not eligible for analysis) and 35 received probenecid
(4 patients not eligible for analysis). Treatment with benzbromarone was
successful in 22/24 patients (92%) and with probenecid in 20/31 patients (65%) (p
= 0.03 compared with benzbromarone). Compared with baseline values, there was a
mean (SD) decrease of sUr concentration of 64 (9)% with benzbromarone and 50 (7)%
with probenecid (p<0.001). CONCLUSION: This study showed that allopurinol 300
mg/day has a poor efficacy and tolerability profile when used to attain a
biochemical predefined target level of sUr < or =0.30 mmol/l, following 2 months 
of treatment. In stage 2, benzbromarone 200 mg/day was more effective and better 
tolerated than probenecid 2 g/day.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 18250112 [PubMed - indexed for MEDLINE]

78: BMJ. 2008 Feb 9;336(7639):309-12. Epub 2008 Jan 31.

Comment in:
    BMJ. 2008 Feb 9;336(7639):285-6.

Soft drinks, fructose consumption, and the risk of gout in men: prospective
cohort study.

Choi HK, Curhan G.

Arthritis Research Centre of Canada, Department of Medicine, Vancouver General
Hospital, University of British Columbia, Vancouver, BC V5Z 1L7, Canada.

OBJECTIVE: To examine the relation between intake of sugar sweetened soft drinks 
and fructose and the risk of incident gout in men. DESIGN: Prospective cohort
over 12 years. SETTING: Health professionals follow-up study. PARTICIPANTS: 46
393 men with no history of gout at baseline who provided information on intake of
soft drinks and fructose through validated food frequency questionnaires. MAIN
OUTCOME MEASURE: Incident cases of gout meeting the American College of
Rheumatology survey criteria for gout. RESULTS: During the 12 years of follow-up 
755 confirmed incident cases of gout were reported. Increasing intake of sugar
sweetened soft drinks was associated with an increasing risk of gout. Compared
with consumption of less than one serving of sugar sweetened soft drinks a month 
the multivariate relative risk of gout for 5-6 servings a week was 1.29 (95%
confidence interval 1.00 to 1.68), for one serving a day was 1.45 (1.02 to 2.08),
and for two or more servings a day was 1.85 (1.08 to 3.16; P for trend=0.002).
Diet soft drinks were not associated with risk of gout (P for trend=0.99). The
multivariate relative risk of gout according to increasing fifths of fructose
intake were 1.00, 1.29, 1.41, 1.84, and 2.02 (1.49 to 2.75; P for trend <0.001). 
Other major contributors to fructose intake such as total fruit juice or fructose
rich fruits (apples and oranges) were also associated with a higher risk of gout 
(P values for trend <0.05). CONCLUSIONS: Prospective data suggest that
consumption of sugar sweetened soft drinks and fructose is strongly associated
with an increased risk of gout in men. Furthermore, fructose rich fruits and
fruit juices may also increase the risk. Diet soft drinks were not associated
with the risk of gout.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18244959 [PubMed - indexed for MEDLINE]

79: Chin J Integr Med. 2008 Mar;14(1):17-22.

Randomized and controlled clinical study of modified prescriptions of Simiao Pill
in the treatment of acute gouty arthritis.

Shi XD, Li GC, Qian ZX, Jin ZQ, Song Y.

China Academy of Chinese Medical Sciences, Beijing, China. shixinde06@163.com

OBJECTIVE: To investigate the compatibility of a modified prescription of Simiao 
Pill in the treatment of acute gouty arthritis and to verify the clinical
efficacy and safety of the drug through a clinical trial. METHODS: A randomized
and controlled clinical trial was designed based on clinical epidemiological
principles. A total of 107 patients with acute gouty arthritis were enrolled and 
randomly assigned to four groups. The first group (Group I) included 27 patients 
taking gout prescription I; the second group (Group II) included 27 patients
taking gout prescription II; the third group (Group III) included 28 patients
taking gout prescription III; and the fourth group (control group) included 25
patients taking indomethacin and Benzobromarone as a control group. The duration 
of the treatment in all 4 groups was two weeks. After the treatment, the index of
blood uric acid, blood leukocyte count, score of clinical symptoms, etc. were
observed and measured. RESULTS: The total clinical effective rate of the three
different modified prescriptions of the Simiao Pill was above 96%, significantly 
superior to that of the control group (68%, P<0.05). In terms of the improvement 
of main symptoms, the scores of four symptoms in all TCM treatment and control
groups decreased after treatment, with statistically significant differences
(P<0.05). Moreover, the scores markedly fell more so in the three Chinese herb
groups than in the control group, and especially in Group III (P<0.05). There was
a statistically significant difference in blood uric acid values before and after
the treatment in the same group but no significant inter-group difference was
seen. CONCLUSION: The modified prescriptions, based on the clinical research,
clinical experience and traditional Chinese medicine theory, did show a better
effect than Western medicine in this clinical study. Moreover, the prescriptions 
were precise, with the herbs inexpensive and readily available. The patients had 
good compliance with less adverse reactions noted. The modified prescription has 
a favorable prospect for future development and is worthy of further blind trials
with larger samples.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18219456 [PubMed - indexed for MEDLINE]

80: J Am Osteopath Assoc. 2007 Dec;107(12):554-6.

Comment in:
    J Am Osteopath Assoc. 2008 Jul;108(7):351-2; author reply 352-3.    J Am Osteopath Assoc. 2008 Jul;108(7):352; author reply 352-3.

Tophaceous gout in a patient with rheumatoid arthritis.

Baker DL, Stroup JS, Gilstrap CA.

Center for Health Sciences at the Oklahoma State University in Tulsa, Tulsa, OK, 
USA.

Chronic gout and rheumatoid arthritis are common medical manifestations with
debilitating effects on patients. However, these conditions are not typically
identified concomitantly and can be hard to distinguish from one another. We
report a rare case of a 50-year-old white woman with a history of chronic gout
and rheumatoid arthritis who presented with intradermal tophaceous gout. Physical
examination and laboratory results are described.

Publication Types: 
    Case Reports

PMID: 18178765 [PubMed - indexed for MEDLINE]

81: Ann Rheum Dis. 2008 Sep;67(9):1310-6. Epub 2008 Jan 4.

Gout is associated with more comorbidities, poorer health-related quality of life
and higher healthcare utilisation in US veterans.

Singh JA, Strand V.

Minneapolis VA Medical Center, Rheumatology (111R), One Veteran's Drive,
Minneapolis, MN 55417, USA. Jasvinder.Singh@va.gov

OBJECTIVE: To better understand the impact of gout on functional status,
health-related quality of life (HRQoL), mortality and healthcare utilisation in
US veterans. METHODS: All veterans seen in Veterans Integrated Service Network-13
from 1 October 1996 to 31 March 1998 received mailed surveys asking about
demographic characteristics; performance of activities of daily living and HRQoL 
by Short Form-36 (SF-36) for Veterans. Administrative data included demographics;
inpatient/outpatient healthcare utilisation; ICD-9 codes for gout, medical
comorbidities and arthritis excluding gout-"arthritic comorbidity" and 1-year
mortality. Multivariable estimates compared results between veterans with/without
gout using least means squared. RESULTS: SUBJECTS: with gout were significantly
older, retired, not married, current non-smokers, with more comorbidities.
Multivariable-adjusted bodily pain was somewhat worse (49.7 vs 47.1, p<0.01) and 
mental health (66.7 vs 68.6, p<0.01) domain scores somewhat better in patients
with gout, both differences significant but not clinically meaningful (less than 
threshold of 5-10 points); other SF-36 domain and summary scores and functional
limitations were similar. Medical or arthritic comorbidities predicted
clinically/statistically lower adjusted scores in all SF-36 domains and physical 
domains (physical component summary), respectively. Patients with gout had
significantly more annual primary care visits (3.5 vs 2.7, p<0.001) and
admissions to hospital (18.3% vs 15.1%, p<0.01), fewer mental health visits
(10.1% vs 13.7%, p<0.01) and similar mortality (2.6% vs 2.2%, p = 0.23).
CONCLUSIONS: Gout is independently associated with higher medical and arthritic
comorbidity, primary care and inpatient utilisation. Poorer HRQoL, functional
limitation and higher mortality noted in univariate analyses in patients with
gout were attributable to higher comorbidity and sociodemographic
characteristics.

Publication Types: 
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 18178692 [PubMed - indexed for MEDLINE]

82: Curr Pain Headache Rep. 2007 Dec;11(6):440-6.

Update on gout: pathophysiology and potential treatments.

Abeles AM, Park JY, Pillinger MH, Cronstein BN.

Division of Rheumatology, Medical Arts and Research Building, 263 Farmington
Avenue, Farmington, CT 06030, USA. aabeles@uchs.edu

After several decades of senescence, the twin fields of hyperuricemia and gout
have again regained attention in both the scientific and clinical spheres, and
this review highlights several recent advancements. Specifically, we review newly
discovered mechanisms of uric acid-induced inflammation, uric acid's putative
role as a "danger signal" in innate immunity, the possible link between
hyperuricemia and cardiovascular disease, and evolutionary evidence suggesting
that hyperuricemia conferred a survival advantage in primates (when the gene for 
uricase was lost) several million years ago. Finally, we provide an overview of
the current approach to gout, as well as what treatments are on the horizon.

Publication Types: 
    Review

PMID: 18173979 [PubMed - indexed for MEDLINE]

83: J Orthop Surg (Hong Kong). 2007 Dec;15(3):384-5.

Gouty synovitis after total knee arthroplasty: a case report.

Crawford L, Kumar A, Shepard GJ.

Department of Orthopaedics, Royal Bolton Hospital, Farnworth, Bolton, United
Kingdom.

We report a case of acute gouty synovitis after total knee arthroplasty (TKA) in 
a patient with no history of gout. The diagnosis was confirmed by the presence of
urate crystals in the synovial fluid. Acute gouty synovitis, though rare, should 
be considered in the differential diagnosis of an inflammed knee after TKA to
avoid unnecessary surgical revision.

Publication Types: 
    Case Reports

PMID: 18162693 [PubMed - indexed for MEDLINE]

84: Surg Obes Relat Dis. 2008 Jan-Feb;4(1):11-3. Epub 2007 Dec 11.

Comment in:
    Surg Obes Relat Dis. 2008 Jan-Feb;4(1):14-5.

Gouty attacks occur frequently in postoperative gastric bypass patients.

Friedman JE, Dallal RM, Lord JL.

Sacred Heart Institute for Surgical Weight Loss, Pensacola, Florida 32503, USA.

BACKGROUND: Both obesity and surgery are known risk factors for instigating gouty
attacks. We describe the incidence and management of postoperative gouty attacks 
after bariatric surgery. METHODS: We performed a retrospective,
multi-institutional review of 411 consecutive laparoscopic gastric bypass
patients and identified all patients with postoperative gouty attacks. RESULTS:
Of the 411 patients reviewed, 21 (5.1%) had had a previous diagnosis of gout. Of 
these 21 patients, 7 (33.3%) had had an acute attack postoperatively. No patient 
who had never had a preoperative episode developed gout. In 4 of the 7 (57.1%)
patients, the attack was severe enough to require treatment with corticosteroids.
Monoarticular attacks occurred in 5 (71.4%) of the 7 patients, and polyarticular 
attacks occurred in 2 (28.6%). The joints involved included the toes, ankles, and
wrists. One patient presented with cervical gout and developed polyarticular gout
that required a significant rehabilitation stay. CONCLUSION: The morbidity of
postoperative gouty attacks in bariatric surgery patients is significant.
Patients with a history of gout should given prophylactic treatment and closely
monitored.

Publication Types: 
    Multicenter Study

PMID: 18065292 [PubMed - indexed for MEDLINE]

85: Vascul Pharmacol. 2008 Jan;48(1):14-20. Epub 2007 Nov 13.

An in vivo and in vitro potential of Indian ayurvedic herbal formulation Triphala
on experimental gouty arthritis in mice.

Sabina EP, Rasool M.

School of Bio-engineering and Biosciences, VIT University, Vellore-632 014, Tamil
Nadu, India.

In the present study, we have investigated the efficacy of Indian ayurvedic
herbal formulation Triphala on monosodium urate crystal-induced inflammation in
mice; an experimental model for gouty arthritis and compared it with that of the 
non-steroidal anti-inflammatory drug, Indomethacin. The anti-arthritic effect of 
Triphala was evaluated by measuring changes in the paw volume, lysosomal enzyme
activities, lipid peroxidation, anti-oxidant status and inflammatory mediator
TNF-alpha in control and monosodium urate crystal-induced mice. The levels of
beta-glucuronidase and lactate dehydrogenase were also measured in monosodium
urate crystal-incubated polymorphonuclear leucocytes (PMNL). Triphala treatment
(1 gm/kg/b.w. orally) significantly inhibited the paw volume and the levels of
lysosomal enzymes, lipid peroxidation and inflammatory mediator tumour necrosis
factor-alpha; however the anti-oxidant status was found to be increased in
plasma, liver and spleen of monosodium urate crystal-induced mice when compared
to control mice. In addition, beta-glucuronidase and lactate dehydrogenase level 
were reduced in Triphala (100 microg/ml) treated monosodium urate
crystal-incubated polymorphonuclear leucocytes. In conclusion, the results
obtained clearly indicated that Triphala exerted a strong anti-inflammatory
effect against gouty arthritis.

PMID: 18065272 [PubMed - indexed for MEDLINE]

86: Clin Rheumatol. 2008 Feb;27(2):231-5. Epub 2007 Dec 7.

Comment in:
    Clin Rheumatol. 2009 Jan;28(1):105.

Rare copresent rheumatoid arthritis and gout: comparison with pure rheumatoid
arthritis and a literature review.

Kuo CF, Tsai WP, Liou LB.

Division of Rheumatology, Allergy and Immunology, Chang-Gung Memorial Hospital,
Kwei-san Hsiang, Tao-Yuan County, Taiwan.

Copresent rheumatoid arthritis (RA) and gout is seldom reported. This study
summarizes the findings of eight cases of copresent RA and gout and compares them
with 31 pure RA cases. Additional reported cases were retrieved from the current 
literature by Medline search. Patients with copresent RA and gout were older (p =
0.014) and predominantly male (p < 0.01). Synovial fluid, positive for urate
crystals, was aspirated most frequently from the knee (five out of eight),
followed by the first metatarsophalangeal joint (three out of eight). Serum
creatinine and urate levels in the copresent group were significantly higher (p <
0.01, both), and serum hemoglobin was lower (p = 0.04) than those with pure RA.
Copresent subjects had much lower percentage of positive rheumatoid factor (RF)
tests than patients with pure RA (37.5 vs 80.6%). Only one copresent subject had 
both RF and anti-cyclic citrullinated peptide antibody. Of copresent subjects,
75% had gouty arthritis before diagnosis of RA, which is consistent with earlier 
reports. Seven copresent subjects had gout attacks under disease-modifying
antirheumatic drug use. This study revealed that polyarthritis negative for RF in
a previously gouty patient may be RA and vice versa. This combination occurs more
frequently in males. Moreover, anti-CCP antibody examination is not helpful for
this diagnosis. Therefore, physicians must obtain synovial fluid for analysis in 
joints with intense swelling, especially in old RA subjects with renal
insufficiency or involvement of lower extremities. Conversely, RA must be
considered in gouty patients with polyarticular involvement.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Review

PMID: 18064397 [PubMed - indexed for MEDLINE]

87: Ann Rheum Dis. 2008 Jun;67(6):888-91. Epub 2007 Nov 29.

Erratum in:
    Ann Rheum Dis. 2008 Nov;67(11):1652.. Mellado, J Vazquez [corrected to
Vazquez-Mellado, J].

A modified Delphi exercise to determine the extent of consensus with OMERACT
outcome domains for studies of acute and chronic gout.

Taylor WJ, Schumacher HR Jr, Baraf HS, Chapman P, Stamp L, Doherty M, McQueen F, 
Dalbeth N, Schlesinger N, Furst DE, Vazquez-Mellado J, Becker MA, Kavanaugh A,
Louthrenoo W, Bardin T, Khanna D, Simon LS, Yamanaka H, Choi HK, Zeng X, Strand
V, Grainger R, Clegg D, Singh JA, Diaz-Torne C, Boers M, Gow P, Barskova VG.

Department of Medicine, University of Otago, Wellington 6242, New Zealand.
will.taylor@otago.ac.nz

OBJECTIVES: To reach consensus with recommendations made by an OMERACT Special
Interest Group (SIG). METHODS: Rheumatologists and industry representatives
interested in gout rated and clarified, in three iterations, the importance of
domains proposed by the OMERACT SIG for use in acute and chronic gout
intervention studies. Consensus was defined as a value of less than 1 of the
UCLA/RAND disagreement index. RESULTS: There were 33 respondents (61% response
rate); all agreed the initial items were necessary, except "total body urate
pool". Additional domains were suggested and clarification sought for defining
"joint inflammation" and "musculoskeletal function". Items that demonstrated no
clear decision were re-rated in the final iteration. There were six highly rated 
items (rating 1-2) with four slightly lower rating items (rating 3) for acute
gout; and 11 highly rated items with eight slightly lower ratings for chronic
gout. CONCLUSIONS: Consensus is that the following domains be considered
mandatory for acute gout studies: pain, joint swelling, joint tenderness, patient
global, physician global, functional disability; and for chronic gout studies:
serum urate, gout flares, tophus regression, health-related quality of life,
functional disability, pain, patient global, physician global, work disability
and joint inflammation. Several additional domains were considered discretionary.

PMID: 18055475 [PubMed - indexed for MEDLINE]

88: Aust Fam Physician. 2007 Nov;36(11):931-4.

Diagnostic dilemmas in unusual presentations of gout.

Chui CH, Lee JY.

Department of Hand Surgery, Singapore General Hospital, Singapore.
chkchui@gmail.com

BACKGROUND: Gout is known to mimic conditions as diverse as joint and soft tissue
infections, skin malignancies, nerve compression syndromes and soft tissue
tumours. Upper limb involvement is unusual. OBJECTIVE: We discuss four cases of
gout in the hand and wrist masquerading as a soft tissue tumour, nodular extensor
tenosynovitis, septic arthritis of the wrist and acute and chronic median nerve
compression. These cases illustrate that gout in the hand and wrist can resemble 
more sinister conditions, often posing a diagnostic challenge even to the
experienced clinician. DISCUSSION: In the management of hand and wrist pain,
swelling and neuropathy, emphasis must be placed on actively excluding limb and
life threatening conditions such as septic arthritis and neoplasia. Laboratory
and radiological investigations cannot accurately distinguish these pathologies
from gout. Invasive surgical exploration or tissue sampling is often needed to
establish the correct diagnosis.

Publication Types: 
    Case Reports

PMID: 18043781 [PubMed - indexed for MEDLINE]

89: Clin Exp Rheumatol. 2007 Nov-Dec;25(6 Suppl 47):114-9.

Quality of care in gout: from measurement to improvement.

Mikuls TR.

Department of Internal Medicine, Section of Rheumatology and Immunology,
University of Nebraska Medical Center, 986270 Nebraska Medical Center, Omaha, NE 
68198-6270, USA. tmikuls@unmc.edu

Gout is a growing health problem, affecting approximately 7% of men and 3% of
women over the age of 65 years. Although effective therapies for gout management 
exist, quality in gout care has been too frequently characterized as being
"suboptimal." This review examines issues pertinent to quality of care in gouty
arthritis with a focus on initial reports examining suboptimal care, subsequent
efforts to develop quality of care indicators for gout management, more recently 
published evidence-based recommendations for gout diagnosis and treatment, and an
ongoing international initiative to develop core outcome measures for acute and
chronic gout. "If you can not measure it, you can not improve it" - Lord Kelvin.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18021516 [PubMed - indexed for MEDLINE]

90: Clin Rheumatol. 2008 May;27(5):581-6. Epub 2007 Nov 20.

Ischemia heart disease and greater waist circumference are risk factors of renal 
function deterioration in male gout patients.

Su BY, Lai HM, Chen CJ, Chen YC, Chiu CK, Lin KM, Yu SF, Cheng TT.

Department of Rheumatology, Immunology and Allergy, Chang Gung Memorial
Hospital-Kaohsiung Medical Center, Chang-Gung University College of Medicine,
No.123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsein 833, Taiwan.

We examined the incidence of renal function deterioration (RFD) in a population
of male gout patients and to identify associated risk factors. Subjects who had
been regularly followed up for more than 2 years and had visited Chang Gung
Memorial Hospital-Kaohsiung Medical Center Rheumatology Clinic between June 1,
2006 and January 31, 2007 were enrolled. Four subjects were excluded as secondary
gout was suspected. Group I (Gr I) comprised subjects without RFD and group II
(Gr II) comprised subjects with RFD during the follow-up period. RFD was defined 
as absolute increment in creatinine (Cr) levels over 0.4 mg/dl for subjects with 
baseline Cr levels <or=1.4 mg/dl or as more than 50% increment of baseline Cr
level per 12-month interval in average for subjects with baseline Cr levels >1.4 
mg/dl. Clinical parameters were analyzed to study the potential risk factors of
RFD. Of 318 male gout patients, 296 (93.1%) were categorized as Gr I, and 22
(6.9%) were categorized as Gr II. The observation periods for Gr I and Gr II were
81.20+/-53.29 and 92.41+/-46.72 months, respectively (p=0.338). Initial Cr levels
are similar between the two groups (1.25+/-0.51 vs 1.25+/-0.61, p=0.963).
Multiple logistic regression analysis revealed that current age, age at disease
onset, disease duration, treatment duration, body weight, height, family history 
of gout, tophi, urolithiasis, tobacco use, alcohol consumption, history of
cerebral vascular accident, hypertension, diabetes mellitus, dyslipidemia,
base-line and final Cr, blood urea nitrogen level, serum uric acid level, and
body-mass index were not independent risk factors. However, history of ischemic
heart disease [IHD; odds ratio (OR) 7.68, 95% confidence interval (CI)
1.99-29.70] and greater waist circumference (WC; OR 1.06, 95% CI 1.01-1.11) were 
two independent risk factors of RFD. Additionally, the Cox multivariable analysis
disclosed that IHD (p<0.001) and greater WC (p=0.011) deteriorated kidney
function in these patients. The incidence of RFD in male gout patients is 6.9%.
History of IHD and greater WC are two independent risk factors for developing
RFD.

PMID: 18030516 [PubMed - indexed for MEDLINE]

91: Ann Rheum Dis. 2008 Sep;67(9):1271-5. Epub 2007 Nov 12.

Clinical features and risk factors of postsurgical gout.

Kang EH, Lee EY, Lee YJ, Song YW, Lee EB.

Department of Internal Medicine, Seoul National University College of Medicine,
28 Yongon-dong, Jongno-gu, Seoul, Korea.

OBJECTIVES: To investigate the clinical characteristics and risk factors of gout 
attacks that develop during the postsurgical period. METHODS: We enrolled 67
patients with gout who developed postsurgical gout and 67 controls who had
histories of gout but did not develop gout attacks after surgery. Features of the
postsurgical gout attacks were analysed and compared to those of presurgical gout
attacks suffered by patients and controls. Demographics, medical backgrounds,
laboratory data and surgical factors were compared between patients and controls 
in order to establish risk factors associated with postsurgical gout. RESULTS:
The mean (SD) time interval to develop postsurgical gout was 4.2 (3.1) days. The 
attacks tended to involve lower extremity joints (65/67, 97.0%), usually the
first metatarsophalangeal joint (42/67, 62.7%), and to affect more than one joint
(34/67, 50.7%). The number of attacked joints was positively correlated with the 
total number of previously involved joints (r = 0.281, p = 0.026). The site of
attacks had a preference for the previously affected sites. A history of cancer
surgery (p = 0.002), elevated presurgical serum urate levels (>/=9 mg/dl; p =
0.002) and failure to administer colchicine prophylaxis (p = 0.008) were found to
be risk factors for postsurgical gout. CONCLUSIONS: Postsurgical gout tends to
develop within 8 days after surgery. The site and number of involved joints
reflect the features of gout attacks the patient suffered before surgery.
Adequate presurgical control of serum uric acid levels and/or prophylactic
administration of colchicine will help prevent gout attacks during the
postsurgical period.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17998214 [PubMed - indexed for MEDLINE]

92: Eur Radiol. 2008 Mar;18(3):621-30. Epub 2007 Nov 10.

Diagnostic imaging of gout: comparison of high-resolution US versus conventional 
X-ray.

Rettenbacher T, Ennemoser S, Weirich H, Ulmer H, Hartig F, Klotz W, Herold M.

Department of Radiology, Innsbruck Medical University, Anichstrasse 35, 6020
Innsbruck, Austria. thomas.rettenbacher@i-med.ac.at

The aim was to compare X-ray and ultrasound (US) in diagnosing gout. In a
prospective study, 105 consecutive patients with clinical suspicion of gout
underwent conventional X-ray und high-resolution US in order to help in arriving 
at a definite diagnosis. X-ray findings suggestive of gout included soft-tissue
opacifications with densities between soft tissue and bone, articular and
periarticular bone erosions, and osteophytes at the margins of opacifications or 
erosions. US findings suggestive of gout included bright stippled foci and
hyperechoic soft-tissue areas. Fifty-five patients had a definite diagnosis of
gout (102 involved sites), 31 patients were diagnosed as having another disease
(59 involved sites), and 19 patients were excluded from the study because a
definite diagnosis could not be established. X-ray suggested gout with a
sensitivity of 31% (32/102) and a specificity of 93% (55/59), whereas US
suggested gout with a sensitivity of 96% (98/102) and a specificity of 73%
(43/59). US was much more sensitive than conventional X-ray but less specific.
Our data show that US often provided additional diagnostic information in
patients with clinical suspicion of gout when laboratory findings and X-ray
results were negative or inconclusive and should therefore be used in these
cases.

Publication Types: 
    Comparative Study

PMID: 17994238 [PubMed - indexed for MEDLINE]

93: Rheumatology (Oxford). 2007 Dec;46(12):1804-7. Epub 2007 Nov 3.

Tophaceous joint disease strongly predicts hand function in patients with gout.

Dalbeth N, Collis J, Gregory K, Clark B, Robinson E, McQueen FM.

Department of Medicine, Faculty of Medical and Health Sciences, University of
Auckland, 85 Park Rd, Grafton, Auckland, New Zealand. n.dalbeth@auckland.ac.nz

OBJECTIVES: The functional impact of gout is poorly understood. The aim of this
study was to determine predictors of hand function in gout. METHODS: Twenty
unselected patients with gout were recruited from rheumatology clinics. No
patient had an acute gout flare at assessment. Participants were assessed for
clinical characteristics of gout, including the site and number of tophi. Hand
function was assessed by the Sollerman hand function test. Fingertip to palm
(FTP) distance measurement, grip strength and the Disability Assessment of
Shoulder and Hand (DASH) questionnaire scores were also recorded. Data were
analysed by simple and multiple linear regression models. RESULTS: The median
Sollerman score was 75.5 (range 31-80). The median hand FTP distance was 2.91
(0.88-6.69) cm, grip strength was 31 (4-71) kg, and DASH score was 28.77
(0-76.47). Of the clinical characteristics measured, the number of joints of the 
hand with overlying tophi (hand tophus joint count) was the strongest single
predictor of the Sollerman score (r2 = 0.59), and also predicted the other
measures of hand mobility and function. A multiple regression model including
hand tophus joint count, sex, number of gout flares in the preceding 6 months,
gout disease duration and hand tender joint count was a better predictor of the
Sollerman score than hand tophus joint count alone (r2 = 0.81, F(4,14) = 3.94, P 
= 0.024). CONCLUSIONS: Measures of chronic and poorly controlled disease predict 
hand function in patients with gout. In particular, tophaceous joint disease has 
a major impact on functional capacity in gout.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17982165 [PubMed - indexed for MEDLINE]

94: Ann Rheum Dis. 2008 Jul;67(7):960-6. Epub 2007 Nov 2.

Gout in the UK and Germany: prevalence, comorbidities and management in general
practice 2000-2005.

Annemans L, Spaepen E, Gaskin M, Bonnemaire M, Malier V, Gilbert T, Nuki G.

Ghent University, Faculty of Medicine, Department of Public Health, Ghent,
Belgium. Lieven.Annemans@UGent.be

OBJECTIVE: To investigate and compare the prevalence, comorbidities and
management of gout in practice in the UK and Germany. METHODS: A retrospective
analysis of patients with gout, identified through the records of 2.5 million
patients in UK general practices and 2.4 million patients attending GPs or
internists in Germany, using the IMS Disease Analyzer. RESULTS: The prevalence of
gout was 1.4% in the UK and Germany. Obesity was the most common comorbidity in
the UK (27.7%), but in Germany the most common comorbidity was diabetes (25.9%). 
The prevalence of comorbidities tended to increase with serum uric acid (sUA)
levels. There was a positive correlation between sUA level and the frequency of
gout flares. Compared with those in whom sUA was <360 micromol/l (<6 mg/dl), odds
ratios for a gout flare were 1.33 and 1.37 at sUA 360-420 micromol/l (6-7 mg/dl),
and 2.15 and 2.48 at sUA >530 micromol/l ( >9 mg/dl) in the UK and Germany,
respectively (p<0.01). CONCLUSIONS: The prevalence of gout in practice in the UK 
and Germany in the years 2000-5 was 1.4%, consistent with previous UK data for
1990-9. Chronic comorbidities were common among patients with gout and included
conditions associated with an increased risk for cardiovascular disease, such as 
obesity, diabetes and hypertension. The importance of regular monitoring of sUA
in order to tailor gout treatment was highlighted by data from this study showing
that patients with sUA levels >or=360 micromol/l (>or=6 mg/dl) had an increased
risk of gout flares.

PMID: 17981913 [PubMed - indexed for MEDLINE]

95: Arthritis Rheum. 2007 Nov;56(11):3854-7.

Misdiagnosis of a chylous cyst as chest wall gouty tophus: a case of true
pseudogout.

Adhikesavan LG, Ayoub WT, Schumacher HR.

Geisinger Medical Center, Danville, Pennsylvania 17822, USA.
lgadhikesavan@geisinger.edu

A patient referred to us for recurrent chest wall gouty tophus, but who was
determined to actually have a chylous cyst, is described herein. Chylous cysts of
the neck or chest wall can be caused by thoracic duct injury. Chyle contains 4-40
gm/liter of lipids, mostly triglycerides, and these can form birefringent
crystals upon drying, leading to a false diagnosis of gout.

Publication Types: 
    Case Reports

PMID: 17968910 [PubMed - indexed for MEDLINE]

96: Expert Opin Drug Saf. 2007 Nov;6(6):625-9.

Reassessing the safety of intravenous and compounded injectable colchicine in
acute gout treatment.

Schlesinger N.

Division of Rheumatology, UMDNJ/Robert Wood Johnson Medical School, New
Brunswick, NJ 08901-1977, USA. schlesna@umdnj.edu

Colchicine has been used for over 2000 years. Intravenous (i.v.) colchicine has
been used for the treatment of acute gout since the 1950s. I.v. and oral
colchicine were 'grandfathered' before the 1969 FDA Phase III trials for drug
toxicity became law. Data on toxic reactions are, therefore, based only on
passive surveillance. The risk of toxicity with i.v. use depends on the total
dose over a period of time, the presence of comorbid conditions and the size of
individual dose. Colchicine toxicity has been compared to arsenic poisoning.
Symptoms start 2-5 h after the toxic dose has been ingested and not uncommonly
lead to death. Injections of compounded colchicine have been implicated in the
deaths of several patients, several of which received off-label i.v. colchicine
for back pain. Given that colchicine has the smallest benefit to toxicity ratio
of the drugs that are used in the management of acute gout and the fact that
acute gout is not life-threatening, one could make a strong case for eliminating 
the use of i.v. colchicine the treatment of acute gout.

Publication Types: 
    Review

PMID: 17967150 [PubMed - indexed for MEDLINE]

97: Neurology. 2007 Oct 23;69(17):1696-700.

Comment in:
    Neurology. 2008 Jul 1;71(1):70; author reply 70.    Neurology. 2008 Jul 1;71(1):70; author reply 70.

Gout and risk of Parkinson disease: a prospective study.

Alonso A, Rodríguez LA, Logroscino G, Hernán MA.

Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
aalogut@alumni.unav.es

BACKGROUND: Several reports suggest that higher levels of serum uric acid are
associated with a lower risk of Parkinson disease (PD). None of these studies,
however, evaluated the potential association between gout, a condition
characterized by hyperuricemia, and the risk of PD. OBJECTIVE: To estimate
prospectively the association between gout diagnosis and the risk of PD. METHODS:
We conducted a case-control study nested in the General Practice Research
Database, a computerized database that gathers information on more than 3 million
Britons followed up by their general practitioners. PD cases occurring between
January 1995 and December 2001 were identified, and matched with up to 10
controls by sex, age, practice, and start of follow-up. We obtained information
on history of gout and use of anti-gout medication using the computerized medical
records. RESULTS: During the study period, we identified 1,052 PD cases and 6,634
controls. Individuals with previous history of gout had a lower risk of
developing PD (OR 0.69, 95% CI 0.48, 0.99). This association was evident among
men (OR 0.60, 95% CI 0.40, 0.91) but not among women (OR 1.26, 95% CI 0.57, 2.81;
p for interaction: 0.11). Initiation of anti-gout medication was associated with 
a lower risk of PD (OR 0.57, 95% CI 0.19, 1.70). CONCLUSION: Gout is associated
with a lower risk of Parkinson disease (PD). Our findings provide additional
support for a potential link between uric acid and PD. Further research is
required to explore a potential effect modification by sex.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17954784 [PubMed - indexed for MEDLINE]

98: Rheumatology (Oxford). 2007 Nov;46(11):1662-6. Epub 2007 Oct 15.

The polymorphism -863C/A in tumour necrosis factor-alpha gene contributes an
independent association to gout.

Chang SJ, Tsai PC, Chen CJ, Lai HM, Ko YC.

Department of Public Health, Faculty of Medicine, College of Medicine, Kaohsiung 
Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.
changsj@kmu.edu.tw

OBJECTIVE: To investigate the associations between polymorphisms in the promoter 
of the tumour necrosis factor-alpha (TNF-alpha) gene and gout. METHODS: The
polymorphisms -308G/A and -863C/A in the TNF-alpha gene were determined in 106
gout patients and 159 healthy controls among male Taiwanese using the Polymerase 
Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The
biochemical markers, including Glutamic-oxaloacetic transaminase (GOT),
Glutamic-pyruvic transaminase (GPT), uric acid, creatinine, total cholesterol
(TC), triglycerides (TG), body mass index (BMI) and hypertension, as well as
alcohol consumption were measured. RESULTS: The gout patients had 9.43% (10/106) 
with genotype AA at polymorphism -863C/A showing a significantly higher fraction 
than controls (0.63%; 1/159, P < 0.001). The crude results also showed that the
gout patients had significantly higher portions of abnormal GOT, GPT, creatinine,
TC, TG, alcohol consumption, hypertension and hyperuricaemia than controls (P <
0.05), but the -308G/A, BMI and genotype CA at -863C/A did not show the same
significant difference (P > 0.05). After adjustment by a stepwise logistic
regression method, the hyperuricaemia, creatinine, GPT, TG and alcohol
consumption as well as genotype AA at polymorphism -863C/A were found to be
significantly associated with gout. CONCLUSION: The genotype AA at polymorphism
-863C/A in a recessive model showed a significant association with developing
gout independent of hyperuricaemia, abnormal creatinine, higher TG, GPT and
alcohol consumption.

PMID: 17938134 [PubMed - indexed for MEDLINE]

99: J Rheumatol. 2007 Nov;34(11):2308-11. Epub 2007 Oct 15.

Juvenile gout in Taiwan associated with family history and overweight.

Chen SY, Shen ML.

Center of Gout, Country Hospital, #61 Sec. 4 Ren-Ai Road, Taipei, Taiwan.
doctor@rahome.idv.tw

OBJECTIVE: To examine the clinical features of juvenile gout and its possible
association with familial juvenile hyperuricemic nephropathy (FJHN). METHODS: A
total of 543 cases of juvenile gout from the Ho-Ping Gout Database were enrolled,
and 5269 gouty cases with onset age of 40 to 50 years were selected as a control 
group. Clinical and laboratory data were compared between the 2 groups. RESULTS: 
In patients with juvenile gout, body mass index, serum urate concentration,
24-hour urinary uric acid excretion, and creatinine clearance were significantly 
higher than those in the control group (p < 0.0001), while fractional excretion
of uric acid was significantly lower. Only 15% of the juvenile gout cases
fulfilled the features of FJHN. The percentage of familial aggregation in
juvenile gout was about 1.9-fold higher than that in the control group (44.3% vs 
23.8%; p < 0.0001). CONCLUSION: Juvenile gout in Taiwan is associated with
overweight and hereditary background, while FJHN may not be primarily
responsible.

PMID: 17937457 [PubMed - indexed for MEDLINE]

100: Arch Orthop Trauma Surg. 2007 Dec;127(10):971-4.

Carpal bone involvement in gout.

Jerome JT, Sankaran B, Thirumagal K.

Department of Orthopedics, St Stephen's Hospital, Tiz Hazari, Delhi, India.
terrencejose@gmail.com

The deposition of gout tophi in the hand occurs relatively late in the disease.
Involvement of carpal bone is rarely reported in the literature. We present a
40-year-old man with a long duration of gouty arthritis involving the carpal
bones.

Publication Types: 
    Case Reports

PMID: 17929042 [PubMed - indexed for MEDLINE]

101: Bull NYU Hosp Jt Dis. 2007;65(3):215-21.

Hyperuricemia and gout: new insights into pathogenesis and treatment.

Pillinger MH, Rosenthal P, Abeles AM.

New York University School of Medicine and Division of Rheumatology, NYU Hospital
for Joint Diseases, New York, NY 10003, USA. michael.pillinger@med.nyu.edu

Over the past decade, significant advances have been made regarding the
pathogenesis, clinical implications, and treatment of hyperuricemia. While
physicians have understood for at least a century that uric acid causes gout, we 
are now beginning to address the question of why hyperuricemia exists and the
mechanisms by which uric acid acts to stimulate inflammation. This review focuses
on (1) previously unknown biological roles of uric acid; (2) why the loss of the 
uricase gene and resultant hyperuricemia may have provided an evolutionary
advantage to primates and, in particular, to humans; (3) the molecular effects of
uric acid on inflammatory cells; and (4) novel antihyperuricemic agents currently
under study.

Publication Types: 
    Review

PMID: 17922673 [PubMed - indexed for MEDLINE]

102: J Am Acad Orthop Surg. 2007 Oct;15(10):625-35.

Gout affecting the hand and wrist.

Fitzgerald BT, Setty A, Mudgal CS.

Naval Medical Center, San Diego, USA.

Tophaceous gout in the hand and wrist often presents de novo as the first sign of
the disease process in the elderly. Tophaceous material may present in a liquid, 
pasty, or chalky/granular state. Treatment may be as simple as aspirating the
liquid or squeezing out pasty tophaceous material. Other nonsurgical treatment
options include lifestyle and dietary modifications and drug therapy. Surgery is 
often indicated for the patient with significant tendon and joint compromise as
well as skin breakdown and for decompression of compressive peripheral
neuropathy.

Publication Types: 
    Review

PMID: 17916786 [PubMed - indexed for MEDLINE]

103: Am Fam Physician. 2007 Sep 15;76(6):801-8.

Comment in:
    Am Fam Physician. 2008 Jul 15;78(2):176.

Summary for patients in:
    Am Fam Physician. 2007 Sep 15;76(6):811-2.

Gout: an update.

Eggebeen AT.

University of Pittsburgh Arthritis Institute, Pittsburgh, Pennsylvania 15261,
USA.

Arthritis caused by gout (i.e., gouty arthritis) accounts for millions of
outpatient visits annually, and the prevalence is increasing. Gout is caused by
monosodium urate crystal deposition in tissues leading to arthritis, soft tissue 
masses (i.e., tophi), nephrolithiasis, and urate nephropathy. The biologic
precursor to gout is elevated serum uric acid levels (i.e., hyperuricemia).
Asymptomatic hyperuricemia is common and usually does not progress to clinical
gout. Acute gout most often presents as attacks of pain, erythema, and swelling
of one or a few joints in the lower extremities. The diagnosis is confirmed if
monosodium urate crystals are present in synovial fluid. First-line therapy for
acute gout is nonsteroidal anti-inflammatory drugs or corticosteroids, depending 
on comorbidities; colchicine is second-line therapy. After the first gout attack,
modifiable risk factors (e.g., high-purine diet, alcohol use, obesity, diuretic
therapy) should be addressed. Urate-lowering therapy for gout is initiated after 
multiple attacks or after the development of tophi or urate nephrolithiasis.
Allopurinol is the most common therapy for chronic gout. Uricosuric agents are
alternative therapies in patients with preserved renal function and no history of
nephrolithiasis. During urate-lowering therapy, the dose should be titrated
upward until the serum uric acid level is less than 6 mg per dL (355 micromol per
L). When initiating urate-lowering therapy, concurrent prophylactic therapy with 
low-dose colchicine for three to six months may reduce flare-ups.

Publication Types: 
    Review

PMID: 17910294 [PubMed - indexed for MEDLINE]

104: Semin Dial. 2007 Sep-Oct;20(5):391-5.

Allopurinol dosing in renal impairment: walking the tightrope between adequate
urate lowering and adverse events.

Dalbeth N, Stamp L.

Department of Medicine, University of Auckland, Auckland, New Zealand.
n.dalbeth@auckland.ac.nz

Allopurinol is the mainstay of urate-lowering therapy for patients with gout and 
impaired renal function. Although rare, a life-threatening hypersensitivity
syndrome may occur with this drug. The risk of this allopurinol hypersensitivity 
syndrome (AHS) is increased in renal impairment. The recognition that AHS may be 
because of delayed-type hypersensitivity to oxypurinol, the main metabolite of
allopurinol, and that oxypurinol concentrations are frequently elevated in
patients with renal impairment prescribed standard doses of allopurinol has led
to the widespread adoption of allopurinol-dosing guidelines. These guidelines
advocate allopurinol dose reduction according to creatinine clearance in patients
with renal impairment. However, recent studies have challenged the role of these 
guidelines, suggesting that AHS may occur even at low doses of allopurinol, and
that these guidelines lead to under-treatment of hyperuricemia, a key therapeutic
target in gout. Based on current data, we advocate gradual introduction of
allopurinol according to current treatment guidelines, with close monitoring of
serum uric acid concentrations. In patients with severe disease and persistent
hyperuricemia, allopurinol dose escalation above those recommended by the
guidelines should be considered, with careful evaluation of the benefits and
risks of therapy. Further work is needed to clarify the safety and efficacy of
allopurinol dose escalation, particularly in patients with renal impairment.

Publication Types: 
    Editorial

PMID: 17897242 [PubMed - indexed for MEDLINE]

105: J Rheumatol. 2007 Oct;34(10):2093-8. Epub 2007 Sep 15.

Rasburicase for tophaceous gout not treatable with allopurinol: an exploratory
study.

Richette P, Brière C, Hoenen-Clavert V, Loeuille D, Bardin T.

Université Paris 7, UFR Médicale, Assistance Publique-Hôpitaux de Paris,
Fédération de Rhumatologie, Hôpital Lariboisière, Paris, France.

OBJECTIVE: To evaluate the short-term safety and outcome of 2 different
experimental applications of rasburicase 0.2 mg/kg (monthly vs daily) in patients
with tophaceous gout not treatable by allopurinol. Rasburicase could be useful
for patients with gout that is unresponsive to allopurinol or who cannot tolerate
the therapy. METHODS: Five patients received 6 monthly infusions of rasburicase
(Group 1) and 5 received 5 daily infusions (Group 2). RESULTS: In Group 1, serum 
uric acid (SUA) level decreased significantly, from 612.6 +/- 162.4 micromol/l at
baseline to 341.2 +/- 91.8 micromol/l after 6 infusions (p = 0.001). Changes in
tophus area were observed in 2 patients. In Group 2, daily infusions produced a
rapid, marked decrease in SUA level during treatment. Yet SUA levels measured at 
1 month (511.5 +/- 128.4 micromol/l) and 2 months (572 +/- 96.2 micromol/l) after
treatment were not significantly lower than at baseline (573.6 +/- 48.2
micromol/l). No patient from Group 2 showed reduced tophus size. Eight of 10
patients experienced an adverse event, the most common being gout flare despite
prophylactic treatment with colchicine. CONCLUSION: Monthly infusions of
rasburicase appear to be a possible therapy for severe gout not treatable by
other means. Tolerance of rasburicase in gout appears to be diminished by
frequent triggering of gout attacks, and hypersensitivity reactions might be an
important limitation to longterm therapy.

PMID: 17896799 [PubMed - indexed for MEDLINE]

106: Adv Drug Deliv Rev. 2008 Jan 3;60(1):59-68. Epub 2007 Aug 14.

PEG-uricase in the management of treatment-resistant gout and hyperuricemia.

Sherman MR, Saifer MG, Perez-Ruiz F.

Mountain View Pharmaceuticals, Inc., 3475-S Edison Way, Menlo Park, CA 94025,
USA. sherman@mvpharm.com

Hyperuricemia results from an imbalance between the rates of production and
excretion of uric acid. Longstanding hyperuricemia can lead to gout, which is
characterized by the deposition of monosodium urate monohydrate crystals in the
joints and periarticular structures. Because such deposits are resolved very
slowly by lowering plasma urate with available drugs or other measures, the
symptoms of gout may become chronic. Persistent hyperuricemia may also increase
the risk of renal and cardiovascular diseases. Unlike most mammals, humans lack
the enzyme uricase (urate oxidase) that catalyzes the oxidation of uric acid to a
more soluble product. This review describes the development of a poly(ethylene
glycol) (PEG) conjugate of recombinant porcine-like uricase with which a
substantial and persistent reduction of plasma urate concentrations has been
demonstrated in a Phase 2 clinical trial. Two ongoing Phase 3 clinical trials
include systematic assessments of gout symptoms, tophus resolution and quality of
life, in addition to the primary endpoint of reduced plasma urate concentration.

Publication Types: 
    Review

PMID: 17826865 [PubMed - indexed for MEDLINE]

107: Ann Rheum Dis. 2008 May;67(5):609-13. Epub 2007 Aug 29.

Uric acid lowering therapy: prescribing patterns in a large cohort of older
adults.

Solomon DH, Avorn J, Levin R, Brookhart MA.

Division of Pharmacoepidemiology, Brigham and Women's Hospital, 1620 Tremont
Street, Suite 3030, Boston, MA 02120, USA. dhsolomon@partners.org

BACKGROUND: Uric acid lowering therapy (UALT) is considered a chronic treatment
for gout. Relatively little is known about adherence to UALT. METHODS: We
assessed adherence with UALT over a 1-year study period among 9823 older adults
enrolled in a pharmacy benefit program. Two adherence measures were calculated,
the percentage of days covered (PDC) and the time until an extended break (at
least 60 days) in treatment. A PDC <80% was considered poor adherence and its
predictors were examined in multivariable logistic models. RESULTS: The mean (SD)
PDC was 54% (36%) with 64% of patients considered poorly compliant over the study
period. A total of 56% had experienced an extended break in UALT. Predictors of
poor adherence included younger age (odds ratio (OR) 1.50, 95% CI 1.33-1.69 for
ages 65-74 compared with 85 and above) and African-American race (OR 1.86, 95% CI
1.52-2.27 compared with Caucasian race). Most patients (93%) received their
initial UALT prescription from a non-specialist and this also predicted poor
adherence (OR 1.15, 95% CI 0.96-1.38 compared with rheumatologists or
nephrologists). CONCLUSION: Adherence with UALT is poor. While uric acid levels
were not measured in this study, poor adherence with UALT is likely to reduce
attainment of goal uric acid levels.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17728328 [PubMed - indexed for MEDLINE]

108: Acta Cytol. 2007 Jul-Aug;51(4):586-8.

Cytology of urate milk in gouty arthritis: a case report.

Siddaraju N, Aier M, Yaranal PJ, Basu D.

Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education
and Research, Pondicherry, India. rajusiddaraju@yahoo.com

BACKGROUND: Synovial fluid (SF) analysis is a useful investigative procedure in
the evaluation of various types of arthritides, including gouty arthritis.
Rarely, gouty arthritis may present with effusion containing thick, milky white
fluid. We report a case of gouty arthritis, describing cytologic features of the 
urate milk. CASE: A 42-year-old man presented with pain and swelling of multiple 
joints of long duration. Approximately 3 mL of milky white SF was obtained for
white blood cell (WBC) count, with a clinical diagnosis of septic arthritis. Due 
to the gross nature of the sample, the WBC count could not be performed; however,
cytologic examination of the sample revealed a massive amount of classic,
needle-shaped urate crystals on routinely stained May-Grünwald-Giemsa smears,
favoring a cytologic diagnosis of gouty arthritis. CONCLUSION: Gouty synovitis
occasionally presents with thick, milky white urate-laden synovial effusions,
which clinically may be mistaken for septic arthritis. This gross nature of the
specimen may interfere with the performace of a WBC count on SF samples.

Publication Types: 
    Case Reports

PMID: 17718129 [PubMed - indexed for MEDLINE]

109: Joint Bone Spine. 2007 Dec;74(6):571-6. Epub 2007 Aug 21.

The inflammasome, autoinflammatory diseases, and gout.

Pétrilli V, Martinon F.

Department of Biochemistry, Lausanne University, Lausanne, Switzerland.
virginie.petrilli@unil.ch

IL-1beta is a cytokine with major roles in inflammation and innate immune
responses. IL-1beta is produced as an inactive proform that must be cleaved
within the cell to generate biologically active IL-1beta. The enzyme caspase-1
catalyzes the reaction. Recent work showed that caspase-1 must be activated by a 
complex known as the inflammasome. The inflammasome comprises NALP, which is an
intracellular receptor involved in innate immunity, and an ASC adapter that
ensures caspase-1 recruitment to the receptor. The most extensively described
inflammasome to date is formed by the NALP3 receptor within monocytes. Mutations 
involving the NALP3 gene cause hereditary periodic fever syndromes in humans.
Increased inflammasome activity responsible for uncontrolled IL-1beta production 
occurs in these syndromes. Inhibition of the IL-1beta pathway by IL-1 receptor
antagonist (anakinra) is a highly effective treatment for inherited periodic
fever syndromes. A major role for inflammasome activity in the development of
gout attacks was established recently. Urate monosodium crystals are specifically
detected via the NALP3 inflammasome, which results in marked IL-1beta
overproduction and initiation of an inflammatory response. This finding opens up 
new possibilities for the management of gouty attacks.

Publication Types: 
    Review

PMID: 17714972 [PubMed - indexed for MEDLINE]

110: Circulation. 2007 Aug 21;116(8):894-900. Epub 2007 Aug 13.

Comment in:
    Circulation. 2007 Aug 21;116(8):880-3.

Independent impact of gout on mortality and risk for coronary heart disease.

Choi HK, Curhan G.

Rheumatology Division, Arthritis Research Centre of Canada, Department of
Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, 
Canada.

BACKGROUND: Although gout and hyperuricemia are related to several conditions
that are associated with reduced survival, no prospective data are available on
the independent impact of gout on mortality. Furthermore, although many studies
have suggested that hyperuricemia is associated with cardiovascular disease
(CVD), limited data are available on the impact of gout on CVD. METHODS AND
RESULTS: Over a 12-year period, we prospectively examined the relation between a 
history of gout and the risk of death and myocardial infarction in 51,297 male
participants of the Health Professionals Follow-Up Study. During the 12 years of 
follow-up, we documented 5825 deaths from all causes, which included 2132 deaths 
from CVD and 1576 deaths from coronary heart disease (CHD). Compared with men
without history of gout and CHD at baseline, the multivariate relative risks
among men with history of gout were 1.28 (95% confidence interval [CI], 1.15 to
1.41) for total mortality, 1.38 (95% CI, 1.15 to 1.66) for CVD deaths, and 1.55
(95% CI, 1.24 to 1.93) for fatal CHD. The corresponding relative risks among men 
with preexisting CHD were 1.25 (95% CI, 1.09 to 1.45), 1.26 (95% CI, 1.07 to
1.50), and 1.24 (95% CI, 1.04 to 1.49), respectively. In addition, men with gout 
had a higher risk of nonfatal myocardial infarction than men without gout
(multivariate relative risk, 1.59; 95% CI, 1.04 to 2.41). CONCLUSIONS: These
prospective data indicate that men with gout have a higher risk of death from all
causes. Among men without preexisting CHD, the increased mortality risk is
primarily a result of an elevated risk of CVD death, particularly from CHD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17698728 [PubMed - indexed for MEDLINE]

111: Arthritis Rheum. 2007 Aug 15;57(6):1067-73.

Validation of a radiographic damage index in chronic gout.

Dalbeth N, Clark B, McQueen F, Doyle A, Taylor W.

University of Auckland, Grafton, Auckland, New Zealand. n.dalbeth@auckland.ac.nz

OBJECTIVE: To identify a valid method to measure radiographic damage in patients 
with chronic gout. METHODS: The scoring method that best represented radiographic
damage in individual joints was analyzed by comparing a gold standard
rheumatologist consensus global score with recognized scoring methods, including 
the Sharp/van der Heijde erosion and narrowing scores, Ratingen destruction
score, and Steinbrocker score. Ninety-five proximal interphalangeal joints from
12 patients with gout were included in this analysis. Scoring of hand and feet
radiographs from an additional 35 patients with gout was used to analyze the
sites to be included in a scoring system and the additional features to be
recorded. RESULTS: For individual joints, the combination of the Sharp/van der
Heijde erosion and narrowing scores correlated best with the consensus global
score. In addition, the limits of agreement were narrowest for the combined
Sharp/van der Heijde erosion and narrowing score. All joint areas in the
Sharp/van der Heijde rheumatoid arthritis score and the distal interphalangeal
joints were affected by chronic gout and contributed to the total score.
Additional features (extraarticular erosions, joint space widening, and
ankylosis) occurred infrequently, and scoring of these features did not increase 
the reliability of the total score. The reliability of the total score was high: 
intraclass correlation coefficient for intraobserver reproducibility was
0.993-0.998 and for interobserver reproducibility was 0.963-0.966. The modified
Sharp/van der Heijde score was able to discriminate between early and advanced
disease. CONCLUSION: A modified Sharp/van der Heijde system accurately and
reliably represents radiographic joint damage in chronic gout.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 17665492 [PubMed - indexed for MEDLINE]

112: Nat Clin Pract Rheumatol. 2007 Aug;3(8):443-9.

Comment in:
    Ann Rheum Dis. 2007 Oct;66(10):1269-70.

The changing epidemiology of gout.

Roddy E, Zhang W, Doherty M.

Primary Care Musculoskeletal Research Centre, Primary Care Sciences,
Staffordshire, Keele University, UK. e.roddy@cphc.keele.ac.uk

Gout is one of the most common inflammatory arthritides, which is considered to
be a true crystal deposition disorder caused by the formation of monosodium urate
crystals in and around joints. A number of epidemiological studies from a diverse
range of countries suggest that gout has increased in prevalence and incidence in
recent years and that the clinical pattern of gout is becoming more complex. In
particular, the greatest increase has been observed in primary gout in older men.
Robust epidemiological studies have established risk factors for gout including
genetic factors, excess alcohol consumption, purine-rich diet, the metabolic
syndrome (obesity, hypertension, hyperlipidemia and insulin resistance), use of
diuretics and chronic renal failure. Trends in alcohol use, diet, obesity and the
metabolic syndrome in the general population might explain changes in the
prevalence and incidence of gout in the community. Osteoarthritis, which is
thought to predispose patients to monosodium urate crystal deposition in their
joints, is becoming more prevalent as a consequence of increased longevity. In
hospital settings, widespread diuretic use, increasing prevalence of end-stage
renal failure and the success of organ transplant programmes have led to an
increase in clinical complexity. Suboptimal management of gout is likely to have 
contributed to the rise in the prevalence of clinically overt, symptomatic,
chronic gout.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17664951 [PubMed - indexed for MEDLINE]

113: J Rheumatol. 2007 Sep;34(9):1888-93. Epub 2007 Jul 15.

Ultrasonographic measurement of tophi as an outcome measure for chronic gout.

Perez-Ruiz F, Martin I, Canteli B.

Seccion de Reumatologia and Servicio de Radiologia, Hospital de Cruces,
Baracaldo, Spain. fperez@hcru.osakidetza.net

OBJECTIVE: To validate the usefulness of measuring tophi with ultrasonography
(US) as an outcome measure for chronic tophaceous gout. METHODS: Patients with
crystal-proven gout were included. To evaluate validity, intraarticular and
articular deep tophi were evaluated with both magnetic resonance imaging (MRI)
and US. Tophi were punctured with US guidance to evaluate face validity.
Interobserver and intraobserver measurement studies were done to evaluate
reliability, and to estimate the smallest detectable difference. Sensitivity to
change was evaluated with a 12-month followup observational study of
urate-lowering therapy. RESULTS: US detected at least one tophus in all joints
where MRI found nodules considered to be tophi. There was a good correlation, but
just fair agreement between measurements with US and MRI. Puncture of nodules
suspected of being tophi recovered urate crystals in 83% of the procedures.
Intraobserver intraclass correlation was > 0.90 for diameters and volume, while
it was 0.71 to 0.83 in the interobserver study. US was found to be sensitive to
change, and there was an inverse correlation between serum urate concentrations
and change from baseline measurement of tophi. CONCLUSION: US measurement of
tophi fulfilled the OMERACT filter for an outcome measure, although it should be 
tested further in randomized clinical trials.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 17659752 [PubMed - indexed for MEDLINE]

114: Rheumatology (Oxford). 2007 Dec;46(12):1751-6. Epub 2007 Jul 24.

Assessment of outcome in clinical trials of gout--a review of current measures.

Taylor WJ, Schumacher HR Jr, Singh JA, Grainger R, Dalbeth N.

Department of Medicine, Wellington School of Medicine and Health Sciences,
University of Otago, PO Box 7343, Wellington 6242, New Zealand.
will.taylor@otago.ac.nz

There has been renewed interest in the treatment of gout with recent reported
intervention studies of new agents such as etoricoxib, febuxostat and
pegylated-uricase. However, these studies have highlighted the relative paucity
of validated outcome measures with which to judge efficacy. This review outlines 
the published information regarding which endpoints have been measured in
randomized clinical trials, what should be measured, what tools or instruments
are available for this and the technical properties of such instruments. It
highlights recent work that validates measures of tophi, radiographic damage and 
patient-reported outcomes. The absence of a valid definition of gout-flare or how
flare reduction defines response is problematic; this forms the basis for a
current ACR-EULAR sponsored project.

Publication Types: 
    Review

PMID: 17650521 [PubMed - indexed for MEDLINE]

115: Value Health. 2007 Jul-Aug;10(4):231-7.

The impact of gout on work absence and productivity.

Kleinman NL, Brook RA, Patel PA, Melkonian AK, Brizee TJ, Smeeding JE,
Joseph-Ridge N.

HCMS Group, Cheyenne, WY 82001, USA. Nathan_Kleinman@hcmsgroup.com

OBJECTIVE: The goal of this analysis was to evaluate the impact of gout, a
painful inflammatory arthritis condition, on an employed population's
health-related work absence and objectively measured productivity output.
METHODS: Payroll, demographic, medical, pharmaceutical, sick leave, short- and
long-term disability, and workers' compensation data were collected from multiple
large employers with employees widely dispersed across the United States. Data
were collected during the time period of 2001 to 2004 from approximately 300,000 
employees. Objective productivity output data were also available for a subset of
employees (captured electronically in the form of units of work processed per
person). T-tests and chi-square tests were used to compare demographic data.
Two-stage multivariate regression models were used to compare annual work absence
and at-work productivity between employees with and without gout, while
controlling for group differences in demographics, salary, other work-related
variables, and comorbidities (using the Charlson Comorbidity Index). RESULTS: The
annual prevalence of gout was 4.7 per 1000 employees from 2001 to 2004. Employees
with gout had 4.56 more annual absence days for all categories of health-related 
work absence than those without gout. Objective productivity (units of work
processed) results were only available for a small subsample of employees (86
with gout and 27,472 without gout). Employees with gout processed 3.51% fewer
units per hour worked and 2.38% fewer units per year than employees without gout 
(nonsignificant at P = 0.49 and P = 0.78, respectively). CONCLUSION: This study
suggests that gout has a substantial impact on work absence and may also
negatively impact productivity.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17645677 [PubMed - indexed for MEDLINE]

116: J Neurosurg Spine. 2007 Jul;7(1):61-4.

Endoscopic biopsy sampling of tophaceous gout of the odontoid process. Case
report and review of the literature.

Fraser JF, Anand VK, Schwartz TH.

Department of Neurological Surgery, Weill Medical Center of Cornell University,
New York Presbyterian Hospital, New York, New York 10021, USA.

The authors present the case of a 71-year-old man who presented with neck pain, a
history of gout, and a mass in the dens. Results of transoral endoscopic biopsy
sampling demonstrated tophaceous gout. The patient was treated medically and the 
pain resolved. Tophaceous gout isolated in the dens is extremely rare and should 
be considered in the differential diagnosis of masses in this region. With the
aid of transoral or transnasal endoscopic biopsy sampling, the diagnosis can be
reached in a minimally invasive manner.

Publication Types: 
    Case Reports
    Review

PMID: 17633489 [PubMed - indexed for MEDLINE]

117: Clin Exp Rheumatol. 2007 May-Jun;25(3):385-9.

Tumor necrosis factor-alpha and interleukin-4 gene polymorphisms in Chinese
patients with gout.

Chen ML, Tsai FJ, Tsai CH, Huang CM.

Department of Medical Genetics, Division of Immunology and Rheumatology, Asia
University, China Medical University Hospital, Taichung, Taiwan.

OBJECTIVE: The purpose of this study was to examine whether polymorphisms of
interleukin-4 (IL-4) (promoter-590 and intron 3) and tumor necrosis factor-alpha 
(TNF-alpha) promoter-308 genes are markers of susceptibility to or clinical
manifestations of gout in Taiwanese patients. METHODS: The study included 196
Taiwanese patients with gout and 103 unrelated healthy control subjects living in
central Taiwan. Polymorphisms of the IL-4 (promoter-590 and intron 3) and
TNF-alpha (promoter-308) genes were typed from genomic DNA. Allelic frequencies
and carriage rates were then compared between gout patients and control subjects.
The correlation between allelic frequencies, carriage rates and clinical
manifestations of gout were evaluated. RESULTS: No significant differences were
observed in the allelic frequencies and carriage rates of the IL-4 (promoter-590 
and intron 3) and TNF-alpha gene polymorphisms between patients with gout and
healthy control subjects. Furthermore, the IL-4 (promoter-590 and intron 3) and
TNF-alpha genotypes were not found to be associated with the clinical and
laboratory profiles in gout patients. However, there was a significant difference
in the TNF-alphapolymorphism genotype between patients with and without
hypertriglyceridemia (P=0.001, xi2=11.47, OR=10.3, 95%CI=3.57-29.7). CONCLUSION: 
The results of our study suggest that polymorphisms of the IL-4 (promoter-590 and
intron 3) and TNF-alpha promoter-308 genes are not related to gout in Chinese
patients in Taiwan.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17631734 [PubMed - indexed for MEDLINE]

118: Clin Rheumatol. 2007 Dec;26(12):2185-7. Epub 2007 Jul 13.

Watch out for 'pins and needles' in hands--it may be a case of gout.

Patil VS, Chopra A.

Hand Clinic, Pune, India.

We encountered only three patients of carpal tunnel syndrome (CTS) due to
tophaceous gout during 25 years of practice in a 'hand clinic' situated in a
large metropolis in West India. In two patients, the CTS was bilateral, a rare
occurrence in gout. There was an unwarranted delay (up to 9 years) in the
diagnosis of both the ailments. In each case, the site of offending tophus was
uniquely different.

Publication Types: 
    Case Reports

PMID: 17628740 [PubMed - indexed for MEDLINE]

119: Clin Rheumatol. 2007 Dec;26(12):2197-9. Epub 2007 Jul 10.

Colchicine-induced rhabdomyolysis.

Altman A, Szyper-Kravitz M, Shoenfeld Y.

Center for Autoimmune Diseases, Sheba Medical Center Tel-Hashomer, Sackler
Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

A case of colchicine-induced rhabdomyolysis is reported. A 79-year-old man with
ischemic heart disease, chronic atrial fibrillation, chronic renal failure,
hypothyroidism, and gout arthritis was hospitalized because of fatigue, myalgia, 
and leg weakness, shortly after starting treatment with colchicine. Investigation
confirmed the diagnosis of rhabdomyolysis, and discontinuation of colchicine
resulted in resolution of clinical and biochemical features of rhabdomylysis.
Colchicine-induced rhabdomyolysis is a rare complication, and the postulated
mechanisms and risk factors for this severe complication are discussed.

Publication Types: 
    Case Reports

PMID: 17619811 [PubMed - indexed for MEDLINE]

120: Aust Fam Physician. 2007 Jul;36(7):538.

Comment in:
    Aust Fam Physician. 2007 Dec;36(12):982.    Aust Fam Physician. 2008 Jan-Feb;37(1-2):6.

Practice tip. How I use the internet.

Qureshi F.

Parklands Medical Practice, The University of Adelaide, South Australia,
Australia. farooq.qureshi@adelaide.edu.au

Ms MC, aged 22 years, has come to ask my advice regarding the discontinuation of 
warfarin after an episode of deep vein thrombosis (DVT) 3 months ago. She is a
hockey player and keen to cease her anticoagulant medication, but is concerned
about the recurrence of DVT.

PMID: 17619670 [PubMed - indexed for MEDLINE]

121: Aust Fam Physician. 2007 Jul;36(7):529-30.

Comment in:
    Aust Fam Physician. 2008 Mar;37(3):103; author reply 103.

Colchicine--what is its place in the management of acute gout?

Winzenberg T, Zochling J.

Menzies Research Institute, University of Tasmania. tania.winzenberg@utas.edu.au

This series of articles facilitated by the Cochrane Musculoskeletal Group (CMSG) 
aims to place the findings of recent Cochrane musculoskeletal reviews in a
context immediately relevant to general practitioners. This article considers the
place of colchicine in the management of acute gout.

PMID: 17619668 [PubMed - indexed for MEDLINE]

122: Arthritis Res Ther. 2007;9(4):R64.

Reduction of urate crystal-induced inflammation by root extracts from traditional
oriental medicinal plants: elevation of prostaglandin D2 levels.

Jung SM, Schumacher HR, Kim H, Kim M, Lee SH, Pessler F.

Division of Rheumatology, University of Pennsylvania, 3600 Spruce St,
Philadelphia, PA 19104, USA.

Dried roots of the plants Acanthopanax senticosus, Angelica sinensis and
Scutellaria baicalensis are used in traditional oriental medicine and reportedly 
possess anti-inflammatory properties. Using the murine air pouch model of
inflammation, we investigated the efficacy and mode of action of an extract from 
these three plants in crystal-induced inflammation. Air pouches were raised on
the backs of 8-week-old BALB/c mice. Mice were fed 100 mg/kg body weight of root 
extracts (A. senticosus:A. sinensis:S. baicalensis mixed in a ratio of 5:4:1 by
weight) or vehicle only on days 3-6. Inflammation was elicited on day 6 by
injecting 2 mg of monosodium urate (MSU) crystals into the pouch. Neutrophil
density and IL-6 and TNF-alpha mRNA levels were determined in the pouch membrane,
and the leukocyte count and IL-6, prostaglandin E2 (PGE2) and prostaglandin D2
(PGD2) levels were determined in the pouch exudate. Treatment with the root
extracts led to a reduction in all inflammatory parameters: the leukocyte count
in the pouch exudate decreased by 82%; the neutrophil density in the pouch
membrane decreased by 68%; IL-6 and TNF-alpha mRNA levels in the pouch membrane
decreased by 100%; the IL-6 concentration in the pouch fluid decreased by 50%;
and the PGE2 concentration in the pouch fluid decreased by 69%. Remarkably, the
concentration of the potentially anti-inflammatory PGD2 rose 5.2-fold in the
pouch exudate (p < 0.005), which led to a normalization of the PGD2:PGE2 ratio. A
3.7-fold rise in hematopoietic PGD synthase (h-PGDS) mRNA paralleled this rise in
PGD2 (p = 0.01). Thus, the root extracts diminished MSU crystal-induced
inflammation by reducing neutrophil recruitment and expression of
pro-inflammatory factors and increasing the level of the potentially
anti-inflammatory PGD2. These results support a need for further studies of the
efficacy of these extracts in the treatment of inflammatory arthropathies and
suggest elevation of PGD2 levels as a novel mechanism for an anti-inflammatory
agent.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17612394 [PubMed - indexed for MEDLINE]

123: Horm Metab Res. 2007 Jul;39(7):511-4.

Relationship between insulin resistance and low urinary pH in patients with gout,
and effects of PPARalpha agonists on urine pH.

Takahashi S, Inokuchi T, Kobayashi T, Ka T, Tsutsumi Z, Moriwaki Y, Yamamoto T.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Hyogo 
College of Medicine, Nishinomiya, Hyogo, Japan.

Patients with gout frequently have low urinary pH, though the underlying
mechanism has not been identified. Recently, nephrolithiasis has been reported to
be involved with renal manifestation of metabolic syndrome. The present study was
conducted to clarify the mechanism of low urinary pH in gout patients. The
relationships between urine pH and factors contributing to metabolic syndrome
were investigated. In addition, the effects of PPAR alpha agonists on urine pH
were examined. Patients with 24-hour urine samples below a level of pH 5.5 showed
higher values for factors constituting metabolic syndrome, compared with those
with 24-hour urine pH equal to or greater than 5.5. Multiple regression analysis 
demonstrated that HOMA index was the only contributing factor to low urinary pH
in gout patients, except for serum uric acid. Administrations of PPAR alpha
agonists significantly raised 24-hour urine pH levels in gout patients in
accordance with a reduction in serum triglyceride concentration, probably through
their activities to improve insulin resistance. Our results suggest that insulin 
resistance plays an important role in the development of low urinary pH in
patients with gout and that PPAR alpha agonist is preferable for raising urinary 
pH of the gout patients with hypertriglyceridemia.

Publication Types: 
    Clinical Trial

PMID: 17611904 [PubMed - indexed for MEDLINE]

124: J Rheumatol. 2007 Jul;34(7):1566-8. Epub 2007 Jun 15.

Treatment of acute gout in hospitalized patients.

Petersel D, Schlesinger N.

Rheumatology Division, Department of Medicine, University of Medicine and
Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New
Jersey 08903-0019, USA.

OBJECTIVE: To record practice patterns of treatment of acute gout in hospitalized
patients. METHODS: We performed a retrospective chart review of hospitalized
patients diagnosed with gout. RESULTS: Seventy-nine (43%) patients were diagnosed
with acute gout during their hospitalization. Fifty-eight (73%) patients with
acute gout were found to have a reduction in their glomerular filtration rate.
Twenty patients (25%) underwent arthrocentesis. The most widely used drugs for
acute gout were colchicine, n = 42 (53%), and nonsteroidal antiinflammatory drugs
(NSAID), n = 40 (51%). Combination therapy was used in 52% of patients with acute
gout. Thiry-six (86%) patients treated with colchicine and 32 (80%) patients
treated with NSAID had renal failure. DISCUSSION: Crystal analysis, the gold
standard for diagnosing gout, was performed in only 25% of patients suspected of 
acute gout. Combination antiinflammatory agents are used in over 50% of patients 
despite the absence of evidence to support use of such combinations. Renal
failure was present in 73% of patients with acute gout. Colchicine and NSAID
should therefore be used with caution in these patients. Practice patterns vary
widely and often appear to be in conflict with recommended diagnostic and
treatment measures for acute gout.

PMID: 17610315 [PubMed - indexed for MEDLINE]

125: Curr Med Res Opin. 2007 Jul;23(7):1685-91.

Association of baseline disease and patient characteristics with response to
etoricoxib and indomethacin for acute gout.

Navarra S, Rubin BR, Yu Q, Smugar SS, Tershakovec AM.

University of Santo Tomas, Manila, Philippines.

BACKGROUND AND OBJECTIVE: Disease history and clinical features can influence
treatment response in patients with acute gout. The purpose of this pooled
subgroup analysis was to assess the association of baseline disease and patient
characteristics with response to treatment in acute gout using data from two
identical studies. METHODS: Patients > or = 18 years of age with onset of acute
gout within 48 h associated with moderate, severe, or extreme pain involving less
than four joints were eligible for inclusion in the primary studies, and were
randomized to etoricoxib 120 mg once daily (N = 178) or indomethacin 50 mg three 
times daily (N = 161). The primary and secondary efficacy endpoints were analyzed
using an analysis of covariance model to detect potential differential treatment 
responses across several subgroups: joint involvement (mono-articular vs.
oligo-articular), baseline pain severity (moderate vs. severe), concomitant
allopurinol and/or colchicine use (users vs. nonusers), age (< 45, 45-55, and >
55 years), gender, and race (white or other). RESULTS: Overall, etoricoxib and
indomethacin demonstrated comparable efficacy across all subgroups. Compared with
patients with oligo-articular disease, those with mono-articular disease had
significantly greater improvements in patient assessment of pain, patient global 
assessment of response to therapy (PGART), investigator global assessment of
response to therapy (IGART), and study joint tenderness (p < 0.001 for all).
Greater improvements were seen in patient assessment of pain (p < 0.001) and
study joint tenderness (p < 0.05) for severe/extreme baseline pain compared with 
moderate baseline pain. Concomitant use of colchicine and/or allopurinol was
associated with significantly worse IGART (p < 0.05). CONCLUSIONS: This pooled
subgroup analysis demonstrated significantly greater response of acute gout to
either etoricoxib or indomethacin among those with monoarticular disease,
severe/extreme baseline pain, and non-use of colchicine and/or allopurinol. These
results should be interpreted in the context of a pooled subgroup analysis with a
limited sample size, and with the understanding that associations identified in
such analyses do not define causation. Despite limitations, the results provide
insights into the types of patients more likely to respond better to
anti-inflammatory medication, and reiterate the importance of earlier effective
control of the disease.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17588299 [PubMed - indexed for MEDLINE]

126: Rheumatology (Oxford). 2007 Sep;46(9):1441-4. Epub 2007 Jun 24.

Is gout associated with reduced quality of life? A case-control study.

Roddy E, Zhang W, Doherty M.

Academic Rheumatology, University of Nottingham, UK. e.roddy@cphc.keele.ac.uk

OBJECTIVES: To compare quality of life (QOL) between gout cases and controls in a
primary care population and to investigate whether impaired QOL in gout is
secondary to co-morbid factors or to intrinsic factors related to gout itself.
METHODS: A postal questionnaire was sent to all adults aged over 30 yrs
registered with two general practices. The questionnaire assessed a history of
gout (doctor diagnosed, or episodes suggestive of acute crystal synovitis) and
medical and musculoskeletal co-morbidities. QOL was assessed using the
WHOQoL-Bref instrument. Possible cases of gout attended for clinical assessment
where the diagnosis was verified on clinical grounds. Overall QOL, satisfaction
with health and QOL across four domains were compared between gout cases and
controls and then entered into a linear regression model adjusting for gout, age,
gender, body mass index and medical and musculoskeletal co-morbidities. RESULTS: 
Of 13 684 questionnaires mailed, 3082 completed questionnaires were returned
(23%). From 289 suggested cases of gout, 137 cases were confirmed by clinical
assessment. Compared with controls, cases had impaired overall QOL (15.67 vs
16.41, P = 0.003), satisfaction with health (13.16 vs 14.45, P < 0.001) and
physical health-related QOL (14.08 vs 15.95, P < 0.001). On multi-variate
analysis, gout remained associated with impaired physical health-related QOL
(beta = -0.059, P = 0.001) but not overall QOL (beta = -0.024, P = 0.198) or
satisfaction with health (beta = -0.028, P = 0.142). CONCLUSIONS: Gout associates
with poor overall QOL mainly resulting from associated co-morbidity. Physical
health-related QOL, however, remains impaired after adjustment for
co-morbidities.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17586863 [PubMed - indexed for MEDLINE]

127: Ann Rheum Dis. 2008 Feb;67(2):273-5. Epub 2007 Jun 8.

First metatarsophalangeal joint aspiration using a 29-gauge needle.

Sivera F, Aragon R, Pascual E.

Rheumatology Unit, Hospital General Universitario de Alicante, Universidad Miguel
Hernándes, Spain.

OBJECTIVES: To asses the clinical feasibility of aspirating symptomatic and
asymptomatic first metatarsophalangeal (MTP) joints with a 29-gauge needle in
order to obtain a synovial fluid (SF) sample. METHODS: All consecutive
aspirations of first MTP joints performed within our department were
prospectively recorded. The procedure was considered successful if SF volume was 
enough to perform a crystal search. Crystals were identified using a polarised
light microscope (magnification x400) with a first order red compensator. Pain
was recorded on a 10-cm visual analogue scale (VAS). RESULTS: Aspirations were
attempted in 33 first MTP joints in 31 patients. SF was drawn from 30 of the
joints (91%), with little difference between asymptomatic (89%) and inflamed
joints (93%). The technique was well tolerated (mean VAS 1.74). Urate monosodium 
crystals were identified in 22 samples (73%) and another sample contained calcium
pyrophosphate dihydrate crystals. CONCLUSIONS: A 29-gauge needle allows easy
aspiration of the first MTP joint with only modest discomfort for the patients,
and generally yields a SF sample of sufficient volume for crystal detection and
identification.

PMID: 17557892 [PubMed - indexed for MEDLINE]

128: J Rheumatol. 2007 Jun;34(6):1381-5.

Outcome evaluations in gout.

Schumacher HR, Taylor W, Joseph-Ridge N, Perez-Ruiz F, Chen LX, Schlesinger N,
Khanna D, Furst DE, Becker MA, Dalbeth N, Edwards NL.

Division of Rheumatology, University of Pennsylvania School of Medicine, and
Veterans Affairs Medical Center, Philadelphia, Pennsylvania 19104, USA.
schumacr@mail.med.upenn.edu

Methods to measure outcomes in gout still require consensus and validation. This 
Special Interest Group was assembled to identify domains of interest and is now
evaluating a series of outcomes for features of acute gouty arthritis and chronic
gout. To accomplish this, working groups have been formed and domains identified.
Delphi methodology has been used to address gouty flares as an outcome of
greatest interest. Studies addressing other outcome measures were reported at the
OMERACT 8 meeting and validation has begun on some outcomes. There has been
progress on developing a definition of a flare, and validating reproducibility of
some chronic gout outcome measures in some domains, such as tophus size and
patient perceptions. Use of these outcomes as well as a health-related quality of
life measure are being studied in clinical trials. Pain on a Likert scale appears
to be a valid outcome in acute gout. Final validation of these outcomes has not
yet been achieved. In summary, the unique problems of evaluating outcomes in gout
are finally being addressed. While no measures are available for use yet, an
agenda has been developed.

Publication Types: 
    Consensus Development Conference
    Research Support, Non-U.S. Gov't

PMID: 17552064 [PubMed - indexed for MEDLINE]

129: Orthopedics. 2007 May;30(5):333, 405-8.

Radiologic case study. Gout.

Spackey J, Demos TC, Lomasney LM.

Department of Radiology, Loyola University Medical Center, Maywood, IL 60153,
USA.

Characteristic imaging finding of chronic gout include eccentric soft-tissue
abnormalities, sometimes calcified, that have overly well defined erosions with
sclerotic margins and overhanging edges, and preservation of bone density. While 
the triad of acute monoarticular arthritis, hyperuricemia, and prompt response to
drug therapy is highly suggestive of acute gouty arthritis, the radiographic
findings during an acute attack are nonspecific.

Publication Types: 
    Case Reports

PMID: 17539201 [PubMed - indexed for MEDLINE]

130: Curr Rheumatol Rep. 2007 Jun;9(3):258-64.

Uricase and other novel agents for the management of patients with
treatment-failure gout.

Sundy JS, Hershfield MS.

Duke University Medical Center, Durham, NC 27710, USA. john.sundy@duke.edu

Successful management of chronic gout depends on reducing body pools of urate.
The benchmark of success is to maintain serum urate levels at less than 6 mg/dL
using therapies such as probenecid or allopurinol. In a subset of patients with
gout, these medications fail to achieve this benchmark, resulting in ongoing
signs and symptoms characteristic of treatment-failure gout. Potential therapies 
now in clinical development show promise for treating this refractory patient
population. In this article, we review the clinical characteristics associated
with treatment-failure gout and discuss recent data from clinical trials of
febuxostat and uricase.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17531181 [PubMed - indexed for MEDLINE]

131: Curr Rheumatol Rep. 2007 Jun;9(3):243-50.

Recent developments in crystal-induced inflammation pathogenesis and management.

Lioté F, Ea HK.

Fédération de Rhumatologie (pôle appareil locomoteur), INSERM U606, Paris 7
Medical University, centre Viggo Petersen (Assistance Publique- Hôpitaux de
Paris), hôpital Lariboisière, 2, rue Ambroise Paré, 75010 PARIS, France.
frederic.liote@lrb.aphp.fr

Crystal-induced inflammation pathogenesis is undergoing a transition with respect
to monosodium urate, calcium pyrophosphate dihydrate, and even basic calcium
phosphate crystals. It is now recognized that innate immunity could be involved
in the earlier pathogenic events and that the inflammasome, along with other
signaling pathways, is activated and results in interleukin-1 processing and
secretion, ultimately activating cells as a paracrine or autocrine cytokine.
Management of acute and chronic monosodium urate crystal-induced inflammation,
namely gout, has been critically reviewed by a dedicated European working group, 
and on the behalf of the European League against Rheumatism, 12 evidence-based
recommendations have been reported. Calcium pyrophosphate dihydrate chronic
inflammation could benefit from colchicine and from methotrexate as an
anti-inflammatory agent.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17531179 [PubMed - indexed for MEDLINE]

132: Arthritis Rheum. 2007 Jun 15;57(5):822-9.

Quality of care for gout in the US needs improvement.

Singh JA, Hodges JS, Toscano JP, Asch SM.

Minneapolis VA Medical Center, University of Minnesota, Minneapolis 55417, USA.
Jasvinder.Singh@med.va.gov

OBJECTIVE: To examine evidence-based quality indicators (QIs) in US veterans with
gout diagnosis, and to examine the effect of demographics, heath care
utilization/access, comorbid conditions, or physican characteristics as
predictors of quality of gout care. METHODS: Using the Minneapolis Veterans
Affairs electronic medical record system, we identified a cohort of veterans
receiving medication to treat gout between January 1, 1999 and December 31, 2003,
and evaluated 3 recently published evidence-based QIs for gout management: QI 1 =
allopurinol dose <300 mg in gout patients with renal insufficiency, QI 2 = uric
acid check within 6 months of starting a new allopurinol prescription, and QI 3 =
complete blood count and creatine kinase check every 6 months for gout patients
receiving prolonged colchicine therapy. We calculated the proportion of patients 
whose therapy adhered to each QI and to all applicable indicators (overall
physician adherence). Logistic regression analysis examined association of
overall physician adherence with sociodemographics, health care utilization,
comorbidity, and provider characteristics. RESULTS: Of 3,658 patients with a
diagnosis of gout, 663 patients qualified for examination of >/=1 QI. Of these
663 patients, therapy in only 144 (22%) adhered to all applicable QIs; 59 (78%)
of 76 adhered to QI 1, 155 (24%) of 643 adhered to QI 2, and 18 (35%) of 52
adhered to QI 3. Overall physician adherence to QIs was significantly lower in
older veterans and in those with more inpatient visits per year, but was higher
in those with more primary care visits or more health care providers. CONCLUSION:
Suboptimal physician adherence to QIs was seen for all 3 QIs tested in this
cohort of veterans with gout. These findings can guide quality improvement
efforts.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17530682 [PubMed - indexed for MEDLINE]

133: Arthritis Rheum. 2007 Jun;56(6):2049-55.

Coffee consumption and risk of incident gout in men: a prospective study.

Choi HK, Willett W, Curhan G.

Arthritis Research Centre of Canada, Vancouver General Hospital, University of
British Columbia, Vancouver, British Columbia, Canada. hchoi@partners.org

OBJECTIVE: Coffee is one of the most widely consumed beverages in the world and
may affect the risk of gout via various mechanisms. We prospectively evaluated
the relationship between coffee intake and the risk of incident gout in a large
cohort of men. METHODS: Over a 12-year period, we studied 45,869 men with no
history of gout at baseline. Intake of coffee, decaffeinated coffee, tea, and
total caffeine was assessed every 4 years through validated questionnaires. We
used a supplementary questionnaire to ascertain whether participants met the
American College of Rheumatology survey criteria for gout. RESULTS: We documented
757 confirmed incident cases of gout. Increasing coffee intake was inversely
associated with the risk of gout. The multivariate relative risks (RRs) for
incident gout according to coffee consumption categories (0, <1, 1-3, 4-5, and > 
or = 6 cups per day) were 1.00, 0.97, 0.92, 0.60 (95% confidence interval [95%
CI] 0.41-0.87), and 0.41 (95% CI 0.19-0.88), respectively (P for trend = 0.009). 
For decaffeinated coffee, the multivariate RRs according to consumption
categories (0, <1, 1-3, and > or = 4 cups per day) were 1.00, 0.83, 0.67 (95% CI 
0.54-0.82), and 0.73 (95% CI 0.46-1.17), respectively (P for trend = 0.002).
Total caffeine from all sources and tea intake were not associated with the risk 
of gout. CONCLUSION: These prospective data suggest that long-term coffee
consumption is associated with a lower risk of incident gout.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17530645 [PubMed - indexed for MEDLINE]

134: Nat Clin Pract Nephrol. 2007 Jun;3(6):345-9.

Pseudotumor of gout in the patella of a kidney transplant recipient.

Staub-Zähner T, Garzoni D, Fretz C, Lampert C, Ohlschlegel C, Wüthrich RP, Fehr
T.

Kantonsspital, St Gallen, Switzerland.

BACKGROUND: A 33-year-old renal transplant recipient presented with painless
swelling of the right knee. Physical examination revealed an impressive knee
joint effusion with no signs of inflammation. The patient did not remember a
recent trauma, but he mentioned a strain 3 years earlier; radiographic findings
had been normal at that time. The patient had suffered from end-stage renal
disease due to chronic glomerulonephritis and had previously undergone two
transplantations. At presentation, his kidney function was stable under treatment
with ciclosporin, azathioprine and steroids. INVESTIGATIONS: Conventional
radiography revealed a tumor at the superolateral pole of the right patella.
Extensive soft tissue invasion and bone destruction was seen on MRI. A knee
arthroscopy with biopsy, performed to aid diagnosis, showed extensive
chondrocalcinosis macroscopically; histologically, gouty tophi were found.
DIAGNOSIS: Pseudotumor of gout in the patella. MANAGEMENT: Uric-acid-lowering
therapy with benzbromarone was started immediately after diagnosis. A local
arthroscopic debridement of the right knee joint was performed 4 months later,
and the patient remained asymptomatic for the next 3 years.

Publication Types: 
    Case Reports

PMID: 17525717 [PubMed - indexed for MEDLINE]

135: J Vet Med A Physiol Pathol Clin Med. 2007 Jun;54(5):265-9.

Comparative frequency of osseous macroscopic pathology and first report of gout
in captive and wild-caught ratites.

Rothschild BM, Rühli FR.

Northeastern Ohio Universities College of Medicine, Rootstown, OH 44272, USA.
bmr@ku.edu

This systematic survey of museum ratite (Pterocnemia, Rhea, Casuarius, Struthio, 
Dromias and Apteryx) skeletal collections was performed to reevaluate previous
perspectives and assess effect of captivity on macroscopically detectable
pathology. Trauma-related pathology (e.g. focal periosteal reaction, malformed
vertebrae) was significantly more common in captive birds (chi2 = 13.414, P <
0.0001) with variable timing of the different injuries. Pathology unrelated to
trauma was equally represented in captive and wild-caught ratites. The latter
included osteophytes of osteoarthritis, osteochondritis dissecans, infectious
arthritis, gout (reported for the first time in a ratite) and neoplasia.

PMID: 17523962 [PubMed - indexed for MEDLINE]

136: Hematol Oncol. 2007 Sep;25(3):140-2.

Senile EBV-associated B-cell lymphoproliferative disorder of prepatellar bursa in
an elderly patient with multifocal urate arthropathy.

Mueller S, Aigner T, Haag J, Schwarz R, Niedobitek G.

Institute for Pathology, University of Leipzig, Leipzig, Germany.

We report a case of an EBV-associated high grade B-cell lymphoproliferative
disorder occurring in the synovial membrane of an elderly patient with gout
arthropathy. The EBV-infected B-cells displayed a pattern of viral gene
expression (EBNA2+/LMP1+) typically seen during primary EBV-infection and in
lymphoproliferations occurring in immunosuppressed individuals. This case
conforms to senile EBV-associated lymphoproliferative disorders previously
reported only in Japanese patients. We suggest that an impaired EBV-specific
T-cell immunity, local or systemic, may play a role in the development of this
disorder and that chronic diseases such as gout may be contributing factors. 2007
John Wiley & Sons, Ltd.

Publication Types: 
    Case Reports

PMID: 17506116 [PubMed - indexed for MEDLINE]

137: Ann Rheum Dis. 2007 Oct;66(10):1311-5. Epub 2007 May 15.

Concordance of the management of chronic gout in a UK primary-care population
with the EULAR gout recommendations.

Roddy E, Zhang W, Doherty M.

Academic Rheumatology, University of Nottingham, UK. e.roddy@cphc.keele.ac.uk

OBJECTIVES: To assess concordance of the management of chronic gout in UK primary
care with the European League Against Rheumatism (EULAR) gout recommendations.
METHODS: A postal questionnaire was sent to all adults aged >30 years registered 
with two general practices. Patients with possible gout attended for clinical
assessment, at which the diagnosis was verified clinically. Aspects of chronic
gout management, including provision of lifestyle modification advice, use of
urate-lowering therapies (ULT) including dose titration to serum urate (SUA)
level, prophylaxis against acute attacks, and diuretic cessation were assessed in
accordance with the EULAR recommendations. RESULTS: Of 4249 (32%) completed
questionnaires returned, 488 reported gout or acute attacks and were invited for 
clinical assessment. Of 359 attendees, 164 clinically confirmed cases of gout
were identified. Advice regarding alcohol consumption was recalled by 59 (41%),
weight loss by 36 (25%) and diet by 42 (29%). Allopurinol was the only ULT used
and was taken by 44 (30%); 31 (70%) were taking 300 mg daily. Mean SUA was lower 
in allopurinol users than non-users (318 vs 434 micromol/l) and was less often
>360 micromol/l in allopurinol users (23% vs 75%). Eight patients had recently
commenced allopurinol; two of these also were taking prophylactic colchicine or
non-steroidal anti-inflammatory drugs. Of 25 patients with diuretic-induced gout,
16 (64%) were still taking a diuretic. CONCLUSION: Treatment of chronic gout is
often suboptimal and poorly concordant with EULAR recommendations. Lifestyle
advice is infrequently offered, and allopurinol is restricted to a minority.
Persistent hyperuricaemia was often seen in allopurinol non-users, but was also
in allopurinol users, suggesting that doses >300 mg are often necessary.

Publication Types: 
    Multicenter Study

PMID: 17504843 [PubMed - indexed for MEDLINE]

138: Rheumatology (Oxford). 2007 Jul;46(7):1126-32. Epub 2007 May 3.

Lumiracoxib 400 mg once daily is comparable to indomethacin 50 mg three times
daily for the treatment of acute flares of gout.

Willburger RE, Mysler E, Derbot J, Jung T, Thurston H, Kreiss A, Litschig S,
Krammer G, Tate GA.

Orthopaedic University Clinic, Bochum, Germany.

OBJECTIVES: To demonstrate non-inferiority of lumiracoxib 400 mg once daily
(o.d.) compared with indomethacin 50 mg three times daily (t.i.d.) in the
treatment of acute gout, and to compare the safety and tolerability of these
treatments. METHODS: In this 1-week, multicentre, randomized, double-blind,
double-dummy, active-controlled, parallel-group study, patients with a clinical
diagnosis of gout, an acute attack of gout in four or more joints within the 48 h
prior to evaluation, and at least moderate pain intensity in the target joint
were randomized to treatment with lumiracoxib 400 mg o.d. (n = 118) or
indomethacin 50 mg t.i.d. (n = 117). The primary efficacy endpoint was the mean
change in pain intensity from baseline over days 2-5, assessed on a 5-point
Likert scale, where non-inferiority could be claimed if the lower limit of the
confidence interval (CI) was greater than -0.5. The patient's and physician's
global assessment of response to treatment, and physician's assessment of
tenderness, swelling and erythema of the study joint were also assessed. RESULTS:
The estimated difference between treatments for the change from baseline in pain 
intensity over days 2-5 was -0.004 (95% CI -0.207 to 0.199, P > 0.05), indicating
that lumiracoxib 400 mg o.d. had comparable efficacy to indomethacin 50 mg t.i.d.
for the primary efficacy variable. There was no significant difference between
treatments in any of the secondary efficacy variables. Adverse events were
reported by 10.2% of patients treated with lumiracoxib and 22.2% of those
receiving indomethacin. CONCLUSIONS: Lumiracoxib is as effective as indomethacin 
for treatment of acute gout and may have a better safety and tolerability
profile.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 17478464 [PubMed - indexed for MEDLINE]

139: J Chin Med Assoc. 2007 Apr;70(4):180-2.

Gouty arthropathy of the cervical spine in a young adult.

Kuo YJ, Chiang CJ, Tsuang YH.

Department of Orthopedic Surgery, Taipei City Hospital, Taipei, Taiwan, R.O.C.

We report a young man with gouty discitis of the cervical spine. To our
knowledge, our patient is the youngest patient with cervical gouty discitis
reported in the literature. The clinical manifestation was similar to that of
cervical spondylosis with radiculopathy. Gouty discitis was diagnosed only when
tophi in the disc were found during surgery and proved by pathologic study.
Surgical decompression followed by optimization of pharmacologic treatment
enabled good recovery from neurologic complications.

Publication Types: 
    Case Reports

PMID: 17475601 [PubMed - indexed for MEDLINE]

140: Rheumatology (Oxford). 2007 Jul;46(7):1116-21. Epub 2007 Apr 27.

Diagnosis of gout by ultrasound.

Thiele RG, Schlesinger N.

Rheumatology Division, Department of Medicine Cooper University Hospital, Camden,
NJ, USA. ralf_thiele@urmc.rochester.edu

OBJECTIVES: To establish the usefulness of ultrasonography (US) for diagnosing
gout and to determine whether there are sonographic features that are
characteristic for gout but not for other arthropathies. METHODS: We
retrospectively compared joint images of gout patients with matching images from 
patients with other rheumatic conditions. Images of 37 joints of 23 patients with
monosodium urate (MSU) crystal-proven gout were reviewed. MSU crystals were
identified in at least one joint in each patient. Our control group had 23
randomly selected patients with 33 examined joints with rheumatic conditions
other than gout. RESULTS: Specific diagnostic features included a hyperechoic,
irregular band over the superficial margin of the articular cartilage described
as a double contour sign in 92% of gouty joints and in none of the controls (P < 
0.001); hypoechoic to hyperechoic, inhomogeneous material surrounded by a small
anechoic rim, representing tophaceous material, was seen in all gouty
metatarsophalangeal (MTP) joints, in all metacarpophalangeal (MCP) joints and in 
none of the controls (P < 0.001); erosions adjacent to tophaceous material were
seen in 65% of MTP joints and in 25% of MCP joints. One erosion was seen in a MTP
joint in a control patient with psoriatic arthritis. CONCLUSIONS: US can detect
deposition of MSU crystals on cartilaginous surfaces (P < 0.001) as well as
tophaceous material and typical erosions. US may serve as a non-invasive means to
diagnose gout.

Publication Types: 
    Comparative Study

PMID: 17468505 [PubMed - indexed for MEDLINE]

141: Arch Orthop Trauma Surg. 2008 May;128(5):521-3. Epub 2007 Apr 11.

Endoscopic resection of the gouty tophi of the first metatarsophalangeal joint.

Lui TH.

Department of Orthopaedics and Traumatology, North District Hospital, 9 Po Kin
Road, Sheung Shui, NT, Hong Kong SAR, China. luithderek@yahoo.co.uk

Gouty tophus of the first metatarsophalangeal joint can cause shoewear problem.
It can ulcerate and lead to secondary infections. Wound complications are common 
after open resection of the tophus. We describe an endoscopic approach to resect 
the tophus in order to minimize the soft tissue complications.

Publication Types: 
    Case Reports

PMID: 17429664 [PubMed - indexed for MEDLINE]

142: J Orthop Surg (Hong Kong). 2007 Apr;15(1):94-101.

Crystal arthropathy of the lumbar spine: a report of 4 cases.

Lam HY, Cheung KY, Law SW, Fung KY.

Department of Orthopaedics and Traumatology, Alice Ho Miu Ling Nethersole
Hospital, Hong Kong. imfiona2000@yahoo.com

Gout or pseudogout, caused by deposition of crystals, rarely affects the spine.
We report 4 cases with gout or pseudogout in the lumbar spine. Two had cauda
equina syndrome and another 2 had spinal stenosis. To avoid unnecessary surgery, 
this should be considered in the differential diagnosis when treating patients
with histories of gout or pseudogout for spinal problems.

Publication Types: 
    Case Reports
    Review

PMID: 17429128 [PubMed - indexed for MEDLINE]

143: Arch Med Res. 2007 May;38(4):460-2.

HPRT deficiency in a two-month-old child presenting acute renal failure and gout 
with a new deletion of two bases in exon 3 of the HPRT gene.

Zamora A, Escárcega RO, Vazquez R, Zamora A, O'Neill JP.

Department of Pediatrics, Hospital Infantil de México Federico Gómez, México
City, México. chamu14@hotmail.com

We describe an HPRT deficiency in a 2-month-old child who presented acute renal
failure and gout with normal mental and motor development for age. The patient
was diagnosed with Lesch-Nyhan disease and showed a new mutation, a deletion of
two bases in exon 3 of the HPRT gene (c.269-270delAT).

Publication Types: 
    Case Reports

PMID: 17416296 [PubMed - indexed for MEDLINE]

144: Int J Med Sci. 2007 Mar 2;4(2):83-93.

Rasburicase represents a new tool for hyperuricemia in tumor lysis syndrome and
in gout.

Cammalleri L, Malaguarnera M.

Dept of Senescence, Urological and Neurological Sciences, University of Catania, 
Catania, Italy.

Hyperuricemia is a feature of several pathologies and requires an appropriate and
often early treatment, owing to the severe consequences that it may cause. A
rapid and massive raise of uric acid, during tumor lysis syndrome (TLS), and also
a lower and chronic hyperuricemia, as in gout, mainly damage the kidney. To
prevent or treat these consequences, a new therapeutic option is represented by
rasburicase, a recombinant form of an enzyme, urate oxidase. This enzyme converts
hypoxanthine and xanthine into allantoin, a more soluble molecule, easily cleared
by kidney. The several types of urate oxidase have followed each other, with
progressive reduction of adverse reactions. The most important among them are
allergenicity and the development of antibodies which compromise their
effectiveness. Nevertheless, a limit of rasburicase's use remains its cost, which
obliges to a judicious choice to prevent TLS in high risk patients with cancer
and in case of allergy or impossibility to take allopurinol orally both in TLS
and in gout. A large body of evidence confirms the efficacy and safety of
rasburicase, even in comparison to the standard drugs used in the aforementioned 
pathologies.

Publication Types: 
    Review

PMID: 17396159 [PubMed - indexed for MEDLINE]

145: Arthritis Rheum. 2007 Apr 15;57(3):461-5.

Computed tomography measurement of tophus volume: comparison with physical
measurement.

Dalbeth N, Clark B, Gregory K, Gamble GD, Doyle A, McQueen FM.

University of Auckland, Auckland, New Zealand.

OBJECTIVE: Computed tomography (CT) has high accuracy for tophus detection. This 
study assessed reliability of CT measurement of tophus volume and compared
reproducibility of CT with physical measurement of tophus size. METHODS:
Forty-seven hand tophi were analyzed in 20 patients with gout. The longest tophus
diameter was recorded by 2 independent observers. All patients proceeded to CT
scanning of the hands on a Philips Brilliance scanner (0.8-mm slices). Two
independent observers measured tophus volume using the Surface Shaded Display
3-dimensional function on the Philips CT workstation. Five patients underwent
repeat physical and CT assessments within 1 week (18 observations). Inter- and
intraobserver reproducibility were analyzed by limits of agreement and
coefficients of variation. RESULTS: Of the 47 lesions identified as tophi on
physical examination, 42 (89%) were also identified on CT. The mean (95%
confidence interval [95% CI]) difference between observers for physical
measurement was 0.45 mm (-4.07, 4.96) and for CT was 65.2 mm(3) (-293.0, 423.3). 
The mean (95% CI) difference between visits for physical measurement was -0.72 mm
(-5.47, 4.03) and for CT was -13.1 mm(3) (-112.5, 86.3). There was no difference 
between coefficients of variation for inter- and intraobserver reproducibility
for the 2 measurement techniques. For tophi identified by physical and CT
assessment, there was good correlation between measurements (r = 0.91, P <
0.0001). CONCLUSION: CT assessment of tophus volume is reliable and reproducible.
However, physical measurement correlates well with CT and has equivalent
reproducibility. These data support the use of physical measurement as a simple
and reliable method to assess tophus size.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 17394233 [PubMed - indexed for MEDLINE]

146: Intern Med J. 2007 Apr;37(4):258-66.

Emerging therapies in the long-term management of hyperuricaemia and gout.

Stamp LK, O'Donnell JL, Chapman PT.

Department of Medicine, Christchurch School of Medicine and Health Sciences,
University of Otago, Christchurch, New Zealand. lisa.stamp@cdhb.govt.nz

Gout is a common chronic arthritis that can lead to significant disability. Gout 
is one of the few rheumatological conditions that can be diagnosed with
certainty, has a known cause and can be cured with appropriate therapy.
Hypouricaemic agents reduce uric acid concentrations through inhibiting uric acid
production (allopurinol) or enhancing uric acid excretion (probenecid,
benzbromarone). Allopurinol is the most commonly used hypouricaemic agent but at 
recommended doses often fails to reduce adequately uric acid concentrations and
prevent acute attacks of gout. The use of probenecid is limited by lack of
efficacy in renal impairment. In the last few years, new agents in the management
of hyperuricaemia and gout have become available. Febuxostat, a new xanthine
oxidase inhibitor, is an effective hypouricaemic agent although further data are 
required for patients with renal impairment and other significant medical
conditions. Rasburicase, a recombinant uricase (which catalyses the conversion of
uric acid to the more readily excreted allantoin) is available for prevention of 
tumour lysis syndrome. However, its repeated use, as would be required in chronic
gout, is limited by antigenicity. A less antigenic PEGylated uricase can rapidly 
reduce serum uric acid concentrations and promote resorption of tophi. However,
further information with regard to the long-term risks and benefits of these
agents is required. These agents may ultimately be used in the short term to
rapidly deplete urate stores (induction therapy) followed by long-term therapy
with an alternative hypouricaemic agent to prevent subsequent accumulation of
uric acid (maintenance therapy).

Publication Types: 
    Review

PMID: 17388867 [PubMed - indexed for MEDLINE]

147: Rheum Dis Clin North Am. 2007 Feb;33(1):33-55.

Crystal-associated arthritis in the elderly.

Wise CM.

Internal Medicine, Division of Rheumatology, Allergy, and Immunology, Medical
College of Virginia, Virginia Commonwealth University Health System, 417 North
11th Street, Box 980647, Richmond, VA 23298, USA. cmwise@hsc.vcu.edu

Since the original recognition of these conditions in 1961, a great deal has been
learned about the pathogenesis, clinical manifestations, and appropriate
treatment of gout and pseudogout, and the role of crystals in osteoarthritis has 
been further defined. The variable manifestations of crystal-induced arthritis in
elderly populations has led to a greater need for proper diagnosis and treatment 
strategies for these increasingly common forms of arthritis.

Publication Types: 
    Review

PMID: 17367691 [PubMed - indexed for MEDLINE]

148: Clin Rheumatol. 2007 Oct;26(10):1655-61. Epub 2007 Mar 14.

Coexisting ankylosing spondylitis and gouty arthritis.

Ho HH, Yu KH, Chen JY, Lin JL, Wu YJ, Luo SF, Liou LB.

Division of Rheumatology, Allergy and Immunology, Department of Internal
Medicine, Chang Gung Memorial Hospital and Chang Gung University, 5 Fu-shin
Street, Kuei-Shan, Tao-Yuan, Taiwan. ling0126@cgmh.org.tw

The aim of this study was to investigate the clinical characteristics of patients
with coexisting ankylosing spondylitis (AS) and gout. Between July 1987, and
October 2004, sixty-five patients with coexisting AS and gout were enrolled. The 
clinical manifestations of both AS and gout in these patients were studied. Of
the 65 patients included in the study, 61 were men and four were women
(men-to-women ratio, 15.3:1). Sixty-three subjects were Han Chinese, and two were
Atayal Aborigines. Mean ages at onset of AS and gout were 29.3 +/- 15.6 years
(range 7-63) and 42.2 +/- 13.2 years (range 20-74), respectively. Fifty-six
patients developed gout after (15.5 +/- 11.2 years; range, 1-51 years) onset of
AS; nine patients developed gout before (average, 3.4 +/- 2.2 years; range. 1-7
years) onset of AS. Forty-four (67.7%) patients had chronic peripheral arthritis 
and all 65 (100%) patients had acute peripheral arthritis. Thirty-three (50.8%)
cases had heel pain (enthesopathy), including 22 (33.9%) with chronic heel pain, 
seven (10.8%) with acute heel pain, and four (6.2%) with concurrent acute and
chronic heel pain. Sixty-one (93.9%) subjects were HLA-B27 antigen positive.
Medical conditions potentially associated with hyperuricemia or gout were
urolithiasis (n = 17), hypertension (n = 21), diabetes mellitus (n = 8),
hyperlipidemia (n = 34), congestive heart failure (n = 6), coronary heart disease
(n = 5), and stroke (n = 3). The following drugs were prescribed: diuretics (n = 
7), low-dose aspirin (n = 4), antituberculous drugs (n = 1), and sulphasalazine
(n = 34). Six (6.2%) patients had iatrogenic Cushing syndrome with adrenal
insufficiency. Patients with coexisting AS and gout are not rare. Distinguishing 
between peripheral arthritis or enthesopathies of AS and gout is essential,
especially when the course of AS arthritis becomes acute or the course of gout
becomes chronic.

PMID: 17356931 [PubMed - indexed for MEDLINE]

149: Curr Med Res Opin. 2007 Mar;23(3):623-30.

Metabolic syndrome-related conditions among people with and without gout:
prevalence and resource use.

Novak S, Melkonian AK, Patel PA, Kleinman NL, Joseph-Ridge N, Brook RA.

Pharmacy Practice, University of Texas at Austin, Austin, TX, USA.

OBJECTIVE: A cohort of employees with gout were compared to those without to
evaluate the differences in prevalence of disorders associated with metabolic
syndrome (both those considered underlying and those associated with end-stage
morbidity and mortality) as well as the cost of annual medical services (AMS)
required for treatment of these conditions. METHODS: Employees with gout were
identified by International Classification of Diseases-9 (ICD-9) code during the 
calendar years of 2001-2004 and compared to propensity-score matched employees
without gout using the Human Capital Management Services Research Reference
Database. T-tests were then used to compare prevalence and average AMS of
comorbid disorders defined from Agency for Healthcare and Research Quality (AHRQ)
diagnostic categories. RESULTS: 'Hyperlipidemia', 'essential hypertension', and
'diabetes mellitus without complications' ranked in the top 10 categories of mean
number of AMS for employees with gout using AHRQ specific categories; the values 
were higher than found for those without gout (all p < 0.0001). 'Essential
hypertension', 'hyperlipidemia', 'diabetes mellitus without complications', and
'coronary atherosclerosis' showed an approximate 2:1 prevalence ratio for
employees with gout over those without (p < or = 0.05). Main study limitations
include the small number of subjects with gout, retrospective study design, and
possible miscoding and/or non-coding of individuals with the studied disorders.
CONCLUSION: These results support the continued need for patients with gout and
their clinicians to be aware of the possibility of the increased risk of
associated metabolic syndrome and related comorbidities in these individuals,
emphasizing the need for prevention when possible and treatment when necessary.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17355743 [PubMed - indexed for MEDLINE]

150: Arthritis Res Ther. 2007;9(2):R28.

A pilot study of IL-1 inhibition by anakinra in acute gout.

So A, De Smedt T, Revaz S, Tschopp J.

Service of Rhumatologie, Department of Medicine, Centre Hospitalier Universtaire 
Vaudois and University of Lausanne, 1011 Lausanne, Switzerland.
AlexanderKai-Lik.So@chuv.ch

Monosodium urate crystals stimulate monocytes and macrophages to release IL-1beta
through the NALP3 component of the inflammasome. The effectiveness of IL-1
inhibition in hereditary autoinflammatory syndromes with mutations in the NALP3
protein suggested that IL-1 inhibition might also be effective in relieving the
inflammatory manifestations of acute gout. The effectiveness of IL-1 inhibition
was first evaluated in a mouse model of monosodium urate crystal-induced
inflammation. IL-1 inhibition prevented peritoneal neutrophil accumulation but
TNF blockade had no effect. Based on these findings, we performed a pilot,
open-labeled study (trial registration number ISRCTN10862635) in 10 patients with
gout who could not tolerate or had failed standard antiinflammatory therapies.
All patients received 100 mg anakinra daily for 3 days. All 10 patients with
acute gout responded rapidly to anakinra. No adverse effects were observed. IL-1 
blockade appears to be an effective therapy for acute gouty arthritis. The
clinical findings need to be confirmed in a controlled study.

Publication Types: 
    Case Reports
    Clinical Trial

PMID: 17352828 [PubMed - indexed for MEDLINE]

151: Am J Med. 2007 Mar;120(3):221-4.

Comment in:
    Am J Med. 2007 Nov;120(11):e31; author reply e33.

Updates in the management of gout.

Keith MP, Gilliland WR.

Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
mpkeith@bethesda.med.navy.mil

The majority of patients with gout are cared for by primary care physicians.
Although both the physician and patient may easily recognize the acute arthritis 
of gout, errors in selecting the most appropriate medication and proper dose are 
common. The clinical stages of gout include asymptomatic hyperuricemia,
intermittent gouty arthritis, and chronic tophaceous gout. Treatment of gout is
usually considered after the first attack of arthritis, typically podagra. The
aims of treatment are to alleviate the pain and inflammation associated with
acute attacks, prevent future attacks, and decrease uric acid levels. Confusion
frequently arises because certain medications such as colchicine may have dual
purposes: to treat an acute attack and to suppress future attacks. The purpose of
this management update is to provide practical advice about prescribing the
proper medication considering both treatment goals and patient comorbidities.

Publication Types: 
    Review

PMID: 17349440 [PubMed - indexed for MEDLINE]

152: Arthritis Rheum. 2007 Mar;56(3):1021-8.

Erratum in:
    Arthritis Rheum. 2007 Apr;56(4):1370.

Pharmacokinetics and pharmacodynamics of intravenous PEGylated recombinant
mammalian urate oxidase in patients with refractory gout.

Sundy JS, Ganson NJ, Kelly SJ, Scarlett EL, Rehrig CD, Huang W, Hershfield MS.

Duke University Medical Center, Durham, North Carolina 27710, USA.

OBJECTIVE: To evaluate the efficacy, immunogenicity, and tolerability of
intravenous (IV) PEGylated recombinant mammalian urate oxidase (PEG-uricase) for 
the treatment of severe gout. METHODS: Single infusions of PEG-uricase (at doses 
ranging from 0.5 mg to 12 mg) were administered to 24 patients (6 cohorts of 4
patients each) in a phase I clinical trial. Plasma uricase activity (pUox), the
plasma urate concentration (pUAc), and the uric acid-to-creatinine ratio (UAc:Cr)
in urine were monitored for 21 days after dosing. Adverse events and the IgG
antibody response to PEG-uricase were followed up for 35 days. RESULTS: All
patients completed the trial. Maximum pUox was linearly related to the IV dose of
PEG-uricase, the area under the curve (AUC) value increased linearly (up to a
dose of 8 mg), and the pUox half-life was 6.4-13.8 days. After doses of 4-12 mg, 
the pUAc fell within 24-72 hours, from a mean +/- SD value of 11.1 +/- 0.6 mg/dl 
to 1.0 +/- 0.5 mg/dl; the AUC value for the pUAc was equivalent to maintaining
the pUAc at 1.2-4.7 mg/dl for 21 days postinfusion. The UAc:Cr ratio in urine
fell in parallel with the pUAc. IgG antibodies to PEG-uricase, mostly IgG2 and
specific for PEG, developed in 9 patients, who had more rapid enzyme clearance
but no allergic reactions. All adverse events were mild to moderate, with gout
flares being most common. CONCLUSION: The bioavailability, efficacy, and
tolerability of IV PEG-uricase were greater than the bioavailability, efficacy,
and tolerability observed in a previous phase I trial of subcutaneous
PEG-uricase. Infusing 4-12 mg of PEG-uricase every 2-4 weeks should maintain the 
pUAc well below the therapeutic target of 6 mg/dl and greatly reduce renal uric
acid excretion. This treatment could be effective in depleting expanded tissue
urate stores in patients with chronic or tophaceous gout.

Publication Types: 
    Clinical Trial, Phase I
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17328081 [PubMed - indexed for MEDLINE]

153: J Rheumatol. 2007 Apr;34(4):794-7. Epub 2007 Feb 15.

Identification of a new single-nucleotide mutation on the hypoxanthine-guanine
phosphoribosyltransferase gene from 983 cases with gout in Taiwan.

Wu CH, Lai HM, Yang MC, Liaw CC, Chang SJ, Ko YC, Chen CJ.

Division of Rheumatology, Allergy and Immunology, Department of Internal
Medicine, Chang Gung Memorial Hospital at Chia-Yi, Chang Gung University College 
of Medicine, Taiwan.

OBJECTIVE: The frequency of hypoxanthine-guanine phosphoribosyltransferase (HPRT)
deficiency within the gout-affected population in Taiwan was unclear. We
evaluated its frequency and sought to identify a new genetic variation in a case 
with HPRT deficiency. METHODS: From 2004 to 2005, a total of 983 patients with
gout were followed among outpatients attending the Department of Rheumatology.
Among these, 12 cases were suspected to have HPRT deficiency, and HPRT activity
was examined by HPLC. In the index case found to have HPRT deficiency, genetic
variation was analyzed by RT-PCR, direct sequencing, and SSCP. RESULTS: Only a
single case proved to have partial HPRT deficiency among 12 suspicious cases.
Both cDNA and genomic DNA analysis identified a new mutation on exon 2 with T to 
G transition at cDNA base 93, resulting in a change from aspartic acid to
glutamic acid at position 31. It was designated as HPRTChia-Yi, from our case's
residence at Chia-Yi Hsein, Taiwan. CONCLUSION: According to this hospital-based 
survey, HPRT deficiency is a rare trait in the Taiwanese gouty population.
However, our index case with HPRT deficiency provided the first proven HPRT
mutation in non-aboriginal Taiwanese patients with gout, which was different from
a mutation previously found in aboriginal Taiwanese. Hence, in non-aboriginal
Taiwanese gouty patients with HPRT deficiency, exon 2, rather than just exon 3,
should be analyzed.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17309125 [PubMed - indexed for MEDLINE]

154: Clin Rheumatol. 2007 Sep;26(9):1459-65. Epub 2007 Feb 17.

Comment in:
    Curr Rheumatol Rep. 2008 Jul;10(3):215.

Biochemical effectiveness of allopurinol and allopurinol-probenecid in previously
benzbromarone-treated gout patients.

Reinders MK, van Roon EN, Houtman PM, Brouwers JR, Jansen TL.

Department of Clinical Pharmacy and Pharmacology, Medical Centre Leeuwarden,
Henri Dunantweg 2, 8934 AD, Leeuwarden, The Netherlands. m.reinders@znb.nl

In 2003, the uricosuric drug benzbromarone was withdrawn from the market. The
first alternative drug of choice was the xanthine oxidase inhibitor allopurinol. 
The purpose was to (1) investigate the efficacy of allopurinol (standard dosage) 
compared with previous treatment with benzbromarone; and (2) investigate the
combination therapy allopurinol-probenecid as an effective alternative treatment 
compared with previous benzbromarone treatment. A prospective, open study was
carried out in a cohort of 51 gout patients who discontinued benzbromarone
therapy because of market withdrawal. Patients were given 200-300 mg allopurinol 
(stage 1). When allopurinol failed to attain the target serum urate (sUr) levels 
<or=0.30 mmol/l, probenecid 1,000 mg/day was added (stage 2). Treatment with
benzbromarone monotherapy (range: 100-200 mg/day; mean 138 mg/day) resulted in
92% of patients reaching target levels sUr <or= 0.30 mmol/l with a decrease of
61[11]% compared to baseline. In stage 1, 32 patients completed treatment with
allopurinol monotherapy (range 200-300 mg/day; mean 256 mg/day), which resulted
in 25% of patients attaining sUr target levels. Decrease in sUr levels was
36[11]%, which was significantly less compared to treatment with benzbromarone (p
< 0.001). In stage 2, 14 patients received allopurinol-probenecid combination
therapy, which resulted in 86% of patients attaining target sUr levels (after
failure on allopurinol monotherapy), which was comparable to previous treatment
with benzbromarone (p = 0.81). Decrease in sUr levels was 53[9]% (CI 95%:
48-58%), which was a non-significant difference compared to previous treatment
with benzbromarone (p = 0.23). Benzbromarone is a very effective
antihyperuricemic drug with 91% success in attainment of target sUr levels
<or=0.30 mmol/l. Allopurinol 200-300 mg/day was shown to be a less potent
alternative for most selected patients to attain target sUr levels (13% success).
In patients failing on allopurinol monotherapy, the addition of probenecid proves
to be an effective treatment strategy for attaining sUr target levels (86%
success).

Publication Types: 
    Clinical Trial

PMID: 17308859 [PubMed - indexed for MEDLINE]

155: Ann Rheum Dis. 2007 Oct;66(10):1374-7. Epub 2007 Feb 6.

Are joints affected by gout also affected by osteoarthritis?

Roddy E, Zhang W, Doherty M.

Academic Rheumatology, University of Nottingham, UK. e.roddy@cphc.keele.ac.uk

OBJECTIVES: To determine whether joints affected by gout are also affected by
osteoarthritis (OA). METHODS: A postal questionnaire was sent to all adults aged 
over 30 years registered with two general practices. The questionnaire assessed a
history of gout (doctor diagnosed, or episodes suggestive of acute crystal
synovitis) and medication use. Patients who possibly had gout attended for
clinical assessment to verify the diagnosis on clinical grounds and assess the
distribution of joints affected by acute attacks of gout and OA. Adjusted odds
ratios (aOR) and 95% confidence intervals (CI) were calculated between the
history of an acute attack of gout and the presence of OA at an individual joint 
adjusted for age, gender, body mass index and prior diuretic use in a binary
logistic regression model. RESULTS: A total of 4249 completed questionnaires were
returned (32%). From 359 attendees, 164 cases of gout were clinically confirmed. 
A highly significant association existed between the site of acute attacks of
gout and the presence of OA (aOR 7.94; 95% CI 6.27, 10.05). Analysis at
individual joint sites revealed a significant association at the first
metatarsophalangeal joint (aOR 2.06; 95% CI 1.28, 3.30), mid-foot (aOR 2.85; 95% 
CI 1.34, 6.03), knee (aOR 3.07; 95% CI 1.05, 8.96) and distal interphalangeal
joints (aOR 12.67; 95% CI 1.46, 109.91). CONCLUSION: Acute attacks of gout at
individual joint sites are associated with the presence of clinically assessed OA
at that joint suggesting that OA may predispose to the localised deposition of
monosodium urate crystals.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17284542 [PubMed - indexed for MEDLINE]

156: Curr Opin Rheumatol. 2007 Mar;19(2):146-50.

Recent advances in crystal-induced acute inflammation.

Akahoshi T, Murakami Y, Kitasato H.

Department of General Medicine, Kitasato University School of Medicine, Kitasato,
Sagamihara, Kanagawa, Japan. akahoshi@med.kitasato-u.ac.jp

PURPOSE OF REVIEW: The aim of this article is to highlight recent advances
suggesting essential involvement of the innate immune system in crystal-induced
acute inflammation. RECENT FINDINGS: Gout is a disease caused by the deposition
of monosodium urate monohydrate crystals. Precise mechanisms underlying the
initiation of monosodium urate monohydrate crystal-induced acute inflammation,
however, are not known. Recent investigations provided novel evidence in the
pathology of acute gout. Immunological study indicated that monosodium urate
monohydrate crystals can act as a 'danger signal' that resembles exogenous
adjuvants. Two laboratories have documented interesting findings that Toll-like
receptor-mediated pathways or MyD88-dependent pathways are involved in monosodium
urate monohydrate crystal-induced acute inflammation. Upregulation of the
triggering receptor expressed on myeloid cells 1 (TREM-1) in phagocytes by the
stimulation with monosodium urate monohydrate crystals has been demonstrated.
Furthermore, pathological significance of NALP 3 inflammasome in gout has been
shown. These findings provide a new concept that the innate immune system may
play a crucial role on the triggering of crystal-induced acute inflammation.
Spontaneous resolution is a characteristic feature of acute gout. Involvement of 
nuclear hormone receptors, peroxisome proliferator-activated receptor gamma and
liver X receptor alpha, during the termination of acute gout has been also shown.
SUMMARY: These studies provided a new insight into the mechanisms underlying the 
initiation and the termination of monosodium urate monohydrate crystal-induced
acute inflammation.

Publication Types: 
    Review

PMID: 17278929 [PubMed - indexed for MEDLINE]

157: Curr Opin Rheumatol. 2007 Mar;19(2):134-45.

Genetics and experimental models of crystal-induced arthritis. Lessons learned
from mice and men: is it crystal clear?

Reginato AM, Olsen BR.

Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
areginato@partners.org

PURPOSE OF REVIEW: We examine the major genes in mice and humans involved in the 
pathogenesis of monosodium urate, calcium pyrophosphate dihydrate and
hydroxyapatite crystal-induced arthritis. RECENT FINDINGS: Several genetic causes
of renal disease associated with hyperuricemia and gout provide insight into
genes involved in renal urate handling. Mutations or polymorphisms in exons 4 and
5 and intron 4 of urate transporter 1 may be independent genetic markers of
hyperuricemia and gout. Genetic analysis supports the role of ANKH mutations in
calcium pyrophosphate dihydrate-induced arthritis. ANKH gain-of-function
mutations were confirmed by functional studies; however, the crystals formed in
ATD5 cells were basic calcium phosphate, not calcium pyrophosphate dihydrate,
underlying the significance of chondrocyte differentiation state and the factors 
regulating normal and pathological mineralization. Animal models have implicated 
a general model of crystal-induced inflammation involving innate immunity through
the NALP3 (Natch domain, leucine-rich repeat, and PYD-containing protein 3)
inflammasome signaling through the interleukin-1 receptor and its signaling
protein myeloid differentiation primary response protein 88. SUMMARY: Genetic
analysis has elucidated genes responsible for crystal formation and animal models
have unveiled mechanisms in the development of crystal-induced arthritis. Future 
studies will hasten understanding of the pathology of crystal-induced arthritis
and provide new therapies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17278928 [PubMed - indexed for MEDLINE]

158: Curr Opin Rheumatol. 2007 Mar;19(2):128-33.

Imaging modalities and monitoring measures of gout.

Perez-Ruiz F, Naredo E.

Department of Rheumatology, Hospital de Cruces, Vizcaya, Spain.
fperez@hcru.osakidetza.net

PURPOSE OF REVIEW: Imaging modalities for gout have been mostly restrained to
radiographs. Ultrasonography, computed tomography and magnetic resonance imaging 
are emerging techniques that could be used for diagnosis, evaluation, and
monitoring acute and chronic gout. RECENT FINDINGS: Diagnosis of gout is based on
urate crystal observation with microscopy. Recently, crystal deposition in the
hyaline cartilage has been described to be different in gout from that of calcium
pyrophosphate, but validation of the findings is pending. Severity of gout with
simple radiographs may not disclose periarticular or intra-articular urate
deposition. Ultrasonography, computed tomography and magnetic resonance imaging
may improve the evaluation of tophi not apparent in clinical examination or
simple radiographs. Monitoring urate deposition may be accomplished with imaging 
techniques. This would be of outstanding interest for clinical trials, but also
for evaluating clinical response to urate-lowering therapy. Although preliminary 
results evaluating for validity and reliability have been very recently reported 
for magnetic resonance imaging, computed tomography and ultrasonography,
sensitivity to change studies are still pending. Also, monitoring of chronic
inflammation with imaging techniques, such as power-Doppler, deserve further
studies. SUMMARY: Evidence exists regarding the usefulness of imaging techniques 
for diagnosis, evaluation of severity, and monitoring of gout, but further
investigation is needed.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17278927 [PubMed - indexed for MEDLINE]

159: Curr Opin Rheumatol. 2007 Mar;19(2):122-7.

Therapeutic advances in gout.

Pascual E, Sivera F.

Rheumatology Section, Hospital General Universitario de Alicante, Alicante,
Spain. pascual_eli@gva.es

PURPOSE OF REVIEW: The purpose of this review is to highlight the recent
developments in the management of gout. RECENT FINDINGS: Guidelines for the
diagnosis and management of gout from EULAR, quality of care indicators, and
outcome measures for clinical trials have been published. The standards of gout
diagnosis and management are very low. Allopurinol remains the mainstay for serum
uric acid lowering therapy. In an important percentage of patients receiving
allopurinol, serum uric acid levels are insufficient to promote crystal
dissolution. Febuxostat, a new serum uric acid lowering drug, has shown good
results. Information on uricase continues to appear. For treatment of gouty
inflammation, etoricoxib (a new cyclooxygenase 2 inhibitor) has been shown to be 
as effective as indomethacin. Finally, the association of gout with the metabolic
syndrome and its comorbidities, and the newly described association of gout with 
myocardial infarction, bring lifestyle and dietary modifications to the front in 
the management of gout. SUMMARY: Proper gout management requires changes to the
physician's attitude towards the disease; essentially: (1) an unequivocal
diagnosis based in urate crystal identification, (2) a clearly settled aim of the
treatment: crystal elimination from the joints and elsewhere, and (3) proper use 
of the available therapeutic alternatives. Promoting a proper lifestyle appears
to be especially important.

Publication Types: 
    Review

PMID: 17278926 [PubMed - indexed for MEDLINE]

160: Ann Emerg Med. 2007 May;49(5):670-7. Epub 2007 Feb 5.

Comment in:
    Curr Rheumatol Rep. 2008 Jul;10(3):216-7.    Evid Based Med. 2007 Dec;12(6):175.    Nat Clin Pract Rheumatol. 2007 Nov;3(11):604-5.

Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol
combination therapy in the treatment of acute goutlike arthritis: a double-blind,
randomized, controlled trial.

Man CY, Cheung IT, Cameron PA, Rainer TH.

Accident and Emergency Medicine Academic Unit, The Chinese University of Hong
Kong, Hong Kong, China.

STUDY OBJECTIVE: We compare the analgesic efficacy and adverse effects of oral
prednisolone/acetaminophen and oral indomethacin/acetaminophen combination
therapy in the treatment of acute goutlike arthritis in patients presenting to an
emergency department (ED). METHODS: This is a double-blind, randomized,
controlled study in a university hospital emergency department (ED) in the New
Territories of Hong Kong. Patients older than 17 years and presenting between
February 1, 2003, and June 30, 2004, with a clinical diagnosis of goutlike
arthritis were randomized to receive either oral prednisolone/acetaminophen or
oral indomethacin/acetaminophen combination therapy. Primary outcome measures
were pain scores, time to resolution of symptoms and signs, and adverse effects. 
Secondary outcome measures were the need for additional acetaminophen and relapse
rate. RESULTS: There were 90 patients randomized: 46 patients to the indomethacin
group and 44 patients to the prednisolone group. Baseline characteristics,
including pain scores, were similar in the 2 groups. Both treatment groups had a 
similar decrease in pain score in the ED. The mean rate of decrease in pain score
with activity for indomethacin was -1.7+/-1.6 (SD) mm per day and for
prednisolone was -2.9+/-2.0 (SD) mm per day (mean difference 1.2 mm/day; 95%
confidence interval 0.4 to 2.0 mm/day; P=.0026). Although these differences were 
statistically significant, at no time was the difference in mean pain score
greater than 13 mm. Therefore, it is unclear whether these differences are
clinically significant. The mean total dose of acetaminophen consumed by the
prednisolone group was significantly more than in the indomethacin group (mean
10.3 g, range 1 to 21 g versus mean 6.4 g, range 1 to 21 g). Twenty-nine patients
in the indomethacin group and 12 patients in the prednisolone group experienced
adverse effects (P<.05). The commonest adverse effects in the indomethacin group 
were nausea, indigestion, epigastric pain, dizziness, and gastrointestinal
bleeding (N=5; 11%). None of the patients in the prednisolone group developed
gastrointestinal bleeding. The relapse rate for both groups was similar.
CONCLUSION: In the treatment of acute goutlike arthritis, oral
prednisolone/acetaminophen combination is as effective as oral
indomethacin/acetaminophen combination in relieving pain but is associated with
fewer adverse effects.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 17276548 [PubMed - indexed for MEDLINE]

161: J Cutan Med Surg. 2007 Jan-Feb;11(1):31-4.

Miliarial gout (a new entity).

Shukla R, Vender RB, Alhabeeb A, Salama S, Murphy F.

Department of Medicine, Mcmaster University, Hamilton, ON, Canada.

BACKGROUND: Tophaceous gout typically presents as a subcutaneous, nodular
collection of monosodium urate crystals sharply circumscribed from surrounding
tissues. Although intradermal cutaneous manifestations of gout have been
described, no reported cases of miliarial gout remain. OBJECTIVE: We describe the
first known presentation of miliarial gout and list other uncommon cutaneous
manifestations of gouty tophi. The treatment of miliarial gout is discussed, as
well as risk factors predisposing an individual to the development of intradermal
tophi. RESULTS: Miliarial gout is an intradermal phenomenon consisting of
multiple tiny papules containing material of a white to cream color scattered on 
an erythematous base that responds to allopurinol administration. Risk factors
predisposing an individual to the development of intradermal gout include renal
insufficiency, hypertension, chronic diuretic therapy, long duration of disease, 
and lack of consistent use of urate-lowering therapy. CONCLUSION: Miliarial gout 
is a unique intradermal manifestation of tophaceous gout.

Publication Types: 
    Case Reports

PMID: 17274936 [PubMed - indexed for MEDLINE]

162: Arthritis Rheum. 2007 Feb 15;57(1):109-15.

Prevalence of the metabolic syndrome in patients with gout: the Third National
Health and Nutrition Examination Survey.

Choi HK, Ford ES, Li C, Curhan G.

Arthritis Research Centre of Canada, Vancouver General Hospital, University of
British Columbia, Vancouver, British Columbia, Canada. hchoi@partners.org

OBJECTIVE: To determine the prevalence of metabolic syndrome among patients with 
gout and to examine the association between the 2 conditions in a nationally
representative sample of US adults. METHODS: Using data from 8,807 participants
age >or=20 years in the Third National Health and Nutrition Examination Survey
(1988-1994), we determined the prevalence of metabolic syndrome among individuals
with gout and quantified the magnitude of association between the 2 conditions.
We used both the revised and original National Cholesterol Education Program
Adult Treatment Panel III (NCEP/ATP III) criteria to define metabolic syndrome.
RESULTS: The prevalence (95% confidence interval [95% CI]) of metabolic syndrome 
according to revised NCEP/ATP III criteria was 62.8% (51.9-73.6) among
individuals with gout and 25.4% (23.5-27.3) among individuals without gout. Using
2002 census data, approximately 3.5 million US adults with a history of gout have
metabolic syndrome. The unadjusted and age- and sex-adjusted odds ratios (95% CI)
of metabolic syndrome for individuals with gout were 4.96 (3.17-7.75) and 3.05
(2.01-4.61), respectively. With the original NCEP/ATP criteria, the corresponding
prevalences were slightly lower, whereas the corresponding odds ratios were
slightly higher. The stratified prevalences of metabolic syndrome by major
associated factors of gout (i.e., body mass index, hypertension, and diabetes)
remained substantially and significantly higher among those with gout than those 
without gout (all P values <0.05). CONCLUSION: These findings indicate that the
prevalence of metabolic syndrome is remarkably high among individuals with gout. 
Given the serious complications associated with metabolic syndrome, this frequent
comorbidity should be recognized and taken into account in long-term treatment
and overall health of individuals with gout.

PMID: 17266099 [PubMed - indexed for MEDLINE]

163: Arthritis Rheum. 2007 Feb 15;57(1):103-8.

Validity of gout diagnoses in administrative data.

Harrold LR, Saag KG, Yood RA, Mikuls TR, Andrade SE, Fouayzi H, Davis J, Chan KA,
Raebel MA, Von Worley A, Platt R.

Meyers Primary Care Institute, University of Massachusetts Medical School, Fallon
Foundation, and Fallon Community Health Plan, Worcester, Massachusetts 01655,
USA. HarroldL@ummhc.org

OBJECTIVE: To determine the utility of using administrative data for
epidemiologic studies of gout by examining the validity of gout diagnoses in
claims data. METHODS: From a population of approximately 800,000 members from 4
managed care plans, we identified patients who had at least 2 ambulatory claims
for a diagnosis of gout between January 1, 1999 and December 31, 2003. From this 
group, a random sample of 200 patients was chosen for medical record review.
Trained medical record reviewers abstracted gout-related clinical, laboratory,
and radiologic data from the medical records. Two rheumatologists independently
evaluated the abstracted information and assessed whether the gout diagnosis was 
probable/definite or unlikely/insufficient information. Discordant physician
ratings were adjudicated by consensus. Based on record reviews, patients were
also classified according to the American College of Rheumatology (ACR), Rome,
and New York gout criteria and these results were compared with the physician
global assessments. RESULTS: There were 121 patients rated as having
probable/definite gout by physician consensus, leading to a positive predictive
value of >or=2 coded diagnoses of gout of 61% (95% confidence interval 53-67).
There was low concordance between physician assessments and established gout
criteria including ACR, Rome, and New York criteria (kappa = 0.17, 0.16, and
0.20, respectively). CONCLUSION: Use of administrative data alone in
epidemiologic and health services research on gout may lead to misclassification.
Medical record reviews for validation of claims data may provide an inadequate
gold standard to confirm gout diagnoses.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Validation Studies

PMID: 17266097 [PubMed - indexed for MEDLINE]

164: Clin Rheumatol. 2007 Sep;26(9):1453-7. Epub 2007 Jan 26.

Manifestations of metabolic syndrome associated with male gout in different age
strata.

Chen SY, Chen CL, Shen ML.

Center of Gout, Country Hospital, 61, Sec. 4, Jen-Ai Road, Taipei, Taiwan.
doctor@rahome.idv.tw

We examined the components of metabolic syndrome associated with gout in
different age strata by a large-scale case-controlled study. Totally, 12,179
gouty subjects were divided into three groups according to their ages at first
visit: young- (19-44 years), middle- (45-64 years), and old-aged (>or=65 years)
groups. Their clinical and laboratory data, as well as the risk of gout by the
metabolic syndrome, were analyzed in three age groups and compared with a control
population. The numbers of the cases in the young-, middle-, and old-aged groups 
in the gout population were 4,698, 4,847, and 2,634, respectively. The serum
urate level and the percentage of positive family history of gout were the
highest in young-aged group and declined with increasing age. When compared with 
the data of the control population, the incidence of overweight (body mass index,
>or=24.2 kg/m(2)) and hypertriglyceridemia (triglyceride, >or=2.26 mmol/l) were
significantly higher in the gout population for all age groups. The incidence of 
type 2 diabetes was significantly higher in the gout as well for all age groups, 
and the odds ratio was highest in the young-aged group [odds ratio (95%
confidence interval), 5.55 (3.05-10.09)]. In all, except for the old-aged groups,
the incidence of hypercholesterolemia was significantly higher in the gout than
in the control population, whereas the incidence of hypertension was
significantly higher in the gout than in the control population only in the
old-aged group. Various clinical and laboratory data were suggested to be the
risks of gout in different degrees between age strata.

PMID: 17256101 [PubMed - indexed for MEDLINE]

165: J Emerg Med. 2007 Jan;32(1):23-6.

Does the presence of crystal arthritis rule out septic arthritis?

Shah K, Spear J, Nathanson LA, McCauley J, Edlow JA.

Department of Emergency Medicine, St. Luke's-Roosevelt Hospital, New York, New
York 10025, USA.

The objective of this study was to determine the incidence of septic arthritis in
the presence of joint crystals. A retrospective study was conducted at a
university tertiary care referral center. The study population included all
patients with synovial fluid crystals in the joint aspirate sent to the
laboratory during the 7-year study period. Septic arthritis was defined as a
positive synovial culture. Of the 265 joint aspirates containing crystals, 183
(69.0%) contained gout crystals, 81 (30.6%) contained pseudogout crystals, and 1 
(0.4%) contained both. Four (1.5%) of the aspirates had positive cultures. The
mean synovial WBC of the 4 samples with concomitant crystals and septic arthritis
was 113,000 (95% confidence interval [CI] 72,700-153,200), which was
significantly higher than the entire population at 23,200 (95% CI 19,400-27,000; 
p < 0.01). Of note, all 4 patients with concomitant disease had significant
co-morbidities and synovial WBC counts greater than 50,000. Septic arthritis and 
acute crystal-induced arthritis can occur simultaneously; there were 4 cases
(1.5%) of concomitant disease in our study population. The presence of crystals
cannot exclude septic arthritis with certainty.

PMID: 17239729 [PubMed - indexed for MEDLINE]

166: Eur J Radiol. 2007 Jun;62(3):437-43. Epub 2007 Jan 17.

Impact of sonography in gouty arthritis: comparison with conventional
radiography, clinical examination, and laboratory findings.

Schueller-Weidekamm C, Schueller G, Aringer M, Weber M, Kainberger F.

Department of Diagnostic Radiology, Medical University of Vienna, Waehringer
Guertel 18-20, A-1090 Vienna, Austria.
claudia.schueller-weidekamm@meduniwien.ac.at

OBJECTIVE: To explore the typical sonographic features of gray-scale and Power
Doppler of acute and chronic gouty arthritis in conjunction with radiographic,
clinical, and laboratory findings. MATERIALS AND METHODS: All hand, finger, and
toe joints of 19 patients with acute and chronic gout were examined with
gray-scale and Power Doppler sonography. The number and size of bone changes
detected with sonography was compared to radiographic findings. Vascularization
of the synovial tissue was scored on Power Doppler (grades 0-3), and was compared
with clinical appearance, including swelling, tenderness, and redness (grades
0-3). RESULTS: In acute gout, mild to moderate echogenic periarticular nodules
with sonotransmission and hypervascularization of the edematous surrounding soft 
tissue were found. In chronic gout, tophaceous nodules completely blocked
transmission of US wave, leading to strong reflexion and dorsal shadowing in a
minority of cases. No significant difference in the detection of large bone
changes (>2mm) was found between sonography and radiography. However, gray-scale 
sonography was significantly more sensitive in the detection of small bone
changes (p<0.001). Power Doppler scores were statistically significantly higher
than clinical examination scores (p<0.001). DISCUSSION: Sonography is superior to
radiographs in evaluating small bone changes. The inflammatory process in joints 
can be better detected with Power Doppler sonography than with clinical
examination. Typical sonographic appearance of acute and in particular of chronic
gout might provide clues on gouty arthritis that adds to the information
available from conventional radiography, clinical, and laboratory findings.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 17234377 [PubMed - indexed for MEDLINE]

167: Drugs Aging. 2007;24(1):21-36.

Management of gout in older adults: barriers to optimal control.

Hoskison KT, Wortmann RL.

Department of Internal Medicine, The University of Oklahoma College of Medicine, 
Tulsa, Oklahoma 74135, USA.

Gout, a common inflammatory arthritis, can be diagnosed with absolute certainty. 
Gout results from the body's reaction to urate crystals deposited in tissues, and
this pathophysiology is well understood. If used appropriately, available
therapies can be entirely effective in not only treating the symptoms of gout,
but also in eliminating the excess urate from the body, thereby eradicating the
disease. Because of these facts, management of patients with gout should be
successful. However, management of gout is particularly challenging in the
elderly, even though the principles of management are the same for all age
groups. The purpose of this article is to review these principles and discuss
them as they pertain to the elderly. The classic gout attack is acute in onset,
extremely painful and associated with marked swelling, warmth, erythema and
tenderness of a single joint. However, the diagnosis of gout may be challenging
in the elderly because atypical presentations are more common in this group.
Treatment of acute gout involves the use of NSAIDs, colchicine, corticosteroids
or corticotropin (adrenocorticotropic hormone). Unfortunately, co-morbid
conditions such as chronic kidney disease, peptic ulcer disease and congestive
heart failure may make the use of these agents dangerous or contraindicated.
Thus, it is important to try to treat an acute flare of gout at the earliest
sign, because the sooner treatment is initiated, the faster the inflammation will
resolve. Urate-lowering agents include allopurinol and uricosuric agents. These
also must be used judiciously in the elderly. However, if used at the lowest dose
that maintains the serum urate level below 5.0-6.0 mg/dL, the excess urate in the
body will be eliminated, acute flares will no longer occur and tophi will
resolve. Gout is often seen in association with hypertension, excessive alcohol
consumption, obesity and hypertriglyceridaemia. These conditions and the
medications used to treat them may contribute to the hyperuricaemia. Treating
these conditions and using medications that do not promote hyperuricaemia will
aid in the management of gout. Despite the challenges that often complicate the
management of gout in the elderly, an understanding of the pathophysiology of the
disease and both the indications and limitations of the medications used should
allow successful treatment.

Publication Types: 
    Review

PMID: 17233545 [PubMed - indexed for MEDLINE]

168: Ann Rheum Dis. 2007 Aug;66(8):1056-8. Epub 2007 Jan 12.

Time required for disappearance of urate crystals from synovial fluid after
successful hypouricaemic treatment relates to the duration of gout.

Pascual E, Sivera F.

Catedrático de Medicina (Reumatología), Hospital General Universitario de
Alicante, Maestro Alonso 109, 03010 Alicante, Spain. pascual_eli@gva.es

OBJECTIVES: To determine whether hypouricaemic treatment results in the
disappearance of urate crystals from gouty joints and to define the time
required. METHODS: In 18 patients with monosodium urate (MSU) crystal proven
gout, and after the initiation of successful serum uric acid (SUA)-lowering
treatment, an arthrocentesis of the asymptomatic signal joint (11 knees, 7 first 
metatarsophalangeal joints) was performed every 3 months to obtain a synovial
fluid (SF) sample. The sample was then analysed for the presence of MSU crystals,
and the number of crystals/400x field was noted. SUA levels and the duration of
gout were also noted. RESULTS: MSU crystals disappeared from the SF of all 18
joints after reduction of SUA to normal levels. The time required for
disappearance ranged from 3 to 33 months; disappearance time correlated with the 
duration of gout (r(s) = 0.71; p<0.01). The median number of MSU crystals in the 
SF samples before urate-lowering treatment was 7.5 (2.5-11) crystals/400x field, 
reducing to 3 (1-6.5) crystals/400x field (p<0.05) at 3 months. Crystal counts
continued to decrease after 3 months. CONCLUSIONS: In gout, reduction of SUA to
normal levels results in disappearance of urate crystals from SF, requiring a
longer time in those patients with gout of longer duration. This indicates that
urate crystal deposition in joints is reversible. Normalisation of SUA levels
results in a decrease in the concentration of MSU crystals in SF in the
asymptomatic gouty joints. This may partially explain the reduced frequency of
gouty attacks when a patient has been treated with SUA-lowering drugs.

PMID: 17223663 [PubMed - indexed for MEDLINE]

169: Minerva Med. 2006 Dec;97(6):495-509.

Pathogenesis, clinical findings and management of acute and chronic gout.

Corrado A, D'Onofrio F, Santoro N, Melillo N, Cantatore FP.

Unit of Rheumatology, University of Foggia, Hospital Colonello D'Avanzo, Foggia, 
Italy. ada_corrado@libero.it

Gout is a chronic metabolic disease caused by a disorder of the purine metabolism
leading to hyperuricaemia. It is determined by the deposition of monosodium urate
crystals in joints and other tissues which causes an acute inflammatory response 
and can induce a permanent tissue damage which defines the urate chronic joint
disease which is characterised by the appearance of ulceration of the joint
cartilage, marginal osteophytosis, geodic and erosive lesions and chronic
inflammation of synovial membrane. Gout and hyperuricaemia usually occur after
the age of 30 years and more frequently in men. Hyperuricaemia is the result of
an increased production of uric acid or its hypoexcretion by the kidneys, or
both. In the pathogenesis of gout and hyperuricaemia are involved genetic and
environmental factors; further, different pathologic condition such as
glycogenosis, renal insufficiency, use of some drugs, are associated with gout.
Treatment of acute gout includes colchicine, nonsteroidal anti-inflammatory drugs
and glucocorticoids, whereas in the intercritical periods colchicine is effective
for preventive purposes. Urate-lowering therapy with xanthine-oxidase inhibitors 
or uricosuric agents is indicate only in patients with more than two gout crisis 
per year, tophaceous deposits, uric acid nephrolithiasis, and interstitial renal 
disease, as asymptomatic hyperuricaemia does not requires any treatment but can
be controlled with preventive dietetic measures and changes in lifestyle.

Publication Types: 
    Review

PMID: 17213786 [PubMed - indexed for MEDLINE]

170: Surg Neurol. 2007 Jan;67(1):65-73; discussion 73. Epub 2006 Oct 6.

Spinal gout in a renal transplant patient: a case report and literature review.

Hou LC, Hsu AR, Veeravagu A, Boakye M.

Department of Neurosurgery, Stanford University Medical Center, Stanford, CA
94305-5327, USA. lewishou@yahoo.com

BACKGROUND: Gout in the axial spine is rare. We present a case report on a renal 
transplant patient who developed fever and acute back pain at the L5 through S1
level secondary to sodium urate deposits. We review the literature on this rare
disease and propose a management algorithm based on a resulting analysis. CASE
DESCRIPTION: A 37-year-old man with a history of gout and a renal transplant for 
IgA nephropathy presented with acute back pain and fever without evidence of
neurological deficits. Magnetic resonance imaging revealed a uniformly
contrast-enhancing infiltrative process involving the right pedicle, lamina, and 
inferior facet of the L5 vertebra. Computed tomography-guided needle biopsy
revealed a friable white tissue consistent with sodium urate crystals.
Conservative treatment with steroids and narcotics was used with good symptomatic
relief. CONCLUSION: Although few cases of gout involving the spine have been
reported, its prevalence is likely grossly underestimated. Most patients have a
history of gout and have elevated levels of serum urate level on presentation.
The disease most commonly involves the lumbar spine. Patients usually have
neurological deficits on presentation, and surgical decompression produces
favorable outcomes. However, conservative medical management is appropriate for
those with back pain only. Aggressive control of hyperuricemia is essential
regardless of the method of treatment.

Publication Types: 
    Case Reports
    Review

PMID: 17210304 [PubMed - indexed for MEDLINE]

171: Spine J. 2007 Jan-Feb;7(1):94-9. Epub 2006 Nov 28.

Tophaceous gout of the lumbar spine mimicking pyogenic discitis.

Suk KS, Kim KT, Lee SH, Park SW, Park YK.

Department of Orthopaedic Surgery, School of Medicine, Kyung-Hee University,
Seoul, Korea. sks111@khmc.or.kr

BACKGROUND CONTEXT: Gout of the spine is very rare. Forty-one cases of gout
affecting the spine have been reported. PURPOSE: To present a patient with
tophaceous gout of the lumbar spine mimicking pyogenic discitis. STUDY DESIGN:
Case report. METHODS: The medical record, including operative notes, progress
notes, discharge summary, clinical notes, radiological study, and pathological
studies was reviewed. RESULTS: The patient had acute low back pain and
radiculopathy with high spiking fever. Therefore, pyogenic discitis was
suspected. However, histological diagnosis revealed tophaceous gout. CONCLUSIONS:
Tophaceous gout of the spine is very rare. However, when a patient presents with 
acute back pain and fever, spinal gout should be considered, particularly in a
patient with a previous history of hyperuricemia or gout.

Publication Types: 
    Case Reports

PMID: 17197341 [PubMed - indexed for MEDLINE]

172: Ann Rheum Dis. 2007 Jul;66(7):859-64. Epub 2006 Dec 21.

High-resolution ultrasonography of the first metatarsal phalangeal joint in gout:
a controlled study.

Wright SA, Filippucci E, McVeigh C, Grey A, McCarron M, Grassi W, Wright GD,
Taggart AJ.

Department of Rheumatology, Musgrave Park Hospital, Belfast BT9 7JB, Northern
Ireland, UK. drsawright@yahoo.co.uk

OBJECTIVE: To compare high-resolution ultrasound (HRUS) with conventional
radiography in the detection of erosions in the first metatarsophalangeal joints 
(1st MTPJs) of patients with gout and to identify the characteristic sonographic 
features of gout. METHODS: HRUS examination of the 1st MTPJs of both feet was
performed by two independent sonographers. The presence of joint and soft-tissue 
pathology was recorded. x Ray examination of the feet was performed on the same
day and reported by the same radiologist. RESULTS: 39 male patients with gout and
22 age-matched control subjects (14 with an inflammatory arthropathy and 8
disease free) were studied. The agreement on erosion between HRUS and x ray was
poor, kappa = 0.229 (non-weighted), with McNemar's test being significant
(p<0.001) indicating a large number of false negative x rays. 22 MTPJs in
patients with gout had never been subjected to a clinical attack of acute gout.
In these MTPJs, there were 10 erosions detected by HRUS and 3 erosions on x ray. 
HRUS features significantly more prevalent in the patients with gout were hard
and soft tophus-like lesions (p<0.01) and the double contour sign (p<0.01).
CONCLUSIONS: These data show that HRUS may assist in the management of gout in
two ways: first, by aiding in the diagnosis by identifying the sonographic
features that may be representative of the disease, and, second, by allowing the 
early detection of erosive joint damage and/or tophaceous deposits even in
clinically silent joints.

Publication Types: 
    Comparative Study

PMID: 17185326 [PubMed - indexed for MEDLINE]

173: Clin Exp Rheumatol. 2006 Sep-Oct;24(5):499-507.

Epidemiology of rheumatoid arthritis, juvenile idiopathic arthritis and gout in
two regions of the Czech Republic in a descriptive population-based survey in
2002-2003.

Hanova P, Pavelka K, Dostal C, Holcatova I, Pikhart H.

Institute of Rheumatology, 1st Medical Faculty, Charles University, Prague, Czech
Republic. p-hanova@seznam.cz

OBJECTIVE: To estimate the annual incidence and prevalence of rheumatoid
arthritis (RA), juvenile arthritis (JIA) and gout in a population based study in 
two regions of the Czech Republic with total population of 186,000 inhabitants.
METHODS: The study was conducted in the Town of Ceske Budejovice and district of 
Cheb in the Czech Republic (with a total population of 186,000 inhabitants) in
the years 2002 and 2003. Incident cases were registered on condition that the
definite diagnosis was confirmed according to existing classification criteria
during the study period. Prevalence was studied on the basis of identification of
established diagnosis from registers of patients of participating rheumatologists
and other specialists. They were asked to report all living patients who had been
diagnosed before 1st March 2002. Patients were only included in the study if
their permanent address was in the selected study area. RESULTS: Overall, we
found 48 incident and 947 prevalent cases of RA among adults (16+ years), 4
incident and 43 prevalent cases of JIA among children (less than 16 years old),
and 64 incident and 425 prevalent cases of gout among adults (16+ years). The
total annual incidence of RA was 31/100,000 in the adult population aged 16 years
and more (95% CI 20 to 42/100,000). The prevalence of RA was 610/100,000 (95% CI 
561 to 658/100,000) in the adult population. An annual incidence of gout in
adults was 41/100,000 (95% CI 28 to 53/100,000). The prevalence of gout was
300/100,000 (95% CI 266 to 334/100,000). The annual incidence of JIA was
13/100,000 in children less than 16 years old (95%CI 1 to 20/100,000). The
prevalence of JIA in children was 140/100,000 (95% CI 117 to 280/100,000).
CONCLUSION: This study estimates the annual incidence and prevalence rates of RA,
gout and JIA in the first population-based survey in the Czech Republic. The
rates of RA and JIA compare well with figures reported from other countries;
figures in gout seem to be lower than reported elsewhere.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17181917 [PubMed - indexed for MEDLINE]

174: J Clin Epidemiol. 2007 Jan;60(1):50-5. Epub 2006 Aug 24.

The online case-crossover study is a novel approach to study triggers for
recurrent disease flares.

Zhang Y, Chaisson CE, McAlindon T, Woods R, Hunter DJ, Niu J, Neogi T, Felson DT.

Boston University Clinical Epidemiology Research and Training Unit, The
Department of Medicine at Boston Medical Center, A203, Boston University School
of Medicine, Boston, MA 02118, USA. yuqing@bu.edu

OBJECTIVES: To evaluate the feasibility of conducting an online case-crossover
study of triggers for recurrent disease flares. METHODS: We conducted an online
case-crossover study of triggers for recurrent flares using gout as a paradigm.
We constructed a Web site and recruited individuals with history of gout via the 
Internet. We confirmed gout diagnosis by reviewing each subject's medical
records. We collected via the Internet exposure information during the
intercritical period using a scheduled Control-period Questionnaire, and prior to
recurrent gout attacks using a Hazard-period Questionnaire. RESULTS: Over 10
months we recruited 197 subjects with a history of gout from 41 states and the
District of Columbia. We obtained medical records from 172 subjects. All
participants had experienced at least one recurrent attack and filled out
required questionnaires. The median time between the date of an attack and the
date of logging on to the Web site was 2 days. The incidence rate of recurrent
gout attacks was 1.03 per person-year. Longer disease duration and presence of
comorbidities appeared to increase the risk of recurrent flares. CONCLUSION: The 
results of this study demonstrate that a case-crossover study can be successfully
conducted through the Internet. This approach has broad applicability to other
diseases typified by recurrent attacks.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17161754 [PubMed - indexed for MEDLINE]

175: J Clin Rheumatol. 2006 Dec;12(6):275-6.

Response to application of ice may help differentiate between gouty arthritis and
other inflammatory arthritides.

Schlesinger N.

Clinical Rheumatology, Department of Medicine, UMDNJ-Robert Wood Johnson Medical 
School, New Brunswick, New Jersey 08903-0019, USA. schlesna@umdnj.edu

AIM: The aim is to determine whether response to topical ice versus heat
differentiates between patients with gout versus other arthritides. METHODS: The 
first 150 patients seen in our clinic with joint pain from February 2004 onward
were asked to fill out questionnaires regarding their response to heat and ice.
Patients who responded that topical ice eased their pain and who did not have a
diagnosis of crystal-induced arthritis were asked to have a joint aspiration if
they had active synovitis on presentation to the clinic. RESULTS: Of 150
completed questionnaires, 26 patients never tried heat or cold as adjuvant
treatment for their arthritis. The remaining 124 patients were divided into 6
groups: patients with crystal-proven gout (n = 20), rheumatoid arthritis (RA; n =
32), osteoarthritis (OA; n = 32), other forms of inflammatory arthritis (n = 18),
and soft tissue conditions (n = 22). None of the patients with gout benefited
from topical heating of their affected joints and all preferred topical ice (P < 
0.001). Most patients with RA preferred heat (n = 24). Of 4 patients with RA who 
preferred topical ice, 3 had effusions and arthrocentesis was performed.
Intracellular monosodium urate (MSU) crystals were seen in 2 and intracellular
calcium pyrophosphate dihydrate (CPPD) crystals were seen in one patient raising 
questions about coexistence of 2 diseases or previous misdiagnoses. Most patients
with OA preferred heat (n = 28). A significantly higher percentage of the
patients with gouty arthritis found that topical ice helped relieve their joint
pain as compared with patients with RA (P = 8 x 10(-11)) and other inflammatory
arthritides (P = 3 x 10(-8)). DISCUSSION: Heat and cold are adjuvant treatments
for arthritis. In gouty arthritis, cold applications are a useful adjunct to
treatment and may help discriminate patients with gout from other forms of
inflammatory arthritis.

Publication Types: 
    Clinical Trial

PMID: 17149056 [PubMed - indexed for MEDLINE]

176: Ann Pharmacother. 2006 Dec;40(12):2187-94. Epub 2006 Nov 28.

Febuxostat: a selective xanthine oxidase inhibitor for the treatment of
hyperuricemia and gout.

Bruce SP.

Albany College of Pharmacy, The Center for Rheumatology, 106 New Scotland Ave.
Albany, NY 12203-3492, USA. bruces@acp.edu

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trial data,
safety profile, precautions, and place in therapy of febuxostat, a novel
nonpurine xanthine oxidase inhibitor in development for the treatment of
hyperuricemia and gout. DATA SOURCES: Available studies and abstracts were
identified through MEDLINE (1990-November 2006), Science Citation Index,
International Pharmaceutical Abstracts, Cochrane Databases, and the American
College of Rheumatology and European League Against Rheumatism Web sites. Key
search terms were febuxostat, TMX-67, TEI-6720, hyperuricemia, and gout. STUDY
SELECTION AND DATA EXTRACTION: All available studies describing the pharmacology 
of febuxostat were included. Human studies formed the basis for discussion of
clinical parameters, including pharmacokinetics, pharmacodynamics, efficacy, and 
safety of febuxostat. DATA SYNTHESIS: Febuxostat significantly reduces uric acid 
levels within 2 weeks after initiation of therapy and up to 48% by the end of 104
weeks of therapy. Approximately 60% of patients achieved the primary goal of
serum uric acid less than 6 mg/dL during the last 3 months following once-daily
administration of febuxostat 80 mg or 120 mg for at least 52 weeks. The most
common adverse reactions to febuxostat were abnormal results from liver function 
tests, diarrhea, headache, arthralgias, and musculoskeletal symptoms. Due to its 
potency, patients are at an increased risk of experiencing gout flares for at
least the first year of therapy. Up to 70% of patients in clinical trials
experienced gout flares despite concomitant prophylactic treatment with
colchicine or naproxen. Additional clinical trial evidence supports the efficacy 
and safety of febuxostat in the treatment of hyperuricemia and gout. CONCLUSIONS:
Febuxostat is a promising alternative to allopurinol for the treatment of gout
and hyperuricemia. The optimal length of prophylactic therapy, clinical
significance of abnormal liver function tests results during therapy, and safety 
in patients with moderate or severe renal insufficiency warrant further
investigation.

Publication Types: 
    Review

PMID: 17132810 [PubMed - indexed for MEDLINE]

177: Bull NYU Hosp Jt Dis. 2006;64(1-2):82-6.

Gout in 2006: the perfect storm.

Terkeltaub R.

VAMC/UCSD, 3350La Jolla Village Drive, 111K, San Diego, California 92161, USA.

Mechanistic and therapeutic advances in gout have been moving swiftly in the past
decade. Clinically, the disease is changing in character. This review discusses
several of the pertinent recent developments in understanding gout and in novel
therapeutics for the disease. Subjects addressed include the role of
URAT1-mediated renal proximal tubule epithelial cell urate anion reabsorption in 
hyperuricemia. We discuss the therapeutic limitations of allopurinol and
uricosurics and the potential applications of novel xanthine oxidase inhibitors
and of recombinant uricase preparations. Last, we summarize understanding of the 
central role of the early induced innate immune response in gouty inflammation,
which has suggested the potential value of new strategies for treating gouty
inflammation by targeting caspase-1 or IL-1beta.

Publication Types: 
    Review

PMID: 17121496 [PubMed - indexed for MEDLINE]

178: Clin Dermatol. 2006 Nov-Dec;24(6):498-508.

Metabolic diseases: gout.

Falasca GF.

Division of Rheumatology, Cooper University Hospital, Robert Wood Johnson Medical
School at Camden, University of Medicine and Dentistry of New Jersey, Camden, NJ 
08103, USA. falasca-gerald@cooperhealth.edu

Gout is a disease of antiquity but is increasing once again in prevalence despite
availability of reasonably effective treatments. This may be related to a
combination of factors, including diet, obesity, and diuretic use. Allergic
reactions, noncompliance, drug interactions, and sometimes inefficacy all limit
the effective use of current hypouricemic agents. There are new treatments for
gout on the horizon, including febuxostat, a nonpurine inhibitor of xanthine
oxidase with a potentially better combination of efficacy and side effects than
allopurinol. Diagnostic progress is being made in that ultrasound may offer a
noninvasive means of diagnosing tophaceous deposits in and around joints. The
increasing prevalence of gout means that dermatologists will see more cutaneous
manifestations of gout, including tophi, draining sinus tracts, panniculitis, and
dystrophic calcifications.

Publication Types: 
    Review

PMID: 17113968 [PubMed - indexed for MEDLINE]

179: Explore (NY). 2006 Nov-Dec;2(6):515-9.

Disease of distinction.

Schwartz SA.

The Rhine Research Center, Virginia Beach, Virginia 23451, USA.
saschwartz@eartlink.net

Gout is one of the rare diseases that defines its sufferers by class and culture.
It is also one of the first chronic diseases to be clinically described. The
Egyptians had identified gout as a distinct disorder by 2640 bce. This paper
traces the history of gout from its earliest recorded period down to modern
times, with a particular emphasis on the cultural, political, geopolitical, and
social aspects. Included is a discussion of its role in the American Revolution. 
Today, gout is a well-understood clinically managed arthritic disease that
excites little comment. This is an entirely modern perspective. For most of human
history, gout was a disease of distinction that dominated much of medicine,
playing the same role in Rome's third century bce aristocracy it would later play
in the aristocracies of 17th and 18th century France and England, when each of
these countries dominated the world. Because it was considered a disease of
lifestyle until modern times, when genetics began to be understood, gout was
associated with rich, high status Caucasian men and their excessive consumption
of drink and rich foods. It was virtually unknown in Asia, until Western dietary 
practices became widespread there. From earliest history, gout has been linked
with high IQ and sexual promiscuity, which made it grist for artists and writers,
and their social commentary up to the time of Dickens; this is discussed, with
examples. Because of its association with the rich, gout also developed a
powerful moralistic aspect, particularly during the Christian era when the
concept of sin was a cultural fundamental. The loose living and indulgence of the
rich and the gout it produced made the disease a parable of Christian ethics. The
Italian poet Francesco Petrarch (1304-1374) was one of the first to establish
this nuance, and it influenced how gout was seen for centuries. Part of what gave
gout its special character was that while it tortured, it rarely killed. Indeed, 
when death was a frequent visitor to families, it was thought a painful but
welcomed prophylactic against diseases that did kill. Even in modern times, gout 
still favors the rich and powerful. American research conducted in the 1960s
found that corporate executives, just like their English gentry, or Roman
senatorial predecessors, had higher urate concentrations than their blue-collar
employees.

Publication Types: 
    Historical Article

PMID: 17113492 [PubMed - indexed for MEDLINE]

180: J Gen Intern Med. 2006 Dec;21(12):C5-7.

Gout, have we met before? No, not like this...

Mirzoyev S, Anavekar N.

Mayo Clinic, Rochester, MN 55905, USA.

LEARNING OBJECTIVES: Extra-articular symptoms could be the first manifestation of
gouty arthritis (GA); polyarticular GA can mimic an infectious arthritis;
infection can complicate GA. CASE: A 66-year-old male with a history of gout
presented with high fever and excruciating bilateral calf pain for 1 day.
Examination revealed chronic knee effusions; range of motion in both knees was
limited by calf pain. Joint aspiration showed negatively birefringent
intracellular crystals and normal gram stain. HOSPITAL COURSE: While receiving
empiric antibiotics fever continued and he developed bilateral knee, right ankle,
and shoulder pain. After demonstration of urate crystals and exclusion of
infection, antibiotics were discontinued and steroids initiated. Fever, calf
pain, and polyarthritis quickly resolved. DISCUSSION: Polyarticular gouty attack 
is an uncommon presentation of gout, and can mimic several other conditions. An
exceptional presentation of this entity is excruciating calf pain, probably
caused by tenosynovitis or referred pain preceding an acute polyarticular gouty
attack.

Publication Types: 
    Case Reports

PMID: 17105518 [PubMed - indexed for MEDLINE]

181: Chem Biol Interact. 2006 Dec 15;164(3):174-80. Epub 2006 Nov 7.

Suppressive effect of Withania somnifera root powder on experimental gouty
arthritis: An in vivo and in vitro study.

Rasool M, Varalakshmi P.

Faculty of Biosciences, School of Bioengineering and Biosciences, Vellore
Institute of Technology (Deemed University), Vellore 632014, Tamil Nadu, India.
mkr474@rediffmail.com

The effect of Withania somnifera L. Dunal root powder on paw volume and serum
lysosomal enzyme activities was investigated in monosodium urate crystal-induced 
rats. The levels of beta-glucuronidase and lactate dehydrogenase were also
measured in monosodium urate crystal incubated polymorphonuclear leucocytes
(PMNL). A significant increase in the level of paw volume and serum lysosomal
enzymes was observed in monosodium urate crystal-induced rats. The increased
beta-glucuronidase and lactate dehydrogenase level were observed in untreated
monosodium urate crystal incubated polymorphonuclear leucocytes. On treatment
with the W. somnifera root powder (500/1000 mg/kg body weight), the above changes
were reverted back to near normal levels. W. somnifera also showed potent
analgesic and antipyretic effect with the absence of gastric damage at different 
dose levels in experimental rats. For comparison purpose, non-steroidal
anti-inflammatory drug (NSAID) indomethacin was used as a standard. These results
provide evidence for the suppressive effect of W. somnifera root powder by
retarding amplification and propagation of the inflammatory response without
causing any gastric damage.

PMID: 17084827 [PubMed - indexed for MEDLINE]

182: FASEB J. 2006 Nov;20(13):2234-41.

Melanocortin 3 receptors control crystal-induced inflammation.

Getting SJ, Lam CW, Chen AS, Grieco P, Perretti M.

The William Harvey Research Institute, Queen Mary School of Medicine and
Dentistry, Charterhouse Sq., London EC1M 6BQ, UK.

In this study we have characterized the anti-inflammatory profile of a selective 
melanocortin type 3 receptor (MC3-R) ligand [D-Trp8]-gamma-MSH, validating in
vitro results with analyses in mice deficient for this receptor subtype. In
wild-type (WT) macrophages, [D-Trp8]-gamma-MSH activated MC3-R (as tested by
accumulation of cyclic AMP) and inhibited (approximately 50%) the release of
interleukin (IL)-1 and the chemokine KC (CXCL1), but was ineffective in cells
taken from MC3-R null mice. In vivo, administration of 3-30 microg
[D-Trp8]-gamma-MSH significantly inhibited leukocyte influx and cytokine
production in a model of crystal-induced peritonitis, and these effects were
absent in MC3-R null mice or blocked by coadministration of an MC3-R antagonist. 
Finally, in a model of gouty arthritis, direct injection of urate crystals into
the rat joint provoked a marked inflammatory reaction that was significantly
inhibited (approximately 70%) by systemic or local administration of
[D-Trp8]-gamma-MSH. In conclusion, using an integrated transgenic and
pharmacological approach, we provide strong proof of concept for the development 
of selective MC3-R agonists as novel anti-inflammatory therapeutics.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17077300 [PubMed - indexed for MEDLINE]

183: Joint Bone Spine. 2006 Dec;73(6):672-8. Epub 2006 Sep 1.

Colchicine today.

Niel E, Scherrmann JM.

Inserm U705, UMR CNRS 7157, Neuropsychopharmacologie des Addictions, Hôpital
Fernand-Widal, Universités Paris-V et -VII, 200, rue du Faubourg-Saint-Denis,
75475 Paris cedex 10, France.

Colchicine is used chiefly in the treatment of gout but is also valuable in other
inflammatory diseases such as familial Mediterranean fever (FMF). Three proteins 
play pivotal roles in colchicine pharmacokinetics: the colchicine receptor,
tubulin, which governs the plasma elimination half-life of the drug; intestinal
and hepatic CYP3A4, which is key to the biotransformation of colchicine; and
P-glycoprotein, a cell efflux pump that regulates the tissue distribution of
colchicine, as well as its excretion via the biliary tract and kidneys.
Pharmacokinetic studies have been performed using a radioimmunology assay to
measure blood colchicine levels. Absorption after oral ingestion varies widely
(from 24% to 88% of the dose), the volume of distribution is extremely large (7
l/kg), and binding to albumin is moderate. Colchicine is excreted chiefly through
the liver and has an elimination half-life of 20-40 hours. With repeated doses of
about 1mg/day, the steady-state is achieved within 8 days and concentrations
range from 0.3 to 2.5 ng/ml. Studies of associations between pharmacokinetic
parameters and pharmacodynamics show that effects are correlated, not to plasma
levels, but to levels in leukocytes. Adverse events are not uncommon, most
notably when colchicine is used in combination with drugs that interact with
CYP3A4 and/or P-glycoprotein, thereby decreasing the renal and/or hepatic
elimination of colchicine. Careful monitoring in this situation is effective in
preventing the development of toxicity.

Publication Types: 
    Review

PMID: 17067838 [PubMed - indexed for MEDLINE]

184: Nucleosides Nucleotides Nucleic Acids. 2006;25(9-11):1305-8.

An unusual cause of renal amyloidosis secondary to gout: the first description of
familial occurrence.

Vernerová Z, Rychlík I, Brunerová L, Dvoráková L, Pavelková A, Sebesta I.

Department of Pathology, 3rd Faculty of Medicine, Charles University, Prague,
Czech Republic.

BACKGROUND: AA amyloidosis caused by the chronic inflammation accompanying gouty 
arthritis is extremely rare and familial occurrence has not been described so
far. CASE REPORT: We present the case of two brothers (47 and 44 years old) with 
7- and 10-year history of hyperuricaemia and chronic tophaceous gout with
polyarticular involvement. The enzymatic assay performed in their erythrocytes
proved the partial hypoxanthine-guanine phosphoribosyl transferase deficiency
(Kelley-Seegmiller syndrome), the genetic defect of purine metabolism. Later on
they developed proteinuria and chronic renal insufficiency /CRI/. Renal biopsy
disclosed the combination of AA amyloidosis and gouty nephropathy in both the
cases. Despite the standard treatment the older brother progressed to chronic
renal failure. On the contrary, the younger one being longterm treated with oral 
colchicin have stabilized CRI. CONCLUSIONS: Only several cases of AA renal
amyloidosis until recently, secondary to gout have been reported. Our case
represents the first report of familial occurrence of this extremely rare
disease.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17065112 [PubMed - indexed for MEDLINE]

185: J Immunol. 2006 Nov 1;177(9):6370-8.

Engagement of CD14 mediates the inflammatory potential of monosodium urate
crystals.

Scott P, Ma H, Viriyakosol S, Terkeltaub R, Liu-Bryan R.

Veterans Affairs Medical Center, Department of Medicine, University of
California-San Diego, San Diego, CA 92161, USA.

Phagocyte ingestion of monosodium urate (MSU) crystals can induce proinflammatory
responses and trigger acute gouty inflammation. Alternatively, the uptake of MSU 
crystals by mature macrophages can be noninflammatory and promote resolution of
gouty inflammation. Macrophage activation by extracellular MSU crystals involves 
apparent recognition and ingestion mediated by TLR2 and TLR4, with subsequent
intracellular recognition linked to caspase-1 activation and IL-1beta processing 
driven by the NACHT-LRR-PYD-containing protein-3 inflammasome. In this study, we 
examined the potential role in gouty inflammation of CD14, a phagocyte-expressed 
pattern recognition receptor that functionally interacts with both TLR2 and TLR4.
MSU crystals, but not latex beads, directly bound recombinant soluble (s) CD14 in
vitro. CD14(-/-) bone marrow-derived macrophages (BMDMs) demonstrated unimpaired 
phagocytosis of MSU crystals but reduced p38 phosphorylation and approximately
90% less IL-1beta and CXCL1 release. Attenuated MSU crystal-induced IL-1beta
release in CD14(-/-) BMDMs was mediated by decreased pro-IL-1beta protein
expression and additionally by decreased caspase-1 activation and IL-1beta
processing consistent with diminished NACHT-LRR-PYD-containing protein-3
inflammasome activation. Coating of MSU crystals with sCD14, but not sTLR2 or
sTLR4, restored IL-1beta and CXCL1 production in CD14(-/-) BMDMs in vitro. Gain
of function of CD14 directly enhanced TLR4-mediated signaling in response to MSU 
crystals in transfected Chinese hamster ovary cells in vitro. Last, MSU
crystal-induced leukocyte influx at 6 h was reduced by approximately 75%, and
local induction of IL-1beta decreased by >80% in CD14(-/-) mouse s.c. air pouches
in vivo. We conclude that engagement of CD14 is a central determinant of the
inflammatory potential of MSU crystals.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17056568 [PubMed - indexed for MEDLINE]

186: Cochrane Database Syst Rev. 2006 Oct 18;(4):CD006190.

Colchicine for acute gout.

Schlesinger N, Schumacher R, Catton M, Maxwell L.

UMDNJ/Robert Wood Medical School, Department of Medicine, MEB 474, PO Box 19, New
Brunswick, New Jersey 08903-0019, USA. schlesna@UMDNJ.EDU

BACKGROUND: Gout is one of the most common rheumatic diseases worldwide.
Colchicine is regarded as beneficial in the treatment of acute gout, but has a
high frequency of gastrointestinal adverse events. OBJECTIVES: To evaluate the
efficacy and safety of colchicine for relief of the signs and symptoms of acute
gouty arthritis, compared to placebo and other treatment interventions. SEARCH
STRATEGY: We searched the following electronic databases to March 2006: Cochrane 
Central Register of Controlled Trials (CENTRAL, Issue 1, 2006), MEDLINE (from
1966), EMBASE (from 1980), CINAHL (from 1982), AMED (from 1985), Web of Science
(from 1945) and Current Controlled Trials. SELECTION CRITERIA: Published
randomised controlled trials (RCTs) and controlled clinical trials evaluating
symptom relief and adverse outcomes of colchicine therapy in acute gout were
considered for this review. DATA COLLECTION AND ANALYSIS: Two reviewers
independently screened search results for inclusion, collected the data in a
standardized form and assessed the methodological quality of the trial using
validated criteria. Results for continuous outcome measures were expressed as
weighted mean differences. Dichotomous outcome measures were pooled using
relative risk. The number needed to treat was calculated for significant
outcomes. MAIN RESULTS: One RCT (N=43) comparing colchicine to placebo for the
treatment of acute gout was included in this review. The results favour the use
of colchicine over placebo with an absolute reduction of 34% for pain and a 30%
reduction in clinical symptoms such as tenderness on palpation, swelling,
redness, and pain. The number needed to treat (NNT) with colchicine versus
placebo to reduce pain was 3 and the NNT to reduce clinical symptoms was 2. All
participants treated with colchicine experienced gastrointestinal side effects
(diarrhea and/or vomiting) and the number needed to harm (NNH) with colchicine
versus placebo was 1. No studies comparing colchicine to NSAIDs or other
treatments such as corticosteroids or ACTH were identified. AUTHORS' CONCLUSIONS:
Colchicine is an effective treatment for the reduction of pain and clinical
symptoms in patients experiencing acute attacks of gout, although in the regimen 
studied its low benefit to toxicity ratio limits its usefulness. It should be
used as a second line therapy when NSAIDs or corticosteroids are contraindicated 
or ineffective. More evidence is needed to compare the efficacy of colchicine to 
that of NSAIDs or corticosteroids, the current first line therapy for acute gout.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17054279 [PubMed - indexed for MEDLINE]

187: Clin Rheumatol. 2007 Sep;26(9):1553-5. Epub 2006 Oct 18.

Excellent response to the clinical treatment of tophaceous gout.

Caldas CA, Fuller R.

Discipline of Rheumatology of the São Paulo University Medical School, Brazil.
cezar_caldas@yahoo.com.br

Gout continues to be a health problem around the world, and the treatment may
turn into a real challenge when the patient presents a certain degree of chronic 
renal failure (CRF). We discuss a case of tophaceous gout in a 68-year-old male
patient without urolithiasis and with uric acid (UA) underexcretion and CRF
(creatinine clearance of 42 ml/min). Uricosuric treatment with benzbromarone and 
urinary alkalinization was administered, and acute gouty attacks improved
substantially. Subsequently, allopurinol was added to the treatment to accelerate
tophi reduction in the hands, feet, elbows and knees. After 30 months of
treatment, serum UA declined from 10 to 3.2 mg/dl. Urinary UA excretion of 0.44
g/24 h in the baseline rose to 0.85 g/24 h, returning to the baseline value after
30 months. UA clearance tripled, rising from 3.05 ml/min before treatment to 9.48
ml/min, and remained at this level. It is worth stressing that even in cases of
severe tophaceous gout, the response to clinical treatment may be satisfactory
with substantial reduction of tophi and full acute gouty attack remission even in
patients presenting a certain degree of CRF.

Publication Types: 
    Case Reports

PMID: 17047891 [PubMed - indexed for MEDLINE]

188: Australas J Dermatol. 2006 Nov;47(4):270-3.

Allopurinol induced generalized eosinophilic pustular folliculitis.

Ooi CG, Walker P, Sidhu SK, Gordon LA, Marshman G.

Department of Dermatology, Flinders Medical Centre, Bedford Park, South
Australia, Australia. drcolinooi@gmail.com

A 71-year-old Cambodian man who was commenced on allopurinol for the treatment of
gout developed a generalized papulopustular follicular eruption 8 weeks following
introduction of the drug. The skin biopsy findings were consistent with that of
eosinophilic pustular folliculitis. Resolution of the rash took place during the 
8 weeks following cessation of allopurinol and treatment with oral and topical
corticosteroids.

Publication Types: 
    Case Reports
    Review

PMID: 17034470 [PubMed - indexed for MEDLINE]

189: Knee. 2006 Dec;13(6):474-7. Epub 2006 Oct 9.

Hemilaterally symptomatic bipartite patella associated with bone erosions arising
from a gouty tophus: a case report.

Enomoto H, Nagosi N, Okada E, Ota N, Iwabu S, Kamiishi S.

Department of Orthopaedic Surgery, Keio University, Tokyo, Japan; Department of
Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, OH, USA.
hiro-eno@joy.ocn.ne.jp

Symptomatic bipartite patella in adults is rare. We have treated an unusual case 
of a bipartite patella in an adult, which became symptomatic in association with 
cystic degeneration localized to the patella and a gouty tophus. Although the
patient had bilateral bipartite patellae, multiplanar reformation with computed
tomography (CT-MPR) clearly demonstrated that the bipartite portion of the
patella was malaligned at the junction of the accessory bone and patella in the
symptomatic knee. Bone erosions were present both in the bipartite fragment and
adjacent portion of the patella. After surgical excision of the bipartite
fragment, the patient's symptoms have improved. This case illustrates that cyst
formation associated with inflammatory arthritis may be a rare cause for a
bipartite patella in an adult to become symptomatic.

Publication Types: 
    Case Reports

PMID: 17029961 [PubMed - indexed for MEDLINE]

190: Mol Genet Metab. 2007 Jan;90(1):70-6. Epub 2006 Oct 4.

Molecular analysis of HPRT deficiencies: an update of the spectrum of Asian
mutations with novel mutations.

Yamada Y, Nomura N, Yamada K, Wakamatsu N.

Department of Genetics, Institute for Developmental Research, Aichi Human Service
Center, Kasugai, Aichi 480-0392, Japan. yasyam@inst-hsc.jp

Inherited mutations of a purine salvage enzyme, hypoxanthine guanine
phosphoribosyltransferase (HPRT, EC 2.4.2.8), give rise to Lesch-Nyhan syndrome
or HPRT-related gout. We have identified a number of HPRT mutations in Asian
patients manifesting different clinical phenotypes, by analyzing all nine exons
of the HPRT gene (HPRT1) from genomic DNA and reverse-transcribed mRNA using the 
PCR technique coupled with direct sequencing. In this study, we update the
spectrum of mutations with nine novel mutations. Two missense mutations (T124P
and D185G) were detected in patients with HRH (HPRT-related hyperuricemia). In a 
patient having a severe partial deficiency of HPRT with neurological dysfunction 
(HRND: HPRT-related neurological dysfunction), a single nucleotide substitution
(27+5G > A) causing a splicing error was found in intron 1. The mutation resulted
in a remarkably decreased level of normal mRNA, and production of an abnormal
mRNA with a 49-bp insert at the 5'-end of intron 1, which caused the frame-shift 
of an amino acid codon (10fs27X). In six typical Lesch-Nyhan families, we found
two 3-bp deletions responsible for single amino acid deletions (V8del and
Y28del), two 1-bp deletions (440delA and 635delG) generating a frame-shift, an
insertion of two amino acids (159insKV), and a 4,131-bp deletion from introns 4
to 6 resulting in two types of abnormal mRNA. Including these nine mutations, 42 
HPRT1 mutations have been identified among 47 Asian families with deficiency of
HPRT.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17027311 [PubMed - indexed for MEDLINE]

191: J Rheumatol. 2006 Oct;33(10):2050-2.

A survey of current evaluation and treatment of gout.

Schlesinger N, Moore DF, Sun JD, Schumacher HR Jr.

Department of Medicine, The School of Public Health, University of Medicine and
Dentistry of New Jersey, New Brunswick, New Jersey 08903-0019, USA.
schlesna@umdnj.edu

OBJECTIVE: To record diagnostic and treatment approaches to gouty arthritis among
US rheumatologists. METHODS: Questionnaires were faxed to 2500 US
rheumatologists. RESULTS: Responses were received from 518 rheumatologists.
Respondents reported performing crystal analysis 80% of the time for new
suspected gout; 64% use combination therapy for acute gout; nonsteroidal
antiinflammatory drugs alone are used in only 27%. Urate-lowering drugs (ULD) are
given to most patients. ULD treatment is given occasionally to patients with
asymptomatic hyperuricemia (4%) but most frequently to patients after 2 (59%) or 
3 (34%) attacks. ULD are given with the aim of achieving a serum urate (SU) level
of 6 mg/dl. CONCLUSION: Combination antiinflammatory agents are used frequently
for acute gout despite absence of evidence in the literature to support this
practice. There seems to be consensus regarding the necessity of lowering SU to <
6 mg/dl. Approaches vary widely, supporting the need for longterm prospective,
placebo controlled studies to provide more evidence-based guidance.

Publication Types: 
    Evaluation Studies

PMID: 17014020 [PubMed - indexed for MEDLINE]

192: J Rheumatol. 2006 Oct;33(10):2041-9.

Comment in:
    J Rheumatol. 2006 Oct;33(10):1921-2.

The management of gout at an academic healthcare center in Beijing: a physician
survey.

Fang W, Zeng X, Li M, Chen LX, Schumacher HR Jr, Zhang F.

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences,
Beijing, China.

OBJECTIVE: Gout is a less commonly diagnosed rheumatic disease in China compared 
with Western countries, but its prevalence appears to be climbing. It is not
known how Chinese physicians diagnose and treat their patients with gout, so we
evaluated physician management of gout at a major academic healthcare center in
Beijing, and investigated factors associated with better decision-making.
METHODS: A 13-question anonymous survey was distributed and collected at a
medical grand rounds and then at a rheumatology grand rounds at a major teaching 
hospital in Beijing. Physician demographic data including educational background,
work experience, job titles, specialty or subspecialties, gout patient volume
seen in a year, and continuing medical education (CME) in gout were also
collected in the survey. Data were analyzed by multivariate regression models to 
identify factors associated with appropriate answers. RESULTS: Twenty-seven
residents and general internists, 26 rheumatologists and fellows, and 28
physicians and fellows of other medical subspecialties from the Department of
Medicine including visiting physicians responded to the survey. Among
respondents, 78% think it is important for a definitive diagnosis of gout, but
few actually perform aspiration of the affected joint fluid. Eighty-four percent 
report that they often follow the serum urate level of their patients with
diagnosed gout. When treating acute gout in otherwise healthy patients, most
physicians (77%) prefer oral colchicine, and in patients with renal impairment,
about half of them (48%) choose corticosteroids or corticotropin as their first
treatment. For longterm urate-lowering therapy, most physicians (87%) described a
variety of indications that we consider less appropriate. They (86%) tend to
initiate it early (< 2 weeks) after acute flares. When urate-lowering therapy is 
used, 80% of physicians sustain it less than 5 years. Further, only 12% of
physicians use antiinflammatory prophylaxis during the initiation of
urate-lowering treatment, and only 5% maintain it for an appropriate period of
time. Logistic regression analysis of physician demographic data, educational
background, and work experience found no consistent independent factors
associated with better decision-making, other than CME, that were associated with
establishing the definite diagnosis correctly. Specifically, the number of gout
patients seen by physicians was not related to better decision-making.
CONCLUSION: The physicians' reported management of gout at this major academic
healthcare center in Beijing was often inconsistent with current evidence. High
quality CME is required to improve Chinese physician management of gout.

PMID: 17014019 [PubMed - indexed for MEDLINE]

193: Arthritis Rheum. 2006 Oct 15;55(5):786-90.

Using serum urate levels to determine the period free of gouty symptoms after
withdrawal of long-term urate-lowering therapy: a prospective study.

Perez-Ruiz F, Atxotegi J, Hernando I, Calabozo M, Nolla JM.

Sección de Reumatologia, Hospital de Cruces, Pais Vasco, Spain.
fperezruiz@telefonica.net

OBJECTIVE: Withdrawal of urate-lowering therapy (ULT) is associated with
recurrence of acute gouty arthritis and tophi, but no data are available about
factors associated with recurrence of gouty symptoms. Therefore, life-long
therapy prescription is usually advised, but the prospect of life-long therapy
may contribute to very low compliance rates. Our objective was to ascertain the
outcome of ULT withdrawal after long-term, documented control of serum urate
levels. METHODS: We conducted a prospective, long-term, followup study of
patients treated with ULT during a 5-year period. Both diagnosis and recurrence
of gout were determined based on monosodium urate crystal identification in
synovial fluid or material aspirated from tophi. RESULTS: Low average serum urate
levels while receiving ULT and during the followup period after ULT withdrawal
were statistically associated with the longest period in which patients were free
of gouty symptoms, suggesting that depletion and formation of the body's urate
pool is dependent on both time and serum urate levels. Patients whose average
serum urate levels were <5.05 mg/dl while receiving ULT and <8.75 mg/dl after ULT
withdrawal had the longest (>4 years) time to recurrence. CONCLUSION: Proper and 
long-term reduction of serum urate level is associated with long-term periods in 
which patients are free of gouty symptoms, probably due to the reduction of the
urate pool. These results suggest that 5-year intermittent, instead of life-long,
ULT could be offered to patients with good serum urate control during ULT.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17013833 [PubMed - indexed for MEDLINE]

194: Semin Arthritis Rheum. 2006 Dec;36(3):197-202. Epub 2006 Sep 29.

Comment in:
    Semin Arthritis Rheum. 2007 Oct;37(2):133-4.

"Crystal clear"-sonographic assessment of gout and calcium pyrophosphate
deposition disease.

Grassi W, Meenagh G, Pascual E, Filippucci E.

Cattedra di Reumatologia, Università Politecnica delle Marche, Ancona, Italy.

OBJECTIVES: To date, high-resolution ultrasound (US) has not been fully exploited
in the field of crystalline arthropathy. Both gout and calcium pyrophosphate
deposition (CPPD) disease are significant diseases within the purview of the
rheumatologist. The aim of this pictorial review was to present the principal
findings in patients with crystal deposition in gout and CPPD. METHODS: US
pictures were obtained from 60 consecutive patients, 34 with CPPD disease and 26 
with gout, whose diagnosis was confirmed by synovial fluid analysis. The US
examinations were performed using the following US systems: Diasus (Dynamic
Imaging, Livingstone, UK) and Logiq 9 (General Electric Medical Systems,
Milwaukee, WI). RESULTS: Pictorial evidence of the principal US findings in gout 
includes monosodium urate (MSU) deposition on the surface of articular cartilage,
various patterns within synovial fluid ranging from completely anechoic fluid to 
collections filled with aggregates of variable shape and echogenicity,
microdeposition within tendons, and tophus formation. In CPPD, the hallmark US
features include crystal deposition within articular cartilage, calcification of 
fibrocartilage, together with focal crystal deposition within tendons.
CONCLUSION: US is an impressive imaging modality in crystalline arthropathy. The 
anatomical location of the crystal deposits, clearly depictable by US, allows
differentiation between MSU and CPPD aggregates.

Publication Types: 
    Review

PMID: 17011611 [PubMed - indexed for MEDLINE]

195: Arthritis Rheum. 2006 Oct;54(10):3363-71.

Transglutaminase 2 limits murine peritoneal acute gout-like inflammation by
regulating macrophage clearance of apoptotic neutrophils.

Rose DM, Sydlaske AD, Agha-Babakhani A, Johnson K, Terkeltaub R.

VA Medical Center, University of California, San Diego, CA 92161, USA.
drose@vapop.ucsd.edu

OBJECTIVE: Monosodium urate monohydrate (MSU) crystals have remarkable
inflammatory potential. However, gouty inflammation is spontaneously
self-limited, an occurrence recognized since antiquity. Gouty synovitis is driven
and sustained by neutrophil influx. Importantly, macrophage phagocytosis of
apoptotic (but not necrotic) neutrophils is antiinflammatory. Therefore, we
tested the hypothesis that efficient clearance of apoptotic neutrophils by
macrophages is one of the factors that restrains the progression of gouty
inflammation. Macrophage expression of transglutaminase 2 (TG2), a
multifunctional protein with reciprocally regulated transamidation and purine
nucleotide-binding activities, promotes apoptotic leukocyte uptake. In this
study, we tested the specific role of macrophage TG2 expression in MSU
crystal-induced inflammation. METHODS: We studied MSU crystal-induced peritonitis
in TG2-/- and congenic TG2+/+ mice. We also studied the effects of TG2 on
apoptotic cell uptake by cultured macrophages. RESULTS: TG2-/- mice demonstrated 
more progressive neutrophilic accumulation than did TG2+/+ mice, which was
associated with delayed clearance of apoptotic neutrophils during MSU
crystal-induced peritonitis. We observed defective phagocytosis of apoptotic
leukocytes by TG2-/- peritoneal macrophages, which was corrected by soluble
extracellular TG2. Transamidation catalytic activity of TG2 was not required to
mediate macrophage uptake of apoptotic leukocytes. In contrast, the TG2
nucleotide binding site residue K173 was critical for this TG2 function. TG2
bound to GDP, ADP, or ATP (but not to GTP) rescued defective apoptotic leukocyte 
uptake by TG2-/- macrophages. CONCLUSION: Enhancement of apoptotic neutrophil
uptake by macrophage-derived TG2 restrains gout-like neutrophilic peritoneal
inflammation. Differential binding of TG2 by purine nucleotides may contribute to
clinical variability in the extent and duration of gouty inflammation.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17009310 [PubMed - indexed for MEDLINE]

196: Chin J Integr Med. 2006 Sep;12(3):212-4.

Comparative study on treatment of acute gouty arthritis by electroacupuncture
with different frequency.

Zou R, Zhang HX, Zhang TF.

Department of Acupuncture, Wuhan Municipal Hospital of Integrative Medicine,
Wuhan, China. zrr520xyxy@yahoo.com.cn

OBJECTIVE: To study the therapeutic effect of treatment of acute gouty arthritis 
(AGA) respectively by electroacupuncture (EA) with different frequency and oral
intake of Western medicine. METHODS: Seventy-two patients of AGA were randomly
assigned into three groups, 24 in each group. Group A was treated with EA 100 Hz;
Group B with EA 2 Hz; and Group C with Western medicine. The analgesic effect,
initiating time and sustaining time of analgesia were observed and the level of
serum uric acid was measured before and after treatment. RESULTS: The initiating 
time of analgesia was shorter while the sustaining time of analgesia was longer
in Group A and B than those in Group C (all P < 0.01). The efficacy of analgesia 
was higher in Group B than that in Group A, and a better effect was shown in
Group B in reducing serum uric acid level than that in Group A (P < 0.01), which 
was near that in Group C (P > 0.05). CONCLUSION: EA is an effective treatment for
AGA, and low frequency (2 Hz) EA showed a better efficacy.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 17005084 [PubMed - indexed for MEDLINE]

197: Best Pract Res Clin Rheumatol. 2006 Aug;20(4):673-84.

Gout: can we create an evidence-based systematic approach to diagnosis and
management?

Chen LX, Schumacher HR.

University of Pennsylvannia, Penn-Presbyterian Medical Center, Philadelphia, PA
19104-4283, USA.

The management of gout can be subdivided into four phases. Asymptomatic
hyperuricaemia represents the basic underlying metabolic abnormality that can
lead to gout. Studies are evaluating whether interventions may be indicated in
some cases. Diagnostic criteria for gout and acute flares are still not well
defined unless urate crystals are found. Acute attacks of gout are treated with
anti-inflammatory measures and the agent of choice is often determined by attack 
stage, severity and comorbidities that may contra-indicate one or more agents.
After attacks subside, there are asymptomatic periods during which decisions must
be made about when and how to start urate-lowering measures. If hyperuricaemia
persists, there is generally persistence of urate crystals in the joint.
Anti-inflammatory prophylaxis is needed when urate-lowering therapy is started.
Lifestyle measures should be addressed. If chronic tophaceous gout is diagnosed, 
urate lowering should be started without delay. New agents are under development 
that may help with difficult cases.

Publication Types: 
    Review

PMID: 16979531 [PubMed - indexed for MEDLINE]

198: J Rheumatol. 2006 Sep;33(9):1813-7.

Characteristics of chronic gout in Northern Sulawesi, Indonesia.

Padang C, Muirden KD, Schumacher HR, Darmawan J, Nasution AR.

Indonesian Rheumatic Centre, Jakarta, Indonesia.

OBJECTIVE: To identify associations and possible risk factors for gout that may
contribute to chronic tophaceous gout in rural and urban districts of North
Sulawesi, Indonesia. METHODS: A total of 190 patients with chronic gout and 190
age and sex matched controls were selected from 28 community health centers.
Potential risk factors including alcohol consumption, food habits, family
history, body weight, related medical conditions, drug use, and laboratory
investigations were sought. RESULTS: Alcohol consumption and certain food habits 
were associated with gout. A positive family history of gout and overweight were 
also significant risk factors. Renal impairment was found in 86.3% of patients
and hyperuricemia in 92.1%. In controls, renal impairment and hyperuricemia were 
7.4% and 32.6%, respectively. Patients with hypertension and nephrolithiasis were
more at risk of having associated gout. There was a significant association
between gout, hyperuricemia, hypercholesterolemia, hypertriglyceridemia, and
higher levels of creatinine and urea. There was also a significantly lower level 
of urine uric acid in gout cases compared with controls. Gouty tophi were found
in 91% of these cases with chronic gout. The use of diuretics for treating
hypertension, continuing excessive alcohol consumption and purine-rich food
habits in untreated gout, and hyperuricemia were associated with chronic and
tophaceous gout. Urate-lowering drugs were not available in the community health 
centers. CONCLUSION: Severe tophaceous gout with deformities and disability is
found in North Sulawesi. Prominent risk factors include alcohol, obesity, renal
impairment, diet, hypertension, and family history. Improved education about gout
seems needed. Urate-lowering drugs are not available in community health centers 
but are needed, especially in rural areas, as studied here.

PMID: 16960942 [PubMed - indexed for MEDLINE]

199: Issues Emerg Health Technol. 2006 Aug;(87):1-4.

Febuxostat for prevention of gout attacks.

Pohar S, Murphy G.

(1) Febuxostat is a selective inhibitor of xanthine oxidase. Its use in the
management of hyperuricemia and gout is being studied. (2) In a 52-week, phase
III randomized clinical trial, febuxostat was superior to allopurinol for
lowering uric acid levels. Its efficacy in preventing gout attacks was similar to
that of allopurinol. Despite a similar rate of adverse effects, individuals on
febuxostat were more likely to stop treatment than those on allopurinol. (3) The 
most commonly observed adverse effects with febuxostat include liver function
test abnormalities, diarrhea, headache, nausea, vomiting, abdominal pain, and
dizziness. (4) Given that renal dysfunction is a risk factor for hyperuricemia
and gout, the safety and efficacy of febuxostat in this population should be
considered, but only limited data are available. (5) The diffusion of febuxostat 
may be limited by its price relative to that of allopurinol, regardless of
whether febuxostat proves to have advantages in specific populations.

PMID: 16958189 [PubMed - indexed for MEDLINE]

200: Clin Exp Rheumatol. 2006 Jul-Aug;24(4):361-5.

Does rofecoxib increase TNF-alpha levels?

Nalbant S, Akmaz I, Kaplan M, Avsar K, Solmazgul E, Sahan B.

Gata Heh Iç Hastaliklari Servisi, Haydarpaşa, Istanbul, Turkey.
nalbantselim@hotmail.com

OBJECTIVE: Rofecoxib (Vioxx), the first COX-2 selective non-steroidal
anti-inflammatory drug (NSAID), was recently withdrawn from the market due to the
increased risk of acute myocardial infarction. The precise mechanism responsible 
for this phenomenon still remains unknown. Tumor necrosis factor alpha
(TNF-alpha) is a cytokine, possibly most responsible for mortality in patients
with acute myocardial infarction. However, this study was designed to study
possible effects of rofecoxib on the level of TNF-alpha by using MSU crystal
induced inflammation in the rat subcutaneous air pouch model. METHODS: Rat
subcutaneous air pouches were produced and examinations commenced 6 days later.
Control groups received only MSU crystals, or no crystals or drugs. To begin
with, rofecoxib (30 mg/kg), indomethacin (20 mg/kg) or diclofenac (3 mg/kg) were 
administered to groups of 5 rats each. Thirty minutes later, MSU crystals were
injected into air pouches, except for the negative control group. Twenty-four
hours later, the rats were sacrificed for aspiration of fluid and for the
dissection of pouch walls to determine leukocyte counts, pouch wall histology,
and to assay IL-10 and TNF-alpha. RESULTS: Intra-pouch injection of MSU crystals,
compared to non-injected pouches, caused an increase in white blood cell count
(WBC) (30 +/- 44.7 versus 4508 +/- 792.3 cells/mm3), in the numbers of pouch wall
vessels (vascular index) (4.8 +/- 0.3 versus 11.4 +/- 1.5 vessels/high-power
field) and in TNF-alpha (50.0 +/- 13.4 versus 70.34 +/- 20.9 ng/mL), but not in
interleukin-10 (IL-10) (60.6 +/- 63.0versus 61.48 +/- 7.1). WBC and vascular
index were significantly reduced in all study groups compared to the control
group (p < 0.05). Levels of TNF- in fluids were unexpectedly and significantly (p
< 0.05) increased in all cases. The highest level of TNF-alpha was found in the
rofecoxib group. In contrast to TNF-alpha, IL-10 levels were significantly (p <
0.05) decreased in all three drug groups. Indomethacin tended to suppress
inflammation more effectively. However, there was no significant difference
between the groups for IL-10 (p > 0.05). CONCLUSION: All three NSAIDs exhibited
anti-inflammatory activity against MSU crystal induced inflammation. The
difference in anti-inflammatory effects of these three non-steroidal drugs is
seen not only in the anti-inflammatory effect on MSU induced inflammation but
also in the nature of the effects. Refocoxib tended to increase the TNF-alpha
level. Whether increased TNF-alpha levels can help explain the side effect of
COX-2 specific inhibitors still requires further studies.

PMID: 16956424 [PubMed - indexed for MEDLINE]

201: Drugs. 2006;66(12):1547-63.

Pathophysiology, clinical presentation and treatment of gout.

Teng GG, Nair R, Saag KG.

Department of Medicine, Division of Clinical Immunology and Rheumatology,
University of Alabama at Birmingham, Birmingham, Alabama 35294-3296, USA.

Gout is a common form of inflammatory arthritis that has been managed primarily
in general medical practices for centuries. It appears that there has been an
increasing prevalence of gout over the past decades, implying a growing public
health burden. Accurate diagnosis and recognition of the various stages and
manifestations of gout enable realistic goal setting for management. Recent
evidence suggests new risk factors and potentially refutes others. Management of 
gout requires characterising and modifying risk factors and associated disorders,
and commonly initiating drug therapy. Pharmacotherapy of gout includes the
management of acute flares with anti-inflammatory agents such as NSAIDs and
glucocorticoids and long-term treatment with urate-lowering drugs. Although
pharmacotherapy is generally safe and effective, there are caveats and
limitations to all gout therapies. Patient non-adherence and errors with the use 
of drugs for gout treatment are important factors leading to medical failures.
With early intervention, careful monitoring and patient education, gout is a
condition that can be managed very effectively. The advent of new drugs (such as 
febuxostat and urate oxidase [uricase]) and enhanced understanding of the
pathogenesis of gout continue to improve our therapeutic options, particularly in
a subset of patients with refractory disease and those who are intolerant to
currently available medications.

Publication Types: 
    Review

PMID: 16956303 [PubMed - indexed for MEDLINE]

202: Pediatr Nephrol. 2006 Dec;21(12):1884-8. Epub 2006 Sep 1.

Hyperuricemia and gout following pediatric renal transplantation.

Spartà G, Kemper MJ, Neuhaus TJ.

Nephrology Unit, University Children's Hospital, Steinwiesstrasse 75, 8032
Zurich, Switzerland.

Hyperuricemia and gout are common complications in adult renal transplant
recipients. In pediatric recipients, however, hyperuricemia seems to be rare, but
data are scarce. Thirty-two children (21 males, 11 females) were investigated for
a median time of 4.8 years (range: 0.4-11.2 years) following renal
transplantation. The median age of this pediatric study group was 13.9 years
(range: 5.7-20.3 years), and the calculated glomerular filtration rate (GFR) was 
61 ml/min per 1.73 m(2) (range:12-88 ml/min per 1.73 m(2)). All patients were
given calcineurin inhibitors, with 22 and ten children receiving cyclosporine A
(CSA) and tacrolimus (TAC), respectively. The median plasma uric acid was 385
micromol/l (range: 62-929 micromol/l); 15 children (47%) were above the
age-related normal range. Only one patient experienced gouty arthritis. There was
a significant correlation between plasma uric acid concentration and both time
span after transplantation and plasma creatinine, and an inverse correlation to
GFR (p<0.05). No significant correlation was found between plasma uric acid and
body mass index (BMI). Plasma uric acid concentrations were neither different
among CSA- and TAC-treated children, nor did they correlate with drug exposure or
blood trough levels of CSA or TAC. Plasma uric acid concentration was not
different when compared to children with chronic renal failure (CRF) of a similar
degree in native kidneys. We conclude that hyperuricemia is common among
pediatric renal transplant recipients and rather a consequence of chronic renal
transplant dysfunction than the use of calcineurin inhibitors. Gout, however, is 
rare.

PMID: 16947031 [PubMed - indexed for MEDLINE]

203: Am J Med. 2006 Sep;119(9):800.e13-8.

Comment in:
    Am J Med. 2007 Oct;120(10):e5; author reply e7.    Curr Rheumatol Rep. 2007 Jun;9(3):229-30.

Alcohol consumption as a trigger of recurrent gout attacks.

Zhang Y, Woods R, Chaisson CE, Neogi T, Niu J, McAlindon TE, Hunter D.

Boston University Clinical Epidemiology Research and Training Unit, the
Department of Medicine at Boston Medical Center, Boston, Mass 02118, USA.
yuqing@bu.edu

BACKGROUND: Alcohol consumption has long been considered a trigger for recurrent 
gout attacks; however, this hypothesis has not been formally tested. METHODS: We 
conducted an Internet-based case-crossover study to assess several putative risk 
factors, including alcohol consumption, thought to trigger recurrent gout
attacks. Subjects who had an attack within the past year were recruited online
and asked to provide access to medical records pertaining to their gout. Data
were obtained on the amount and type of alcoholic beverage consumed on each day
over the 2-day period before a gout attack and on each day over a 2-day period
during the intercritical period. We examined the amount and type of alcohol
consumption and the risk of recurrent gout attacks using a conditional logistic
regression adjusting for diuretic use and purine intake. RESULTS: A total of 197 
subjects were recruited online over a 10-month period. Of those, 179 (91%)
fulfilled the American College of Rheumatology Criteria for gout. Compared with
no alcohol consumption, odds ratios for recurrent gout attacks were 1.1, 0.9,
2.0, and 2.5 for 1 to 2, 3 to 4, 5 to 6, and 7 or more drinks consumed over the
2-day period, respectively (P<.005). A dose-response relationship of risk of gout
attacks was more evident for alcohol consumed over the last 24 hours. An
increased risk of recurrent gout attacks was found for each type of beverage
consumed. CONCLUSION: Alcohol consumption triggers recurrent gout attacks. This
effect was likely to occur within 24 hours after its consumption.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16945617 [PubMed - indexed for MEDLINE]

204: Indian J Pathol Microbiol. 2006 Apr;49(2):244-5.

Fine needle aspiration of tophi in asymptomatic gout--a case report.

Rao S, Gupta K, Arora R, Arulselvi S.

Department of Pathology, VMMC & Safdarjung Hospital. csydr@rediffmail.com

Gout, a chronic hyperuricemic crystal induced arthropathy, may produce soft
tissue masses (tophi). Tophi may be found in synovial membranes, periarticular
ligaments, tendons, soft tissues as well as internal organs. We present a case in
which diagnosis of gout was made by fine needle aspiration of tophus. The patient
had a painless nodule over right ankle which was progressively increasing in
size. He gave a past history of painful arthropathy, but serum uric acid levels
were within normal limits. At this juncture, FNAC of the ankle tophus was
performed which revealed aggregated and innumerable dissociated needle-shaped
negatively birefringent crystals of monosodium urate (MSU) on polarization
microscopy.

Publication Types: 
    Case Reports

PMID: 16933725 [PubMed - indexed for MEDLINE]

205: Nat Clin Pract Rheumatol. 2006 Jun;2(6):338-42; quiz 343.

Successful treatment with rasburicase of a tophaceous gout in a patient allergic 
to allopurinol.

Richette P, Bardin T.

Department of Rheumatology, Centre Viggo Petersen, Lariboisiere Hospital,
University Paris VII, France. pascal.richette@lrb.ap-hop-paris.fr

BACKGROUND: A 56-year-old white woman was referred to our institution with a
16-month history of severe, gouty, recurrent, acute polyarthritis involving the
finger joints. She also had numerous small subcutaneous tophi in her hands. The
patient was intolerant to allopurinol and had mild renal insufficiency attributed
to uric-acid nephrolithiasis and interstitial nephropathy. INVESTIGATIONS:
Physical examination, laboratory testing, X-rays of the hands, feet and pelvis,
CT of the pelvis, microscopic analysis of an aspirate from a finger tophus.
DIAGNOSIS: Tophaceous gout associated with urate nephropathy in a patient
intolerant to allopurinol. MANAGEMENT: Acute polyarthritis was successfully
managed by intravenous bolus methylprednisolone combined with codeine, diclofenac
and low-dose colchicine. Rasburicase infusions combined with fenofibrate and
sodium bicarbonate achieved to maintain serum acid uric below 360 micromol/l.

Publication Types: 
    Case Reports

PMID: 16932713 [PubMed - indexed for MEDLINE]

206: Korean J Intern Med. 2006 Jun;21(2):89-93.

Effect of fenofibrate in combination with urate lowering agents in patients with 
gout.

Lee YH, Lee CH, Lee J.

Division of Rheumatology, College of Medicine, Ewha Womans University, Seoul,
Korea.

BACKGROUND: To assess the efficacy of fenofibrate treatment in combination with
urate lowering agents in patients with gout. METHODS: Fourteen male patients with
chronic tophaceous or recurrent acute attacks of gout were evaluated in an
open-label pilot study of the hypolipidemic agent, fenofibrate (Lipidil Supra 160
mg/d). Patients were stable on urate lowering agents (allopurinol or
benzbromarone) for > or = three months without acute attack for the most recent
one month before participating. All patients were being treated with established 
doses of urate lowering agents without modification throughout the study.
Clinical and biochemical assessments including serum uric acid, creatinine, liver
function test and fasting serum lipid were measured at (1) baseline (2) after two
months of fenofibrate treatment and (3) two months after fenofibrate was
withdrawn. RESULTS: Serum uric acid was lowered by 23% after two months of
fenofibrate treatment (6.93 +/- 2.16 vs. 5.22 +/- 1.16 mg/dL; p = 0.016).
Triglyceride levels were also reduced after fenofibrate treatment (p = 0.001).
However, this effect was reversed after the withdrawal (p = 0.002) of the drug.
Alkaline phosphatase was reduced after fenofibrate treatment (p = 0.006), but
increased 21% after the withdrawal of the drug (p = 0.002). By contrast, serum
levels of high density lipoprotein and creatinine were increased 9% (p = 0.018)
and 12% (p = 0.006), respectively; however, both levels were significantly
decreased to the baseline levels upon withdrawal of fenofibrate. CONCLUSIONS:
Fenofibrate can effectively reduce uric acid levels in addition to its known
hypolipidemic effect. Fenofibrate may be used as a potential urate lowering agent
in patients with gout, especially in those with coexisting hyperlipidemia.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16913436 [PubMed - indexed for MEDLINE]

207: Int J Clin Pract. 2006 Oct;60(10):1210-7. Epub 2006 Aug 15.

Gout Assessment Questionnaire: Initial results of reliability, validity and
responsiveness.

Colwell HH, Hunt BJ, Pasta DJ, Palo WA, Mathias SD, Joseph-Ridge N.

Ovation Research Group, San Francisco, CA, USA.

We evaluated the psychometric properties of a new gout-specific patient reported 
outcomes questionnaire. The Gout Assessment Questionnaire (GAQ) and the SF-36
were administered to 126 subjects in a multicenter Phase II program of
febuxostat, an investigational treatment for hyperuricemia (serum uric acid >8.0 
mg/dl) in patients with chronic gout. The questionnaire was administered at
baseline and 1, 6 and 12 months later. The majority of subjects, mean age 54
years, were male, Caucasian and had experienced a gout flare within the last
year. Seven domains were identified, all met criteria for reliability and
validity. Cronbach's alpha ranged from 0.78 to 0.97. Pearson correlations between
GAQ and SF-36 scales were generally low to moderate, with the highest correlation
between Gout Pain and Severity and SF-36 Bodily Pain, r = 0.45. Guyatt's
statistic (measure of responsiveness) ranged from 0.24 to 1.00 at 12 months.
Minimal clinically important differences ranged from 2 (Gout Concern) to 10
points (Productivity). The GAQ has acceptable psychometric properties. Further
research is required to confirm results, which may provide more information to
improve the GAQ for use in clinical trials.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 16911575 [PubMed - indexed for MEDLINE]

208: Arthroscopy. 2006 Aug;22(8):910.e1-3.

Arthroscopic treatment for gouty tophi mimicking an intra-articular synovial
tumor of the knee.

Li TJ, Lue KH, Lin ZI, Lu KH.

Department of Orthopaedic Surgery, Chung Shan Medical University Hospital,
Taichung, Taiwan, Republic of China.

Tophi deposition is a well-recognized complication of chronic gout, but usually
lacks obvious symptoms. Magnetic resonance imaging (MRI) findings may allow a
relatively specific diagnosis to be rendered. In this study, we report an unusual
case of gouty tophi presenting as an intra-articular synovial tumor of the knee, 
blocking the range of motion. We also describe its MRI appearance, which was
compatible with the clinical suspicion. After arthroscopic excision of the
"tumor," the patient was symptom free.

Publication Types: 
    Case Reports

PMID: 16904600 [PubMed - indexed for MEDLINE]

209: Curr Rheumatol Rep. 2006 Jun;8(3):231-5.

The advanced imaging of gouty tophi.

Gentili A.

Department of Radiology, UCSD-Thornton Hospital, 9300 Campus Point Dr, La Jolla, 
CA 92037, USA. agentili@ucsd.edu

Gout is a metabolic disorder in which there is hyperuricemia caused by an
increase in production or a decrease in excretion of uric acid. Long-lasting
hyperuricemia causes the deposition of monosodium urate crystals in the joints
and soft tissues, triggering gouty arthritis and, if not properly treated, the
formation of gouty tophi. The diagnosis of gout is usually based on clinical
presentation and laboratory examinations, long before any abnormality can be
demonstrated with imaging. Radiography is the primary imaging modality used in
the initial evaluation of gouty arthritis. Ultrasonography, CT, MRI, and nuclear 
medicine are seldom necessary. Occasionally a tophus has an unusual presentation 
and simulates neoplasm or infection prompting the utilization of cross-sectional 
imaging for further evaluation and surgical planning. Cross-sectional imaging is 
also used in areas that are difficult to visualize on radiographs such as spine, 
sacroiliac joints, and soft tissues.

Publication Types: 
    Review

PMID: 16901082 [PubMed - indexed for MEDLINE]

210: Curr Rheumatol Rep. 2006 Jun;8(3):215-23.

New developments in the epidemiology and genetics of gout.

Zaka R, Williams CJ.

The prevalence of gout appears to be rapidly increasing worldwide and is no
longer a disorder suffered primarily by over-fed alcohol consumers. Emerging risk
factors include longevity, metabolic syndrome, and new classes of pharmacologic
agents. In some ethnic populations, no obvious risk factors can explain the high 
incidence of hyperuricemia and gout, suggesting a genetic liability. Studies to
identify genes associated with gout have included families with defects in purine
metabolism, as well as families in whom the occurrence of gout is secondary to
renal disorders such as juvenile hyperuricemic nephropathy and medullary cystic
kidney disease. Case-control studies of isolated aboriginal cohorts suffering
from primary gout have revealed several chromosomal loci that may harbor genes
that are important to the development and/or progression of gout.

Publication Types: 
    Review

PMID: 16901080 [PubMed - indexed for MEDLINE]

211: Curr Rheumatol Rep. 2006 Jun;8(3):209-14.

Innate immunity in triggering and resolution of acute gouty inflammation.

Rose DM, Liu-Bryan R.

Gout has long been recognized as a disease of recurrent bouts of acute
inflammation that undergo self-resolution. This inflammation is triggered by the 
body's response to monosodium urate (MSU) crystals. In this paper, we focus on
recent studies that describe how interactions of MSU crystals with the components
of the innate immune system trigger acute gouty inflammation as well as
mechanisms that are involved in the resolution of this inflammation.
Specifically, we describe how toll-like receptors mediate the uptake of MSU
crystals involved in the initiation and resolution of gouty inflammation. We also
describe recent findings on the role of apoptotic clearance in the resolution of 
gouty inflammation. In addition, how therapies used to treat gout act on the
innate immune system to inhibit MSU crystal-induced inflammation and promote the 
resolution of inflammation is discussed.

Publication Types: 
    Review

PMID: 16901079 [PubMed - indexed for MEDLINE]

212: Nephrology (Carlton). 2006 Aug;11(4):367-71.

Gout in renal transplant recipients.

Stamp L, Ha L, Searle M, O'Donnell J, Frampton C, Chapman P.

Department of Medicine, Christchurch School of Medicine and Health Sciences,
Christchurch, New Zealand. lisa.stamp@cdhb.govt.nz

AIMS: The aims of the present audit were to determine the prevalence of gout in
renal transplant recipients in Canterbury, New Zealand, to identify risk factors 
for gout, and to assess the range of treatments used, their efficacy and
complications. In addition, the authors wished to assess the impact of post-renal
transplant gout on the patient. METHODS: Patients with post-transplantation gout 
were identified from the Christchurch Hospital Nephrology database. For each
patient with gout a post-renal transplantation recipient without gout post
transplant was found matched for age, sex and date of transplant. Case notes were
audited and patients interviewed. RESULTS: In total, 47/202 (23%) living renal
transplant recipients had gout post transplant. Those patients with gout were
more likely to be taking a loop diuretic (68%vs 34%, P < 0.001), to have a higher
serum urate and impaired renal function and to have had gout prior to the
transplant. Of those patients who developed gout post transplant 70% had an
attack at least every 3 months. Of those who returned to work post transplant 48%
required time off work because of gout. CONCLUSION: out is an important problem
in the post-transplant population causing significant morbidity and time off
work. Diuretics, impaired renal function, gout prior to transplantation and
hyperuricaemia are important risk factors. The need for diuretic therapy should
be kept under review in these patients. Hypouricaemic therapy should be
considered early in those who develop gout post renal transplantation. Further
studies are required to determine whether treatment for asymptomatic
hyperuricaemia is justified.

PMID: 16889578 [PubMed - indexed for MEDLINE]

213: J Clin Invest. 2006 Aug;116(8):2262-71.

Comment in:
    J Clin Invest. 2006 Aug;116(8):2073-5.

MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation
stimulated by monosodium urate crystals.

Chen CJ, Shi Y, Hearn A, Fitzgerald K, Golenbock D, Reed G, Akira S, Rock KL.

Department of Pathology, University of Massachusetts Medical School, Worcester,
Massachusetts 01655, USA.

While it is known that monosodium urate (MSU) crystals cause the disease gout,
the mechanism by which these crystals stimulate this inflammatory condition has
not been clear. Here we find that the Toll/IL-1R (TIR) signal transduction
adaptor myeloid differentiation primary response protein 88 (MyD88) is required
for acute gouty inflammation. In contrast, other TIR adaptor molecules,
TIRAP/Mal, TRIF, and TRAM, are not required for this process. The MyD88-dependent
TLR1, -2, -4, -6, -7, -9, and -11 and IL-18 receptor (IL-18R) are not essential
for MSU-induced inflammation. Moreover, MSU does not stimulate HEK cells
expressing TLR1-11 to activate NF-kappaB. In contrast, mice deficient in the
MyD88-dependent IL-1R showed reduced inflammatory responses, similar to those
observed in MyD88-deficient mice. Similarly, mice treated with IL-1 neutralizing 
antibodies also showed reduced MSU-induced inflammation, demonstrating that IL-1 
production and IL-1R activation play essential roles in MSU-triggered
inflammation. IL-1R deficiency in bone marrow-derived cells did not affect the
inflammatory response; however, it was required in non-bone marrow-derived cells.
These results indicate that IL-1 is essential for the MSU-induced inflammatory
response and that the requirement of MyD88 in this process is primarily through
its function as an adaptor molecule in the IL-1R signaling pathway.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16886064 [PubMed - indexed for MEDLINE]

214: J Clin Invest. 2006 Aug;116(8):2073-5.

Comment on:
    J Clin Invest. 2006 Aug;116(8):2262-71.

Gout: new insights into an old disease.

Martinon F, Glimcher LH.

Department of Immunology and Infectious Diseases, Harvard School of Public
Health, Boston, Massachusetts 02115, USA.

Gout is an autoinflammatory disorder associated with deposition of monosodium
urate (MSU) crystals in joints and periarticular tissues. Recent advances suggest
that the innate immune system may drive the gouty inflammatory response to MSU.
These findings prompt questions concerning how the innate immune system
recognizes MSU and the identities of the receptors involved. In this issue of the
JCI, Chen et al. show that the IL-1 receptor and its signaling protein myeloid
differentiation primary response protein 88 (MyD88) but not the "classical"
innate immune receptors, TLRs, are central for MSU-induced inflammation (see the 
related article beginning on page 2262).

Publication Types: 
    Comment

PMID: 16886051 [PubMed - indexed for MEDLINE]

215: Scand J Rheumatol. 2006 Jul-Aug;35(4):251-60.

Advances in the management of gout and hyperuricaemia.

Hoskison TK, Wortmann RL.

Department of Internal Medicine, The University of Oklahoma College of
Medicine-Tulsa, 4502 East 41st Street, Tulsa, OK 74135, USA.

An acute attack of gouty arthritis is one of the most painful experiences
reported throughout medical history. Therefore it is paramount to initiate
appropriate therapy quickly in order to terminate the acute phase. This goal can 
be achieved with non-steroidal anti-inflammatory agents, colchicine, or
corticosteroid-based therapies. Rarely, because of contraindications to these
agents, only symptomatic treatment can be given until the attack subsides. The
next step is to lower the serum urate level below the limit of solubility (i.e., 
below 40.8 mmol/L, or 6.8mg/dL) which reduces recurrences and begins to return
the total body urate pool to normal. This equally important goal can be achieved 
by uricosuric agents or xanthine oxidase inhibitors, although the latter is
generally favored. Allopurinol is the agent most commonly preferred because of
its safety profile and ease of use, but there are known serious allergic
reactions and untoward side effects that occasionally require discontinuation.
Febuxostat, a xanthine oxidase inhibitor, and pegylated uricase are new agents
under development and may be beneficial in these situations or when other
comorbid conditions prevent the use of conventional treatments. Alcohol and
dietary consumption are also related to hyperuricemia and acute gout. Recently
beer, wine, and liquor were studied and the risk of gout varied according to the 
alcohol ingested. Furthermore, recent data sheds light on important dietary
modifications that may help in the treatment of gout, and dispels certain beliefs
about protein ingestion and the occurrence of acute gout. As we learn more about 
the associated conditions of hypertriglyceridemia, hypertension, and the
metabolic syndrome, it may allow the tailoring of medical regimens that directly 
prevent or reduce recurrent attacks of gouty arthritis. There are specific
approved treatments for these common comorbidities that have parallel effects of 
lowering serum urate levels. These recent findings may be especially important
for treating refractory cases. While patient education remains a cornerstone to
ensure compliance, other quality indicators for the management of this disease
have been reported and should guide the clinician in the treatment of gout and
result in improved care.

Publication Types: 
    Review

PMID: 16882587 [PubMed - indexed for MEDLINE]

216: Arthritis Rheum. 2006 Aug;54(8):2688-96.

Gout and the risk of acute myocardial infarction.

Krishnan E, Baker JF, Furst DE, Schumacher HR.

University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Arthritis.MD@gmail.com

OBJECTIVE: To determine if hyperuricemia and gouty arthritis are independent risk
factors for acute myocardial infarction (MI) and, if so, whether they are
independent of renal function, diuretic use, metabolic syndrome, and other
established risk factors. METHODS: We performed multivariable logistic and
instrumental variable probit regressions on data from the Multiple Risk Factor
Intervention Trial (MRFIT). RESULTS: Overall, there were 12,866 men in the MRFIT 
who were followed up for a mean of 6.5 years. There were 118 events of acute MI
in the group with gout (10.5%) and 990 events in the group without gout (8.43%; P
= 0.018). Hyperuricemia was an independent risk factor for acute MI in the
multivariable regression models, with an odds ratio (OR) of 1.11 (95% confidence 
interval [95% CI] 1.08-1.15, P < 0.001). In multivariable regressions in which
the above risk factors were used as covariates, gout was found to be associated
with a higher risk of acute MI (OR 1.26 [95% CI 1.14-1.40], P < 0.001). Subgroup 
analyses showed that a relationship between gout and the risk of acute MI was
present among nonusers of alcohol, diuretics, or aspirin and among those who did 
not have metabolic syndrome, diabetes mellitus, or obesity. In separate analyses,
a relationship between gout and the risk of acute MI was evident among those with
and without those hyperuricemia. CONCLUSION: The independent risk relationship
between hyperuricemia and acute MI is confirmed. Gouty arthritis is associated
with an excess risk of acute MI, and this is not explained by its well-known
links with renal function, metabolic syndrome, diuretic use, and traditional
cardiovascular risk factors.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16871533 [PubMed - indexed for MEDLINE]

217: Clin Exp Rheumatol. 2006 May-Jun;24(3):233-8.

Severe tophaceous gout. Characterization of low socioeconomic level patients from
México.

Vázquez-Mellado J, Cruz J, Guzmán S, Casasola-Vargas J, Lino L, Burgos-Vargas R.

Rheumatology Service, Hospital General de México, Facultad de Medicina,
Universidad Nacional Autónoma de México. jvazquezmellado@prodigy.net.mx

OBJECTIVE: To describe a group of patients with frequent tophaceous gout, the
variables associated with severe tophaceous gout and to compare them with other
patients with gout described elsewhere. METHODS: We looked for 65 demographic
clinical and paraclinical variables from patients with gout who attended our gout
clinic from 1995-2000 and were evaluated by the same group of physicians.
RESULTS: Three hundred and sixteen patients were included, 98% males, 82% live in
México city, the mean age at onset, educational level and disease duration were
37.5 +/- 12.4, 6.3 +/- 3.9 and 12.6 +/- 10.3 years respectively. Tophaceous gout 
was present in 62% of the patients with a mean tophi number of 4.7 +/- 6.3 and
mean HAQ score 0.13 +/- 0.37. Severe tophaceous gout (>or= 5 tophi) was found in 
34% and these patients had significantly: earlier age at onset, longer duration
of the disease, lesser frequency of obesity and higher frequency of: intradermal 
tophi, HAQ > 0.5, hospitalizations, radiographic score III/IV, uric acid
under-excretion, renal function impairment and previous (oral and parenteral)
auto-prescribed chronic glucocorticoid treatment compared with patients with
non-severe tophaceous gout. In the multiple logistic regression the significant
variables were renal function impairment (p = 0.000) and previous chronic
parenteral glucocorticoid treatment (p = 0.011) . CONCLUSION: Our patients
compared with those from other countries who have earlier age at onset, very low 
frequency of gout among females, frequent tophaceous gout and severe tophaceous
gout. Severe tophaceous gout in this group is associated with renal function
impairment and previous chronic parenteral glucocorticoid treatment.

PMID: 16870088 [PubMed - indexed for MEDLINE]

218: Rheumatology (Oxford). 2007 Feb;46(2):215-9. Epub 2006 Jul 11.

Molecular analysis of the SLC22A12 (URAT1) gene in patients with primary gout.

Vázquez-Mellado J, Jiménez-Vaca AL, Cuevas-Covarrubias S, Alvarado-Romano V,
Pozo-Molina G, Burgos-Vargas R.

Rheumatology Service, Hospital General de México. Dr Balmis 148, Colonia
Doctores, Mexico City, C.P. 06726. México. jvazquezmellado@prodigy.net.mx

OBJECTIVE: To analyse the SLC22A12 (URAT1) gene in primary gout patients,
first-grade relatives and healthy controls and the possible association of them
with demographic and clinical data. Subjects and METHODS: We included 69
consecutive patients with diagnosis of primary gout, as well as 29 first-grade
relatives and 120 healthy volunteers. Demographic and clinical data were obtained
from the patients and relatives. DNA was purified from peripheral blood and all
10 exons of the SLC22A12 (URAT1) gene were sequenced. RESULTS: We found six
different mutations in the SLC22A12 gene in 16 out of 69 (23%) patients with
primary gout. Five mutations were in exon 5 and one in exon 4; five out of six
mutations were heterozygous (one compound heterozygous) and one homozygous. The
C850G mutation (exon 5) was found in 11 gout patients, these patients have lower 
levels of triglycerides than the rest of the group: 160 +/- 56 vs 292 +/- 203
mg/dl (P = 0.038). In one family, we found SLC22A12 mutations in three relatives 
within exon 5. We did not find mutations in the other exons studied (1-3 and
6-10), nor in any of the 10 exons of the 120 healthy volunteers. CONCLUSIONS: We 
found several mutations in SLC22A12 gene associated with primary gout, the
definite role of these mutations in URAT1 activity needs to be further studied.

PMID: 16837472 [PubMed - indexed for MEDLINE]

219: Mayo Clin Proc. 2006 Jul;81(7):925-34.

Comment in:
    Mayo Clin Proc. 2006 Nov;81(11):1508-9; author reply 1509.

Gout medication treatment patterns and adherence to standards of care from a
managed care perspective.

Sarawate CA, Brewer KK, Yang W, Patel PA, Schumacher HR, Saag KG, Bakst AW.

Health Outcomes Research, HealthCore, Inc, 800 Delaware Ave, Fifth Floor,
Wilmington, DE 19801-1366, USA. csarawate@healthcore.com

OBJECTIVE: To determine allopurinol treatment patterns and adherence to published
standards of care for patients with gout. PATIENTS AND METHODS: This
retrospective claims analysis in a managed care database included patients 18
years or older, with continuous eligibility for 1 year before and after the start
date and 2 or more visits during which the gout disease code (274.xx) was
assigned or 1 or more pharmacy prescriptions for a gout-specific medication
between January 1, 2000, and December 31, 2002 (intake period). Factors
associated with compliance with allopurinol therapy were measured based on the
medication possession ratio, and adherence to 2 quality-of-care indicators for
gout management was assessed using multivariable logistic regression analysis.
RESULTS: A total of 64.9% of allopurinol users had a modal daily dose or the most
commonly observed daily dose of 300 mg/d, median length of therapy was 3 months, 
and a high proportion of patients had a medication possession ratio of 10% or
less. Suggested quality-of-care Indicators for gout had low performance: 53% of
patients with renal impairment received a modal daily dose of 300 mg or greater, 
and 83% of patients who started taking allopurinol did not have their serum urate
levels measured within 180 days. Patients with gout flares were less likely to be
compliant with allopurinol (odds ratio, 0.50; 95% confidence interval,
0.40-0.63). Patients with renal impairment at baseline were 3.2 times more likely
to undergo serum urate testing than patients without renal impairment (odds
ratio, 3.20; 95% confidence Interval, 1.25-8.23). CONCLUSION: There was low
compliance with allopurinol therapy for treatment of gout. Patients potentially
received suboptimal quality of care as measured by serum urate testing and
appropriateness of allopurinol dosing in patients with renal impairment.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16835972 [PubMed - indexed for MEDLINE]

220: Curr Med Res Opin. 2006 Jul;22(7):1381-9.

The economic burden of gout on an employed population.

Brook RA, Kleinman NL, Patel PA, Melkonian AK, Brizee TJ, Smeeding JE,
Joseph-Ridge N.

The JeSTARx Group, Newfoundland, NJ 07435-1710, USA. RBrook@JeSTARx.xom

OBJECTIVE: To examine the economic burden of illness of gout in an employed
population, quantifying the impact on employers annual health benefit costs for
medical and prescription claims, sick leave, short- and long-term disability, and
workers' compensation. METHODS: Adjudicated claims data from 300000 employees
from 2001 through 2004 were utilized. T-tests were used to compare demographic
data and medical costs and services by Agency for Healthcare Research and Quality
(AHRQ) diagnostic categories. Two-part models were used to determine average
annual health benefit costs overall and medical costs by place of delivery. A
risk stratification quintile analysis was also performed utilizing gout-specific 
medical and pharmaceutical costs. RESULTS: There were 1171 employees with gout
identified (total n = 249 038). All demographic variables between the two groups 
were statistically different (p <or= 0.05). The total annual cost for the
employee with gout versus without gout was $6870 versus $3705, respectively, with
significantly higher costs for medical claims, prescription claims, sick leave,
short-term disability, and workers' compensation benefits. Costs were
significantly higher by location of service for office, outpatient hospital or
clinic, inpatient hospital, and laboratory. For the gout cohort, the top major
diagnostic category in average cost was 'circulatory system' and in average
services was 'endocrine, nutritional, metabolic, and immunologic systems'. Only
0.9% of employees with gout generated 20% of the total gout-specific medical and 
prescription costs. CONCLUSION: Gout inflicts a substantial burden of illness
upon employers in terms of medical and prescription costs, as well as other
work-related benefits.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16834837 [PubMed - indexed for MEDLINE]

221: J Rheumatol. 2006 Jul;33(7):1346-50.

The prevalence of hyperuricemia in a population of the coastal city of Qingdao,
China.

Nan H, Qiao Q, Dong Y, Gao W, Tang B, Qian R, Tuomilehto J.

Qingdao Diabetes Epidemiology Study Group, Qingdao Endocrine and Diabetes
Institute, Qingdao, China. hairong.nan@helsinki.fi

OBJECTIVE: Hyperuricemia and gout have shown an increase worldwide. Data are
lacking for the prevalence of hyperuricemia and gout and their correlates in
China. We studied the occurrence of these conditions in Chinese adults in the
city of Qingdao. METHODS: A population-based cross-sectional survey for
hyperuricemia and gout was performed among 2438 adults (1535 women, 903 men; aged
20-74 yrs) in 2002. Fasting serum uric acid (UA) and lipid profiles were
determined, as well as height, weight, and blood pressure. Hyperuricemia was
defined as serum UA levels >or= 420 micromol/l in men and >or= 360 micromol/l in 
women. Diagnosis of gout was self-reported. Complete biochemical and
questionnaire data were available for analysis from 1303 women and 720 men.
RESULTS: The age-standardized prevalence was 25.3% for hyperuricemia and 0.36%
for gout in adults aged 20 to 74 years. Hyperuricemia was more prevalent in men
than in women (32.1% vs 21.8%; p < 0.001). Age-adjusted mean serum UA level was
389.3 micromol/l in men and 315.7 micromol/l in women. Serum UA increased with
age in women only (p for trend < 0.001). Body mass index and serum triglycerides 
had the strongest associations with serum UA in both genders, followed by alcohol
drinking and diastolic blood pressure in men, and systolic blood pressure and
total cholesterol in women. CONCLUSION: The prevalence of hyperuricemia in the
urban adult population in Qingdao city is high, while the frequency of gout is
lower. Obesity, hypertension, and dyslipidemia are the major factors associated
with hyperuricemia in this study.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16821269 [PubMed - indexed for MEDLINE]

222: Arthritis Res Ther. 2006;8 Suppl 1:S3. Epub 2006 Apr 12.

Comment in:
    Arthritis Res Ther. 2006;8(5):405.

The inflammatory process of gout and its treatment.

Cronstein BN, Terkeltaub R.

Department of Medicine and Division of Clinical Pharmacology, New York University
School of Medicine, New York, New York, USA. Bruce.Cronstein@nyumc.org

Gouty arthritis is a characteristically intense acute inflammatory reaction that 
erupts in response to articular deposits of monosodium urate (MSU) crystals.
Important recent molecular biologic advances in this field have given us a clear 
picture of the mechanistic basis of gouty inflammation. The innate immune
inflammatory response is critically involved in the pathology of gout.
Specifically, MSU crystals promote inflammation directly by stimulating cells via
Toll-like receptor signaling and by providing a surface for cleavage of C5 and
formation of complement membrane attack complex (C5b-9), culminating in secretion
of cytokines, chemokines, and other inflammatory mediators with a dramatic influx
of neutrophils into the joint. Despite the detailed mechanistic picture for gouty
inflammation, there are no placebo-controlled, randomized clinical studies for
any of the therapies commonly used, although comparative studies have
demonstrated that many nonsteroidal anti-inflammatory drugs are equivalent to
indomethacin with respect to controlling acute gouty attacks. In general, the
first line of anti-inflammatory therapy for acute gout is nonsteroidal
anti-inflammatory drugs, and the selective cyclo-oxygenase-2 inhibitor celecoxib 
can be used where appropriate. The second line of treatment is
glucocorticosteroids, given systemically (oral, intravenous, or intramuscular) or
intra-articularly. Alternatively, synthetic adrenocorticotropic hormone is
effective, partly via induction of adrenal glucocorticosteroids and partly via
rapid peripheral suppression of leukocyte activation by melatonin receptor 3
signaling. The third line of treatment is oral colchicine, which is highly
effective when given early in an acute gouty attack, but it is poorly tolerated
because of predictable gastrointestinal side effects.

Publication Types: 
    Review

PMID: 16820042 [PubMed - indexed for MEDLINE]

223: Arthritis Res Ther. 2006;8 Suppl 1:S2. Epub 2006 Apr 12.

Epidemiology, risk factors, and lifestyle modifications for gout.

Saag KG, Choi H.

UAB Center for Education and Research (CERTs) on Therapeutics of Musculoskeletal 
Disorders, Division of Clinical Immunology and Rheumatology, University of
Alabama at Birmingham, Birmingham, Alabama, USA. ksaag@uab.edu

Gout affects more than 1% of adults in the USA, and it is the most common form of
inflammatory arthritis among men. Accumulating data support an increase in the
prevalence of gout that is potentially attributable to recent shifts in diet and 
lifestyle, improved medical care, and increased longevity. There are both
nonmodifiable and modifiable risk factors for hyperuricemia and gout.
Nonmodifiable risk factors include age and sex. Gout prevalence increases in
direct association with age; the increased longevity of populations in
industrialized nations may contribute to a higher prevalence of gout through the 
disorder's association with aging-related diseases such as metabolic syndrome and
hypertension, and treatments for these diseases such as thiazide diuretics for
hypertension. Although gout is considered to be primarily a male disease, there
is a more equal sex distribution among elderly patients. Modifiable risk factors 
for gout include obesity, the use of certain medications, high purine intake, and
consumption of purine-rich alcoholic beverages. The increasing prevalence of gout
worldwide indicates that there is an urgent need for improved efforts to identify
patients with hyperuricemia early in the disease process, before the clinical
manifestations of gout become apparent.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16820041 [PubMed - indexed for MEDLINE]

224: Arthritis Res Ther. 2006;8 Suppl 1:S1. Epub 2006 Apr 12.

A concise history of gout and hyperuricemia and their treatment.

Nuki G, Simkin PA.

University of Edinburgh Rheumatic Diseases Unit, Scotland, UK. g.nuki@ed.ac.uk

First identified by the Egyptians in 2640 BC, podagra (acute gout occurring in
the first metatarsophalangeal joint) was later recognized by Hippocrates in the
fifth century BC, who referred to it as 'the unwalkable disease'. The term is
derived from the Latin word gutta (or 'drop'), and referred to the prevailing
medieval belief that an excess of one of the four 'humors'--which in equilibrium 
were thought to maintain health--would, under certain circumstances, 'drop' or
flow into a joint, causing pain and inflammation. Throughout history, gout has
been associated with rich foods and excessive alcohol consumption. Because it is 
clearly associated with a lifestyle that, at least in the past, could only be
afforded by the affluent, gout has been referred to as the 'disease of kings'.
Although there is evidence that colchicine, an alkaloid derived from the autumn
crocus (Colchicum autumnale), was used as a powerful purgative in ancient Greece 
more than 2000 years ago, its first use as a selective and specific treatment for
gout is attributed to the Byzantine Christian physician Alexander of Tralles in
the sixth century AD. Uricosuric agents were first used at the end of the 19th
century. In the modern era, nonsteroidal anti-inflammatory drugs are usually the 
drugs of choice for treating acute gout. Perhaps the most important historical
advance in the treatment of hyperuricemia was the development of xanthine oxidase
inhibitors, which are effective in reducing plasma and urinary urate levels and
have been shown to reverse the development of tophaceous deposits.

Publication Types: 
    Historical Article
    Review

PMID: 16820040 [PubMed - indexed for MEDLINE]

225: J Rheumatol. 2006 Aug;33(8):1646-50.

Dose adjustment of allopurinol according to creatinine clearance does not provide
adequate control of hyperuricemia in patients with gout.

Dalbeth N, Kumar S, Stamp L, Gow P.

Department of Medicine, University of Auckland, Auckland, New Zealand.
n.dalbeth@auckland.ac.nz

OBJECTIVE: Published guidelines state that allopurinol doses should be adjusted
according to creatinine clearance. We investigated whether such dosing provides
adequate control of hyperuricemia. METHODS: We studied 250 patients with gout
attending rheumatology clinics in South Auckland from 2001 to 2004. Allopurinol
dose, creatinine clearance, and serum uric acid (SUA) level were recorded. We
analyzed the relationship between recommended allopurinol dose and SUA lowering
to <or= 0.36 mmol/l. RESULTS: For patients taking allopurinol, 70.9% were taking 
recommended doses, based on published allopurinol dosing guidelines. There were 4
(1.6%) patients with cutaneous hypersensitivity reactions to allopurinol, but
none of these patients were taking higher than recommended allopurinol doses. The
proportion of patients achieving SUA <or= 0.36 mmol/l was lower in those taking
recommended doses, compared with those taking higher than recommended doses (19% 
vs 38.1%; p < 0.01). CONCLUSION: Adherence to published allopurinol dosing
guidelines led to suboptimal control of hyperuricemia in this population of
patients with gout. Further work is required to clarify the safety and efficacy
of allopurinol dose escalation, particularly in patients with renal impairment.

PMID: 16783857 [PubMed - indexed for MEDLINE]

226: J Plast Reconstr Aesthet Surg. 2006;59(7):775-8. Epub 2006 Mar 14.

Malignant fibrous histiocytoma arising in a gouty tophus at the second
metacarpophalangeal joint.

Carnero S, Terán P, Trillo E.

Department of Plastic Surgery, General Yagüe Hospital, Burgos, Spain.
susana_carnero@yahoo.es

We report a case of concomitant malignant fibrous histiocytoma (MFH) and
tophaceous deposit at the second metacarpophalangeal joint in a 76-year-old man. 
The patient underwent surgical treatment, local radiotherapy and adjuvant
chemotherapy and was disease free at the time of his last examination. We use
this case to highlight the features of this clinical entity, which has never
previously been described in the surgical literature.

Publication Types: 
    Case Reports

PMID: 16782578 [PubMed - indexed for MEDLINE]

227: AJNR Am J Neuroradiol. 2006 Jun-Jul;27(6):1201-3.

Spinal cord compression by tophaceous gout with
fluorodeoxyglucose-positron-emission tomographic/MR fusion imaging.

Popovich T, Carpenter JS, Rai AT, Carson LV, Williams HJ, Marano GD.

Department of Radiology, West Virginia University School of Medicine, Morgantown,
WV, USA.

A 36-year-old woman presented with lower extremity paralysis. Her past medical
history included gout. Conventional radiography and MR imaging revealed bone
erosion and soft tissue lesions of the thoracic spine.
Fluorodeoxyglucose-positron-emission tomographic (FDG-PET) images revealed
hypermetabolic lesions of the thoracic spine. A CT-guided biopsy was diagnostic
for inflammatory tophaceous gout. This case describes the CT, MR, and FDG-PET
imaging characteristics of acute inflammatory gout. FDG-PET imaging
characteristics of this disorder have not been previously described.

Publication Types: 
    Case Reports

PMID: 16775264 [PubMed - indexed for MEDLINE]

228: J Rheumatol. 2006 Jul;33(7):1341-5. Epub 2006 Jun 1.

Erratum in:
    J Rheumatol. 2006 Aug;33(8):1714.

Comment in:
    Nat Clin Pract Rheumatol. 2006 Dec;2(12):650-1.

Recent diuretic use and the risk of recurrent gout attacks: the online
case-crossover gout study.

Hunter DJ, York M, Chaisson CE, Woods R, Niu J, Zhang Y.

Boston University Clinical Epidemiology Research and Training Unit, Arthritis
Center, the Department of Medicine at Boston Medical Center, Boston,
Massachusetts 02118, USA. djhunter@bu.edu

OBJECTIVE: To assess several putative risk factors, including thiazide and loop
diuretics use, thought to trigger recurrent gout attacks. METHODS: We conducted
an internet-based case-crossover study involving subjects who had a gout attack
within the past year. Patients were recruited online and asked to provide access 
to medical records. Data were obtained on specific diuretic use on each day over 
the 2-day period prior to an acute gout attack (hazard period) and on each day of
2 days during the intercritical period (control period). We examined the relation
of all diuretic use and use of specific diuretics, i.e., thiazide and loop, to
the risk of recurrent gout attacks using a conditional logistic regression model 
adjusting for alcohol consumption and purine intake. RESULTS: One hundred
ninety-seven subjects completed both control and hazard period questionnaires.
Participants were predominantly male (80%) and over half had a college education.
The median time between onset of gout attack and logging on to the website was 2 
days. Adjusting for alcohol consumption and purine intake, the odds ratio (OR)
for recurrent gout attacks from all diuretic use over the last 48 h was 3.6 (95% 
confidence interval 1.4-9.7). OR of recurrent gout attacks were 3.2 and 3.8 for
use of thiazide and loop, respectively. CONCLUSION: Recent use of diuretics is
associated with a significantly increased risk for recurrent gouty arthritis. The
increased risk of gout attacks from either thiazide or possibly loop diuretic
therapies represents an important modifiable risk factor in patients with gout.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16758506 [PubMed - indexed for MEDLINE]

229: Rheum Dis Clin North Am. 2006 May;32(2):427-46, viii.

Imaging features of crystal-induced arthropathy.

Choi MH, MacKenzie JD, Dalinka MK.

Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce 
Street/1 Silverstein, Philadelphia, PA 19104, USA.

Crystal-induced arthropathies constitute a spectrum of inflammatory arthritides
that is induced by cellular reaction to crystal deposition in and around joints. 
A variety of microcrystals may be deposited and can induce an inflammatory
response. The three most common types of crystal-induced arthropathy are gout,
calcium pyrophosphate dihydrate deposition disease, and calcium hydroxyapatite
deposition disease. Each has a characteristic clinical presentation, crystal type
that may be aspirated from affected tissues, and radiographic appearance. Each of
these entities may occur as a primary abnormality or secondary to an underlying
disorder. Sometimes these diseases may coexist in the same joint or individual.
Imaging frequently plays a crucial role in the diagnosis of crystal-induced
arthropathies and may help to monitor disease progression and treatment response.

Publication Types: 
    Review

PMID: 16716888 [PubMed - indexed for MEDLINE]

230: Rheum Dis Clin North Am. 2006 May;32(2):359-82, vii.

Clinical trials in crystal arthropathy.

Joseph-Ridge N, Cazzetta S, MacDonald P.

TAP Pharmaceutical Products, Inc., Lake Forest, IL, USA.
Nancy.joseph-ridge@TAP.com

A few clinical trials have evaluated therapeutic agents for crystal-associated
arthropathy. Most of the studies are uncontrolled and observational. Management
of patients who have acute crystal arthropathies usually is symptomatic with
long-term management depending on crystal composition. In trials of gout, studies
focus on acute symptomatic treatment, foregoing chronic management, which is
aimed at reducing the concentration of serum urate. In those who have calcium
crystals, however, there is no definitive or effective long-term treatment in
chronic gout. The xanthine oxidase inhibitor and uricosurics are the agents used 
most commonly. Newer compounds in clinical trials show promise as effective and
safe therapeutic options.

Publication Types: 
    Review

PMID: 16716884 [PubMed - indexed for MEDLINE]

231: Rheum Dis Clin North Am. 2006 May;32(2):333-57, vi.

Treatment of crystal arthropathy--history and advances.

Nuki G.

Queen's Medical Research Institute, University of Edinburgh, Scotland, UK.
g.nuki@ed.ac.uk

The history of gout and the many distinguished historical figures who have
suffered the agonies of this crystal deposition disorder have claimed the
attention of medical historians like no other disease. Its treatment with uric
acid lowering drugs became a twentieth century paradigm for the successful
management and prevention of a chronic rheumatic disease, but the colorful
history of the treatment of gout and crystal deposition disorders stretches back 
over 4,000 years.

Publication Types: 
    Historical Article
    Review

PMID: 16716883 [PubMed - indexed for MEDLINE]

232: Rheum Dis Clin North Am. 2006 May;32(2):313-31, vi.

Renal urate transport.

Mount DB, Kwon CY, Zandi-Nejad K.

Harvard Medical School, Boston, MA, USA. dmount@rics.bwh.harvard.edu

Serum uric acid is determined by a balance between production and renal
excretion. Luminal reabsorption of urate by the proximal tubule from the
glomerular ultrafiltrate involves coupling between sodium-anion cotransport and
urate-anion exchange. Apical sodium-coupled cotransport of lactate, ketoacids,
nicotinate, and pyrazinoate increases intracellular levels of these anions in
proximal tubular cells, stimulating the apical absorption of luminal urate via
anion exchange. Hyperuricemia occurs when plasma levels of these anions increase;
for example, hyperuricemia is a well-recognized concomitant of lactic acidosis
and ketoacidosis. Relevant developments in the molecular and renal physiology of 
urate homeostasis are reviewed.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Review

PMID: 16716882 [PubMed - indexed for MEDLINE]

233: Rheum Dis Clin North Am. 2006 May;32(2):295-311, vi.

Gout: update on some pathogenic and clinical aspects.

Lioté F, Ea HK.

Fédération de Rhumatologie, Pôle Appareil Locomoteur (Centre Viggo Petersen),
Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris,
France. frederic.liote@lrb.aphp.fr

Pathogenesis of gout inflammation remains unknown, but recent advances have been 
made with respect to initiation, amplification, and self-limitation. Direct
crystal-cell membrane contact leads to cell activation, involving
membrane-associated molecules. Resolution of acute gout inflammation is a
mechanism that is controlled by monocyte-macrophage switch, which results in the 
loss of cytokine production capability and, conversely, the ability to produce
anti-inflammatory molecules. MRI and ultrasound findings provide preliminary data
that are not yet used in clinical trials. Diagnosis and management
recommendations are missing, but this gap will be filled soon with the upcoming
European League Against Rheumatism Task Force's recommendations on gout.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16716881 [PubMed - indexed for MEDLINE]

234: Rheum Dis Clin North Am. 2006 May;32(2):255-73, v.

Epidemiology of crystal arthropathy.

Choi H.

Division of Rheumatology, Vancouver General Hospital, The University of British
Columbia, Arthritis Research Centre of Canada, Suite 300, 895 West 10th Avenue,
Vancouver, BC V5Z 1L7, Canada. hchoi@partners.org

Gout is an inflammatory arthritis mediated by the crystallization of uric acid
within the joints and often is associated with hyperuricemia. Data suggest that
the overall disease burden of gout remains substantial and may be increasing.
Identifying and characterizing modifiable risk factors for gout is a major step
in preventing and managing this painful condition. As more scientific data on the
risk factors and comorbidities of gout become available, their integration into
gout prevention and care strategies may become essential. This article reviews
the relevant epidemiologic data, with a focus on recent progress and data on
other crystal arthropathies.

Publication Types: 
    Review

PMID: 16716879 [PubMed - indexed for MEDLINE]

235: Ann Rheum Dis. 2006 Oct;65(10):1301-11. Epub 2006 May 17.

Comment in:
    Evid Based Med. 2007 Apr;12(2):56.

EULAR evidence based recommendations for gout. Part I: Diagnosis. Report of a
task force of the Standing Committee for International Clinical Studies Including
Therapeutics (ESCISIT).

Zhang W, Doherty M, Pascual E, Bardin T, Barskova V, Conaghan P, Gerster J,
Jacobs J, Leeb B, Lioté F, McCarthy G, Netter P, Nuki G, Perez-Ruiz F, Pignone A,
Pimentão J, Punzi L, Roddy E, Uhlig T, Zimmermann-Gòrska I; EULAR Standing
Committee for International Clinical Studies Including Therapeutics.

Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City
Hospital, Nottingham NG5 1PB, UK. weiya.zhang@nottingham.ac.uk

OBJECTIVE: To develop evidence based recommendations for the diagnosis of gout.
METHODS: The multidisciplinary guideline development group comprised 19
rheumatologists and one evidence based medicine expert, representing 13 European 
countries. Ten key propositions regarding diagnosis were generated using a Delphi
consensus approach. Research evidence was searched systematically for each
proposition. Wherever possible the sensitivity, specificity, likelihood ratio
(LR), and incremental cost-effectiveness ratio were calculated for diagnostic
tests. Relative risk and odds ratios were estimated for risk factors and
co-morbidities associated with gout. The quality of evidence was categorised
according to the evidence hierarchy. The strength of recommendation (SOR) was
assessed using the EULAR visual analogue and ordinal scales. RESULTS: 10 key
propositions were generated though three Delphi rounds including diagnostic
topics in clinical manifestations, urate crystal identification, biochemical
tests, radiographs, and risk factors/co-morbidities. Urate crystal identification
varies according to symptoms and observer skill but is very likely to be positive
in symptomatic gout (LR = 567 (95% confidence interval (CI), 35.5 to 9053)).
Classic podagra and presence of tophi have the highest clinical diagnostic value 
for gout (LR = 30.64 (95% CI, 20.51 to 45.77), and LR = 39.95 (21.06 to 75.79),
respectively). Hyperuricaemia is a major risk factor for gout and may be a useful
diagnostic marker when defined by the normal range of the local population (LR = 
9.74 (7.45 to 12.72)), although some gouty patients may have normal serum uric
acid concentrations at the time of investigation. Radiographs have little role in
diagnosis, though in late or severe gout radiographic changes of asymmetrical
swelling (LR = 4.13 (2.97 to 5.74)) and subcortical cysts without erosion (LR =
6.39 (3.00 to 13.57)) may be useful to differentiate chronic gout from other
joint conditions. In addition, risk factors (sex, diuretics, purine-rich foods,
alcohol, lead) and co-morbidities (cardiovascular diseases, hypertension,
diabetes, obesity, and chronic renal failure) are associated with gout. SOR for
each proposition varied according to both the research evidence and expert
opinion. CONCLUSIONS: 10 key recommendations for diagnosis of gout were developed
using a combination of research based evidence and expert consensus. The evidence
for diagnostic tests, risk factors, and co-morbidities was evaluated and the
strength of recommendation was provided.

Publication Types: 
    Practice Guideline
    Research Support, Non-U.S. Gov't
    Review

PMID: 16707533 [PubMed - indexed for MEDLINE]

236: Ann Rheum Dis. 2006 Oct;65(10):1312-24. Epub 2006 May 17.

EULAR evidence based recommendations for gout. Part II: Management. Report of a
task force of the EULAR Standing Committee for International Clinical Studies
Including Therapeutics (ESCISIT).

Zhang W, Doherty M, Bardin T, Pascual E, Barskova V, Conaghan P, Gerster J,
Jacobs J, Leeb B, Lioté F, McCarthy G, Netter P, Nuki G, Perez-Ruiz F, Pignone A,
Pimentão J, Punzi L, Roddy E, Uhlig T, Zimmermann-Gòrska I; EULAR Standing
Committee for International Clinical Studies Including Therapeutics.

Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City
Hospital, Nottingham NG5 1PB, UK. weiya.zhang@nottingham.ac.uk

OBJECTIVE: To develop evidence based recommendations for the management of gout. 
METHODS: The multidisciplinary guideline development group comprised 19
rheumatologists and one evidence based medicine expert representing 13 European
countries. Key propositions on management were generated using a Delphi consensus
approach. Research evidence was searched systematically for each proposition.
Where possible, effect size (ES), number needed to treat, relative risk, odds
ratio, and incremental cost-effectiveness ratio were calculated. The quality of
evidence was categorised according to the level of evidence. The strength of
recommendation (SOR) was assessed using the EULAR visual analogue and ordinal
scales. RESULTS: 12 key propositions were generated after three Delphi rounds.
Propositions included both non-pharmacological and pharmacological treatments and
addressed symptomatic control of acute gout, urate lowering therapy (ULT), and
prophylaxis of acute attacks. The importance of patient education, modification
of adverse lifestyle (weight loss if obese; reduced alcohol consumption; low
animal purine diet) and treatment of associated comorbidity and risk factors were
emphasised. Recommended drugs for acute attacks were oral non-steroidal
anti-inflammatory drugs (NSAIDs), oral colchicine (ES = 0.87 (95% confidence
interval, 0.25 to 1.50)), or joint aspiration and injection of corticosteroid.
ULT is indicated in patients with recurrent acute attacks, arthropathy, tophi, or
radiographic changes of gout. Allopurinol was confirmed as effective long term
ULT (ES = 1.39 (0.78 to 2.01)). If allopurinol toxicity occurs, options include
other xanthine oxidase inhibitors, allopurinol desensitisation, or a uricosuric. 
The uricosuric benzbromarone is more effective than allopurinol (ES = 1.50 (0.76 
to 2.24)) and can be used in patients with mild to moderate renal insufficiency
but may be hepatotoxic. When gout is associated with the use of diuretics, the
diuretic should be stopped if possible. For prophylaxis against acute attacks,
either colchicine 0.5-1 mg daily or an NSAID (with gastroprotection if indicated)
are recommended. CONCLUSIONS: 12 key recommendations for management of gout were 
developed, using a combination of research based evidence and expert consensus.
The evidence was evaluated and the SOR provided for each proposition.

Publication Types: 
    Practice Guideline
    Research Support, Non-U.S. Gov't
    Review

PMID: 16707532 [PubMed - indexed for MEDLINE]

237: Photomed Laser Surg. 2006 Apr;24(2):140-50.

Photobiomodulation of pain and inflammation in microcrystalline arthropathies:
experimental and clinical results.

Soriano F, Campana V, Moya M, Gavotto A, Simes J, Soriano M, Soriano R, Spitale
L, Palma J.

Instituto Argentino de Medicina Láser (IAMEL), Rosario, Argentina.
soriano@steel.com.ar

OBJECTIVE: This article presents the results of laser therapy in crystal
(hydroxyapatite, calcium pyrophosphate, and urates) deposition-induced arthritis 
in rats and the clinical applications in humans. BACKGROUND DATA:
Microcrystalline arthropathies are prevalent among geriatric patients, who are
more vulnerable to the side effects of drugs. The effectiveness of laser therapy 
for pain relief, free of side effects, has been reported in painful conditions.
METHODS: Two milligrams of each of the above-mentioned crystals was injected in
both joints of the back limbs in three groups of rats; these groups were then
treated with laser irradiation. Three other groups received no treatment after
the injections. We determined the plasmatic levels of inflammatory markers
(fibrinogen, prostaglandin E2, and TNF(alpha)), tissues (prostaglandin E(2)) and 
conducted anatomopathological studies. Twenty-five patients with acute gout
arthritis were randomized into two groups and treated over 5 days: group A,
diclofenac 75 mg orally, twice a day; and group B, laser irradiation once a day. 
Forty-nine patients with knee chronic pyrophosphate arthropathy were randomized
into two groups and treated over 21 days; group A, diclofenac 50 mg orally, twice
a day; and group B, laser irradiation once a day. Thirty patients with shoulder
chronic hydroxyapatite arthropathy were randomized into two groups and treated
over 21 days; group A, diclofenac 50 mg orally, twice a day; and group B, laser
irradiation once a day. RESULTS: Fibrinogen, prostaglandin E(2), and TNF(alpha)
concentrations in the rats injected with crystals and treated with laser
decreased significantly as compared with the groups injected with crystals
without treatment. Both laser therapy and diclofenac achieved rapid pain relief
in patients with acute gouty arthritis without significant differences in
efficacy. Laser therapy was more effective than diclofenac in patients with
chronic pyrophosphate arthropathy and in patients with chronic apatite deposition
disease. CONCLUSION: Laser therapy represents an effective treatment in the
therapeutic arsenal of microcrystalline arthropathies.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16706692 [PubMed - indexed for MEDLINE]

238: Clin Rheumatol. 2007 Mar;26(3):308-13. Epub 2006 May 11.

Severity of gouty arthritis is associated with Q-wave myocardial infarction: a
large-scale, cross-sectional study.

Chen SY, Chen CL, Shen ML.

Department of Internal Medicine, Heping Branch, Taipei City Hospital, 33, Sec. 2,
Junghua Rd., Taipei, Taiwan, Republic of China. doctor@rahome.idv.tw

To examine whether serum urate level and other aspects of gouty arthritis are
independently associated with Q-wave myocardial infarction (QWMI) in gouty
population, we performed a cross-sectional study. A total of 22,572 gouty cases
were enrolled. QWMI was defined as a positive finding by resting
electrocardiographic criteria excluding the conditions producing
pseudoinfarction. The variables of gout were tested univariately and
multivariately, controlling for the covariates by logistic regression analysis.
The above analysis was then repeated in subgroups of young-aged (<50 years),
old-aged (> or = 50 years), male, and female patients. Increased serum urate
level was significantly associated with QWMI in all subjects and male subgroup
[odds ratio (OR), 1.120; 95% confidence interval (CI), 1.020-1.229; OR, 1.106;
95% CI, 1.001-1.223, respectively, for each mg/dl increment]. After controlling
for serum urate level and the covariates, increased affected joint count was also
independently associated with QWMI finding in all subjects, male and old-aged
subgroups (OR, 1.098; 95% CI, 1.014-1.189; OR, 1.094; 95% CI, 1.005-1.192; OR,
1.095; 95% CI, 1.001-1.199, respectively). Tophi formation was independently
associated with QWMI in young-aged subgroup (OR, 2.494; 95% CI, 1.159-5.366).
None of the variables of gout including hyperuricemia was significantly
associated with QWMI in female subgroup after controlling for covariates. This
study first demonstrates that gout is associated with QWMI by both the severity
of gouty arthritis and serum urate level, while the association of urate to QWMI 
could be different between age strata and genders.

PMID: 16688395 [PubMed - indexed for MEDLINE]

239: Breast J. 2006 May-Jun;12(3):263-5.

Mammary gouty tophus: a case report and review of the literature.

Sharifabad MA, Tzeng J, Gharibshahi S.

Department of Medicine, Englewood Hospital and Medical Center, NJ 07631, USA.
mashrif@yahoo.com

We present an uncommon presentation of a common disease in a completely
asymptomatic woman. She presented with a solitary breast nodule incidentally
found on her first mammography. A step-by-step evaluation of the breast nodule,
including fine-needle aspiration and excisional biopsy, was done which revealed
mammary gouty tophus.

Publication Types: 
    Case Reports
    Review

PMID: 16684326 [PubMed - indexed for MEDLINE]

240: Nephrology (Carlton). 2006 Apr;11(2):147-50.

Comment in:
    Nephrology (Carlton). 2006 Oct;11(5):481-2; author reply 482.

Colchicine myoneuropathy in chronic renal failure patients with gout.

Lai IC, Cheng CY, Chen HH, Chen WY, Chen PY.

Department of Nephrology, Taipei Medical University Hospital, Taipei, Taiwan.

Colchicine myoneuropathy is a rare and often underdiagnosed disease. It often
presents as painless subacute muscle weakness. We present a case of painful
colchicine myoneuropathy in a 76-year-old man with chronic renal failure and
gout. Published work about clinical presentations of colchicine myoneuropathy in 
gouty arthritis patients are reviewed. During the previous year, the patient had 
a drug regimen of colchicine 0.5 mg three times per day for a 3 day course each
month. He developed bilateral lower leg weakness and severe myalgia. His serum
creatinine level was 680.7 micromol/L and creatinine kinase was 959 IU/L on
admission. Laboratory findings included decreasing amplitude of motor and sensory
nerve conduction velocity and an electromyogram showed small amplitude, short
duration polyphasic waves over the right biceps. A muscle biopsy disclosed
vacuolar changes in the cytoplasm. These results all supported a diagnosis of
colchicine myoneuropathy. After cessation of colchicine, the creatinine kinase
level decreased approximately 50% in 6 days, myalgia subsided and his muscle
weakness improved gradually over the next 2 weeks.

Publication Types: 
    Case Reports

PMID: 16669978 [PubMed - indexed for MEDLINE]

241: J Assoc Physicians India. 2006 Jan;54:49-52.

Partial HPRT deficiency (Kelley-Seegmiller syndrome).

Saigal R, Chakraborty A, Yadav RN, Prashant RK.

Department of Medicine, SMS Medical College, Jaipur.

Hypoxanthine-guanine phosphoribosyl transferase (HPRT) deficiency is an X-linked 
defect of purine metabolism. Clinical manifestations are usually related to the
degree of enzyme deficiency; complete HPRT deficiency (Lesh-Nyhan Syndrome)
presenting with severe neurological or renal symptoms, or partial HPRT deficiency
(Kelley-Seegmiller syndrome) manifesting as a gout-urolithiasis syndrome. We
report a case of partial HPRT deficiency presenting as chronic tophaceous gout,
mental retardation, nephrolithiasis and family history suggestive of X-linked
inheritance, for its rarity.

Publication Types: 
    Case Reports

PMID: 16649740 [PubMed - indexed for MEDLINE]

242: Ann Rheum Dis. 2006 Oct;65(10):1368-72. Epub 2006 Apr 27.

Sex differences in gout epidemiology: evaluation and treatment.

Harrold LR, Yood RA, Mikuls TR, Andrade SE, Davis J, Fuller J, Chan KA, Roblin D,
Raebel MA, Von Worley A, Platt R, Saag KG.

Meyers Primary Care Institute, University of Massachusetts Medical School,
Worcester, MA 01655, USA. HarroldL@ummhc.org

BACKGROUND: Little is known about the characteristics, evaluation and treatment
of women with gout. OBJECTIVE: To examine the epidemiological differences and
differences in treatment between men and women in a large patient population.
METHODS: The data from approximately 1.4 million people who were members of seven
managed care plans in the USA for at least 1 year between 1 January 1999 and 31
December 2003 were examined. Adult members who had pharmacy benefits and at least
two ambulatory claims specifying a diagnosis of gout were identified. In
addition, men and women who were new users of urate-lowering drugs (ULDs) were
identified to assess adherence with recommended surveillance of serum urate
levels within 6 months of initiating urate-lowering treatment. RESULTS: A total
of 6133 people (4975 men and 1158 women) with two or more International
Classification of Disease-9 codes for gout were identified. As compared with men 
with gout, women were older (mean age 70 (SD 13) v 58 (SD 14), p<0.001) and had
comorbidities and received diuretics more often (77% v 40%; p<0.001). Only 37% of
new users of urate-lowering treatment had appropriate surveillance of serum urate
levels post-initiation of urate-lowering treatment. After controlling for age,
comorbidities, gout treatments, number of ULD dispensings and health plan, women 
were more likely (odds ratio 1.36, 95% confidence interval 1.11 to 1.67) to
receive the recommended serum urate level testing. CONCLUSIONS: Women with gout
were older, had greater comorbidities and more often used diuretics and received 
appropriate surveillance of serum urate levels, suggesting that the factors
leading to gout as well as monitoring of treatment are very different in women
and men.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16644784 [PubMed - indexed for MEDLINE]

243: Rheumatology (Oxford). 2006 Nov;45(11):1422-31. Epub 2006 Apr 21.

Effectiveness of interventions for the treatment of acute and prevention of
recurrent gout--a systematic review.

Sutaria S, Katbamna R, Underwood M.

Barts and The London, Queen Mary, University of London, Institute of Health
Sciences, London, UK. shailen000@yahoo.co.uk

OBJECTIVE: To determine the evidence for the effectiveness of treatments for
acute gout and the prevention of recurrent gout. METHOD: Seven electronic
databases were searched for randomized controlled trials of treatments for gout
from their inception to the end of 2004. No language restrictions were applied.
All randomized controlled trials of treatments routinely available for the
treatment of gout were included. Trials of the prevention of recurrence were
included only if patients who had had gout and had at least 6 months of follow-up
were studied. RESULTS: We found 13 randomized controlled trials of treatment for 
acute gout, two of which were placebo controlled. Colchicine was found to be
effective in one study; however, the entire colchicine group developed toxicity. 
The only robust conclusion from studies of non-steroidal anti-inflammatory drugs 
is that pain relief from indometacin and etoricoxib are equivalent. We found one 
randomized controlled trial, reported only as a conference abstract, of recurrent
gout prevention. CONCLUSION: The shortage of robust data to inform the management
of a common problem such as gout is surprising. All of the drugs used to treat
gout can have serious side effects. The incidence of gout is highest in the
elderly population. It is in this group, who are at a high risk of serious
adverse events, that we are using drugs of known toxicity. The balance of risks
and benefits for the drug treatment of gout needs to be reassessed.

Publication Types: 
    Review

PMID: 16632483 [PubMed - indexed for MEDLINE]

244: Indian J Pathol Microbiol. 2006 Jan;49(1):42-3.

FNAC of gouty tophi--a case report.

Purohit MB, Purohit TM, Tandon RK.

Departments of Pathology and P & S. M, P.D.U. Medical College, Rajkot, Gujarat.
mitimilan03@rediff.com

A 52 yrs old male presented with multiple, painless, firm nodules over
extremities, which were mimicking benign neoplastic lesion. Fine needle
aspiration was performed from three such nodules which revealed chalky white
aspirate. After staining the smears with H&E and Giemsa stains, smears show
amorphous pink material, needle shaped crystalline structures, many macrophages
and foreign body type giant cells. A diagnosis of gouty tophi was offered which
was confirmed by histopathology and serum uric acid level.

Publication Types: 
    Case Reports

PMID: 16625976 [PubMed - indexed for MEDLINE]

245: Int J Cardiol. 2007 Jan 18;114(3):393-5. Epub 2006 Apr 19.

An unusual cause of fatal pulmonary embolism.

De Giorgio F, Abbate A, Zoccai GB, Pascali VL, d'Aloja E, Capelli A, Arena V.

We report on a case of a fatal pulmonary embolism--an unexpected finding at
autopsy of a 71-year-old man who had suffered from severe erosive gouty
arthritis. Using morphological findings, medical history and histopathological
results, we show the potentially devastating complications of this fairly common 
medical condition, occurring as a result of massive bone marrow erosion and
detachment and finally leading to embolization of the lungs.

Publication Types: 
    Case Reports
    Letter

PMID: 16624430 [PubMed - indexed for MEDLINE]

246: Int J Clin Pract. 2006 Apr;60(4):408-14.

Erratum in:
    Int J Clin Pract. 2006 May;60(5):630.

Magnetic resonance imaging in the quantitative assessment of gouty tophi.

Schumacher HR Jr, Becker MA, Edwards NL, Palmer WE, MacDonald PA, Palo W,
Joseph-Ridge N.

University of Pennsylvania, Philadelphia, PA 19104-4283, USA.
schumacr@mail.med.upenn.edu

Measurements of tophus size can be important in monitoring the course of gout
therapy, as tophus resolution is proposed as one measure of success of treatment.
This multicentre study assessed the intra- and interreader reproducibility of
quantitative tophus volume measurements from magnetic resonance images (MRI) in
subjects with palpable gouty tophi. Subjects first underwent radiographic imaging
of a selected tophus followed by MRI before and at <or=5, 10 and 20-min after
gadolinium administration. After choosing optimal parameters, subjects underwent 
pre- and postgadolinium-enhanced MRIs of a selected tophus on two occasions
separated by 5-10 days. Unenhanced spin-echo images provided satisfactory tophi
images and were less subject to interfering artefacts than gadolinium-enhanced
gradient-echo images. Intrareader reproducibility was excellent, with no
statistically significant difference in mean tophus volume between visits (mean
difference - 0.05 +/- 0.97 cm3). A small but statistically significant difference
in interreader mean tophus volume was detected (mean difference 0.89 +/- 2.05
cm3; p < 0.05). MRI can quantify tophus size in gout and deserves further
comparison with other techniques for tophus size monitoring in assessing effects 
of gout therapy.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16620352 [PubMed - indexed for MEDLINE]

247: Acta Vet Hung. 2006 Mar;54(1):51-60.

Molecular diagnosis of avian nephritis: preliminary report.

Mándoki M, Dobos-Kovács M, Bakonyi T, Rusvai M.

Department of Pathology and Forensic Veterinary Medicine, Veterinary Faculty,
Szent István University, H-1400 Budapest, P.O. Box 2, Hungary.
Mandoki.Mira@aotk.szie.hu

Kidney samples from chickens diagnosed with acute nephritis and gout were
subjected to histological and electron microscopic examination. The
investigations revealed cytoplasmic inclusion bodies in the tubular epithelial
cells containing round virions of about 30 nm in diameter. Since avian nephritis 
virus (ANV) is known as a potential causative agent of the so-called baby chick
nephropathy, an RT-PCR assay was developed for the molecular detection of
ANV-specific nucleic acid in the specimen. The specificity of the assay was
confirmed by direct sequencing of the amplicon obtained in the reaction. The
nucleotide sequence of the PCR product showed 92% identity with the reference ANV
sequence deposited in the GenBank database. After having been validated on some
other suspicious cases of avian nephritis, the PCR method described in this study
can be a potential tool for routine diagnostic examination of samples submitted
from cases of gout and nephropathy in chickens.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 16613026 [PubMed - indexed for MEDLINE]

248: J Clin Rheumatol. 2006 Apr;12(2):61-5.

Serum urate levels and gout flares: analysis from managed care data.

Sarawate CA, Patel PA, Schumacher HR, Yang W, Brewer KK, Bakst AW.

Health Outcomes Research, HealthCore, Inc., 800 Delaware Avenue, Wilmington, DE
19801-1366, USA. csarawate@healthcore.com

BACKGROUND: The desired serum urate level (SUA) for prevention of gout attacks is
widely recommended to be in the subsaturating range, <6.0 mg/dL. OBJECTIVES: The 
objectives of this study were to evaluate attainment of this target SUA among
gout patients on allopurinol in a naturalistic setting and to assess its impact
on gout flare risk. METHODS:: This was a retrospective, observational study in a 
southeastern U.S. managed care organization of approximately 2.2 million members.
The first gout claim/prescription within the intake period (January 1,
2000-December 31, 2002) was the index date. Included patients had > or =2 visits 
with gout International Classification of Diseases, 9th Revision code (274.xx) or
> or =1 pharmacy script(s) for allopurinol, colchicine, probenecid, or
sulfinpyrazone. Excluded patients were <18 years and/or did not have a 1-year
continuous eligibility pre-/postindex date. Gout flares were defined by
office/emergency room visit with gout or joint pain code(s) and > or =1 of the
following within 7 days of the visit: intraarticular aspiration/injection, joint 
fluid microscopy, or pharmacy claim for nonsteroidal antiinflammatory drug,
colchicine, corticosteroid, or ACTH. Multivariable regression analyses were
conducted to evaluate gout flare risk/rate and association with target SUA.
RESULTS: Approximately 40% of 5942 gout patients identified used allopurinol
postindex. Among allopurinol users with pre-/postindex SUA data (n = 162), mean
SUA was lowered from 8.7 mg/dL to 7.1 mg/dL; reduction was significant (P <
0.001). Among allopurinol users who did not have SUA <6.0 mg/dL preindex (n =
147), only 25% reached target levels during postindex. Despite pharmacotherapy,
patients with nontarget levels were 59% more likely to flare than those at
target. Allopurinol users who were not at target were 75% more likely to flare.
CONCLUSION: The failure of allopurinol users to achieve target SUA levels of <6.0
mg/dL may be attributed to lack of awareness of optimal SUA, allopurinol dosing, 
compliance, and efficacy. Patients who did not achieve target SUA were at
increased flare risk.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16601538 [PubMed - indexed for MEDLINE]

249: Clin Orthop Relat Res. 2006 Apr;445:250-3.

Erratum in:
    Clin Orthop Relat Res. 2006 May;446:297.

Case reports: pathologic fracture of the patella from a gouty tophus.

Price MD, Padera RF, Harris MB, Vrahas MS.

Harvard Combined Program in Orthopedic Surgery, Harvard Medical School, Boston,
Massachusetts 02114, USA. mdprice@partners.org

Fracture of the patella is a relatively common condition seen in patients with
trauma. We report one patient with known gout who sustained relatively minor
trauma that resulted in a patellar fracture. An intraoperative biopsy confirmed
that much of the patella had been replaced with gouty tophus. Gout is a rare
cause of patellar fracture, with few documented cases. Postoperative management
of patients with patella fractures secondary to gout may be routine with the
addition of medical management for the underlying pathologic process.

Publication Types: 
    Case Reports

PMID: 16601419 [PubMed - indexed for MEDLINE]

250: Curr Opin Rheumatol. 2006 May;18(3):249-55.

Crystal-induced arthropathies: recent investigative advances.

Ellman MH, Becker MA.

University of Chicago, Pritzker School of Medicine, Rheumatology Section,
Department of Medicine, University of Chicago Medical Center, Chicago, Illinois
60637, USA.

PURPOSE OF REVIEW: To highlight recent investigations that have stimulated
renewed interest in crystal-induced arthropathies. RECENT FINDINGS: Specific
diet-related and alcohol-related risks for gout have been clarified, and
alternative urate-lowering treatments likely to benefit patients with
difficult-to-treat gout are in development. Progress toward understanding
mechanisms underlying the renal deficits defining most cases of gout includes
characterization of a urate-specific renal tubule transporter explaining many
aspects of renal uric acid handling and identification of mutations in the UMOD
gene, resulting in altered uromodulin protein in the gout-associated disorders
familial juvenile hyperuricemic nephropathy and medullary cystic kidney disease
type 2. A genetic marker associated with the risk for severe allopurinol toxicity
has been reported. Hyperuricemia and gout are increasing in incidence, as is
complicated gout, especially among the elderly and patients with cardiovascular
and renal comorbidities, organ transplants, or complex concomitant medication
regimens. Asymptomatic hyperuricemia is clearly associated with hypertension,
chronic kidney disease, cardiovascular disease, and the insulin resistance
syndrome, and the pathogenetic significance of these associations is under
intensive study. Mutation in the ANKH gene has been found among some patients
with sporadic as well as familial calcium pyrophosphate deposition disease.
SUMMARY: The results of these clinical, epidemiologic, experimental, and
therapeutic investigations presage advances in the management of crystal-induced 
arthropathies.

Publication Types: 
    Review

PMID: 16582687 [PubMed - indexed for MEDLINE]

251: Adv Chronic Kidney Dis. 2006 Apr;13(2):124-30.

Genetic factors associated with gout and hyperuricemia.

Bleyer AJ, Hart TC.

Department of Internal Medicine, Section on Nephrology, The Wake Forest
University School of Medicine, Winston-Salem, NC 27157-1053, USA.
ableyer@wfubmc.edu

Hyperuricemia and gout are common conditions that have long been known to have a 
heritable component. Obesity, diabetes, and chronic kidney failure are conditions
with multifactorial inheritance that are associated with gout. In addition,
social factors such as protein and alcohol intake affect serum uric acid levels. 
The current review discusses basic uric acid metabolism and the multigenetic
inheritance of hyperuricemia. Several monogenic disorders affecting uric acid
metabolism are reviewed. The genetics, pathophysiology, diagnosis, and treatment 
of familial juvenile hyperuricemic nephropathy/medullary cystic kidney disease,
autosomal dominant disorders associated with hyperuricemia and progressive kidney
failure, are described.

Publication Types: 
    Research Support, N.I.H., Extramural
    Review

PMID: 16580613 [PubMed - indexed for MEDLINE]

252: Skeletal Radiol. 2006 Dec;35(12):942-5. Epub 2006 Mar 18.

A rare cause of spinal cord compression: imaging appearances of gout of the
cervical spine.

Dharmadhikari R, Dildey P, Hide IG.

Department of Radiology, Freeman Hospital, Freeman Road, High Heaton,
Newcastle-upon-Tyne, UK. geoff.hide@nuth.nhs.uk

Gout is a metabolic disorder typically affecting the peripheral joints, more
commonly in males. Spinal involvement is uncommon and is usually associated with 
hyperuricemia. We present the imaging findings of a case of spinal gout in a
female patient with no previous history of hyperuricaemia, involving multiple
spinal segments.

Publication Types: 
    Case Reports

PMID: 16547746 [PubMed - indexed for MEDLINE]

253: Clin Rheumatol. 2006 Nov;25(6):886-8. Epub 2006 Mar 7.

Serum-synovial gradient data of normouricemic patients with history of gout and
acute knee effusion.

Rozin AP, Braun-Moscovici Y, Balbir-Gurman A.

The B. Shine Department of Rheumatology, Rambam Medical Center, B. Rappaport
Faculty of Medicine, Technion, POB 9602, Haifa, 31096, Israel.
a_rozin@rambam.health.gov.il

The etiology of arthritis episodes in normouricemic patients with gout is still
unclear. We propose that the fluctuation in synovial urate level, as well as pH, 
ion strength, albumin, and globulin values relative to serum levels, could be
involved in crystal formation. To assess serum-synovial gradient (SSG), the sera 
and synovial fluid (SF) of six normouricemic patients (men, age 48-79) with a
history of gout (American College of Rheumatology criteria) and acute knee
effusion were screened for uric acid, pH, osmolality (Osm), P/Ca, albumin,
globulin, and SSG. Monosodium urate monohydrate (MSUM) crystals were determined
by polarized light (PL). Infectious arthritis was ruled out via Gram staining and
synovial fluid culture. Negative X-ray and PL microscopy results excluded
chondrocalcinosis. Five patients (1-5) had inflammatory knee effusion (WBC
>2,000/mm(3)), and one (patient 6) had noninflammatory knee effusion (600
WBC/mm(3)). MSUM crystals were found in the WBC of patient 1 only. He had
tophaceous gout with normal serum uric acid levels and showed significant
negative Osm and P and positive Ca SSG. Two crystal negative patients had severe 
negative pH SSG with alkaline synovial fluid, significant P/Ca SSG, and high
positive globulin SSG, while one of them had supersaturated SF uric acid content.
The other patients displayed an increased Osm and P/Ca SSG. All SSG values were
five to ten times higher than the coefficient of variance for used methods.
Noninflammatory SF of patient 6 does not appear to be related to active gout. The
data on SSG for MSUM, pH, Osm, Alb/Glob, and P/Ca in normouricemic patients with 
gout history and acute knee effusion was not homogeneous. We propose that
acid-base and ionic-protein gradient may lead to instability of subsaturated
urate solution, thereby predisposing to MSUM deposits within synovial membrane
and inducing inflammation.

PMID: 16521049 [PubMed - indexed for MEDLINE]

254: Acta Cytol. 2006 Jan-Feb;50(1):101-4.

Diagnostic value of fine needle aspiration cytology in gouty tophi: a report of 7
cases.

Bhadani PP, Sah SP, Sen R, Singh RK.

Department of Pathology, BP Koirala Institute of Health Sciences, Dharan, Nepal. 
ukbhadani275@yahoo.com

BACKGROUND The diagnosis of gout can be problematic when the presentation is
atypical and serum uric acid is borderline elevated. Demonstration of monosodium 
urate (MSU) crystals in fine needle aspiration (FNA) smears from nodular masses
clinically suspected to be tophi establishes the diagnosis unequivocally. CASES: 
Of the 7 cases in this study, 4 were suspected clinically to have gouty tophi.
Giant cell tumor of tendon sheath, giant cell tumor of bone and metastatic tumor 
with multicentric involvement of bone were the clinical diagnoses in 1 case each.
Serum uric acid levels high enough to be in the diagnostic range for gout were
reported in 3 cases, within normal limits in 3 cases and low in 1 chronic
alcoholic patient. Bright field microscopy of FNA smears revealed singly
scattered or stacks of MSU crystals with variable number of inflammatory cells,
with or without foreign body giant cells in 6 cases. In 1 patient, FNA showed
stacks of MSU crystals only. Characteristic birefringence of MSU crystals was
observed on polarizing microscopy. CONCLUSION: FNA demonstration of MSU crystals 
on polarizing microscopy can easily establish the nature of the nodules in and
around the joints and in soft tissue as gouty tophi and is thus an investigation 
differentiating this lesion from other masses clinically simulating it.

Publication Types: 
    Case Reports

PMID: 16514850 [PubMed - indexed for MEDLINE]

255: Ophthalmology. 2006 Mar;113(3):462-5.

Comment in:
    Ophthalmology. 2007 Oct;114(10):1958; author reply 1958-9.

Urate deposition in the iris and anterior chamber.

Coassin M, Piovanetti O, Stark WJ, Green WR.

Eye Pathology Laboratory, Wilmer Eye Institute, The Johns Hopkins Medical
Institutions, Baltimore, Maryland, USA.

OBJECTIVE: To report on a patient with clear gelatinoid deposits on the iris and 
in the anterior chamber (AC). DESIGN: Observational case report. METHODS:
Examination of AC aspirate and iris and conjunctival biopsies by light and
transmission electron microscopy. MAIN OUTCOME MEASURES: Clinical and
histopathological findings. RESULTS: Analysis of the aqueous humor and iris
ultrastructure disclosed the presence of urate deposits. CONCLUSIONS: Urate
deposition in the iris and anterior chamber rarely occurs.

Publication Types: 
    Case Reports

PMID: 16513461 [PubMed - indexed for MEDLINE]

256: Rheum Dis Clin North Am. 2006 Feb;32(1):235-44, xii.

Newer therapeutic approaches: gout.

Schumacher HR Jr, Chen LX.

Division of Rheumatology, Philadelphia Veterans Affairs Medical Center,
Philadelphia, PA 19104, USA. schumacr@mail.med.upenn.edu

Newer approaches to the treatment of gout have included modifications and further
attention to aspects of current therapies, and development of interesting new
therapies. Colchicine prophylaxis appears to be needed longer than previously
recognized after introduction of a urate-lowering agent. Diet has received
attention, though most dietary effects are small. New agents under investigation 
include pegylated formulations of uricase and a new potent xanthine oxidase
inhibitor, febuxostat. Some cardiovascular drugs have been shown to be
uricosuric.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16504833 [PubMed - indexed for MEDLINE]

257: Clin Chim Acta. 2006 Jul 15;369(1):89-94. Epub 2006 Feb 28.

Proteomic analysis of Down's syndrome patients with gout.

Chen YC, Wang PW, Pan TL, Wallace CG, Chen CJ.

Department of Rheumatology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.

BACKGROUND: In this study, the expression of hypoxanthine-guanine phosphoribosyl 
transferase (HPRT) in Down's syndrome patients with gout (DS/G) was determined,
and possible underlying mechanisms of gout were characterized using proteomic
tools. METHODS: Serum was obtained from DS/G, healthy controls and gout patients 
(without DS), recruited from the rheumatology clinic. Baseline enzyme assays were
recorded and RT-PCR used to identify HPRT gene expression. 2-D electrophoresis
and mass spectrometry were utilized to determine a plausible explanation
concerning the mechanisms leading to increased uric acid levels in DS patients.
RESULTS: Two DS patients were diagnosed with gouty arthritis. Their HPRT enzyme
activity was slightly lower than that of normal controls. HPRT expression was
also slightly decreased in DS/G patients compared with controls. Serum protein
profiles of these two DS/G patients revealed that haptoglobin alpha chain and
apolipoprotein A1 (ApoA1) were both significantly down-regulated. Protein
expression was validated by immunoblot. CONCLUSION: Our results revealed that low
levels of haptoglobin in the two DS/G patients were related to renal dysfunction 
may have affected uric acid excretion and caused gout. However, decreased ApoA1
revealed a positive correlation between defective lipid metabolism and gouty
arthritis in DS/G patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16500633 [PubMed - indexed for MEDLINE]

258: J Rheumatol. 2006 Mar;33(3):562-6. Epub 2006 Feb 15.

Medication errors with the use of allopurinol and colchicine: a retrospective
study of a national, anonymous Internet-accessible error reporting system.

Mikuls TR, Curtis JR, Allison JJ, Hicks RW, Saag KG.

Department of Medicine, University of Nebraska Medical Center, Omaha, USA.

OBJECTIVE: To more closely assess medication errors in gout care, we examined
data from a national, Internet-accessible error reporting program over a 5-year
reporting period. METHODS: We examined data from the MEDMARX database, covering
the period from January 1, 1999 through December 31, 2003. For allopurinol and
colchicine, we examined error severity, source, type, contributing factors, and
healthcare personnel involved in errors, and we detailed errors resulting in
patient harm. Causes of error and the frequency of other error characteristics
were compared for gout medications versus other musculoskeletal treatments using 
the chi-square statistic. RESULTS: Gout medication errors occurred in 39% (n =
273) of facilities participating in the MEDMARX program. Reported errors were
predominantly from the inpatient hospital setting and related to the use of
allopurinol (n = 524), followed by colchicine (n = 315), probenecid (n = 50), and
sulfinpyrazone (n = 2). Compared to errors involving other musculoskeletal
treatments, allopurinol and colchicine errors were more often ascribed to
problems with physician prescribing (7% for other therapies versus 23-39% for
allopurinol and colchicine, p < 0.0001) and less often due to problems with drug 
administration or nursing error (50% vs 23-27%, p < 0.0001). CONCLUSION: Our
results suggest that inappropriate prescribing practices are characteristic of
errors occurring with the use of allopurinol and colchicine. Physician
prescribing practices are a potential target for quality improvement
interventions in gout care.

PMID: 16482645 [PubMed - indexed for MEDLINE]

259: J Rheumatol. 2006 Feb;33(2):311-7.

Urokinase-type plasminogen activator, receptor, and inhibitor correlating with
gelatinase-B (MMP-9) contribute to inflammation in gouty arthritis of the knee.

Chu SC, Yang SF, Lue KH, Hsieh YS, Hsiao TY, Lu KH.

Institute of Biochemistry, School of Medicine, Chung Shan Medical University,
Taiwan.

OBJECTIVE: To determine the possible role of the plasminogen activator
(PA)/plasmin system in gouty arthritis. METHODS: We compared the antigenic values
of urokinase-type PA (uPA), soluble uPA receptor (suPAR), and PA inhibitor type-1
(PAI-1) and the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 in 63
synovial fluid (SF) samples from knee joints of 38 patients with gouty arthritis 
and 20 SF samples from knee joints of 20 patients with osteoarthritis (OA).
RESULTS: The increases of uPA, suPAR, and PAI-1 antigenic values in SF were
associated with increased levels of latent MMP-9 (pro-MMP-9) (p < 0.001, p <
0.001, p < 0.001, respectively) in gouty arthritis, whereas a correlation was not
observed between uPA, suPAR, and PAI-1 antigenic values and MMP-2 levels.
Increased uPA, suPAR, and PAI-1 antigenic values in gouty arthritis SF were also 
correlated to each other (p < 0.001, p < 0.001, p < 0.001). In gouty arthritis
SF, no significant relations were observed between uPA and suPAR antigenic values
and leukocyte, neutrophil, or monocyte counts, while increased values of PAI-1
corresponded closely with increased leukocyte and neutrophil counts (p = 0.005, p
= 0.004). Significantly higher values of the uPA, suPAR, and PAI-1 (p < 0.001, p 
< 0.001, p = 0.012) appeared in SF of gouty arthritis than in SF from patients
with OA. CONCLUSION: These results show a correlation of the PA/plasmin system
and MMP-9 in SF from patients with gouty arthritis, resulting in increased PA
catalytic activity and contributing to inflammation in gouty arthritis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16465663 [PubMed - indexed for MEDLINE]

260: Curr Opin Rheumatol. 2006 Mar;18(2):199-203.

New insights into gout epidemiology.

Mikuls TR, Saag KG.

University of Nebraska Medical Center and Omaha VA Medical Center, Omaha,
Nebraska, USA.

PURPOSE OF REVIEW: The systematic study of gout dates to antiquity, to
Hippocrates' initial descriptions of disease risk factors including advancing
age, female menopause, and male sex. Although urate crystal diagnosis remains the
gold standard for diagnosis it is impractical at a population level. Beyond
crystal diagnosis, progress in gout epidemiology has been hampered by the lack of
a standardized approach in defining case status. RECENT FINDINGS: Substantial
progress has been made in furthering our understanding of gout over the last few 
decades. Taken together, epidemiologic investigations suggest that gout frequency
is on the rise worldwide. Our understanding of gout risk factors continues to
expand with the recent availability of well designed prospective cohort studies
from both the USA and abroad. Moreover, recent investigations have shed important
insight on the complex relationships of hyperuricemia, gout, and comorbid
conditions, particularly the association of serum urate levels with
cardiovascular morbidity and mortality. SUMMARY: Despite our growing
understanding of the many facets of this age-old condition, current evidence
continues to underscore the frequency with which gout is characterized by
suboptimal care. Below we review our current knowledge of gout epidemiology with 
an emphasis on the association of hyperuricemia with cardiovascular comorbidity
and evidence and determinants of continued suboptimal care in gout.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 16462529 [PubMed - indexed for MEDLINE]

261: Curr Opin Rheumatol. 2006 Mar;18(2):193-8.

Recent developments in diet and gout.

Lee SJ, Terkeltaub RA, Kavanaugh A.

Center for Innovative Therapy, University of San Diego, La Jolla, California
92037, USA. s2lee@ucsd.edu

PURPOSE OF REVIEW: Gout is the most common inflammatory arthritis in men,
affecting approximately 1-2% of adult men in Western countries. United States
gout prevalence has approximately doubled over the past two decades. In recent
years, key prospective epidemiological and open-labeled dietary studies, coupled 
with recent advances in molecular biology elucidating proximal tubular urate
transport, have provided novel insights into roles of diet and alcohol in
hyperuricemia and gout. This review focuses on recent developments and their
implications for clinical practice, including how we advise patients on
appropriate diets and alcoholic beverage consumption. RECENT FINDINGS: Studies
have observed an increased risk of gout among those who consumed the highest
quintile of meat, seafood and alcohol. Although limited by confounding variables,
low-fat dairy products, ascorbic acid and wine consumption appeared to be
protective for the development of gout. SUMMARY: The most effective forms of
dietary regimen for both hyperuricemia and gout flares remains to be
unidentified. Until confirmed by a large, controlled study, it is prudent to
advise patients to consume meat, seafood and alcoholic beverages in moderation,
with special attention to food portion size and content of non-complex
carbohydrates which are essential for weight loss and improved insulin
sensitivity.

Publication Types: 
    Review

PMID: 16462528 [PubMed - indexed for MEDLINE]

262: Curr Opin Rheumatol. 2006 Mar;18(2):171-3.

Current trends in crystal identification.

Chen LX, Schumacher HR.

VA Medical Center, Rheumatology Research 151K, Philadelphia, Pennsylvania 19104, 
USA.

PURPOSE OF REVIEW: This review is an attempt to keep current in the sparse
literature addressing the still underutilized area of crystal identification.
RECENT FINDINGS: The emphasis has been on the subtleties of the microscopic
identification of common crystals and other less common potentially confusing
crystals. Imaging is noted to provide increasing help, but microscopic crystal
identification remains the gold standard. SUMMARY: Quality control is still a
concern as is the infrequency of attempted arthrocentesis for crystal
identification.

Publication Types: 
    Review

PMID: 16462524 [PubMed - indexed for MEDLINE]

263: Nature. 2006 Mar 9;440(7081):237-41. Epub 2006 Jan 11.

Gout-associated uric acid crystals activate the NALP3 inflammasome.

Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J.

Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155,
1066 Epalinges, Switzerland.

Development of the acute and chronic inflammatory responses known as gout and
pseudogout are associated with the deposition of monosodium urate (MSU) or
calcium pyrophosphate dihydrate (CPPD) crystals, respectively, in joints and
periarticular tissues. Although MSU crystals were first identified as the
aetiological agent of gout in the eighteenth century and more recently as a
'danger signal' released from dying cells, little is known about the molecular
mechanisms underlying MSU- or CPPD-induced inflammation. Here we show that MSU
and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin)
inflammasome, resulting in the production of active interleukin (IL)-1beta and
IL-18. Macrophages from mice deficient in various components of the inflammasome 
such as caspase-1, ASC and NALP3 are defective in crystal-induced IL-1beta
activation. Moreover, an impaired neutrophil influx is found in an in vivo model 
of crystal-induced peritonitis in inflammasome-deficient mice or mice deficient
in the IL-1beta receptor (IL-1R). These findings provide insight into the
molecular processes underlying the inflammatory conditions of gout and
pseudogout, and further support a pivotal role of the inflammasome in several
autoinflammatory diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16407889 [PubMed - indexed for MEDLINE]

264: Cytokine. 2006 Jan 7;33(1):21-7. Epub 2006 Jan 5.

Plasma interleukin (IL)-18 (interferon-gamma-inducing factor) and other
inflammatory cytokines in patients with gouty arthritis and monosodium urate
monohydrate crystal-induced secretion of IL-18.

Inokuchi T, Moriwaki Y, Tsutsui H, Yamamoto A, Takahashi S, Tsutsumi Z, Ka T,
Nakanishi K, Yamamoto T.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Hyogo 
College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo 663-8501, Japan.

To determine whether levels of interleukin (IL)-18, together with those of
IL-1beta, tumor necrosis factor-alpha, IL-6, and IL-8, are elevated in the plasma
of patients with gouty arthritis, the plasma concentrations of those cytokines
were measured in 31 males with gouty arthritis. Further, CD14+ cells were
obtained from human blood and thioglycolate medium-induced peritoneal cells
obtained from caspase 1-deficient mice, and then separately cultured in the
presence of monosodium urate monohydrate (MSU) crystals. In addition, in an
animal in vivo experiment, MSU crystals were injected into subcutaneous air
pouches of IL-18-deficient mice. The plasma concentrations of IL-18, IL-6, and
IL-8 were elevated in the presence of gouty arthritis in the gout patients. In
the in vitro study, the presence of MSU crystals stimulated CD14+ cells
(monocytes) to secrete IL-18 and increased the activity of caspase 1 in CD14+
cells, whereas there was no significant effect on IL-18 messenger RNA in CD14+
cells and only a slight induction of IL-18 secretion from thioglycolate
medium-induced caspase 1-deficient peritoneal cells. In the in vivo experiment,
MSU crystals injected into the air pouch promoted neutrophil accumulation along
with an increase in concentrations of keratinocyte-derived chemokine (KC) and
macrophage inflammatory protein (MIP)-1alpha in air-pouch fluids in both
IL-18-deficient and wild-type mice. However, there was no increase in the
concentration of IL-18 in air-pouch fluids in either mouse strain. Our results
suggest that plasma IL-18, IL-6, IL-8, and C-reactive protein (CRP) levels
reflect local inflammation associated with gouty arthritis, though IL-18 does not
play an important role in neutrophil accumulation. Further, they suggest that MSU
crystals accelerate the processing of IL-18 from an inactive to active form via
the activation of caspase 1.

PMID: 16406656 [PubMed - indexed for MEDLINE]

265: J Rheumatol. 2006 Jan;33(1):193-5.

Knee locking due to a single gouty tophus.

Espejo-Baena A, Coretti SM, Fernandez JM, Garcia-Herrera JM, Del Pino JR.

University Hospital Virgen de la Victoria, Malaga, Spain. espejoreina@terra.es

Knee locking is a highly incapacitating condition attributable to mechanical or
functional factors. Pain, mostly of capsuloligamentous or intraosseous origin, is
the cause of functional locking. Meniscal injuries are the most frequent
arthroscopic finding in the locked knee, due to mechanical factors. We describe a
patient experiencing locking during extension whose history and examination
suggested a tear of the anterior horn of the lateral meniscus of the right knee; 
a diagnostic/therapeutic arthroscopy revealed an intraarticular gouty tophus
growing from the anterior horn of the lateral meniscus.

Publication Types: 
    Case Reports

PMID: 16395768 [PubMed - indexed for MEDLINE]

266: Drugs. 2005;65(18):2593-611.

Gout in solid organ transplantation: a challenging clinical problem.

Stamp L, Searle M, O'Donnell J, Chapman P.

Department of Medicine, Christchurch School of Medicine and Health Sciences,
University of Otago, Christchurch, New Zealand. lisa.stamp@cdhb.govt.nz

Hyperuricaemia occurs in 5-84% and gout in 1.7-28% of recipients of solid organ
transplants. Gout may be severe and crippling, and may hinder the improved
quality of life gained through organ transplantation. Risk factors for gout in
the general population include hyperuricaemia, obesity, weight gain, hypertension
and diuretic use. In transplant recipients, therapy with ciclosporin
(cyclosporin) is an additional risk factor.Hyperuricaemia is recognised as an
independent risk factor for cardiovascular disease; however, whether
anti-hyperuricaemic therapy reduces cardiovascular events remains to be
determined.Dietary advice is important in the management of gout and patients
should be educated to partake in a low-calorie diet with moderate carbohydrate
restriction and increased proportional intake of protein and unsaturated fat.
While gout is curable, its pharmacological management in transplant recipients is
complicated by the risk of adverse effects and potentially severe interactions
between immunosuppressive and hypouricaemic drugs. NSAIDs, colchicine and
corticosteroids may be used to treat acute gouty attacks. NSAIDs have effects on 
renal haemodynamics, and must be used with caution and with close monitoring of
renal function. Colchicine myotoxicty is of particular concern in transplant
recipients with renal impairment or when used in combination with ciclosporin.
Long-term urate-lowering therapy is required to promote dissolution of uric acid 
crystals, thereby preventing recurrent attacks of gout. Allopurinol should be
used with caution because of its interaction with azathioprine, which results in 
bone marrow suppression. Substitution of mycophenylate mofetil for azathioprine
avoids this interaction. Uricosuric agents, such as probenecid, are ineffective
in patients with renal impairment. The exception is benzbromarone, which is
effective in those with a creatinine clearance >25 mL/min. Benzbromarone is
indicated in allopurinol-intolerant patients with renal failure, solid organ
transplant or tophaceous/polyarticular gout. Monitoring for hepatotoxicty is
essential for patients taking benzbromarone.Physicians should carefully consider 
therapeutic options for the management of hypertension and hyperlipidaemia, which
are common in transplant recipients. While loop and thiazide diuretics increase
serum urate, amlodipine and losartan have the same antihypertensive effect with
the additional benefit of lowering serum urate. Atorvastatin, but not
simvastatin, may lower uric acid, and while fenofibrate may reduce serum urate it
has been associated with a decline in renal function.Gout in solid organ
transplantation is an increasing and challenging clinical problem; it impacts
adversely on patients' quality of life. Recognition and, if possible, alleviation
of risk factors, prompt treatment of acute attacks and early introduction of
hypouricaemic therapy with careful monitoring are the keys to successful
management.

Publication Types: 
    Review

PMID: 16392875 [PubMed - indexed for MEDLINE]

267: J Neurosurg Spine. 2005 Dec;3(6):485-7.

A large, erosive intraspinal and paravertebral gout tophus. Case report.

Beier CP, Hartmann A, Woertgen C, Brawanski A, Rothoerl RD.

Department of Neurosurgery, University of Regensburg, Germany.
christoph.beier@gmx.de

Symptomatic gout tophi of the spine are a rare but well-characterized
complication of tophaceous gout. The authors report the case of a 29-year-old
previously healthy man who presented with L-5 radiculopathy. Lumbar magnetic
resonance (MR) imaging revealed a 4.5 x 4.5 x 2.8-cm large gout tophus mimicking 
a malignant spinal tumor or abscess. The tophus completely destroyed both L-4 and
L-5 facet joints and the left L-4 lamina and spread epidurally from L-3 to L-5,
compressing the left L-5 nerve root. There has been no similar case reported so
far with respect to the extent of bone destruction. The authors describe the case
history and present intraoperative, MR imaging, and histological findings.

Publication Types: 
    Case Reports

PMID: 16381213 [PubMed - indexed for MEDLINE]

268: Am J Ophthalmol. 2005 Dec;140(6):1152-4.

Histopathologic examination of conjunctival tophi in gouty arthritis.

Lo WR, Broocker G, Grossniklaus HE.

Department of Ophthalmology, Emory University School of Medicine, and Emory Eye
Center, 1365B Clifton Road NE, Atlanta, GA 30322, USA.

PURPOSE: To report a case of conjunctival tophi in a 59-year-old woman with gouty
arthritis. DESIGN: Observational case report. METHODS: A 59-year-old woman with a
25-year history of severe gouty arthritis presented with bilateral chalky white
conjunctival deposits. Conjunctival biopsies were obtained, and light and
electron microscopy studies were performed. RESULTS: Light microscopy confirmed
multiple gouty tophi. Transmission electron microscopy revealed intracytoplasmic 
crystalline deposits within histiocytes. Extracellular aggregates of the
crystalline deposits were enclosed by membranous material. CONCLUSIONS:
Conjunctival crystals may aid in identifying undiagnosed patients. In addition to
conjunctival tophi, patients may also have uveitis, corneal crystals, and band
keratopathy.

Publication Types: 
    Case Reports

PMID: 16376674 [PubMed - indexed for MEDLINE]

269: Curr Pharm Des. 2005;11(32):4117-24.

Overview of hyperuricaemia and gout.

Masseoud D, Rott K, Liu-Bryan R, Agudelo C.

Division of Rheumatology, Emory University School of Medicine/The Emory Clinic,
1365A Clifton Rd NE, 4th floor, Atlanta, GA 30322, USA.

In most mammals purine degradation ultimately leads to the formation of
allantoin. Humans lack the enzyme uricase, which catalyzes the conversion of uric
acid to allantoin. The resulting higher level of uric acid has been hypothesized 
to play a role as an antioxidant. Hyperuricaemia is usually an asymptomatic
condition which is hypothesized to play a role in cardiovascular disease and
hypertension. Some hyperuricaemic individuals develop gout, an inflammatory
arthritis caused by the deposition of monosodium urate crystals in joints. Over
time, acute intermittent gouty arthritis can develop into a chronic condition
with deposits of monosodium urate (MSU) crystals in joints and as tophi. The
mechanisms by which MSU crystals lead to an acute inflammatory arthritis are
under investigation and current knowledge is reviewed here. Treatment of gout
includes management of acute flares with anti-inflammatory medications such as
non-steroidal anti-inflammatory drugs or corticosteroids and long term management
with urate-lowering therapy when indicated. Future directions in the treatment of
gout, in part guided by a better understanding of pathophysiology, are discussed.

Publication Types: 
    Review

PMID: 16375732 [PubMed - indexed for MEDLINE]

270: J Korean Med Sci. 2005 Dec;20(6):1029-33.

The prevalence of metabolic syndrome in patients with gout: a multicenter study.

Rho YH, Choi SJ, Lee YH, Ji JD, Choi KM, Baik SH, Chung SH, Kim CG, Choe JY, Lee 
SW, Chung WT, Song GG.

Division of Rheumatology, Korea University Anam Hospital, Seoul, Korea.

It has been suggested that hyperuricemia and possibly gout are associated with
the metabolic syndrome, but there have been no direct studies. This study was
undertaken to obtain the prevalence of the metabolic syndrome in patients with
gout and to compare it with those from the general population studies. This was a
4-institutional case-historical control study composed of 168 patients with gout.
We assessed the prevalence of metabolic syndrome according to the ATP III
criteria and compared the prevalence with that of the historical controls. To
elucidate the factors in gout that were associated with metabolic syndrome, a
multivariate analysis was done. The age-adjusted prevalence of metabolic syndrome
in gout patients was 43.6%, which was significantly higher than that of the
Korean control population (5.2%) from the previous studies. Patients with gout
had more components of metabolic syndrome than did the controls. Body mass index 
(BMI, OR = 1.357 (95%CI 1.111-1.657)) and high density lipoprotein (HDL, OR =
0.774 (95%CI 0.705-0.850)) were the variables most significantly associated with 
the occurrence of metabolic syndrome in gout, but alcohol consumption did not
show such associations. Gout is associated with the metabolic syndrome, and
furthermore, obesity and dyslipidemia were the factors most associated with the
syndrome in these patients.

Publication Types: 
    Multicenter Study

PMID: 16361817 [PubMed - indexed for MEDLINE]

271: Br Poult Sci. 2005 Oct;46(5):641-6.

Clinicopathology of gout in growing layers induced by high calcium and high
protein diets.

Guo X, Huang K, Tang J.

Institute of Nutritional and Metabolic Disorder in Domestic Animals and Fowls,
Nanjing Agricultural University, China.

1. An experiment was conducted to test the independent and combined effects of
high dietary calcium and protein concentrations on the induction of visceral gout
in growing birds of a layer strain. 2. One hundred and sixty healthy birds were
randomly divided into 4 groups at 35 d of age. The different groups were given 4 
diets containing normal or high concentrations of dietary calcium or crude
protein in a 2 x 2 factorial experiment for 30 d. The diets contained normal
calcium (Ca) and crude protein (CP) (NCNP, 8.5 g Ca/kg and 175g CP/kg), high
calcium and normal protein (HC, 36.3 g Ca/kg and 175 g CP/kg), normal calcium and
high protein (HP, 8.8 g Ca/kg and 245 g CP/kg) or high calcium and high protein
(HCHP, 36.8 g Ca/kg and 242 g CP/kg), respectively. 3. Typical visceral gout was 
induced by the HCHP diet. The HCHP and HC diet caused severe kidney damage. The
HP diet did not cause kidney damage, but significantly increased plasma uric acid
and inorganic phosphorus concentrations. 4. The HC diet significantly increased
plasma uric acid, calcium and sodium, but significantly decreased plasma
inorganic phosphorus, potassium and magnesium concentrations. The HCHP diet
significantly increased plasma uric acid, calcium and sodium. 5. Urine volumes
were significantly higher on the HCHP and HC diets than on the control. The
growers raised on HC and HCHP diets had significantly higher total quantity of 24
h urinary excretion of uric acid, calcium, magnesium, inorganic phosphorus and
potassium and a significantly lower 24 h urinary excretion of sodium. The growers
fed on the HP diet had a higher 24 h urinary excretion of uric acid and inorganic
phosphorus than the control. 6. It is concluded that growing layer birds should
not be fed on layer rations.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16359121 [PubMed - indexed for MEDLINE]

272: J Clin Rheumatol. 2005 Oct;11(5):277-9.

Suspected gouty tophus in a woman's breast.

Van Linthoudt D, Joris F, Christen B, Pazera A, Nobel M, Magnanelli L, Malterre
L.

Département de Rhumatologie, Hôpital, La Chaux-de-Fonds, La Chaux-de-Fonds,
Switzerland. daniel.vanlinthoudt@ne.ch

A postmenopausal woman treated with diuretics for hypertension and who underwent 
surgery for a previous fibroadenoma of the left breast presented, in December
2003, with a sudden bloody discharge of the left nipple with local swelling,
redness, and pain. Radiologic investigations revealed a well-delimited tumor
under the areola. Needle aspiration disclosed many histiocytes but no bacteria.
Despite improvement with antibiotics, the tumor was removed. Pathological
examination shows features suggesting the tumor was a gouty tophus. Birefringent 
crystals were retrospectively found on the smears of the aspirated material. To
our knowledge, only 3 similar cases have been reported in the literature.

Publication Types: 
    Case Reports

PMID: 16357777 [PubMed - indexed for MEDLINE]

273: Arthritis Res Ther. 2006;8(1):R12.

Control of hyperuricemia in subjects with refractory gout, and induction of
antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous 
PEGylated urate oxidase.

Ganson NJ, Kelly SJ, Scarlett E, Sundy JS, Hershfield MS.

Division of Rheumatology, Box 3049, Duke University Medical Center, Durham, NC
27710, USA. njgan@duke.edu

PEG-modified recombinant mammalian urate oxidase (PEG-uricase) is being developed
as a treatment for patients with chronic gout who are intolerant of, or
refractory to, available therapy for controlling hyperuricemia. In an open-label 
phase I trial, single subcutaneous injections of PEG-uricase (4 to 24 mg) were
administered to 13 such subjects (11 had tophaceous gout), whose plasma uric acid
concentration (pUAc) was 11.3 +/- 2.1 mg/dl (mean +/- SD). By day seven after
injection of PEG-uricase, pUAc had declined by an average of 7.9 mg/dl and had
normalized in 11 subjects, whose mean pUAc decreased to 2.8 +/- 2.2 mg/dl. At
doses of 8, 12, and 24 mg, the mean pUAc at 21 days after injection remained no
more than 6 mg/dl. In eight subjects, plasma uricase activity was still
measurable at 21 days after injection (half-life 10.5 to 19.9 days). In the other
five subjects, plasma uricase activity could not be detected beyond ten days
after injection; this was associated with the appearance of relatively low-titer 
IgM and IgG antibodies against PEG-uricase. Unexpectedly, these antibodies were
directed against PEG itself rather than the uricase protein. Three PEG
antibody-positive subjects had injection-site reactions at 8 to 9 days after
injection. Gout flares in six subjects were the only other significant adverse
reactions, and PEG-uricase was otherwise well tolerated. A prolonged circulating 
life and the ability to normalize plasma uric acid in markedly hyperuricemic
subjects suggest that PEG-uricase could be effective in depleting expanded tissue
stores of uric acid in subjects with chronic or tophaceous gout. The development 
of anti-PEG antibodies, which may limit efficacy in some patients, is contrary to
the general assumption that PEG is non-immunogenic. PEG immunogenicity deserves
further investigation, because it has potential implications for other PEGylated 
therapeutic agents in clinical use.

Publication Types: 
    Clinical Trial, Phase I
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16356199 [PubMed - indexed for MEDLINE]

274: Transplantation. 2005 Nov 27;80(10):1383-91.

New-onset gout after kidney transplantation: incidence, risk factors and
implications.

Abbott KC, Kimmel PL, Dharnidharka V, Oglesby RJ, Agodoa LY, Caillard S.

Nephrology Service, Walter Reed Army Medical Center, Washington, DC, USA.
kevin.abbott@na.amedd.army.mil

BACKGROUND: Although cyclosporine use has been associated with an increased risk 
of new-onset gout after renal transplantation, the incidence and risk factors for
new-onset gout have not been reported in the era of modern immunosuppression.
METHODS: We conducted a retrospective cohort study of Medicare primary renal
transplant patients reported in the United States Renal Data System (USRDS),
using Medicare claims data to determine the incidence of new-onset gout. Cox
regression analysis was used to calculate adjusted hazard ratios (AHR) for
cyclosporine (including separate analysis of Neoral) compared directly with
tacrolimus, for the risk of new-onset gout, adjusted for baseline demographic
factors and posttransplant renal function. RESULTS: The cumulative incidence of
new-onset gout was 7.6% at 3 years posttransplant. The following factors were
independently associated with an increased risk of new-onset gout: use of Neoral 
(vs. tacrolimus, AHR 1.25, 95% CI 1.07-1.47) at discharge, recipient male sex
(AHR 1.44, 95% CI 1.25-1.67), older age, higher body mass index, and more recent 
year of transplant. No other immunosuppressive medications were associated with
new-onset gout. Diabetes was associated with a significantly lower risk of
new-onset gout. The development of new-onset gout was independently associated
with decreased patient survival (AHR 1.26, 95% CI 1.08-1.47) as well as
death-censored graft survival. CONCLUSIONS: Cyclosporine is an independent risk
factor for new-onset gout after transplantation. The incidence of new-onset gout 
appears to be increasing even while the use of cyclosporine is decreasing, and
the development of new-onset gout was an independent predictor for death and
graft loss in this population.

PMID: 16340779 [PubMed - indexed for MEDLINE]

275: N Engl J Med. 2005 Dec 8;353(23):2450-61.

Comment in:
    N Engl J Med. 2005 Dec 8;353(23):2505-7.    N Engl J Med. 2006 Apr 6;354(14):1532-3; author reply 1532-3.    N Engl J Med. 2006 Apr 6;354(14):1532-3; author reply 1532-3.

Febuxostat compared with allopurinol in patients with hyperuricemia and gout.

Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Eustace D, Palo WA,
Streit J, Joseph-Ridge N.

University of Chicago Pritzker School of Medicine, Chicago, USA.
mbecker@medicine.bsd.uchicago.edu

BACKGROUND: Febuxostat, a novel nonpurine selective inhibitor of xanthine
oxidase, is a potential alternative to allopurinol for patients with
hyperuricemia and gout. METHODS: We randomly assigned 762 patients with gout and 
with serum urate concentrations of at least 8.0 mg per deciliter (480 micromol
per liter) to receive either febuxostat (80 mg or 120 mg) or allopurinol (300 mg)
once daily for 52 weeks; 760 received the study drug. Prophylaxis against gout
flares with naproxen or colchicine was provided during weeks 1 through 8. The
primary end point was a serum urate concentration of less than 6.0 mg per
deciliter (360 micromol per liter) at the last three monthly measurements. The
secondary end points included reduction in the incidence of gout flares and in
tophus area. RESULTS: The primary end point was reached in 53 percent of patients
receiving 80 mg of febuxostat, 62 percent of those receiving 120 mg of
febuxostat, and 21 percent of those receiving allopurinol (P<0.001 for the
comparison of each febuxostat group with the allopurinol group). Although the
incidence of gout flares diminished with continued treatment, the overall
incidence during weeks 9 through 52 was similar in all groups: 64 percent of
patients receiving 80 mg of febuxostat, 70 percent of those receiving 120 mg of
febuxostat, and 64 percent of those receiving allopurinol (P=0.99 for 80 mg of
febuxostat vs. allopurinol; P=0.23 for 120 mg of febuxostat vs. allopurinol). The
median reduction in tophus area was 83 percent in patients receiving 80 mg of
febuxostat and 66 percent in those receiving 120 mg of febuxostat, as compared
with 50 percent in those receiving allopurinol (P=0.08 for 80 mg of febuxostat
vs. allopurinol; P=0.16 for 120 mg of febuxostat vs. allopurinol). More patients 
in the high-dose febuxostat group than in the allopurinol group (P=0.003) or the 
low-dose febuxostat group discontinued the study. Four of the 507 patients in the
two febuxostat groups (0.8 percent) and none of the 253 patients in the
allopurinol group died; all deaths were from causes that the investigators (while
still blinded to treatment) judged to be unrelated to the study drugs (P=0.31 for
the comparison between the combined febuxostat groups and the allopurinol group).
CONCLUSIONS: Febuxostat, at a daily dose of 80 mg or 120 mg, was more effective
than allopurinol at the commonly used fixed daily dose of 300 mg in lowering
serum urate. Similar reductions in gout flares and tophus area occurred in all
treatment groups. Copyright 2005 Massachusetts Medical Society.

Publication Types: 
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 16339094 [PubMed - indexed for MEDLINE]

276: J Rheumatol. 2005 Dec;32(12):2452-5.

Outcome measures for acute and chronic gout.

Schumacher HR Jr, Edwards LN, Perez-Ruiz F, Becker M, Chen LX, Furst DE,
Joseph-Ridge N, Schlesinger N, Horowitz Z, Saag K, Boice JA, Yamanaka H; OMERACT 
7 Special Interest Group.

University of Florida, Gainesville, Florida, USA. schumacr@mail.med.upenn.edu

Gout provides some unique challenges in classification and measurement of
outcomes. Our aim was to evaluate criteria for classification and to develop and 
validate optimal instruments to measure outcomes for acute and chronic gout. A
planning committee and interested attendees met to propose classification
criteria and domains for outcomes. Seven of the current American Rheumatism
Association preliminary criteria for classification were proposed as the best
current criteria for acute gouty arthritis, pending further studies. The presence
of gout is best established by crystal identification, although this technique
has limitations. Five domains for acute gout outcomes and 9 for chronic gout were
identified along with proposed instruments for testing and validation. The unique
problems of gout evaluation can and will be addressed.

Publication Types: 
    Review

PMID: 16331785 [PubMed - indexed for MEDLINE]

277: J Rheumatol. 2005 Dec;32(12):2368-72.

Tophaceous gout: quantitative evaluation by direct physical measurement.

Schumacher HR Jr, Becker MA, Palo WA, Streit J, MacDonald PA, Joseph-Ridge N.

Division of Rheumatology, University of Pennsylvania/Veterans Affairs Medical
Center, Philadelphia, Pennsylvania 19104, USA. schumacr@mail.med.upenn.edu

OBJECTIVE: The absence of accepted standardized methods for monitoring tophaceous
gout limits the ability to track tophus progression or regression. This
multicenter study assessed intra- and interrater reproducibility of a simple and 
direct physical measurement. METHODS: The quantitative evaluation was the area
(mm2) of each measurable tophus and was determined independently by 2 raters on 2
occasions within 10 days. Intra- and interrater reproducibilities were determined
by calculating mean differences and average percentage differences (APD) in
measurements of areas for the same tophus at each of 2 visits and by each rater, 
respectively. RESULTS: Fifty-two tophi were measured in 13 subjects: 22 on the
hand/wrist, 16 on the elbow, and 14 on the foot/ankle. The mean (+/- SD)
difference in tophus areas between visits was -0.2 +/- 835 mm2 (95% CI -162 to
162 mm2) and the mean (+/- SD) APD was 29% +/- 33%. The mean (+/- SD) APD between
raters was 32% +/- 27%. The largest variations in measurements were noted for
elbow tophi and variations were least for well demarcated tophi on the hands.
CONCLUSION: This simple and reproducible method can be easily utilized in
clinical trials and in practice as a measure of efficacy of urate-lowering
treatment in tophaceous gout. Among factors contributing to variability in these 
measurements were the anatomic site of tophi and rater experience with the
method. Restriction of measurements to well circumscribed hand or foot tophi
could improve reliability, but major changes, as expected with effective therapy,
can clearly be documented with this simple technique.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16331766 [PubMed - indexed for MEDLINE]

278: Curr Opin Investig Drugs. 2005 Nov;6(11):1168-78.

Febuxostat (Teijin/Ipsen/TAP).

Tomlinson B.

Division of Clinical Pharmacology, Department of Medicine & Therapeutics, The
Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New
Territories, Hong Kong, SAR China. btomlinson@cuhk.edu.hk

Febuxostat (TEI-6720; TMX-67), an oral non-purine, selective inhibitor of
xanthine oxidase (NP-SIXO), is being developed by Teijin, with licensees Ipsen
and TAP Holdings, for the potential treatment of gout. In February 2005, it was
reported that launch in Japan was expected to be delayed for several years due to
the need for additional clinical trials; in May 2005, an EU filing was expected
by the end of 2005.

PMID: 16312139 [PubMed - indexed for MEDLINE]

279: Am J Manag Care. 2005 Nov;11(15 Suppl):S459-64; quiz S465-8.

Clinical, humanistic, and economic outcomes of gout.

Brixner DI, Ho MJ.

Gout is a low prevalence disease not often considered by managed care
organizations with regard to cost management. Understanding the development of
the disease and its potential long-term, high-cost consequences can lead to
appropriate treatment strategies and cost-management opportunities that can
improve patient outcomes and potentially lower the overall cost of treatment of
patients with gout in a managed care organization. The acute and chronic nature
of the disease is best managed up front to avoid negative long-term effects.
Adherence to medications can also impact the manifestation of the disease.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16300460 [PubMed - indexed for MEDLINE]

280: Am J Manag Care. 2005 Nov;11(15 Suppl):S451-8; quiz S465-8.

Understanding treatments for gout.

Cannella AC, Mikuls TR.

Gout is one of the most readily manageable of the rheumatic diseases. This
article reviews basic pathways in purine metabolism, uric acid handling, and the 
pathogenic mechanism of clinical gout, as well as the areas in those pathways
amenable to intervention. Attention is also given to associated comorbidities,
such as hyperuricemia and obesity, hypertension, hyperinsulinemia, and coronary
artery disease. The significance of lifestyle modifications, such as weight loss 
and alcohol reduction, is discussed as an important adjunct to pharmacotherapy in
gout. Current and investigational agents used in gout management are also
reviewed. Finally, treatment recommendations for acute and chronic gout are
suggested.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16300459 [PubMed - indexed for MEDLINE]

281: Am J Manag Care. 2005 Nov;11(15 Suppl):S443-50; quiz S465-8.

Diagnosis of gout: clinical, laboratory, and radiologic findings.

Schlesinger N.

Acute gouty arthritis typically presents with a sudden and severe exquisitely
painful joint, most classically in the first metatarsophalangeal joint (toe).
Demonstrating the presence of monosodium urate (MSU) crystals in the joint fluid 
or tophus has been the gold standard for the diagnosis of gout. However, many
physicians do not perform synovial fluid analysis. In the absence of
demonstrating the presence of MSU crystals in aspirated joint fluid or tophus,
clinical, radiologic, and laboratory criteria are helpful. This article presents 
an overview of the various classification criteria, clinical presentations, and
laboratory and radiologic studies needed to make the diagnosis of gout.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16300458 [PubMed - indexed for MEDLINE]

282: Am J Manag Care. 2005 Nov;11(15 Suppl):S435-42; quiz S465-8.

Epidemiology of hyperuricemia and gout.

Luk AJ, Simkin PA.

Gout is an increasingly common medical problem. The traditional risk factors of
male sex and high red meat or alcohol consumption have been joined by a wave of
newer risk factors, such as increased longevity, the metabolic syndrome
(hypertension, diabetes, dyslipidemia, truncal obesity, increased cardiovascular 
disease risk), use of diuretics, low-dose aspirin, or cyclosporine, and end-stage
renal disease. Atypical presentations of gout in the elderly can mimic
osteoarthritis and rheumatoid arthritis. There is a resurgence of interest in
hyperuricemia as an independent and potentially modifiable cardiovascular risk
factor. The pharmacologic management of gout in general practice suffers from a
number of quality-control issues. This article reviews these and other new
epidemiologic data on this ancient disease.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16300457 [PubMed - indexed for MEDLINE]

283: Ann Rheum Dis. 2006 Aug;65(8):1080-3. Epub 2005 Nov 16.

Comment in:
    Ann Rheum Dis. 2006 Aug;65(8):981-2.

Republished in:
    Ned Tijdschr Geneeskd. 2007 Feb 24;151(8):472-7.

Gout, not induced by diuretics? A case-control study from primary care.

Janssens HJ, van de Lisdonk EH, Janssen M, van den Hoogen HJ, Verbeek AL.

Department of General Practice and Family Medicine, 229 University Medical Centre
Nijmegen, PO Box 9191, 6500 HB Nijmegen, The Netherlands. h.janssens@hag.umcn.nl

BACKGROUND: It is taken for granted that diuretics may induce gout, but there is 
a general lack of evidence on this topic. OBJECTIVES: To determine the incidence 
of gout in patients who use diuretics, taking into account concurrent
hypertension and cardiovascular diseases. METHODS: A case-control study was
designed. From a primary care population all patients with a first gout
registration (59 men, 11 women; mean (SD) age 55.1 (13.5)) were identified as
cases. To relate the occurrence of gout to diuretic use a matched reference
series of three controls for each case was compiled. Conditional logistic
regression analyses were applied to estimate incidence rate ratios (IRRs) of
gout, and 95% confidence intervals (CIs), in subjects with and without diuretic
treatment, hypertension, and cardiovascular diseases. Additional stratification
analyses were made, particularly in the subjects not using diuretics. RESULTS:
The IRRs of gout in subjects with v those without diuretic treatment,
hypertension, heart failure, and myocardial infarction were 2.8 (95% CI 1.2 to
6.6), 2.6 (95% CI 1.2 to 5.6), 20.9 (95% CI 2.5 to 173.8), and 1.9 (95% CI 0.7 to
4.7), respectively. After adjustment, the IRR of gout for diuretic use dropped to
0.6 (95% CI 0.2 to 2.0), while the IRRs of gout for hypertension, heart failure, 
and myocardial infarction were still >1. This was also the case for subjects with
hypertension or myocardial infarction, who had not used diuretics. CONCLUSION:
The results suggest that diuretics do not actually increase the risk of gout.
Cardiovascular indications for treatment may have confounded previous inferences.

PMID: 16291814 [PubMed - indexed for MEDLINE]

284: J Rheumatol. 2006 Jan;33(1):104-9. Epub 2005 Nov 1.

Frequency and predictors of inappropriate management of recurrent gout attacks in
a longitudinal study.

Neogi T, Hunter DJ, Chaisson CE, Allensworth-Davies D, Zhang Y.

Clinical Epidemiology Research and Training Unit, Boston University School of
Medicine, Boston, Massachusetts 02118, USA. tneogi@bu.edu

OBJECTIVE: To evaluate the patterns and determinants of medication use during
recurrent gout attacks. METHODS: We followed participants with documented gout in
an online prospective case-crossover study. During an attack, subjects were asked
if they had consulted a physician for the attack and what medications they were
using. Definitely inappropriate therapy was defined as use of allopurinol or a
uricosuric agent acutely without having used it as a prophylactic. Potentially
inappropriate therapy was defined as use of analgesics alone, alternative
remedies, or no medications. We estimated the risk of having >or= 1 attack in 1
year using life table methods. We examined the relation of various risk factors
to the risk of inappropriate therapy using Poisson regression. RESULTS: Among 232
participants (mean age 52 yrs, 81% male) with documented gout, the risk of having
>or= 1 attack in a year was 69%. One hundred ten participants consulted a
physician for each attack, 49 did so for only some attacks, while 43 never
consulted a physician for any attack. Fifty-three participants had definitely (n 
= 10) or potentially (n = 43) inappropriate therapy for their recurrent attacks. 
Physician consultation for an attack was associated with increased risk of
inappropriate therapy (risk ratio, RR, 2.5, p = 0.006), whereas an increasing
number of gout attacks was associated with lower risk of inappropriate therapy
(RR 0.8, p = 0.01). CONCLUSION: Given the high risk of recurrent attacks and the 
substantial number of persons whose attacks are not appropriately managed,
further education about management of gout attacks for both patients and
physicians may be warranted.

Publication Types: 
    Clinical Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16267879 [PubMed - indexed for MEDLINE]

285: J Rheumatol. 2005 Nov;32(11):2189-91.

Prevalence and risk factors for urolithiasis in primary gout: is a reappraisal
needed?

Alvarez-Nemegyei J, Medina-Escobedo M, Villanueva-Jorge S, Vazquez-Mellado J.

Unidad de Investigación en Epidemiología Clínica, HE CMN Ignacio García Tellez,
Instituto Mexicano del Seguro Social, Mérida, Yucatán, México.
nemegyei@hotmail.com

OBJECTIVE: To assess the prevalence and risk factors for urolithiasis in primary 
gout. METHODS: One hundred forty patients with primary gout were studied.
Urolithiasis was defined as a history of urolithiasis, or nephrolithiasis
detected via ultrasonography in patients with no previous record of urolithiasis.
Patient age, duration of gout, presence of tophi, obesity, alcoholism, high blood
pressure, diabetes, hyperlipidemia, family history of urolithiasis, daily urine
output, uricemia, urine pH, FeNa, FeUrate, urine pH/FeUrate index, and daily
urine excretion of urate, sodium, calcium and potassium were compared between
lithiasic and non-lithiasic subjects. RESULTS: Fifty-five (39%; 95% CI 31-47)
patients had urolithiasis, of which 37 (26%) were diagnosed by clinical history
and 18 (13%) by ultrasonography. Patients with a silent kidney stone diagnosed by
ultrasound tended to have shorter evolution of gout. Aside from urinary H+ ion
concentration (lithiasic subjects 5.17 +/- 3.9 microM/l; non-lithiasic subjects
3.80 +/- 3.01 microM/l; p = 0.02), no difference was found between lithiasic and 
non-lithiasic subjects for the other variables studied. CONCLUSION:
Ultrasonography increased the probability of diagnosing urolithiasis by 50%,
meaning the prevalence of urolithiasis in gout is likely higher than previously
reported. A higher urinary H+ ion concentration was the only variable associated 
with urolithiasis. Due to advances in diagnosis of gout and urolithiasis, as well
as biochemical assays, the prevalence and risk factors for urolithiasis in gout
require reassessment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16265701 [PubMed - indexed for MEDLINE]

286: J Rheumatol. 2005 Nov;32(11):2186-8.

Female gout: clinical and laboratory features.

De Souza AW, Fernandes V, Ferrari AJ.

Rheumatology Division, Universidade Federal de São Paulo, São Paulo-SP, Brazil.

OBJECTIVE: To evaluate and compare clinical and laboratory features of gout in
men and women. METHODS: Twenty-seven women and 31 men with gout underwent
clinical and laboratory evaluation and review of medical records. RESULTS:
Disease onset in women was a mean of 7 years later than in men. There were no
differences between women and men regarding systemic hypertension, diabetes
mellitus, hyperlipidemia, chronic renal failure, renal stones, ischemic heart
disease, or heavy alcohol consumption. Tophaceous gout was similar in both
groups, although female gender seemed to be protective against risk of developing
tophi (odds ratio: 0.449; 95% confidence interval: 0.151-1.330). Podagra was more
common in men, and women showed a higher frequency of upper limb joint
involvement. Most patients had low urate excretion rates. Achieving disease
control was similar in women and men. Of the 8 women who were premenopausal at
disease onset, 7 had secondary causes for gout; 5 of the 8 had high serum urate
despite treatment. CONCLUSION: Gout in women had a later onset and higher
frequency of upper limb joint involvement in comparison to men. Those with
premenopausal onset tended to be refractory to standard therapy.

Publication Types: 
    Comparative Study

PMID: 16265700 [PubMed - indexed for MEDLINE]

287: Expert Opin Pharmacother. 2005 Nov;6(14):2443-53.

An update on the treatment options for gout and calcium pyrophosphate deposition.

Choy G.

Division of Rheumatology, University of Toronto, Sunnybrook and Women's College
Health Science Centre, M1-401, Toronto, ON, M4N 3M5, Canada.

Gout and calcium pyrophosphate deposition disease are two common causes of
inflammatory joint disease. Despite differences underlying their pathogenesis,
their clinical presentation and treatment share some common features. Optimal
treatment for both requires prompt resolution of acute synovitis, reduction of
chronic joint damage and management of associated conditions. Available
therapeutic interventions and future strategies are reviewed in this article.

Publication Types: 
    Review

PMID: 16259576 [PubMed - indexed for MEDLINE]

288: Isr Med Assoc J. 2005 Oct;7(10):656-60.

Allopurinol-induced DRESS syndrome.

Markel A.

Department of Internal Medicine A, HaEmek Medical Center, Afula, Israel.
markel_ar@clalit.org.il

Hyperuricemia is present in approximately 5% of the population, the vast majority
of whom are asymptomatic and at no clinical risk. Complications, including renal 
calculi, uric acid nephropathy and gout, occur in a small proportion of patients.
Allopurinol, an analog of hypoxanthine, has been widely used in clinical practice
for over 30 years for the treatment of hyperuricemia and gout. Two percent of
patients taking this medication develop a mild exanthema. A syndrome
characterized by exfoliative dermatitis, hepatitis, interstitial nephritis and
eosinophilia has been described previously. Termed allopurinol hypersensitivity
syndrome, its etiology is related to the accumulation of one of the allopurinol
metabolites, oxypurinol; clearance of oxypurinol is decreased in the setting of
renal insufficiency and the use of thiazide diuretics. The term DRESS syndrome
(Drug Rash with Eosinophilia and Systemic Symptoms) was recently introduced to
describe a disorder associated with various drugs or viral infections and
characterized by similar features. The pathophysiology of allopurinol-induced
hypersensitivity, clinical presentation and treatment are reviewed.

Publication Types: 
    Review

PMID: 16259349 [PubMed - indexed for MEDLINE]

289: Clin Rheumatol. 2006 Sep;25(5):749-52. Epub 2005 Oct 25.

Rasburicase treatment in severe tophaceous gout: a novel therapeutic option.

Moolenburgh JD, Reinders MK, Jansen TL.

Department of Rheumatology, Medical Centre Alkmaar, Wilhelminalaan 12, 1815JD
Alkmaar, The Netherlands. d.moolenburgh@mca.nl

We recently encountered a destructive case of tophaceous gout in a 57-year-old
patient. Despite perfect therapy compliance, the patient failed in the
conventional urate-lowering treatment, accounting for the ongoing urate retention
and accumulation with progressive tophaceous bulky disease. Application of an
experimental scheme of uricolytical therapy on this patient was able to reduce
bulky disease significantly. In modern medicine, potent urate-debulking
medication with urate oxidase (uricase) derivatives is at our disposal, and it is
a challenge for rheumatologists to install the right strategy including
innovative approaches with potent uricolytic therapy on the right patient at the 
right time.

Publication Types: 
    Case Reports

PMID: 16247589 [PubMed - indexed for MEDLINE]

290: J Hand Surg [Br]. 2006 Feb;31(1):101-3. Epub 2005 Oct 21.

Management of tophaceous gout of the distal interphalangeal joint.

Mudgal CS.

Orthopaedic Hand Service, Massachusetts General Hospital, Yawkey Center, Suite
2100, 55 Fruit Street, Boston, MA 02114, USA. cmudgal@partners.org

Surgical management of acute tophaceous gout of the distal interphalangeal joint 
is often associated with delayed wound healing. Aspiration through neighbouring
uninvolved skin is a safe method of treating these tophi. For persistently
symptomatic, unstable DIP joints, arthrodesis should be considered.

PMID: 16243417 [PubMed - indexed for MEDLINE]

291: Clin Orthop Relat Res. 2005 Nov;440:38-44.

The Mark Coventry Award: white blood cell gene expression: a new approach toward 
the study and diagnosis of infection.

Deirmengian C, Lonner JH, Booth RE Jr.

3B Orthopaedics, Pennsylvania Hospital, University of Pennsylvania Health System,
Philadelphia, PA 19107, USA. deirmenc@gmail.com

We introduce a new genomic approach toward the study and diagnosis of infection. 
Our purpose is to show that synovial fluid white blood cells express a gene
expression "signature" that differentiates septic from aseptic inflammation.
Synovial fluid was aspirated from patients with acute Staphylococcus aureus
infections or acute gout of the knee. Differential cell counts included
predominantly neutrophils in all aspirates. Ribonucleic acid was isolated from
the synovial-fluid white blood cells and was analyzed on the Affymetrix U133A
GeneChip. The neutrophils from a patient whose knee is infected with
Staphylococcus aureus can be distinguished from the neutrophils found in gout by 
nature of their differential gene expression. There are 1615 genes that have an
expression level that is significantly different between the groups. The 124 most
significant differences are in genes from immune pathways including the
interleukin pathway, the tumor necrosis factor pathway, and the antibacterial
response. The neutrophils at a site of infection (Staphylococcus aureus) express 
different genes than the neutrophils at a site of aseptic inflammation (gout). To
our knowledge, this is the first in vivo demonstration of this principle. The
differences in neutrophil gene expression may be used to develop simple
laboratory tests that distinguish the causes of inflammation in a total joint
arthroplasty. LEVEL OF EVIDENCE: Diagnostic study, Level II-1. See the Guidelines
for Authors for a complete description of levels of evidence.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16239781 [PubMed - indexed for MEDLINE]

292: J Rheumatol. 2005 Oct;32(10):2006-8.

Synovial sarcoma of the foot mimicking acute gouty arthritis.

Du Y, Pullman-Mooar S, Schumacher HR.

Division of Rheumatology, Department of Medicine, University of Pennsylvania
School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104, USA.

Synovial sarcoma is a slow-growing soft tissue sarcoma that mainly affects young 
adults. Patients commonly present with a slowly enlarging mass in the
paraarticular regions of extremities. We describe a case of synovial sarcoma with
an unusually acute presentation near the first metatarsophalangeal joint that
resembled acute gouty arthritis.

Publication Types: 
    Case Reports

PMID: 16206359 [PubMed - indexed for MEDLINE]

293: J Rheumatol. 2005 Oct;32(10):1923-7.

Factors associated with musculoskeletal disability and chronic renal failure in
clinically diagnosed primary gout.

Alvarez-Nemegyei J, Cen-Pisté JC, Medina-Escobedo M, Villanueva-Jorge S.

Instituto Mexicano del Seguro Social, Calle 57 # 503 x 50 y 62, Col. Centro,
97000 Mérida, Yucatán, México. nemegyei@hotmail.com

OBJECTIVE:. To assess the association between a set of sociodemographic,
clinical, and biochemical variables and the presence of musculoskeletal (MSK)
disability and chronic renal failure in patients with primary gout defined using 
Wallace criteria. METHODS: Subjects were 90 patients with primary gout (98% male,
age 54 +/- 12 years, 11.3 +/- 9.8 years with gout). A cohort nested case-control 
design was used. Analysis was done of the association between MSK disability or
renal failure and a series of variables: age; duration of gout; body mass index; 
education level; income; serum glucose, cholesterol, triglycerides, and uric
acid; Health Assessment Questionnaire score; obesity; family history of gout;
high blood pressure; alcoholism; smoking habit; presence of tophi; ischemic
cardiopathy; and use of colchicine, glucocorticoids, nonsteroidal
antiinflammatory drug, or allopurinol. RESULTS: Forty-two patients (47%) had MSK 
disability, and 25/80 (31%) had renal failure. On logistic regression, presence
of tophi (relative risk 4.3, 95% confidence interval 1.2-15.1),
hypertriglyceridemia (RR 3.4, 95% CI 1.1-10), and history of ischemic heart
disease (RR 8.3, 95% CI 1.6-41) were associated with MSK disability. Patient age 
was the only variable associated with renal failure. CONCLUSION: Optimal medical 
control of gout and its comorbidities may improve prognosis of gout, as suggested
by our findings, in which a marker for poorly controlled gout such as presence of
tophi in addition to high blood triglyceride levels and ischemic heart disease
were associated with MSK disability. Older age was the only factor associated
with renal failure, although this may only reflect declining renal function in
the elderly.

PMID: 16206348 [PubMed - indexed for MEDLINE]

294: Int J Exp Pathol. 2005 Oct;86(5):297-307.

Evaluation of human knee meniscus biopsies with near-infrared, reflectance
confocal microscopy. A pilot study.

Campo-Ruiz V, Patel D, Anderson RR, Delgado-Baeza E, González S.

Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Harvard
University, Boston, MA 02114, USA.

Knee cartilage biopsy is used to confirm the pathology in both clinical and
experimental conditions and often guides diagnosis and therapeutic strategies.
Current histopathological techniques are time consuming, induce tissue artefacts 
and often prevent further evaluation, once the tissue has been fixed. Hence,
there is a potential need for a fast and nondestructive imaging technique for
unfixed tissue. Near-infrared, reflectance confocal microscopy (CM) allows
real-time, virtual sectioning of unstained, bulk tissue samples. This pilot study
evaluates the use of CM in the assessment of meniscus histopathology in a series 
of 26 freshly-excised human meniscus samples compared to standard light
microscopy of stained sections. CM images of the meniscus show cell and matrix
detail, depicting morphologic features of collagen and elastic fibres, vessels
and nerve endings. In addition, crystal deposits of gout and pseudogout are also 
demonstrable. Thus, CM is a novel imaging technique that could enable the
pathologist to make a rapid microscopic evaluation of cartilage in a fresh and
unfixed fashion.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16191102 [PubMed - indexed for MEDLINE]

295: Asia Pac J Clin Nutr. 2005;14(3):285-92.

High prevalence of hyperuricemia in elderly Taiwanese.

Lee MS, Lin SC, Chang HY, Lyu LC, Tsai KS, Pan WH.

School of Public Health, National Defense Medical Center, and Department of
Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
mmsl@ndmctsgh.edu.tw

Serum urate status, the prevalence of hyperuricemia and their relationship to the
metabolic syndrome in elderly Taiwanese were described using data from the
Elderly Nutrition and Health Survey in Taiwan (1999-2000), in which a stratified 
multi-stage clustered sampling scheme was applied. Complete data from biochemical
assays and anthropometric measures for 1225 males and 1167 females were included 
in the analysis. The mean urate level and 95% confidence interval was 411 (398,
424) microM for males and 357 (347, 367) microM for females. Males had
significantly higher serum urate levels than females across all age groups
(P<0.05). No significant difference in mean serum urate was found among the four 
age groups of males. On the other hand, females of 75-79 years had significantly 
higher serum urate levels (376 microM) than that of the 65-69 and>or=80 age
groups. The overall prevalence of hyperuricemia (>or=416.7 microM (7.0 mg/dL) in 
the elderly was 36% (46% for males and 26% for females). Among the participants, 
4.2% of males and 1.1% of females were taking medication to lower uric acid. The 
elderly (males 455 microM; females 416 microM) of the Mountain areas, mainly
indigenes, had the highest mean serum urate overall, however, the highest
prevalence of hyperuricemia in males was found in the PengHu islands (62%) and
that for females in the Mountain areas (51%). The odds ratio (OR) for
hyperuricemia was 2.84 for males in the PengHu islands and 4.33 for females in
Mountain areas, compared with their counterparts in the third stratum in the
northern areas. Adjusting for obesity, alcohol and other related covariates did
not alter the relative rank of the ORs in the various strata. Elderly males (22%)
had a significantly lower rate of metabolic syndrome (MS) than females (39%)
(P<0.05). For both genders, those with MS had a significantly higher mean serum
urate (males 436 microM vs. 405 microM; females 389 microM vs. 338 microM) and
prevalence of hyperuricemia (males 56% vs. 43%; females 38% vs.19%) (P<0.05). The
population attributable risk for MS from hyperuricemia was 18.8% in men and 15.5%
in women. In conclusion, the mean serum urate and prevalence of hyperuricemia in 
the elderly in Taiwan were higher than those found in other populations and was
significantly associated with MS. Gene-environmental interaction may play a key
role since great geographical variation exists within various Han Chinese groups 
in Taiwan and between Han Chinese and Taiwanese indigenes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16169841 [PubMed - indexed for MEDLINE]

296: Cutis. 2005 Jul;76(1):54-6.

Gouty panniculitis: a case report and review of the literature.

Snider AA, Barsky S.

John H Stroger, Jr, Hospital of Cook County, Chicago, Illinois, USA.
skindoc2b@yahoo.com

Gouty panniculitis, with deposits of urate crystals in the subcutaneous tissue,
is a rare dermatologic sequela of gout. We report a case of a 37-year-old
Hispanic man who presented with ulcerating nodules on the posterolateral aspect
of his legs. An elevated serum uric acid level along with the findings of the
histopathologic examination supported a diagnosis of gouty panniculitis. The
clinical features, histology, and therapy of this rare manifestation of gout are 
reviewed.

Publication Types: 
    Case Reports
    Review

PMID: 16144290 [PubMed - indexed for MEDLINE]

297: Postgrad Med J. 2005 Sep;81(959):572-9.

Diagnosis and management of gout: a rational approach.

Suresh E.

Rheumatology Department, Kettering General Hospital, Rothwell Road, Kettering
NN16 8UZ, UK. dr_esuresh@hotmail.com

Gout is one of the best understood among the rheumatological disorders and one of
the most satisfying to treat. Even non-specialists should be able to diagnose and
treat most patients provided some important principles are appreciated.
Management of a minority of patients, including those with renal impairment is
difficult and often unsatisfactory, because of restricted treatment options. In
this paper, the basic principles underlying the diagnosis and management of gout 
are discussed first, followed by practical approaches.

Publication Types: 
    Review

PMID: 16143687 [PubMed - indexed for MEDLINE]

298: J Rheumatol. 2005 Sep;32(9):1762-4.

Prophylactic effect of highly selective COX-2 inhibition in acute monosodium
urate crystal induced inflammation in the rat subcutaneous air pouch.

Nalbant S, Chen LX, Sieck MS, Clayburne G, Schumacher HR.

University of Pennsylvania School of Medicine and the Arthritis Center, VA
Medical Center, Philadelphia, Pennsylvania 19104-4283, USA.

OBJECTIVE: To examine the ability of rofecoxib prophylaxis to blunt the effect of
monosodium urate (MSU) crystal inflammation induced in the rat subcutaneous air
pouch. METHODS: Eight rats were used in each of 4 groups. On day one, air was
injected subcutaneously to create the pouches and gavage feedings were started
with placebo or 2 different doses of rofecoxib. Six days later MSU crystals or
saline were injected into the pouches. Twenty-four hours later, rats were
examined, sacrificed, and pouch fluid studied. RESULTS: Rofecoxib 15 or 30 mg/kg 
given for 6 days before MSU crystal injection into rat air pouches significantly 
suppressed the inflammation following injection of 10 mg crystals (p = 0.001) and
tended to suppress the milder inflammation induced by 5 mg MSU. Greater effects
on phagocytosis were seen with 30 mg/kg rofecoxib. Tumor necrosis factor-alpha
levels in pouch fluid measured by ELISA were not suppressed by the rofecoxib.
CONCLUSION: Prophylactic use of this cyclooxygenase 2 (COX-2) selective inhibitor
in this pilot study suppressed acute MSU crystal induced inflammation. Effects on
cytokines need further investigation. COX-2 inhibitors deserve consideration for 
prophylactic use in interim gout.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16142876 [PubMed - indexed for MEDLINE]

299: Arthritis Rheum. 2005 Sep;52(9):2936-46.

Innate immunity conferred by Toll-like receptors 2 and 4 and myeloid
differentiation factor 88 expression is pivotal to monosodium urate monohydrate
crystal-induced inflammation.

Liu-Bryan R, Scott P, Sydlaske A, Rose DM, Terkeltaub R.

VA Medical Center, University of California, San Diego 92161, USA.
rliu@vapop.ucsd.edu

OBJECTIVE: In gout, incompletely defined molecular factors alter recognition of
dormant articular and bursal monosodium urate monohydrate (MSU) crystal deposits,
thereby inducing self-limiting bouts of characteristically severe neutrophilic
inflammation. To define primary determinants of cellular recognition, uptake, and
inflammatory responses to MSU crystals, we conducted a study to test the role of 
Toll-like receptor 2 (TLR-2), TLR-4, and the cytosolic TLR adapter protein
myeloid differentiation factor 88 (MyD88), which are centrally involved in innate
immune recognition of microbial pathogens. METHODS: We isolated bone
marrow-derived macrophages (BMDMs) in TLR-2-/-, TLR-4-/-, MyD88-/-, and congenic 
wild-type mice, and assessed phagocytosis and cytokine expression in response to 
endotoxin-free MSU crystals under serum-free conditions. MSU crystals also were
injected into mouse synovium-like subcutaneous air pouches. RESULTS: TLR-2-/-,
TLR-4-/-, and MyD88-/- BMDMs demonstrated impaired uptake of MSU crystals in
vitro. MSU crystal-induced production of interleukin-1beta (IL-1beta), tumor
necrosis factor alpha, keratinocyte-derived cytokine/growth-related oncogene
alpha, and transforming growth factor beta1 also were significantly suppressed in
TLR-2-/- and TLR-4-/- BMDMs and were blunted in MyD88-/- BMDMs in vitro.
Neutrophil influx and local induction of IL-1beta in subcutaneous air pouches
were suppressed 6 hours after injection of MSU crystals in TLR-2-/- and TLR-4-/- 
mice and were attenuated in MyD88-/- mice. CONCLUSION: The murine host requires
TLR-2, TLR-4, and MyD88 for macrophage activation and development of full-blown
neutrophilic, air pouch inflammation in response to MSU crystals. Our findings
implicate innate immune cellular recognition of naked MSU crystals by specific
TLRs as a major factor in determining the inflammatory potential of MSU crystal
deposits and the course of gouty arthritis.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16142712 [PubMed - indexed for MEDLINE]

300: Am J Ophthalmol. 2005 Sep;140(3):542-4.

Medial canthal tophus associated with gout.

Chu YC, Hsieh YY, Ma L.

Department of Ophthalmology, Chang Gung Memorial Hospital, No. 5 Fu-Hsin Street, 
Kwei-Shan Shiang, Taoyuan, Taiwan.

PURPOSE: To report a case with a gouty tophus at the medial canthus. DESIGN:
Observational case report. METHODS: Review of the clinical, laboratory,
photographic, and pathologic records of a patient with a gouty tophus at the
medial canthus. RESULTS: A 27-year-old man had a 3-year history of gouty
arthritis and poorly controlled hyperuricemia. A medial canthal mass without
discomfort developed gradually over 3 months. An excisional biopsy was performed,
and the tissue was fixed in formalin for pathology. Analysis of a routine
hematoxylin-and-eosin-stained section disclosed a multilobulated pseudocyst
filled with amorphous eosinophilic material. Further staining with nonaqueous
alcoholic eosin and viewed under a polarizing microscope indicated the presence
of birefringent urate crystals. CONCLUSIONS: Gouty tophus can develop
progressively at the medial canthus, especially in people with uncontrolled
hyperuricemia. A formalin-fixed specimen, stained with nonaqueous alcoholic
eosin, demonstrates abundant birefringent urate crystals under a polarizing
microscope.

Publication Types: 
    Case Reports

PMID: 16139012 [PubMed - indexed for MEDLINE]

301: Clin Med. 2005 Jul-Aug;5(4):396-9.

Three clinical problems: weird thyroid function tests, difficult gout, and
dementia.

Fry A, Vanderpump M, Doherty M, Kennedy A, Firth J.

Department of Renal Medicine, Addenbrooke's Hospital, Cambridge.
andyfry@doctors.org.uk

Speakers at the course were given vignettes describing one or more clinical
scenarios on which to base their talks, selected because they represent common
but challenging problems likely to be encountered by any physician practising in 
general internal medicine. Three of the subjects covered--weird thyroid function 
tests, difficult gout, and dementia--are presented here.

Publication Types: 
    Case Reports

PMID: 16138497 [PubMed - indexed for MEDLINE]

302: J Orthop Surg (Hong Kong). 2005 Aug;13(2):203-6.

Tophaceous gout causing atlanto-axial subluxation mimicking rheumatoid arthritis:
a case report.

Wazir NN, Moorthy V, Amalourde A, Lim HH.

Department of Orthopaedic surgery, University Malaya Medical Centre, Kuala
Lumpur, Malaysia. naveed@imu.edu.my

This is a case report of an extremely rare condition of atlanto-axial subluxation
secondary to gouty arthritis, which mimicked rheumatoid arthritis at
presentation. Gouty arthritis involving the spine is a rare condition. We
highlight a case of gouty arthritis involving the atlanto-axial joint resulting
in joint instability, subluxation, and neurological deficit. A 66-year-old obese 
woman who had a polyarticular disease for the previous 3 years presented with
neck pain and progressive neurology. A 2-stage procedure was performed: posterior
decompression and occipitocervical fusion followed by further anterior trans-oral
decompression. However, after an initial neurological improvement, she succumbed 
to aspirational pneumonia and septicaemia. Atlanto-axial subluxation caused by
gouty arthritis can present in the same way as rheumatoid arthritis. Therefore,
the possibility of this as a differential diagnosis should be kept in mind.

Publication Types: 
    Case Reports

PMID: 16131689 [PubMed - indexed for MEDLINE]

303: J Orthop Surg (Hong Kong). 2005 Aug;13(2):199-202.

Tophaceous gout in the bipartite patella with intra-osseous and intra-articular
lesions: a case report.

Kobayashi K, Deie M, Okuhara A, Adachi N, Yasumoto M, Ochi M.

Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences,
Hiroshima University, Hiroshima city, Hiroshima, Japan.

We report a case of a 34-year-old man who had an acute gouty attack with tophi
around the accessory bone of the bipartite patella with intra-osseous lesions. As
the symptoms did not respond to conservative treatments, the patient was treated 
surgically. Arthroscopy revealed urate crystals surrounded by inflammatory
synovitis on the surface of the bipartite patella. Arthrotomy exposed the
abundant crystals around the accessory bone and in the intra-osseous lesion.
These findings made us speculate that some pre-existing inflammatory conditions
around the accessory bone induced deposition of urate crystals, and the
destruction of the barrier between the deposits and the joint led to an acute
arthritis. Curettage of the tophi resulted in immediate improvement of knee
function. There had been no recurrence of symptoms at the 2-year follow-up.

Publication Types: 
    Case Reports

PMID: 16131688 [PubMed - indexed for MEDLINE]

304: Intern Med. 2005 Jul;44(7):706-9.

Frequency of gouty arthritis in patients with end-stage renal disease in Japan.

Ohno I, Ichida K, Okabe H, Hikita M, Uetake D, Kimura H, Saikawa H, Hosoya T.

Division of Kidney and Hypertension, Department of Internal Medicine, Jikei
University School of Medicine, Tokyo.

OBJECTIVE: The purpose of this study was to investigate gouty arthritis in
Japanese patients with end-stage renal disease (ESRD). METHODS: Questionnaires
plus patient interviews and reviews of medical records were used to investigate
gouty arthritis in 493 Japanese patients with ESRD receiving maintenance
dialysis. RESULTS: The frequency of gouty arthritis was 4.1% for female patients 
and 15.4% for male patients greater than 2 years before the start of dialysis,
and 0.6% for female patients and 7.7% for male patients less than 2 years before 
the start of dialysis. After the start of dialysis the frequency was 3.4% for the
first 2 years and 1.2% thereafter in male patients, but no gouty arthritis
appeared in female patients. Although the annual number of gouty attacks was
2.0+/-4.2 greater than 2 years before the start of dialysis, and 1.9+/-6.6 less
than 2 years before the start of dialysis, the annual number of attacks decreased
significantly after the start of dialysis to 0.2+/-0.7 in the first 2 years and
0.1+/-0.6 thereafter. CONCLUSIONS: The frequency of gouty arthritis in Japanese
patients with ESRD is similar to that of patients with hyperuricemia in the
general population and it is decreased slightly before dialysis; however, the
frequency decreases markedly after dialysis.

PMID: 16093591 [PubMed - indexed for MEDLINE]

305: Skeletal Radiol. 2005 Dec;34(12):803-6. Epub 2005 Jul 19.

Tophaceous gout in the cervical spine.

Cabot J, Mosel L, Kong A, Hayward M.

Department of Orthopaedic Surgery, Royal Adelaide Hospital, Adelaide, South
Australia, Australia, 5000.

Gout is a common metabolic disorder typically affecting the distal joints of the 
appendicular skeleton. Involvement of the axial skeleton, particularly the facet 
joints and posterior column of the cervical spine, is rare. This case report
highlights such a presentation in a 76-year old female who presented with
cervical spine pain following a fall. Her radiological findings were suggestive
of a destructive metastatic process. Histological diagnosis confirmed tophaceous 
gout.

Publication Types: 
    Case Reports

PMID: 16028084 [PubMed - indexed for MEDLINE]

306: Geriatrics. 2005 Jul;60(7):24-31.

Gouty arthritis. A primer on late-onset gout.

Ene-Stroescu D, Gorbien MJ.

Internal Medicine Northwest, Tacoma, Washington, USA.

Gouty arthritis, a common source of pain and disability, is the most common form 
of inflammatory arthritis affecting older people. The authors review the
epidemiology and pathogenesis of hyperuricemia and gout, as well as the clinical 
forms of gouty arthritis. Gout is part of a clinical spectrum of conditions
(obesity, diabetes mellitus, hyperlipidemia, coronary artery disease) and need
for better patient education on management of these associated conditions is
emphasized. The general algorithm of gout management is presented. Clinical
particularities of gout presentation in older patients (increased incidence in
women, polyarticular onset with hand involvement, earlier development of tophi,
association with use of diuretics) are reviewed. Barriers against an optimal
control of gout include lack of patient education, presence of comorbid
conditions, particularly renal impairment, use of multiple drugs such as
diuretics, and cognitive decline. Gout management in older adults remains
unsatisfactory.

Publication Types: 
    Review

PMID: 16026179 [PubMed - indexed for MEDLINE]

307: Clin Chim Acta. 2005 Dec;362(1-2):170-5. Epub 2005 Jul 14.

Formation of 8-nitroguanine in blood of patients with inflammatory gouty
arthritis.

Chang HR, Lai CC, Lian JD, Lin CC, Wang CJ.

Division of Nephrology, Department of Internal Medicine, Chung-Shan Medical
University Hospital, Taichung, Taiwan.

BACKGROUND: NOx causes DNA damage due to an inflammatory effect of gouty
arthritis. We investigated the concentration of 8-nitroguanine (8-NO(2)-G) in the
blood of patients with arthritis. METHODS: Subjects were divided into 3 groups:
(1) high inflammatory (HI) group (n = 21) with hyperuricemia (mean, 8.9 mg/dl)
and leukocytosis, (2) low inflammatory (LI) group (n = 14) with mild
hyperuricemia (mean, 7.6 mg/dl) but normal leukocyte count, (3) non-inflammatory 
(NI) healthy control (n = 19) with mean serum uric acid concentration 5.3 mg/dl
and normal leukocyte count. Serum C-reactive protein (CRP) concentrations were
measured by a visual agglutination method. The blood concentrations of 8-NO(2)-G 
were determined by high performance liquid chromatography-electrochemical
detection and were compared between groups. RESULTS: There was significant
difference in percentage of positive CRP (NI: 55.6%, LI: 64.3%, HI: 100%, p =
0.003) between the 3 groups. The leukocyte count (mean +/- S.E., NI: 7400 +/-
528, LI: 7686 +/- 433, HI: 10952 +/- 691/mm(3), p < 0.001), uric acid (NI: 5.3
+/- 0.24, LI: 7.6 +/- 0.4, HI: 8.9 +/- 0.36 mg/dl, p < 0.001), NO(2) (NI: 6.5 +/-
1.2, LI: 11.1 +/- 2.9, HI: 35.6 +/- 5.1 microg/ml, p < 0.001) and the 8-NO(2)-G
(NI: 0.08 +/- 0.03; LI: 0.34 +/- 0.13; HI: 0.59 +/- 0.09 ng/microg DNA, p =
0.002) were significantly increased by inflammation. CONCLUSION: Gouty
inflammation induces DNA damage by increasing 8-NO(2)-G through endogenous NO and
ROS formation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16023632 [PubMed - indexed for MEDLINE]

308: Expert Opin Investig Drugs. 2005 Jul;14(7):893-903.

Febuxostat: a non-purine, selective inhibitor of xanthine oxidase for the
management of hyperuricaemia in patients with gout.

Schumacher HR Jr.

University of Pennsylvania, VA Medical Center, Philadelphia, Pennsylvania, USA.
schumacr@mail.med.upenn.edu

Febuxostat is a non-purine, selective inhibitor of xanthine oxidase being
developed for the management of hyperuricaemia in patients with gout. With
febuxostat 10-120 mg, the pharmacokinetics are linear. No dose adjustment appears
to be necessary in those with renal insufficiency or mild-to-moderate hepatic
impairment. Febuxostat 10-120 mg/day rapidly and sustainably reduces serum uric
acid by 25-70% in uric acid underexcretors and overproducers. Prophylaxis with
colchicine or a non-steroidal anti-inflammatory drug can mitigate the gout-flare 
risk from the rapid urate lowering after febuxostat initiation. Febuxostat is
well tolerated, the majority of treatment-related adverse events are transient
and mild-to-moderate in severity. Febuxostat can broaden the therapeutic options 
for urate-lowering therapy in those with gout.

Publication Types: 
    Review

PMID: 16022578 [PubMed - indexed for MEDLINE]

309: Skeletal Radiol. 2006 Sep;35(9):684-6. Epub 2005 Jul 8.

Tophaceous gout of the first costochondral junction in a heart transplant
patient.

Chang PC, Seeger LL, Motamedi K, Chan JB.

Department of Radiology, David Geffen School of Medicine at UCLA, 200 UCLA
Medical Plaza, Suite 165-57, Los Angeles, CA 90095-6952, USA.

We report the case of a 49-year-old man with a 10-year history of gout, who
presented with a painful left first costochondral junction mass. A computed
tomography (CT)-guided biopsy of the mass revealed foreign body giant cell
reaction and crystalline deposition consistent with tophaceous gout.

Publication Types: 
    Case Reports

PMID: 16003547 [PubMed - indexed for MEDLINE]

310: J Laryngol Otol. 2005 Jun;119(6):492-4.

Comment in:
    J Laryngol Otol. 2006 Feb;120(2):161.

Tophaceous gout presenting as a dorsal nasal lump.

Hughes JP, Di Palma S, Rowe-Jones J.

Department of Otorhinolaryngology, Head and Neck Surgery/Facial Plastic Surgery, 
The Royal Surrey County Hospital, Guildford, Surrey, UK. jph@dr.com

A literature review reveals that gout has been described as affecting many sites 
in the head and neck region, both in the arthritic and tophaceous form. Gout can 
often mimic malignancy or infection, and has been described as causing acute
airway problems requiring emergency tracheotomy. Here we describe the first
published case of tophaceous gout affecting the soft tissues overlying the nasal 
bones. The patient presented with a bony, hard, dorsal hump and requested
aesthetic rhinoplasty. We also describe an endoscopic technique for removal of
tophi using a powered microdebrider system with a protected burr head. Endoscopic
powered microdebrider blade excision of tophi affecting the limbs has already
been described, with reduced complications when compared with conventional
curettage and debridement techniques. This is the first such application to the
nose.

Publication Types: 
    Case Reports

PMID: 15992482 [PubMed - indexed for MEDLINE]

311: N Z Med J. 2005 Jun 24;118(1217):U1528.

Comment in:
    N Z Med J. 2005 Jun 24;118(1217):U1533.

Benzbromarone therapy in management of refractory gout.

Kumar S, Ng J, Gow P.

Department of Medicine and Rheumatology, Middlemore Hospital, Otahuhu, South
Auckland. Skumar@middlemore.co.nz

AIM: To assess the efficacy and safety of benzbromarone in patients with renal
impairment and severe tophaceous gout (despite receiving optimal conventional
therapy). METHODS: Six patients with refractory gout (despite optimal therapy)
were treated with benzbromarone. Uric acid levels and number of gout attacks were
recorded monthly. Adverse events to medications were also recorded. RESULTS:
After 1 year of treatment with benzbromarone, average uric acid level reduced
from 0.61 mmol/L to 0.46 mmol/L. Repeated measures tests on the changes in uric
acid were clinically significant (p=0.01). The frequency of acute attacks of gout
was reduced from 16 (8-20) to 7.3 (1-16); p=0.01. None of the patients reported
adverse events with the medications. There were no acute flares resulting from
initiation of medications. CONCLUSION: Benzbromarone is effective in lowering
uric acid levels and in reducing the number of acute attacks of gout in patients 
who have failed optimal treatment. Making this drug more readily available will
increase our therapeutic choices for urate reduction and help decrease the
morbidity associated with gout.

Publication Types: 
    Clinical Trial

PMID: 15980902 [PubMed - indexed for MEDLINE]

312: Chin J Integr Med. 2005 Mar;11(1):15-21.

Effects of Rebixiao granules on blood uric acid in patients with repeatedly
attacking acute gouty arthritis.

Ji W, Zhu XX, Tan WF, Lu Y.

Rheumatism Immunity Department of The First Hospital Affiliated to Nanjing
University of Traditional Chinese Medicine. jiweitong@hotmail.com

OBJECTIVE: To observe the clinical effect of Rebixiao granule (RBXG) in treating 
repeatedly attacking acute gouty arthritis and through experimental study on
blood uric acid to explore RBXG's therapeutic mechanism. METHODS: Ninety
repeatedly attacking acute gouty arthritis patients were divided into the treated
group (n = 60) and control group (n = 30). The treated group was treated with
RBXG, and the control group was treated with Futalin tablets (diclofenac sodium).
The baseline treatment including good rest, low purine diet, sufficient water
drinking and urine alkalization, etc. was then given to both groups. Hypoxanthine
600 mg/kg and niacin 100 mg/kg was applied to hyperuricemic mice by gastrogavage 
to establish the animal models. RESULTS: The clinical effective rate of the
treated group was 95.0% and that of the control 90.0%. Good therapeutic effects
were won, insignificant difference (P > 0.05)was shown between the two groups.
However, the cure rate of the treated group was 26.7% while that of the control
group was 10.0%, with significant difference (P < 0.01) shown between them. The
treated group had its blood uric acid lowered, which was significantly different 
(P < 0.05) from that of the control group. The animal experiment indicated that
all the three groups treated with different dosages of RBXG, as well as the Ash
bark and Smilax glabra rhizome groups had their blood uric acid content reduced
in the hyperuricemic mice. CONCLUSION: RBXG has a quicker initiation and better
treatment effects than sole anti-inflammatory and analgesic agents on the
treatment of repeatedly attacking acute gouty arthritis, showing no obvious toxic
or adverse reactions and therefore good for long-term administration and likely
to be a safe TCM preparation to control the symptoms and reduce the onsets of
repeatedly attacking of acute gouty arthritis. The animal experiment shows that
both the compound preparation and part of the single ingredients in the recipe
have the function of reducing blood uric acid. However, the compound recipe has
better therapeutic effects, proving to be superior to single drugs.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15975301 [PubMed - indexed for MEDLINE]

313: Int J STD AIDS. 2005 May;16(5):362-4.

Is ritonavir boosting associated with gout?

Creighton S, Miller R, Edwards S, Copas A, French P.

Department of Genitourinary Medicine, Camden Primary Care Trust, Mortimer Market 
Centre, Mortimer Market, off Capper Street, London WC1E 6AU, UK.
creightonsarah@hotmail.com

Asymptomatic hyperuricaemia is associated with ritonavir therapy, but gout has
rarely been reported. We present a retrospective cohort study of 1825
HIV-positive patients seen at one inner London HIV clinic over a two-year period.
In all, 18 patients had gout, of whom 15 were receiving antiretroviral therapy.
Seven had predisposing risk factors for gout (e.g. pyrazinamide therapy,
haematological malignancy). Of the remaining 11 patients, two were on no
medication and eight (73%) were receiving ritonavir as a boosted protease
inhibitor (PI). By comparison, 11% of HIV-positive patients without gout were
receiving ritonavir (odds ratio = 22; confidence interval = 5-104). Seven of the 
18 patients had documented features of lipodystrophy and dyslipidaemia. Gout was 
seen in patients with known risk factors for gout or who were receiving ritonavir
as a boosted PI and who also had lipodystrophy.

PMID: 15949066 [PubMed - indexed for MEDLINE]

314: J Foot Ankle Surg. 2005 May-Jun;44(3):222-4.

Longitudinal tears of both peroneal tendons associated with tophaceous gouty
infiltration. A case report.

Lagoutaris ED, Adams HB, DiDomenico LA, Rothenberg RJ.

PGY III, Podiatric Surgical Resident, Forum Health Western Reserve Care System,
Youngstown, OH, USA.

The authors report a case of longitudinal tendon tears of the peroneus longus and
brevis in the presence of tophaceous gouty infiltration. There are a limited
number of reports discussing similar processes affecting various tendons
throughout the body. There has been 1 prior case of peroneal tendon involvement
affecting only the peroneus brevis. A 35-year-old man presented with a 4-year
history of left-sided lateral ankle pain, redness, and swelling. The patient
described the "attacks" as occurring off and on, with a recent increase in
frequency. The symptoms were relieved with indomethacin, colchicine, and narcotic
analgesics. Upon clinical evaluation, there was a cavus foot type with moderate
calcaneal varus. Peroneal subluxation was elicited with resisted eversion. An MRI
evaluation revealed longitudinal tears of both peroneal tendons. During surgical 
repair, a chalky-white substance resembling gouty tophi was present within both
tendon tears. The tendons were remodeled and repaired. The patient had an
uneventful postoperative course with nearly completed resolution of his symptoms 
at 1-year follow-up. The patient was referred to his primary care physician for
further evaluation and long-term control of elevated uric acid levels.

Publication Types: 
    Case Reports

PMID: 15940602 [PubMed - indexed for MEDLINE]

315: Pediatr Radiol. 2005 Sep;35(9):899-901. Epub 2005 Jun 7.

Juvenile intraosseous gout of the calcaneus.

Yun CH, Shih SL, Fang YK, Hung YC, Huang JK.

Department of Radiology, Mackay Memorial Hospital, No. 92, Sec. 2, Chung-Shan N. 
Road, Taipei 104, Taiwan.

Gout presenting as an osteolytic lesion is exceedingly rare in children with
asymptomatic hyperuricemia. We report the clinical and radiological presentation 
of intraosseous gout in a 13-year-old boy.

Publication Types: 
    Case Reports

PMID: 15940392 [PubMed - indexed for MEDLINE]

316: Curr Rheumatol Rep. 2005 Jun;7(3):242-9.

Gout treatment: what is evidence-based and how do we determine and promote
optimized clinical care?

Mikuls TR, Saag KG.

University of Nebraska Medical Center and the Omaha VA Medical Center, 983025 NE 
Med Center, Omaha, NE 68198-3025, USA. tmikuls@unmc.edu.

Gout, a common form of inflammatory arthritis, has been markedly understudied
relative to other rheumatologic conditions. As a result, evidence guiding
clinical management in gout has traditionally been lacking. Burgeoning data
suggests that quality of gout care in gout is frequently suboptimal. In this
paper, we examine the evidence supporting gout management strategies in clinical 
practice. In addition, we examine consensus building efforts that have culminated
in the recent publication of gout management quality indicators. We also discuss 
the need for future initiatives aimed at improving patient safety and quality of 
care in gout.

Publication Types: 
    Review

PMID: 15919002 [PubMed - indexed for MEDLINE]

317: Curr Rheumatol Rep. 2005 Jun;7(3):235-41.

Recent advances in the epidemiology of gout.

Saag KG, Mikuls TR.

Division of Clinical Immunology and Rheumatology, University of Alabama at
Birmingham, 820 Faculty Office Tower, 510 20th Street South, Birmingham, AL
35294-3408, USA. ksaag@uab.edu

Gout remains among the most common of all inflammatory arthridities with an
incidence that appears to have risen. Evidence is accumulating to support
lifestyle and dietary factors, such as heavy consumption of beer and liquor as
well as diets rich in meats and seafood as important gout risk factors. There is 
also a renewed interest in important associations between gout and other
comorbidities like hypertension and cardiovascular disease. The importance of
hyperuricemia on health considerations beyond the musculoskeletal system is an
area worthy of even more study.

Publication Types: 
    Review

PMID: 15919001 [PubMed - indexed for MEDLINE]

318: Curr Rheumatol Rep. 2005 Jun;7(3):227-34.

Renal urate handling: clinical relevance of recent advances.

Anzai N, Enomoto A, Endou H.

Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 
6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan. endouh@kyorin-u.ac.jp

Urate is the major inert end product of purine degradation in higher primates in 
contrast to most other mammals because of the genetic silencing of hepatic
oxidative enzyme uricase. The kidney plays a dominant role in urate elimination. 
The kidney excretes 70% of the daily urate production. Therefore, it is important
to understand renal urate handling mechanism because the under excretion of urate
has been implicated in the development of hyperuricemia that leads to gout. The
urate transport systems exist in the proximal tubule but they are complicated
because of their bidirectional transport and the species differences. Recently,
we have identified the urate-anion exchanger URAT1 (SLC22A12) in the human kidney
and found that defects in SLC22A12 lead to idiopathic renal hypouricemia. URAT1
is targeted by uricosuric and antiuricosuric agents that affect urate excretion. 
Molecular identification of urate transporting proteins will lead to the new drug
development for hyperuricemia.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15919000 [PubMed - indexed for MEDLINE]

319: Curr Rheumatol Rep. 2005 Jun;7(3):220-6.

Diet, alcohol, and gout: how do we advise patients given recent developments?

Choi HK.

Rheumatology Unit, Bulfinch 165, Massachusetts General Hospital, 55 Fruit Street,
Boston, MA 02114, USA. hchoi@partners.org

The disease burden of gout remains substantial and may be increasing as a result 
of trends in demographics and lifestyles. Recent scientific data serve to
illuminate the links between dietary and other factors and risk for gout. These
lifestyle factors affect not only the risk for gout, but also are risk factors
for other chronic diseases of public health importance. Accordingly, dietary and 
lifestyle recommendations related to gout should consider their effect on many
diseases beyond gout. These recommendations should reinforce established
recommendations where the influence on gout parallels the influence on other
diseases, and consider modifying the recommendations where they are divergent.

Publication Types: 
    Review

PMID: 15918999 [PubMed - indexed for MEDLINE]

320: Clin Geriatr Med. 2005 Aug;21(3):491-511, v-vi.

Crystal-associated arthritis in the elderly.

Wise CM.

Internal Medicine Division of Rheumatology, Allergy, and Immunology, Medical
College of Virginia, Virginia Commonwealth University Health System, Richmond, VA
23298, USA. cmwise@hsc.vcu.edu

Since the original descriptions of the involvement of crystals in arthritis, our 
understanding of the clinical syndromes of gout and pseudogout, and the role of
basic calcium crystals in arthritis has increased. Gout is usually considered an 
affliction confined to middle-aged men, but has an increasing prevalence in older
populations, with unique and often atypical features. Calcium pyrophosphate
dihydrate crystal deposition disease is common in elderly patients. The diagnosis
of both of these common forms of arthritis and the need to individualize therapy 
in patients with other medical problems remain important clinical challenges to
the practicing physician.

PMID: 15911203 [PubMed - indexed for MEDLINE]

321: Arch Orthop Trauma Surg. 2005 May;125(4):281-4. Epub 2004 Jun 15.

Spontaneous rupture of extensor pollicis longus tendon with tophaceous gout
infiltration.

Hung JY, Wang SJ, Wu SS.

Department of Orthopedics, Tri-Service General Hospital, National Defense Medical
Center, Taipei, Taiwan, Republic of China.

INTRODUCTION: Spontaneous rupture of the extensor pollicis longus (EPL) tendon
has been reported in the literature. Various mechanisms have been proposed to
account for this problem, but gouty infiltration is a rare mechanism. Here we
report a patient with a long-standing history of gout who presented with sudden
loss of interphalangeal extension of the left thumb. Spontaneous rupture of the
EPL tendon caused by gout was discovered. MATERIALS AND METHODS: The successful
treatment done involved surgical exploration and extensor indicis proprius tendon
transfer. Postoperative thumb spica immobilization for 6 weeks was applied.
RESULTS: Pathology disclosed urate crystals deposited within the ruptured EPL
tendon. The functional recovery is satisfactory at the 1-year follow-up.
CONCLUSION: Spontaneous rupture of the EPL tendon caused by gout is rare.
Successful treatment was done with surgical management. Life-long medical
follow-up to prevent a repeated acute attack can lower the risk of a large amount
of tophaceous gout infiltration in tendons and may possibly prevent acute
spontaneous tendon rupture.

Publication Types: 
    Case Reports

PMID: 15875233 [PubMed - indexed for MEDLINE]

322: Rheumatology (Oxford). 2005 Aug;44(8):1038-42. Epub 2005 May 3.

Suboptimal physician adherence to quality indicators for the management of gout
and asymptomatic hyperuricaemia: results from the UK General Practice Research
Database (GPRD).

Mikuls TR, Farrar JT, Bilker WB, Fernandes S, Saag KG.

Department of Medicine, Division of Clinical Immunology and Rheumatology, 510
20th Street South, FOT 8th Floor, Birmingham, AL 35294, USA.

OBJECTIVES: : To examine adherence to validated quality indicators assessing the 
quality of allopurinol use in the treatment of gout and asymptomatic
hyperuricaemia. METHODS: We determined physician adherence in the UK General
Practice Research Database (GPRD) to three validated quality indicators developed
to assess the quality of allopurinol prescribing practices. These indicators were
developed to assess: (i) dosing in renal impairment; (ii) concomitant use with
azathioprine or 6-mercaptopurine; and (iii) use in the treatment of asymptomatic 
hyperuricaemia. We also examined the association of patient-level factors
(sociodemographics, comorbidity, follow-up duration and concomitant medicine use)
with the treatment of asymptomatic hyperuricaemia using multivariable logistic
regression. RESULTS: Of the 63 105 gout patients, 185 (0.3%) were eligible for
Quality Indicator 1 and 52 (0.1%) were eligible for Quality Indicator 2. There
were an additional 471 patients with asymptomatic hyperuricaemia eligible for
Quality Indicator 3. Rates of practice deviation for the three individual quality
indicators ranged from 25 to 57%. Male sex, older age, a history of chronic renal
failure, and a greater number of concomitant medications were significantly
associated with increased odds of inappropriate treatment for asymptomatic
hyperuricaemia. Hypertension and diuretic use were associated with lower odds of 
this practice. CONCLUSIONS: One-quarter to one-half of all patients eligible for 
at least one of the validated quality of care indicators were subject to possible
allopurinol prescribing error, suggesting that inappropriate prescribing
practices are widespread with this agent. Future interventions aimed at reducing 
inappropriate allopurinol use are needed and should be targeted towards high-risk
groups, including older men and those receiving multiple concomitant medications.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15870145 [PubMed - indexed for MEDLINE]

323: Drug Chem Toxicol. 2005;28(2):245-61.

Gout induced by intoxication of sodium bicarbonate in Korean native broilers.

Ejaz S, Kim BS, Lim CW.

Biosafety Research Institute, Chonbuk National University, Jeonju, South Korea.

Gout is a metabolic disorder that results in hyperuricemia and the deposition of 
positively birefringent monosodium urate crystals in various parts of the body.
Intoxication of sodium bicarbonate (SBC) for 35 days in Korean native broilers
was investigated. Sixty birds, aged 2 weeks, divided into 5 groups were exposed
to excess SBC: 2 g/L (group A), 7.5 g/L (group B), 20 g/L (group C), 40 g/L
(group D). Toxicopathological examination of all exposed birds revealed the
manifestation of visceral and articular gout in group C, while birds of group D
showed acute kidney damage with manifestation of excessive visceral gout.
Interestingly, few birds in group D also showed signs of rare condition of acute 
articular gout. Dose-dependent increments in erythrocytic count, hematocrit
values, and hemoglobin levels of the exposed birds were observed. Hypernatremia, 
hyperuricemia, hypokalemia, and hypochloremia were common findings among exposed 
birds. Microscopic examination of birds that manifested visceral gout revealed
significant urate deposit, tubular necrosis, and tophi formation in renal
interstitium. These findings provide a pathophysiological link that SBC
intoxication may support hyperuricemia, which is an independent risk factor for
gout and other renal dysfunctions. Further study is required to delineate the
effect of lowering uric acid on progression of gout and other renal diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15865264 [PubMed - indexed for MEDLINE]

324: Mol Genet Metab. 2005 May;85(1):78-80. Epub 2005 Feb 16.

Normal HPRT coding region in a male with gout due to HPRT deficiency.

Dawson PA, Gordon RB, Keough DT, Emmerson BT.

Department of Medicine, University of Queensland, Princess Alexandra Hospital,
Brisbane, Qld 4102, Australia. paul.dawson@uq.edu.au

A deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT; 
EC 2.4.2.8) is associated with a spectrum of disease that ranges from gouty
arthritis (OMIM 300323) to the more severe Lesch-Nyhan syndrome (OMIM 300322). To
date, all cases of HPRT deficiency have shown a mutation within the HPRT cDNA. In
the present study of an individual with gout due to HPRT deficiency, we found a
normal HPRT cDNA sequence. This is the first study to provide an example of HPRT 
deficiency which appears to be due to a defect in the regulation of the gene.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 15862284 [PubMed - indexed for MEDLINE]

325: Eur Radiol. 2006 Feb;16(2):459-68. Epub 2005 Apr 23.

Cervical spine and crystal-associated diseases: imaging findings.

Feydy A, Lioté F, Carlier R, Chevrot A, Drapé JL.

Service de Radiologie B, Hôpital Cochin, 27, rue du faubourg Saint Jacques,
75679, Paris Cedex 14, France. antoine.feydy@cch.aphp.fr

The cervical spine may be specifically involved in crystal-associated
arthropathies. In this article, we focus on the three common crystals and
diseases: hydroxyapatite crystal deposition disease, calcium pyrophosphate
dihydrate (CPPD) deposition disease, and monosodium urate crystals (gout). The
cervical involvement in crystal-associated diseases may provoke a misleading
clinical presentation with acute neck pain, fever, or neurological symptoms.
Imaging allows an accurate diagnosis in typical cases with calcific deposits and 
destructive lesions of the discs and joints. Most of the cases are related to
CPPD or hydroxyapatite crystal deposition; gout is much less common.

PMID: 15856241 [PubMed - indexed for MEDLINE]

326: Curr Opin Rheumatol. 2005 May;17(3):341-5.

Gout: epidemiology and lifestyle choices.

Choi HK, Curhan G.

Rheumatology Unit, Department of Medicine, Massachusetts General Hospital,
Harvard Medical School, Boston, Massachusetts 02114, USA. hchoi@partners.org

PURPOSE OF REVIEW: Recent scientific data serve to illuminate the links between
dietary and other factors and the incidence of gout. This review summarizes
recent literature about the prevalence and incidence of gout as well as risk
factors for gout. RECENT FINDINGS: Epidemiologic studies suggest that the overall
disease burden of gout is substantial and growing. Gout seems to be relatively
common not only in men but also in older women. A recent large prospective study 
investigated several purported dietary factors for gout and confirmed some of the
long-standing suspicions (red meats, seafood, beer, and liquor), exonerated
others (total protein, wine, and purine-rich vegetables), and also identified
potentially new protective factors (dairy products). A study based on the Third
National Health and Nutrition Examination Survey suggested that these factors
affect serum uric acid levels parallel to the direction of risk of gout. In
addition, adiposity, weight gain, hypertension, and diuretics were all found to
be independent risk factors for incident gout, whereas weight loss was found to
be protective. SUMMARY: The disease burden of gout remains substantial and may be
increasing. Some of the recently confirmed lifestyle factors may explain the
increasing incidence of gout. The public health implications of dietary and
lifestyle recommendations should take into account other associated health
benefits and risks, because many of these factors have health effects beyond
their influence on gout.

Publication Types: 
    Review

PMID: 15838248 [PubMed - indexed for MEDLINE]

327: Curr Opin Rheumatol. 2005 May;17(3):319-24.

Recent advances in the management of gout and hyperuricemia.

Wortmann RL.

Department of Internal Medicine, University of Oklahoma College of Medicine,
Tulsa, Oklahoma 74135, USA. Robert-wortmann@ouhsc.edu

PURPOSE OF REVIEW: To review the recent advances in the management of gout and
hyperuricemia. RECENT FINDINGS: The first quality indicators for gout management 
have been proposed. Selective COX II inhibitors, as well as traditional NSAIDs,
are effective in acute gout. A new xanthine oxidase inhibitor, febuxostat, and
pegylated uricases are in clinical trials. SUMMARY: The therapeutic aims in gout 
include termination of the acute attack as promptly and gently as possible,
prevention of future attacks, prevention or reversal of complications of the, and
prevention or reversal of associated features such as obesity,
hypertriglyceridemia, hypertension, or alcoholism.

Publication Types: 
    Review

PMID: 15838244 [PubMed - indexed for MEDLINE]

328: Curr Opin Rheumatol. 2005 May;17(3):314-8.

Inflammation and tissue damage in crystal deposition diseases.

Dalbeth N, Haskard DO.

Eric Bywaters Centre, Faculty of Medicine, Imperial College London, Hammersmith
Campus, London, UK.

PURPOSE OF REVIEW: The crystal-induced arthropathies are characterized by
self-limiting episodes of acute inflammation and chronic tissue damage. This
review summarizes recent advances in the understanding of the cellular responses 
to monosodium urate, calcium pyrophosphate dihydrate and basic calcium phosphate 
crystals. RECENT FINDINGS: Factors such as the myeloid related proteins,
endothelin-1 and the complement membrane attack complex have been recently
identified as mediators of acute crystal-induced inflammation. In addition,
signalling pathways involved in both acute inflammation and tissue damage in
crystal arthropathies have been further clarified. The potential of
macrophage-derived transforming growth factor beta1 to play a key role in the
resolution phase of acute gout has also been demonstrated. SUMMARY: Recent work
has provided new insights into the regulation of both acute and chronic articular
responses to inflammatory microcrystals. Further analysis of these responses may 
identify potential therapeutic targets for management of the crystal-induced
arthropathies.

PMID: 15838243 [PubMed - indexed for MEDLINE]

329: Obes Surg. 2005 Mar;15(3):405-7.

Development of acute gouty attack in the morbidly obese population after
bariatric surgery.

Antozzi P, Soto F, Arias F, Carrodeguas L, Ropos T, Zundel N, Szomstein S,
Rosenthal R.

Bariatric Institute, Section of Minimally Invasive Surgery, Cleveland Clinic
Florida, Weston, FL 33331, USA.

BACKGROUND: Gout is associated with increased body weight. We evaluated the
prevalence of gout and acute gouty attacks in the morbidly obese population who
underwent bariatric surgery. METHODS: The medical records and operative reports
of 1,240 patients who underwent bariatric surgery were reviewed retrospectively
for weight parameters, BMI, weight loss, medical history of gout, and onset of
acute gouty attacks. RESULTS: Of the 1,240 patients, 5 (0.4%) had been previously
diagnosed with gout. 2 of these 5 had acute attacks during the postoperative
period, and responded successfully to intravenous colchicine. CONCLUSION:
Although rare, gout must be considered a co-morbid illness in obese and morbidly 
obese patients. Surgeons should be familiar with the signs and symptoms of
attacks in the postoperative period, and be knowledgeable in the management.

PMID: 15826477 [PubMed - indexed for MEDLINE]

330: Arch Intern Med. 2005 Apr 11;165(7):742-8.

Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the 
health professionals follow-up study.

Choi HK, Atkinson K, Karlson EW, Curhan G.

Rheumatology Unit, Department of Medicine, Massachusetts General Hospital, MA
02114, USA. hchoi@partners.org

BACKGROUND: Limited prospective information exists on the relation between
obesity and weight change and the risk of gout. Similarly, both hypertension and 
diuretic use have been considered risk factors for gout; however, their
independent contributions have not been established prospectively. METHODS: We
prospectively examined over a 12-year period (1986-1998) the relation between
adiposity, weight change, hypertension, and diuretic use and incident gout in
47,150 male participants with no history of gout at baseline. We used a
supplementary questionnaire to ascertain the American College of Rheumatology
criteria for gout. RESULTS: During 12 years we documented 730 confirmed incident 
cases of gout. Compared with men with a body mass index (BMI) of 21 to 22.9, the 
multivariate relative risks (RRs) of gout were 1.95 (95% confidence interval
[CI], 1.44-2.65) for men with a BMI of 25 to 29.9, 2.33 (95% CI, 1.62-3.36) for
men with a BMI of 30 to 34.9, and 2.97 (95% CI, 1.73-5.10) for men with a BMI of 
35 or greater (P for trend <.001). Compared with men who had maintained their
weight (+/-4 lb) since age 21 years, the multivariate RR of gout for men who had 
gained 30 lb or more since age 21 years was 1.99 (95% CI, 1.49-2.66). In
contrast, the multivariate RR for men who had lost 10 lb or more since the study 
baseline was 0.61 (95% CI, 0.40-0.92). The multivariate RRs of gout were 2.31
(95% CI, 1.96-2.72) for the presence of hypertension and 1.77 (95% CI, 1.42-2.20)
for diuretic use. CONCLUSIONS: Higher adiposity and weight gain are strong risk
factors for gout in men, while weight loss is protective. Hypertension and
diuretic use are also important independent risk factors for gout.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15824292 [PubMed - indexed for MEDLINE]

331: J Urol. 2005 May;173(5):1606-9.

Physicochemical metabolic characteristics for calcium oxalate stone formation in 
patients with gouty diathesis.

Pak CY, Moe OW, Sakhaee K, Peterson RD, Poindexter JR.

Center for Mineral Metabolism and Clinical Research, The University of Texas
Southwestern Medical Center, Dallas, Texas 75390-8885, USA.
charles.pak@utsouthwestern.edu

PURPOSE: We determined why calcium oxalate stones instead of uric acid stones
form in some patients with gouty diathesis. MATERIALS AND METHODS: Gouty
diathesis was diagnosed from absence of secondary causes of uric acid stones or
low urinary pH, and reduced fractional excretion of urate with discriminant score
of the relationship between urinary pH and fractional excretion of urate less
than 80. From the stone registry 163 patients with gouty diathesis were
identified, including 62 with uric acid stones (GD + UA) and 101 patients with
calcium oxalate stones (GD + Ca). Metabolic data and 24-hour urinary chemistry
study were compared between the 2 groups. RESULTS: Compared with GD + UA, GD + Ca
had significantly greater urinary calcium (196 +/- 96 mg per day vs 162 +/- 82 mg
per day, p <0.05) and significantly lower urinary citrate (430 +/- 228 vs 519 +/-
288 mg per day, p <0.05), resulting in higher urinary saturation of calcium
oxalate. Both groups had low urinary pH (less than 5.5) and high urinary
undissociated uric acid (greater than 100 mg/dl). Urinary calcium post-oral
calcium load was significantly higher in GD + Ca than in GD + UA (0.227 vs 0.168 
mg/dl glomerular filtrate, p <0.001). CONCLUSIONS: Calcium oxalate stones may
form in some patients with gouty diathesis due to increased urinary excretion of 
calcium and reduced excretion of citrate. Relative hypercalciuria in GD + Ca may 
be due to intestinal hyperabsorption of calcium.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 15821508 [PubMed - indexed for MEDLINE]

332: Clin Orthop Relat Res. 2005 Apr;(433):106-10.

Surgical versus pharmacologic treatment of intraspinal gout.

Chang IC.

Institute of Medicine, Chung-Shan Medical University and Department of
Orthopaedic Surgery, Chung-Shan Medical University Hospital, No. 110 Section 1
Chien-Kuo N. Road, 402 Taichung, Taiwan. ic40249@ms.34.hinet.net

A controversy between pharmacologic and surgical treatment of intraspinal gout
exists in the literature. If gout is diagnosed timely, pharmacologic therapy may 
avert the need of surgery. The lack of readily available synovial fluid makes the
diagnosis particularly difficult. The purpose of this study was to evaluate the
clinical pictures and magnetic resonance imaging features in rapid
differentiations of intraspinal gout. I retrospectively evaluated lumbar
intraspinal tophaceous gout without the classic radiographic punched-out lesions.
Four patients (average age, 65 years) had a history of hyperuricemia with
multiple tophaceous deposits in the joints or visceral organs or both. The common
presentations were low back pain with or without inflammatory reaction (fever,
elevated C-reactive protein level, and mild leukocytosis). The patients also
presented with intermittent claudication or radiculopathy of variable duration or
both. The gouty tophi yielded homogeneous and hypointense masses on T1- and
T2-weighted images, with multiple hypointense speckles. The masses were located
in bilateral lumbar facet joints in all patients, with additional midline
extension along the ligamentum flavum in three. All patients had uneventful
outcomes after surgical decompression and pharmacologic treatment. Rapid
deposition of tophi may aggravate nerve compression. If neurologic deficits are
found, surgical decompression can provide a satisfactory outcome. LEVEL OF
EVIDENCE: Therapeutic study, Level IV. See the Guidelines for Authors for a
complete description of levels of evidence.

Publication Types: 
    Comparative Study

PMID: 15805944 [PubMed - indexed for MEDLINE]

333: Proc Biol Sci. 2004 Dec 7;271 Suppl 6:S458-60.

Diclofenac poisoning is widespread in declining vulture populations across the
Indian subcontinent.

Shultz S, Baral HS, Charman S, Cunningham AA, Das D, Ghalsasi GR, Goudar MS,
Green RE, Jones A, Nighot P, Pain DJ, Prakash V.

Royal Society for the Protection of Birds, The Lodge, Sandy SG19 2DL, UK.

Recent declines in the populations of three species of vultures in the Indian
subcontinent are among the most rapid ever recorded in any bird species. Evidence
from a previous study of one of these species, Gyps bengalensis, in the Punjab
province of Pakistan, strongly implicates mortality caused by ingestion of
residues of the veterinary non-steroidal anti-inflammatory drug diclofenac as the
major cause of the decline. We show that a high proportion of Gyps bengalensis
and G. indicus found dead or dying in a much larger area of India and Nepal also 
have residues of diclofenac and visceral gout, a post-mortem finding that is
strongly associated with diclofenac contamination in both species. Hence,
veterinary use of diclofenac is likely to have been the major cause of the rapid 
vulture population declines across the subcontinent.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15801603 [PubMed - indexed for MEDLINE]

334: J Bone Joint Surg Br. 2005 Apr;87(4):513-7.

Crystal arthropathy of the lumbar spine: a series of six cases and a review of
the literature.

Mahmud T, Basu D, Dyson PH.

Departmernt of Orthopaedics, Hemel Hempstead Hospital, Hillfield Road, Hemel
Hempstead HP2 4AD, UK.

There have been very few reports in the literature of gout and pseudogout of the 
spine. We describe six patients who presented with acute sciatica attributable to
spinal stenosis with cyst formation in the facet joints. Cytopathological studies
confirmed the diagnosis of crystal arthropathy in each case.Specific formation of
a synovial cyst was identified pre-operatively by MRI in five patients. In the
sixth, the diagnosis was made incidentally during decompressive surgery. Surgical
decompression alone was undertaken in four patients. In one with an associated
degenerative spondylolisthesis, an additional intertransverse fusion was
performed. Another patient had previously undergone a spinal fusion adjacent to
the involved spinal segment, and spinal stabilisation was undertaken as well as a
decompression.In addition to standard histological examination material was sent 
for examination under polarised light which revealed deposition of urate or
calcium pyrophosphate dihydrate crystals in all cases.It is not possible to
diagnose gout and pseudogout of the spine by standard examination of a fixed
specimen. However, examining dry specimens under polarised light suggests that
crystal arthropathy is a significant aetiological factor in the development of
symptomatic spinal stenosis associated with cyst formation in a facet joint.

Publication Types: 
    Case Reports
    Review

PMID: 15795202 [PubMed - indexed for MEDLINE]

335: Clin Exp Rheumatol. 2005 Jan-Feb;23(1):85-8.

Interleukin-1 receptor antagonist gene polymorphism in Taiwanese patients with
gout.

Lo SF, Huang CM, Tsai CH, Chen ML, Tsai FJ.

Department of Physical Medicine and Rehabilitation, China Medical University
Hospital, Taiwan.

OBJECTIVE: The purpose of this study was to examine whether interleukin-1
receptor antagonist (IL-1Ra) gene polymorphism is a marker of susceptibility to
or of the clinical characteristics of gout in Taiwanese patients. METHODS: 196
Taiwanese patients with gout and 103 unrelated normal healthy control subjects
living in central Taiwan were studied. Polymorphism of the gene for IL-1Ra was
typed from genomic DNA. Allelic frequencies and carriage rates were compared
between gout patients and control subjects. The relationship between IL-1Ra
genotypes and the clinical characteristics of gout was also evaluated. RESULTS:
No significant differences were observed in genetic and allelic frequencies of
the IL-1Ra gene polymorphism between patients with gout and healthy control
subjects. Furthermore, we did not detect any association of IL-1Ra genotype with 
the clinical and laboratory profiles in patients with gout. CONCLUSION: The
results from the present study suggest that the interleukin-1 receptor antagonist
gene polymorphism is not a genetic marker of susceptibility to gout for
Taiwanese. Furthermore, our study also suggests that the IL-1Ra gene polymorphism
is unrelated to the clinical characteristics of gout.

Publication Types: 
    Comparative Study

PMID: 15789892 [PubMed - indexed for MEDLINE]

336: Skeletal Radiol. 2005 Apr;34(4):229-33. Epub 2004 Nov 20.

Intra-abdominal gout mimicking pelvic abscess.

Chen CH, Chen CK, Yeh LR, Pan HB, Yang CF.

Department of Radiology, Kaohsiung Veterans General Hospital, and School of
Medicine, National Yang-Ming University, Taipei, Taiwan. chiachen@yahoo.com.tw

Gout is the most common crystal-induced arthritis. Gouty tophi typically deposit 
in the extremities, especially toes and fingers. We present an unusual case of
intrapelvic tophaceous gout in a patient suffering from chronic gouty arthritis. 
CT and MRI of the abdomen and pelvic cavity disclosed calcified gouty tophi
around both hips, and a cystic lesion with peripheral enhancement in the pelvic
cavity along the course of the iliopsoas muscle. The intra-abdominal tophus
mimicked pelvic abscess.

Publication Types: 
    Case Reports

PMID: 15778870 [PubMed - indexed for MEDLINE]

337: J Endocrinol Invest. 2004 Nov;27(10):965-6.

A rare and asymptomatic case of mitral valve tophus associated with severe gouty 
tophaceous arthritis.

Iacobellis G, Iacobellis G.

Department of Clinical Sciences, La Sapienza University, Rome, Italy.
gianluca.iaco@tin.it

Gouty arthritis is characterized by the deposition of monosodium urate crystals
in the joints and soft tissues. Clinical manifestations include acute and chronic
arthritis and tophaceous deposits. Chronic tophaceous gout has become less common
since the introduction of the pharmacological treatment. Moreover, cardiac valve 
gouty tophi have been very rarely reported.

Publication Types: 
    Case Reports

PMID: 15762047 [PubMed - indexed for MEDLINE]

338: Occup Med (Lond). 2005 Mar;55(2):145-8.

Occupational molybdenum exposure and a gouty electrician.

Seldén AI, Berg NP, Söderbergh A, Bergström BE.

Department of Occupational and Environmental Medicine, Orebro University
Hospital, SE-701 85 Orebro, Sweden. anders.selden@orebroll.se

BACKGROUND: Molybdenum is an essential trace element and a component of xanthine 
oxidase, which catalyses the formation of urate. The toxicity of molybdenum in
humans is considered to be low, but hyperuricaemia and gout-like symptoms have
been observed sporadically. METHODS: A case of hyperuricaemia and gouty arthritis
in a young man with occupational exposure to molybdenum is described. Improvement
during an exposure-free period was followed by a relapse after a reconstruction
designed to quantify his molybdenum exposure. CONCLUSION: This case seems to
represent the first observation of gout associated with occupational molybdenum
exposure, but the association might also be entirely circumstantial.

Publication Types: 
    Case Reports

PMID: 15757993 [PubMed - indexed for MEDLINE]

339: Arthritis Rheum. 2005 Mar;52(3):916-23.

Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a
twenty-eight-day, multicenter, phase II, randomized, double-blind,
placebo-controlled, dose-response clinical trial examining safety and efficacy in
patients with gout.

Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Palo WA, Eustace D,
Vernillet L, Joseph-Ridge N.

Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA.
mbecker@medicine.bsd.uchicago.edu

OBJECTIVE: Gout affects approximately 1-2% of the American population. Current
options for treating hyperuricemia in chronic gout are limited. The purpose of
this study was to assess the safety and efficacy of febuxostat, a nonpurine
selective inhibitor of xanthine oxidase, in establishing normal serum urate (sUA)
concentrations in gout patients with hyperuricemia (>or=8.0 mg/dl). METHODS: We
conducted a phase II, randomized, double-blind, placebo-controlled trial in 153
patients (ages 23-80 years). Subjects received febuxostat (40 mg, 80 mg, 120 mg) 
or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to
and 14 days after randomization. The primary end point was the proportion of
subjects with sUA levels <6.0 mg/dl on day 28. RESULTS: Greater proportions of
febuxostat-treated patients than placebo-treated patients achieved an sUA level
<6.0 mg/dl at each visit (P < 0.001 for each comparison). The targeted sUA level 
was attained on day 28 in 0% of those taking placebo and in 56% of those taking
40 mg, 76% taking 80 mg, and 94% taking 120 mg of febuxostat. The mean sUA
reduction from baseline to day 28 was 2% in the placebo group and 37% in the
40-mg, 44% in the 80-mg, and 59% in the 120-mg febuxostat groups. Gout flares
occurred with similar frequency in the placebo (37%) and 40-mg febuxostat (35%)
groups and with increased frequency in the higher dosage febuxostat groups (43%
taking 80 mg; 55% taking 120 mg). During colchicine prophylaxis, gout flares
occurred less frequently (8-13%). Incidences of treatment-related adverse events 
were similar in the febuxostat and placebo groups. CONCLUSION: Treatment with
febuxostat resulted in a significant reduction of sUA levels at all dosages.
Febuxostat therapy was safe and well tolerated.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial

PMID: 15751090 [PubMed - indexed for MEDLINE]

340: J Neurosurg Spine. 2005 Feb;2(2):215-7.

Topacheous gout as a rare cause of spinal stenosis in the lumbar region. Case
report.

Kelly J, Lim C, Kamel M, Keohane C, O'Sullivan M.

Cork University Hospital, Cork, Ireland.

Despite the fact that gout is a common metabolic disorder, because its
involvement of the axial skeleton is rare the diagnosis is often delayed, even in
patients with long-standing gout who present with neurological deficits. The
authors report the case of a woman with a history of extensive gout, emphasizing 
the clinical, radiological, and pathological features of a lumbar spinal
stenosis.

Publication Types: 
    Case Reports

PMID: 15739537 [PubMed - indexed for MEDLINE]

341: Anal Bioanal Chem. 2004 Dec;380(7-8):913-7. Epub 2004 Nov 20.

Determination of uric acid in human saliva by capillary electrophoresis with
electrochemical detection: potential application in fast diagnosis of gout.

Guan Y, Chu Q, Ye J.

Department of Chemistry, East China Normal University, Shanghai 200062, Peoples
Republic of China.

The clinical manifestations of gout result from the formation and deposition of
uric acid (UA) crystals. The monitoring of UA level in less invasive biological
samples such as saliva is suggested for diagnosis and therapy of gout,
hyperuricemia and the Lesch-Nyhan syndrome. In order to investigate the
correlation between trace amounts of UA in human saliva and urine and explore the
potential application in fast diagnosis of gout, capillary electrophoresis with
electrochemical detection (CE-ED) was applied for the determination of UA in
human saliva and urine in this work. Under the optimum conditions, UA and three
coexisting analytes could be well separated within 14 min at the separation
voltage of 14 kV in 80 mmol L(-1) borax running buffer (pH 7.8). A good linear
relationship was established between peak current and concentration of analytes
over two orders of magnitude with detection limits (S/N = 3) ranging from 1.09 x 
10(-7) to 5.0 x 10(-7) mol L(-1) for all analytes. This proposed method has been 
successfully applied for study of the correlation between the UA content of human
saliva and urine, providing an alternative and convenient method for rapid
diagnosis of gout.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15700169 [PubMed - indexed for MEDLINE]

342: Clin Rheumatol. 2005 Feb;24(1):70-1. Epub 2004 Jul 15.

Chyle and gout causing acute monoarthritis: some unusual findings.

Kodali VR, Dunn NA.

General Internal Medicine, Diabetes and Endocrinology, Jenny O'Neill Diabetes
Centre, Derbyshire Royal Infirmary, London Road, Derby, DE2 1QY, UK.
kodali@doctors.org.uk

A 67-year-old man presented with acute monoarthritis of the right knee.
Aspiration was carried out under aseptic precautions. This yielded a milky
appearing fluid. Polarized microscopic examination confirmed uric acid crystals. 
The patient had a history of trauma to the joint. Acute monoarthritis of the knee
can occur due to gout. Chylous effusions in the knee are rare. This combination
of findings in the same joint has not been described in the literature. We
emphasise the importance of history of trauma in acute monoarthritis. We discuss 
the unusual features of this case.

Publication Types: 
    Case Reports

PMID: 15674658 [PubMed - indexed for MEDLINE]

343: Ann Rheum Dis. 2005 Feb;64(2):267-72.

Gout epidemiology: results from the UK General Practice Research Database,
1990-1999.

Mikuls TR, Farrar JT, Bilker WB, Fernandes S, Schumacher HR Jr, Saag KG.

Department of Medicine, University of Nebraska Medical Center and Omaha VA
Medical Center, Omaha, NE, USA.

OBJECTIVE: To examine the epidemiology of gout and gout treatment in the United
Kingdom using a large national practice based population. METHODS: Data from the 
UK General Practice Research Database from 1990 to 1999 were examined. Physician 
diagnoses and drug codes were used, and trends in gout incidence and treatment
examined. Additionally, disease prevalence for the year 1999 was assessed. To
examine the association of gout with comorbid disease, the prevalence of select
health conditions and drug use was compared with the corresponding prevalences
seen in osteoarthritis, adjusting for both age and sex. RESULTS: From 1 January
1990 to 31 December 1999 overall gout incidence remained relatively stable,
ranging from a low of 11.9 cases (95% confidence interval (CI) 11.5 to 12.3) in
1991 to a high of 18.0 cases (95% CI 17.6 to 18.4) per 10 000 patient-years in
1994. Gout prevalence in 1999 was 1.4% with rates approaching 7% in men over the 
age of 65. Drugs used for the treatment of gout remained constant in prevalent
cases with the exception of a significant decline in non-steroidal
anti-inflammatory drug use over the 10 year follow up. Compared with patients
with osteoarthritis, patients with gout were significantly more likely to have
cardiovascular disease, hypertension, diabetes, and chronic renal failure, and
were more likely to have used diuretics or ciclosporin, or both. CONCLUSION:
Although gout is common in the UK, particularly among older men, the incidence of
the disease seems to have remained stable during the 1990s.

PMID: 15647434 [PubMed - indexed for MEDLINE]

344: J Clin Neurosci. 2005 Jan;12(1):44-6.

Tophaceous gout of the lumbar spine mimicking infectious spondylodiscitis and
epidural abscess: MR imaging findings.

Yen PS, Lin JF, Chen SY, Lin SZ.

Department of Radiology, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan.

We report a case of surgically proven tophaceous gout of the lumbar spine at the 
L5-S1 level that mimicked infectious spondylodiscitis and epidural abscess on
magnetic resonance (MR) images in a 65-year-old woman. The spinal tophi were
hypointense on T1-weighted images; focally and strongly hyperintense on
T2-weighted images; and heterogeneously, marginally enhancing on
contrast-enhanced T1-weighted images. The aim of this report is to emphasize the 
importance of considering this disease entity in the differential diagnosis of an
epidural mass in a patient with chronic back pain.

Publication Types: 
    Case Reports

PMID: 15639411 [PubMed - indexed for MEDLINE]

345: Joint Bone Spine. 2004 Nov;71(6):481-5.

Current management of gout in patients unresponsive or allergic to allopurinol.

Bardin T.

Rheumatology Federation, Lariboisière Teaching Hospital, 2, rue Ambroise Paré,
75010 Paris, France. thomas.bardin@lrb.ap-hop-paris.fr

The manifestations of gout can be abolished permanently by lifelong
urate-lowering therapy maintaining serum urate levels under 360 mmol/l, as this
ensures dissolution of pathogenic crystals of monosodium urate monohydrate.
Benzbromarone has been withdrawn from the market, leaving allopurinol as the only
urate-lowering drug readily available in France. Allopurinol may induce
unacceptable side effects, and in patients with dose-limiting renal failure it
may not be sufficiently effective. Because allopurinol can induce serious side
effects when given concomitantly with purine antimetabolites, it is
contraindicated in organ transplant recipients. In patients who cannot tolerate
allopurinol, dietary treatment, discontinuation of diuretic agents, and use of
losartan or fenofibrate to treat concomitant hypertension or dyslipidemia,
respectively, may ensure adequate control of serum urate levels. Desensitization 
to allopurinol can be attempted in patients with mild cutaneous hypersensitivity 
reactions but is difficult to perform and rarely used. Uricosuric agents may be
helpful in patients with normal or diminished urate excretion. Probenecid is
available in France from hospital pharmacies, and benzbromarone can be prescribed
via a time-limited authorization procedure. Rasburicase, an Aspergillus urate
oxidase produced by genetic engineering, is indicated to prevent acute
hyperuricemia induced by chemotherapy for hematological malignancies. Factors
that limit the use of rasburicase include the absence of a marketing
authorization, the need for parenteral administration, and the absence of
validated treatment schedules. Patients with renal failure precluding the use of 
effective allopurinol dosages are good candidates for benzbromarone therapy.
Organ transplant recipients can be given benzbromarone, within the current
restrictions to its use; alternatively, mycophenolate mofetil can be substituted 
for calcineurin inhibitors, which elevate serum urate levels, or for
azathioprine, which contraindicates the use of allopurinol.

Publication Types: 
    Review

PMID: 15589427 [PubMed - indexed for MEDLINE]

346: Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1119-22.

Pharmacokinetics and pharmacodynamics of febuxostat (TMX-67), a non-purine
selective inhibitor of xanthine oxidase/xanthine dehydrogenase (NPSIXO) in
patients with gout and/or hyperuricemia.

Komoriya K, Hoshide S, Takeda K, Kobayashi H, Kubo J, Tsuchimoto M, Nakachi T,
Yamanaka H, Kamatani N.

Teijin Ltd., Tokyo, Japan.

The diurnal change of sUA and the effect of febuxostat on this change were
investigated in 10 patients with gout and/or hyperuricemia. The diurnal sUA
change after the last dose during the 4-week treatment phase (20 mg, QD) was
almost the same as the pre-treatment value. Considering the dose, the AUC(obs)
and Cmax of unchanged drug in patients with gout and/or hyperuricemia were
estimated to be similar to those of healthy male adults. The results show that a 
6-week treatment with febuxostat is safe and well-tolerated in the target patient
population for this drug.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase II

PMID: 15571213 [PubMed - indexed for MEDLINE]

347: J Rheumatol. 2004 Dec;31(12):2429-32.

Colchicine for prophylaxis of acute flares when initiating allopurinol for
chronic gouty arthritis.

Borstad GC, Bryant LR, Abel MP, Scroggie DA, Harris MD, Alloway JA.

Department of Rheumatology, Wilford Hall US Air Force Medical Center, Lackland
AFB, San Antonio, Texas, USA.

OBJECTIVE: The use of colchicine to prevent acute gout flares during initiation
of allopurinol therapy is widely practiced despite lack of proven benefit. We
investigated if colchicine administration during initiation of allopurinol for
chronic gouty arthritis reduces the frequency and/or severity of acute gout
flares. METHODS: Patients starting allopurinol for crystal-proven chronic gouty
arthritis were randomized to receive colchicine 0.6 mg po bid or placebo in a
randomized, prospective, double blind, placebo controlled trial. Subjects were
followed for evidence of acute gout flares and remained on study drug for 3
months beyond attaining a serum urate concentration < 6.5 mg/dl. Treatment arms
were analyzed regarding frequency of flares, likelihood of any flare or multiple 
flares, severity of flares on the visual analog scale (VAS), and length of flares
in days. RESULTS: Forty-three subjects were studied. Subjects treated with
colchicine experienced fewer total flares (0.52 vs 2.91, p = 0.008), fewer flares
from 0 to 3 months (0.57 vs 1.91, p = 0.022), fewer flares 3-6 months (0 vs 1.05,
p = 0.033), less severe flares as reported on VAS (3.64 vs 5.08, p = 0.018), and 
fewer recurrent gout flares (p = 0.001). Colchicine was well tolerated.
CONCLUSION: Colchicine prophylaxis during initiation of allopurinol for chronic
gouty arthritis reduces the frequency and severity of acute flares, and reduces
the likelihood of recurrent flares. Treating patients with colchicine during
initiation of allopurinol therapy for 6 months is supported by our data.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 15570646 [PubMed - indexed for MEDLINE]

348: Nitric Oxide. 2004 Nov;11(3):228-36.

Stimulation of inducible nitric oxide synthase by monosodium urate crystals in
macrophages and expression of iNOS in gouty arthritis.

Chen L, Hsieh MS, Ho HC, Liu YH, Chou DT, Tsai SH.

Department of Orthopaedics and Traumatology, School of Medicine, Taipei Medical
University Hospital, Taipei Medical University, Taipei, Taiwan, ROC.

From the studies on the involvement of iNOS in arthritis, it is clear that
attention has focused primarily on rheumatoid arthritis (RA) and osteoarthritis
(OA). To date, little is known about the role of iNOS in the pathophysiology of
gouty arthritis (GA). Here, we investigated the significance of iNOS expression
in cell culture system as well as in GA patients. Gouty crystals monosodium urate
(MSU) appeared to up-regulate inducible nitric oxide synthase (iNOS) mRNA and
protein expression in a concentration- and time-dependent manner in RAW264.7
macrophages. This increase of iNOS expression is attributable to the activation
of multiple signaling pathways. Evidence for this was initially established by
inhibitor treatment of cells in the presence of MSU. While the JAK inhibitor
AG490, the PI3K inhibitor LY294002, and the NFkappaB inhibitor PDTC abrogated
almost completely the expression of iNOS induced by MSU, the ERK1/2 inhibitor
PD98059 was only partially effective. Furthermore, the effect of MSU on the
activation of PI3K/Akt, JAK/STAT, ERK1/2, and NFkappaB signaling molecules was
carefully examined. Moreover, it was shown that GAS and NFkappaB motifs are
required for iNOS expression mediated by MSU. In addition, synovial tissues
obtained from GA patients displayed enhanced expression of iNOS when compared
with normal synovium. Taken together, these findings provide the first evidence
for the potential importance of iNOS in the pathogenesis of GA as well as RA and 
OA, and in turn raise the possibility that iNOS may be an ideal target for
preventive therapy in human arthritis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15566969 [PubMed - indexed for MEDLINE]

349: Arthroscopy. 2004 Nov;20(9):e117-21.

An unusual case of tophaceous gout involving the anterior cruciate ligament.

Melloni P, Valls R, Yuguero M, Sáez A.

Servei de Diagnòstic per Imatge, Unitat de Diagnòstic d'Alta Tecnologia,
Sabadell, Barcelona, Spain. pmelloni@cspt.es

Abstract We describe a very unusual case of a 49-year-old man with tophaceous
gout involving and infiltrating the base of the anterior cruciate ligament of the
left knee. To our knowledge, such a case has never been reported in the
literature, although gout is well known and widely studied. Magnetic resonance
imaging findings and differential diagnosis were analyzed before arthroscopy.
Tophaceous gout was suspected at arthroscopy and confirmed on pathologic
examination. Treatment consisted of partial removal of the tumor by arthroscopy, 
conserving the anterior cruciate ligament.

Publication Types: 
    Case Reports

PMID: 15525921 [PubMed - indexed for MEDLINE]

350: J Med Assoc Thai. 2004 Sep;87(9):1087-91.

The efficacy of combined low dose of Allopurinol and benzbromarone compared to
standard dose of Allopurinol in hyperuricemia.

Akkasilpa S, Osiri M, Deesomchok U, Avihingsanon Y.

Department of Medicine, Faculty of Medicine, Chulalongkorn University, Thailand.

OBJECTIVE: To compare the efficacy of combined low dose of hypouricemic drugs
(Allopurinol 100 mg and benzbromarone 20 mg; Allomaron) and standard dose 300 mg 
of allopurinol in hyperuricemia. MATERIAL AND METHOD: A prospective, open study
of 94 hyperuricemic patients was done at King Chulalongkorn Memorial Hospital.
Each group of 47 patients was given a combined low dose of hypouricemic drugs
(Allopurinol 100 mg and benzbromarone 20 mg; Allomaron) and a standard dose 300
mg of allopurinol. Serum uric acid was measured before and 4 weeks after
receiving the drugs. The efficacy was measured from the difference of the level
of serum uric acid before and after receiving the drugs. RESULTS: The patients
receiving the combined low dose of hypouricemic drugs and standard dose of
allopurinol showed a mean reduction of serum uric acid of 2.5+/-3.4 mg/dl and
4.1+/-2.7 mg/dl consecutively. There was a statistically significant difference
between the 2 groups (P = 0.010). CONCLUSION: This study demonstrates that the
efficacy of standard dose 300 mg of allopurinol is superior to a combined low
dose of allopurinol and benzbromarone in lowering the level of serum uric acid
level.

Publication Types: 
    Comparative Study

PMID: 15516011 [PubMed - indexed for MEDLINE]

351: J Tradit Chin Med. 2004 Sep;24(3):185-7.

Clinical analysis for the acupuncture treatment in 42 cases of gouty renal
damage.

Ma X.

Hai'an County Hospital of Traditional Chinese Medicine, Jiangsu Province 226600.

OBJECTIVE: To observe the therapeutic effects of acupuncture on gouty renal
damage. METHOD: 72 cases of gouty renal damage were randomly divided into a
treatment group of 42 cases and a control group of 30 cases to observe the
therapeutic effects and the changes in 24-hour urinary protein content, blood
creatinine, uric acid and urea nitrogen in blood before treatment and one month
after treatment. RESULTS: The total effective rate in the treatment group reached
95.24%, which was remarkably higher than 63.33% in the control group. After one
month of treatment, the indexes were found reduced in both groups, but the
reduction rate in the treatment group was obviously superior to that in the
control group. CONCLUSION: The patients with repeated attacks of gout may have a 
higher possibility to suffer from renal damage. Therefore, attention should be
paid to its early diagnosis and treatment. Acupuncture may exert good therapeutic
effects on early gout complicated with renal damage by adjusting the metabolism
and improving the renal function.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15510795 [PubMed - indexed for MEDLINE]

352: Drugs. 2004;64(21):2399-416.

Management of acute and chronic gouty arthritis: present state-of-the-art.

Schlesinger N.

Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert
Wood Johnson Medical School, New Brunswick, New Jersey 08903-0019, USA.
schlesna@umdnj.edu

There are three stages in the management of gout: (i) treating the acute attack; 
(ii) lowering excess stores of uric acid to prevent flares of gouty arthritis and
to prevent tissue deposition of urate; and (iii) providing prophylaxis to prevent
acute flares. It is important to distinguish between therapy to reduce acute
inflammation in acute gout and therapy to manage hyperuricaemia in patients with 
chronic gouty arthritis.During the acute gouty attack nonpharmacological
treatments such as topical ice and rest of the inflamed joint are useful. NSAIDs 
are the preferred treatment in acute gout. The most important determinant of
therapeutic success is not which NSAID is chosen, but rather how soon NSAID
therapy is initiated. Other treatments include oral and intravenous colchicine,
intra-articular and systemic corticosteroids, and intramuscular
corticotropin.Optimal treatment of chronic gout requires long-standing reduction 
in serum uric acid. The urate-lowering drugs used to treat chronic gout are the
uricosuric drugs, the uricostatic drugs, which are xanthine oxidase inhibitors,
and the uricolytic drugs. Xanthine oxidase inhibitors such as allopurinol,
oxipurinol and febuxastat should be used as first-line treatment in patients with
renal calculi, renal insufficiency, concomitant diuretic therapy and ciclosporin 
(cyclosporine) therapy, and urate overproduction. Uricosuric drugs include
probenecid, benzbromarone, micronised fenofibrate and losartan. They are the
urate-lowering drugs of choice in allopurinol-allergic patients and
underexcretors with normal renal function and no history of urolithiasis. The use
of recombinant urate oxidase in patients with chronic gout is limited by the need
for parenteral administration, the potential antigenicity and production of
anti-urate oxidase antibodies, and declining efficacy.The effectiveness of
colchicine prophylaxis as an isolated therapy is still to be confirmed by
placebo-controlled trials. Another issue is prophylaxis with NSAIDs. There are no
comparative studies with colchicine.

Publication Types: 
    Review

PMID: 15481999 [PubMed - indexed for MEDLINE]

353: Acta Orthop Belg. 2004 Aug;70(4):368-70.

Gouty flexor tenosynovitis mimicking infection: a case report emphasising the
value of ultrasound in diagnosis.

Aslam N, Lo S, McNab I.

Nuffield Orthopaedic Centre, Oxford, UK. nadimaslam@hotmail.com

Tenosynovitis of the flexor tendons of the hand is a rare manifestation of gout. 
We present an unusual case of gouty tenosynovitis mimicking infection. The role
of ultrasound in the management of this condition is emphasised.

Publication Types: 
    Case Reports
    Review

PMID: 15481424 [PubMed - indexed for MEDLINE]

354: Geriatrics. 2004 Sep;59(9):25-30; quiz 31.

Crystal arthritis. Gout and pseudogout in the geriatric patient.

Cassetta M, Gorevic PD.

Mount Sinai Medical Center, New York, NY, USA.

Gout and pseudogout are inflammatory arthritides due to monosodium urate and
calcium pyrophosphate dihydrate crystal formation. Both are prevalent among
geriatric patients, and can present as acute mono- or oligoarticular disease, or 
as a chronic polyarthropathy resembling osteoarthritis or rheumatoid arthritis.
Gout in the geriatric patient is a disease affecting women, commonly associated
with diuretic usage, often involves the fingers, may be complicated by the
development of masses of uric acid crystals (tophi) in soft tissues, and is
frequently polyarticular. Pseudogout in the geriatric patient has a variety of
clinical presentations, may be acute or chronic, and should be considered in
evaluating any patient with osteoarthritis occurring in an atypical distribution.
Treatment includes the use of nonsteroidal anti-inflammatory drugs, colchicine,
or corticosteroids. Gout may be impacted by dietary factors, weight reduction,
and avoidance of certain forms of alcohol; uric acid-lowering agents are
effective for refractory or chronic tophaceous disease.

Publication Types: 
    Review

PMID: 15461235 [PubMed - indexed for MEDLINE]

355: Clin Rheumatol. 2005 Apr;24(2):103-6. Epub 2004 Sep 16.

Elevated serum homocysteine levels for gouty patients.

Cheng TT, Lai HM, Chang HW, Luo SF.

Graduate Institute of Clinical Medical Sciences, Chang Gung University,
Kaohsiung, Taiwan, ROC.

Our objective was to analyze serum total homocysteine (tHcy) levels for gouty
patients and to study whether there are any level changes following treatment
with allopurinol. We enrolled 90 male participants including patients with
primary gout (n=51) and community-based healthy controls (n=39). Fasting tHcy
levels were determined for all subjects and repeat measurements performed for 29 
patients following treatment with allopurinol. The results revealed that gouty
patients exhibited significantly greater serum tHcy levels (12.10+/-3.19
micromol/l) than healthy controls did (9.96+/-2.16 micromol/l) (p=0.0003),
although there was no obvious difference between the pre-allopurinol treatment
group (12.54+/-3.31 micromol/l) and its post-treatment analogue (11.90+/-4.68
micromol/l) (n=29, p=0.33). Elevated serum levels of tHcy were noted for this
cohort of male gouty patients as compared to healthy controls, and these tHcy
levels did not appear to change substantially following treatment with
allopurinol. Although the pathogenesis of hyperhomocysteinemia for gouty patients
still remains somewhat obscure, this study suggests that tHcy levels cannot be
effectively modulated by treatment with allopurinol.

PMID: 15378395 [PubMed - indexed for MEDLINE]

356: Scand J Rheumatol. 2004;33(4):233-8.

Community-based study in Taiwan aborigines concerning renal dysfunction in gout
patients.

Chang SJ, Chen CJ, Hung HP, Ou TT, Ko YC.

Department of Public Health, School of Medicine, Kaohsiung Medical University,
Taiwan.

OBJECTIVE: To reveal the factors associated with renal dysfunction among gout
patients in Taiwan aborigines. METHODS: Social demographic data, alcohol
consumption data, anthropometric measurements, blood samples, and 24-h urine
samples were collected from 128 aboriginals (101 men, 27 women) suffering from
gout. RESULTS: The men displayed higher mean creatinine clearance (Ccr) values
than women. Twenty-two post-menopausal women had significantly lower Ccr values
compared to the five pre-menopausal women [probability (p)<0.001]. The males
displayed higher 24-h urinary creatinine value than females (8.60+/-5.39 versus
5.58+/-2.14 mmol/L; p<0.05), and showed a significantly higher positive
relationship between 24-h urinary creatinine and uric acid excretion [correlation
coefficient (r)=0.7304; p<0.001], whereas the females did not (r=0.1144;
p=0.5691). Overall, those who were older members of the Tsou tribe, or had
excreted less uric acid from urine in 24 h tended to suffer renal dysfunction.
CONCLUSIONS: Gout patients displayed diversity in renal function. An exogenous
source of creatinine in men was more likely than in women.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15370718 [PubMed - indexed for MEDLINE]

357: Orthopedics. 2004 Aug;27(8):862-3.

Carpal tunnel syndrome due to tophaceous gout.

Rich JT, Bush DC, Lincoski CJ, Harrington TM.

Department of Orthopedic Surgery, Geisinger Medical Center, Danville, Pa 17822,
USA.

Tophaceous gout is a recognized cause of carpal tunnel syndrome. Of 2649 carpal
tunnel releases, 15 hands in 13 patients were identified with tophaceous gout in 
the carpal tunnel. The incidence of tophaceous gout in the carpal tunnel was
0.6%. Twelve of 13 patients were male, and 8 of 10 patients with a history of
gout developed carpal tunnel syndrome despite adequate medical treatment. Thus,
consideration should be given for tophi as a cause of carpal tunnel syndrome,
especially in older men despite medical treatment for gout.

PMID: 15369009 [PubMed - indexed for MEDLINE]

358: Folia Med (Plovdiv). 2000;42(4):23-6.

Ultrasonographic evaluation of knee joint cartilage in rheumatoid arthritis
patients.

Batalov AZ, Kuzmanova SI, Penev DP.

Higher Medical Institute, Clinic of Rheumatology 15A Vassil Aprilov St., 4000
Plovdiv, Bulgaria.

The non-invasive methods used to study joint cartilage are restricted in their
scope. No direct visualization of the joint cartilage is possible in conventional
radiology and tomography and the decrease in joint space is only indirect
evidence for joint destruction. CT is a radiologic method for direct
visualization of joint cartilage but its diagnostic precision in the evaluation
of early cartilage lesions is limited because it can not produce an image in a
plane other than the transversal plane perpendicular to the direction of the main
axis of the body and because it has limited spatial resolution. Other methods for
direct visualization of joint cartilage are arthrography and arthroscopy which
are little used in clinical practice because of their invasiveness and limited
indications. MRI is a promising technique but its usage is limited by the high
price and limited accessibility. Our object in the present study was to evaluate 
the significance of arthro-sonography in the diagnosis of early arthritic lesions
of knee cartilage, based on the ultrasonographic assessment of the joint surface 
and cartilage thickness. Femoral cartilage was our choice for the study as there 
is statistically well documented high incidence of early arthritic changes in
this area; moreover, the area is easily accessible for ultrasound evaluation
using a scan perpendicular to the articular surface, incl. the cases with
complete flexion of the knee joint, where the pressure areas of the condyles are 
apositioned to the tibial plateau. Using a 7.5 MHz transducer we managed to
measure and document early arthritic changes in joint thickness and the contour
of the joint surfaces before they can be detected using routine radiologic
methods.

Publication Types: 
    Comparative Study

PMID: 15359509 [PubMed - indexed for MEDLINE]

359: Indian J Med Sci. 2004 Aug;58(8):349-52.

Concomitant gout and rheumatoid arthritis--a case report.

Khosla P, Gogia A, Agarwal PK, Pahuja A, Jain S, Saxena KK.

Department of Medicine, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi - 110
060, India.

We report a case of definite rheumatoid arthritis and co-existing gout. Although 
gout and rheumatoid arthritis are relatively common entities individually, the
co-existence of these two conditions is rare.

Publication Types: 
    Case Reports

PMID: 15345889 [PubMed - indexed for MEDLINE]

360: Arthritis Rheum. 2004 Aug;50(8):2633-9.

Central role of complement membrane attack complex in monosodium urate
crystal-induced neutrophilic rabbit knee synovitis.

Tramontini N, Huber C, Liu-Bryan R, Terkeltaub RA, Kilgore KS.

Pfizer Global Research and Development, Ann Arbor, Michigan, USA.

OBJECTIVE: Monosodium urate monohydrate (MSU) crystals promote gouty inflammation
that is critically mediated by neutrophil recruitment and activation.
Interleukin-8 (IL-8) and closely related chemokines are major neutrophil
chemotaxins in experimental gout. But MSU crystals also activate the classical
and alternative pathways of complement, and MSU crystals directly cleave C5 on
the crystal surface. Unlike IL-8, the roles in acute gout of individual
complement-derived peptides and of the terminal C5b-9 complement components that 
comprise the membrane attack complex (MAC) are unclear. Hence, we studied rabbits
deficient in the MAC component C6 to determine if MAC mediated urate
crystal-induced arthritis. METHODS: We injected C6-deficient and C6-sufficient
rabbit knee joints with 10 mg of pyrogen-free urate crystals and analyzed IL-8
levels, leukocyte influx, and joint inflammation 24 hours later. RESULTS: There
was a significant decrease (>60%) in swelling in MSU crystal-injected knees of
C6-deficient animals as compared with C6-sufficient animals (P < 0.05). An
attenuated rise in MSU crystal-induced joint effusion levels of IL-8 also was
observed, which was concordant with diminished numbers of neutrophils (P < 0.05) 
but not monocytes in MSU crystal-induced knee synovial fluid from C6-deficient
animals. Synovial tissue analysis confirmed mononuclear leukocyte infiltration in
response to MSU crystal injection in all animals, but substantial neutrophil
infiltration only in C6-sufficient animals. CONCLUSION: MAC activation appears to
play a major role in intraarticular IL-8 generation and in neutrophil recruitment
in experimental acute gouty arthritis of the rabbit knee. C6 and MAC activation
may represent novel therapeutic targets for suppression of neutrophil-mediated
joint inflammation in gout.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

PMID: 15334478 [PubMed - indexed for MEDLINE]

361: Hong Kong Med J. 2004 Aug;10(4):261-70.

Comment in:
    Hong Kong Med J. 2004 Oct;10(5):367.

Gout: a review of its aetiology and treatment.

Li EK.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong,
Prince of Wales Hospital, Shatin, Hong Kong. edmundli@cuhk.edu.hk

OBJECTIVE: To review the current understanding of the causes and the management
of gout. DATA SOURCES: Publications on all peer-review literature from MEDLINE
from 1965 to January 2004. STUDY SELECTION: Selected and evaluated by the author.
DATA EXTRACTION: Extracted and evaluated by the author. DATA SYNTHESIS: The
underlying metabolic disorder in gout is hyperuricaemia. Most patients with
hyperuricaemia remain asymptomatic throughout their lifetime. The phase of
asymptomatic hyperuricaemia ends with the first attack of gouty arthritis or
urolithiasis. The risk of gout and stone formation is increased with the degree
and duration of hyperuricaemia. Drugs available for the treatment of acute gouty 
arthritis, such as non-steroidal anti-inflammatory drugs, selective
cyclo-oxygenase 2 inhibitors, systemic corticosteroids, or colchicine, are
effective. For periods between attacks, prophylactic therapy, such as low-dose
colchicine, is effective. In those with recurrent attacks of more than two to
three times yearly, a uric acid-lowering agent as a long-term therapy should be
considered to avoid recurrence and the development of tophaceous gout.
CONCLUSIONS: Effective management of gout can be achieved through better
understanding of the causes of the condition, preventive measures as well as drug
treatment.

Publication Types: 
    Review

PMID: 15299172 [PubMed - indexed for MEDLINE]

362: J Rheumatol. 2004 Aug;31(8):1582-7.

Increasing prevalence of gout and hyperuricemia over 10 years among older adults 
in a managed care population.

Wallace KL, Riedel AA, Joseph-Ridge N, Wortmann R.

Health Economics and Outcomes Research, TAP Pharmaceutical Products Inc., Lake
Forest, IL 60045, USA. kwalla2@uic.edu

OBJECTIVE: To determine whether the prevalence of gout and/or clinically
significant hyperuricemia increased in a managed care population over 10 years.
METHODS: The study was a descriptive analysis utilizing an administrative claims 
database to ascertain 10-year trends in prevalence of gout and/or hyperuricemia. 
Prevalence rates were calculated cross-sectionally for each year (1990-99) and
expressed/compared as rates per 1000 enrollees. RESULTS: The prevalence of gout
and/or hyperuricemia in the overall population increased by about 2 cases per
1000 enrollees over 10 years. In the > 75 year age group, rates increased from 21
per 1000 persons in 1990 to 41 per 1000 in 1999. In the 65-74 year age group,
prevalence increased from between 21 and 24 per 1000 persons in the years 1990-92
to over 31 per 1000 during the years 1997-99. Prevalence rates in younger age
groups (< 65 years) stayed consistently low during the years under study. There
were sex differences in most age groups, with men having the greater burden of
disease at every time point. CONCLUSION: Prevalence of gout and/or hyperuricemia 
in the overall study population increased during the 10-year period. When
stratified by age, there were increases in prevalence among groups over age 65 in
both sexes. Although gout prevalence increased in both sexes over the 10-year
period, men still had most of the burden of disease. In ages younger than 65, men
had 4 times higher prevalence than women (4:1 ratio), but in the older age groups
(> 65), the gender gap narrowed to 1 woman to every 3 men with gout and/or
hyperuricemia (3:1 ratio).

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15290739 [PubMed - indexed for MEDLINE]

363: J Rheumatol. 2004 Aug;31(8):1575-81.

Compliance with allopurinol therapy among managed care enrollees with gout: a
retrospective analysis of administrative claims.

Riedel AA, Nelson M, Joseph-Ridge N, Wallace K, MacDonald P, Becker M.

Research and Data Services Group, Ingenix Pharmaceutical Services, Eden Prairie, 
Minnesota 55344, USA.

OBJECTIVE: Poor compliance with gout medications has been recognized, but seldom 
studied. We investigated compliance with allopurinol among managed care enrollees
suspected to have gout. METHODS: This was a retrospective, administrative
claims-based analysis of patients with gout. Compliance with allopurinol was
measured using prescription-fill dates and days-supplied amounts. Compliance was 
defined for each prescription period as the presumed use of allopurinol on at
least 80% of the days of that period. RESULTS: Of 9482 patients identified, 65.9%
filled at least one prescription for allopurinol during the 24 month followup
period; 10.4% of allopurinol users filled one prescription and then discontinued 
use. Of the remaining patients, 13.7% never achieved compliance with therapy; 18%
were compliant throughout the entire followup period. Patients were compliant
with therapy for an average of 56% of their treatment periods and noncompliant
for an average of 44%. In multivariate analysis, male sex was associated with
decreased compliance (p < 0.01), although the effect was mitigated by increasing 
age. For subjects of both sexes, increasing age was associated with increased
compliance (p < 0.05). CONCLUSION: Compliance with allopurinol in this population
was low. Because untreated gouty arthritis can lead to serious adverse outcomes
(such as recurrent gouty arthritis, chronic gouty arthropathy, tophi, and
urolithiasis) that are usually avoidable with antihyperuricemic therapy, efforts 
to achieve better compliance are warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15290738 [PubMed - indexed for MEDLINE]

364: Prog Transplant. 2004 Jun;14(2):143-7.

Treating gout in kidney transplant recipients.

Baroletti S, Bencivenga GA, Gabardi S.

Brigham and Women's Hospital, Boston, MA, USA.

OBJECTIVE: To review the etiology, treatment, and preventive strategies of
hyperuricemia and gout in kidney transplant recipients. DATA SOURCES: Primary
literature was obtained via Medline (1966-June 2003). STUDY SELECTION AND DATA
EXTRACTION: Studies evaluating treatment and prevention of hyperuricemia and gout
in kidney transplantation were considered for evaluation. English-language
studies were selected for inclusion. DATA SYNTHESIS: Approximately 14,000 kidney 
transplantations were performed in the United States in 2003, and of those
transplant recipients, nearly 13% will experience a new onset of gout. The
prevalence of hyperuricemia is even greater. There are several mechanisms by
which hyperuricemia and gout develop in kidney transplant recipients.
Medication-induced hyperuricemia and renal dysfunction are 2 of the more common
mechanisms. Prophylactic and treatment options include allopurinol, colchicine,
corticosteroids, and, if absolutely necessary, nonsteroidal antiinflammatory
drugs. CONCLUSION: It is generally recommended to decide whether the risks of
prophylactic therapy and treatment outweigh the benefits. Often, the risk of
adverse events associated with agents to treat these ailments tends to outweigh
the benefits; therefore, treatment is usually reserved for symptomatic episodes
of acute gout. Practitioners must also decide if changes in immunosuppressive
regimens may be of benefit on a patient-by-patient basis.

Publication Types: 
    Review

PMID: 15264458 [PubMed - indexed for MEDLINE]

365: Hum Pathol. 2004 Jul;35(7):897-9.

Intestinal pseudotumorous gouty nodulosis: a colonic tophus without manifestation
of gouty arthritis.

Wu H, Klein MJ, Stahl RE, Sanchez MA.

Department of Pathology, Mount Sinai School of Medicine, New York, NY, USA.

A 37-year-old black woman with nephritis secondary to systemic lupus
erythematosus, steroid-induced diabetes mellitus, and hypertension presented with
fever, nausea, vomiting, and right upper quadrant abdominal pain with distension.
Abdominal computed tomography (CT) scan revealed a colonic mass, and CT- guided
fine-needle aspiration demonstrated birefringent crystalline material. After
several weeks of antibiotic therapy, the patient underwent laparoscopic
examination followed by extended right hemicolectomy for a large mass in the
subserosa of the transverse colon. Pathological examination of this mass revealed
it to be a gouty tophus. To our knowledge, no case of tophaceous gout presenting 
as an intestinal mass has previously been reported.

Publication Types: 
    Case Reports

PMID: 15257557 [PubMed - indexed for MEDLINE]

366: Am J Hum Genet. 2004 Sep;75(3):498-503. Epub 2004 Jul 13.

Genomewide scan for gout in taiwanese aborigines reveals linkage to chromosome
4q25.

Cheng LS, Chiang SL, Tu HP, Chang SJ, Wang TN, Ko AM, Chakraborty R, Ko YC.

Division of Information Science, City of Hope Medical Center, Duarte, CA, USA.

Gout is a disorder of uric-acid metabolism. The Pacific Austronesian population, 
including Taiwanese aborigines, has a remarkably high prevalence of hyperuricemia
and gout, which suggests a founder effect across the Pacific region. We report
here a genomewide linkage study of 21 multiplex pedigrees with gout from an
aboriginal tribe in Taiwan. From observations of familial clustering, early onset
of gout, and clinically severe manifestations, we hypothesized that a major gene 
plays a role in this trait. Using 382 random polymorphic markers spread across 22
autosomes, we demonstrated a highly significant linkage for gout at marker
D4S2623 on chromosome 4q25 (P=.0002 by nonparametric linkage [the NPL(all)
statistic]; empirical P=.0006; LOD=4.3, P=4.4x10-6 by logistic regression). When 
alcohol consumption was included as a covariate in the model, the LOD score
increased to 5.66 (P=1.3x10-6). Quantitative traits, including serum uric acid
and creatinine, also showed a moderate linkage to this region. To our knowledge, 
this is the first genome-scan report to identify a genetic locus harboring a
gout-susceptibility gene.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 15252757 [PubMed - indexed for MEDLINE]

367: Transplantation. 2004 May 27;77(10):1576-80.

Reduced incidence of hyperuricemia, gout, and renal failure following liver
transplantation in comparison to heart transplantation: a long-term follow-up
study.

Shibolet O, Elinav E, Ilan Y, Safadi R, Ashur Y, Eid A, Zamir G, Fridlander M,
Bdolah-Abram T, Shouval D, Admon D.

Liver Unit, Department of Medicine, Hadassah University Hospital, PO Box 12000,
Jerusalem 91120, Israel. shibolet@hadassah.org.il

BACKGROUND: Hyperuricemia and gout are common complications of heart
transplantation, reaching a prevalence of 84% and 30%, respectively, in heart
transplant recipients. In contrast, they are seldom reported following orthotopic
liver transplantation (OLT). METHODS: We retrospectively evaluated 75 consecutive
liver transplant recipients and 47 consecutive heart transplant recipients,
followed for at least 3 years after transplantation in a single transplantation
center in Jerusalem, Israel. Data was collected on demographic and clinical
variables, levels of uric acid, the occurrence of gout, renal function, and
variables effecting hyperuricemia, such as weight and medications. RESULTS:
Clinical gout was significantly more prevalent in heart recipients than in liver 
recipients (25.5% and 2.6%, respectively). Hyperuricemia was present in 100% of
heart recipients, with an average uric acid level of 451 micromol/l, as compared 
with 85.7% and 403 micromol/l for liver recipients (P < 0.001 for both
variables). Univariate analysis identified several parameters which significantly
influenced the difference in hyperuricemia and gout among the two groups
including age, gender, rejection episodes, hypertension, diabetes mellitus, the
level of uric acid prior to transplantation, and the use of cyclosporine A,
diuretics, steroids, and aspirin. Use of tacrolimus and azathioprine were
associated with decreased incidence of hyperuricemia and gout. Multivariate
analysis identified the type of transplantation as the only independent risk
factor predicting the development of hyperuricemia and gout. CONCLUSION: Clinical
gout and hyperuricemia were significantly more prevalent in heart recipients than
in liver recipients. The disparity can be explained by differences in age, gender
and renal function among the groups, as well as by the use of different
medication regimens.

Publication Types: 
    Comparative Study

PMID: 15239625 [PubMed - indexed for MEDLINE]

368: Arthritis Rheum. 2004 Jun 15;51(3):321-5.

A retrospective study of the relationship between serum urate level and recurrent
attacks of gouty arthritis: evidence for reduction of recurrent gouty arthritis
with antihyperuricemic therapy.

Shoji A, Yamanaka H, Kamatani N.

Tokyo Women's Medical University, Tokyo, Japan.

OBJECTIVE: To evaluate the proposed relationship between persistent reduction of 
serum urate into the subsaturating range and reduction in the frequency of acute 
gouty attacks. METHODS: We retrospectively examined data derived from 267
patients who had experienced at least 1 gouty attack before their first visit to 
our clinic. Serum urate concentration, history of recurrent gouty attacks, and
information about antihyperuricemic drug use were collected on each visit for up 
to 3 years from the first visit of each patient. Data derived from visits >1 year
after study entry were subjected to statistical analysis. RESULTS: When adjusted 
for baseline serum urate level and the number of gouty attacks prior to study
entry, reduction of followup serum urate concentration and antihyperuricemic drug
use were each significantly associated with a reduced risk of gouty attacks (odds
ratio [OR] 0.42, 95% confidence interval [95% CI] 0.31-0.57; OR 0.22, 95% CI
0.10-0.47, respectively). CONCLUSION: The data indicate that reduction of serum
urate concentrations to 6 mg/dl or lower will eventually result in a reduced
frequency or prevention of future gouty attacks.

PMID: 15188314 [PubMed - indexed for MEDLINE]

369: Drug Ther Bull. 2004 May;42(5):37-40.

Gout in primary care.

[No authors listed]

Gout affects around 1% of people in the UK, most aged over 45 years. The
condition, which is five times more common in men than women, usually presents as
a painful inflammatory monoarthritis, which can be diagnosed clinically and
successfully treated with a high dose of an NSAID. Problems arise when the
features are atypical or when high doses of an NSAID are inappropriate. Also;
there is no robust evidence to guide when to start prophylactic therapy or what
advice to give on lifestyle changes. Here we review current practice and offer
advice on managing patients with this increasingly common condition,
concentrating on approaches to be taken by the non-specialist.

Publication Types: 
    Review

PMID: 15179818 [PubMed - indexed for MEDLINE]

370: Curr Rheumatol Rep. 2004 Jun;6(3):235-9.

Treatment of acute gouty arthritis: one physician's approach and where this
management stands relative to developments in the field.

Wortmann RL.

Department of Internal Medicine, The University of Oklahoma College of Medicine, 
4502 East 41st Street, Tulsa, OK 74137, USA. Robert-wortmann@ouhsc.edu

An attack of acute gouty arthritis is one the most painful episodes that can be
experienced by humans. Fortunately, there are three classes of agents that can
effectively terminate the acute attack. These include colchicine, nonsteroidal
anti-inflammatory drugs, and glucocorticoids. If therapy with any one of these is
initiated promptly after the onset of symptoms, relief should occur quickly.
Recent observations have increased the knowledge of crystal-induced acute
inflammatory responses. These observations allow a better understanding of the
mechanisms of action of these agents and provide the rationale for using them in 
combination in severe or refractory cases.

Publication Types: 
    Review

PMID: 15134604 [PubMed - indexed for MEDLINE]

371: Ann Rheum Dis. 2005 Jan;64(1):85-8. Epub 2004 Apr 28.

Contribution of polymorphisms in the apolipoprotein AI-CIII-AIV cluster to
hyperlipidaemia in patients with gout.

Cardona F, Tinahones FJ, Collantes E, Escudero A, García-Fuentes E, Soriguer FJ.

Servicio de Endocrinología y Nutrición, Complejo Hospitalario Universitario
Carlos Haya, Malaga, Spain. fernando.cardona.exts@juntadeandalucia.es

BACKGROUND: Studies have shown that hyperuricaemia is independently related to
the insulin resistance syndrome and that polymorphisms of the apolipoprotein
AI-CIII-AIV cluster are also related to insulin resistance. OBJECTIVE: To study
the prevalence of polymorphisms of the apolipoprotein AI-CIII-AIV cluster in
persons with gout and to determine whether these polymorphisms contribute to the 
pathophysiology of gout or to altered lipid concentrations. METHODS: Plasma
cholesterol, triglycerides, uric acid, VLDL, LDL, IDL, and HDL triglycerides,
cholesterol, and the renal excretion of uric acid were measured in 68 patients
with gout with gout and 165 healthy subjects. Polymorphisms were studied by
amplification and RFLP in all subjects, using XmnI and MspI in the apolipoprotein
AI gene and SstI in the apolipoprotein CIII gene. RESULTS: The A allele at
position -75 bp in the apolipoprotein AI gene was more common in patients with
gout than in controls (p = 0.01). Levels of cholesterol, triglycerides, uric
acid, basal glycaemia, and HDL cholesterol were higher in the patients (p<0.001).
In the patients there was also an interaction between mutations at the two
polymorphic loci studied in the apolipoprotein AI gene (p = 0.04). An absence of 
the mutation at position -75 bp of the apolipoprotein AI gene resulted in
increased plasma triglyceride levels. CONCLUSIONS: Gouty patients have an altered
allelic distribution in the apolipoprotein AI-CIII-AIV cluster, which could lead 
to changes in levels of lipoproteins. This is not caused by a single mutation but
rather by a combination of different mutations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15115711 [PubMed - indexed for MEDLINE]

372: Clin Ther. 2004 Mar;26(3):399-406.

A single-blind, randomized, controlled trial to assess the efficacy and
tolerability of rofecoxib, diclofenac sodium, and meloxicam in patients with
acute gouty arthritis.

Cheng TT, Lai HM, Chiu CK, Chem YC.

Section of Allergy, Immunology and Rheumatology, Department of Internal Medicine,
Chang Gung Memorial Hospital, Taiwan, Republic of China. tiantsai@ms2.hinet.net

BACKGROUND: Acute attacks of gouty arthritis are characterized by the rapid onset
of severe pain, swelling, and erythema of the affected joint. Nonsteroidal
anti-inflammatory drugs are considered the drugs of first choice for treating
acute gout. Rofecoxib is a specific cyclooxygenase-2 inhibitor, which has
demonstrated analgesic efficacy in the setting of acute pain. Whether it is
effective in the treatment of acute gouty arthritis remains to be evaluated.
OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of
rofecoxib compared with diclofenac sodium sustained release (SR) and meloxicam in
the treatment of acute gouty arthritis. METHODS: In this single-blind,
randomized, controlled, parallel-group study, patients aged > or =18 years with
acute gout within 48 hours of onset were randomized to receive oral treatment
with 2 tablets of rofecoxib (25 mg), diclofenac (75 mg), or meloxicam (7.5 mg)
once daily for 7 days. The primary outcome measures were patients global
assessment of response to therapy and investigator assessment of response to
therapy on days 3 and 8. Other efficacy measurements included investigator
assessment of total inflammatory scores on days 3 and 8 and patient assessment of
pain intensity during the first 12 hours of treatment. RESULTS: Sixty-two
patients (53 men, 9 women; mean [SD] age, 51.1 [12.1] years) were assigned to
receive rofexocib (n = 20), diclofenac (n = 21), or meloxicam (n = 21). For
patient global response to therapy on days 3 and 8, rofecoxib was associated with
analgesic efficacy in significantly more patients compared with meloxicam (84.2% 
vs 40.0% of patients [ P=0.005] and 94.7% vs 60.0% of patients [ P=0.02],
respectively); no significant differences versus diclofenac were found.
Similarly, for investigator global assessment of response to therapy, a greater
percentage of responders was found in the rofecoxib group compared with the
meloxicam group on day 3 (88.9% vs 40.0% of patients [ P=0.02 ]), but the
difference was not significant on day 8. A greater percentage of responders was
found in the rofecoxib group compared with the diclofenac group on day 3 (88.9%
vs 47.3% [ P=0.007 ]), but the difference was not significant on day 8. Compared 
with baseline, all regimens showed significant improvement in total inflammatory 
scores on days 3 and 8 (all P<0.01 ). During the first 12 hours after dosing,
pain intensity score was significantly reduced with rofecoxib starting at 0.5
hours ( P<0.05 ), but not with diclofenac or meloxicam. Clinical adverse events
(AEs) were reported in 4 (20.0%), 7 (33.3%), and 6 (28.6%) patients in the
rofecoxib, diclofenac, and meloxicam groups, respectively; the most common AEs
reported were edema in 1 patient each in the rofecoxib (5.0%) and meloxicam
(4.8%) groups and 2 patients (9.5%) in the diclofenac group and abdominal (1
[5.0%], 1 [4.8%], and 2 [9.5%], respectively). No significant differences in
tolerability were found among the 3 treatment groups. CONCLUSIONS: In this study 
of patients with acute gouty arthritis, rofecoxib 50 mg once daily provided more 
effective treatment than diclofenac sodium SR 150 mg and meloxicam 15 mg
administered orally once daily for 7 days in > or = 1 efficacy assessment of
overall analgesic effect on day 3 or day 8. Rofecoxib achieved a rapid onset of
pain relief, demonstrating significant improvement 30 minutes after dosing. All
of the regimens appeared well tolerated in the population studied.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15110132 [PubMed - indexed for MEDLINE]

373: Reumatismo. 2004 Jan-Mar;56(1):61-6.

"Like a virgin": Absence of rheumatoid arthritis and treponematosis, good
sanitation and only rare gout in Italy prior to the 15th century.

Rothschild BM, Coppa A, Petrone PP.

Arthritis Center of Northeast Ohio, Youngstown, 44512, USA. bmr@neoucom.edu

OBJECTIVES: This study was conducted to test several hypotheses: 1. That
rheumatoid arthritis and syphilis were New World diseases, only transmitted to
the Old World subsequent to the passages of Christopher Columbus; 2. To
indirectly test the hypothesis that lead poisoning was prevalent in Roman Italy
by looking for its byproduct, gout; 3. To test the hypothesis of compromised
sanitation in ancient Italy, on the basis of spondyloarthropathy frequency; and
4. To assess variation of trauma frequencies in ancient Italy, by examining
frequency of focal periosteal reaction. METHODS: Skeletons from sites ranging
from the Bronze Age to the Black Plague epidemic of 1485-1486 were
macroscopically evaluated for focal periosteal reaction and for the cardinal
signs of rheumatoid arthritis, treponemal disease, gout and spondyloarthropathy. 
RESULTS: Examination of 688 individuals revealed low frequency of focally
distributed periosteal reaction (bumps) in sites dated from the 3400-700 years
before present, sharply increasing in the 15th century. Diffuse periosteal
reaction was present only as isolated occurrences secondary to hypertrophic
osteoarthropathy and sabre shin reaction was notably absent. Erosive disease was 
uncommon and always oligoarticular in distribution. No marginal erosions were
present, with the exception of an isolated metatarsal with classic overhanging
edge sign of gout. Subchondral erosions, peripheral joint fusion and axial
skeletal involvement identified spondyloarthropathy frequencies of 1-3%,
independent of the antiquity of the site. CONCLUSIONS: Italy, prior to Columbus
was like a virgin. Rheumatoid arthritis and treponemal disease (specifically
syphilis) were not present, further supporting the contention that they are New
World-derived diseases. Periosteal signs of minor trauma were rare prior to
fifteenth century plague times. This suggests a potential role of domestic (as
opposed to outside environment activities) in is development. The hypothesis for 
a role of lead poisoning in the demise of the Roman Empire is falsified by the
rarity of gout. The frequency of spondyloarthropathy was significantly below that
found in sanitarily challenged populations, suggesting high standards of hygiene 
in ancient Italy.

Publication Types: 
    Historical Article

PMID: 15105912 [PubMed - indexed for MEDLINE]

374: Curr Opin Rheumatol. 2004 May;16(3):282-6.

Gout.

Pascual E, Pedraz T.

Sección de Reumatología, Hospital General Universitario de Alicante, Maestro
Alonso 109, 03010 Alicante, Spain. pascual_eli@gva.es

PURPOSE OF THE REVIEW: We have reviewed the latest publications on epidemiology
of gout; also there have been new insights into the regulation of the
inflammation resulting from the regular interaction occurring between MSU
crystals and cells in both asymptomatic and symptomatic gouty joints. Finally we 
review different publications of clinical interest. RECENT FINDINGS: The
incidence of gout has been found to be increasing, and the disease starts at an
earlier age; this likely relates to changes in dietary habits that lead to the
development of the insulin resistance syndrome to which hyperuricemia, and thus
gout, relates. Dietary modifications to correct the insulin resistance syndrome
and reduce uricemia by increasing renal clearance of urate have heath
consequences that go far beyond their beneficial effect on gout. Monosodium urate
crystals and cells interact in the asymptomatic joints of gouty patients. The
mechanisms that trigger a gouty attack with this background and those responsible
for the self-limitation of gouty attacks are not understood. The degree of
maturation of the monocytes-macrophages present in the fluid appears to modulate 
the consequences of the crystal-cell interaction and gives a hint of how from the
crystal-cell interaction may result in such divergent consequences as intense
inflammation or the absence of symptoms. Interest in gout treatment continues, as
shown by the number of papers on the subject reviewed. In most cases, gout is an 
easy disease to treat, but we do not have enough information about how to handle 
those few patients with "difficult" disease, and what we refer colloquially to as
difficult gout has not been properly defined yet. SUMMARY: Gout incidence and
severity appear to be increasing likely in relation to dietary habits. Switching 
the pattern of secretion of inflammatory mediators with maturating macrophages
which contain MSU crystals may be the key to self limitation of gouty attacks. We
must define better which gout is a "difficult" one.

Publication Types: 
    Review

PMID: 15103259 [PubMed - indexed for MEDLINE]

375: Lancet. 2004 Apr 17;363(9417):1277-81.

Comment in:
    Lancet. 2004 Apr 17;363(9417):1251-2.    Lancet. 2004 Jul 17-23;364(9430):246-7; author reply 247.

Alcohol intake and risk of incident gout in men: a prospective study.

Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G.

Rheumatology Unit, Department of Medicine, Massachusetts General Hospital,
Harvard Medical School, Boston, MA 02114, USA. hchoi@partners.org

BACKGROUND: The association between alcohol consumption and risk of gout has been
suspected since ancient times, but has not been prospectively confirmed.
Additionally, potential differences in risk of gout posed by different alcoholic 
beverages have not been assessed. METHODS: Over 12 years (1986-98) we used
biennial questionnaires to investigate the relation between alcohol consumption
and risk of incident gout in 47?150 male participants with no history of gout at 
baseline. We used a supplementary questionnaire to ascertain whether reported
cases of gout met the American College of Rheumatology survey gout criteria.
FINDINGS: We documented 730 confirmed incident cases of gout. Compared with men
who did not drink alcohol, the multivariate relative risk (RR) of gout was 1.32
(95% CI 0.99-1.75) for alcohol consumption 10.0-14.9 g/day, 1.49 (1.14-1.94) for 
15.0-29.9 g/day, 1.96 (1.48-2.60) for 30.0-49.9 g/day, and 2.53 (1.73-3.70) for >
or =50 g/day (p for trend <0.0001). Beer consumption showed the strongest
independent association with the risk of gout (multivariate RR per 12-oz serving 
per day 1.49; 95% CI 1.32-1.70). Consumption of spirits was also significantly
associated with gout (multivariate RR per drink or shot per day 1.15; 95% CI
1.04-1.28); however, wine consumption was not (multivariate RR per 4-oz serving
per day 1.04; 95% CI 0.88-1.22). INTERPRETATION: Alcohol intake is strongly
associated with an increased risk of gout. This risk varies substantially
according to type of alcoholic beverage: beer confers a larger risk than spirits,
whereas moderate wine drinking does not increase the risk.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15094272 [PubMed - indexed for MEDLINE]

376: Radiol Clin North Am. 2004 Jan;42(1):169-84.

Gout: a clinical and radiologic review.

Monu JU, Pope TL Jr.

Department of Musculoskeletal Radiology, University of Rochester School of
Medicine and Dentistry, 601 Elmwood Avenue, Box 648, Rochester, NY 14642, USA.
johnny_monu@urmc.rochester.edu

Gout is a group of diseases characterized by arthritis and results from a
disturbance of urate metabolism with the deposition of monosodium urate crystals 
in the joints and soft tissues. Often, but not invariably, the serum urate levels
are elevated as a result of overproduction or underexcretion of uric acid.
Clinical manifestations include acute and chronic arthritis, tophaceous deposits,
interstitial renal disease, and uric acid nephrolithiasis. The diagnosis is based
on the identification of uric acid crystals in joints, tissues, or body fluids.
Acute episodes are treated with colchicine, NSAIDs, or steroids. Long-term
management includes treatment with uricosuric agents or xanthine oxidase
inhibitors.

Publication Types: 
    Review

PMID: 15049530 [PubMed - indexed for MEDLINE]

377: Ann Allergy Asthma Immunol. 2004 Mar;92(3):374-6.

Intravenous desensitization to allopurinol in a heart transplant patient with
gout.

Schumacher MJ, Copeland JG.

Department of Pediatrics, University of Arizona Health Sciences Center, Tucson,
Arizona 85724, USA. schumach@u.arizona.edu

BACKGROUND: Oral desensitization with allopurinol presents a problem for patients
with allopurinol hypersensitivity and gout that needs to be controlled rapidly.
To our knowledge, only 1 case report of intravenous (i.v.) desensitization has
been previously published. OBJECTIVE: To present a case report of a patient with 
cutaneous reactions to allopurinol who underwent i.v. allopurinol
desensitization. METHODS: Intravenous infusion of allopurinol was performed using
an escalating, 19-dose protocol. RESULTS: No adverse reactions were precipitated 
by 2 i.v., escalating dose procedures, allowing continuation of effective
treatment of the patient's hyperuricemia. CONCLUSIONS: This case of safe and
effective desensitization with allopurinol by the i.v. route should emphasize the
need for a trial of this protocol in additional patients in whom rapid
desensitization would be advantageous.

PMID: 15049403 [PubMed - indexed for MEDLINE]

378: Vet Clin Pathol. 2004;33(1):43-6.

Synovial fluid from an African spur-thighed tortoise (Geochelone sulcata).

Casimire-Etzioni AL, Wellehan JF, Embury JE, Terrell SP, Raskin RE.

Clinical Patholology Service, Department of Physiological Sciences, College of
Veterinary Medicine, University of Florida, Gainesville, FL, USA.
acasimir@purdue.edu

A 4.5-year old, male African spur-thighed tortoise (Geochelone sulcata) was
presented to the University of Florida Veterinary Teaching Hospital with a 2-week
history of lethargy, anorexia, constipation, dyspnea, and coughing up fluid or
vomiting. Laboratory results included an inflammatory leukogram and a marked
increase in plasma uric acid concentration. Synovial fluid from multiple joints
was thick, chalky white, and opaque, with a grainy consistency. Microscopically, 
the fluid contained numerous brown, needle-like crystals consistent with urates
(gout). Gross necropsy findings and histopathology confirmed a diagnosis of
systemic gout, with urate deposition, gout tophi, and underlying necrosis in
multiple organs, including kidneys, lung, and liver. Dehydration with concurrent 
renal insufficiency may have impaired urate excretion and led to a build-up of
urates in the blood and tissues of this tortoise. A high protein diet also may
have contributed to the development of gout. Cytologic evaluation of synovial
fluid can be used as a quick and definitive tool to diagnose gout in tortoises.

Publication Types: 
    Case Reports

PMID: 15048627 [PubMed - indexed for MEDLINE]

379: Singapore Med J. 2004 Mar;45(3):125-6.

Mucinous adenocarcinoma of the renal pelvis associated with lithiasis and chronic
gout.

Kaur G, Naik VR, Rahman MN.

Department of Pathology, Universiti Sains Malaysia, Kota Bharu, 16150 Kelantan,
Malaysia. gurjeet@notes.usm.my

Diffusely-infiltrating mucinous adenocarcinoma of the renal pelvis associated
with lithiasis and chronic gout is reported in a 61-year-old Malay man. The
patient underwent left nephrectomy and vesiculo-lithotomy. This tumour is
postulated to arise in response to chronic irritation of the urothelium.

Publication Types: 
    Case Reports

PMID: 15029415 [PubMed - indexed for MEDLINE]

380: Arthritis Rheum. 2004 Mar;50(3):937-43.

Quality of care indicators for gout management.

Mikuls TR, MacLean CH, Olivieri J, Patino F, Allison JJ, Farrar JT, Bilker WB,
Saag KG.

University of Nebraska Medical Center, and Omaha Veterans Administration Medical 
Center, Omaha, Nebraska 68198-3025, USA. tmikuls@unmc.edu

OBJECTIVE: Despite the significant health impact of gout, there is no consensus
on management standards. To guide physician practice, we sought to develop
quality of care indicators for gout management. METHODS: A systematic literature 
review of gout therapy was performed using the Medline database. Two abstractors 
independently reviewed each of the articles for relevance and satisfaction of
minimal inclusion criteria. Based on the review of the literature, 11 preliminary
quality indicators were developed and then reviewed and refined by an initial
feasibility panel of community and academic rheumatologists. A twelfth indicator 
was added at the request of the first panel. Using a modification of the
RAND/University of California at Los Angeles appropriateness method (bridging
teleconference and white-board Internet technology were added), a second expert
panel rated each of the proposed indicators for validity using a 9-point scale,
in which ratings of 1-3, 4-6, and 7-9 were considered "invalid," "indeterminate,"
and "highly valid," respectively. Indicators were considered valid if the median 
panel rating was > or =7 and there was no evidence of panel disagreement (defined
to occur when 2 of 6 panelists provided a validity rating of 1-3 and 2 panelists 
provided a validity rating of 7-9). RESULTS: Ten of the 12 draft indicators were 
rated to be valid by our second expert panel. Validated indicators pertained to
1) the use of urate-lowering medications in chronic gout, 2) the use of
antiinflammatory drugs, and 3) counseling on lifestyle modifications. CONCLUSION:
Using a combination of evidence and expert opinion, 10 indicators for quality of 
gout care were developed. These indicators represent an important initial step in
quality improvement initiatives for gout care.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.
    Review
    Validation Studies

PMID: 15022337 [PubMed - indexed for MEDLINE]

381: N Engl J Med. 2004 Mar 11;350(11):1093-103.

Comment in:
    N Engl J Med. 2004 Jun 10;350(24):2520-1; author reply 2520-1.    N Engl J Med. 2004 Jun 10;350(24):2520-1; author reply 2520-1.    N Engl J Med. 2004 Mar 11;350(11):1071-3.

Purine-rich foods, dairy and protein intake, and the risk of gout in men.

Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G.

Rheumatology Unit, Department of Medicine, Massachusetts General Hospital,
Boston, MA 02114, USA. hchoi@partners.org

BACKGROUND: Various purine-rich foods and high protein intake have long been
thought to be risk factors for gout. Similarly, the possibility that the
consumption of dairy products has a role in protecting against gout has been
raised by metabolic studies. We prospectively investigated the association of
these dietary factors with new cases of gout. METHODS: Over a 12-year period, we 
prospectively examined the relationship between purported dietary risk factors
and new cases of gout among 47,150 men who had no history of gout at base line.
We used a supplementary questionnaire to ascertain whether participants met the
American College of Rheumatology survey criteria for gout. Diet was assessed
every four years by means of a food-frequency questionnaire. RESULTS: During the 
12 years of the study, we documented 730 confirmed new cases of gout. The
multivariate relative risk of gout among men in the highest quintile of meat
intake, as compared with those in the lowest quintile, was 1.41 (95 percent
confidence interval, 1.07 to 1.86; P for trend = 0.02), and the corresponding
relative risk associated with seafood intake was 1.51 (95 percent confidence
interval, 1.17 to 1.95; P for trend = 0.02). In contrast, the incidence of gout
decreased with increasing intake of dairy products; the multivariate relative
risk among men in the highest quintile, as compared with those in the lowest
quintile, was 0.56 (95 percent confidence interval, 0.42 to 0.74; P for trend
<0.001). The level of consumption of purine-rich vegetables and the total protein
intake were not associated with an increased risk of gout. CONCLUSIONS: Higher
levels of meat and seafood consumption are associated with an increased risk of
gout, whereas a higher level of consumption of dairy products is associated with 
a decreased risk. Moderate intake of purine-rich vegetables or protein is not
associated with an increased risk of gout. Copyright 2004 Massachusetts Medical
Society

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15014182 [PubMed - indexed for MEDLINE]

382: Rheumatology (Oxford). 2004 Mar;43(3):349-52. Epub 2004 Jan 6.

Systemic lupus erythematosus and gouty arthritis: an uncommon association.

Bajaj S, Fessler BJ, Alarcón GS.

Division of Clinical Immunology and Rheumatology, Department of Medicine, The
University of Alabama at Birmingham, Birmingham, AL 35294-3408, USA.

OBJECTIVE: To examine the frequency of gouty arthritis in patients with systemic 
lupus erythematosus (SLE) and elucidate the clinical factors that predispose to
this occurrence. METHODS: A chart review of in-patients (1989-2001) and
out-patients (1999-2001) with ICD9 billing codes for gouty arthritis/tophaceous
gout and SLE was performed. Twenty-six patients were identified. Patients meeting
American College of Rheumatism criteria for SLE and crystal-proven gout or a
self-limited inflammatory arthritis felt to be crystal-induced (i.e. definite
gout) were included. RESULTS: Ten patients were identified. Their mean age was
46.5 yr; 80% were African-American and 70% were women. Nine of the ten had lupus 
nephritis and four had undergone renal transplantation. An acute worsening of
renal function unrelated to lupus activity preceded almost all gout flares. Lupus
activity at the time of the first gout attack as measured by the Systemic Lupus
Activity Measure (SLAM) was low. Eight patients were on prednisone (mean dose 8
mg/day) for their SLE at the time the attack of gout occurred. CONCLUSIONS: Gouty
arthritis is uncommon in SLE; it occurs primarily in patients with long-standing 
SLE and nephritis. Worsening renal function usually preceded gout attacks, but
SLE disease activity was minimal. Crystal-induced arthritis should be included in
the differential diagnosis of a lupus patient presenting with acute inflammatory 
arthritis because the long-term treatment of the two conditions differs
substantially.

PMID: 14963203 [PubMed - indexed for MEDLINE]

383: Arthritis Rheum. 2004 Feb;50(2):598-606.

Efficacy and safety profile of treatment with etoricoxib 120 mg once daily
compared with indomethacin 50 mg three times daily in acute gout: a randomized
controlled trial.

Rubin BR, Burton R, Navarra S, Antigua J, Londoño J, Pryhuber KG, Lund M, Chen E,
Najarian DK, Petruschke RA, Ozturk ZE, Geba GP.

University of North Texas, Fort Worth, TX, USA.

OBJECTIVE: To evaluate the efficacy and safety of etoricoxib and indomethacin in 
the treatment of patients with acute gout. METHODS: A randomized, double-blind,
active-comparator study was conducted at 42 sites. A total of 189 men and women
(> or =18 years of age) who were experiencing an acute attack (< or =48 hours) of
clinically diagnosed gout were treated for 8 days with etoricoxib, 120 mg/day (n 
= 103), or indomethacin, 50 mg 3 times a day (n = 86). The primary efficacy end
point was the patient's assessment of pain in the study joint (0-4-point Likert
scale) over days 2-5. Safety was assessed by adverse experiences (AEs) occurring 
during the trial. RESULTS: Etoricoxib demonstrated clinical efficacy comparable
to that of indomethacin in terms of the patient's assessment of pain in the study
joint. The difference in the mean change from baseline over days 2-5 was -0.08
(95% confidence interval -0.29, 0.13) (P = 0.46), which fell within the
prespecified comparability bounds of -0.5 to 0.5. Secondary end points over the
8-day study, including the onset of efficacy, reduction in signs of inflammation,
and patient's and investigator's global assessments of response to therapy,
confirmed the comparable efficacy of the two treatments. The etoricoxib-treated
patients had a numerically lower incidence of AEs (43.7%) than did the
indomethacin-treated patients (57.0%) and a significantly lower incidence of
drug-related AEs (16.5% versus 37.2%; P < 0.05). CONCLUSION: Etoricoxib at a
dosage of 120 mg once daily was confirmed to be an effective treatment for acute 
gout. Etoricoxib was comparable in efficacy to indomethacin at a dosage of 50 mg 
3 times daily, and it was generally safe and well tolerated.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14872504 [PubMed - indexed for MEDLINE]

384: Orthopedics. 2004 Jan;27(1):18, 90-2.

Radiologic case study. Gouty tophus involving the distal quadriceps tendon.

Bond JR, Sim FH, Sundaram M.

Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA.

This case depicts an unusual presentation of gout, which could be mistaken for
sarcoma. The radiographic and MRI findings suggest gout whereas the CT appearance
is most specific. Therefore, CT should be considered when MRI demonstrates low to
intermediate T2 signal in a heterogeneously enhancing soft-tissue mass around a
joint, tendon, or bursa, especially when radiographs show adjacent erosion with a
sclerotic margin. Gouty tophus is not excluded by a normal serum uric acid level.
Computed tomography or ultrasound can be used to guide needle biopsy to provide
diagnostic tissue.

Publication Types: 
    Case Reports

PMID: 14763524 [PubMed - indexed for MEDLINE]

385: Arthritis Rheum. 2004 Jan;50(1):242-6.

Complex segregation and linkage analysis of familial gout in Taiwanese
aborigines.

Wang WH, Chang SJ, Wang TN, Cheng LS, Feng YP, Chen CJ, Huang CH, Ko YC.

Kaohsiung Medical University, Kaohsiung, Taiwan.

OBJECTIVE: The prevalence of gout and hyperuricemia in Taiwanese aborigines is
remarkably high. Although previous studies have failed to find evidence of a
major gene responsible for gout, the disease is thought to involve genetic
predisposition. We sought to determine whether genetic factors for familial gout 
exist among Taiwanese aborigines, and, if so, their chromosomal location.
METHODS: We first performed complex segregation analysis. The study sample
comprised 945 relatives distributed in 64 pedigrees; among them, 261 affected
members (including probands) were found. In all of the aboriginal probands with
gout, the disease was diagnosed and confirmed by rheumatologists. Blood specimens
were then collected from 127 individuals living in one community that was used in
the segregation analysis (from 25 pedigrees, 36 nuclear families, and 112 full
sibpairs), and sibpair linkage analysis and a combined transmission
disequilibrium test (TDT) method were used to test the genetic components.
RESULTS: In segregation analysis, after adjusting for sex and age, an
autosomal-arbitrary major gene model was found to fit the data best, with disease
allelic frequency of 0.31 and susceptibility of 0.92. In sibpair analysis, there 
was a clustering of many flanking markers showing significant linkage, including 
D1S498 (regression coefficient -0.52), D1S2635 (regression coefficient -0.47),
and D1S196 (regression coefficient -0.51), in the 1q21 region of chromosome 1
(all P < 0.005). Results of the combined TDT showed that the marker D1S484 was
significantly associated (had linkage) with allele 1 and was transmitted more
frequently than other markers to the affected offspring (P < 0.005). CONCLUSION: 
Results of this study provide evidence of a genetic basis for familial gout in
the aboriginal Taiwanese population and suggest that a susceptibility locus may
be located in the 1q21 region of chromosome 1.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14730622 [PubMed - indexed for MEDLINE]

386: Rheumatology (Oxford). 2004 Apr;43(4):518-21. Epub 2004 Jan 13.

Gout complicated with necrotizing fasciitis--report of 15 cases.

Yu KH, Ho HH, Chen JY, Luo SF.

Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital,
Tao-Yuan, Taiwan, Republic of China.

OBJECTIVE: To analyse the clinical features and outcomes of gout complicated with
necrotizing fasciitis. METHODS: From the database of our hospital, we identified 
15 hospitalized cases of gout complicated with necrotizing fasciitis from 1987 to
2001. The medical records of the patients were analysed in detail. RESULTS: Mean 
patient age was 54.7 +/- 12.8 yr. Fever was found in only 10 (66.7%) patients,
while the remaining five patients were afebrile on presentation. The peripheral
blood white count was raised in only nine (60%) patients. The median time from
the onset of symptoms to hospital visit was 4 days (range 2 to 25). Formation of 
bullae occurred in 60% of patients. Six patients had previous wound infection,
two patients had concomitant septic arthritis and the remaining seven patients
had no obvious source of infection. Diabetes mellitus and iatrogenic Cushing
syndrome were each found in three patients. The identified causative
microorganisms were Gram-positive cocci (eight cases) and Gram-negative bacilli
(four cases); but in three patients the causative organisms were unknown.
Thirteen patients received surgery, including amputation in four cases. Finally, 
six patients suffered septic shock, three of whom died as a result. CONCLUSIONS: 
Necrotizing fasciitis in gout patients represents a surgical and medical
emergency, and is associated with a high mortality rate. Prompt diagnosis and
treatment is imperative and may be lifesaving. Early diagnosis requires a high
level of suspicion, even in patients without fever or leucocytosis.

PMID: 14722350 [PubMed - indexed for MEDLINE]

387: Clin Chim Acta. 2004 Jan;339(1-2):117-22.

Oxidized low-density lipoprotein autoantibodies in patients with primary gout:
effect of urate-lowering therapy.

Tsutsumi Z, Moriwaki Y, Takahashi S, Ka T, Yamamoto T.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Hyogo 
College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.

BACKGROUND: Uric acid is a strong scavenger of reactive oxygen species, which are
known to contribute to the development of atherosclerosis, while the incidence of
atherosclerotic diseases is rather high in patients with gout. Among the
established risk factors for atherosclerosis, oxidized LDL is believed to play a 
major role in its development and progression. Allopurinol and its active
metabolite, oxypurinol, have been suggested to possess an antioxidant ability to 
scavenge the hydroxyl radical. Therefore, allopurinol may be beneficial in the
prevention of LDL oxidation, as well as in the treatment of hyperuricemia. The
objective of this work was to determine the degree of LDL oxidation in gout and
the effect of allopurinol on LDL oxidation. METHODS: Age-matched male patients
with primary intercritical gout and healthy male adults were included in the
study. The serum concentrations of oxidized LDL autoantibodies and total
antioxidant status were measured using an enzyme immunoassay. RESULTS: Serum
concentrations of oxidized LDL autoantibodies were significantly higher in
patients with gout than the control subjects (p < 0.05) and were significantly
decreased after allopurinol treatment (p < 0.05), but not by benzbromarone
treatment, in spite of the similar concentrations of uric acid and total
antioxidant status in serum following their separate administration. CONCLUSIONS:
Although the exact mechanism remains unclear, increased serum concentrations of
oxidized LDL may play a role in the high incidence of coronary artery disease in 
gout. In addition, allopurinol may be more preferable to benzbromarone for
treatment of gout in light of its inhibitory action toward LDL oxidation.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 14687901 [PubMed - indexed for MEDLINE]

388: Clin Chim Acta. 2004 Jan;339(1-2):77-83.

The clinical significance of gelatinase B in gouty arthritis of the knee.

Chu SC, Yang SF, Lue KH, Hsieh YS, Hsiao TY, Lu KH.

Department of Food Science, Chungtai Institute of Health Sciences and Technology,
Taichung 406, Taiwan.

BACKGROUND: Clinically, gouty arthritis is associated with severe inflammation,
such as pain, swelling and erythema of the joints. Gelatinase A and B (matrix
metalloproteinase-2 and -9, MMP-2 and -9) participate in the degradation of the
extracellular matrix (ECM) components in a variety of arthritis, especially in
the inflammatory arthritis. METHODS: We examined the levels of MMP-2 and -9 in 40
synovial fluids (SFs) from the knee joints of 24 patients with gouty arthritis
and compared them with the clinical and laboratory variables of inflammation.
RESULTS: Gelatin zymography revealed that not only activated MMP-2 levels but
also proMMP-9 levels in SF from the knee joints of gouty arthritis were
associated with the local arthritis activity scores (LAS) (p < 0.001) and
correlated well with the neutrophil counts in SF as well (p < 0.001). A similar
correlation between proMMP-9 levels and LAS was also found within the individual 
patients before and during treatment with nonsteroidal antiinflammatory drugs
(NSAIDs; p < 0.001). ProMMP-2 appeared in all SFs irrespective of LAS and
neutrophil counts. CONCLUSIONS: The analysis of MMP-9 in SF samples can reveal
the inflammatory condition of the knee joints with gouty arthritis. Joint
aspiration may decrease the amount of MMPs in SF to attack the ECM of joint
whether it is normal or not.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14687896 [PubMed - indexed for MEDLINE]

389: J Rheumatol. 2003 Nov;30(11):2437-43.

Comment in:
    J Rheumatol. 2003 Nov;30(11):2312-4.

The effect of control and self-medication of chronic gout in a developing
country. Outcome after 10 years.

Darmawan J, Rasker JJ, Nuralim H.

World Health Organization Collaborating Center, Community-based Epidemiology,
Prevention, and Treatment of Rheumatic Disease, Seroja Rheumatic Center, Jalan
Seroja Dalam 7, Semarang 50136, Indonesia. jd131035@hotmail.com

OBJECTIVE: We describe a 10 year observation of the effect of control of
hyperuricemia compared with self-medication alone in patients with chronic gout. 
METHODS: We studied 299 consecutively self-referred Malayo-Polynesian men with
chronic gout, mean age 35 +/- 14.3 SD years. Subjects comprised 228 cases with
chronic gout without tophi or urolithiasis (Group 1) and 71 with those
complications (Group 2). Attacks of acute gouty arthritis were treated with
nonsteroidal antiinflammatory drugs (NSAID) and/or corticosteroids. After acute
arthritis had settled, urate-lowering drugs were instituted in both groups
combined with low dose colchicine and/or low dose NSAID for at least 0.5-2 years.
Urate levels were maintained longterm at a mean of < 5 mg/dl. After 10 years, the
dropouts were traced and evaluated for comparison with baseline and those who
remained in the study. In Group 2 the urate-lowering drugs were continued.
RESULTS: Control of gout and hyperuricemia was achieved in all patients who
remained under control: 91.6% of the 299 patients for at least 2 years
(short-term), up to 5 years in 87.5% (medium term), and up to 10 years in 79.6%
(longterm). In Group 1 (chronic gout without complication) only 36.8% had no
attacks during 8 years, after they had tapered urate-lowering drug after the
first 2 years of the study. In the 61 dropouts the intermittent symptomatic
treatment and/or self-medication without longterm control of hyperuricemia
resulted after 1 decade in chronic gout with more complications and associated
conditions leading to increased morbidity, disability, and comorbidity, and 3
early mortalities. CONCLUSION: By controlling hyperuricemia, improvement of the
prognosis of chronic gout, comorbidity, and early death was achieved compared
with self-medication alone. Self-medication in a developing country if continued 
unchecked may become a public health problem in a population with a high
prevalence rate of gout.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14677190 [PubMed - indexed for MEDLINE]

390: Rheumatol Int. 2005 Apr;25(3):179-82. Epub 2003 Dec 6.

Interleukin-1beta gene polymorphisms in Taiwanese patients with gout.

Chen ML, Huang CM, Tsai CH, Tsai FJ.

Department of Medical Genetics, China Medical University Hospital, College of
Chinese Medicine, China Medical University, Taichung, Taiwan.

The purpose of this study was to examine whether interleukin-1 beta (IL-1beta)
promoter and exon 5 gene polymorphisms are markers of susceptibility or clinical 
manifestations in Taiwanese patients with gout. The study included 196 patients
in addition to 103 unrelated healthy control subjects living in central Taiwan.
From genomic DNA, polymorphisms of the gene for IL-1beta promoter and IL-1beta
exon 5 were typed. Allelic frequencies were compared between the two groups, and 
the relationship between allelic frequencies and clinical manifestations of gout 
was evaluated. No significant differences were observed in the allelic
frequencies of the IL-1beta promoter between patients with gout and healthy
control subjects. Additionally, we did not detect any association of the IL-1beta
promoter genotype with the clinical and laboratory profiles of gout patients.
However, there was a significant difference between the two groups in terms of
hypertriglyceridemia (P=0.0004, chi(2)=12.52, OR 7.14, 95%CI 0.012-0.22). There
was also a significant difference in the genotype of IL-1beta exon 5 polymorphism
between patients with and without hypertriglyceridemia. Results of the present
study suggest that polymorphisms of the IL-1beta promoter and IL-1beta exon 5 are
not related to gout patients in central Taiwan.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14661113 [PubMed - indexed for MEDLINE]

391: J Med Assoc Thai. 2003 Sep;86(9):868-75.

A clinical study of crystal-proven gouty arthritis in a university hospital.

Louthrenoo W, Kasitanon N, Sukitawut W, Wichainun R.

Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chiang Mai
University, Chiang Mai 50200, Thailand.

The clinical features of 567 patients with crystal proven gout (489 males, 78
females) seen in a University Hospital in northern Thailand was reviewed. The
mean age at onset and mean duration of disease was 60.0 +/- 11.7 years and 5.2 + 
4.8 years, respectively. Recurrent attacks accounted for 94 per cent. The knee
and ankle were the 2 most common joints affected during the first attack and each
one was seen in 55.6 per cent of cases. During a recurrent attack, the ankle,
knee and first metatarsophalangeal joint were the 3 most common joints affected
and were seen in 94.5 per cent, 81.2 per cent and 80.2 per cent of cases,
respectively. Thirty-six per cent of the patients had tophi. Hypertension,
hyperlipidemia, diabetes mellitus and ischemic heart disease were commonly
associated diseases. Thirty-five per cent had renal calculi, and fifty-four per
cent had renal insufficiency. Of 59 patients who tested with normal renal
function, twelve per cent were hyperexcretor. The clinical features of gout seen 
in the university hospital in northern Thailand were similar to those reported in
Bangkok, but with a higher incidence of tophaceous gout, renal failure and renal 
calculi.

PMID: 14649972 [PubMed - indexed for MEDLINE]

392: Semin Musculoskelet Radiol. 2003 Sep;7(3):165-74.

Advanced imaging of gout.

Gentili A.

Department of Radiology, UCSD-Thornton Hospital, La Jolla, CA 92037, USA.

Gout is a metabolic disorder in which there is either an increase in production
or a decrease in excretion of uric acid leading to hyperuricemia. Long-lasting
hyperuricemia causes the deposition of monosodium urate crystals in the joints
and soft tissues triggering gouty arthritis and, if not properly treated, the
formation of gouty tophi. Characteristic of gout are well-defined, punched-out
erosion with overhanging edges, with preservation of the joint space, lack of
periarticular osteopenia, asymmetrical involvement, soft tissue nodules, and
intraosseous calcifications. On magnetic resonance imaging, tophi usually have
low signal intensity on both TI- and T2-weighted images and a variable
enhancement pattern.

Publication Types: 
    Review

PMID: 14593558 [PubMed - indexed for MEDLINE]

393: Clin Rheumatol. 2003 Oct;22(4-5):295-8.

Gout in systemic lupus erythematosus and overlap syndrome - a hospital-based
study.

Ho HH, Lin JL, Wu YJ, Yu KH, Chen JY, Luo SF.

Chang Gung Memorial Hospital, Tao-Yuan, Taiwan. ling0126@adm.cgmh.org.tw

The negative association between gout and rheumatoid arthritis is widely
accepted, and gout is also speculated to be rare in systemic lupus erythematosus 
(SLE), as only a few sporadic cases have been reported. From 1985 to 2001 we
encountered 15 lupus patients at Chang-Gung Memorial Hospital, including two with
lupus-scleroderma and one with lupus-scleroderma-polymyositis overlap syndrome
coexisting with gout. This study retrospectively analyses the clinical and
laboratory characteristics of these patients. A lower female predominance is
found, and most patients developed gout after the onset of SLE, although gout
preceded SLE in two cases. Measurement of serum uric acid and 24-h urine uric
acid found all of the patients to be hyperuricaemic and underexcretors of uric
acid. Furthermore, most of the patients (14/15) were receiving diuretics. Also,
many had hypertension and serious cardiovascular diseases. Renal impairment
during gouty attacks seemed to be a predisposing factor for developing end-stage 
renal disease. Gouty arthritis usually occurred during relative SLE inactivity,
podagra was frequent, and tophi were found in a few patients. Compared with the
unselected population of SLE patients, the cases studied here had a higher
incidence of chronic arthritis, malar rash, haematologic disorder,
photosensitivity, serositis and neurologic disorder. Renal disease in the
patients sampled was frequently membranous nephropathy.

Publication Types: 
    Comparative Study

PMID: 14579159 [PubMed - indexed for MEDLINE]

394: Arthritis Rheum. 2003 Oct;48(10):2931-41.

Inhibition of monosodium urate monohydrate crystal-induced acute inflammation by 
retrovirally transfected prostaglandin D synthase.

Murakami Y, Akahoshi T, Hayashi I, Endo H, Hashimoto A, Kono S, Kondo H, Kawai S,
Inoue M, Kitasato H.

Kitasato University School of Medicine, Sagamihara, Japan.

OBJECTIVE: Hematopoietic prostaglandin D synthase (H-PGDS) is a key enzyme in the
production of prostaglandin D and its J series metabolites. We evaluated the
antiinflammatory effect of retrovirally transfected H-PGDS in order to
investigate the role of H-PGDS in monosodium urate monohydrate (MSU)
crystal-induced acute inflammation. METHODS: Expression of endogenous PGDS in a
murine air-pouch model of MSU crystal-induced acute inflammation was determined
by real-time polymerase chain reaction. H-PGDS complementary DNA (cDNA) was
retrovirally transfected into C57BL/6J fibroblasts, and the cells were designated
as C57-PGDS cells. Production of prostaglandins by C57-PGDS cells was measured by
enzyme immunoassay. The effect of C57-PGDS cells on crystal-induced inflammation 
was investigated. RESULTS: Injection of the crystals caused a rapid decrease in
H-PGDS expression by infiltrating cells and by the soft tissues around the air
pouches. In contrast, expression of interleukin-1beta (IL-1beta) and macrophage
inflammatory protein 2 (MIP-2) as well as cellular infiltration were
significantly increased during the early stage of inflammation. C57-PGDS cells,
but not control cells, produced an increased amount of PGD(2) in vitro, but
suppressed production of PGE(2). Injection of C57-PGDS cells into air pouches
inhibited cellular infiltration and MIP-2 and IL-1beta expression. CONCLUSION: In
this murine air-pouch model of MSU crystal-induced inflammation, retrovirally
transfected H-PGDS cDNA could reduce cellular infiltration, at least partly by
inhibiting MIP-2 and IL-1beta. These findings suggest that gene therapy with
H-PGDS may be useful for treating inflammatory diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14558100 [PubMed - indexed for MEDLINE]

395: J Rheumatol. 2003 Oct;30(10):2245-51.

Comment in:
    J Rheumatol. 2003 Oct;30(10):2090-1.

Prevalence of rheumatic symptoms, rheumatoid arthritis, ankylosing spondylitis,
and gout in Shanghai, China: a COPCORD study.

Dai SM, Han XH, Zhao DB, Shi YQ, Liu Y, Meng JM.

Department of Rheumatology and Immunology, Changhai Hospital, Second Military
Medical University, 174 Changhai Road, Shanghai 200 433, China.
daism69@yahoo.com.cn

OBJECTIVE: To carry out a cross-sectional survey on prevalence of musculoskeletal
symptoms, rheumatoid arthritis (RA), ankylosing spondylitis (AS), and gout.
METHODS: In Shanghai, 4 communities comprising 7603 inhabitants over 15 years of 
age in an urban population were randomly selected from 13 communities. Interviews
were conducted from September 1997 to March 1998 by trained physicians using the 
COPCORD Core Questionnaire. Physical and radiographic examinations and serologic 
tests were carried out when required to classify categories of rheumatic
diseases. The diagnoses of RA, systemic lupus erythematosus (SLE), and gout were 
based on American Rheumatism Association criteria. The diagnosis of AS strictly
followed the modified New York criteria of 1984. Crude prevalence rates were
standardized according to a standard Chinese population for age and sex
structure. RESULTS: A total of 6584 adults (3394 women, 3190 men) were
interviewed, and response rate was 86.6%. The age and sex standardized prevalence
rate of rheumatic symptoms at any site amounted to 13.3% (95% CI 12.5-14.1%).
Symptoms occurred more frequently in the following sites: knee 7.0% (95% CI
6.4-7.6%), lower back 5.6% (95% CI 5.0-6.2%), shoulder 4.7% (95% CI 4.2-5.2%),
and neck 2.4% (95% CI 2.0-2.8%). Women complained of rheumatic symptoms more
frequently than men. The standardized rates of RA, AS, gout, symptomatic knee
osteoarthritis, and soft tissue rheumatism were 0.28% (95% CI 0.15-0.41%), 0.11% 
(95% CI 0.03-0.19%), 0.22% (95% CI 0.11-0.33%), 4.1% (95% CI 3.6-4.6%), and 3.4% 
(95% CI 3.0-3.8%), respectively. Two cases of SLE, one case of dermatomyositis,
and one case of systemic sclerosis were found. CONCLUSION: Compared with rates in
European and Western countries the prevalence rates of RA, AS, and gout are low
in Shanghai, China, although the prevalence rates of rheumatic symptoms are high.

PMID: 14528524 [PubMed - indexed for MEDLINE]

396: Am J Clin Nutr. 2003 Oct;78(4):690-701.

A case-control study of the association of diet and obesity with gout in Taiwan.

Lyu LC, Hsu CY, Yeh CY, Lee MS, Huang SH, Chen CL.

Graduate Program of Nutrition, National Taiwan Normal University, Taipei, Taiwan.
t10010@cc.ntnu.edu.tw

BACKGROUND: Gout has been a significant metabolic disorder for Chinese men in
Taiwan; however, there is insufficient information on diet and lifestyle risk
factors in this population. OBJECTIVE: The purpose of this case-control study was
to explore potential dietary and lifestyle risk factors associated with gout in
Chinese men. DESIGN: Between 1998 and 1999, we recruited and conducted
face-to-face interviews with patients from outpatient clinics in Taipei who had
incident gout (n = 92) and with their healthy coworkers (controls; n = 92).
RESULTS: Systolic blood pressure, diastolic blood pressure, waist-to-hip ratio,
waist-to-height ratio, and body mass index were significantly higher in cases
than in controls. Family histories of gout and diabetes mellitus were strong risk
factors for gout. Frequencies of vegetable and fruit consumption were
significantly lower in cases than in controls. Logistic regression analyses
showed that high alcohol intake and low intakes of fiber, folate, and vitamin C
increased the risk of gout, but no association was found with purine intake.
After covariates were controlled for, the adjusted odds ratios for the middle and
highest tertiles of waist-to-height ratio (0.50-0.54 and >/==" BORDER="0"> 0.55, 
respectively) were 3.89 (95% CI: 1.32, 11.46) and 4.37 (1.18, 16.22),
respectively, but no linear association was found for waist-to-hip ratio and
waist circumference. CONCLUSIONS: Consumption of alcohol, but not of purine, may 
be a significant dietary risk factor for gout. Food sources rich in dietary
fiber, folate, and vitamin C, such as fruit and vegetables, protect against gout.
Waist-to-height ratio, which indicates central obesity, has a significant linear 
effect on gout occurrence, independent of body mass index.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14522726 [PubMed - indexed for MEDLINE]

397: Ann Plast Surg. 2003 Oct;51(4):372-5.

The soft-tissue shaving procedure for deformity management of chronic tophaceous 
gout.

Lee SS, Lin SD, Lai CS, Lin TM, Chang KP, Yang YL.

Department of Plastic and Reconstructive Surgery, Chung-Ho Memorial Hospital,
Kaohsiung Medical University, Kaohsiung, Taiwan.

Gout is a condition characterized by the deposition of monosodium urate crystals 
in the joints or soft tissue. A gouty tophus occasionally mimics an infectious or
neoplastic process. However, the conventional enucleating procedure might cause
complications. In severe cases, skin necrosis and tendon or joint exposure can
occur after debridements. In this series, the soft-tissue shaver is used for
deformity management of the chronic tophaceous patients and the results are
encouraging. From November 2000 to August 2002, 17 patients with chronic
tophaceous gout were treated by the shaver technique. Suction and irrigation were
performed simultaneously while the shaver was operating, and chalky deposits of
sodium urate could be removed efficiently. Skin necrosis was minimized by means
of proper incision planning. Also, bedside debridements and wound wet dressing
were helpful for improving the outcomes. The families and patients were satisfied
with the results. In conclusion, severe chronic tophaceous gout can be a surgical
challenge. The soft-tissue shaving technique can be useful for cosmetic debulking
of large tophi in patients with advanced chronic tophaceous gouty arthritis.

PMID: 14520064 [PubMed - indexed for MEDLINE]

398: Skeletal Radiol. 2003 Nov;32(11):647-50. Epub 2003 Sep 27.

Isolated intraosseous gout in hallux sesamoid mimicking a bone tumor in a
teenaged patient.

Liu SZ, Yeh L, Chou YJ, Chen CK, Pan HB.

Department of Radiology, Kaohsiung Veterans General Hospital, 386 Ta-Chung first 
Rd., 813 Kaohsiung, Taiwan, ROC.

We are reporting an unusual case of isolated intraosseous tophus in medial hallux
sesamoid presenting as tumor-like lesion in a teenage patient without prior
history of gouty attack and underlying systemic disorders. The lesion manifested 
isointensity to surrounding muscles with internal low signal on spin echo (SE)
T1-weighted images, and heterogeneous low signal intensity on fast spin echo
(FSE) T2-weighted images. Computed tomography (CT) scan disclosed expansion and
diffusely increased attenuation of the medial hallux sesamoid with focal cortical
erosion and extraosseous extension of high attenuation content. The subsequent
resection and pathology revealed intraosseous tophus deposition, which is
particularly rare at this site and at this age. Imaging studies revealed some
characteristic imaging features which can retrospectively be attributed to gouty 
tophus. When an expansile osteolytic lesion manifesting low signal intensity on
T2-weighted image and internal calcifications on CT scan is encountered, the
possibility of intraosseous tophus should be included in the list of differential
diagnoses, even in a teenage patient without prior history of gout.

Publication Types: 
    Case Reports

PMID: 14517698 [PubMed - indexed for MEDLINE]

399: J Hand Surg [Am]. 2003 Sep;28(5):871-4.

Associated giant cell tumor and tophaceous deposits in a finger pulp: a case
report.

Schuind FA, Stallenberg B, Remmelink M, Pasteels JL.

Department of Orthopedics and Traumatology, Cliniques Universitaires de
Bruxelles, Université Libre de Bruxelles, Hôpital Erasme, Brussels, Belgium.

A case of concomitant giant cell tumor of soft tissue and tophaceous deposits
within the finger pulp is presented. The local hemorrhage and increased turnover 
with giant cell tumor may explain the deposits of aggregated crystals of
monosodium urate in this patient with hyperuricemia.

Publication Types: 
    Case Reports

PMID: 14507521 [PubMed - indexed for MEDLINE]

400: Rheumatology (Oxford). 2003 Dec;42(12):1529-33. Epub 2003 Sep 16.

Trends in the manifestations of gout in Taiwan.

Chen SY, Chen CL, Shen ML, Kamatani N.

Department of Internal Meidcine, Taipei Municipal Ho-Ping Hospital, Taiwan.
shihyangchen1@mac.com

OBJECTIVE: To elucidate the recent changes in the clinical manifestations, risk
factors and disorders associated with gout. METHODS: All gouty cases in Ho-Ping
Gout Database were divided into two groups according to the date of first visit
to our clinic: 1983-1991 (earlier group) and 1992-1999 (later group). Study
variables were compared between these two groups. RESULTS: In the later group,
the age at onset of gout was lower by 2.7 yr (P < 0.0001) and the percentages of 
female gout and familial gout were higher (P = 0.0046 and P < 0.0001,
respectively). Joint counts and the percentage of frequency of attacks > or =6
times/yr were lower in the later group (P < 0.0001), while the percentage of
tophaceous gout was higher by 0.8% in the later group (P = 0.0004). The
percentage of first attack at ankle was higher (P < 0.0001), while those at
Achilles tendon, knee and upper extremity were lower in the later group (P <
0.0001). The percentages of diuretic use and alcohol consumption were lower in
the later group (P < 0.0001). The percentages of obesity, hypertriglyceridaemia
and nephrolithiasis were higher (P < 0.0001), while the percentages of
hypertension and hypercholesterolaemia were lower in the later group (P < 0.0001 
and P = 0.0003, respectively). The percentages of type 2 diabetes mellitus and
renal insufficiency were not significantly different in multivariate analyses.
CONCLUSION: The age of onset, clinical manifestations, risk factors and disorders
associated with gout have recently changed in Taiwan.

PMID: 13130146 [PubMed - indexed for MEDLINE]

401: Rheumatology (Oxford). 2004 Feb;43(2):191-4. Epub 2003 Aug 29.

Limited knee joint range of motion due to invisible gouty tophi.

Yu KH, Lien LC, Ho HH.

Division of Rheumatology, Allergy, and Immunology, Chang Gung Memorial Hospital, 
Tau-Yuan, Taiwan, Republic of China. gout@adm.cgmh.org.tw

OBJECTIVES: Tophi deposits are a well-known cause of joint destruction, gouty
nephropathy and spinal cord compression. This study reports another major
complication of gout, namely tophi deposition causing limited knee joint
excursion. METHODS: Seven gout patients with limited knee joint excursion owing
to tophi deposition were studied to reveal clinical features and magnetic
resonance imaging (MRI) findings. None of the patients were able to assume a full
squatting posture. RESULTS: No patients had visible subcutaneous tophi over the
knee joints, except for one case in which a pea-sized subcutaneous tophus was
noted. Additionally, two patients even lacked visible tophi elsewhere. All knee
problems in the study group were initially regarded as being due to degenerative 
or other internal derangements, but MRI unexpectedly revealed multiple tophaceous
depositions within and around the joint. CONCLUSIONS: Intra-articular and
periarticular tophi limiting knee joint range of motion are a rare but important 
cause of walking disability in gout patients. Although most patients do not
display visible subcutaneous tophi over the knee on physical examination, the
differential diagnosis should consider intra-articular tophi and MRI is valuable 
in this clinical setting.

Publication Types: 
    Case Reports

PMID: 12949254 [PubMed - indexed for MEDLINE]

402: Hand Surg. 2003 Jul;8(1):121-5.

Carpal tunnel syndrome due to gouty infiltration of the lumbrical muscles and
flexor tendons.

Tan G, Chew W, Lai CH.

Department of Orthopaedic Surgery, Tan Tock Seng Hospital, No. 11 Jalan Tan Tock 
Seng, Singapore. Gamaliel_Tan@ttsh.com.sg

A case of gout first presenting as carpal tunnel syndrome due to intratendinous
and lumbrical muscle involvement with tophi is reported. Surgical decompression
with excision of tophi and diseased muscle produced symptomatic relief.

Publication Types: 
    Case Reports

PMID: 12923948 [PubMed - indexed for MEDLINE]

403: Hand Surg. 2003 Jul;8(1):107-9.

Co-existent gout and septic arthritis at the wrist: a case report.

Schuind FA, Remmelink M, Pasteels JL.

Department of Orthopedics, Université libre de Bruxelles, Erasme University
Hospital, Brussels, Belgium.

This article presents an exceptional clinical manifestation of gout in the wrist.
The patient suffered from an association of septic and urate-crystal-induced
arthritis. At the time, the serum uric acid concentration was still normal. The
association of septic and urate-crystal-induced arthritis has been reported in
other locations. The pathophysiology of the precipitation of urate crystals in
the presence of an infectious process is discussed.

Publication Types: 
    Case Reports

PMID: 12923944 [PubMed - indexed for MEDLINE]

404: J Rheumatol. 2003 Aug;30(8):1868-70.

Intraarticular tophi in a joint without a previous gouty attack.

Yu KH.

Division of Rheumatology, Allergy, and Immunology, Chang Gung Memorial Hospital, 
Tao-Yuan, Taiwan. gout@adm.cgmh.org.tw

Subcutaneous tophi are usually a late clinical manifestation of gout. However,
intraarticular tophi may develop very early, since crystal shedding has been
presumed to precipitate an acute gouty attack. There is little direct evidence of
intraarticular tophi before the initial gouty attack. We describe a patient who
had gout for 3 years without subcutaneous tophi. Whitish intraarticular deposits,
presumably representing urate tophi, were noted during right knee arthroscopy for
a posterior cruciate ligament tear. This observation illustrates that tophi
deposition may occur early, even in previously unaffected joints.

Publication Types: 
    Case Reports

PMID: 12913949 [PubMed - indexed for MEDLINE]

405: Kidney Int. 2003 Sep;64(3):1022-6.

The association between gout and nephrolithiasis in men: The Health
Professionals' Follow-Up Study.

Kramer HJ, Choi HK, Atkinson K, Stampfer M, Curhan GC.

Department of Preventive Medicine and Epidemiology, Division of Nephrology,
Loyola University Medical Center, Maywood, Illinois, USA.

Approximately 10 million adults in the United States have experienced the passage
of a kidney stone, and up to 5 million have been diagnosed with gout by a
physician. Previous reports have suggested that gout increases the risk for the
development of kidney stones, but there are no prospective data. We used data
from a cohort of 51,529 male health care professionals to examine the independent
association between gout and kidney stone disease. In a cross-sectional analysis 
of gout and kidney stone disease reported on the 1986 baseline questionnaire, the
prevalence of kidney stone disease was almost twofold higher in men with history 
of gout compared to those without (15% vs. 8%). After adjusting for age and body 
mass index (BMI), a history of gout remained significantly associated with kidney
stone disease (OR 1.88; 95% CI 1.68 to 2.11). We then prospectively examined the 
risk of incident kidney stones in men with and without a confirmed diagnosis of
gout after excluding men who reported a history of kidney stone disease or gout
on the baseline questionnaire. A confirmed diagnosis of gout increased the
multivariate relative risk of incident kidney stones (RR 2.12; 95% CI 1.22 to
3.68). In contrast, a history of kidney stone disease was not associated with
increased risk of gout (RR 1.05; 95% CI 0.54 to 2.07). In conclusion, a history
of gout independently increases the risk for incident kidney stones in men.
Physicians should provide dietary counseling, such as increasing fluid intake and
decreasing salt consumption, to subjects with gout in addition to other risk
factors, such as family history of kidney stones, in order to decrease the
likelihood of stone formation.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12911552 [PubMed - indexed for MEDLINE]

406: Arthritis Rheum. 2003 Aug;48(8):2310-20.

Role of S100A8 and S100A9 in neutrophil recruitment in response to monosodium
urate monohydrate crystals in the air-pouch model of acute gouty arthritis.

Ryckman C, McColl SR, Vandal K, de Médicis R, Lussier A, Poubelle PE, Tessier PA.

Infectious Diseases Research Center, Centre de Recherche du Centre Hospitalier de
l'Université Laval, 2705 Laurier Boulevard, Sainte-Foy, Quebec G1V 4G2, Canada.

OBJECTIVE: To examine the role of chemokines, S100A8, and S100A9 in neutrophil
accumulation induced by the causative agent of gout, monosodium urate monohydrate
(MSU) crystals. METHODS: MSU crystal-induced neutrophil migration was studied in 
the murine air-pouch model. Release of chemokines, S100A8, S100A9, and S100A8/A9 
in response to MSU crystals was quantified by enzyme-linked immunosorbent assays.
Recruited cells were counted following acetic blue staining, and the
subpopulations were characterized by Wright-Giemsa staining of cytospins.
RESULTS: MSU crystals induced the accumulation of neutrophils following injection
in the air pouch, which correlated with the release of the chemokines CXCL1,
CXCL2, CCL2, and CCL3. However, none of these was found to play an important role
in neutrophil migration induced by MSU crystals by passive immunization with
antibodies directed against each chemokine. S100A8, S100A9, and S100A8/A9 were
also found at high levels in the pouch exudates following injection of MSU
crystals. In addition, injection of S100A8, S100A9, or S100A8/A9 led to the
accumulation of neutrophils in the murine air pouch, demonstrating their
proinflammatory activities in vivo. Passive immunization with anti-S100A8 and
anti-S100A9 led to a total inhibition of the accumulation of neutrophils.
Finally, S100A8/A9 was found at high concentrations in the synovial fluid of
patients with gout. CONCLUSION: S100A8 and S100A8/A9 are essential to neutrophil 
migration induced by MSU crystals. These results suggest that they might be
involved in the pathogenesis of gout.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12905486 [PubMed - indexed for MEDLINE]

407: J Hand Surg [Am]. 2003 Jul;28(4):669-72.

Comment in:
    J Hand Surg [Am]. 2004 May;29(3):526; author reply 526.

Gouty flexor tenosynovitis of the digits: report of three cases.

Weniger FG, Davison SP, Risin M, Salyapongse AN, Manders EK.

Divisions of Plastic Surgery, University of Pittsburgh School of Medicine,
Pittsburgh, PA 15261, USA.

Gouty tenosynovitis in the hand is a rare entity. To date the limited cases
described have involved predominantly extensor tendons in the fingers and flexor 
tendons in the palm or wrist. Flexor tendon involvement is less common and has
been reported only twice to our knowledge distal to the palm. We report 3 cases
of extra-articular gout presenting as tophaceous involvement of flexor tendons in
the fingers. All cases were treated surgically. These cases are presented to
heighten awareness of this rare entity and to provide a setting for a discussion 
of management.

Publication Types: 
    Case Reports

PMID: 12877858 [PubMed - indexed for MEDLINE]

408: Fam Pract. 2003 Aug;20(4):413-6.

Gout, just a nasty event or a cardiovascular signal? A study from primary care.

Janssens HJ, van de Lisdonk EH, Bor H, van den Hoogen HJ, Janssen M.

University Medical Centre, Department of General Practice and Family Medicine
229, PO Box 9101, 6500 HB Nijmegen, The Netherlands.

OBJECTIVE: Our aim was to examine the relationship between gout on the one hand
and cardiovascular diseases and cardiovascular risk indicators on the other.
METHODS: A case-control study was carried out in an aggregate primary care
population of approximately 12 000 patients from four Dutch general practices,
with follow-up of the cases free of cardiovascular diseases at the time of the
first registered episode of gout. The subjects comprised 261 patients with a
first episode of gout, 170 of whom were without prevalent cardiovascular
diseases, and two control patients for each case matched for age, sex and
practice. In the case-control study, the main outcome measures were the
prevalence of cardiovascular morbidity (angina pectoris, myocardial infarction,
heart failure, cerebrovascular accident, transient ischaemic attack, peripheral
vascular disease), hypertension, diabetes mellitus, obesity and
hypercholesterolaemia; in the follow-up study, the main outcome measure was the
incidence of cardiovascular morbidity. RESULTS: Thirty-five percent of 261 gout
patients and 26% of 522 controls had one or more prevalent cardiovascular
diseases. Compared with controls, patients had a higher prevalence of
hypertension (43% versus 18%), hypercholesterolaemia (14% versus 6%) and obesity 
(56% versus 30%). A total of 170 gout patients without prevalent cardiovascular
diseases (compared with 340 controls) had a higher prevalence of hypertension
(39% versus 14%), hypercholesterolaemia (8% versus 4%), diabetes mellitus (5%
versus 1%) and obesity (52% versus 27%). The first occurrence of a cardiovascular
disease (real end-point) was seen in 26% of the patients free of cardiovascular
morbidity and in 21% of the controls. This difference was not significant. In a
Cox proportional hazard model, controlling for the cardiovascular risk
indicators, gout did not prove to be an independent determinant for the
development of cardiovascular disease. CONCLUSION: Gout was found to be
associated with cardiovascular diseases and with cardiovascular risk indicators, 
without evidence of it being an independent risk indicator itself. A gout attack 
should be an incentive to assess the cardiovascular risk profile, when a patient 
seeks medical help.

Publication Types: 
    Comparative Study

PMID: 12876112 [PubMed - indexed for MEDLINE]

409: Am J Med. 2003 Jul;115(1):26-32.

Predictive value of kidney stone composition in the detection of metabolic
abnormalities.

Pak CY, Poindexter JR, Adams-Huet B, Pearle MS.

Center for Mineral Metabolism and Clinical Research, University of Texas
Southwestern Medical Center, Dallas, Texas 75390-8885, USA.
charles.pak@utsouthwestern.edu

PURPOSE: To determine if kidney stone composition can predict the underlying
medical diagnosis, and vice versa. METHODS: We studied 1392 patients with kidney 
stones who underwent a complete ambulatory evaluation and who submitted one or
more stones for analysis. We ascertained the associations between medical
diagnosis and stone composition. RESULTS: The most common kidney stones were
composed of calcium oxalate (n = 1041 patients [74.8%]), mixed calcium
oxalate-calcium apatite (n = 485 [34.8%]), and calcium apatite alone (n = 146
[10.5%]). The most common medical diagnoses were hypocitraturia (n = 616 patients
[44.3%]), absorptive hypercalciuria (n = 511 [36.7%]), and hyperuricosuria (n =
395 [28.4%]). Calcium apatite and mixed calcium oxalate-calcium apatite stones
were associated with the diagnoses of renal tubular acidosis and primary
hyperparathyroidism (odds ratios >/=2), but not with chronic diarrheal syndromes.
As the phosphate content of the stone increased from calcium oxalate to mixed
calcium oxalate-calcium apatite, and finally to calcium apatite, the percentage
of patients with renal tubular acidosis increased from 5% (57/1041) to 39%
(57/146), and those with primary hyperparathyroidism increased from 2% (26/1041) 
to 10% (14/146). Calcium oxalate stones were associated with chronic diarrheal
syndromes, but not with renal tubular acidosis. Pure and mixed uric acid stones
were strongly associated with a gouty diathesis, and vice versa. Chronic
diarrheal syndromes and uric acid stones were associated with one another, and
brushite stones were associated with renal tubular acidosis. As expected, there
was a very strong association between infection stones and infection, and between
cystine stones and cystinuria. CONCLUSION: Stone composition has some predictive 
value in diagnosing medical conditions, and vice versa, especially for
noncalcareous stones.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12867231 [PubMed - indexed for MEDLINE]

410: Clin Ther. 2003 Jun;25(6):1593-617.

A literature review of the epidemiology and treatment of acute gout.

Kim KY, Ralph Schumacher H, Hunsche E, Wertheimer AI, Kong SX.

Temple University, School of Pharmacy, Philadephia, USA.

BACKGROUND: Gout is the most common cause of inflammatory arthritis in men aged
>40 years and is frequently encountered in clinical practice. OBJECTIVE: The goal
of this article was to review the published literature on the epidemiology,
treatment, and estimated burden of illness of acute gout. METHODS: Articles on
gout published in English between 1980 and June 2002 were identified through a
MEDLINE search. Relevant clinical studies and review articles were found using
the text- and keyword-search term gout alone and in combination with
epidemiology, prevalence, incidence, complications, outcome, quality of life,
economics, cost, prevention or drug therapy. The reference lists of identified
articles, especially review articles, were checked for any additional studies
that might have been missed in the original MEDLINE search. RESULTS: The
epidemiology of gout in various geographic regions has been well documented. Data
suggest that environmental, racial, and hereditary factors may influence the
development of gout, and that the prevalence of gout appears to be on the rise
worldwide. Evidence from well-designed clinical studies evaluating drug therapies
for gout is limited. Therapies for acute gout include corticotropin,
corticosteroids, colchicine or, more often, nonsteroidal anti-inflammatory drugs 
(NSAIDs), which have shown comparable efficacy. A recent study suggests that
etoricoxib, a new cyclooxygenase-2-selective inhibitor, may be as effective as
and better tolerated than traditional NSAIDs in the treatment of gout.
Urate-lowering therapy, prophylactic colchicine, and low-dose NSAIDs are used for
the long-term prophylaxis of gout. However, all acute and prophylactic therapies 
are associated with adverse events. Using an economic model for gout, the annual 
direct burden of illness for new cases of acute gout can be estimated at
27,378,494 US dollars in the United States. CONCLUSIONS: Gout is an increasingly 
prevalent condition worldwide and creates a heavy economic burden. Available
treatments are generally effective; however, they are not devoid of adverse
events. Well-designed, long-term, controlled clinical trials evaluating the
comparative efficacy and tolerability of treatments for gout are needed.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12860487 [PubMed - indexed for MEDLINE]

411: J Cell Biochem. 2003 Jul 1;89(4):791-9.

Expression of matrix metalloproteinase-9 (gelatinase B) in gouty arthritis and
stimulation of MMP-9 by urate crystals in macrophages.

Hsieh MS, Ho HC, Chou DT, Pan S, Liang YC, Hsieh TY, Lan JL, Tsai SH.

Department of Orthopaedics and Traumatology, School of Medicine, Taipei Medical
University Hospital, Taipei Medical University, Taipei, Taiwan.

To investigate the relevance of gelatinase-B (matrix metalloproteinase 9, MMP-9) 
in gouty arthritis (GA), we tested the occurrence of MMP-9 in GA patients and
cell culture system. Gelatinolytic activity in the synovial fluid (SF) of
patients with different kinds of arthritis was assessed by gelatin zymography. A 
predominant 92-kDa MMP-9 gelatinolytic activity was evident in rheumatoid
arthritis (RA) and GA samples, but no activity was observed in osteoarthritis
(OA) samples. Among the 53 SF samples (9 RA, 24 GA, and 20 OA) analyzed for MMP-9
and tissue inhibitor of metalloproteinase (TIMP-1) antigen levels by ELISA, MMP-9
antigen levels were elevated tenfold in GA SF compared with OA SF. In addition,
GA synovial tissue extracts revealed elevated levels of MMP-9 expression as
compared to OA tissue extracts by Western blot and RT-PCR analysis.
Immunohistochemical studies demonstrated that MMP-9 immunoreactivity was more
intense in GA than in OA synovial tissues. Furthermore, macrophages activation by
gouty crystals in vitro was examined. Crystals stimulated MMP-9 gene expression
in macrophage cell line and such stimulation was suppressed by PD98059. These
findings suggest that the abnormal production of MMP-9 by macrophages is a
reflection of the pathological conditions in joints of patients with GA, and that
the activation of MMP-9 in the joint is known to play an important role in joint 
disease. Copyright 2003 Wiley-Liss, Inc.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12858344 [PubMed - indexed for MEDLINE]

412: Scand J Plast Reconstr Surg Hand Surg. 2003;37(3):186-7.

Carpal tunnel syndrome secondary to intratendinous infiltration by tophaceous
gout.

Mockford BJ, Kincaid RJ, Mackay I.

Department of Orthopaedic Surgery, Crosshouse Hospital, Kilmarnock, Scotland.
Bmockjmock@aol.com

Carpal tunnel syndrome caused by gout is rare. We describe a case of entrapment
of the median nerve secondary to intratendinous infiltration by gouty tophi in a 
54-year-old man. The tophus was excised from the profundus tendon but the
superficialis was too infiltrated and destroyed to be saved. The patient made an 
uneventful recovery with relief of his symptoms. This case illustrates the
potential consequences this could have for hand function.

Publication Types: 
    Case Reports
    Review

PMID: 12841622 [PubMed - indexed for MEDLINE]

413: Rheumatology (Oxford). 2003 Dec;42(12):1550-5. Epub 2003 Jun 27.

Near-iron deficiency-induced remission of gouty arthritis.

Facchini FS.

Department of Medicine, San Francisco General Hospital and University of
California San Francisco, 94143, USA. fste2000@yahoo.com

OBJECTIVES: Previous evidence supports a role for iron in the pathogenesis of
gout. For example, iron, when added to media containing urate crystals,
stimulated oxidative stress with subsequent complement and neutrophil activation.
Conversely, iron removal inhibited these responses as well as
urate-crystal-induced foot pad inflammation in rats in-vivo. The objective of the
present study was to investigate whether or not iron removal may improve the
outcome of gouty arthritis in humans as well. METHODS: Quantitative phlebotomy
was used to remove iron in 12 hyperuricaemic patients with gouty arthritis and
maintain their body iron at near-iron deficiency (NID) level (i.e. the lowest
body iron store compatible with normal erythropoiesis and therefore absence of
anaemia). RESULTS: During maintenance of NID for 28 months, gouty attacks
markedly diminished in every patient, from a cumulative amount of 48 and 53
attacks per year before (year -2, -1), to 32, 11 and 7 during induction (year 0) 
and maintenance (year +1, +2) of NID, respectively. During NID, attacks were also
more often of milder severity. CONCLUSIONS: During a 28-month follow-up,
maintenance of NID was found to be safe and beneficial in all patients, with
effects ranging from a complete remission to a marked reduction of incidence and 
severity of gouty attacks.

Publication Types: 
    Clinical Trial

PMID: 12832712 [PubMed - indexed for MEDLINE]

414: Kidney Int. 2003 Jul;64(1):36-42.

Comment in:
    Kidney Int. 2003 Nov;64(5):1920-1.

Clinical characterization of a family with a mutation in the uromodulin
(Tamm-Horsfall glycoprotein) gene.

Bleyer AJ, Woodard AS, Shihabi Z, Sandhu J, Zhu H, Satko SG, Weller N, Deterding 
E, McBride D, Gorry MC, Xu L, Ganier D, Hart TC.

Section on Nephrology, Wake Forest University School of Medicine, Winston-Salem, 
North Carolina 27157, USA. ableyer@wfubmc.edu

BACKGROUND: We have recently identified a mutation in the uromodulin gene in a
large family affected with hyperuricemia, gout, and renal failure. The purpose of
this investigation is to provide a comprehensive characterization of the clinical
findings of this syndrome in family members who had a mutation in the uromodulin 
gene. METHODS: An extended family suffering from hyperuricemia and gout was
identified by a local practitioner. After consent was obtained, patients provided
a directed clinical history and blood and urine specimens for chemical and
genetic testing. All family members were tested for the presence of uromodulin
gene mutations by direct DNA sequence analysis. The clinical and biochemical
characteristics of family members carrying the affected mutation were then
investigated. RESULTS: Thirty-nine family members were found to have an exon 5
uromodulin gene mutation (g.1966 1922 del), and 29 unaffected family members were
identified. The cardinal clinical features in individuals with the uromodulin
mutation included hyperuricemia, decreased fractional excretion of uric acid, and
chronic interstitial renal disease leading to end-stage renal disease (ESRD) in
the fifth through seventh decade. Women did not always develop hyperuricemia or
gout, but still developed progressive chronic renal failure. CONCLUSION: Mutation
of the uromodulin gene resulted in hyperuricemia, reduced fractional excretion of
uric acid, and renal failure. Genetic testing will be required to definitively
identify individuals suffering from this condition. We are interested in studying
other families that may suffer from this condition and would appreciate any such 
referrals.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12787393 [PubMed - indexed for MEDLINE]

415: Skeletal Radiol. 2003 Jul;32(7):429-31. Epub 2003 Jun 3.

Tophaceous gout in an amputation stump in a patient with chronic myelogenous
leukemia.

Chung CB, Mohana-Borges A, Pathria M.

Department of Radiology, UCSD and VAHCS, 3350 La Village Drive, La Jolla, CA
92161, USA. cbchung@ucsd.edu

Gout is a common rheumatologic disorder that can have an unusual clinical
presentation. This case report describes the development of a gouty tophus at a
site of remote traumatic forearm amputation in a patient with chronic myelogenous
leukemia (CML). It further addresses the imaging characteristics of tophaceous
gout as well as the differential diagnostic considerations as regards both the
imaging findings and the clinical presentation.

Publication Types: 
    Case Reports

PMID: 12783222 [PubMed - indexed for MEDLINE]

416: Rheumatology (Oxford). 2003 Sep;42(9):1093-100. Epub 2003 May 30.

Intra-articular corticosteroid preparations: different characteristics and their 
effect during inflammation induced by monosodium urate crystals in the rat
subcutaneous air pouch.

Rull M, Clayburne G, Sieck M, Schumacher HR.

Veterans Affairs Medical Center and University of Pennsylvania, Philadelphia, PA 
19104, USA.

OBJECTIVE: To examine the effects of three commonly used intra-articular depot
corticosteroid preparations tested in a rat air pouch model and their effect
against monosodium urate (MSU) crystal-induced inflammation. Rheumatologists use 
intra-articular corticosteroid preparations to relieve pain and inflammation of
acute monoarthritis without really knowing their effects on the synovial fluid
and membrane or the differences between distinct preparations. This work compares
the effect of three commonly used corticosteroid preparations in vivo, showing
that they behave differently. METHODS: A subcutaneous air pouch was formed in
male Sprague-Dawley rats. A first group of 6-day-old air pouches were injected
with 10 ml of 6 mg/ml normal saline solution, 6 mg/ml betamethasone containing
both depot betamethasone acetate and soluble betamethasone phosphate (Celestone) 
in 9 ml of normal saline solution, 20 mg/ml of prednisolone tebutate (Hydeltra)
in 9 ml of normal saline solution or 20 mg/ml of triamcinolone hexacetonide
(Aristospan) in 9 ml of normal saline solution. A second group (group 2) of air
pouches were injected with 15 mg of synthetic MSU crystals and 24 h later they
were reinjected with 1 ml of the same three corticosteroid suspensions. For each 
condition four rats were killed at 6, 24, 48 h and 7 days. Pouch fluid and tissue
were analysed. RESULTS: In the first 6 h after normal saline solution or
corticosteroid injection into the air pouch there were mildly increased leucocyte
counts in the air pouch fluid. Betamethasone-injected pouches showed no cells in 
the fluid after 6 h and no crystals after 24 h, triamcinolone-injected pouches
still showed rare cells at 7 days. Both triamcinolone and prednisolone crystals
persisted in higher numbers and lasted longer in the fluid than did betamethasone
(P<0.05). In group 2 MSU crystal phagocytosis in the fluid was decreased in the
betamethasone- (P<0.01), prednisolone- (P<0.003) and triamcinolone- (P<0.006)
injected pouches when compared with the MSU crystal-injected pouches alone.
Pouches injected with MSU crystals alone showed the most intense tissue
inflammation at all times. After MSU, betamethasone-injected pouches had a rapid 
but mild decrease in the number of lining cells and inflammation. In contrast,
triamcinolone- and prednisolone-injected pouches showed a very thin tissue with
few or no vessels and almost no inflammation at 7 days. The pouches injected with
MSU crystals and any of the corticoid preparations had three times more
tophus-like structures and persistent crystals identified than the ones injected 
with MSU crystals alone. CONCLUSION: Each of the corticosteroid preparations by
themselves produced very mild transient inflammation. The betamethasone
preparation with a soluble steroid component had a quicker but milder
anti-inflammatory effect on MSU crystal-induced inflammation. In contrast to the 
doses used, prednisolone tebutate and triamcinolone hexacetonide preparations
dramatically suppressed urate crystal-induced inflammation at 7 days, but both
produced atrophy and necrosis of the membrane, yielding a very thin membrane with
almost no vessels. When used for MSU crystal-induced inflammation these
corticosteroid preparations suppressed some aspects of inflammation but may
actually promote the persistence of MSU crystals and the formation of tophi.

Publication Types: 
    Comparative Study

PMID: 12777646 [PubMed - indexed for MEDLINE]

417: Curr Rheumatol Rep. 2003 Jun;5(3):227-34.

Hyperuricemia and gout.

Lioté F.

Centre Viggo Petersen, INSERUM U349 Hôpital Lariboisière, 2 Rue Ambroise Paré,
F75475 Paris, France. frederic.liote@rb.ap-hop-paris.fr

Gout is not a new disease for clinicians; nevertheless, there are still many
secrets awaiting discovery for improving knowledge with respect to uric acid
metabolism and monosodium urate crystal-induced inflammation. This review of the 
literature will focus on new insights on the pathogenesis of idiopathic
hyperuricemia, and on secondary hyperuricemia and gout. There are also important 
advances on the pathophysiology of acute gout, especially as a self-limited
process (switch from monocyte to macrophage, peroxisome proliferator activated
receptor-gamma, and nitric oxide), but also of chronic gouty arthropathy.
Armaments for treating hyperuricemia and gout may be already improved by losartan
or fenofibrate and, in the future, by urate oxydase-polyethylene glycol 20 and
renal handling regulatory molecules. Finally, control of hyperuricemia may also
be considered in the prevention and treatment of cardiovascular disease.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12744816 [PubMed - indexed for MEDLINE]

418: Arch Ophthalmol. 2003 May;121(5):674-8.

Association of emphysema, gout, and inflammatory markers with long-term incidence
of age-related maculopathy.

Klein R, Klein BE, Tomany SC, Cruickshanks KJ.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison, 53726-2397, USA. kleinr@epi.ophth.wisc.edu

OBJECTIVE: To examine the relationship of 2 diseases associated with systemic
inflammatory response, emphysema and gout, and selected markers of systemic
inflammation with the 10-year incidence of age-related maculopathy. DESIGN:
Population-based cohort study. PARTICIPANTS: We included persons aged 43 to 86
years at baseline examination from 1988 to 1990 living in Beaver Dam, Wis, of
whom 3684 subjects participated in a 5-year follow-up examination and 2764
participated in a 10-year follow-up. METHODS: Standardized protocols for physical
examination, blood collection, administration of a questionnaire, and
stereoscopic color fundus photography to determine the presence of age-related
maculopathy. Standard univariate and multivariate analyses were performed. MAIN
OUTCOME MEASURES: Incidence and progression of age-related maculopathy. RESULTS: 
While controlling for age, sex, and other factors (history of heavy drinking or
smoking, systolic blood pressure, and vitamin use), a higher white blood cell
count at baseline was associated with the 10-year incidence of drusen 125 microm 
or greater in diameter (risk ratio [RR] per 10(6)/ microL = 1.10; 95% confidence 
interval [CI], 1.03-1.17), retinal pigment epithelial depigmentation (RR = 2.08; 
95% CI, 1.01-1.16), and progression of age-related maculopathy (RR = 1.09; 95%
CI, 1.03-1.15). A lower serum albumin level was associated with the incidence of 
exudative macular degeneration (RR per grams per deciliter = 0.31; 95% CI,
0.13-0.76). A history of emphysema at baseline was associated with the incidence 
of retinal pigment epithelial depigmentation (RR = 2.84; 95% CI, 1.40-5.78),
increased retinal pigment (RR = 2.20; 95% CI, 1.11-4.35), and exudative macular
degeneration (RR = 5.12; 95% CI, 1.63-16.06); a history of gout was associated
with the incidence of pure geographic atrophy (RR = 3.48; 95% CI, 1.27-9.53).
CONCLUSIONS: These findings indicate modest relationships between both increased 
white blood cell count and emphysema and the increased 10-year incidence of
lesions defining early and late age-related maculopathy. Further investigation of
these relationships in other studies is needed.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12742845 [PubMed - indexed for MEDLINE]

419: Clin Rheumatol. 2003 May;22(2):154-5.

Comment in:
    Clin Rheumatol. 2005 Feb;24(1):91.

Rheumatoid nodules indicating seronegative rheumatoid arthritis in a patient with
gout.

Bachmeyer C, Charoud A, Mougeot-Martin M.

Département de Médecine Interne, Centre Hospitalier Laënnec, Boulevard Laënnec, B
P 72, F-60109 Creil Cedex, France. claude.bachmeyer@ch-creil.fr

The association of gout and rheumatoid arthritis is rare. We report the case of a
patient with gout who presented with rheumatoid nodules indicating seronegative
rheumatoid arthritis.

Publication Types: 
    Case Reports

PMID: 12740684 [PubMed - indexed for MEDLINE]

420: Rheumatology (Oxford). 2003 Sep;42(9):1062-6. Epub 2003 Apr 16.

Concomitant septic and gouty arthritis--an analysis of 30 cases.

Yu KH, Luo SF, Liou LB, Wu YJ, Tsai WP, Chen JY, Ho HH.

Division of Rheumatology, Allergy, and Immunology, Chang Gung Memorial Hospital, 
Tao-Yuan, Taiwan, Republic of China.

OBJECTIVES: To analyse the clinical features and outcomes of gouty patients with 
concomitant septic arthritis in a medical centre. METHODS: From the hospital
database, we collected 30 hospitalized cases with concomitant septic arthritis
and gouty arthritis from 1987 to 2001. All patients had positive bacterial
culture and monosodium urate crystals in the affected joints. Medical records of 
the patients were analysed in detail. RESULTS: The mean age of patients was
52.8+/-12.5 yr. One-third of patients were afebrile at presentation, 30% had a
normal blood leucocyte count and 10% had a synovial fluid leucocyte count less
than 6000/mm3. The knee joint was the most common site of involvement, followed
by the ankle, shoulder and wrist joints. Most patients had long-standing disease 
and subcutaneous tophi. Subcutaneous tophi rupture with secondary wound infection
is the most common route of infection. Causative micro-organisms were
Staphylococcus aureus (16 cases, 7 of whom were oxacillin-resistant),
Streptococcus sp. (5 cases), Pediococcus sp. (1 case), and Gram-negative bacilli 
(9 cases). Fourteen patients received surgical debridement, among them two
patients had an arthrodesis owing to severe joint destruction and one received
above-knee amputation. Two patients died. One died of septic complications and
the other died of acute myocardial infarction. CONCLUSIONS: Septic arthritis
coexistent with gout presented a diagnostic difficulty. An early diagnosis
requires a high level of suspicion. Prompt aspiration and analysis of the
synovial fluid is imperative, regardless of the absence of fever or leucocytosis.
Culture of the aspirated synovial fluid is warranted in gouty attack, even when
it has a low white cell count or the Gram stain reveals no organisms.

PMID: 12730521 [PubMed - indexed for MEDLINE]

421: Chir Main. 2003 Feb;22(1):46-50.

Gouty involvement of flexor tendons.

Schuind FA, Clermont D, Stallenberg B, Remmelink M, Pasteels JL.

Department of Orthopedics and Traumatology, cliniques universitaires de
Bruxelles, université libre de Bruxelles, Erasme University Hospital, 808, route 
de Lennik, 1070 Brussels, Belgium. fschuind@ulb.ac.be

This article presents three patients suffering from complications related to
tophi deposited within the hand and wrist synovium and flexor tendons. One
patient had no previous history of gout or acute arthritis, with uricemia within 
normal values upon admission. The pathophysiology and treatment of gout in these 
special circumstances are discussed.

Publication Types: 
    Case Reports

PMID: 12723310 [PubMed - indexed for MEDLINE]

422: Joint Bone Spine. 2003 Mar;70(2):149-53.

Gouty tendinitis revealing glycogen storage disease Type Ia in two adolescents.

Carvès C, Duquenoy A, Toutain F, Trioche P, Zarnitski C, Le Roux P, Le Luyer B.

Pediatrics department, Groupe Hospitalier du Havre, Le Havre, France.

Hyperuricemia is a well-known consequence of glucose-6-phosphatase (G6Pase)
deficiency, the enzymatic abnormality that characterizes glycogen storage disease
(GSD) Type Ia. However, acute gout as the presenting manifestation of GSD Type Ia
has been reported in only a few patients. We report a new case in a 17-year-old
male evaluated for acute gouty tendinitis in the right Achilles tendon. Blood
tests showed chronic acidosis with high levels of uric acid, lactic acid, and
cholesterol. A liver enzyme study confirmed the diagnosis of GSD Type Ia. A
genetic study showed that the index patient and his sister were composite
heterozygotes for the known mutation R83C and the previously unreported mutation 
M5R. Acute gout in an adolescent with liver enlargement and high blood levels of 
uric acid and cholesterol should suggest GSD. Demonstration by molecular biology 
techniques of a mutation in both alleles of the G6Pase gene establishes the
diagnosis of GSD Type Ia, obviating the need for a liver biopsy.

Publication Types: 
    Case Reports

PMID: 12713862 [PubMed - indexed for MEDLINE]

423: Kidney Int. 2003 May;63(5):1645-51.

Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte
nuclear factor-1beta gene mutation.

Bingham C, Ellard S, van't Hoff WG, Simmonds HA, Marinaki AM, Badman MK, Winocour
PH, Stride A, Lockwood CR, Nicholls AJ, Owen KR, Spyer G, Pearson ER, Hattersley 
AT.

Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, United Kingdom.
C.Bingham@exeter.ac.uk

BACKGROUND: Familial juvenile hyperuricemic nephropathy (FJHN) is a dominantly
inherited condition characterized by young-onset hyperuricemia, gout, and renal
disease. The etiologic genes are unknown, although a locus on chromosome 16 has
been identified in some kindreds. Mutations in the gene encoding hepatocyte
nuclear factor (HNF)-1beta have been associated with dominant inheritance of a
variety of disorders of renal development, particularly renal cystic disease and 
early onset diabetes; hyperuricemia has been reported in some kindreds. METHODS: 
To assess a possible role for the HNF-1beta gene in some FJHN kindreds we
sequenced the HNF-1beta gene in subjects from three unrelated FJHN families with 
atypical features of renal cysts or abnormalities of renal development. We also
compared serum urate levels in subjects with HNF-1beta mutations with populations
of controls, type 2 diabetic subjects, and subjects with mild chronic renal
failure without HNF-1beta mutations. RESULTS: A splice-site mutation in intron 2,
designated IVS2+1G>T, showed complete co-segregation with FJHN in one family with
diabetes. Serum urate levels were significantly higher in the HNF-1beta subjects 
compared with the normal control subjects (384 micromol/L vs. 264 micromol/L, P =
0.002) and the type 2 diabetic subjects (397 micromol/L vs. 271 micromol/L, P =
0.01). Comparison of serum urate levels in the HNF-1beta subjects with
gender-matched subjects with renal impairment of other causes did not reach
significance (402 micromol/L vs. 352 micromol/L, P = 0.2). CONCLUSION:
Hyperuricemia and young-onset gout are consistent features of the phenotype
associated with HNF-1beta mutations, but the mechanism is uncertain. Families
with HNF-1beta mutations may fit diagnostic criteria for FJHN. Identification of 
HNF-1beta patients by recognizing the features of diabetes and disorders of renal
development is important in resolving the genetic heterogeneity in FJHN.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12675839 [PubMed - indexed for MEDLINE]

424: J Rheumatol. 2003 Apr;30(4):849-50.

Acute gout precipitated by total parenteral nutrition.

Moyer RA, John DS.

Osteoporosis Center of Dover, Delaware 19904, USA.

Hypouricemia is seen in a variety of clinical situations. Although precipitation 
of gout is well known following initiation of uricosuric therapy, it has been
reported rarely following the institution of total parenteral nutrition (TPN),
despite its known uricosuric effect. We describe a patient who developed
polyarticular gout on 2 occasions after a sudden decline in serum uric acid after
initiation of purine-free TPN. Potential etiologies include increased urate
clearance due to the infusion of glycine or amino acids. Monitoring of serum uric
acid concentrations in patients with a history of gout may help predict a gout
attack. Prophylactic treatment or alternative TPN formulations may be indicated.

Publication Types: 
    Case Reports

PMID: 12672211 [PubMed - indexed for MEDLINE]

425: Chin Med J (Engl). 2003 Jan;116(1):66-9.

Primary gout in Shantou: a clinical and epidemiological study.

Zeng Q, Wang Q, Chen R, Xiao Z, Huang S, Xu J.

Department of Rheumatology, The First Affiliated Hospital of Shantou University
Medical College, Shantou University Medical College, Shantou, Guangdong 515031,
China. qyzeng@stu.edu.cn

OBJECTIVE: To evaluate the prevalence of primary gout in the Shantou area, China,
and to understand its clinical features. METHODS: Samples from three surveys of
the Chenghai across ten years were studied. Clinical, laboratory and radiology
data of 419 cases of primary gout were collected and analyzed. RESULTS:
Prevalence of primary gout in the three surveys were 0.17%, 0.15% and 0.26%,
respectively. Among the clinical patients, the ratio of male to female was 21:1; 
the average age of onset of women was significantly higher than that of men. The 
number of cases in the last ten years has been increasing. In the first wave of
cases, the first metatarsophalangeal joint was involved in 82.1% of all cases; no
fourth metatarsophalangeal joint involvement had been observed. Hyperlipemia was 
the most common accompanying abnormal laboratory test (57.1%). Radiographic bone 
erosion was found in 49.4% patients, most of them with disease duration more than
5 years. CONCLUSIONS: The prevalence of primary gout in Shantou area has been
increasing in the last ten years. Changes in diet and lifestyle may be
responsible for this rapid increase.

PMID: 12667391 [PubMed - indexed for MEDLINE]

426: Orthop Nurs. 2003 Jan-Feb;22(1):16-20; quiz 21-2.

Gout: not just for the rich and famous! Everyman's disease.

Kamienski M.

St. Peter's College, Nursing Department, Montville, NJ, USA.

Gout is a painful form of arthritis that affects more than a million Americans
annually. Using a case study, a discussion of the clinical onset, signs and
symptoms, diagnosis, and treatment of acute and chronic gout is presented. The
incidence and etiology of gout is presented, along with current diagnostic
criteria and the most common differential diagnoses to consider. The current
trends in diagnosing and treating the acute and chronic forms of gout are also
addressed as well as some of the controversies and concerns about treatment
options. The treatment plan and follow-up for the patient in the case
presentation conclude the discussion.

Publication Types: 
    Case Reports

PMID: 12640948 [PubMed - indexed for MEDLINE]

427: Rheumatology (Oxford). 2003 Mar;42(3):468-72.

The elevated prevalence of apolipoprotein E2 in patients with gout is associated 
with reduced renal excretion of urates.

Cardona F, Tinahones FJ, Collantes E, Escudero A, García-Fuentes E, Soriguer FJ.

Endocrinology and Nutrition Service, Pabellon 1 sotano Hospital Civil, Complejo
hospitalario Carlos Haya, Plza del Hospital Civil s/n 29009 Málaga, Spain.

OBJECTIVE: Previous studies have demonstrated that the lower renal excretion of
urates in patients with hyperuricaemia is inversely related to plasma very
low-density lipoprotein (VLDL) levels, and the different genotypes of the
apolipoprotein E gene are related to the plasma levels of lipids. The aim of this
study was to determine the prevalence of apolipoprotein E in hyperuricaemic
patients and to investigate whether the renal excretion of urates is conditioned 
by the apoliprotein E genotype. METHOD: The plasma levels of lipoproteins,
cholesterol, triglycerides and uric acid, and the renal excretion of uric acid
were studied in 68 patients with gout and in another control group of 50 healthy 
subjects. Both groups were genotyped for apolipoprotein E by means of an
amplification technique and inverse hybridization. RESULTS: The prevalence of the
E2 allele was greater in the patients than in the control group. The levels of
cholesterol, triglycerides and uric acid were greater in the patients, whereas
the levels of high-density lipoprotein were lower. The patients with the E2
allele had higher levels of triglycerides in VLDL and intermediate-density
lipoproteins and a lower renal excretion of urates. CONCLUSIONS: These results
show that the reduced renal excretion of uric acid in patients with gout is
mediated by high levels of VLDL and by the high prevalence of the E2 allele of
apolipoprotein E.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12626798 [PubMed - indexed for MEDLINE]

428: Clin Rheumatol. 2003 Feb;22(1):73-6.

Long-term remission from gout associated with fenofibrate therapy.

Hepburn AL, Kaye SA, Feher MD.

Rheumatology Section, Faculty of Medicine, Imperial College of Science,
Technology and Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. 
a.hepburn@ic.ac.uk

Short-term studies with fenofibrate, an established treatment for
hyperlipidaemia, have shown that its unique side effect of urate lowering is
mediated through enhanced renal urate clearance. The long-term effects of
fenofibrate on hyperuricaemia and gout have not previously been reported. We
report two patients with hyperlipidaemia in association with hyperuricaemia in
whom long-term fenofibrate therapy was associated with a sustained reduction in
serum urate and lipid levels, together with remission from recurrent attacks of
acute gout. The mechanisms involved in these effects and the potential role for
fenofibrate in the management of gout are discussed.

Publication Types: 
    Case Reports

PMID: 12605325 [PubMed - indexed for MEDLINE]

429: Rheumatology (Oxford). 2003 Feb;42(2):321-5.

Fenofibrate enhances urate reduction in men treated with allopurinol for
hyperuricaemia and gout.

Feher MD, Hepburn AL, Hogarth MB, Ball SG, Kaye SA.

Lipid Clinic, London SW10 9NH, UK. m.feher@chelwest.nhs.uk

OBJECTIVE: To assess the short-term urate-lowering effect of fenofibrate in men
on long-term allopurinol therapy for hyperuricaemia and gout. METHODS: Ten male
patients (38-74 yr) with a history of chronic tophaceous or recurrent acute gout 
with hyperuricaemia and on established allopurinol at 300-900 mg/day for > or =3 
months were studied in an open-crossover study of fenofibrate therapy.
Allopurinol at the established dose was continued throughout the study. Clinical 
and biochemical assessments (serum urate and creatinine, 24-h urinary excretion
of urate and creatinine, liver function tests, creatine kinase and fasting serum 
lipids) were undertaken at: (i) baseline, (ii) after 3 weeks of once-daily
therapy with micronized fenofibrate (Lipantil Micro) at 200 mg and (iii) 3 weeks 
after fenofibrate was withdrawn. RESULTS: Fenofibrate was associated with a 19%
reduction in serum urate after 3 weeks of treatment (mean+/-S.E. 0.37+/-0.04 vs
0.30+/-0.02 mM/l; P=0.004). The effect was reversed after a 3-week fenofibrate
withdrawal period (0.30+/-0.02 vs 0.38+/-0.03 mM/l). There was a rise in uric
acid clearance with fenofibrate treatment of 36% (7.2+/-0.9 vs 11.4+/-1.6 ml/min,
normal range 6-11; P=0.006) without a significant change in creatinine clearance.
Both total cholesterol and serum triglycerides were also reduced. No patient
developed acute gout whilst taking fenofibrate. CONCLUSIONS: Fenofibrate has a
rapid and reversible urate-lowering effect in patients with hyperuricaemia and
gout on established allopurinol prophylaxis. Fenofibrate may be a potential new
treatment for hyperuricaemia and the prevention of gout, particularly in patients
with coexisting hyperlipidaemia or those resistant to conventional therapy for
hyperuricaemia.

Publication Types: 
    Clinical Trial

PMID: 12595630 [PubMed - indexed for MEDLINE]

430: Arthritis Rheum. 2003 Jan;48(1):231-9.

Rapid induction of peroxisome proliferator-activated receptor gamma expression in
human monocytes by monosodium urate monohydrate crystals.

Akahoshi T, Namai R, Murakami Y, Watanabe M, Matsui T, Nishimura A, Kitasato H,
Kameya T, Kondo H.

Department of Laboratory Medicine, Kitasato University School of Medicine,
Sagamihara, Kanagawa, Japan. akahoshi@med.kitasato-u.ac.jp

OBJECTIVE: Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a
member of the nuclear hormone receptor superfamily and functions as a key
regulator of lipid and glucose metabolism, atherosclerosis, and inflammatory
responses. This study was undertaken to evaluate the biologic role of PPAR gamma 
in self-limiting episodes of acute gouty arthritis. To do this, we investigated
PPAR gamma expression by monosodium urate monohydrate (MSU) crystal-stimulated
monocytes, and we studied the effects of PPAR gamma ligands on crystal-induced
acute inflammation. METHODS: PPAR gamma expression by MSU crystal-stimulated
human peripheral blood mononuclear cells was determined by reverse
transcription-polymerase chain reaction and immunostaining. Expression of CD36 on
monocytes was detected by flow cytometric analysis. The effects of PPAR gamma
ligands on in vitro crystal-induced cytokine production and on in vivo cellular
infiltration during crystal-induced acute inflammation were also investigated.
RESULTS: MSU crystals rapidly and selectively induced PPAR gamma expression by
monocytes. Gene expression was detected as early as 2 hours, and maximum
expression was observed at 4 hours after stimulation. The induced PPAR gamma was 
functional, since a PPAR gamma ligand was able to up-regulate CD36 expression on 
monocytes. A natural ligand of PPAR gamma, 15-deoxy-Delta(12,14)-prostaglandin
J(2) (15deoxy-PGJ(2)), significantly reduced the crystal-induced production of
cytokines by monocytes. Indomethacin inhibited cytokine production only at high
concentrations, and an antidiabetic thiazolidinedione (troglitazone) failed to
exert significant effects. Administration of troglitazone and 15deoxy-PGJ(2)
significantly prevented cellular accumulation in a mouse air-pouch model of MSU
crystal-induced acute inflammation. CONCLUSION: Rapid induction of PPAR gamma
expression on monocytes by MSU crystals may contribute, at least in part, to the 
spontaneous resolution of acute attacks of gout.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12528124 [PubMed - indexed for MEDLINE]

431: Arthritis Rheum. 2002 Dec 15;47(6):610-3.

Comment in:
    Arthritis Rheum. 2003 Oct 15;49(5):735-6; author reply 736-7.

Renal underexcretion of uric acid is present in patients with apparent high
urinary uric acid output.

Perez-Ruiz F, Calabozo M, Erauskin GG, Ruibal A, Herrero-Beites AM.

Hospital de Cruces, Baracaldo, Vizcaya, Spain. fperez@hcru.osakidetza.net

OBJECTIVE: To compare renal handling of uric acid in patients with primary gout
with that of a control group. METHODS: A case-control study of 100 patients with 
primary gout and 72 healthy controls was undertaken. Creatinine clearance, uric
acid clearance, 24-hour uric acid urinary excretion, fractional excretion of uric
acid, excretion of uric acid per volume of glomerular filtration, urinary uric
acid to creatinine ratio, and glomerular uric acid filtered load were calculated 
using 24-hour urine samples. After treatment with allopurinol to achieve similar 
glomerular filtered load of uric acid, patients were again compared with
controls. RESULTS: Patients with gout showed lower uric acid clearance,
fractional excretion of uric acid, excretion of uric acid per volume of
glomerular filtration, and urinary uric acid to creatinine ratio than controls at
baseline, when patients showed hyperuricemia. Although the glomerular uric acid
filtered load was much higher in patients with gout than controls, 24-hour uric
acid excretion was not statistically different. After treatment with allopurinol,
and achieving similar uric acid filtered loads, patients still showed lower
figures than controls. When patients with 24-hour urinary uric acids levels >700 
mg/day were compared with controls, they had lower uric acid clearance and
fractional excretion of uric acid than controls, both at baseline and after
achieving similar filtered loads with allopurinol therapy. CONCLUSIONS: Renal
underexcretion is the main mechanism for the development of primary hyperuricemia
in gout, but even patients showing apparent high 24-hour uric acid output show
lower uric acid clearance than controls, indicating that relative, low-grade
underexcretion of uric acid is at work.

PMID: 12522834 [PubMed - indexed for MEDLINE]

432: Mt Sinai J Med. 2003 Jan;70(1):23-6.

Inflammatory arthritis in the elderly.

Kerr LD.

Division of Rheumatology, Box 1244, Mount Sinai School of Medicine, One East
100th Street, New York, NY 10029, USA.

The three most common inflammatory arthritic conditions affecting the elderly are
reviewed, along with current information about the various treatments.

Publication Types: 
    Review

PMID: 12516006 [PubMed - indexed for MEDLINE]

433: Rheumatology (Oxford). 2003 Jan;42(1):166-70.

Younger age of onset of gout in Taiwan.

Yu KH, Luo SF.

Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, 5
Fu-Shin Street, Kuei-Shan, Tao-Yuan, Taiwan, Republic of China.

OBJECTIVE: To study the clinical features of gout in the community and in medical
centres, and to describe the recent changes in gout in Chinese patients. METHODS:
We analysed retrospectively the clinical features of 1079 Chinese gout patients
seen by a rheumatologist between 1993 and 2000. These included 558 patients from 
a private clinic and 521 patients from a medical centre. The data were compared
with those in previous reports of large Caucasian and non-Caucasian series.
RESULTS: The mean age of onset was 41.6 yr and the mean disease duration before
first visit was 4.2 yr. For medical centre patients, the mean age of onset was
43.0 yr and mean disease duration before the first visit was 4.8 yr. For private 
clinic patients, the mean age of onset was 40.2 yr and mean disease duration
before the first visit was 3.6 yr. Young patients with gout, with onset before
age 30, constituted 23.3 and 26.7% of the medical centre and private clinic
patients respectively. Female patients constituted 10.6 and 5.6% respectively,
the family history was positive in 27.1 and 28.7%, and urolithiasis occurred in
11.5 and 10.9%. Tophi were found in 21.1% of medical centre and 12.7% of private 
clinic patients. The mean time from first gouty attack to visible tophi was 6.6
yr in those who developed tophi. CONCLUSIONS: The age at onset of gout was much
earlier than in previous reports. Twenty-five per cent of patients had their
first gouty attack before age 30. The first attack frequently occurred between
the third and fifth decades (68.2%) rather than between the fourth and sixth
decades, as reported in previous papers. The incidence of gout in females had
increased (8.0% of the patients were female) and the incidence of tophi was high 
(16.8%). Besides, our patients had more frequent gouty attacks and the interval
from the first attack to visible tophi was shorter than in previous reports of
the disease in Caucasians.

Publication Types: 
    Comparative Study

PMID: 12509631 [PubMed - indexed for MEDLINE]

434: Kidney Int. 2003 Jan;63(1):143-55.

Urate transport via human PAH transporter hOAT1 and its gene structure.

Ichida K, Hosoyamada M, Kimura H, Takeda M, Utsunomiya Y, Hosoya T, Endou H.

Department of Internal Medicine, Jikei University School of Medicine, Kyorin
University School of Medicine, Tokyo, Japan.

BACKGROUND: We recently cloned the human organic anion transporter 1 (hOAT1) as a
p-aminohippurate (PAH) transporter. Whether urate is transported by the PAH
transporter in humans remains unclear. Familial juvenile gouty nephropathy (FJGN)
is thought to develop as a result of an abnormality in the urate transporter.
METHODS: To determine if hOAT1 transported urate, the cellular uptakes of PAH and
urate were determined, as were the inhibition profiles of inorganic anions, and
uricosuric and antiuricosuric agents using a mouse S2 cell line expressing hOAT1.
The hOAT1 gene was cloned from a genomic library using full-length hOAT1-1 cDNA
as a probe. The coding regions of the hOAT1 genes of two sisters with FJGN were
sequenced. Also, immunohistochemical fluorescence analysis of hOAT1 in the kidney
of the younger sister with FJGN was performed. RESULTS: The Km and Vmax values of
urate transport via hOAT1 were 943 +/- 84 micromol/L and 1286 +/- 162 pmol/mg
protein/min, respectively. The order of the IC50 of urate transport via hOAT1 was
benzbromarone < probenecid < salicylate or pyrazine carboxylic acid. The 10.9 kb 
hOAT1 gene was found to be interrupted by nine introns. Mutations in the coding
region of the hOAT1 gene from the two sisters with FJGN were undetectable.
Immunohistochemical fluorescent staining showed that hOAT1 in the kidney of the
younger sister was similar to that of control individuals. CONCLUSIONS: Our data 
show that hOAT1 transports urate, and the inhibition profiles of uricosuric and
antiuricosuric agents are defined. hOAT1 is not responsible for FJGN in the two
sisters examined in this study.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12472777 [PubMed - indexed for MEDLINE]

435: Urology. 2002 Nov;60(5):789-94.

Biochemical distinction between hyperuricosuric calcium urolithiasis and gouty
diathesis.

Pak CY, Poindexter JR, Peterson RD, Koska J, Sakhaee K.

Center for Mineral Metabolism and Clinical Research, University of Texas
Southwestern Medical Center, Dallas, Texas 75390-8885, USA.

OBJECTIVES: To determine whether the biochemical presentation and urinary
physicochemical environment of patients with hyperuricosuria presenting with
calcium stones (hyperuricosuric calcium urolithiasis [HUCU]) differs from those
of patients with gouty diathesis (GD) or idiopathic uric acid urolithiasis.
METHODS: A total of 122 patients with HUCU and 68 patients with GD were
identified from our "stone registry" of patients who underwent a full ambulatory 
evaluation. All patients with HUCU had urinary uric acid greater than 800 mg/day 
in men and greater than 750 mg/day in women and presented with calcium stones.
Those with GD had pure uric acid stones or mixed uric acid-calcium stones and did
not have secondary causes of uric acid urolithiasis. Data derived from the
fasting serum and 24-hour urine samples collected on a random diet and on a diet 
restricted in calcium, sodium, and oxalate were compared between the two groups. 
RESULTS: Compared with patients with HUCU, those with GD had significantly higher
serum uric acid and lower urinary uric acid and pH levels (mean value 5.38 and
5.35 on random and restricted diets versus 6.09 and 6.14, respectively). The
fractional excretion of urate and the discriminant score of the relationship
between urinary pH and the fractional excretion of urate were significantly lower
in those with GD than in those with HUCU. Patients with HUCU displayed a greater 
urinary saturation of sodium urate and calcium oxalate compared with those with
GD, and those with GD had a higher urinary content of undissociated uric acid and
lower urinary saturation of brushite (calcium phosphate). CONCLUSIONS: Patients
with HUCU presented with normal urinary pH and hyperuricosuria, accompanied
sometimes by hypercalciuria, which produced increased urinary saturation of
sodium urate and calcium oxalate. In contrast, those with GD had a low fractional
excretion of urate (that contributed to hyperuricemia) and low urinary pH (that
led to increased amount of undissociated uric acid). The varying biochemical and 
physicochemical presentations of the two conditions can be ascribed to
overindulgence with purine-rich foods in those with HUCU and underlying primary
gout in those with GD.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 12429297 [PubMed - indexed for MEDLINE]

436: Bull Exp Biol Med. 2002 May;133(5):491-3.

Dyshormonal disorders in gout: experimental and clinical studies.

Mukhin IV, Ignatenko GA, Nikolenko VY.

Donetsk State Medical University.

A total of 107 patients with primary gout were examined. The pituitary-gonadal
system is imbalanced in male patients with gout, which manifests by
hyperproduction of progesterone and suppressed production of testosterone and
estradiol. These changes are more pronounced in patients with chronic arthritis
and proteinuric nephropathy. Similar dyshormonal changes are experimentally
simulated in rats by induction of purine metabolism disorders. Exogenous
injection of androgens in experimental hyperuricemia led to normalization of
purine metabolism and hormonal homeostasis.

PMID: 12420070 [PubMed - indexed for MEDLINE]

437: J Rheumatol. 2002 Nov;29(11):2403-6.

Epidemiology of gout: is the incidence rising?

Arromdee E, Michet CJ, Crowson CS, O'Fallon WM, Gabriel SE.

Division of Rheumatology, Mayo Clinic, Rochester, Minnesota 55905, USA.

OBJECTIVE: To determine whether the incidence of gout is higher in 1995-1996
compared to 1977-1978. METHODS: Using the Rochester Epidemiology Project
computerized medical record system, all potential cases of acute gout in the city
of Rochester, Minnesota during the time intervals of 1977-1978 and 1995-1996 were
identified. The complete medical records of all potential cases were screened and
all who fulfilled the 1977 American College of Rheumatology proposed criteria for
gout were included as incidence cases. Demographic data, body mass index,
clinical presentation, and associated comorbid conditions were abstracted. The
overall and age-gender adjusted incidence rates from the 2 cohorts were
calculated and compared. RESULTS: A total of 39 new cases of acute gout were
identified during the 2 year interval 1977-1978 representing an age and
sex-adjusted annual incidence rate of 45.0/100,000 (95% CI: 30.7, 59.3). For the 
interval 1995-1996, 81 cases were diagnosed, representing an annual incidence
rate of 62.3/100,000 (95% CI: 48.4, 76.2). There was a greater than 2-fold
increase in the rate of primary gout (i.e., no history of diuretic exposure) in
the recent compared to the older time periods (p = 0.002). The incidence of
secondary, diuretic related gout did not increase over time (p = 0.140).
CONCLUSION: Our results indicate that the incidence of primary gout has increased
significantly over the past 20 years. While this increase might be a result of
improved ascertainment of atypical gout, it may also be related to other, as yet 
unidentified, risk factors.

PMID: 12415600 [PubMed - indexed for MEDLINE]

438: Clin Radiol. 2002 Oct;57(10):919-25.

Tophaceous gout of the spine: MR imaging features.

Hsu CY, Shih TT, Huang KM, Chen PQ, Sheu JJ, Li YW.

Department of Medical Imaging, National Taiwan University, Medical College and
Hospital, 7, Chung-Shan S. Rd, Taipei, Taiwan.

AIM: To define the magnetic resonance (MR) imaging features of tophaceous gout of
the spine. MATERIALS AND METHODS: We present the MR imaging examinations of 4
patients with spinal tophaceous gout. Spin-echo T1-weighted and fast spin-echo
T2-weighted images were obtained for all patients, and 2 patients had
gadolinium-enhanced MR imaging studies. Corresponding computed tomography (CT)
was performed in one patient. All images were evaluated for the characteristics
of the gouty tophi. RESULTS: The gouty tophi were located at the lower thoracic
(n=1) and lumbar (n=3) levels. All tophi yielded homogeneous intermediate to low 
signal on T1-weighted images and variable signal intensity on T2-weighted images,
comprising small foci of very low signal intensity on all sequences.
Gadolinium-enhanced MR imaging studies revealed homogeneous enhancement or
heterogeneous peripheral enhancement. Diffuse stippled calcifications were found 
in the tophi on CT images. Periarticular tophi with juxtaarticular bony erosions 
around facet joints occurred in 3 patients. CONCLUSION: Spinal tophaceous gout
should be considered in the differential diagnosis when periarticular deposits
contain very low signal foci on all MR imaging sequences.

PMID: 12413917 [PubMed - indexed for MEDLINE]

439: Arthritis Rheum. 2002 Oct;46(10):2765-75.

Activation of melanocortin type 3 receptor as a molecular mechanism for
adrenocorticotropic hormone efficacy in gouty arthritis.

Getting SJ, Christian HC, Flower RJ, Perretti M.

Immunopharmacology Unit, The William Harvey Research Institute, St
Bartholomew's/Royal London School of Medicine and Dentistry, Charterhouse Square,
London EC1M 6BQ, UK.

OBJECTIVE: To test the hypothesis that local activation of melanocortin
receptor(s) by adrenocorticotropic hormone (ACTH) could be responsible, at least 
in part, for its efficacy in human gouty arthritis. METHODS: Monosodium urate
monohydrate (MSU) crystals were administered into rat knee joints either alone or
with ACTH or a selective melanocortin type 3 receptor (MC3-R) agonist. Neutrophil
migration, arthritis score, increases in joint size, and cytokine levels were
measured over time. MC3-R expression on rat knee joint macrophages was monitored 
by electron microscopy and intracellular accumulation of cyclic adenosine
monophosphate. RESULTS: MSU crystals produced a knee joint inflammation that was 
time dependent and was characterized by cell influx and cytokine release that was
sensitive to treatment with classic anti-arthritic drugs (indomethacin,
colchicine, dexamethasone). Local, but not systemic, ACTH had an antiinflammatory
effect in normal rats, a dose that did not alter circulating corticosterone (5
microg). This treatment was also effective in adrenalectomized rats. Rat knee
joint macrophages expressed functional MC3-R. The MC3-R antagonist (SHU9119, 10
microg) blocked ACTH antiinflammatory actions, whereas antiinflammatory activity 
was retained with a selective MC3-R agonist (gamma(2)-melanocyte-stimulating
hormone). CONCLUSION: This research provides evidence for a separate mechanism of
action of ACTH in experimental gouty arthritis and points to a novel
antiinflammatory target (selective agonists at MC3-R) for clinical management of 
human gouty arthritis and possibly other chronic inflammatory conditions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12384937 [PubMed - indexed for MEDLINE]

440: Nephron. 2002;92(3):573-5.

Familial juvenile gouty nephropathy: exclusion of 16p12 from the candidate locus.

Ohno I, Ichida K, Okabe H, Moritani M, Itakura M, Saito M, Kamatani N, Hosoya T.

Division of Kidney and Hypertension, Department of Internal Medicine, Jikei
University School of Medicine, Tokyo, Japan. i-ohno@jikei.ac.jp

BACKGROUND/AIMS: Familial juvenile gouty nephropathy (FJGN, MIM 162000) is an
autosomal-dominant renal disease characterized by underexcretion-type
hyperuricemia, gouty arthritis, and progressive renal disease at younger ages. We
analyzed the localization of the responsible gene for FJGN concerning the
chromosomal region of 16p12 using parametric linkage analysis in our FJGN.
METHODS: The affected members of this family were accompanied with polyuria due
to nephrogenic diabetes insipidus and without hypertension. Fifteen samples were 
collected from 9 affected and 6 nonaffected members of the family. By using
microsatellite markers mainly focused on the short arm of chromosome 16, two
point and multipoint linkage analyses were carried out. RESULTS: All of the
2-point logarithm of odds (LOD) scores were typically negative and all of the
multipoint LOD scores were less than -3.0 in our FJGN family. CONCLUSIONS: The
results suggested that the localization of the responsible gene to 16p12 can be
excluded in our FJGN family. This finding means that the responsible gene for
FJGN is not common. Copyright 2002 S. Karger AG, Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12372939 [PubMed - indexed for MEDLINE]

441: N Z Med J. 2002 Jul 26;115(1158):U109.

Erratum in:
    N Z Med J 2002 Aug 23;115(1160):1.

A survey of indications, results and complications of surgery for tophaceous
gout.

Kumar S, Gow P.

Department of Rheumatology, Middlemore Hospital, Auckland, New Zealand.

AIMS: To document the indications, results and complications associated with
surgery for tophaceous gout in Middlemore Hospital. METHODS: A retrospective
study of the notes of all patients who underwent surgery for tophaceous gout at
Middlemore Hospital from July 1995 to July 2001 was performed. Serum creatinine
and uric acid results were obtained and the use of allopurinol assessed. RESULTS:
45 patients underwent surgery for gouty tophi. 89% were males and 11% females.
16% were Maori, 38% Pacific people, 42% Europeans and 4% were from other ethnic
backgrounds. Renal impairment (serum creatinine. >0.11 mmol/L) was the most
common associated medical problem (38%), followed by hypertension (27%),
ischaemic heart disease and/or congestive heart disease (20%) and diabetes
mellitus (18%). 68% of patients had elevated serum urate levels (>0.42 mmol/L)
and only 31% had previously been taking allopurinol. Sepsis control in infected
or ulcerated tophi was the main indication for surgery (51%), followed by
mechanical problems caused by foot, elbow and hand tophi (27%). The diagnosis of 
soft tissue masses was unclear in 18% of the patients prior to surgery. 4% of
patients underwent tophus surgery mainly for pain control. 53% of patients
experienced delayed wound healing as a result of complications of surgery with
the majority of these patients (16/24, 67%) having infected or ulcerated tophi
prior to surgery. Three patients (7%) required digital amputations for ongoing
sepsis. 47% of patients did not have any complication of surgery and had complete
wound healing within one week. CONCLUSIONS: Surgery for tophaceous gout is
associated with a relatively high rate of complication when sepsis is the main
indication. Patients with gout in this study population had several associated
medical co-morbidities, which contributed to the high complication rate. Gout
control was poor as evidenced by a high rate of hyperuricaemia, and less than one
third of the study population were on allopurinol. Better control of gout would
reduce the risk of tophi formation and the need for surgery.

PMID: 12362184 [PubMed - indexed for MEDLINE]

442: J Rheumatol. 2002 Sep;29(9):1950-3.

The inflammatory process in the mechanism of decreased serum uric acid
concentrations during acute gouty arthritis.

Urano W, Yamanaka H, Tsutani H, Nakajima H, Matsuda Y, Taniguchi A, Hara M,
Kamatani N.

The Institute of Rheumatology, Tokyo Women's Medical University, Japan.
wako@ior.twmu.ac.jp

OBJECTIVE: To clarify the mechanism of decreased serum uric acid (SUA)
concentrations during acute gouty arthritis. METHODS: Data from patients with
acute gouty arthritis during and after an attack were investigated
retrospectively. Other investigations, including changes in urinary excretion and
biochemical markers, were performed prospectively. RESULTS: SUA was significantly
lower in the acute phase (7.5 +/- 1.4 mg/dl) than in the intercritical phase (8.5
+/- 0.9 mg/dl) (p < 0.0001). During the acute gout phase, a normal SUA level was 
found in 20 of 41 patients (49%). C-reactive protein (CRP) during acute attacks
was significantly correlated with plasma interleukin 6 (IL-6) and cortisol (r =
0.645, p < 0.005; r = 0.460, p < 0.05). Percentage change in SUA at onset of
attack correlated with CRP and IL-6 (r = 0.762, p < 0.0001; r = 0.630, p <
0.005), as well as with increased urinary excretion of uric acid, estimated by
percentage change in fractional excretion of uric acid (FEua) during attack (r = 
0.447, p < 0.05). Further, change in FEua was correlated with plasma cortisol
levels during the acute attack (r = 0.534, p < 0.05). CONCLUSION: Decrease in SUA
during acute gouty arthritis is associated with increased urinary excretion of
uric acid; an inflammatory process may play a role in the mechanism.

Publication Types: 
    Comparative Study

PMID: 12233891 [PubMed - indexed for MEDLINE]

443: J Rheumatol. 2002 Sep;29(9):1937-41.

A simple method of selecting gout patients for treatment with uricosuric agents, 
using spot urine and blood samples.

Yamamoto T, Moriwaki Y, Takahashi S, Tsutsumi Z, Ka T, Fukuchi M, Hada T.

Department of Internal Medicine, Hyogo College of Medicine, Japan.
tetsuya@hyo-med.ac.jp

OBJECTIVE: To develop a simple means of selecting gout patients for treatment
with uricosuric agents. METHODS: In 124 gout patients, spot urine and blood were 
sampled before breakfast and after overnight fast (except water) on the day of 24
h urine collection. Spot urine uric acid/creatinine ratio (Ua/Cr mmol/mmol) and
serum creatinine x Ua/Cr (Scr*Ua/Cr micromol/l) were calculated together with 24 
h urinary uric acid excretion/body surface (24 Ua/S). The patients were then
classified either below or above 2.84 mmol/m2/day for 24 Ua/S. RESULTS:
Classifications based on spot urine Ua/Cr (cut off value set at 0.34), spot urine
Scr*Ua/Cr (cut off value set at 28.1), and a combination of spot urine Ua/Cr and 
Scr*Ua/Cr were found to be not significantly different in diagnostic accuracy for
the detection of patients with 24 Ua/S below 2.84 mmol/m2 (77%, 81%, and 81%,
respectively) and sensitivity (80%, 83%, and 76%, respectively). However,
specificity by a combination of spot urine Ua/Cr, and spot urine Scr*Ua/Cr was
higher than by spot urine Ua/Cr alone (91% vs 74%, P < 0.05), although the
specificity was not significantly different between a combination and spot urine 
Scr*Ua/Cr alone (91% vs 78%) or between spot urine Ua/Cr and spot urine Scr*Ua/Cr
(74% vs 78%). CONCLUSION: A combination of spot urine Ua/Cr and spot urine
Scr*Ua/Cr may be clinically useful in selecting gout patients with 24 Ua/S below 
2.84 mmol/m2 for treatment with uricosuric agents without adverse effects.

Publication Types: 
    Comparative Study

PMID: 12233889 [PubMed - indexed for MEDLINE]

444: Arthritis Rheum. 2002 Aug;47(4):356-60.

Effect of urate-lowering therapy on the velocity of size reduction of tophi in
chronic gout.

Perez-Ruiz F, Calabozo M, Pijoan JI, Herrero-Beites AM, Ruibal A.

Hospital de Cruces, Pais Vasco, Spain. fperez@hcru.osakidetza.net

OBJECTIVE: The optimal serum urate levels necessary for elimination of tissue
deposits of monosodium urate in patients with chronic gout is controversial. This
observational, prospective study evaluates the relationship between serum urate
levels during therapy and the velocity of reduction of tophi in patients with
chronic tophaceous gout. METHOD: Sixty-three patients with crystal-confirmed
tophaceous gout were treated with allopurinol, benzbromarone, or combined therapy
to achieve serum uric acid levels less than the threshold for saturation of urate
in tissues. The tophi targeted for evaluation during followup were the largest in
diameter found during physical examination. RESULTS: Patients taking
benzbromarone alone or combined allopurinol and benzbromarone therapy achieved
faster velocity of reduction of tophi than patients taking allopurinol alone. The
velocity of tophi reduction was linearly related to the mean serum urate level
during therapy. The lower the serum urate levels, the faster the velocity of
tophi reduction. CONCLUSION: Serum urate levels should be lowered enough to
promote dissolution of urate deposits in patients with tophaceous gout.
Allopurinol and benzbromarone are equally effective when optimal serum urate
levels are achieved during therapy. Combined therapy may be useful in patients
who do not show enough reduction in serum urate levels with single-drug therapy.

Publication Types: 
    Clinical Trial

PMID: 12209479 [PubMed - indexed for MEDLINE]

445: J Med Assoc Thai. 2002 Jun;85 Suppl 1:S40-7.

Efficacy of benzbromarone compared to allopurinol in lowering serum uric acid
level in hyperuricemic patients.

Hanvivadhanakul P, Akkasilpa S, Deesomchok U.

Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok,
Thailand.

This study was aimed to evaluate the efficacy of benzbromarone compared to
allopurinol in lowering serum uric acid level in hyperuricemic patients with
normal renal function (serum creatinine < or = 1.5). The authors conducted a
crossover study consisting of two four-week treatment periods of allopurinol 300 
mg/day and benzbromarone 100 mg/day separated by a four-week washout period.
Fourteen patients with mean age and duration of hyperuricemia of 60.78 +/- 8.62
and 6.93 +/- 3.69 years, respectively, were recruited and all completed our study
protocol. This study was a crossover design consisting of two four-week
treatments of allopurinol and benzbromarone separated by a four-week washout
period. The serum uric acid level was reduced from 9.89 +/- 1.43 mg/dl to 5.52
+/- 0.83 mg/dl and from 9.53 +/- 1.48 to 4.05 +/- 0.87 mg/dl by allopurinol and
benzbromarone, respectively. The efficacy of benzbromarone in lowering serum uric
acid level was significantly superior to allopurinol (p=0.005). No patient
reported clinical side effects during treatment with either drug. In conclusion, 
the authors have shown that benzbromarone is more effective than allopurinol in
the reduction of serum uric acid levels in hyperuricemic patients with normal
renal function.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 12188443 [PubMed - indexed for MEDLINE]

446: Cleve Clin J Med. 2002 Aug;69(8):594, 597, 600-2 passim.

Comment in:
    Cleve Clin J Med. 2002 Aug;69(8):589-90, 592-3.

Asymptomatic hyperuricemia: to treat or not to treat.

Dincer HE, Dincer AP, Levinson DJ.

Department of Medicine, Michael Reese Hospital and Medical Center, Chicago, USA. 
hdincer@mcw.edu

Treatment of asymptomatic hyperuricemia is not necessary in most patients, unless
perhaps they have very high levels of uric acid or are otherwise at risk of
complications, such as those with a personal or strong family history of gout,
urolithiasis, or uric acid nephropathy.

Publication Types: 
    Review

PMID: 12184468 [PubMed - indexed for MEDLINE]

447: Joint Bone Spine. 2002 Jun;69(4):409-11.

Lead-related gout. A case report.

Niamane R, El Hassani S, Bezza A, Lazrak N, Hajjaj-Hassouni N.

Hĵpital El Ayachi Salé, Morocco. rniamane@caramail.com

Gout secondary to lead-induced nephropathy is a long-term complication of
occupational lead exposure. We report a case of this now-rare condition. The
patient was a 63-year-old man who had been a miner from 1950 to 1970. Thirty
years after cessation of his exposure to lead, he experienced onset of
inflammatory symmetric polyarthritis with joint deformities. Hyperuricemia,
moderately severe renal failure, and tubular acidosis were found, indicating
gouty polyarthritis. Blood lead levels were high, establishing that the cause was
lead poisoning. EDTA chelation therapy was effective. Lead poisoning is
frequently under-recognized because the clinical manifestations are often minimal
and the diagnosis difficult to establish. We suggest that lead bound to bone may 
result in continued exposure to lead after cessation of industrial or
environmental exposure. Chelating agents are valuable for the diagnosis and can
ensure a full recovery.

Publication Types: 
    Case Reports

PMID: 12184440 [PubMed - indexed for MEDLINE]

448: Ren Fail. 2002 May;24(3):361-7.

Hyperuricemia and gout in renal transplant recipients.

Abdelrahman M, Rafi A, Ghacha R, Youmbissi JT, Qayyum T, Karkar A.

Nephrology Department, Kanoo Kidney Center, Dammam Central Hospital, Saudi
Arabia. mrabdelrahman@hotmail.com

Hyperuricemia, unlike clinical gout, is extremely common in renal transplant
patients. The high prevalence of hyperuricemia is related to prolonged exposure
to cyclosporine rather than to its dose or serum concentration. Serum creatinine 
levels do not show significant correlation with hyperuricemia, behaving more like
a surrogate marker for cyclosporine dose and trough level. The low incidence of
gout in renal transplant patients, despite the hyperuricemia, may be related to
the prolonged immunosuppression effect.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 12166703 [PubMed - indexed for MEDLINE]

449: Dermatol Surg. 2002 Jul;28(7):636-8.

Gouty tophi: a squamous cell carcinoma mimicker?

Dacko A, Hardick K, McCormack P, Szaniawski W, Davis I.

Department of Dermatology, Beth Israel Medical Center New York, New York 10003,
USA.

BACKGROUND: Digital lesions can have a broad differential diagnosis. Squamous
cell carcinoma (SCC), the most common digital malignant neoplasm, must be
excluded as the cause of persistent digital lesions causing nail dystrophy.
OBJECTIVE: To describe a patient with a periungual hyperkeratotic lesion on the
left fifth digit which, upon initial dermatopathologic examination, appeared to
be a malignancy. However, on further biopsy, the lesion proved to be a gouty
tophus. METHODS: Case report and literature review. RESULTS: An 84-year-old white
man presented with a hyperkeratotic papule on the lateral proximal nail fold of
the left fifth digit, which resulted in nail dystrophy for 1 year. Similar
lesions were present on several other digits which did not affect the nail plate.
Initial biopsy was consistent with actinic keratosis and was treated with
cryotherapy. When the lesion persisted, repeat biopsy was performed,
demonstrating fragments of squamous epithelium with focal atypia and an
infiltrative growth pattern. SCC could not be excluded and the patient was
referred for Mohs micrographic surgery (MMS) consultation. An excisional biopsy
was performed and a white chalky material was observed at the base of the defect.
Histopathology confirmed a gouty tophus. The patient was referred to his primary 
care physician and was treated with allopurinol. CONCLUSION: This is the first
report of gouty tophus of the periungual region presenting as a hyperkeratotic
lesion. Initial clinical diagnosis favored SCC and histologic evidence suggested 
a possible early SCC. This lesion can be confused with digital squamous cell
carcinoma. The presence of pseu- docarcinomatous hyperplasia may complicate
accurate diagnosis.

Publication Types: 
    Case Reports

PMID: 12135525 [PubMed - indexed for MEDLINE]

450: J Hand Surg [Am]. 2002 Jul;27(4):591-3.

Flexor tendon rupture caused by gout: a case report.

Wurapa RK, Zelouf DS.

Department of Orthopedics, Division of Hand Surgery, The Philadelphia Hand
Center, Thomas Jefferson University, Philadelphia, PA, USA.

We present a case of primary gouty infiltration of flexor tendons in the hand,
causing rupture of both flexor digitorum superficialis and profundus tendons in a
single digit. The patient was managed by a single-stage reconstruction of the
less involved flexor digitorum superficialis tendon using a segment of the
proximal stump of flexor digitorum profundus tendon as a bridge graft. This
uncommon etiology of tendon rupture should be considered in all patients with a
history of gout presenting with tendon insufficiency.

Publication Types: 
    Case Reports

PMID: 12132081 [PubMed - indexed for MEDLINE]

451: Transpl Int. 2002 Jul;15(7):374-6. Epub 2002 Jun 20.

Colchicine myoneuropathy in a renal transplant patient.

Dupont P, Hunt I, Goldberg L, Warrens A.

Department of Renal Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN,
UK.

Colchicine is widely employed for the treatment of gout in renal transplant
patients where NSAIDs are contra-indicated and allopurinol prophylaxis is often
avoided due to concomitant azathioprine immunosuppression. We report here a case 
of colchicine-induced myoneuropathy in a renal transplant recipient. Our patient 
had myalgia, muscle weakness, elevated creatine kinase levels, myopathic changes 
on electromyography and peripheral neuropathy. Withdrawal of colchicine resulted 
in recovery within 4 weeks. Renal transplant recipients are likely to be at
greater risk of colchicine-induced myoneuropathy due to the unique concurrence of
risk factors predisposing to toxicity in such patients. These risk factors
include the high incidence of gout in this population, widespread use of
colchicine as first-line therapy, impaired renal function and concomitant
cyclosporin treatment. The diagnosis should be considered in any renal transplant
recipient receiving the drug who develops myopathy. Prompt withdrawal of
colchicine therapy should result in rapid clinical and biochemical improvement.

Publication Types: 
    Case Reports

PMID: 12122515 [PubMed - indexed for MEDLINE]

452: Arthritis Rheum. 2002 Jun;46(6):1643-50.

Monosodium urate monohydrate crystal-induced inflammation in vivo: quantitative
histomorphometric analysis of cellular events.

Schiltz C, Lioté F, Prudhommeaux F, Meunier A, Champy R, Callebert J, Bardin T.

Laboratoire de Radiologie Expérimentale et de Physiopathologie Articulaire
(JE2149), Centre Viggo Petersen, Hôpital Lariboisière, 2 rue Ambroise Paré, 75475
Paris Cedex 10, France. corinne.schiltz@lrb.ap-hop-paris.fr

OBJECTIVE: To quantify the inflammatory cell response in rat air pouch
pseudosynovial membrane during monosodium urate monohydrate (MSU) crystal-induced
inflammation. METHODS: In the rat air-pouch model, we used a computer-assisted
histomorphometric method to quantify cell distributions, based on cell linear
densities, in histologic sections of membranes from pouches injected with MSU or 
saline. The volume, white blood cell (WBC) count, and histamine content of the
pouch exudates were determined at several time points. RESULTS: Injection of 10
mg of MSU crystals into the pouch produced an acute exudate. After peaking at 24 
hours, the exudate volume and WBC count decreased spontaneously over the next 3
days, simulating the self-limited course of acute gout. Membrane thickness
followed a parallel course. Membrane polymorphonuclear cell (PMN) linear
densities were closely correlated with exudate WBC counts, suggesting PMN
recruitment from the subintimal synovial membrane. Both monocyte/macrophage and
mast cell linear densities increased in the subintimal layer 2 hours after
crystal injection (P = 0.038 and P = 0.03, respectively, versus controls),
whereas PMN linear densities showed 2 peaks, one at 4 hours and the other 24
hours. The exudate histamine content peaked 6 hours after crystal injection, when
mast cell linear densities were minimal in the membranes, suggesting mast cell
degranulation. CONCLUSION: An increase in monocyte/macrophage and mast cell
densities in the membrane preceded the PMN influx in the pouch membrane and
exudate, suggesting that mast cells may be involved in the early phase of MSU
crystal-induced inflammation, at least in this rat model.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12115197 [PubMed - indexed for MEDLINE]

453: J Emerg Med. 2002 May;22(4):385-7.

Deaths associated with inappropriate intravenous colchicine administration.

Bonnel RA, Villalba ML, Karwoski CB, Beitz J.

Office of Drug Safety, Center for Drug Evaluation and Research, US Food and Drug 
Administration, Rockville, Maryland 20857, USA.

Intravenous (IV) colchicine is occasionally prescribed for the treatment of acute
gouty arthritis. The Food and Drug Administration (FDA) recently received a
report of death in a patient that was associated with inappropriate IV dosing of 
colchicine. This report prompted further investigation of other deaths associated
with IV colchicine use in the FDA Adverse Event Reporting System (AERS) and the
medical literature. A total of 20 deaths were identified. Eight patients were
females, 11 were males, and the gender was unknown in 1. In all cases, the
recommended maximum cumulative dose of 2 to 4 mg during a course of therapy was
exceeded. Dose reductions are recommended in patients with renal or hepatic
disease and in the elderly. All reported adverse events were associated with
colchicine toxicity, including thrombocytopenia, leukopenia, pancytopenia,
agranulocytosis, aplastic anemia, acute renal failure, and disseminated
intravascular coagulopathy. Death occurred within 1 to 40 days after drug
administration. Therapeutic guidelines exist for use of IV colchicine and these
guidelines should be followed to prevent serious toxicities and death.

Publication Types: 
    Case Reports

PMID: 12113850 [PubMed - indexed for MEDLINE]

454: Arthritis Res. 2002;4 Suppl 3:S91-7. Epub 2002 May 9.

Interactions between leukocytes and endothelial cells in gout: lessons from a
self-limiting inflammatory response.

Haskard DO, Landis RC.

BHF Cardiovascular Medicine Unit, Faculty of Medicine, Imperial College,
Hammersmith Hospital, London, UK. d.haskard@ic.ac.uk

Interactions with endothelium are necessary for leukocytes to pass from the blood
into extravascular tissues, and such interactions are facilitated in inflammation
by the coordinated expression of endothelial adhesion molecules and
chemoattractants. Although the general mechanisms and intracellular pathways of
endothelial activation are now fairly well characterised in vitro, relatively
little detailed information exists on how endothelial activation changes during
the course of inflammatory responses and how such change influences the amount of
leukocyte recruitment and the types of leukocytes recruited. Having developed a
radiolabelled-antibody-uptake technique for quantifying the expression of
endothelial adhesion molecules in relation to leukocyte trafficking, we have
analysed the acute, self-limiting inflammatory response to injection of
monosodium urate (MSU) crystals. Our studies have supported the view that
endothelial activation is closely paralleled by leukocyte recruitment at the
onset of the response and have highlighted separate vascular and extravascular
stages of downregulation. More recent studies addressing the extravascular
contribution to downregulation point to an important role for monocyte-macrophage
differentiation in limiting further endothelial activation as a consequence of
phagocytosis of MSU crystals.

Publication Types: 
    Review

PMID: 12110127 [PubMed - indexed for MEDLINE]

455: Am J Kidney Dis. 2002 Jul;40(1):37-42.

The association between gout and nephrolithiasis: the National Health and
Nutrition Examination Survey III, 1988-1994.

Kramer HM, Curhan G.

Renal Unit, Department of Medicine, Massachusetts General Hospital, USA.

BACKGROUND: Gout, an inflammatory arthritis, reportedly afflicts more than 2
million men and women in the United States. Previous reports have suggested an
association between gout and kidney stone disease; however, these studies did not
adjust for such important potential confounders as obesity and the presence of
hypertension. To our knowledge, no published study has examined the independent
association between gout and kidney stone disease. METHODS: We used a national
probability sample of the US population to determine the independent association 
between reported gout and history of kidney stone disease. RESULTS: Among men and
women 20 years and older, 5.6% (10 million) reported the previous passage of a
kidney stone and 2.7% (5.1 million) reported a diagnosis of gout by a physician. 
Moreover, 8.6% of individuals who reported the passage of a kidney stone on two
or more occasions had a history of gout. Conversely, the prevalence of previous
kidney stones in subjects with reported gout was 13.9%. In the age-adjusted
model, gout was associated with an increased odds ratio (OR) for previous kidney 
stones (OR, 1.97; 95% confidence interval [CI], 1.37 to 2.83). After further
adjustment for sex, race, body mass index, and presence of hypertension, the OR
for previous kidney stones in individuals with gout decreased to 1.49 (95% CI,
1.04 to 2.14). CONCLUSION: Showing an independent association between kidney
stone disease and gout strongly suggests that they share common underlying
pathophysiological mechanisms. Identification of these mechanisms may lead to
improved preventive strategies for both conditions. Copyright 2002 by the
National Kidney Foundation, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12087559 [PubMed - indexed for MEDLINE]

456: BMJ. 2002 Jun 22;324(7352):1488-92.

Randomised double blind trial of etoricoxib and indometacin in treatment of acute
gouty arthritis.

Schumacher HR Jr, Boice JA, Daikh DI, Mukhopadhyay S, Malmstrom K, Ng J, Tate GA,
Molina J.

Division of Rheumatology, University of Pennsylvania School of Medicine and
Department of Veterans Affairs Medical Center, Philadelphia, PA 19104, USA.

OBJECTIVE: To assess the safety and efficacy of etoricoxib, a selective
cyclo-oxygenase-2 inhibitor, in comparison with indometacin in the treatment of
acute gouty arthritis. DESIGN: Randomised, double blind, active comparator
controlled trial. SETTING: 43 outpatient study centres in 11 countries.
PARTICIPANTS: 142 men and eight women (75 patients per treatment group) aged 18
years or over presenting with clinically diagnosed acute gout within 48 hours of 
onset. Interventions: Etoricoxib 120 mg administered orally once daily versus
indometacin 50 mg administered orally three times daily, both for 8 days. MAIN
OUTCOME MEASURES: Patients' assessment of pain in the study joint over days 2 to 
5 (primary end point); investigators' and patients' global assessments of
response to treatment and tenderness of the study joint (key secondary end
points). RESULTS: Etoricoxib showed efficacy comparable to indometacin. Patients'
assessment of pain in the study joint (0-4 point Likert scale, "no pain" to
"extreme pain") over days 2 to 5 showed a least squares mean change from baseline
of -1.72 (95% confidence interval -1.90 to -1.55) for etoricoxib and -1.83 (-2.01
to -1.65) for indometacin. The difference between treatment groups met
prespecified comparability criteria. All other efficacy end points, including
those reflecting reduction in inflammation and analgesia, provided corroborative 
evidence of comparable efficacy. Significant pain relief was evident at the first
measurement, 4 hours after the first dose of treatment. Prespecified safety
analyses revealed that drug related adverse experiences occurred significantly
less frequently with etoricoxib (22.7%) than with indometacin (46.7%) (P=0.003), 
although overall adverse experience rates were similar between the two treatment 
groups. CONCLUSION: Etoricoxib 120 mg once daily provides rapid and effective
treatment for acute gouty arthritis comparable to indometacin 50 mg three times
daily. Etoricoxib was generally safe and well tolerated in this study.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12077033 [PubMed - indexed for MEDLINE]

457: Clin Exp Rheumatol. 2002 Mar-Apr;20(2):228-30.

Involvement of the thoracic spine in tophaceous gout. A case report.

Souza AW, Fontenele S, Carrete H Jr, Fernandes AR, Ferrari AJ.

Rheumatology Division, UNIFESP-EPM, São Paolo, Brazil.

The presence of tophi involving the spine is an atypical complication of
tophaceous gout and its diagnosis may be difficult. The authors present a case of
tophaceous gout involving the thoracic spine and discuss the topic.

Publication Types: 
    Case Reports

PMID: 12051405 [PubMed - indexed for MEDLINE]

458: Curr Rheumatol Rep. 2002 Jun;4(3):252-6.

Update on colchicine and its mechanism of action.

Molad Y.

Rabin Medical Center, Beilinson Campus, Rheumatology Unit, Petah Tikva 49100,
Israel. ymolad@clalit.org.il

Colchicine is a unique anti-inflammatory drug with respect to its limited
clinical usefulness and its mode of action. Colchicine is mainly indicated for
the treatment and prophylaxis of gout and familial Mediterranean fever. Its mode 
of action includes modulation of chemokine and prostanoid production and
inhibition of neutrophil and endothelial cell adhesion molecules by which it
interferes with the initiation and amplification of the joint inflammation. This 
paper discusses its adverse effects and indications.

Publication Types: 
    Review

PMID: 12010611 [PubMed - indexed for MEDLINE]

459: Curr Opin Rheumatol. 2002 May;14(3):281-6.

Gout and hyperuricemia.

Wortmann RL.

Department of Internal Medicine, The University of Oklahoma College of Medicine, 
Tulsa 74135, USA. Robert-wortmann@ouhsc.edu

Gout continues to be a health problem around the world despite the availability
of effective therapies. Although the prevalence is influenced by genetic factors,
the associations of alcohol consumption, obesity, and hypertension appear to be
partially responsible for the increased prevalence of gout and hyperuricemia in
African and Oriental countries. The association between hyperuricemia and
cardiovascular disease seems linked to insulin resistance. This relation, in
part, explains the common coexistence of hyperlipidemia and glucose intolerance
in patients with gout. Accordingly, it is recommended that one pay more attention
to dietary manipulation in patients with gout in addition to managing
hypertension, obesity, and other medical problems. Although acute gout attacks
can be treated, eliminating gout requires effective removal of urate from the
body. Allopurinol remains a dominant urate-lowering agent, however its use may be
limited by allergic reactions. Uricosuric agents are also effective
urate-lowering agents and provide an alternative to allopurinol. Strategies to
treat patients who are sensitive to allopurinol continue to evolve.

Publication Types: 
    Review

PMID: 11981327 [PubMed - indexed for MEDLINE]

460: Ann Rheum Dis. 2002 May;61(5):444-7.

Delayed examination of synovial fluid by ordinary and polarised light microscopy 
to detect and identify crystals.

Gálvez J, Sáiz E, Linares LF, Climent A, Marras C, Pina MF, Castellón P.

Rheumatology Unit, Hospital General Universitario "JM Morales Meseguer", Murcia, 
Spain. pgalvis@eresmas.com

OBJECTIVE: To determine the reliability of a delay in the microscopic examination
of synovial fluid (SF) to detect and identify crystals. METHODS: Ninety one SF
samples were examined, 31 with monosodium urate (MSU) crystals, 30 with crystals 
of calcium pyrophosphate dihydrate (CPPD), and 30 containing no crystals. The
specimens were stored with EDTA, sodium heparin, and without anticoagulant at 4
degrees C before examination at 24 and 72 hours with ordinary and polarised light
microscopy. Another aliquot of the same samples was stored in a plastic container
without anticoagulant at -80 degrees C and examined after two months. RESULTS:
When the samples stored at 4 degrees C were re-examined after 24 hours,
intracellular crystals of MSU were seen in 90/93 (97%) cases where they had been 
identified previously and 89/93 (96%) cases after 72 hours. Similarly, CPPD
crystals were identified in 90/90 (100%) and 87/90 (97%) cases after 24 and 72
hours. Examination of the samples stored at -80 degrees C showed intracellular
MSU crystals in 25/31 (81%) of cases and CPPD crystals in 25/30 (83%). No
crystals were seen in any sample which had previously been diagnosed as
crystal-free. CONCLUSIONS: Deferred microscopic examination of refrigerated or
deep frozen SF provides a strong probability of detecting MSU or CPPD crystals if
these are present initially.

PMID: 11959769 [PubMed - indexed for MEDLINE]

461: J Rheumatol. 2002 Apr;29(4):837-42.

High prevalence of hyperuricemia in adolescent Taiwan aborigines.

Ko YC, Wang TN, Tsai LY, Chang FT, Chang SJ.

Graduate Institute of Medicine and School of Medicine, Kaohsiung Medical
University, Taiwan.

OBJECTIVE: To explore the prevalence and related factors of hyperuricemia among
adolescent Taiwan aborigines in tribes with a high prevalence of adult gout,
compared with adolescents of low prevalence aboriginal and non-aboriginal tribes.
METHODS: The participants were aborigines and non-aborigines in Taiwan, age 12 to
15 years and free of gout. Each participant provided information on sex, age, and
parents' tribal background as well as body weight and height. Serum samples were 
analyzed for biochemical markers. A logistic regression model was used to study
factors related to hyperuricemia. RESULTS: In total 940 adolescents participated.
The hyperuricemia rate in tribes with high gout prevalence (57.7%) was higher
than in non-aborigines (48.2%) and in aboriginal tribes with low gout prevalence 
(34.0%). Factors statistically significantly related to hyperuricemia were tribe,
sex, obesity, creatinine, and cholesterol levels in preliminary analysis. After
adjustment by the logistic regression model, obese boys with higher creatinine
were most likely to have hyperuricemia. Adolescents whose parents originated from
tribes with high gout prevalence had a tendency to have hyperuricemia, and those 
aborigines from tribes with low gout prevalence had a low prevalence of
hyperuricemia compared to non-aborigines. CONCLUSION: The prevalence of
hyperuricemia in aboriginal adolescents mirrors the incidence of adult gout,
implying a predisposition for adult gout in childhood, with genetic and/or
environmental components presumably contributing to the differences between
tribes; this may be of potential benefit to preventive efforts.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11950030 [PubMed - indexed for MEDLINE]

462: Acta Neurochir (Wien). 2002 Feb;144(2):205-7.

Cervical myelopathy due to gouty tophi in the intervertebral disc space.

Yen HL, Cheng CH, Lin JW.

Department of Neurosurgery, Chang Gung Memorial Hospital, Kaohsiung, 123 Ta-Pei
Road, Niao-Sung Hsiang, Kao-hsiung Hsien, Taiwan.

Gout, like diabetes mellitus, is a common metabolic disorder. Typically affecting
the distal joint of the appendicular skeleton, its occurrence in the spine is
rare. We report the case of a 68-year-old male with a long history of diabetes
mellitus and hyperuricemic gout. Neck pain developed over two weeks with
subsequent quadriparesis, with concomitant subcutaneous deposition of gouty tophi
in the right elbow. Magnetic resonance image of the cervical spine revealed
multiple segmental narrowing of the thecal sac at the C3-6 levels due to
hypertrophic spurs and bulging discs. Anterior discectomies of C3-4 and C4-5 were
performed, with a chalky-white, granular material noted in the C4-5 disc space.
Histological examination of the surgical specimen revealed deposits of
needle-like crystals surrounded by histiocytes and multinucleated giant cells,
with the appearance compatible with gout. The patient was ambulatory with the
assistance of a walking frame six months after the operation. We emphasize that
gouty tophi can be deposited in the spine over a relatively short time,
subsequently precipitating a variety of symptoms, from pain to cord compression. 
The regular administration of antihyperuricemia drug treatment for hyperuricemic 
gout is necessary to prevent this deposition. If neurological defects are found, 
surgical decompression can provide satisfactory results.

Publication Types: 
    Case Reports

PMID: 11862523 [PubMed - indexed for MEDLINE]

463: J Rheumatol. 2002 Feb;29(2):331-4.

Local ice therapy during bouts of acute gouty arthritis.

Schlesinger N, Detry MA, Holland BK, Baker DG, Beutler AM, Rull M, Hoffman BI,
Schumacher HR Jr.

Department of Medicine and New Jersey Medical School-University of Medicine and
Dentistry of New Jersey, Newark, USA.

OBJECTIVE: To evaluate the effect of local application of ice on duration and
severity of acute gouty arthritis. METHODS: Nineteen patients with acute gout
were enrolled and randomized into 2 groups. Group A (n = 10) received topical ice
therapy, oral prednisone 30 mg PO tapered to 0 over 6 days and colchicine 0.6
mg/day. Group B was the control group (n = 9), given the same regimen but without
the ice therapy. The patients were followed for one week. RESULTS: The mean
reduction in pain for those patients treated with ice therapy was 7.75 cm (on 10 
cm visual analog scale) with standard deviation +/- 2.58 compared with 4.42 cm
(+/- SD 2.96) for the control group. Using a Wilcoxon rank-sum test there was a
significant difference (p = 0.021 ) in pain reduction between the ice therapy and
control groups. Joint circumference and synovial fluid volume also tended to be
more effectively reduced after one week of therapy in the ice group compared with
controls, but these did not achieve statistical significance. CONCLUSION: The
group treated with ice had a significantly greater reduction in pain compared
with the control group. Although the clinical improvement was impressive, due to 
the small sample size we could not show statistically significant improvement in 
all the variables that tended to suggest that effect was more than simply
analgesic. Cold applications may be a useful adjunct to treatment of acute gouty 
arthritis.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Randomized Controlled Trial

PMID: 11838852 [PubMed - indexed for MEDLINE]

464: J Laryngol Otol. 2002 Feb;116(2):140-2.

Laryngeal gout.

Tsikoudas A, Coatesworth AP, Martin-Hirsch DP.

Department of Otolaryngology, Hull Royal Infirmary, Hull, UK.
atsikoudas@yahoo.com

A review of the literature reveals only 12 reported cases of laryngeal gout. We
describe three further cases of laryngeal gout, the largest series ever
published. The first case is previously undescribed acute gouty
cricoarytenoiditis resulting in acute airway embarrassment requiring tracheotomy,
and then we describe two cases of chronic tophaceous involvement of the thyroid
lamina with computed tomography (CT) images of this process. The paucity of
literature on this subject may not only be due to rarity but also lack of
clinical awareness. Gouty involvement of the larynx must be considered in any
patient with a history of gout who presents with hoarseness, odynophagia,
dysphagia, stridor or neck lump. Acute airway compromise may require tracheotomy,
whereas chronic airway problems may necessitate endoscopic tophi removal,
lateralization procedures or even permanent tracheostomy.

Publication Types: 
    Case Reports

PMID: 11827592 [PubMed - indexed for MEDLINE]

465: J Orthop Sci. 2002;7(1):38-42.

Influence of aerobic exercise with an intermission, using a bicycle ergometer, on
fat metabolism in obese patients with gonarthrosis.

Tsumura H, Kataoka M, Uchida K, Torisu T.

Department of Orthopedic Surgery, Faculty of Medicine, Oita Medical University,
1-1 Idaigaoka, Hasama-machi, Oita-gun, Oita 879-5593, Japan.

Our study was conducted to acquire essential information on the fat metabolism of
obese patients with gonarthrosis during aerobic exercise, with a bicycle
ergometer, with an intermission and without an intermission. Two experiments were
conducted. Six women with gonarthrosis participated in the first experiment and
another six women with gonarthrosis participated in the second experiment. The
first experiment was conducted to investigate the influence of the total
programmed workload on fat metabolism during bicycle aerobic exercise, and the
second was conducted to investigate the effect of an intermission on fat
metabolism when exercise consisted of an equally distributed total 50-W workload.
During the experiment three exercise patterns were tested (six training sessions,
each with 5 min of aerobic bicycle exercise with of 5 min, three training
sessions each with 10 min of exercise with intermissions of 5 min, and 30 min of 
continuous exercise). The first experiment revealed that there was a significant 
relationship between the increase in free fatty acids (FFA) after exercise and
the workload (P < 0.05). The second experiment revealed that there was no
significant difference in the increase of FFA among the three exercise patterns. 
Exercise that was undertaken at a 50-W workload had a negligible effect on the
women's vital signs. The bicycle ergometer aerobic exercise with an intermission 
actually led to an increase in FFA values compared with the effects of the
continuous aerobic exercise.

Publication Types: 
    Comparative Study

PMID: 11819130 [PubMed - indexed for MEDLINE]

466: IEEE Trans Biomed Eng. 2002 Jan;49(1):72-6.

Risk-factor fusion for predicting multifactorial diseases.

Phegley J, Perkins K, Gupta L, Dorsey JK.

Department of Electrical Engineering, Southern Illinois University, Carbondale
62901, USA.

A generalized classification methodology is developed to predict the presence or 
absence of a multifactorial disease from a set of risk factors thought to be
correlated with the disease. The methodology includes fusion to combine risk
factors into a single feature vector, normalization to overcome the problems
associated with fusing features which have different formats and ranges, discrete
Karhunen-Loeve transform (DKLT)-based transformation to facilitate parametric
classifier development, the selection of features with high interclass
separations, and the design of parametric classifiers. The validity of the method
is demonstrated by applying it to predict the occurrence of gout from 14 risk
factors. Cross-validation evaluations on 96 patients, 48 clinically diagnosed to 
have gout and 48 diagnosed to not have gout, showed that an average
classification accuracy of 75.7% can be obtained. Even more promising is that
higher classification accuracies can be achieved through the careful selection of
the DKLT transformation matrix which in turn involves selecting design sets that 
are good representatives of the gout and nongout classes. It is concluded that
the generalized methodology developed in this paper is quite effective in
predicting multifactorial diseases and can, therefore, assist/support a physician
in diagnosing a multifactorial disease.

PMID: 11794774 [PubMed - indexed for MEDLINE]

467: J Orthop Sci. 2001;6(6):604-7.

Gouty tophus of the patella evaluated by PET imaging.

Sato J, Watanabe H, Shinozaki T, Fukuda T, Shirakura K, Takagishi K.

Department of Orthopedic Surgery, Gunma University Faculty of Medicine, 3-39-22
Showa, Maebashi, Gunma 371-8511, Japan.

We report a case of gouty tophus of the patella, a rare lesion, which was
evaluated using positron emission tomography (PET). This modality, which uses a
combination of an amino-acid analog emitter, L-[3-(18)F]-alpha-methyl tyrosine
(FMT), which neglects malignancies, and a glucose analog emitter,
(18)F-fluoro-2-deoxy-D-glucose (FDG), which neglects benign lesions, simulating
the radiographic findings, may be useful for the preoperative evaluation of gouty
tophus occurring in patella partita, including detection, differentiation from
malignant tumors, and possible pathogenetic diagnosis.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11793187 [PubMed - indexed for MEDLINE]

468: Clin Exp Rheumatol. 2001 Nov-Dec;19(6):661-5.

Hyperuricemia and gout in thyroid endocrine disorders.

Giordano N, Santacroce C, Mattii G, Geraci S, Amendola A, Gennari C.

Institute of Internal Medicine, University of Siena, Italy. Giordanon@unisi.it

OBJECTIVE: A significant correlation between thyroid function and purine
nucleotide metabolism has been established in hypothyroidism. On the contrary,
the relationship between hyperthyroidism and purine metabolism is more
controversial. The present study evaluates the prevalence of hyperuricemia and
gout in patients affected by primary hypothyroidism and hyperthyroidism. METHODS:
We studied 28 patients with primary hypothyroidism and 18 patients with primary
hyperthyroidism, all hospitalized because of endocrine dysfunction. All underwent
a series of clinical, biochemical and instrumental evaluations; in particular,
thyroid-stimulatin hormone (TSH), free thyroxine (fT4), blood urea, serum
creatinine, creatinine clearance, serum and urinary uric acid levels were
measured. RESULTS: In comparison to the prevalence reported in the general
population, a significant increase of both hyperuricemia and gout was found in
the hypothyroid patients, and of hyperuricemia in the hyperthyroid patients. In
hyperthyroidism the hyperuricemia is due to the increased urate production, while
in hypothyroidism the hyperuricemia is secondary to a decreased renal plasma flow
and impaired glomerular filtration. CONCLUSIONS: Ourfindings confirm the data in 
the literature concerning the high prevalence of hyperuricemia and gout in
hypothyroidism. It shows that hyperthyroidism can cause a significant increase in
serum uric acid, as well, although lower than the hyperuricemia due to thyroid
hormone deficiency.

PMID: 11791637 [PubMed - indexed for MEDLINE]

469: Ann Rheum Dis. 2002 Jan;61(1):52-4.

Imaging of tophaceous gout: computed tomography provides specific images compared
with magnetic resonance imaging and ultrasonography.

Gerster JC, Landry M, Dufresne L, Meuwly JY.

Department of Rheumatology, University Hospital (CHUV), Lausanne, Switzerland.
Jean.Charles.Gerster@chuv.hospvd.ch

OBJECTIVE: To determine the usefulness of computed tomography (CT), magnetic
resonance imaging (MRI), and Doppler ultrasonography (US) in providing specific
images of gouty tophi. METHODS: Four male patients with chronic gout with tophi
affecting the knee joints (three cases) or the olecranon processes of the elbows 
(one case) were assessed. Crystallographic analyses of the synovial fluid or
tissue aspirates of the areas of interest were made with polarising light
microscopy, alizarin red staining, and x ray diffraction. CT was performed with a
GE scanner, MR imaging was obtained with a 1.5 T Magneton (Siemens), and
ultrasonography with colour Doppler was carried out by standard technique.
RESULTS: Crystallographic analyses showed monosodium urate (MSU) crystals in the 
specimens of the four patients; hydroxyapatite and calcium pyrophosphate
dihydrate (CPPD) crystals were not found. A diffuse soft tissue thickening was
seen on plain radiographs but no calcifications or ossifications of the tophi. CT
disclosed lesions containing round and oval opacities, with a mean density of
about 160 Hounsfield units (HU). With MRI, lesions were of low to intermediate
signal intensity on T(1) and T(2) weighting. After contrast injection in two
cases, enhancement of the tophus was seen in one. Colour Doppler US showed the
tophi to be hypoechogenic with peripheral increase of the blood flow in three
cases. CONCLUSION: The MR and colour Doppler US images showed the tophi as masses
surrounded by a hypervascular area, which cannot be considered as specific for
gout. But on CT images, masses of about 160 HU density were clearly seen, which
correspond to MSU crystal deposits.

Publication Types: 
    Comparative Study

PMID: 11779759 [PubMed - indexed for MEDLINE]

470: J Int Neuropsychol Soc. 2001 Nov;7(7):805-12.

Neurocognitive functioning in Lesch-Nyhan disease and partial
hypoxanthine-guanine phosphoribosyltransferase deficiency.

Schretlen DJ, Harris JC, Park KS, Jinnah HA, del Pozo NO.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School
of Medicine, Baltimore, Maryland, USA. dschret@jhmi.edu

Lesch-Nyhan disease (LND) is a rare, X-linked genetic disorder that involves the 
nearly complete absence of an enzyme (hypoxanthine-guanine
phosphoribosyltransferase, or HPRT) that is essential for purine salvage. In
addition to hyperuricemia, all patients with classic LND suffer from movement
disorder and compulsive self-injury, and most have mental retardation. Patients
with partial HPRT deficiency (variants) always have hyperuricemia and often have 
neurologic abnormalities, but do not self-injure and usually are described as
having normal intelligence. Here we compare 15 patients with LND to 9 variants
and 13 normal adolescents and adults. Testing revealed unambiguous and
qualitatively similar cognitive deficits in both patient groups. The variants
produced scores that were intermediate between those of patients with LND and
normal participants on nearly every cognitive measure. We discuss these findings 
in terms of what is known about the neuropathology of LND.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11771623 [PubMed - indexed for MEDLINE]

471: J Rheumatol. 2001 Dec;28(12):2674-80.

Inhibitory effect of low density lipoprotein on the inflammation-inducing
activity of calcium pyrophosphate dihydrate crystals.

Kumagai Y, Watanabe W, Kobayashi A, Sato K, Onuma S, Sakamoto H.

Department of Orthopedic Surgery, Akita University School of Medicine, Japan.

OBJECTIVE: It has been proposed that low density lipoprotein (LDL) plays a role
in the self-limiting nature of pseudogout inflammation. We investigated changes
of LDL concentration in rat air pouch fluid during periods of acute and subsiding
inflammation to evaluate whether LDL contributes to inhibiting inflammation of
pseudogout. We examined whether LDL binds to calcium pyrophosphate dihydrate
(CPPD) crystals as a possible mechanism for reduction of inflammation. METHODS:
In this in vivo study, 5 mg suspensions of CPPD crystals and saline were injected
into the rat air pouch. Fluid samples were taken from rat air pouch at 0, 3, 6,
12, 24, and 48 h after injection. White blood cells in the samples were counted; 
the remaining fluid was centrifuged and concentrations of beta-glucuronidase and 
PGE2 in the supernatant were measured as inflammatory markers. LDL in the
supernatant was immunochemically identified by Western blotting, then pellets
containing crystals were examined by the same technique. RESULTS: LDL was
identified in the air pouch 3 h after CPPD crystal injection, and its
concentration increased and reached a peak level after 24 h. Inflammatory markers
reached maximal level from 6 to 12 h, then decreased after 24 h. In the pellets
containing crystals, LDL could not be identified in every specimen. CONCLUSION:
LDL in the rat air pouch increased during the inflammatory course induced by CPPD
crystal and the inflammation subsided as the LDL increased. Since some reports
indicate LDL was related to reduction of crystal induced inflammation such as
gout or pseudogout, we concluded that LDL could contribute to the resolution of
acute pseudogout arthritis in vivo with or without binding to CPPD crystals.

PMID: 11764217 [PubMed - indexed for MEDLINE]

472: Transplantation. 2001 Nov 27;72(10):1703-5.

Tacrolimus for the treatment of gout in renal transplantation: two case reports
and review of the literature.

Pilmore HL, Faire B, Dittmer I.

Department of Renal Medicine, Auckland Hospital, Park Road, Grafton, Auckland,
New Zealand. hpilmore@adhb.gov.inz

Episodes of gout are common in the setting of renal transplantation.
Hyperuricemia and gout have been associated with the use of the calcineurin
inhibitor, cyclosporine. We report two cases of severe polyarticular gout
resistant to conventional therapy in renal transplant recipients that resolved
after switching from cyclosporine to tacrolimus-based immunosuppression. There
was no alteration in renal function, and trough concentrations of both
cyclosporine and tacrolimus were within the recommended range. Resolution of gout
occurred within a month of discontinuation of cyclosporine and commencement of
tacrolimus. Use of tacrolimus may be beneficial in the renal transplant recipient
with refractory gout.

Publication Types: 
    Case Reports

PMID: 11726837 [PubMed - indexed for MEDLINE]

473: Transplantation. 2001 Nov 27;72(10):1689-91.

Hyperuricemia, gout, and renal function after liver transplantation.

Neal DA, Tom BD, Gimson AE, Gibbs P, Alexander GJ.

Department of Medicine, University of Cambridge, School of Clinical Medicine,
Addenbrooke's NHS Trust, United Kingdom.

BACKGROUND: Hyperuricemia is a recognized complication of renal and cardiac
transplantation, but the development of hyperuricemia and gout following liver
transplantation have received less attention. We have retrospectively assessed
the prevalence of hyperuricemia in 134 consecutive liver transplant recipients.
RESULTS: Forty-seven percent of the liver transplant recipients studied had
hyperuricemia. Serum creatinine was higher in hyperuricemic than in
nonhyperuricemic patients. Peak uric acid correlated significantly with
corresponding serum creatinine (rs=0.694). Only 6% developed gout. All the
patients with gout and 10 hyperuricemic patients with renal impairment but
without gout were treated with allopurinol. Over a median period of 3 months,
mean serum creatinine fell from 177 micromol/l to 160 micromol/l (P=0.01),
without change in type or dose of immuno-suppression. CONCLUSIONS: There is an
important association between liver transplantation and hyperuricemia. Treatment 
with allopurinol results in a significant reduction in serum creatinine in
patients with gout and in those with hyperuricemia and renal impairment.

PMID: 11726834 [PubMed - indexed for MEDLINE]

474: Clin Orthop Relat Res. 2001 Nov;(392):377-82.

Gout-induced arthropathy after total knee arthroplasty: a report of two cases.

Archibeck MJ, Rosenberg AG, Sheinkop MB, Berger RA, Jacobs JJ.

Department of Orthopaedic Surgery, Rush-Presbyterian-St Luke's Medical Center,
Chicago, IL 60612, USA.

Gout, although relatively rare in joint replacements, can present as an acute or 
chronic painful knee or hip arthroplasty. Gout and acute infection of a joint
replacement can be difficult to differentiate, with the physical examination and 
laboratory study results frequently being similar. Both conditions can present
with a rapid onset of joint pain, swelling, erythema, and constitutional
symptoms, including fevers and malaise. Laboratory findings in both conditions
often include an elevated leukocyte count, erythrocyte sedimentation rate, and
C-reactive protein level. Negatively birefringent, needle-shaped crystals in the 
synovial fluid confirm the diagnosis of gout. The mistaken diagnosis of septic
arthritis in a joint replacement with crystal-induced synovitis can lead to
inappropriate open debridement or component removal. The current study includes a
review of the literature and presents two cases of gout after total knee
arthroplasty. These cases suggest that in situations of suspected sepsis without 
synovial fluid crystals, operative intervention is indicated with a presumed
diagnosis of septic arthritis. The identification of chalky white or yellow
deposits in the synovium or bone is highly suggestive of gout. The definitive
diagnosis is made by polarized light histologic evaluation of these tissues. If
these deposits are present in the absence of a positive preoperative culture,
positive Gram stain for bacteria, or component loosening, component retention is 
indicated.

Publication Types: 
    Case Reports

PMID: 11716410 [PubMed - indexed for MEDLINE]

475: Skeletal Radiol. 2001 Oct;30(10):565-9.

Gout: radiographic findings mimicking infection.

Rousseau I, Cardinal E E, Raymond-Tremblay D, Beauregard CG, Braunstein EM,
Saint-Pierre A.

Department of Diagnostic Radiology, Centre hospitalier de l'Université de
Montréal, Hôpital Notre-Dame, Montreal, Quebec, Canada.

OBJECTIVE: To describe radiographic features of gout that may mimic infection.
DESIGN AND PATIENTS: We report five patients with acute bacterial gout who
presented with clinical as well as radiological findings mimicking acute
bacterial septic arthritis or osteomyelitis. Three patients had delay in the
appropriate treatment with the final diagnosis being established after needle
aspiration and identification of urate crystals under polarized light microscopy.
Two patients underwent digit amputation for not responding to antibiotic
treatment and had histological findings confirming the diagnosis of gout.
CONCLUSION: It is important for the radiologist to be aware of the radiological
manifestations of acute gout that can resemble infection in order to avoid
inappropriate diagnosis and delay in adequate treatment. The definitive diagnosis
should rely on needle aspiration and a specific search for urate crystals.

Publication Types: 
    Case Reports
    Comparative Study

PMID: 11685479 [PubMed - indexed for MEDLINE]

476: J Craniomaxillofac Surg. 2001 Oct;29(5):307-10.

Gout of the temporomandibular joint: pitfalls in diagnosis.

Barthélémy I, Karanas Y, Sannajust JP, Emering C, Mondié JM.

Department of Oral and Maxillo-facial Surgery, Facial Plastic Surgery,
Clermont-Ferrand Cedex, France. isabarth@aol.com

Gout is a frequent benign disease that rarely affects the temporomandibular joint
(TMJ) alone. When it does, the disease is usually confined to the joint space and
leads to pain and limitation of jaw opening (acute gout). The case described in
this report is atypical in so far as it extended beyond the joint capsule into
the pterygoid muscle and destroyed the head of the mandible, the temporal bone
and the greater wing of the sphenoid bone. This clinical behaviour in combination
with the radiographic appearance created the appearance of a benign but
osteolytic lesion. The clinical, radiographic and biological features of gout in 
the TMJ are reviewed and treatment options are discussed. Copyright 2001 European
Association for Cranio-Maxillofacial Surgery.

Publication Types: 
    Case Reports

PMID: 11673927 [PubMed - indexed for MEDLINE]

477: Clin Rheumatol. 2001;20(5):372-5.

An atypical case of primary renal tubular hypokalaemic metabolic alkalosis with
chronic tophaceous gout.

Moriwaki Y, Yamamoto T, Takahashi S, Tsutsumi Z, Hada T.

Third Department of Internal Medicine, Hyogo College of Medicine, Japan.

A 55-year-old woman was referred to our ward for further evaluation of marked
hyperuricaemia and suspected tophi. On physical examination, huge subcutaneous
nodules were observed on the knee joints as well as a small nodule on the lateral
side of the left sole. Blood chemistry showed marked hyperuricaemia (0.85
mmol/l), hypokalaemia (2.7 mmol/l) and a mild degree of renal insufficiency.
Arterial blood gas analysis showed signs of metabolic alkalosis. Daily urinary
uric acid excretion on a purine non-restricted diet was 8.9 mmol/day. Uric acid
clearance and fractional uric acid clearance were 0.8 ml/min and 2.6%,
respectively. Plasma renin activity was 21.8 ng/ml/h, and plasma angiotensin II
and aldosterone concentrations were 61 and 121 pg/ml, respectively. However,
pressor response to an intravenous administration of angiotensin II was normal.
The urinary calcium to creatinine molar ratio was 0.069, and serum magnesium
concentration was normal to supranormal. A biopsy of the subcutaneous nodule
showed a typical appearance of tophus. Based on these findings, the patient was
diagnosed with an atypical case of renal tubular hypokalaemic metabolic
alkalosis, with marked hyperuricaemia and tophi as the initial manifestations. So
far, only four cases of Bartter's syndrome with gout and/or hyperuricaemia have
been described in Japan. This rare case is presented and its mechanism of
hyperuricaemia discussed.

Publication Types: 
    Case Reports

PMID: 11642522 [PubMed - indexed for MEDLINE]

478: J Hypertens. 2001 Oct;19(10):1855-60.

Comment in:
    J Hypertens. 2002 Feb;20(2):347.

Comparative effects of losartan and irbesartan on serum uric acid in hypertensive
patients with hyperuricaemia and gout.

Würzner G, Gerster JC, Chiolero A, Maillard M, Fallab-Stubi CL, Brunner HR,
Burnier M.

Division of Hypertension and Vascular Medicine, CHUV, 1011 Lausanne, Switzerland.

OBJECTIVE: Losartan has been shown to increase urinary uric acid excretion and
hence to lower serum uric acid levels. The purposes of the present study were:
(1) to evaluate the effects of losartan on serum uric acid in hypertensive
patients with hyperuricemia and gout, (2) to compare the effects of losartan with
those of irbesartan, another angiotensin II receptor antagonist and (3) to
evaluate whether losartan 50 mg b.i.d. has a greater impact on serum uric acid
levels than losartan 50 mg once a day. METHODS: Thirteen hypertensive patients
with hyperuricaemia and gout completed this prospective, randomized,
double-blind, cross-over study. Uric acid-lowering drugs were stopped 3 weeks
before the beginning of the study. Patients were randomized to receive either
losartan 50 mg or irbesartan 150 mg once a day, for 4 weeks. During this phase, a
placebo was given in the evening. After 4 weeks, the dose was increased to
losartan 50 mg b.i.d., or irbesartan 150 mg b.i.d. for another 4 week period.
Subsequently, the patients were switched to the alternative treatment modality.
Enalapril (20 mg o.d.) was given during the run-in period and between the two
treatment phases. Serum and urinary uric acid were measured at the beginning and 
at the end of each treatment phase. RESULTS: Our results show that losartan 50 mg
once daily decreased serum uric acid levels from 538 +/- 26 to 491 +/- 20
micromol/l (P < 0.01). Irbesartan had no effect on serum uric acid. Increasing
the dose of losartan from 50 mg o.d. to 50 mg twice a day, did not further
decrease serum uric acid. This may in part be due to a low compliance to the
evening dose as measured with an electronic device. Indeed, whatever the
prescribed drug, the mean compliance of the evening dose was always significantly
lower than that of the morning dose. The uricosuric effect of losartan appears to
decrease with time when a new steady state of lower serum uric acid is reached.
CONCLUSIONS: In contrast to irbesartan, losartan was uricosuric and decreased
serum uric acid levels. Losartan 50 mg b.i.d. did not produce a greater fall in
serum uric acid than losartan once a day. Losartan might be a useful therapeutic 
tool to control blood pressure and reduce serum uric acid levels in hypertensive 
patients with hyperuricaemia and gout.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11593107 [PubMed - indexed for MEDLINE]

479: Metabolism. 2001 Oct;50(10):1203-7.

Clinical features of familial gout and effects of probable genetic association
between gout and its related disorders.

Chen SY, Chen CL, Shen ML, Kamatani N.

Taipei Municipal Hospital Gout Research Group, Taipei, Taiwan.

We examined whether the age at onset, gender, arthritic manifestations, and
tophus formation in familial gout are different from those in nonfamilial gout,
and we also examined the contributory effect of genetic association to the
concurrence of hypertriglyceridemia, hypercholesterolemia, type 2 diabetes
mellitus (DM), hypertension, obesity, and renal insufficiency with gout in
Taiwan. A total of 21,373 gout patients' data from Ho-Ping Gout database were
analyzed in this study retrospectively. The clinical and laboratory data were
compared between familial and nonfamilial gout. Mean age at onset of gout in
familial subjects was significantly 7.5 years lower than that of nonfamilial
subjects (40.9 +/- 13.4 v 48.4 +/- 14.2 years, P =.0001), while gender, arthritic
severity, and tophus formation were not significantly different between these 2
groups. Familial gout had lower serum triglyceride (TG), total cholesterol (TC), 
and percentage of hypertension than nonfamilial gout (182.4 +/- 125.3 v 195.9 +/-
135.8 mg/dL, P =.0001; 207.5 +/- 42.5 v 210.4 +/- 48.8 mg/dL, P =.0003; and
19.57% v 22.56%, P <.0001, respectively). Their serum creatinine, body mass index
(BMI), and percentage of type 2 DM were not significantly different. Our results 
demonstrate that familial gout is associated with precocious onset. Furthermore, 
the contributory effect of genetic association to the concurrence of
hyperlipidemia and hypertension with gout is less than that of environmental
factors, while the effect of genetic association to the concurrence of obesity,
type 2 DM, and renal insufficiency with gout is equivalent to that of
environmental factors. Copyright 2001 by W.B. Saunders Company

PMID: 11586494 [PubMed - indexed for MEDLINE]

480: J Dermatol. 2001 Aug;28(8):433-6.

Chronic tophaceous gout presenting as hyperpigmented nodules in the limbs of a
patient with coexisting psoriasis.

Cho S, Koh GJ, Choi JH, Sung KJ, Moon KC, Koh JK.

Department of Dermatology, Asan Medical Center, College of Medicine, University
of Ulsan, Seoul, Korea.

We describe a 53-year-old male renal transplant recipient with hypertension and
triglyceridemia, who showed rare manifestations of gout presenting as brownish
nodules on the arms and legs as well as chronic tophaceous gouty arthritis of the
hands and feet mimicking rheumatoid arthritis, in association with subsequently
developed psoriasis of the palms. In elderly Asian men, hypertension and renal
insufficiency may be risk factors predisposing to the development of multiple
hyperpigmented nodules of tophi in the more proximal extremities.

Publication Types: 
    Case Reports

PMID: 11560160 [PubMed - indexed for MEDLINE]

481: Ann Rheum Dis. 2001 Oct;60(10):981-3.

Relation between adverse events associated with allopurinol and renal function in
patients with gout.

Vázquez-Mellado J, Morales EM, Pacheco-Tena C, Burgos-Vargas R.

Rheumatology Unit, Hospital General de México, México DF.
jvazquezmellado@yahoo.com

BACKGROUND: Because serious adverse reactions to allopurinol have been related to
a reduce creatinine clearance rate and prolonged half life of oxypurinol, it has 
been recommended that the dose should be adjusted according to the rate of
creatinine clearance. However, in some patients with gout the dose is not
sufficient to reduce serum levels of uric acid (< or =390 micromol/l) and to halt
disease progression. OBJECTIVE: To determine the prevalence of adverse reactions 
attributable to allopurinol in patients with primary gout according to dose and
creatinine clearance rate. METHODS: Data on 120 patients with gout receiving
allopurinol, in whom the starting dose was adjusted according to creatinine
clearance rate and later increased in some patients to control the disease, were 
retrospectively reviewed. Two groups were compared: group A, 52 patients
receiving creatinine clearance adjusted maintenance doses of allopurinol and
group B, 68 patients receiving non-adjusted higher maintenance doses of
allopurinol. RESULTS: During follow up 57% required higher allopurinol doses than
those recommended according to their creatinine clearance rate. Only five (4%) of
120 consecutive patients developed allopurinol related adverse reactions: four
minor skin reactions and one allopurinol hypersensitivity syndrome (AHS). Three
of these (including the case of AHS) occurred in group A and two in group B
(p=NS). The duration of allopurinol treatment was the same in both groups (group 
A: 2.3 (3.3) years; group B: 3.7 (4.8) years). No patient in group A, but 44% in 
group B had a creatinine clearance rate of <50 ml/min. None of the patients
received concomitant diuretics, ampicillin, or azathioprine. CONCLUSIONS: No
increase was seen in the prevalence of adverse reactions to allopurinol in
patients who received higher allopurinol maintenance doses than those recommended
according to creatinine clearance rate.

Publication Types: 
    Comparative Study

PMID: 11557658 [PubMed - indexed for MEDLINE]

482: South Med J. 2001 Jul;94(7):732-4.

Gout, bradycardia, and hypercholesterolemia after renal transplantation.

Kelleher SP, Davis WR, Paraskevopoulos N.

Department of Internal Medicine, Texas Tech Medical Center, Amarillo 79106, USA.

Approximately 17,000 solid organ transplantations are done annually in the United
States. Increasingly, care of these patients will be provided by primary care
physicians. In this report, we illustrate the complexity of common medical
problems in a patient who had cellulitis and who had had a cadaveric renal
transplantation 10 years earlier. Immunosuppressive therapy was cyclosporine (100
mg twice a day) and prednisone (10 mg once a day). The patient's hospital course 
was complicated by acute gout and symptomatic bradycardia. In both instances,
usual treatment--full-dose indomethacin for gout and withholding verapamil for
bradycardia--could have had significant interaction with the cyclosporine. At the
time of discharge, a therapeutic plan for long-term management of
hypercholesterolemia included possible drug interactions with cyclosporine. The
potential for drug toxicity in the transplant patient necessitates careful
monitoring of immunosuppressive drug levels. Ongoing communication with the
transplant center is also needed.

Publication Types: 
    Case Reports

PMID: 11531183 [PubMed - indexed for MEDLINE]

483: Clin Rheumatol. 2001;20(4):288-9.

Chronic myeloid leukemia presenting as gout.

Pavithran K, Thomas M.

Medical College Hospital, Trivandrum, India. drkpavithran@hotmail.com

A 53-year-old man presented with gouty arthritis. A physical examination and
haematological and biochemical tests showed that he had chronic myeloid leukemia.
He was treated with allopurinol, hydroxyurea and analgesics. The arthritis
subsided completely within 2 weeks. He continues in haematologic remission (on
interferon) with no further recurrence of the gout.

Publication Types: 
    Case Reports

PMID: 11529641 [PubMed - indexed for MEDLINE]

484: Mod Pathol. 2001 Aug;14(8):806-10.

Evaluation of crystals in formalin-fixed, paraffin-embedded tissue sections for
the differential diagnosis of pseudogout, gout, and tumoral calcinosis.

Shidham V, Chivukula M, Basir Z, Shidham G.

Department of Pathology, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, 
Milwaukee, WI 53226, USA. vshidham@mcw.edu

Hematoxylin-eosin (H&E)-stained sections may not allow proper evaluation of
birefringence properties of the crystals in the lesions of pseudogout, gout, and 
tumoral calcinosis. This study was undertaken to verify the application of a
special stain that could facilitate the evaluation of the birefringence
properties of these crystals for definitive diagnosis. We evaluated previously
described nonaqueous alcoholic eosin staining (NAES) method based on the
principle of using alcoholic eosin without hematoxylin and any other aqueous
reagents for staining of formalin-fixed, paraffin-embedded tissue sections. Two
observers, in a blinded fashion, evaluated the sections stained with routine H&E 
and NEAS method without the knowledge about clinical diagnosis. All pseudogout
(nine sections from seven cases) and gout (eight sections from five cases)
lesions demonstrated birefringence in the sections stained with NAES method.
H&E-stained sections showing the respective diagnostic histomorphology failed to 
demonstrate the birefringent crystals by polarizing microscopy in all the eight
sections from gout and in seven of nine sections from pseudogout. Only two
H&E-stained sections showed scant calcium pyrophosphate dihydrate (CPPD) crystals
in pseudogout. None of the three sections from two cases of tumoral calcinosis
showed birefringence with either stain. We conclude that CPPD in pseudogout and
monosodium urate in gout may not polarize in the routine H&E-stained sections.
However, polarizing microscopy of sections stained with NAES method allowed
demonstration of CPPD crystals with positive birefringence in pseudogout, MSU
crystals with negative birefringence in gout, and calcium hydroxyapatite crystals
without birefringence in tumoral calcinosis. Section stained with NAES method is 
a significantly useful adjunct to the routine H&E stain for proper evaluation of 
the crystals under polarizing microscope in these lesions.

Publication Types: 
    Comparative Study

PMID: 11504841 [PubMed - indexed for MEDLINE]

485: Auris Nasus Larynx. 2001 Aug;28(3):265-7.

Laryngeal manifestation of gout: a case report of a subglottic gout tophus.

Habermann W, Kiesler K, Eherer A, Beham A, Friedrich G.

Department of ENT, University of Graz, Medical School, Auenbruggerplatz 20,
A-8036 Graz, Austria. w_habermann@yahoo.com

A subglottic tophaceous deposition of urate crystals is a rare finding. We report
on a case of a male Caucasian who had a moderate dysphonia without any further
laryngeal symptoms. The laryngoscopy revealed a hemispheric lesion on the left
subglottic region. An excision biopsy was performed, and the histopathological
examination of the dissected specimen showed a tophus. Diagnostic and therapeutic
strategies are discussed.

Publication Types: 
    Case Reports

PMID: 11489374 [PubMed - indexed for MEDLINE]

486: Am J Orthop. 2001 Jul;30(7):562-5.

Gouty tenosynovitis of the wrist.

Gonzalez MH, Cooper ME.

Orthopaedic Surgery, Cook County Hospital, Chicago, Illinois, USA.

A 56-year-old man presented with a mass of the right wrist limiting excursion of 
the digits. Operative exploration demonstrated gouty infiltration of the flexor
tendons. The tendons were debrided of the urate crystalline material and the
motion of the digits returned, preserving all tendon function. The patient later 
returned with symptoms of carpal tunnel in the contralateral wrist. Exploration
of the carpal tunnel revealed similar infiltration of the flexor tendons. The
tendons were debrided and the carpal tunnel syndrome resolved.

Publication Types: 
    Case Reports

PMID: 11482511 [PubMed - indexed for MEDLINE]

487: Metabolism. 2001 Aug;50(8):952-4.

Decreased activities of lipoprotein lipase and hepatic triglyceride lipase in
patients with gout.

Tsutsumi Z, Yamamoto T, Moriwaki Y, Takahashi S, Hada T.

Third Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya,
Hyogo, Japan.

Postheparin plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase
(HTGL) activities were measured in 30 male primary gout patients as well as in
control subjects. The activities of these lipolytic enzymes were significantly
decreased in the patients as compared with the controls (gout v control; LPL, 5.4
+/- 0.4 v 7.9 +/- 0.9 U; HTGL, 14.6 +/- 2.0 v 17.9 +/- 3.4 U) when matched with
serum triglyceride concentration. Further, LPL activity was negatively correlated
with serum- and very-low-density lipoprotein (VLDL)-triglyceride in gout
patients, while that of HTGL was negatively correlated with low-density
lipoprotein (LDL)-triglyceride in both gout patients and control subjects. These 
results suggest that decreased activities of LPL and HTGL may contribute, in
part, to the increased concentrations of serum-, VLDL-, and LDL-triglyceride seen
in gout patients, leading to a higher risk for coronary atherosclerotic diseases 
in gout. Copyright 2001 by W.B. Saunders Company

Publication Types: 
    Comparative Study

PMID: 11474484 [PubMed - indexed for MEDLINE]

488: J Rheumatol. 2001 Jul;28(7):1640-6.

Hyperuricemia and gout in Taiwan: results from the Nutritional and Health Survey 
in Taiwan (1993-96).

Chang HY, Pan WH, Yeh WT, Tsai KS.

Division of Health Policy Research, National Health Research Institutes,
Nan-Kang, Taipei.

OBJECTIVE: To evaluate the prevalence of hyperuricemia in Taiwan. METHODS: A
multi-stage stratified sampling scheme was used in Nutrition and Health Survey,
which was conducted in Taiwan between 1993 and 96. Complete biochemical and
questionnaire data for 2754 males and 2953 females aged 4 years and older were
included in the analysis. The colorimetric enzymatic method was used to measure
plasma uric acid in fasting blood samples. Information on self-reported,
physician-diagnosed gout was also obtained. RESULTS: The uric acid values of
males were found to reach a peak between the ages of 13 and 18 and decrease
slightly after 18. The uric acid values of females were stable before the age of 
18, decreasing slightly between 19 and 44 years, and increasing in the mid to
older age groups (> or = 45 years). Twenty-six percent of adult males (> or = 19 
years) and 22% of older males (> or = 45 years) either had hyperuricemia (serum
uric acid > 458.0 microM or 7.7 mg/dl) or were taking medication for it.
Seventeen percent of adult females and 23% of older females either had
hyperuricemia (serum uric acid > 392.57 microM or 6.6 mg/dl) or were taking
medication for it. Both adult males and females in mountainous areas, who were
primarily aboriginal, had the highest prevalence of hyperuricemia (> 50%) among
the 7 survey areas. Mean body mass index (BMI), alcohol consumption, and
prevalence of gout were among the highest in mountainous people compared to all
included in the study. Multivariate analysis showed that mountainous area, age
and BMI are important factors associated with hyperuricemia in males, whereas
mountainous area, Class II townships, and BMI are the factors associated with
hyperuricemia in females. CONCLUSIONS: We found a high prevalence of
hyperuricemia in Han Chinese in Taiwan despite a lack both of obesity and high
alcohol consumption. Mountainous people (mainly aborigines) in Taiwan have an
even higher prevalence of hyperuricemia, which cannot be completely explained by 
obesity and alcohol consumption. Genetic components and other environmental
factors may have contributed to this pattern of hyperuricemia.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11469473 [PubMed - indexed for MEDLINE]

489: J Am Podiatr Med Assoc. 2001 Jul-Aug;91(7):379-80.

Isolated gouty tophus of a tibial sesamoid of the foot.

Lemont H, Sabo M.

Laboratory of Podiatric Pathology, Department of Medicine, Temple University
School of Podiatric Medicine, Eighth at Race St, Philadelphia, PA 19107, USA.

A case of tophaceous gout involving a foot sesamoid is described in a middle-aged
man with a history of chronic gout. Microscopic findings consisting of tophaceous
foci located beneath an intact hyaline articulating surface are correlated with
associated radiographs.

Publication Types: 
    Case Reports

PMID: 11466466 [PubMed - indexed for MEDLINE]

490: Med Hypotheses. 2001 Aug;57(2):241-2.

Self-treatment for gout.

Symons MC.

Bone & Joint Research Unit, St Bartholomew's and The Royal London School of
Medicine and Dentistry, Charterhouse Square, London, UK.

After describing some of the symptoms of gout and considering some causes, such
as an excess of ethanol, the source of the pain in the infected joint is
discussed. This is known to be from urate crystals formed in the synovial fluid
inside the joint. It is suggested herein that the pain is due to grinding from
the crystals through the surface film of the joint, and possibly into the bone
itself, which is relatively soft. The pain then stems in part from the resulting 
inflammation. The key hypothesis is that these urate crystals dissolve on
warming. Hence, by warming the joint concerned in hot water, and moving the joint
around to encourage diffusion, the urate concentration is reduced and crystals no
longer form, provided the treatment is continued. Copyright 2001 Harcourt
Publishers Ltd.

PMID: 11461181 [PubMed - indexed for MEDLINE]

491: Intern Med. 2001 Jun;40(6):493-8.

Inflammatory pseudotumor of the liver complicated with recurrent gouty arthritis.

Takahashi T, Haneda T, Nagano T, Kawahito Y, Mori Y, Senga K, Nakamura K,
Ishiguro T, Imai K.

Department of Internal Medicine, Mikasa City Hospital, Mikasa.

Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion of unknown
etiology and is often accompanied by fever. Unexplained persistent fever
unresponsive to antibiotics developed in a 70-year-old man suffering from
intractable recurrent gouty arthritis. 67Ga-scintigraphy disclosed intense focal 
uptake in the upper abdomen. The lesion in the left lobe of the liver was an
ill-defined hypodensity mass on computed tomographic scan and was enhanced on
dynamic magnetic resonance imaging. The tumor was surgically removed and a
diagnosis of IPT was made. Fever and arthritis resolved completely after surgery.
Possible interaction between IPT of the liver and gouty arthritis was suggested.

Publication Types: 
    Case Reports

PMID: 11446673 [PubMed - indexed for MEDLINE]

492: Kidney Int. 2001 Jul;60(1):266-71.

Lead chelation therapy and urate excretion in patients with chronic renal
diseases and gout.

Lin JL, Yu CC, Lin-Tan DT, Ho HH.

Division of Nephrology and Rheumatology, Department of Internal Medicine, Chang
Gung Memorial Hospital, Lin-Kou Medical Center, Chang Gung Medical College and
University, Taipei, Taiwan, Republic of China. jllin99@hotmail.com

BACKGROUND: It is known that chronic renal insufficiency (CRI) patients with gout
may have subtle lead poisoning. In addition, gout episodes frequently aggravate
progressive renal insufficiency because of the use of nephrotoxic drugs and urate
deposition. Our study was arranged to evaluate the causal effect of environmental
lead exposure on urate excretion in CRI patients. METHODS: A cross-section study 
and a randomized, controlled trial were performed. Initially, 101 patients with
CRI and without a history of previous lead exposure received
ethylenediaminetetraacetic acid mobilization tests to assess body lead stores
(BLS). Then, a clinical trial was performed; 30 CRI patients with gout and
high-normal BLS and the changes of urate excretion in these patients were
compared before and after lead chelating therapy. The treated group received
four-week chelating therapy, and the control group received a placebo therapy.
RESULTS: The BLS of patients with CRI and gout was higher than that of patients
with CRI only, and none had subtle lead poisoning. The BLS, not the blood lead
level (BLL), significantly correlated to indices of urate excretion in all CRI
patients after related factors were adjusted. In addition, after lead chelating
therapy, urate clearance markedly improved after a reduction of the BLS of
patients with CRI and gout (study group 67.9 +/- 80.0% vs. control group 1.2 +/- 
34.0%, P = 0.0056). CONCLUSION: Our findings suggest that the chronic low-level
environmental lead exposure may interfere with urate excretion of CRI patients.
Importantly, the inhibition of urate excretion can be markedly improved by lead
chelating therapies. These data shed light on additional treatment of CRI
patients with gout; however, more studies are needed to confirm our findings.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11422760 [PubMed - indexed for MEDLINE]

493: J Rheumatol. 2001 Jun;28(6):1306-10.

Comment in:
    J Rheumatol. 2001 Jun;28(6):1207-10.

Spot urine uric acid to creatinine ratio used in the estimation of uric acid
excretion in primary gout.

Moriwaki Y, Yamamoto T, Takahashi S, Yamakita J, Tsutsumi Z, Hada T.

Third Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho
1-1, Nishinomiya, Hyogo 663-8501, Japan.

OBJECTIVE: Uric acid overexcretion in patients with gout is frequently assessed
by the measurement of 24 hour urinary uric acid excretion, which is cumbersome
with ambulatory patients, and requires accurate timing and complete collection of
the specimen. We assessed whether uric acid to creatinine ratio (Uua/Ucr) in spot
urine is useful for the estimation of uric acid overexcretion in patients with
gout. METHODS: One hundred thirty male patients with gout and 33 non-gout male
control subjects were studied. Early morning urine and/or a portion of 24 h
collected urine (24 h urine) were used as spot urine samples. Uric acid
overexcreters were defined as those with a 24 h urinary uric acid excretion > or 
= 1000 mg/day, while uric acid underexcreters were defined as those with uric
acid clearance < 6 ml/min. RESULTS: There was a significant relationship between 
24 h urinary uric acid excretion and early morning urine Uua/Ucr in patients with
gout, while no such relationship was observed in controls. No significant
difference in Uua/Ucr was observed between patients with gout and controls, or in
Uua/Ucr between gout uric acid overexcreters and underexcreters in early morning 
urine. A significant difference in this value was observed between the 2 groups
in the 24 h urine specimens. Although the diagnostic accuracy of gout uric acid
overexcretion was 87.2% using early morning urine and 89.6% using 24 h urine, the
sensitivity of gout uric acid overexcretion was only 25.0% when using early
morning urine and 25.0% when using 24 h urine, when the cutoff value of Uua/Ucr
was 0.63 and 0.64, respectively. CONCLUSION: Uua/Ucr using spot urine, especially
early morning urine, is not an accurate indicator of uric acid overexcretion in
patients with gout.

Publication Types: 
    Clinical Trial

PMID: 11409124 [PubMed - indexed for MEDLINE]

494: Geriatr Nurs. 2001 May-Jun;22(3):132-4.

Gouty arthritis: not just a big toe problem.

Meiner SE.

University of Nevada in Las Vegas' College of Health Sciences, USA.

Gout is a metabolic disease characterized by recurrent episodes of acute
arthritis. High blood levels of uric acid lead to inflammation, joint swelling,
and severe pain. Treatment is aimed at relieving the acute attack and preventing 
recurrent episodes of gouty arthritis.

PMID: 11410763 [PubMed - indexed for MEDLINE]

495: J Formos Med Assoc. 2001 Mar;100(3):205-8.

Acute paraplegia in a patient with spinal tophi: a case report.

Wang LC, Hung YC, Lee EJ, Chen HH.

Neurosurgical Service, Department of Surgery, National Cheng Kung University
Hospital, College of Medicine, 138 Shen-Li Road, Tainan, Taiwan.

A 28-year-old man with a 5-year history of gouty arthritis suffered from an acute
episode of lower back pain. He visited a rehabilitative clinic and received
physical therapy following his examination. Weakness and numbness of both lower
legs developed rapidly after physical therapy. He was sent to our hospital with
complete paralysis of both lower limbs and complete sensory loss below the
umbilicus 3 hours after the physical therapy. No peripheral tophi were found.
Myelography showed an extrinsic compression of the dura sac at T10. Emergency
decompressive laminectomy of T9 to T11 was performed. During the surgery, caseous
material was found deposited in the ligamentum flavum and the left T9 to T10
facet joint, with indentation of the dura sac. The pathologic diagnosis was
spinal tophi. After surgery, the patient's neurologic function recovered rapidly.
It was suspected that inappropriate physical therapy might have aggravated acute 
inflammation of spinal gout and resulted in a rapid deterioration of neurologic
function. Though gout is a chronic medical disease, an acute attack of spinal
gout may be disastrous and requires emergency neurosurgical intervention.

Publication Types: 
    Case Reports

PMID: 11393117 [PubMed - indexed for MEDLINE]

496: Neurosurgery. 2001 May;48(5):1170-2; discussion 1172-3.

Tophaceous gout of the spine mimicking epidural infection: case report and review
of the literature.

Barrett K, Miller ML, Wilson JT.

Division of Nephrology, Maine Medical Center, Portland 04102, USA.
kbinyork@hotmail.com

OBJECTIVE AND IMPORTANCE: Tophaceous gout uncommonly affects the axial skeleton. 
The clinical presentations of gout of the spine range from back pain to
quadriplegia. Gout that presents as back pain and fever may be difficult to
distinguish from spinal infection. We present a case of a patient with tophaceous
gout of the lumbar spine who was initially diagnosed with and treated for an
epidural infection. The clinical and diagnostic features of tophaceous gout of
the spine are reviewed. CLINICAL PRESENTATION: A 70-year-old man presented with a
2-day history of fever and back pain. A physical examination revealed that he had
flank tenderness and evidence of polyarthritis affecting the elbows, knees, and
right first metatarsophalangeal joint. A magnetic resonance imaging scan of the
patient's lumbar spine showed an extensive area of abnormal gadolinium
enhancement of the paramedian posterior soft tissues from L3 to S1 with an area
of focal enhancement extending into the right L4-L5 facet joint. INTERVENTION: A 
laminectomy was performed at L4-L5, and a chalky white material in the facet
joint was found eroding into the adjacent pars intra-articularis. Light and
polarizing microscopy confirmed the presence of gouty tophus. No evidence of
infection was found. CONCLUSION: Gouty arthritis of the spine is rare.
Thirty-seven previous cases have been reported. When the clinical presentation
includes acute back pain and fever, differentiation of spinal gout from spinal
infection may be difficult. The clinical suspicion of spinal gout may lead to the
correct diagnosis by a less invasive approach than exploration and laminectomy.

Publication Types: 
    Case Reports
    Review

PMID: 11334288 [PubMed - indexed for MEDLINE]

497: Curr Opin Rheumatol. 2001 May;13(3):240-4.

Gout: can management be improved?

Schlesinger N, Schumacher HR Jr.

Section of Rheumatology, UMDNJ/New Jersey Medical School, Newark, New Jersey
07103-2714, USA. schlesna@umdnj.edu

Ongoing reviews of Cochrane collaboration show that there is still very little
reliable information based on randomized controlled trials on which to base
treatment decisions in acute and chronic gout. Recent studies have stressed that 
avoidance of factors contributing to development of gouty attacks such as
diuretic therapy, weight gain, and alcohol consumption may lead to a decrease in 
gouty arthritis. Attention to minidose aspirin and its effect on serum uric acid 
levels was addressed. A low carbohydrate, high protein and unsaturated fat diet
was recommended for gouty patients since they all enhance insulin sensitivity and
therefore may promote a reduction in serum uric acid levels. Treatment of gout in
transplant recipients brings into focus some of the issues regarding management
of gout, because gout is a common problem among transplant patients.

Publication Types: 
    Review

PMID: 11333356 [PubMed - indexed for MEDLINE]

498: Curr Opin Rheumatol. 2001 May;13(3):234-9.

Gout: diagnosis, pathogenesis, and clinical manifestations.

Agudelo CA, Wise CM.

Rheumatology Section, Emory University School of Medicine, and Atlanta Veterans
Affairs Medical Center, Decatur, Georgia, USA.

Gout is a common form of arthritis, in which many of the risk factors,
pathogenetic mechanisms, and clinical features have been recognized for years.
Nevertheless, new information has become available regarding the normal
physiologic role of uric acid as an antioxidant, and greater insight has been
obtained regarding the inflammatory process in acute gout. New studies have
improved our understanding of the role of genetic and environmental factors
responsible for hyperuricemia, and we know more about the significance of the
association of hyperuricemia with other diseases. Clinically, rare complications 
and disease manifestations in new populations continue to be discussed, and
diagnostic methods continue to be refined.

Publication Types: 
    Review

PMID: 11333355 [PubMed - indexed for MEDLINE]

499: J Rheumatol. 2001 Mar;28(3):577-80.

Treatment of chronic gout. Can we determine when urate stores are depleted enough
to prevent attacks of gout?

Li-Yu J, Clayburne G, Sieck M, Beutler A, Rull M, Eisner E, Schumacher HR Jr.

Department of Medicine, Hospital of the University of Pennsylvania, USA.
julielyu@mozcom.com

OBJECTIVE: To determine if lowering of serum uric acid (SUA) concentrations below
6 mg/dl or longer duration of lowered SUA will result in depletion of urate
crystals from the knee joints and prevent further attacks of gout. METHODS: A
prospective study was initiated 10 years ago at Philadelphia VA Medical Center to
attempt to maintain SUA levels of patients with crystal proven gout at < 6.0
mg/dl. We recalled all 57 patients who were available during 1999. Patients were 
divided into 2 groups: Group A, with SUA still > 6 mg/dl, and Group B, with SUA <
or = 6 mg/dl. A knee joint aspirate was requested from all asymptomatic Group B
patients and many in Group A. Aspirates were examined by polarized light
microscopy for identification of crystals. RESULTS: There were no differences
between the groups in age, sex, duration of gout, or serum creatinine. Group A (n
= 38) had a mean of 6 attacks of gout for the recent year, those with tophi
having the most frequent attacks. Among the 16 patients in this group who agreed 
to knee aspiration, monosodium urate (MSU) crystals were found in 14, although
they were asymptomatic at the time. Nineteen patients (Group B) were able to
maintain serum urate levels < or = 6 mg/dl for > 12 months. Nearly half of them
had no attack of gout for 2 or more years, with a mean of 1 attack in the last
year for the whole group. Three patients in whom tophi were found did not have
major flares of gout within the past year. Knee joint aspiration was done on 16
asymptomatic patients. Seven (44%) still had MSU crystals present in their knees.
Patients in this group who were taking prophylactic colchicine did not differ
with respect to the character of synovial fluid from those who had discontinued
it for up to several years, although the frequency of attacks was less in those
who continued colchicine. CONCLUSION: A majority of patients were able to deplete
urate crystal stores in their knee joint fluids when their SUA levels were kept
to < or = 6 mg/dl for several years. The mechanisms for persistence in some
patients, and whether such crystals have clinical implications, are not known.
Patients with chronic gout need serum urate concentrations to be kept low to
prevent further attacks.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11296962 [PubMed - indexed for MEDLINE]

500: Metabolism. 2001 Apr;50(4):393-8.

Increased visceral fat accumulation further aggravates the risks of insulin
resistance in gout.

Takahashi S, Moriwaki Y, Tsutsumi Z, Yamakita J, Yamamoto T, Hada T.

Third Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.

We performed the present study to determine the degree of visceral fat
accumulation and incidence of visceral fat obesity in 138 gout patients who were 
classified as overexcretion type (n = 53) and underexcretion type (n = 85) by
their levels of uric acid clearance and urinary uric acid excretion. We also
investigated the relationship between visceral fat accumulation and insulin
resistance expressed by the homeostasis model assessment (HOMA) index. Visceral
fat area (VFA)/surface body area (SBA) was significantly increased in patients
with gout as compared with control subjects (79.7 +/- 30.8 cm(2)/m(2) v 65.1 +/- 
24.1 cm(2)/m(2), P <.001). It was also shown that VFA/SBA in the gout
overexcretion group was significantly increased as compared with the gout
underexcretion group (88.3 +/- 32.8 cm(2)/m(2) v 74.3 +/- 28.3 cm(2)/m(2), P
<.01). Although the incidence of visceral fat obesity (VFO) was not different
between gout patients and control subjects, the incidence of VFO was
significantly higher in the gout overexcretion type than the gout underexcretion 
type (19 of 53 v 11 of 85, P <.01). Further, there was a significant relationship
between visceral fat area and HOMA index. Gout patients possess some factors that
are included in the insulin resistance syndrome, irrespective of the presence of 
VFO, and the insulin resistance risk factors observed in gout become more
prominent when it is complicated with VFO. Our results suggest that gout
patients, especially the overexcretion type who have greater levels of visceral
fat accumulation, may be more vulnerable to atherosclerotic diseases. Copyright
2001 by W.B. Saunders Company

Publication Types: 
    Clinical Trial

PMID: 11288032 [PubMed - indexed for MEDLINE]

501: Rheumatol Int. 2001 Feb;20(2):61-4.

Hyperuricemia in Saudi Arabia.

Al-Arfaj AS.

Department of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia.
asarfaj@ksu.edu.sa

The objective of this prospective study was to determine the prevalence of
hyperuricemia and gout in a sample of Saudi individuals and their relationship to
certain risk factors, namely, obesity, serum glucose, triglycerides, cholesterol,
age, and sex. A total of 487 Saudis (250 males and 237 females) from 14 primary
care clinics were interviewed, examined, and investigated. The mean age for the
males was 46.89 +/- 17.01 years (range 14-83) and for the females 45.08 +/- 13.67
years (range 21-80). Serum uric acid (SUA) values above 420 micromol/l for males 
and 360 micromol/l for females were considered to be high. Of the 487
individuals, 41 (8.42%; 20 males and 21 females) had hyperuricemia. The mean SUA 
was 308.41 +/- 90.64 micromol/l for males and 254.59 +/- 85.79 micromol/l for
females. In females, uric acid levels correlated significantly with age, body
mass index (BMI), serum creatinine, and the erythrocyte sedimentation rate (ESR),
but not with serum cholesterol or triglycerides. In males, uric acid levels only 
correlated significantly with BMI and serum creatinine. No case of gout was
found.

PMID: 11269534 [PubMed - indexed for MEDLINE]

502: Ann Pharmacother. 2001 Mar;35(3):365-8.

Corticotropin for acute management of gout.

Taylor CT, Brooks NC, Kelley KW.

Department of Pharmacy Practice, School of Pharmacy, Auburn University, AL, USA. 
ctaylor@cchs.ua.edu

OBJECTIVE: To evaluate safety and efficacy of corticotropin for acute gout. DATA 
SOURCES: Clinical literature was accessed through MEDLINE (1966-August 2000). Key
search terms included gout, ACTH, adrenocorticotropic hormone, and corticotropin.
DATA SYNTHESIS: Joint pain and local signs of inflammation characterize gout.
Acutely, colchicine and nonsteroidal antiinflammatory drugs (NSAIDs) are
first-line therapy. Adverse effects or concomitant diseases limit therapy and
necessitate alternative options. An evaluation of studies involving corticotropin
was conducted. CONCLUSIONS: Corticotropin alone or in combination with colchicine
was more rapidly effective and associated with fewer adverse effects than
indomethacin. This regimen may be considered an alternative, especially for
patients with medical problems in which other regimens are contraindicated.

Publication Types: 
    Review

PMID: 11261536 [PubMed - indexed for MEDLINE]

503: Curr Rheumatol Rep. 2001 Feb;3(1):36-41.

Pathogenesis of crystal-induced inflammation.

Landis RC, Haskard DO.

BHF Cardiovascular Medicine Unit, Imperial College School of Medicine,
Hammersmith Hospital, Du Cane Road, London W12 ONN, United Kingdom.

Crystals are an important cause of inflammatory rheumatic diseases and provide
relatively simple paradigms for modelling inflammatory responses in general.
Thus, in the case of gout, we know that hyperuricemia leads to precipitation of
monosodium urate (MSU) crystals in joints, which are taken up by leukocytes, and 
then an acute attack of arthritis is triggered. However, fundamental questions
remain unanswered. Why are only certain hyperuricemic individuals, and then only 
certain joints, affected? What factors maintain joints in a quiescent state, what
prompts the resolution of an inflammatory attack, and are these related? This
article draws on developments during the past year to support the idea that the
mononuclear phagocyte may play a key role within the synovial compartment,
tipping the balance from the asymptomatic state to acute inflammation, or vice
versa, depending on their state of monocyte to macrophage differentiation.

Publication Types: 
    Review

PMID: 11177769 [PubMed - indexed for MEDLINE]

504: Curr Rheumatol Rep. 2001 Feb;3(1):29-35.

Difficult gout and new approaches for control of hyperuricemia in the
allopurinol-allergic patient.

Fam AG.

Sunnybrook and Women's College Health Sciences Centre, 2075 Bayview Avenue
M-1402, Toronto, Ontario, M4M 3M5, Canada. kathy.carey@swchsc.on.ca

A major obstacle to the treatment of hyperuricemia in patients allergic to
allopurinol is the limited availability of suitable, equally effective,
alternative, urate-lowering drugs. Conventional uricosuric drugs, including
probenecid and sulfinpyrazone, are recommended for allopurinol- intolerant
patients with gout and "underexcretion" hyperuricemia who have normal renal
function and no history of nephrolithiasis. Therapeutic options in those in whom 
traditional uricosuric drugs are contraindicated, ineffective, or poorly
tolerated include slow oral desensitization to allopurinol and cautious
administration of oxipurinol. Allopurinol desensitization is useful particularly 
in those who have failed other treatment modalities. If available (as in Europe, 
South Africa, and Japan), benzbromarone may be tried in patients with gout and
mild-to-moderate renal insufficiency. Recombinant urate oxidase can be used in
the short-term prophylaxis and treatment of chemotherapy- associated
hyperuricemia in patients with lymphoproliferative and myeloproliferative
disorders. Hyperuricemia and gout occur with increased frequency in
cyclosporine-treated allograft transplant recipients. The management of gout in
these patients is complicated by two main factors: cyclosporine-induced renal
impairment, and interactions with medications used to preserve the allograft.

Publication Types: 
    Review

PMID: 11177768 [PubMed - indexed for MEDLINE]

505: J Assoc Physicians India. 2000 Mar;48(3):354-5.

An unusual systemic presentation of gout.

Kini S, Mittal G, Balakrishna C, Mangat G, Hegde AV, Joshi VR.

PD Hinduja National Hospital and Medical Research Centre, Mahim, Mumbai 400 016.

An elderly female presented with a systemic febrile illness and acute
polyarthritis as the first manifestation of gout. She improved dramatically with 
anti-inflammatory therapy.

Publication Types: 
    Case Reports

PMID: 11229128 [PubMed - indexed for MEDLINE]

506: Postgrad Med J. 2001 Mar;77(905):191-2.

Colchicine induced rhabdomyolysis.

Chattopadhyay I, Shetty HG, Routledge PA, Jeffery J.

Department of Geriatric Medicine, Ysbyty Gwynedd Hospital, Bangor, UK.

A case of colchicine induced rhabdomyolysis is reported. A 73 year old man with
ischaemic heart disease, atrial fibrillation, chronic congestive cardiac failure,
and chronic gout presented with diffuse muscle pain. He had been taking an
increased dose of colchicine (1.5 mg daily) for an exacerbation of gout for six
weeks before the presentation. Investigations confirmed the diagnosis of
rhabdomyolysis and discontinuation of colchicine resulted in resolution of
clinical and biochemical features of rhabdomyolysis. Although neuromuscular
adverse effects of colchicine are well recognised, rhabdomyolysis is rare and
this is only the fourth reported case of colchicine induced rhabdomyolysis in the
literature.

Publication Types: 
    Case Reports

PMID: 11222829 [PubMed - indexed for MEDLINE]

507: J Leukoc Biol. 2001 Jan;69(1):98-104.

Natural and synthetic agonists of the melanocortin receptor type 3 possess
anti-inflammatory properties.

Getting SJ, Allcock GH, Flower R, Perretti M.

The William Harvey Research Institute, London, England. S.J.Getting@mds.qmw.ac.uk

The effects of the natural and synthetic ligands for the melanocortin receptor
type 3 (MC3-R) have been evaluated in a murine model of experimental gout.
Systemic treatment of mice with gamma2-melanocyte-stimulating hormone
(gamma2-MSH) and the synthetic agonist MTII inhibited accumulation of KC,
interleukin-1 beta (IL-1beta), and PMN elicited by urate crystals in the
peritoneal cavity. In vitro, macrophage (Mø) activation, determined as release of
KC and IL-1beta, was inhibited by gamma2-MSH and MTII. The mixed MC3/4-R
antagonist SHU9119 prevented the inhibitory actions of gamma2-MSH and MTII in
vitro and in vivo, whereas the selective MC4-R antagonist HS024 was without
effect. Western blotting also showed the presence of MC3-R protein on murine
peritoneal Mø. Furthermore, agonism at the MC3-R evoked accumulation of cAMP
within the Mø, which was inhibited by SHU9119. Thus, naturally occurring
melanocortins, as well as the synthetic long-acting compound MTII, activate MC3-R
on peritoneal Mø to inhibit the experimental inflammatory response.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11200074 [PubMed - indexed for MEDLINE]

508: Virchows Arch. 2000 Nov;437(5):534-9.

Continuous recruitment, co-expression of tumour necrosis factor-alpha and matrix 
metalloproteinases, and apoptosis of macrophages in gout tophi.

Schweyer S, Hemmerlein B, Radzun HJ, Fayyazi A.

Abteilung Pathologie, Zentrum Pathologie, Universität Göttingen,
Robert-Koch-Strasse 40, 37075 Göttingen, Germany. sswyer@med.uni-goettingen.de

Gout tophi are characterised by foreign body granulomas consisting of mono- and
multinucleated macrophages surrounding deposits of monosodium urate
microcrystals. After primary formation, granulomas grow associated with
degradation of the extracellular matrix. Based on this background, we have sought
(1) to investigate whether during granuloma's growth new macrophages are
recruited into the tophi, (2) to find in situ evidence for macrophages' active
role in matrix degradation and (3) to examine whether shrunk cells seen within
gout tophi are apoptotic. Immunohistochemistry showed that perivascular localised
mononuclear cells are CD68+, S100A8+, S100A9+, 25F9-, representing freshly
migrated monocytes/macrophages. In contrast, almost all CD68+ mono- and
multinucleated cells arranged within granulomas were S100A8-, S100A9-, 25F9+,
representing mature (non-migrating) macrophages. Serial sections revealed that
macrophages co-express tumour necrosis factor (TNF)-alpha and matrix
metalloproteinases (MMPs) 2 and 9. In situ end-labelling of fragmented DNA
demonstrated that CD68+ macrophages undergo apoptosis within gout tophi. Our data
show that macrophages are continuously recruited into the gout tophi. These
macrophages co-produce the proinflammatory cytokine TNF-alpha and two TNF-alpha
inducible lytic enzymes, MMP-2 and MMP-9, suggesting that TNF-alpha may induce
MMP production followed by matrix degradation within foreign body granulomas. In 
parallel, macrophages undergo apoptosis, a phenomenon that may restrict the
destructive potential of inflammatory macrophages.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11147175 [PubMed - indexed for MEDLINE]

509: Joint Bone Spine. 2000;67(5):441-5.

Risk factors for gout in Togolese patients.

Mijiyawa M, Oniankitan O.

Service de rhumatologie, CHU Tokoin de Lomé, Togo.

OBJECTIVE: To determine the risk factors for gout in Togolese patients. METHODS: 
The medical records of patients admitted to the Lomé Teaching Hospital (Togo)
rheumatology department over a ten-year period were reviewed retrospectively.
RESULTS: Of the 8351 study patients, 160 (1.9%) fulfilled American Rheumatism
Association criteria for gout; 159 were male. Mean age at disease onset was 44
years, and mean disease duration was six years. Tophi were recorded in 35 cases
and a history of renal colic in one. Only five patients (3.1%) had no
identifiable risk factors. The main risk factors in the remaining patients were
alcohol abuse (133/160, 83.12%), overweight/obesity (64/160, 40%), and
hypertension (42/160, 26.25%); 153 patients (95.6%) had at least one of these
risk factors, 58 patients (36.32%) had two, and 14 (8.8%) had all three. Of the
42 hypertensive patients, 20 were on diuretic therapy. Seventeen patients
(10.62%) had a family history of gout. There was no evidence that AS or AC
hemoglobinopathy (32 and 13 cases, respectively) influenced the course or natural
history of gout. CONCLUSION: Although population-based studies are needed for
confirmation, our study suggests that risk factors for gout in Togolese patients 
are similar to those in other parts of Africa and in Western countries.

PMID: 11143911 [PubMed - indexed for MEDLINE]

510: J Rheumatol. 2000 Dec;27(12):2873-6.

Effect of low dose daily aspirin on serum urate levels and urinary excretion in
patients receiving probenecid for gouty arthritis.

Harris M, Bryant LR, Danaher P, Alloway J.

Department of Rheumatology and Medicine, San Antonio 78236-5300, USA.
Mark.Harris@59MDW.whmc.af.mil

OBJECTIVE: To determine if low dose daily enteric coated aspirin significantly
affects the therapeutic actions of probenecid with respect to serum urate levels 
or urinary urate excretion. METHODS: Patients with gouty arthritis taking a
stable dose of probenecid for at least 3 months were enrolled in a prospective
crossover study. Twenty-four hour urinary and serum uric acid levels were
measured after 14 days in patients crossed over to receive probenecid alone;
probenecid and aspirin 325 mg taken concomitantly; and probenecid followed by
aspirin 325 mg at 6 hours. RESULTS: Eleven patients completed the crossover
study. The addition of aspirin to a stable dose of probenecid had no significant 
effect upon serum urate levels or 24 h urinary urate excretion (p > 0.05, paired 
t test). CONCLUSION: Low dose daily enteric coated aspirin does not significantly
interfere with the uricosuric effects of probenecid in patients with gouty
arthritis.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11128679 [PubMed - indexed for MEDLINE]

511: Aust N Z J Med. 2000 Oct;30(5):567-72.

The optimal use of allopurinol: an audit of allopurinol use in South Auckland.

Stamp L, Gow P, Sharples K, Raill B.

Middlemore Hospital, South Auckland, New Zealand.

BACKGROUND: Gout is a common and challenging problem in South Auckland, New
Zealand. Allopurinol is widely used but urate reduction remains unsatisfactory.
Allopurinol dosing guidelines and a therapeutic range for plasma oxypurinol
levels have been published. AIMS: We aimed to determine the appropriateness of
allopurinol dosing according to current guidelines and to assess the relationship
between plasma creatinine, oxypurinol and urate. In addition, we assessed the
clinical usefulness of the oxypurinol level. METHODS: Thirty-one patients, on a
stable dose of allopurinol for at least three weeks, had plasma creatinine, urate
and oxypurinol measured as part of routine clinical assessment. Relationships
between the various methods were examined using regression analysis. Fisher's
exact test was used to test associations with categorical variables. RESULTS:
Fifty-five per cent of patients were on higher than recommended doses of
allopurinol. There was a statistically significant relationship between
calculated creatinine clearance and plasma oxypurinol level. Only 50% of patients
with a plasma oxypurinol within the therapeutic range (30-100 micromol/L) had a
plasma urate < 0.42 mmol/L and this did not increase significantly in the
patients with an oxypurinol level > 100 micromol/L. CONCLUSIONS: There is poor
adherence to the current recommended dosing guidelines for allopurinol.
Creatinine clearance rather than plasma creatinine needs to be used to predict
the dose of allopurinol. The current role of the oxypurinol level is to identify 
non-compliers with allopurinol therapy. We need further research to clarify
whether increasing the dose of allopurinol outside the recommended dose range to 
reach an oxypurinol level of close to 100 micromol/L may be of benefit in those
who have not had sufficient urate reduction.

PMID: 11108066 [PubMed - indexed for MEDLINE]

512: Nephron. 2000 Nov;86(3):287-91.

Improvement of renal function in patients with chronic gout after proper control 
of hyperuricemia and gouty bouts.

Perez-Ruiz F, Calabozo M, Herrero-Beites AM, García-Erauskin G, Pijoan JI.

Rheumatology Section, Hospital de Cruces, Barakaldo, Spain.
fperez@hcru.osakidetza.net

AIM: To evaluate the effect of nonsteroidal anti-inflammatory drug (NSAID)
withdrawal on renal function in patients with chronic gout after proper control
of hyperuricemia and gouty symptoms. METHODS: Patients with chronic gout, who
regularly used NSAIDs to control gouty symptoms prior to urate-lowering therapy, 
were prospectively followed up in an observational study. Risk factors for renal 
function impairment were recorded, and the clearance of creatinine (Ccr) was
initially measured while on colchinine therapy to prevent gouty bouts. Therapy
with urate-lowering drugs was started in order to keep serum urate levels under
6.0 mg/dl (275 micromol/l), and the Ccr was monitored during the follow-up
period. Final assessment of the renal function was made after 1 year free from
gouty bouts and without NSAID therapy during this period. RESULTS: 87 patients
completed a 1-year period of NSAID withdrawal. Low initial Ccr was related to
age, hypertension, hypertriglyceridemia and the presence of previous renal
diseases. After proper control of gout and NSAID withdrawal during 1 year, the
mean Ccr significantly raised from 94 to 104 ml/min. The improvement was
especially significant in patients whose initial Ccr was under 80 ml/min. Their
mean Ccr rose from 60 to 78 ml/min, and 12 of 29 patients achieved normal Ccr at 
the end of the study. No risk factor correlated with improvement of the renal
function. CONCLUSIONS: Renal function impairment in patients with chronic gout is
mainly related to vascular risk factors, but improvement of the renal function
was observed after proper control of hyperuricemia and NSAID withdrawal. Optimal 
control of hyperuricemia and, therefore, of symptoms of gout should be especially
considered in patients with vascular risk factors in order to avoid renal
function loss due to NSAID use. Copyright 2000 S. Karger AG, Basel

Publication Types: 
    Clinical Trial

PMID: 11096285 [PubMed - indexed for MEDLINE]

513: Eur J Radiol. 2000 Dec;36(3):123-5.

Tophaceous gout of the lumbar spine in a renal transplant patient: a case report 
and literature review.

Thornton FJ, Torreggiani WC, Brennan P.

Academic Department of Radiology, Beaumont Hospital, Beaumont Road, Dublin 9,
Ireland. frankclo@indigo.ie

Tophaceous gout of the spine is rare. We report the case of a 27-year-old male,
renal transplant recipient, who presented with an acute onset of lower back pain.
Radiological, biochemical and histo-pathological findings confirmed a diagnosis
of tophaceous gout of the lumbar spine. We present the case history with the
radiological findings and discuss the literature.

Publication Types: 
    Case Reports
    Review

PMID: 11091009 [PubMed - indexed for MEDLINE]

514: Prescrire Int. 2000 Aug;9(48):116.

Dangers of low-dose colchicine in patients with renal failure.

[No authors listed]

(1) Life-threatening colchicine intoxication can occur in patients with renal
failure, even with low-dose regimens. (2) Diarrhoea, nausea and vomiting are the 
first manifestations of overdose. Colchicine must be withdrawn immediately to
avoid severe complications (especially haematological and neuromuscular). (3)
Colchicine must not be prescribed without first assessing creatinine clearance
(using the Cockroft formula, for example), especially in elderly patients.

PMID: 11067723 [PubMed - indexed for MEDLINE]

515: Am J Dermatopathol. 2000 Oct;22(5):418-21.

Cutaneous angiosarcoma arising in a gouty tophus: report of a unique case and a
review of foreign material-associated angiosarcomas.

Folpe AL, Johnston CA, Weiss SW.

Department of Pathology and Laboratory Medicine, Emory University Medical Center,
Atlanta, USA.

Rare cases of angiosarcoma have been reported to arise in the setting of retained
foreign material or in association with arteriovenous fistulae. No previous case 
of angiosarcoma, or any other malignancy, has been reported to arise with a gouty
tophus. We present a case of an 86-year-old man with a high-grade angiosarcoma
that arose within a long-standing tophus.

Publication Types: 
    Case Reports

PMID: 11048977 [PubMed - indexed for MEDLINE]

516: J Heart Lung Transplant. 2000 Oct;19(10):951-6.

Post-cardiac transplantation gout: incidence of therapeutic complications.

Wluka AE, Ryan PF, Miller AM, Richardson M, Bergin PJ, Page JL, Esmore DS.

Rheumatology Unit, Alfred Hospital, Melbourne, Australia.
anita.wluka@med.monash.edu.au

OBJECTIVE: To study the clinical impact of gout treatment following cardiac
transplantation. METHODS: We performed an audit of all cardiac transplant
recipients of the Alfred Hospital before August 1998 who lived in Victoria.
RESULTS: We studied 225 patients (81% men), with a mean post-transplant follow-up
of 50.8 months (SD 36). Forty-three (19%) had pre-transplant gout, 19 recurring
post-transplantation. Twenty-three patients developed gout de novo.Of the 24
patients who received allopurinol, 6 developed pancytopenia and required
hospitalization. Fourteen received a change in immunosuppression: in 5 patients
following pancytopenia, and in 9 to enable safe use of allopurinol. Thirty-two
patients received colchicine; 5 developed neuromyopathy. Impaired renal function,
diuretic use, and hypertension were more common in this sub-group. Non-steroidal 
anti-inflammatory agents, used in 16 patients, caused serious complications in 1 
patient (life-threatening peptic ulceration and hemorrhage, precipitating
dialysis-dependent chronic renal failure). CONCLUSIONS: Cardiac transplant
recipients, when treated for gout, are at high risk of therapeutic complications.
Thus, gout treatment significantly affects care, health, and immunosuppression of
these patients.

PMID: 11044689 [PubMed - indexed for MEDLINE]

517: J Ethnopharmacol. 2000 Nov;73(1-2):199-207.

Inhibition of xanthine oxidase by some Chinese medicinal plants used to treat
gout.

Kong LD, Cai Y, Huang WW, Cheng CH, Tan RX.

Institute of Functional Biomolecule, State Key Laboratory of Pharmaceutical
Biotechnology, School of Life Sciences, Nanjing University, 210093, Nanjing,
People's Republic of China.

The enzyme xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine
and then to uric acid, which plays a crucial role in gout. A total of 122
traditional Chinese medicinal plants, selected according to the clinical efficacy
and prescription frequency for the treatment of gout and other
hyperuricemia-related disorders, have been evaluated for the enzyme inhibitory
activity. Among the 122 methanol extracts derived from these species, 69 were
shown to be inhibitory at 100 microg/ml, with 29 having greater than 50%
inhibition. As to the equal amount of water extracts, 40 were disclosed to be
active at 100 microg/ml, with 13 possessing more than 50% inhibition. At 50
microg/ml, 58 methanol and 24 water extracts exhibited inhibitory activity, with 
15 of the former and two of the latter showing greater than 50% inhibition. The
most active was the methanol extract of the twig of Cinnamomum cassia (Lauraceae)
(IC(50), 18 microg/ml), which was followed immediately by those of the flower of 
Chrysanthemum indicum (Asteraceae) (IC(50), 22 microg/ml) and the leaves of
Lycopus europaeus (Lamiatae) (IC(50), 26 microg/ml). Among the water extracts,
the strongest inhibition of the enzyme was observed with that of the rhizome of
Polygonum cuspidatum (Polygonaceae) (IC(50), 38 microg/ml). The IC(50) value of
allopurinol used as a positive control was 1.06 microg/ml. The study demonstrated
that the effects for these medicinal plants used for the gout treatment were
based, at least in part, on the xanthine oxidase inhibitory action.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11025157 [PubMed - indexed for MEDLINE]

518: Med Hypotheses. 2000 Jul;55(1):24-5.

Gout attacks and lunar cycle.

Mikulecký M, Rovenský J.

Institute of Preventive and Clinical Medicine, Bratislava, Slovakia.
mikuleky@upkm.sk

The aim was to search for periodical fluctuations in daily occurrence of gout
attacks during the synodic lunar cycle. 126 gout attacks were recorded between
1972 and 1994 at known calendar dates. The synodic plexogram, displaying the
number of attacks for each day of the cycle, was processed by cosinor regression.
A pronounced cycling was found, with highest peaks under the new and full moon
(syzygigies). Thus, the maximal occurrence of attacks coincides with the peaking 
lunisolar tidal effect. Similar relation of attacks to synodic moon was seen in
bronchial asthma of children, and a reciprocal one in paroxysmal tachyarrhythmia.
Differing pathogenetic backgrounds of these diseases substantiate the observed
differences in their putative reactions on the changing cosmogeophysical
environment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11021320 [PubMed - indexed for MEDLINE]

519: Rheum Dis Clin North Am. 2000 Aug;26(3):527-46, vii.

Crystal-associated arthritis in the elderly.

Agudelo CA, Wise CM.

Section of Rheumatology, Emory University School of Medicine, Decatur, Georgia,
USA.

The understanding of the clinical syndromes of gout and pseudogout, and the role 
of basic calcium crystals in arthritis has increased since the original
descriptions of the involvement of crystals in arthritis. Gout is usually
considered an affliction confined to middle aged males but has an increasing
prevalence in older populations, with unique and often atypical features. Calcium
pyrophosphate dihydrate crystal deposition disease is common in elderly patients.
The diagnosis of these common forms of arthritis and the need to individualize
therapy in patients with other medical problems remain important clinical
challenges to the practicing physician.

Publication Types: 
    Review

PMID: 10989511 [PubMed - indexed for MEDLINE]

520: Baillieres Best Pract Res Clin Rheumatol. 2000 Sep;14(3):445-60.

Gout and other crystal-associated arthropathies.

McGill NW.

Royal Prince Alfred Hospital and the University of Sydney, Australia.

Intra-articular crystals (monosodium urate monohydrate, calcium pyrophosphate
dihydrate, basic calcium phosphates) can cause acute and chronic inflammation and
joint damage. Identification of the crystals by polarized microscopy is the key
step in diagnosis but improved reliability of synovial examination is required.
Treatment of disorders associated with gout or calcium pyrophosphate deposition
may reduce non-joint morbidity and assist treatment of the arthritis. Various
forms of anti-inflammatory therapy work for acute crystal-induced arthritis;
prompt commencement is usually more important than which option is used. In gout,
recurrent attacks are usual, but hypouricaemic therapy is almost never urgent, is
life-long, and is too often negated by poor compliance. In most patients,
allopurinol or any of the potent uricosuric drugs will allow maintenance of
normouricaemia but renal failure, renal calculi, transplantation, and allopurinol
allergy narrow the options and complicate management.

Publication Types: 
    Review

PMID: 10985980 [PubMed - indexed for MEDLINE]

521: Arch Orthop Trauma Surg. 2000;120(7-8):482-3.

Surgical management of tophaceous gout in the hand.

Ertuğrul Sener E, Güzel VB, Takka S.

Gazi University Medical Faculty, Department of Orthopaedics and Traumatology,
Ankara, Turkey.

A patient who suffered from severe deforming arthritis secondary to chronic
tophaceous gout with multilobular, solid, tender, enlarged subcutaneous nodules
and draining tophi in both hands was evaluated and treated by second ray
amputation of the most deformed second finger to provide a more functional
result.

Publication Types: 
    Case Reports

PMID: 10968548 [PubMed - indexed for MEDLINE]

522: Foot Ankle Int. 2000 Aug;21(8):697-700.

Spontaneous rupture of the tibialis anterior tendon: a case report and literature
review.

Patten A, Pun WK.

Toowoomba Base Hospital, Queensland, Australia.

Spontaneous rupture of the tibialis anterior tendon is uncommon. This article
presents a case report in which spontaneous rupture of the tibialis anterior
tendon occurred secondary to a gouty tophaceous deposit within the tendon. This
report adds to the list of pathological conditions that should be considered in
closed spontaneous rupture of the tibialis anterior tendon.

Publication Types: 
    Case Reports
    Review

PMID: 10966372 [PubMed - indexed for MEDLINE]

523: AJR Am J Roentgenol. 2000 Sep;175(3):655-9.

Carpal tunnel syndrome caused by tophaceous gout: CT and MR imaging features in
20 patients.

Chen CK, Chung CB, Yeh L, Pan HB, Yang CF, Lai PH, Liang HL, Resnick D.

Department of Radiology, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st
Rd. Kaohsiung, 813 Taiwan.

OBJECTIVE: The objective of this study is to describe the CT and MR imaging
findings of gouty tophi in the wrist and present this entity as a cause of carpal
tunnel syndrome. MATERIALS AND METHODS: Retrospective review of the CT (n = 18)
and MR imaging (n = 20) studies of the wrist in patients with a documented
diagnosis of gout who presented with gout-related carpal tunnel syndrome was
performed; images of 24 wrists were collected over a 5-year period. Patient
population included 20 men, who ranged in age from 35 to 76 years. All images
were reviewed by two musculoskeletal radiologists who reached a consensus
opinion. Surgical correlation was available in 12 patients. RESULTS: Tophi were
found in the floor of the carpal tunnel (n = 18), carpal bones (n = 17),
radiocarpal joint (n = 17), and extensor tendons or tendon sheaths (n = 16) of
the wrist. All tophi showed similar signal characteristics (from low to
intermediate signal intensity on T1-weighted images with heterogeneous signal
intensity on T2-weighted images) with the exception of tophi in the floor of the 
carpal tunnel (low signal intensity on T2-weighted images). Varying degrees of
calcification were noted on CT and MR imaging studies. Gadolinium-enhanced MR
studies showed heterogeneous enhancement. CONCLUSION: Gouty tophi should be
entertained as a cause of carpal tunnel syndrome in the appropriate patient
population. Familiarity with this entity and its imaging characteristics may
prove helpful in diagnosis and preoperative planning.

PMID: 10954446 [PubMed - indexed for MEDLINE]

524: Am J Orthop. 2000 Jul;29(7):544-7.

Monoarticular acromioclavicular joint gout: a case report.

Musgrave DS, Ziran BH.

Department of Orthopaedic Surgery, University of Pittsburgh Medical Center,
Pennsylvania, USA.

Acromioclavicular joint gout is extremely rare. The case presented represents the
first case of monoarticular acromioclavicular joint gout reported. It is also the
first reported case of acromioclavicular joint gout in an immunosuppressed
patient. The diagnostic pitfalls inherent in the evaluation of acute
monoarticular arthritis in an immunosuppressed patient are illustrated.
Furthermore, the case demonstrates one of the atypical presentations of gout that
may occur in renal transplant patients taking cyclosporin A.

Publication Types: 
    Case Reports

PMID: 10926404 [PubMed - indexed for MEDLINE]

525: J Formos Med Assoc. 2000 Jul;99(7):572-5.

Thoracic cord compression due to gout: a case report and literature review.

Kao MC, Huang SC, Chiu CT, Yao YT.

Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.

An 82-year-old man developed progressive weakness of both legs 1 month prior to
admission. He reported no previous history of trauma. Spine radiography revealed 
marked thoracic and lumbar spondylosis. Magnetic resonance imaging of the spine
disclosed segmental stenosis with cord compression at T10-11 due to an extradural
soft tissue lesion. Based on a diagnosis of thoracic spondylosis with cord
compression, decompression laminectomy was performed. During the operation,
fragile chalky-white material was noted over the epidural space, compressing the 
thoracic cord. The granular lesion was meticulously removed until the dura was
identified and the cord was decompressed. Histologic examination of the surgical 
specimen revealed deposits of needle-like crystals that were consistent with
monosodium urate, demonstrating that a gouty lesion of the thoracic spine had
caused the cord compression. The patient had previously experienced several
attacks of gouty arthritis of his feet. The postoperative serum uric acid
concentration was 8.5 mg/dL. After surgery, he was treated with benzbromarone 100
mg per day. He was able to walk 3 months after the operation. A high index of
suspicion of gouty involvement of the spine is necessary in patients with gout.
Surgical decompression followed by regular administration of antigout drugs can
provide satisfactory results.

Publication Types: 
    Case Reports

PMID: 10925570 [PubMed - indexed for MEDLINE]

526: Hiroshima J Med Sci. 2000 Jun;49(2):101-3.

Subjective sensation of heaviness in gout patients.

Toda K.

Department of Orthopedic Surgery, Miharashi Ishikai Hospital, Japan.

The main objective of the treatment of gout is to protect the major organs.
Almost all gout patients require medication throughout their lives. Gout patients
are asymptomatic during intercritical periods, even if they are not receiving
antihyperuricemic drugs. Some patients, therefore, misinterpret that their gout
is cured and may cease taking medication of their own accord. Thirty-two gout
patients who had received continuous treatment with antihyperuricemic drugs for
more than 3 months were selected. The sensation of heaviness was relieved by
antihyperuricemic drugs in 14 (44%) of 32 patients. The heaviness did not exist
or change in the other patients. Benzbromarone, probenecid, and allopurinol were 
found to be effective. The sensation of heaviness occurred after increased
physical activity in 10 of 14 patients. Of 14 patients, 12 did not notice that
the sensation of heaviness was relieved by antihyperuricemic drugs. Two
hypotheses for the cause of heaviness are considered. One is mild gouty
neuropathy, the other low-grade inflammation. A proper understanding that this
symptom is relieved by antihyperuricemic drugs may serve as additional motivation
for gout patients to take their medication regularly.

PMID: 10920575 [PubMed - indexed for MEDLINE]

527: J Rheumatol. 2000 Jul;27(7):1708-12.

Effect of low level lead exposure on hyperuricemia and gout among middle aged and
elderly men: the normative aging study.

Shadick NA, Kim R, Weiss S, Liang MH, Sparrow D, Hu H.

Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.

OBJECTIVE: To determine whether longterm lead accumulation is associated with
hyperuricemia and gouty arthritis among middle aged and elderly men. METHODS: In 
a retrospective cohort study, 777 male participants were evaluated between August
1991 and October 1996 in the Department of Veterans Affairs Normative Aging
Study, a 35 year longitudinal study of aging. We examined the development of gout
and an increased uric acid level in relation to lead, adjusting for other known
risk factors. Lead levels were measured in blood and by K x-ray fluorescence
(K-XRF) technique in tibial (cortical) and patellar (trabecular) bone. RESULTS:
Blood lead levels in this mostly Caucasian (97%) population were low (mean 5.9
microg/dl, SD 3.5). Bone lead levels were comparable to those described in other 
general populations. In a multivariate analysis adjusting for the risk factors,
age, body mass index, diastolic blood pressure, alcohol intake, and serum
creatinine level, there was a positive association between patellar bone lead and
uric acid levels (p = 0.02). Of 777 participants, 52 (6.7%) had developed gouty
arthritis. In logistic regression of similar covariates, body mass index (p <
0.0001) and serum creatinine level (p = 0.005) were the strongest determinants of
gout; neither bone nor blood lead levels predicted gout in this cohort.
CONCLUSION: The longterm accumulation of lead is associated with an increased
uric acid level in middle aged and elderly men. However, this study shows no
association between lead and gouty arthritis at the levels arising from community
exposure.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

PMID: 10914856 [PubMed - indexed for MEDLINE]

528: Med J Aust. 2000 May 15;172(10):493-7.

Clinical manifestations of gout and their management.

van Doornum S, Ryan PF.

Department of Rheumatology, Alfred Hospital, Melbourne, VIC.

Gout is an inflammatory response to deposition of monosodium urate crystals in
and around joints. It is primarily a disease of adult men. In acute gout,
treatment options include non-steroidal anti-inflammatory drugs (NSAIDs),
colchicine and corticosteroids, administered either intra-articularly, orally or 
parenterally. Asymptomatic hyperuricaemia does not require specific treatment,
but should prompt screening for atherosclerosis risk factors, and general
lifestyle modification to reduce serum urate levels. Gout presents differently in
the elderly. Both women and men are affected, attacks are frequently
polyarticular and in the upper limbs, and the gout may be associated with
diuretic use, hypertension and renal impairment. In patients with peptic ulcer
disease, selective COX-2 inhibitors provide another treatment option. In the
presence of renal impairment, allopurinol is the treatment of choice for urate
lowering therapy, but doses of allopurinol and colchicine must be adjusted. Urate
lowering therapy should only be used if recurrent episodes of gout occur despite 
aggressive attempts to reverse or control the underlying causes. It should not be
introduced or discontinued during an acute episode of gout, and gout prophylaxis 
(NSAIDs or colchicine) should be prescribed during the introduction of urate
lowering therapy.

Publication Types: 
    Review

PMID: 10901773 [PubMed - indexed for MEDLINE]

529: Scand J Plast Reconstr Surg Hand Surg. 2000 Jun;34(2):189-91.

Scapholunate dissociation caused by gouty arthritis of the wrist. Case report.

Ohishi T, Koide Y, Takahashi M, Miyata R, Kushida K.

Department of Orthopaedic Surgery, Hamamatsu University School of Medicine,
Shizuoka, Japan.

Gouty arthritis of the wrist is rare, and may be associated with scapholunate
dissociation. To our knowledge, only two cases have been reported so far. In this
report, we describe a 40-year-old patient with scapholunate dissociation caused
by acute gouty arthritis of the wrist. His clinical findings and radiographs
mimicked infectious arthritis or osteomyelitis of the carpal bones.

Publication Types: 
    Case Reports

PMID: 10900639 [PubMed - indexed for MEDLINE]

530: Ann Rheum Dis. 2000 Jul;59(7):539-43.

Beneficial effects of weight loss associated with moderate calorie/carbohydrate
restriction, and increased proportional intake of protein and unsaturated fat on 
serum urate and lipoprotein levels in gout: a pilot study.

Dessein PH, Shipton EA, Stanwix AE, Joffe BI, Ramokgadi J.

Rheumatology Unit, Milpark Hospital, Pain Relief and Research Unit, CH
Baragwanath Hospital, University of Witwatersrand, Johannesburg, South Africa.
Dessein@elink.co.za

OBJECTIVES: Insulin resistance (IR) has been increasingly implicated in the
pathogenesis of gout. The lipoprotein abnormalities described in hyperuricaemic
subjects are similar to those associated with IR, and insulin influences renal
urate excretion. In this study it was investigated whether dietary measures,
reported to be beneficial in IR, have serum uric acid (SU) and lipid lowering
effects in gout. METHODS: Thirteen non-diabetic men (median age 50, range 38-62) 
were enrolled. Each patient had had at least two gouty attacks during the four
months before enrollment. Dietary recommendations consisted of calorie
restriction to 6690 kJ (1600 kcal) a day with 40% derived from carbohydrate, 30% 
from protein, and 30% from fat; replacement of refined carbohydrates with complex
ones and saturated fats with mono- and polyunsaturated ones. At onset and after
16 weeks, fasting blood samples were taken for determination of SU, serum
cholesterol (C), low density lipoprotein cholesterol (LDL-C), high density
lipoprotein cholesterol (HDL-C), and triglycerides (TGs). Results were expressed 
as median (SD). RESULTS: At onset, the body mass index (BMI) was 30.5 (8.1)
kg/m(2). Dietary measures resulted in weight loss of 7.7 (5.4) kg (p=0.002) and a
decrease in the frequency of monthly attacks from 2.1 (0.8) to 0.6 (0.7)
(p=0.002). The SU decreased from 0.57 (0.10) to 0.47 (0.09) mmol/l (p=0.001) and 
normalised in 7 (58%) of the 12 patients with an initially raised level. Serum
cholesterol decreased from 6.0 (1.7) to 4.7 (0. 9) mmol/l (p=0.002), LDL-C from
3.5 (1.2) to 2.7 (0.8) mmol/l (p=0. 004), TGs from 4.7 (4.2) to 1.9 (1.0) mmol/l 
(p=0.001), and C:HDL-C ratios from 6.7 (1.7) to 5.2 (1.0) (p=0.002). HDL-C levels
increased insignificantly. High baseline SU, frequency of attacks, total
cholesterol, LDL-C and TG levels, and total C:HDL-C ratios correlated with higher
decreases in the respective variables upon dietary intervention (p<0.05).
CONCLUSION: The results suggest that weight reduction associated with a change in
proportional macronutrient intake, as recently recommended in IR, is beneficial, 
reducing the SU levels and dyslipidaemia in gout. Current dietary recommendations
for gout may need re-evaluation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10873964 [PubMed - indexed for MEDLINE]

531: J Rheumatol. 2000 Jun;27(6):1501-5.

The interaction between uric acid level and other risk factors on the development
of gout among asymptomatic hyperuricemic men in a prospective study.

Lin KC, Lin HY, Chou P.

Community Medicine Research Center & Institute of Public Health, National
Yang-Ming University, and Veterans General Hospital, Taipei, Taiwan, ROC.

OBJECTIVE: To investigate the incidence of gout and the interaction between uric 
acid level and other risk factors in the development of gout. METHODS: Two
hundred twenty-three asymptomatic hyperuricemic men initially studied in 1991-92 
were reassessed in 1996-97. Gout was clinically diagnosed by a senior
rheumatologist based on history and physical according to the clinical criteria
of Wallace. Basic demographic and lifestyle variables as well as biochemical data
were collected in both baseline and followup periods. Both the stability analysis
and the analysis of repeated relationships were applied. RESULTS: The 5-year
cumulative incidence of gout was 18.83% (42/223). The risk factors for gout based
on the analysis of repeated relationships were uric acid level, alcohol
consumption, use of diuretics, and obesity. The only predictor of gout at
baseline was uric acid level. After adjusting for baseline uric acid level,
followup uric acid increase, persistent alcohol consumption, use of diuretics in 
the followup period, and body mass index increase were independent predictors for
gout among asymptomatic hyperuricemic men. Excessive alcohol consumption,
particularly if occasional, was the most important factor in the development of
gout, even when the concentration of uric acid level was below 8 mg/dl.
CONCLUSION: Uric acid level is the key factor for prevention of gout and needs
constant monitoring. Other contributing or possible etiologic factors such as
alcohol consumption, diuretics use, and excess weight gain carry an increased
risk of gout attack among patients with hyperuricemia.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10852278 [PubMed - indexed for MEDLINE]

532: Acta Cytol. 2000 May-Jun;44(3):433-6.

Comment in:
    Acta Cytol. 2002 Jul-Aug;46(4):784-5.

Fine needle aspiration of tophi for crystal identification in problematic cases
of gout. A report of two cases.

Rege J, Shet T, Naik L.

Department of Pathology, Bai Yamunabai Laxmanrao Nair Charitable Hospital,
Mumbai, India.

BACKGROUND: The definitive diagnosis of gout is best established by demonstration
of monosodium urate (MSU) crystals in the synovial fluid or biopsy. Fine needle
aspiration cytology (FNAC) of tophi can play a crucial role in diagnosis. CASES: 
A 36-year-old chronic alcoholic male developed subcutaneous nodules on both
malleoli without a history of arthropathy and with normal serum uric acid levels.
FNAC of the nodules demonstrated stacks and sheaves of needle-shaped crystals of 
MSU. A 50-year-old diabetic male developed multiple nodules on the feet. He gave 
a past history of painful athropathy. A roentgenogram of the feet was suspicious 
for gout; however, joint aspiration failed, and the serum uric acid levels were
normal. At this juncture FNAC of the feet tophi clinched the diagnosis of gout.
In both cases, polarization of needle washings (wet mount) and the fixed,
Papanicolaoustained smears showed negatively birefringent, needle-shaped crystals
of MSU, thus confirming the diagnosis of gout. CONCLUSION: FNAC of gouty tophi is
an easy alternative to synovial biopsy and joint fluid analysis. It is simpler,
easier and less painful. As crystals are preserved in stained smears, they can be
employed for polarization and confirmation of gout.

Publication Types: 
    Case Reports

PMID: 10834006 [PubMed - indexed for MEDLINE]

533: J Qual Clin Pract. 2000 Mar;20(1):42-3.

Quality use of allopurinol in the elderly.

Smith P, Karlson N, Nair BR.

Department of Geriatric Medicine, John Hunter Hospital, University of Newcastle, 
NSW, Australia.

Allupurinol is a commonly prescribed drug. However, the use of this drug is not
based on evidence and guidelines. We audited Allopurinol prescriptions in
patients aged 65 years and over in a teaching hospital over 22 weeks. In 47% of
patients the dose was higher than recommended and in 40% it was lower. Quality
use of medications is an important issue to maintain quality of life in the
elderly.

PMID: 10821456 [PubMed - indexed for MEDLINE]

534: Ann Clin Biochem. 2000 May;37 ( Pt 3):355-9.

Effect of urine storage on urinary uric acid concentrations.

Yamakita J, Yamamoto T, Moriwaki Y, Takahashi S, Tsutsumi Z, Hada T.

Third Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya,
Japan.

Accurate determination of serum and urinary uric acid concentrations is essential
for the diagnosis and classification of gout according to uric acid metabolism
derangement. Urine and/or serum samples are often kept at either 4 degrees C or
-20 degrees C until assayed, when a large number of samples are handled
simultaneously. Our preliminary study indicated a significant decrease in urinary
uric acid concentration after preservation, regardless of the storage
temperature. Uric acid crystals were often observed in these cases which showed a
marked decrease in urinary uric acid concentration after storage. In the present 
study, we sought the factor(s) that might cause this decrease in urinary uric
acid concentration, as well as measures to overcome the problem. High urinary
uric acid concentration and low pH proved to play major roles in the decrease in 
urinary uric acid concentration after storage. In contrast, dilution of the urine
samples before storage resulted in no significant change in urinary uric acid
concentration. Based on these results, we recommend diluting urine before storage
for determination of uric acid concentration and avoiding underestimation.

PMID: 10817251 [PubMed - indexed for MEDLINE]

535: Nephrol Dial Transplant. 2000 May;15(5):644-9.

Reduced secretion of proinflammatory cytokines of monosodium urate
crystal-stimulated monocytes in chronic renal failure: an explanation for
infrequent gout episodes in chronic renal failure patients?

Schreiner O, Wandel E, Himmelsbach F, Galle PR, Märker-Hermann E.

First Department of Medicine, University of Mainz, Mainz, Germany.

BACKGROUND: In gouty arthritis, monosodium urate (MSU) crystals interact with
monocytes and neutrophils to produce inflammatory reactions associated with acute
synovitis. In patients with end-stage renal disease (ESRD), gouty arthritis is a 
rare condition despite often severe hyperuricaemia. We wondered whether
differences in the secretion of proinflammatory cytokines by MSU
crystal-stimulated monocytes might be one explanation for the low incidence of
gouty arthritis in patients with ESRD compared with healthy controls. METHODS:
Thirteen patients with ESRD on intermittent haemodialysis treatment, six patients
with chronic renal failure not yet on dialysis, and 15 age- and sex-matched
healthy controls were examined. Monocytes, purified from peripheral blood
mononuclear cells (PBMC) by immunomagnetic bead separation, were incubated for 18
h in the presence of MSU crystals, Escherichia coli lipopolysaccharide (LPS) or
medium alone. The supernatants were studied for the presence of interleukin
(IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) using
cytokine-specific enzyme-linked immunosorbent assays. RESULTS: Monocytes from
patients with ESRD produced significantly lower amounts of IL-1beta, IL-6 and
TNF-alpha after stimulation with MSU crystals or LPS than did monocytes from
healthy subjects. Cytokine production was not significantly different between
ESRD patients on haemodialysis and chronic renal failure patients not yet on
dialysis. Artificial MSU crystals were stronger stimuli than tophus-derived
'natural' MSU crystals. CONCLUSION: We demonstrate that monocyte-associated
immunosuppression in ESRD leads to reduced secretion of proinflammatory cytokines
in response to stimuli such as MSU crystals. This may be one of the factors
preventing many ESRD patients from the manifestation of acute gout despite often 
severe hyperuricaemia.

PMID: 10809805 [PubMed - indexed for MEDLINE]

536: Curr Opin Rheumatol. 2000 May;12(3):213-8.

Gout update: from lab to the clinic and back.

Pascual E.

Hospital General Universitario de Alicante, Spain. pascual_eli@gva.es

Reviews and opinion articles stressing the need for better reproducibility of
crystal identification in synovial fluid continue to be published. The
possibility of definitive diagnosis of gout by crystal identification during
intercritical periods appears now established. The problems associated with the
use of allopurinol have also received some attention, as well as the strategies
of dealing with allopurinol hypersensitivity. Gout in transplanted patients is
reviewed, with special attention to the difficulties related to its treatment;
various therapeutic options for this group are reviewed. The use of benzbromarone
to reduce uricemia appears to be especially appropriate for this group of
patients, in whom allopurinol is problematic. Finally, the pathogenetic
mechanisms of the disease, and the relation between urate crystals and
inflammation are reviewed.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 10803751 [PubMed - indexed for MEDLINE]

537: Clin Rheumatol. 2000;19(2):142-6.

Clinical manifestations of Korean female gouty patients.

Park YB, Park YS, Song J, Lee WK, Suh CH, Lee SK.

Department of Internal Medicine, Yonsei University College of Medicine, Seoul,
Korea.

In an endeavor to analyse the clinical characteristics of female gout, we
reviewed 36 women with gout. Twenty-seven (75%) developed the first symptomatic
episode of gout after the onset of the menopause. The mean age at onset of gout
was 54.3 years (range 15-87 years). Twenty-two patients (61%) had hypertension,
17 (47%) had renal insufficiency, 13 (36%) used diuretics and 10 (28%) were
taking cyclosporine for a renal allograft. Tophaceous gout occurred in 10
patients (27%) and polyarticular involvement was seen in 16 (44%) at initial
presentation. Five of nine premenopausal patients were taking cyclosporine and
four had renal insufficiency. A comparison with a control group of 72 randomly
selected male patients with gout showed that the female patients were frequently 
receiving diuretics at the time of the attack and had significantly lower mean
uric acid excretion, whereas significantly more male patients showed heavy
alcohol consumption and precipitating events for an acute attack compared with
the female patients. There were no significant differences between the sexes for 
onset age, hypertension, renal insufficiency, distribution of joint involvement, 
tophi and mean serum uric acid concentration. The female patients in this study
had a lower mean age at onset of gout than in previous studies, which was
attributed to the inclusion of renal transplantation patients. Transplantation
gout patients receiving cyclosporine lower the mean age at onset of female gout
and this is an emerging problem in female gout.

PMID: 10791627 [PubMed - indexed for MEDLINE]

538: J Rheumatol. 2000 Apr;27(4):1045-50.

Community based epidemiological study on hyperuricemia and gout in Kin-Hu,
Kinmen.

Lin KC, Lin HY, Chou P.

Community Medicine Research Center and Institute of Public Health, National
Yang-Ming University, Taipei, Taiwan, ROC.

OBJECTIVE: This is a population survey conducted in 1991-92 among residents aged 
> or =30 years in Kin-Hu, Kinmen, with a 77.7% response rate to study the
prevalence of hyperuricemia and hyperuricemia associated gout. A stratified
analysis based on sex and age was used to assess the interaction and analyze the 
associated risk factors for hyperuricemia and gout. METHODS: Hyperuricemia was
defined as uric acid > or =7.0 mg/dl for men and > or =6.0 mg/dl for women. Gout 
was clinically diagnosed by a senior rheumatologist based on patient's history
and examination according to the clinical criteria of Wallace. Basic demographic 
and lifestyle variables as well as biochemical data were collected. RESULTS: The 
prevalence of hyperuricemia was 25.8% (391/1515) in men and 15.0% (250/1670) in
women. The prevalence of gout among hyperuricemic subjects was 11.5% for men and 
3% for women. According to age spectrum, the risk factor for hyperuricemia was
hyperlipidemia in young adults (30-39 yrs); lifestyle and some clinical syndromes
played a significant role in middle aged persons (40-59 yrs). The different risk 
factors between the sexes in middle age were alcohol consumption effect in men
and menopause effect in women. Impaired renal function and use of diuretics
became the important factors in the elderly (> or =60 yrs). The risk factors for 
gout among either the general population or subjects with hyperuricemia were
concentration of serum uric acid, alcohol consumption, and central obesity.
CONCLUSION: Risk factors for hyperuricemia tended to be different with respect to
sex and age. Alcohol consumption and central obesity were independent predictors 
of gout among hyperuricemic subjects irrespective of uric acid level.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10782835 [PubMed - indexed for MEDLINE]

539: Am J Hum Genet. 2000 Jun;66(6):1989-94. Epub 2000 Apr 25.

Familial juvenile hyperuricemic nephropathy: localization of the gene on
chromosome 16p11.2-and evidence for genetic heterogeneity.

Stibůrková B, Majewski J, Sebesta I, Zhang W, Ott J, Kmoch S.

Institute for Inherited Metabolic Disorders, 128 00 Prague 2, Czech Republic.

Familial juvenile hyperuricemic nephropathy (FJHN), is an autosomal dominant
renal disease characterized by juvenile onset of hyperuricemia, gouty arthritis, 
and progressive renal failure at an early age. Using a genomewide linkage
analysis in three Czech affected families, we have identified, on chromosome
16p11.2, a locus for FJHN and have found evidence for genetic heterogeneity and
reduced penetrance of the disease. The maximum two-point LOD score calculated
with allowance for heterogeneity (HLOD) was 4.70, obtained at recombination
fraction 0, with marker D16S3036; multipoint linkage analysis yielded a maximum
HLOD score of 4.76 at the same location. Haplotype analysis defined a 10-cM
candidate region between flanking markers D16S501 and D16S3113, exhibiting
crossover events with the disease locus. The candidate interval contains several 
genes expressed in the kidney, two of which-uromodulin and NADP-regulated
thyroid-hormone-binding protein-represent promising candidates for further
analysis.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10780922 [PubMed - indexed for MEDLINE]

540: Arthritis Rheum. 2000 Apr;43(4):925-9.

Localization of a gene for familial juvenile hyperuricemic nephropathy causing
underexcretion-type gout to 16p12 by genome-wide linkage analysis of a large
family.

Kamatani N, Moritani M, Yamanaka H, Takeuchi F, Hosoya T, Itakura M.

Institute of Rheumatology, Tokyo Women's Medical University, Japan.

OBJECTIVE: Familial juvenile hyperuricemic nephropathy (FJHN, MIM 162000) is an
autosomal-dominant disease characterized by underexcretion-type hyperuricemia,
gout, and chronic renal failure. No loci responsible for this disease or any
underexcretion-type hyperuricemia/gout have ever been identified. The aim of the 
study was to localize a gene responsible for FJHN by linkage analysis. METHODS: A
single large family with at least 20 affected members was analyzed. DNA was
obtained from 13 affected and 18 non-affected members after lymphoblastoid cell
lines were established. Initially, polymorphic data were obtained for 343
microsatellite loci covering all chromosomes except the X chromosome. Parametric 
linkage analysis was performed using the obtained data with LINKAGE package
software. RESULTS: Following a genome-wide search using a set of highly
polymorphic microsatellite markers, initial evidence for linkage was obtained for
a marker on chromosome 16p. We subsequently genotyped the same subjects for 12
additional markers spanning approximately 30 cM on the short arm of chromosome
16. We obtained a maximum 2-point logarithm of odds (LOD) score of 6.04 at theta 
= 0 with the marker D16S401; multipoint linkage analysis yielded a maximum LOD
score of 6.14 with markers D16S401 and D16S3113, and established a minimum
candidate interval of approximately 9 cM. CONCLUSION: A gene for FJHN was
localized to a candidate interval of approximately 9 cM at 16p12. These findings 
will be useful for the presymptomatic diagnosis of FJHN in some families and for 
testing genetic heterogeneity of FJHN in general.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10765940 [PubMed - indexed for MEDLINE]

541: Neurosurgery. 2000 Apr;46(4):986-8.

Lumbar radiculopathy secondary to gouty tophi in the filum terminale in a patient
without systemic gout: case report.

Paquette S, Lach B, Guiot B.

Division of Neurosurgery, Ottawa Hospital and University of Ottawa, Ontario,
Canada.

OBJECTIVE AND IMPORTANCE: Gouty arthritis and gouty tophi of the spine are very
rare. We present a patient with the clinical manifestations of an intradural
tumor and histologically proven gouty deposits in the filum terminale. CLINICAL
PRESENTATION: The patient presented with typical symptoms of lumbar radiculopathy
and neurogenic claudication. There was no evidence of peripheral gout.
INTERVENTION: Imaging studies, including computed tomography and magnetic
resonance imaging, demonstrated a 1-cm, round, intradural, calcified lesion at
the L3 vertebral level, causing moderate spinal stenosis. The patient underwent a
two-level laminectomy and removal of the mass. A pathological examination of the 
specimen revealed gouty deposits in the region of the filum terminale.
CONCLUSION: Spinal involvement in gout is very rare, and intradural gouty
deposits have not been previously described. Intradural gout should be considered
in the differential diagnosis of intradural masses.

Publication Types: 
    Case Reports

PMID: 10764275 [PubMed - indexed for MEDLINE]

542: Clin Rheumatol. 2000;19(1):67-9.

Gouty arthritis in a female patient with mixed connective tissue disease.

Huang CM.

Department of Internal Medicine, China Medical College Hospital, Taichung,
Taiwan, ROC.

Gout with systemic lupus erythematosus (SLE) or progressive systemic sclerosis
(PSS) has rarely been reported, whereas mixed connective tissue disease (MCTD)
with the demonstration of intra-articular monosodium urate crystals has never
been reported. We describe an unusual case of MCTD (SLE-PSS) in a 37-year-old
woman who developed acute gouty arthritis. Arthrocentesis and synovianalysis may 
be necessary to differentiate gout from the arthropathy of MCTD.

Publication Types: 
    Case Reports

PMID: 10752504 [PubMed - indexed for MEDLINE]

543: Clin Rheumatol. 2000;19(1):21-5.

How is gout managed in primary care? A review of current practice and proposed
guidelines.

Pal B, Foxall M, Dysart T, Carey F, Whittaker M.

Department of Rheumatology and Clinical Audit, Withington Hospital, Didsbury,
Manchester, UK. bpal@fsl.with.man.ac.uk

Twelve practices with a total list of 74,111 patients were audited; 429 patients 
were identified with a diagnosis of gout. A wide variation in various clinical
and laboratory assessments was detected. Similar variations were also noted
regarding dietary advice and medical treatment. Monitoring of patients was
infrequent. As a result of this audit, guidelines are proposed to improve the
diagnosis and management of gout in the community.

Publication Types: 
    Comparative Study

PMID: 10752494 [PubMed - indexed for MEDLINE]
