    
1: Chang Gung Med J. 2008 Sep-Oct;31(5):492-502.

Vascular response of Raynaud's phenomenon to nifedipine or herbal medication
(duhuo-tisheng tang with danggui-sini tang): a preliminary study.

Wu YJ, Luo SF, Yang SH, Chen JY, Yu KH, See LC.

Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital,
Keelung, Chang Gung University College of Medicine, Taoyuan, Taiwan.

BACKGROUND: Raynaud's phenomenon (RP) is a common manifestation in connective
tissue diseases. Calcium channel antagonists are most effective and frequently
used for treating RP. This study compared the efficacy, digital vascular
response, and tolerability between nifedipine and a combination of 2 Chinese
herbal medications (duhuo-tisheng tang and danggui-sini tang) for treating RP.
METHODS: This open-label non-randomized clinical trial included 47 connective
tissue disease patients with RP. The herbal group and the nifedipine group
included 26 and 21 patients, respectively. The duration of therapy was 4 weeks.
Baseline and posttreatment laser Doppler blood flow imaging of both hands were
performed at room temperature and after cold challenge. Nailfold capillary
microscopy was performed at the baseline and after 4 weeks of therapy. Serum
levels of soluble intercellular adhesion molecule-1 (sICAM-1), prostaglandin E2
(PGE2), nitrite (NO2), and nitrate (NO3), and plasma levels of endothelin-1
(ET-1) were also measured. Self-reported symptoms, using a visual analog scale
(VAS) and a physician global assessment (PGA), were recorded at the baseline and 
after treatment. RESULTS: After 4 weeks of treatment, VAS scores improved (p =
0.0035) and the physician's global assessment of RP severity decreased in the
nifedipine group (p = 0.0078) but not in the herbal group. Episodes of RP attacks
decreased in the nifedipine group after treatment (p = 0.008). The nifedipine
group had increased laser Doppler flow (116.3 +/- 70.7 AU) compared to the
baseline (72.4 +/- 49.0 AU, p = 0.0008). Laser Doppler images improved at various
time points after cold challenge in the nifedipine group after therapy. Laser
Doppler flow in the herbal group did not significantly change with therapy.
Capillary microscopy demonstrated no significant difference in enlargements,
avascularity, or hemorrhagic spots between groups. Serum NO2 concentrations were 
higher in the nifedipine group than in the herbal group. Levels of sICAM-1, PGE2,
NO3, and ET-1 after therapy were similar to those at the baseline in both groups.
CONCLUSIONS: The digital vascular response in RP improved with nifedipine but was
unchanged with a combination of the Chinese medicines Duhuo-Tisheng Tang and
Danggui-Sini Tang.

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

PMID: 19097597 [PubMed - indexed for MEDLINE]

2: Arthritis Rheum. 2008 Dec;58(12):3902-12.

Autoantibodies and microvascular damage are independent predictive factors for
the progression of Raynaud's phenomenon to systemic sclerosis: a twenty-year
prospective study of 586 patients, with validation of proposed criteria for early
systemic sclerosis.

Koenig M, Joyal F, Fritzler MJ, Roussin A, Abrahamowicz M, Boire G, Goulet JR,
Rich E, Grodzicky T, Raymond Y, Senécal JL.

Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, Montreal,
Quebec, Canada.

OBJECTIVE: To identify in patients with Raynaud's phenomenon (RP) independent
markers that predict progression to definite systemic sclerosis (SSc) and to
determine in patients with progression to SSc the type and sequence of
microvascular damage and its relationship to SSc-specific autoantibodies.
METHODS: Consecutive patients referred for evaluation of RP who had no definite
connective tissue disease were evaluated for microvascular damage by nailfold
capillary microscopy (NCM) and for anticentromere (anti-CENP-B), anti-Th/To,
anti-topoisomerase I, and anti-RNA polymerase III (anti-RNAP III) autoantibodies 
by specific assays. Patients were studied prospectively. RESULTS: Of the 586
patients who were followed up for 3,197 person-years, 74 (12.6%) developed
definite SSc. A characteristic sequence of microvascular damage was identified,
starting with enlarged capillaries, followed by capillary loss, and then by
capillary telangiectases. Definite SSc was diagnosed in close temporal
relationship to capillary loss. Enlarged capillaries, capillary loss, and
SSc-specific autoantibodies independently predicted definite SSc. Anti-CENP-B and
anti-Th/To antibodies predicted enlarged capillaries; these autoantibodies and
anti-RNAP III predicted capillary loss. Each autoantibody was associated with a
distinct time course of microvascular damage. At followup, 79.5% of patients with
1 of these autoantibodies and abnormal findings on NCM at baseline had developed 
definite SSc. Patients with both baseline predictors were 60 times more likely to
develop definite SSc. The data validated the proposed criteria for early SSc.
CONCLUSION: In RP evolving to definite SSc, microvascular damage is dynamic and
sequential, while SSc-specific autoantibodies are associated with the course and 
type of capillary abnormalities. Abnormal findings on NCM at baseline together
with an SSc-specific autoantibody indicate a very high probability of developing 
definite SSc, whereas their absence rules out this outcome.

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

PMID: 19035499 [PubMed - indexed for MEDLINE]

3: Clin Exp Rheumatol. 2008 May-Jun;26(3 Suppl 49):S105-7.

Iloprost treatment for refractory Raynaud's phenomenon in two infants.

Shouval DS, Mukamel M, Zulian F, Amir J, Harel L.

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petah 
Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
dror_sho@netvision.net.il

Raynaud's phenomenon (RP) is rare in young children. We describe two infants with
severe RP, manifesting as fingertip necrosis, who were resistant to conventional 
vasodilators and were treated successfully with iloprost, a prostacyclin
analogue. The application of iloprost is safe and should be considered in
children with threatening ischemic digits.

PMID: 18799065 [PubMed - indexed for MEDLINE]

4: World J Surg Oncol. 2008 Oct 1;6:106.

Adenocarcinoma of the third portion of the duodenum in a man with CREST syndrome.

Anastasopoulos G, Marinis A, Konstantinidis C, Theodosopoulos T, Fragulidis G,
Vassiliou I.

Second Department of Surgery, Areteion University Hospital, Athens, Greece.

BACKGROUND: CREST (Calcinosis, Raynaud's phenomenon, Esophageal dysmotility,
Sclerodactyly and Telangiectasias) syndrome has been rarely associated with other
malignancies (lung, esophagus).This is the first report of a primary
adenocarcinoma of the third portion of the duodenum in a patient with CREST
syndrome. CASE PRESENTATION: A 54-year-old male patient with CREST syndrome
presented with colicky postprandial pain of the upper abdomen, diminished food
uptake and a 6-Kg-body weight loss during the previous 2 months. An ulcerative
lesion in the third portion of the duodenum was revealed during duodenoscopy,
with a diagnosis of adenocarcinoma on biopsy specimen histology. The patient
underwent a partial pancreatoduodenectomy. No adjuvant therapy was instituted and
follow-up is negative for local recurrence or metastases 21 months
postoperatively. CONCLUSION: CREST syndrome has been associated with colon
cancer, gastric polyps, familial adenomatous polyposis (FAP) syndrome and Crohn's
disease; however, this is the first report of a primary adenocarcinoma of the
duodenum in a patient with CREST syndrome. However, any etiologic relationship
remains to be further investigated.

Publication Types: 
    Case Reports

PMID: 18828905 [PubMed - indexed for MEDLINE]

5: Br J Hosp Med (Lond). 2008 Aug;69(8):464-70.

Systemic sclerosis: an update for clinicians.

Herrick AL.

Rheumatic Diseases Centre, Clinical Sciences Building, University of Manchester, 
Salford Royal NHS Foundation Trust, Salford M6 8HD.

Recent advances in the management of systemic sclerosis highlight the importance 
of early diagnosis and assessment, before irreversible tissue injury has
occurred. This review will discuss diagnosis, subtyping, and the major clinical
features and their management.

Publication Types: 
    Case Reports
    Review

PMID: 18783099 [PubMed - indexed for MEDLINE]

6: Ocul Immunol Inflamm. 2008 Jul-Aug;16(4):195-7.

Juxtafoveolar telangiectasis associated with CREST syndrome.

Huerva V, Sánchez MC.

Department of Ophthalmology, University Hospital Arnau de Vilanova, Lleida,
Spain. vhuerva@mixmail.com

PURPOSE: To report a case of CREST syndrome associated with juxtafoveolar
telangiectasias (JT). DESIGN: Case report. METHODS: Observational case report.
RESULTS: A 64-year-old woman affected with CREST syndrome developed bilateral
visual loss. Capillary dilatation and permeability changes in the outer retina
were noticed during an angiographic study. Optical coherence tomography (OCT)
showed thickening with loss of the foveal depression and inner lamellar cyst. The
patient was diagnosed as stage 3, group 2A JT associated with CREST syndrome.
CONCLUSIONS: Finding JT in association with CREST syndrome suggests a common
pathophysiologic process.

Publication Types: 
    Case Reports

PMID: 18716957 [PubMed - indexed for MEDLINE]

7: Cutis. 2008 Jul;82(1):55-9.

Primary localized cutaneous nodular amyloidosis and CREST syndrome: a case report
and review of the literature.

Summers EM, Kendrick CG.

Department of Internal Medicine, Harvard Medical Faculty Physicians, Beth Israel 
Deaconess Medical Center, Boston, MA 02215, USA. esummers@bidmc.harvard.edu

Primary localized cutaneous nodular amyloidosis (PLCNA) is a form of primary
localized cutaneous amyloidosis (PLCA) that presents as yellowish waxy nodules on
the extremities, face, trunk, or genitalia. We report the case of a patient with 
PLCNA and CREST (calcinosis, Raynaud phenomenon, esophageal motility disorders,
sclerodactyly, and telangiectasia) syndrome. A diagnosis of her extensive PLCNA
was made after biopsy specimens from the bilateral shins stained positive for
amyloid extending from the superficial papillary dermis to the subcutis. Results 
of a workup were negative for paraproteinemia or signs of systemic amyloidosis
and have remained so after 8 years of follow-up. We present a review of the
literature describing the presentation and histopathology of the varying forms of
amyloidosis.

Publication Types: 
    Case Reports
    Review

PMID: 18712025 [PubMed - indexed for MEDLINE]

8: J Rheumatol. 2008 Sep;35(9):1801-8. Epub 2008 Aug 15.

Statins: potentially useful in therapy of systemic sclerosis-related Raynaud's
phenomenon and digital ulcers.

Abou-Raya A, Abou-Raya S, Helmii M.

Department of Rheumatology, University of Alexandria, Alexandria, Egypt.
annaaraya@yahoo.com

OBJECTIVE: Systemic sclerosis (SSc) is characterized by fibrosis and widespread
vascular pathology. Raynaud's phenomenon (RP) and digital ulceration are
prominent manifestations of vascular involvement in SSc. Digital ulcers (DU)
remain a serious complication, and effective therapy remains elusive. Statins
display pleiotropic effects on endothelial function that may potentially retard
vascular injury. We evaluated the potential efficacy of statin therapy in
endothelial dysfunction and in management of RP and DU. METHODS: Eighty-four SSc 
patients who fulfilled the American College of Rheumatology criteria for
classification of SSc with secondary RP despite ongoing vasodilator therapy were 
randomized into 2 groups; the first group (n = 56) received 40 mg/day
atorvastatin for 4 months; the second group (n = 28) received placebo.
Seventy-five healthy volunteers served as controls. Assessment of RP and DU was
performed monthly. The primary outcome measure was the number of DU. Secondary
endpoints included the modified Scleroderma Health Assessment Questionnaire
Disability Index (SHAQ-DI), safety, and tolerability. Measurement of functional
status in relation to RP included the SHAQ-DI, visual analog scale (VAS) for RP, 
DU and pain scales, and VAS for physician's global assessment for health.
Endothelial damage markers were also assessed. Endothelium-dependent
flow-mediated dilatation was measured by high-resolution echo-Doppler
ultrasonography. RESULTS: The overall number of DU was significantly reduced in
the statin group. Among patients in the statin group a mean of 1.6 new ulcers
developed per patient compared to 2.5 new ulcers per patient in the placebo
group. There was a statistically significant improvement in SHAQ-DI score in
patients receiving statin versus those on placebo. VAS for RP, DU severity, and
pain scales and the VAS for physician global assessment improved significantly in
the statin group compared to the placebo group. Endothelial markers of activation
showed statistically significant improvement from baseline values in the statin
versus the placebo group. CONCLUSION: Our results showed that statins retarded
vascular injury and improved patient function. The findings suggest that statins 
may aid in treating RP and DU in SSc patients. Given the safety and relative low 
cost of statins and good patient tolerability to this class of drugs, statins may
be of clinical benefit in SSc patients.

Publication Types: 
    Randomized Controlled Trial

PMID: 18709692 [PubMed - indexed for MEDLINE]

9: J Am Acad Dermatol. 2008 Oct;59(4):633-53. Epub 2008 Jul 24.

Raynaud's phenomenon: pathogenesis and management.

Bakst R, Merola JF, Franks AG Jr, Sanchez M.

Ronald O. Perelman Department of Dermatology, New York University Medical Center,
New York, New York 10016, USA.

Raynaud's phenomenon is a common clinical disorder for which patients frequently 
seek the expertise and care of dermatologists. It is manifested by recurrent
vasospasm of the fingers and toes, often associated with exposure to cold
temperature or emotional stress. The phenomenon is named after Maurice Raynaud,
who, as a medical student, defined the first case in 1862 as episodic, symmetric,
acral vasospasm characterized by pallor, cyanosis, suffusion, and a sense of
fullness or tautness, which may be painful. Despite more than 140 years of
research, the pathophysiology of Raynaud's phenomenon continues to elude
investigators. Accordingly, although many pharmacologic treatments have been
reported, there is still no cure or gold standard therapy. Further, response to
treatment varies and is difficult to predict. Recently, there has been renewed
interest in finding the pathogenetic mechanisms of Raynaud's phenomenon, an
effort that has led to more potential targeted therapeutics. The purpose of this 
review is to discuss recent breakthroughs in the pathogenesis and treatment of
Raynaud's phenomenon.

Publication Types: 
    Review

PMID: 18656283 [PubMed - indexed for MEDLINE]

10: J Rheumatol. 2008 Sep;35(9):1830-7. Epub 2008 Jul 15.

Low versus high-dose iloprost therapy over 21 days in patients with secondary
Raynaud's phenomenon and systemic sclerosis: a randomized, open, single-center
study.

Kawald A, Burmester GR, Huscher D, Sunderkötter C, Riemekasten G.

Department of Rheumatology and Clinical Immunology, Charité University Hospital, 
Berlin, Germany.

OBJECTIVE: We compared the efficacy of different dosages of longterm iloprost
treatment on Raynaud's phenomenon (RP), ulcer healing, skin thickening, and
progression of internal organ sclerosis in patients with systemic sclerosis
(SSc). METHODS: Fifty patients with SSc were randomized 1:1 for the maximally
tolerated dose up to 2 ng/kg body weight per minute or low-dose (0.5 ng/kg bw per
min) intravenous iloprost administration, applied for 6 hours daily over 21 days.
Effects on RP, ulcer healing, skin thickness, esophageal function, and lung
involvement assessed by forced vital capacity (FVC) and DLCO were measured, as
well as side effects. RESULTS: Both regimens yielded 70% reduction of digital
ulcers, 40% reduction in frequency of RP, and 30% reduction in duration of RP.
One year after therapy, the modified Rodnan skin score appeared to be unchanged. 
FVC and DLCO-SB were stable in 87% and 74% of the patients, respectively. The
effect of iloprost on skin thickness and lung function was sustained in a
subgroup of patients receiving several courses of iloprost. As assessed by a
patient questionnaire, 12% of all patients did not respond to iloprost therapy,
but 78% experienced a longlasting effect. Mild side effects were common in both
groups, but did not lead to discontinuation of therapy. CONCLUSION: Low-dose
iloprost was shown to be equally effective as high-dose iloprost in longterm
treatment and was very effective in therapy of digital ulcers. Registered in
www.ClinicalTrials.gov (registration no. NCT00622687).

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

PMID: 18634152 [PubMed - indexed for MEDLINE]

11: J Rheumatol. 2008 Aug;35(8):1591-8. Epub 2008 Jul 15.

Color Doppler ultrasonography of hand and finger arteries to differentiate
primary from secondary forms of Raynaud's phenomenon.

Schmidt WA, Krause A, Schicke B, Wernicke D.

Medical Center for Rheumatology Berlin-Buch, Berlin, Germany.
w.schmidt@immanuel.de

OBJECTIVE: Modern ultrasound (US) equipment allows rheumatologists to directly
visualize hand and finger arteries. How does US aid in diagnosis of Raynaud's
phenomenon (RP)? METHODS: Color Doppler US of the proper and common palmar
digital, radial, and ulnar arteries and the superficial palmar arch of both hands
was performed in 135 consecutive patients who presented with suspected RP.
RESULTS: US was pathologic in 63% of patients with secondary RP, in 6% with
primary RP, and in none with pseudo-RP (p < 0.0001). We found 3 types of vascular
pathology: Type 1 showed narrowing or chronic occlusion of some proper digital
arteries; Type 2 was characterized by the same finding in all proper digital
arteries; and Type 3 involved acute occlusions. Type 1 was found in 3 of 53
patients with primary RP and in 19 patients with secondary RP including 5 of 9
patients with anti-centromere positive systemic sclerosis (SSc); Type 2 occurred 
in 16 patients with SSc, MCTD, and dermatomyositis; and Type 3 was found in 8
patients with antiphospholipid antibody syndrome, thromboangiitis obliterans,
vibration trauma, or vasculitis. The ulnar arteries were more commonly affected
than the radial arteries. The 2nd radial, 3rd radial, 4th ulnar, and 5th ulnar
proper palmar digital arteries were most commonly involved. CONCLUSION: Aiding in
differentiating primary versus secondary RP, severe versus less severe disease,
and acute versus chronic vascular occlusion, digital artery US depicts the same
anatomical structures as angiography, but it is cheaper, faster, and noninvasive.

PMID: 18634148 [PubMed - indexed for MEDLINE]

12: J Cutan Med Surg. 2008 Jul-Aug;12(4):189-93.

Improvement in both Raynaud disease and hyperhidrosis in response to botulinum
toxin type A treatment.

Kossintseva I, Barankin B.

Division of Dermatology, University of Alberta, Edmonton, AB

BACKGROUND: A patient with concurrent Raynaud disease presented for hyperhidrosis
of the axillae and palms. After a positive response to botulinum toxin type A
(BoNTA) for axillary hyperhidrosis, she returned requesting palmar treatment.
OBJECTIVES: Our goal was to investigate the effect of BoNTA on Raynaud disease in
concurrent hyperhidrosis with respect to color change, swelling, and digital
pain. METHODS: The patient had treatment with 100 units of BoNTA to one hand at
first, with the other being a negative control, followed by treatment of the
second hand 1 week later. RESULTS: After the injection into the first palm, the
patient demonstrated an 85% reduction in palmar hyperhidrosis and a significant
improvement in her Raynaud symptoms. Specifically, the BoNTA-treated hand had
reduced swelling, color change, and pain, whereas the untreated control hand
remained affected. After the second hand was treated, it, too, demonstrated the
same positive results. CONCLUSIONS: Our case report of concurrent Raynaud disease
and palmar hyperhidrosis shows significant improvement in both conditions to
BoNTA administration. The physiology is multifactorial and relates to BoNTA's
effect on acetylcholine, noradrenaline, substance P, calcitonin gene-related
peptide, and glutamate release from nerve terminals. These results present an
encouraging novel treatment option in dermatology for patients with Raynaud
disease.

Publication Types: 
    Case Reports

PMID: 18627700 [PubMed - indexed for MEDLINE]

13: Arch Ophthalmol. 2008 Jul;126(7):964-7.

Bilateral infusion pump implants as therapy for refractory corneal ulcers in a
patient with CREST syndrome: an interdisciplinary approach.

De Andrés J, García-Delpech S, Pérez VL, Díaz-Llopis M, Udaondo P, Sánchez MT,
Salom D.

Departments of Anesthesia, Critical Care, and PainManagement, University General 
Hospital, Valencia, Spain.

Internal infusion pumps are implantable and programmable systems that have been
widely used for years in the management of chronic pain. During the past few
years, these devices have had an increasingly prominent role given the
possibility of insulin infusions in patients with diabetes mellitus because they 
provide patients with higher autonomy in the management of their disease, despite
the fact that they are expensive systems and require surgery for implantation.
These features make internal infusion pumps a suitable therapeutic option for
those patients who need to use artificial tears continuously because of severe
dry eyes. We report a case of severe eye pain due to xerophthalmia in a patient
with CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility,
sclerodactyly, and telangiectasia) syndrome who was treated with an implanted
pump reservoir.

Publication Types: 
    Case Reports

PMID: 18625944 [PubMed - indexed for MEDLINE]

14: Arthritis Rheum. 2008 Jul;58(7):2174-82.

Prognostic model based on nailfold capillaroscopy for identifying Raynaud's
phenomenon patients at high risk for the development of a scleroderma spectrum
disorder: PRINCE (prognostic index for nailfold capillaroscopic examination).

Ingegnoli F, Boracchi P, Gualtierotti R, Lubatti C, Meani L, Zahalkova L, Zeni S,
Fantini F.

Department of Rheumatology, Instituto Gaetano Pini, University of Milan, Milan,
Italy. francesca.ingegnoli@unimi.it

OBJECTIVE: To construct a prognostic index based on nailfold capillaroscopic
examinations that is capable of predicting the 5-year transition from isolated
Raynaud's phenomenon (RP) to RP secondary to scleroderma spectrum disorders
(SSDs). METHODS: The study involved 104 consecutive adult patients with a
clinical history of isolated RP, and the index was externally validated in
another cohort of 100 patients with the same characteristics. Both groups were
followed up for 1-8 years. Six variables were examined because of their potential
prognostic relevance (branching, enlarged and giant loops, capillary
disorganization, microhemorrhages, and the number of capillaries). RESULTS: The
only factors that played a significant prognostic role were the presence of giant
loops (hazard ratio [HR] 2.64, P = 0.008) and microhemorrhages (HR 2.33, P =
0.01), and the number of capillaries (analyzed as a continuous variable). The
adjusted prognostic role of these factors was evaluated by means of multivariate 
regression analysis, and the results were used to construct an algorithm-based
prognostic index. The model was internally and externally validated. CONCLUSION: 
Our prognostic capillaroscopic index identifies RP patients in whom the risk of
developing SSDs is high. This model is a weighted combination of different
capillaroscopy parameters that allows physicians to stratify RP patients easily, 
using a relatively simple diagram to deduce the prognosis. Our results suggest
that this index could be used in clinical practice, and its further inclusion in 
prospective studies will undoubtedly help in exploring its potential in
predicting treatment response.

Publication Types: 
    Clinical Trial

PMID: 18576359 [PubMed - indexed for MEDLINE]

15: Occup Med (Lond). 2008 Sep;58(6):431-5. Epub 2008 Jun 20.

The validity of Raynaud's phenomenon symptoms in HAVS cases.

Youakim S.

Department of Medicine, University of British Columbia, Vancouver, British
Columbia, Canada. syouakim@telusplanet.net

BACKGROUND: Raynaud's phenomenon, a common manifestation of the hand-arm
vibration syndrome (HAVS), is typically diagnosed by a subjective history
provided by employees. AIM: This study evaluates the validity of the subjective
history of Raynaud's phenomenon provided by individuals applying for compensation
for HAVS. METHODS: Thirty-six workers with a history of occupational hand-arm
vibration exposure who were labelled as having Raynaud's phenomenon were asked to
photographically document their finger symptoms before undergoing a detailed
clinical assessment. Each individual was provided with a disposable camera and
instructions. Returned photographs were reviewed for signs of Raynaud's
phenomenon. The reliability of photograph interpretation was tested with three
physicians and a non-physician. RESULTS: Inter and intra-rater reliability was
very good, Kappa coefficient >0.80. Six individuals (17%) did not return cameras.
Thirty individuals provided photographs and underwent a clinical evaluation. The 
photographs of 13 individuals (43%) did not show Raynaud's phenomenon and for
four of these the diagnosis was not supported by careful symptom history.
Seventeen individuals (57%) had photographic evidence of Raynaud's phenomenon.
CONCLUSIONS: A presenting history of Raynaud's phenomenon in workers seeking
compensation for HAVS may not be accurate since approximately half the cases are 
unable to provide objective photographic evidence of Raynaud's phenomenon.

Publication Types: 
    Validation Studies

PMID: 18567613 [PubMed - indexed for MEDLINE]

16: Ostomy Wound Manage. 2008 Apr;54(4):62-5.

Acoustic pressure wound therapy in the treatment of a vasculopathy-associated
digital ulcer: a case study.

Fleming CP.

Monticello-Big Lake Hospital Wound Care Center, Monticello, Minnesota, USA.

Digital vasculopathy and subsequent digital ulceration are common and painful
complications of limited cutaneous systemic sclerosis. Although the use of
hydrocolloid occlusive dressings has been found to reduce pain, frequently
required surgical or chemical debridement can be intensely painful in such
ulcers. Acoustic pressure wound therapy is a noncontact, low-frequency ultrasound
therapy used for painless debridement in a variety of acute and chronic wounds.
It was administered to treat an intensely painful, methicillin-resistant
Staphylococcus aureus-infected finger ulcer resulting from peripheral, bilateral 
vasculopathy in a 68-year-old man with a history of three prior fingertip
amputations secondary to limited cutaneous systemic sclerosis-associated digital 
vasculopathy. At treatment initiation, 90% of the 11 cm2 wound was covered with
firmly adherent fibrin slough. Acoustic pressure wound therapy was performed
three times weekly for 5 minutes per treatment and the wound was covered with a
hydrocolloid occlusive dressings. Pain scores decreased from 10 (visual analog
scale, 0 = none, 10 = extreme) at the beginning of treatment to 0 at the week 8
assessment and his analgesics were discontinued. After 10 weeks (31 acoustic
pressure wound therapy treatments), the wound was completely closed.

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

PMID: 18480507 [PubMed - indexed for MEDLINE]

17: Clin Ter. 2008 Mar-Apr;159(2):77-81.

Oxidant/antioxidant status in patients with Raynaud's disease.

Biondi R, Coaccioli S, Lattanzi S, Puxeddu A, Papini M.

Department of Internal Medicine and Dermatology Unit, Perugia University School
of Medicine, S. Maria General Hospital, Terni, Italy.

OBJECTIVE: Despite several studies concerning the oxidative stress in Raynaud's
phenomenon secondary to systemic sclerosis (secondary Raynaud, SR), little is
known regarding the relationship between Raynaud's disease (primary Raynaud, PR) 
and oxidative stress at present. The aim of the present research was to study the
parameters of oxidative stress in PR patients and to compare them to those of SR 
patients. MATERIALS AND METHODS: Serum hydroperoxide (Hydrop) level, serum total 
antioxidant capacity (TAC) and serum total thiol (-SHp) barrier were measured in 
19 patients with SR, 15 patients with PR and 14 healthy control subjects (CS).
The statistical contrasts were performed via one-way ANOVA. RESULTS: The serum
Hydrop concentrations were significantly higher in SR (p = 0.0043) and PR (p =
0.0038) groups in comparison with CS. A significant decrease in serum TAC level
in SR (p = 0.00005) and PR (p = 0.00128) patients in respect to the CS was
revealed. No significant change in the -SHp barrier in SR and PR patients in
respect to CS has been demonstrated. However, there were no significant
differences in serum Hydrop and TAC levels between the groups of patients.
CONCLUSIONS: The study of serum oxidative stress parameters, in terms of Hydro
and TAC levels may be used as a routine and rapid test to verify the oxidative
stress status in SR and PR patients and to undertake a strategy of treatments by 
a supplementation of antioxidant molecules.

PMID: 18463765 [PubMed - indexed for MEDLINE]

18: J Clin Rheumatol. 2008 Feb;14(1):30-3.

Methylphenidate and dextroamphetamine-induced peripheral vasculopathy.

Syed RH, Moore TL.

Division of Rheumatology, Saint Louis University Medical Center, Saint Louis,
Missouri 63104, USA.

Methylphenidate and dextroamphetamine are central nervous system stimulants used 
in the treatment of attention deficit hyperactivity disorders in children. These 
medications have been associated with cerebral arteritis, renal necrotizing
vasculitis, and systemic and pulmonary hypertension. We report 4 patients, 2 on
methylphenidate and 2 on dextroamphetamine who presented with acral cyanosis,
livedo reticularis, or Raynaud phenomenon. Two patients were found to have a
positive ANA at low titers, 1 of whom had histopathologic evidence of stratum
malgiphian necrosis with perivascular lymphocytic infiltration on skin biopsy.
Two had positive antihistone antibodies. One patient improved after withdrawal of
dextroamphetamine; others had worsening of their symptoms on higher doses of
medications. These cases indicate the potential for development of acral
cyanosis, livedo reticularis, or Raynaud symptoms with these medications and
their potential contribution to a vasculopathy.

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

PMID: 18431096 [PubMed - indexed for MEDLINE]

19: Cochrane Database Syst Rev. 2008 Apr 16;(2):CD006687.

Oral vasodilators for primary Raynaud's phenomenon.

Vinjar B, Stewart M.

Møre and Romsdal County, Department of Health and Social Services, Fylkeshusa,
Molde, Norway, 6407. bergljot.vinjar@nesset.post.no

BACKGROUND: Many different drugs have been suggested for the symptomatic
treatment of primary Raynaud's phenomenon. Apart from calcium channel blockers,
which are considered the drugs of choice, the evidence of the effects of
alternative pharmacological treatments is limited. OBJECTIVES: To assess the
effects of various drugs with vasodilator actions on primary Raynaud's
phenomenon. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group
searched their Specialised Register (last searched 24 July 2007), and the
Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 3, 
2007). In addition, we searched MEDLINE (January 1966 to July 2007), EMBASE (1980
to July 2007) and reference lists of relevant articles. We contacted
pharmaceutical companies. There were no language restrictions. SELECTION
CRITERIA: Randomised controlled trials evaluating the effects of oral
formulations of any drug with vasodilator effects on subjective symptoms in
primary Raynaud's phenomenon. Treatment with, or comparison with, calcium channel
blockers was not assessed in this review. DATA COLLECTION AND ANALYSIS: Both
authors assessed the trials for inclusion and their quality. One author (BV)
extracted the data MS checked the results. Data extraction included adverse
events. we contacted trial authors for missing data. MAIN RESULTS: Eight studies 
involving 290 participants were included. Two trials examined the effects of
captopril, the rest were single trials on single drugs. All comparisons were with
placebo. The methodological quality of most trials was poor. Enalapril was
associated with a small increase in the frequency of attacks per week (difference
in means 0.8; 95% CI 0.43 to 1.17). The difference between the intervention
groups on a subjective improvement score was non-significant. There was a
significant effect of buflomedil on the frequency of attacks per week (weighted
mean difference (WMD) -8.8; 95% CI -17.55 to -0.09), but there was no evidence of
effect on the severity score. The proportion with fewer attacks was significantly
higher on moxisylyte than on placebo (relative risk (RR) 4.33; 95% CI 1.36 to
13.81). For captopril, beraprost, dazoxiben and ketanserin there was no evidence 
of an effect on the frequency, severity or duration of attacks. Beraprost and
moxisylyte gave significantly more adverse effects than placebo. AUTHORS'
CONCLUSIONS: Poor methodological quality, small sample sizes and the limited data
available resulted in low precision of the statistical results and limited value 
of the overall results .The overall results show that there is no evidence for an
effect of vasodilator drugs on primary Raynaud's phenomenon.

Publication Types: 
    Meta-Analysis
    Review

PMID: 18425964 [PubMed - indexed for MEDLINE]

20: Nat Clin Pract Rheumatol. 2008 Jun;4(6):328-32. Epub 2008 Apr 15.

A case of undifferentiated connective tissue disease: is it a distinct clinical
entity?

Mosca M, Tani C, Bombardieri S.

Rheumatology Unit, Department of Internal Medicine, University of Pisa, Pisa,
Italy. marta.mosca@int.med.unipi.it

BACKGROUND: In November 2001, a 24-year-old woman with thrombocytopenia and
Raynaud's phenomenon presented to our clinic. Her physical examination was
unremarkable except for bruising on her legs and arms. INVESTIGATIONS: Laboratory
assays detected the presence of antinuclear and anti-ribonucleoprotein
antibodies. Tests for antibodies to double-stranded DNA and for antiphospholipid 
(lupus anticoagulant and anticardiolipin), anticentromere, anti-Scl-70, and
antiplatelet antibodies were negative, as was a Coombs test. An echocardiogram,
chest X-ray, and abdominal scan showed no abnormalities. Nailfold digital
capillaroscopy revealed minor capillary changes not specific for scleroderma.
DIAGNOSIS: Undifferentiated connective tissue disease. MANAGEMENT: The patient
was successfully treated initially with high doses of corticosteroids and
azathioprine, followed by rapid dose tapering. Therapy was continued for 2 years 
and then stopped. Over the next 4 years the patient's disease history was
unremarkable, apart from mild Raynaud's phenomenon of the hands and the presence 
antinuclear and anti-ribonucleoprotein antibodies. The diagnosis of
undifferentiated connective tissue disease was confirmed at her most-recent
assessment, in October 2007.

Publication Types: 
    Case Reports
    Review

PMID: 18414458 [PubMed - indexed for MEDLINE]

21: Lupus. 2008;17(3):206-9.

Severe digital ischemia-a presenting symptom of malignancy-associated
antiphospholipid syndrome.

Grossman A, Gafter-Gvili A, Green H, Ben Aharon I, Stemmer SM, Molad Y, Krause I.

Department of Internal Medicine E, Rabin Medical Center, Beilinson Campus, Petach
Tikva Israel. Affiliated to Sackler Medical School, Tel Aviv University, Tel
Aviv, Israel. alon2206@012.net.il

The association of the antiphospholipid syndrome with malignancy has been
extensively reported. Raynaud's phenomenon has also been reported to be
associated with various malignancies. In this report, we describe two patients
who presented with severe digital ischemia mimicking Raynaud's phenomenon. The
patients were found to have antiphospholipid syndrome, and upon extensive
evaluation, a diagnosis of a malignancy was made. This report highlights the
importance of malignancy workup in patients with severe digital ischemia
associated with antiphospholipid syndrome.

Publication Types: 
    Case Reports

PMID: 18372361 [PubMed - indexed for MEDLINE]

22: Rheum Dis Clin North Am. 2008 Feb;34(1):89-114; vii.

Diagnosis and management of scleroderma peripheral vascular disease.

Herrick A.

Rheumatic Diseases Centre, University of Manchester, Salford Royal NHS Foundation
Trust, Salford M6 8HD, UK. ariane.herrick@manchester.ac.uk

The manifestations of peripheral vascular disease in patients who have systemic
sclerosis (SSc) range from episodic Raynaud's phenomenon to irreversible tissue
injury with ulceration and gangrene. Structural and functional changes may occur 
in the microvessels, digital arteries, and sometimes more proximal vessels. This 
article discusses the assessment of patients who have Raynaud's phenomenon in
whom an underlying scleroderma-spectrum disorder is suspected and patients who
have SSc with critical digital ischemia/ulceration. Different imaging techniques,
including capillaroscopy and angiography, complement the history and examination,
and developments in vascular imaging should facilitate future studies of
pathogenesis and treatment response. New vasoactive treatments are currently
being researched and older treatments revisited; therefore new approaches to
therapy will likely be developed over the next 5 to 10 years.

Publication Types: 
    Review

PMID: 18329535 [PubMed - indexed for MEDLINE]

23: Rheum Dis Clin North Am. 2008 Feb;34(1):81-7; vii.

Regulation of vascular reactivity in scleroderma: new insights into Raynaud's
phenomenon.

Flavahan NA.

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins
University, Ross Research Building R370, 720 Rutland Avenue, Baltimore, MD 21205,
USA.

Because of the role of the RhoA/Rho kinase (ROCK) pathway in regulating numerous 
pathologic processes including vasoconstriction, vascular remodeling, and
fibrosis, ROCK inhibitors may be especially beneficial in treating Raynaud's
phenomenon and scleroderma.

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

PMID: 18329534 [PubMed - indexed for MEDLINE]

24: Rheumatol Int. 2008 Aug;28(10):1023-9. Epub 2008 Mar 5.

Management of cutaneous vascular complications in systemic scleroderma:
experience from the German network.

Herrgott I, Riemekasten G, Hunzelmann N, Sunderkötter C.

Department of Dermatology, University Hospital Münster, Münster, Germany.

Major cutaneous vascular complications of systemic sclerosis (SSc) are secondary 
Raynaud's phenomenon (RP) and digital ulcers. Even though SSc is a rare disease, 
timely and appropriate management of its vascular complications is mandatory for 
reducing the rate of major impairment. It should therefore be aware to physicians
from different specialties. We evaluated the diagnostic and therapeutic approach 
toward secondary RP and ulceration in SSc patients at 28 German clinical centers 
at the time of initiation of the German network for Systemic Scleroderma (DNSS). 
We retrieved data via questionnaires and from the DNSS patient registry.
Management of RP and ulcerations in SSc were heterogeneous at initiation of the
network, reflecting a sometimes insufficient use of the diagnostic and
therapeutic possibilities. As such, (1) calcium channel blockers were the first
line therapy in most centers; but often in insufficient dosages, and (2) only
21.2% of patients with acral ulceration had received prostacyclins when recruited
into the network. The sometimes insufficient care of vascular complications of
SSc in Germany revealed the need for their standardized management, e.g. within a
network for SSc and for consensus on a diagnostic or therapeutic algorithm.

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

PMID: 18320192 [PubMed - indexed for MEDLINE]

25: Clin Rheumatol. 2008 Jun;27(6):783-6. Epub 2008 Feb 2.

The diagnostic accuracy of power Doppler ultrasonography for differentiating
secondary from primary Raynaud's phenomenon in undifferentiated connective tissue
disease.

Kim SH, Kim HO, Jeong YG, Lee SY, Yoo WH, Choi TH, Lee SI.

Department of Internal Medicine, Chosun University College of Medicine, Gwangju, 
Republic of Korea.

This study was conducted to evaluate the diagnostic accuracy of power Doppler
ultrasonography (PDU) for differentiating secondary from primary Raynaud's
phenomenon (RP), and also compared PDU with nailfold capillaroscopy (NFC) for the
assessment of microvascularity in undifferentiated connective tissue disease
(UCTD) patients with RP. Microvascularity in the nailfold and finger tip was
evaluated using PDU with cold challenge, and the findings of PDU were classified 
according to the qualitative grading system before and after cold challenge. NFC 
was performed at the same day in all persons. The results of PDU were compared
with the clinical, laboratory data, and the findings of NFC. The 14 UCTD patients
with RP were included in our study. Seven patients were suspected of secondary RP
in NFC examination, thus NFC yielded a correct classification into secondary RP
in 50% of the UCTD patients. The PDU finding of pattern II, which is regarded as 
the finding of secondary RP, was observed in 12 UCTD patients with RP. Thus, PDU 
yielded a correct classification into secondary RP in 86% of UCTD patients. In
conclusion, we confirmed that PDU has a higher correct classification rate than
NFC for the diagnosing of secondary RP in UCTD patients. Our results suggest that
PDU has better accuracy than NFC in differentiating secondary from primary RP,
and PDU is more useful in assessing microvascular abnormalities in UCTD patients 
with RP.

Publication Types: 
    Clinical Trial
    Validation Studies

PMID: 18246378 [PubMed - indexed for MEDLINE]

26: Arthritis Rheum. 2008 Feb;58(2):563-6.

Association between treatment with central nervous system stimulants and
Raynaud's syndrome in children: a retrospective case-control study of
rheumatology patients.

Goldman W, Seltzer R, Reuman P.

Akron Children's Hospital and Medical Center, Akron, Ohio 44308, USA.
wgoldman@chmca.org

OBJECTIVE: To investigate whether central nervous system (CNS) stimulants used
for the treatment of attention deficit hyperactivity disorder (ADHD) are
associated with the development of Raynaud's syndrome (RS). METHODS: A
case-control design was used for this study. All patients seen in a pediatric
rheumatology practice during a 5-year period who had signs and symptoms of RS and
met diagnostic criteria for RS as determined by pulse volume recording were
studied as cases. Controls were randomly selected patients at the same clinic who
did not have signs or symptoms of RS. They were matched to the cases for age,
sex, and time of presentation. We tested for associations between various CNS
medications and presence of RS. We also evaluated differences in laboratory test 
results between RS cases and matched controls. RESULTS: Sixty-four patients were 
enrolled in the study (32 cases with RS [23 female, 9 male] and 32 control
patients). McNemar's test showed a significant association between the presence
of RS and past or current use of ADHD stimulants (methylphenidate and
dextroamphetamine) (chi(2) = 5.00, P = 0.01). The use of other CNS medications
was not found to be significantly associated with RS (chi(2) = 1.33, P = 0.25 by 
McNemar's test). C-reactive protein levels and erythrocyte sedimentation rates
were significantly higher in controls than in cases. CONCLUSION: The results of
this study indicate that there is a significant association between development
of RS and therapy with CNS stimulants used for the treatment of ADHD. Although
this was a small study, these findings provide preliminary evidence of an adverse
effect of CNS stimulant medications in patients seen in rheumatology practice.

PMID: 18240233 [PubMed - indexed for MEDLINE]

27: Rheumatology (Oxford). 2008 Feb;47(2):219-21.

Comment in:
    Rheumatology (Oxford). 2008 Aug;47(8):1260; author reply 1260.

Sparing of the thumb in Raynaud's phenomenon.

Chikura B, Moore TL, Manning JB, Vail A, Herrick AL.

The Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, UK.
docbatsi@aol.com

OBJECTIVES: To conduct a prospective study to determine which digits are affected
(and whether the thumb is spared or not) in a cohort of patients with RP as
assessed by symptoms and thermography and to determine whether the degree of
thumb involvement differs between primary (PRP) and secondary Raynaud's
phenomenon (SRP). METHODS: This was a cross-sectional study of 44 patients with
RP. The following characteristics were recorded to allow comparisons between
digits: symptoms of RP in each digit (graded on a scale of 'never', 'sometimes'
and 'always' affected during an attack of RP) and thermography at 23 degrees C. A
distal-dorsal difference (DDD) in temperature at 23 degrees C of -1 degree C or
less was considered to be clinically relevant. RESULTS: Symptom scores in the
thumb were significantly better, i.e. less severe than in each finger (P <
0.001). As only three participants had any finger better than the thumb, there
was no power to compare whether the thumb was spared more in PRP compared with
SRP. Mean DDD was significantly higher (i.e. better) in the thumb compared with
each finger (P < 0.001). Although DDD scores were higher in PRP compared with SRP
(P = 0.01), there was no evidence that the relative effect of the thumb differed 
between the two groups (P = 0.26). CONCLUSIONS: Our findings confirm that the
thumbs are spared in RP, both primary and secondary, as demonstrated by both
symptoms and thermography. The reasons for sparing of the thumb were not
addressed in this study but raised questions regarding pathophysiology.

PMID: 18208825 [PubMed - indexed for MEDLINE]

28: Pain Physician. 2008 Jan;11(1):91-6.

Successful treatment of digital ulcers in a scleroderma patient with continuous
bilateral thoracic sympathetic block.

Han KR, Kim C, Park EJ.

Pain Clinic, Department of Anesthesiology and Pain Medicine, Ajou University
Hospital, Suwon, Korea.

BACKGROUND: Raynaud's phenomenon (RP) associated with connective tissue disease
(secondary RP) may be difficult to manage with conservative therapy. A
combination of sympathetically mediated vasospasm and vaso-occlusion has been
implicated as the etiology of digital ischemic phenomenon. Thoracic sympathetic
outflow blocking has been performed with various techniques. However, there have 
been some limitations in all treatment options. OBJECTIVE: We report on a patient
with medically refractory digital ulceration and gangrene caused by scleroderma
who was successfully treated with a continuous infusion of mepivacaine into the
thoracic sympathetic ganglions as a means to improve finger circulation. CASE
REPORT: We are reporting on a 32-year-old female patient suffering from a
medically intractable gangrenous ulcer in the right third finger and the left
second and third fingers, accompanied by aching pain (VAS, visual analogue scale,
5 - 6/10) and numbness in both forearms. She underwent continuous infusion of
mepivacaine through the thoracic sympathetic catheter placed in T2 vertebral
segment for 13 days on the right and for 11 days on the left and cervical
epidural infusion of mepivcaine with fentanyl for 10 days after the medical
treatment failed. Her finger temperature increased 2 degrees C - 5 degrees C
during the thoracic sympathetic block with continuous infusion of mepivacine. Her
finger wounds healed completely with 13 days of the continuous thoracic
sympathetic block without any complications. CONCLUSIONS: Continuous infusion of 
mepivacaine into the thoracic sympathetic ganglionic space led to the healing of 
the medically refractory gangrenous ulcer of the fingers in the patient with
scleroderma.

Publication Types: 
    Case Reports

PMID: 18196175 [PubMed - indexed for MEDLINE]

29: Clin Rheumatol. 2008 Jul;27(7):827-31. Epub 2007 Dec 19.

Manganese superoxide dismutase Ala-9Val mitochondrial targeting sequence
polymorphism in systemic lupus erythematosus in Poland.

Sobkowiak A, Lianeri M, Wudarski M, Lacki JK, Jagodziński PP.

Department of Biochemistry and Molecular Biology, Poznan University of Medical
Sciences, 6 Swiecickiego St., 60-781 Poznań, Poland.

Systemic lupus erythematosus (SLE) is a chronic and progressive autoimmune
disease in which reactive oxygen species contribute to pathogenesis. We analysed 
the distribution of manganese superoxide dismutase (MnSOD2) 47C>T (Ala-9Val)
functional polymorphic variants within the mitochondrial targeting sequence in
SLE patients (n = 102) and controls (n = 199). We did not find significant
differences in the distribution of MnSOD2 47C>T polymorphic variants in SLE
patients and controls. However, we found that MnSOD2 Val/Val genotype (recessive 
model) showed a significant association with Raynaud's phenomenon, odds ratio
(OR) = 12.000 [95% confidence interval (CI) = 2.315-62.193], p = 0.0015. We also 
found that the MnSOD2 Val/Val genotype contributes to immunologic manifestations,
OR = 2.957 (95% CI = 1.207-7.243), p = 0.0222, and anti-dsDNA antibody presence
OR = 3.365 (95% CI = 1.364-8.304), p = 0.0107, in patients. Our observations
indicate that MnSOD2 Val/Val variant can be linked to some clinical
manifestations in patients with SLE.

PMID: 18095014 [PubMed - indexed for MEDLINE]

30: Rheumatology (Oxford). 2008 Jan;47(1):80-3.

Cold stimulus fingertip lacticemy test--an effective method to monitor acute
therapeutic intervention on primary Raynaud's phenomenon and systemic sclerosis.

Fontenelle SM, Kayser C, Pucinelli ML, Andrade LE.

Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São
Paulo, SP 04023-062, Brazil.

OBJECTIVES: The recently developed cold stimulus fingertip lacticemy test
(CS-FTL) provides biochemical assessment of peripheral perfusion in patients with
Raynaud's phenomenon (RP). We evaluated how the CS-FTL test can assess the acute 
effect of nifedipine in microvascular dynamics on primary RP and RP secondary to 
SSc. METHODS: A double-blinded controlled trial with crossover design was
performed in 20 primary RP and 20 SSc patients. Patients received one single
sublingual placebo or 10 mg nifedipine capsule, with crossover after a 15-day
washout period. FTL was determined in resting conditions (pre-CS-FTL) and 10 min 
after CS (post-CS-FTL), before and 1 h after drug administration. Percent
variation in post- vs pre-CS-FTL was expressed as deltaCS-FTL. RESULTS: Before
intervention, CS induced FTL decrease in primary RP (deltaCS-FTL = -21.3 +/-
13.0%) and FTL increase in SSc patients (deltaCS-FTL = +24.5 +/- 21.2%). Placebo 
had no effect on pre-CS-FTL, post-CS-FTL and deltaCS-FTL in primary RP and SSc.
Nifedipine induced a significant decrease in pre-CS-FTL (1.94 +/- 0.45 vs 1.57
+/- 0.41 mg/dl; P = 0.005) and post-CS-FTL (1.53 +/- 0.35 vs 1.32 +/- 0.37 mg/dl;
P = 0.004) in primary RP and a significant decrease in post-CS-FTL (3.18 +/- 1.43
vs 2.56 +/- 1.30 mg/dl; P = 0.028) and deltaCS-FTL (+15.9 +/- 24.7% vs -12.9 +/- 
16.6%; P = 0.001) in SSc. CONCLUSIONS: The CS-FTL test was able to demonstrate
and quantify a dual effect of nifedipine on the biochemical dimension of
peripheral perfusion in primary RP and in SSc patients in which there was a
significant improvement in tissue perfusion in resting conditions and after
exposure to a CS. The CS-FTL test will enrich the armamentarium for investigation
and clinical evaluation of conditions associated with RP.

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

PMID: 18077495 [PubMed - indexed for MEDLINE]

31: Rheumatology (Oxford). 2008 Jan;47(1):76-9.

Vasodilator iontophoresis a possible new therapy for digital ischaemia in
systemic sclerosis?

Murray AK, Moore TL, King TA, Herrick AL.

Rheumatic Diseases Centre, Hope Hospital, Salford M6 8HD, UK.
andrea.murray@manchester.ac.uk

OBJECTIVE: This study investigated whether whole finger vasodilator iontophoresis
increases digital blood flow in patients with systemic sclerosis (SSc): If so,
this might indicate a novel approach to therapy. METHODS: Eight patients and 8
healthy controls underwent whole finger iontophoresis using a specially designed 
chamber. Treatment was with 0.5% sodium nitroprusside (NaNP) or 1% acetylcholine 
chloride (ACh), and the procedure then repeated with the other vasodilator
(randomly assigned order). Three treatments were carried out for each chemical; 2
min treatments were carried out bilaterally at 200 microA, a third was then
carried out for 5 min on one digit only (randomly assigned to left or right).
Blood flow increases were monitored with laser Doppler imaging (LDI). Maximum
perfusion increase from baseline (MAX) and the area under the time perfusion
curve (AUC), normalized for baseline, were calculated. Data were compared with a 
three-way analysis of variance test. RESULTS: Perfusion increased in both
patients and controls, but significantly more so in controls (P(MAX) = 0.001,
P(AUC) = 0.005, respectively). Values were significantly higher for the 5 min
treatment compared with the 2 min treatment (P(MAX) = 0.011 and P(AUC) = 0.008
for both groups). No significant differences were found between the use of NaNP
and ACh. CONCLUSIONS: The increased perfusion with both ACh and NaNP in the
patient group (albeit to a lesser degree than in the control group) indicates
that this local approach to vasodilation is effective. Increasing iontophoresis
time causes more sustained vasodilation. Further studies are indicated to
investigate a possible therapeutic effect in patients with severe digital
ischaemia.

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

PMID: 18077494 [PubMed - indexed for MEDLINE]

32: Am J Physiol Regul Integr Comp Physiol. 2008 Feb;294(2):R630-8. Epub 2007 Nov
28.

Chronobiological characterization of women with primary vasospastic syndrome:
body heat loss capacity in relation to sleep initiation and phase of entrainment.

Vollenweider S, Wirz-Justice A, Flammer J, Orgül S, Kräuchi K.

Psychiatric University Clinics, Thermophysiological Chronobiology, Centre for
Chronobiology, Wilhelm Klein-Strasse 27, Basel, Switzerland.

Women with primary vasospastic syndrome (VS), but otherwise healthy, exhibit a
functional disorder of vascular regulation (main symptom: cold extremities) and
often suffer from difficulties initiating sleep (DIS). Diverse studies have shown
a close association between distal vasodilatation before lights off and a rapid
onset of sleep. Therefore, we hypothesized that DIS in women with VS could be due
to a reduced heat loss capacity in the evening, i.e., subjects are
physiologically not ready for sleep. The aim of the study was to elucidate
whether women having both VS and DIS (WVD) or not (controls) show different
circadian characteristics (e.g., phase delay of the circadian thermoregulatory
system with respect to the sleep-wake cycle). Healthy young women (n = 9 WVD and 
n = 9 control) completed a 40-h constant routine protocol (adjusted to habitual
bedtime) before and after an 8-h sleep episode. Skin temperatures [off-line
calculated as distal-proximal skin temperature gradient (DPG)] and core body
temperature (CBT; rectal) were continuously recorded. Half-hourly saliva samples 
were collected for melatonin assay and subjective sleepiness was assessed on the 
Karolinska Sleepiness Scale (KSS). Compared with control, WVD showed no
differences in habitual bed times, but a 1-h circadian phase delay of dim
light-melatonin onset (hours after lights on: WVD 14.6 +/- 0.3 h; control 13.5
+/- 0.2 h; P = 0.01). Similar phase shifts were observed in CBT, DPG, and KSS
ratings. In conclusion, WVD exhibit a phase delay of the endogenous circadian
system with respect to their habitual sleep-wake cycle, which could be a cause of
DIS.

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

PMID: 18046019 [PubMed - indexed for MEDLINE]

33: Medicine (Baltimore). 2007 Nov;86(6):334-43.

Long-term follow-up of hypothenar hammer syndrome: a series of 47 patients.

Marie I, Hervé F, Primard E, Cailleux N, Levesque H.

Department of Internal Medicine, Rouen University Hospital, Rouen, France.
isabelle.marie@chu-rouen.fr

Hypothenar hammer syndrome (HHS) is an uncommon form of secondary Raynaud
phenomenon, occurring mainly in subjects who use the hypothenar part of the hand 
as a hammer; the hook of the hamate strikes the superficial palmar branch of the 
ulnar artery in the Guyon space, leading to occlusion and/or aneurysm of the
ulnar artery. In patients with HHS, such injuries of the palmar ulnar artery may 
lead to severe vascular insufficiency in the hand with occlusion of digital
artery. To date, only a few series have analyzed the long-term outcome of
patients with HHS. This prompted us to conduct the current retrospective study to
1) evaluate the prevalence of HHS in patients with Raynaud phenomenon and 2)
assess the short-term and long-term outcome in patients with HHS.From 1990 to
2006, 4148 consecutive patients were referred to the Department of Internal
Medicine at the University of Rouen medical center for evaluation of Raynaud
phenomenon using nailfold capillaroscopy. HHS was diagnosed in 47 of these 4148
patients (1.13% of cases).Forty-three patients (91.5%) had occupational exposure 
to repetitive palmar trauma. The more common occupations were factory worker
(21.3%), mason (12.8%), carpenter (10.6%), and metal worker (10.6%); the mean
duration of occupational exposure to repetitive palmar trauma at HHS diagnosis
was 21 years. One patient (2.1%) had recreational exposure (aikido training) to
repetitive trauma of the palmar ulnar artery, and 3 other patients (6.4%)
developed HHS related to a single direct injury to the hypothenar area. Clinical 
manifestations were more often unilateral (87.2%) involving the dominant hand
(93%). HHS complications included digital ischemic symptoms (ischemia: n = 21,
necrosis: n = 20) and irritation of the sensory branch of the ulnar nerve (n =
11). In HHS patients, angiography demonstrated occlusion of the ulnar artery in
the area of the Guyon space (59.6%), aneurysm of the ulnar artery in the area of 
the Guyon space (40.4%), and embolic multiple occlusions of the digital arteries 
(57.4%).All patients were advised to change their occupational exposure. They
were given vasodilators, including calcium channel blocker (n = 37) and
buflomedil (n = 12); 36 patients (76.6%) also received oral platelet aggregation 
inhibitors. Twenty-one patients with digital ischemia/necrosis were further given
hemodilution therapy to reduce the hematocrit level to 35%. In 3 patients with
HHS-related digital necrosis who exhibited partial improvement with vasodilators,
prostacyclin analog therapy (a 5-day regimen of intravenous prostacyclin analog) 
was instituted, resulting in complete healing of digital ulcer in these 3
patients. Other conservative treatment options included controlling risk factors 
(smoking cessation, low-lipid diet, therapy for arterial hypertension) and
careful local wound care of fingers in the 20 patients with digital necrosis.
Only 2 patients, exhibiting digital necrosis and multiple digital artery
occlusions, with nonthrombotic ulnar artery aneurysm underwent reconstructive
surgery, that is, resection of the aneurysm with end-to-end anastomosis of the
ulnar artery. The median length of follow-up in patients with HHS was 15.9
months. Thirteen patients (27.7%) exhibited clinical recurrences of HHS; the
median time of HHS recurrence onset was 11 months. Outcome of HHS relapse was
favorable with conservative measures in all cases.Awareness of HHS is required to
increase suspicion of the disorder so that further exposure to risk factors like 
repetitive hypothenar trauma can be avoided for these patients; this is of great 
importance for their overall prognosis. We found favorable outcomes in most
patients after conservative measures were initiated; therefore we suggest that
surgery may be undertaken in the subgroup of patients who exhibit partial
improvement while receiving conservative therapy. Finally, because we observed
recurrence of HHS in 27.7% of patients, we note that HHS patients require close
follow-up, including both regular and systematic physical vascular examination.

PMID: 18004178 [PubMed - indexed for MEDLINE]

34: Arthritis Rheum. 2007 Nov;56(11):3837-46.

Prevention of vascular damage in scleroderma and autoimmune Raynaud's phenomenon:
a multicenter, randomized, double-blind, placebo-controlled trial of the
angiotensin-converting enzyme inhibitor quinapril.

Gliddon AE, Doré CJ, Black CM, McHugh N, Moots R, Denton CP, Herrick A, Barnes T,
Camilleri J, Chakravarty K, Emery P, Griffiths B, Hopkinson ND, Hickling P,
Lanyon P, Laversuch C, Lawson T, Mallya R, Nisar M, Rhys-Dillon C, Sheeran T,
Maddison PJ.

University of Wales, Bangor, UK.

OBJECTIVE: To evaluate the efficacy and tolerability of prolonged administration 
of quinapril, a long-acting angiotensin-converting enzyme inhibitor, in the
management of the peripheral vascular manifestations of limited cutaneous
systemic sclerosis (lcSSc) and in the prevention of the progression of visceral
organ involvement in the disease. METHODS: This was a multicenter, randomized,
double-blind, placebo-controlled study evaluating quinapril 80 mg/day, or the
maximum tolerated dosage, in 210 patients with lcSSc or with Raynaud's phenomenon
(RP) and the presence of SSc-specific antinuclear antibodies. Treatment was for
2-3 years. The primary outcome measure was the number of new ischemic ulcers
appearing on the hands; secondary measures were the frequency and severity of RP 
attacks, skin score, treatments for ischemia, health status (measured by the
Short Form 36 instrument), measures of kidney and lung function, and
echocardiographic estimates of pulmonary artery pressure. An intent-to-treat
analysis was used. RESULTS: Quinapril did not affect the occurrence of digital
ulcers or the frequency or severity of RP episodes. It did not alter the
treatments that were prescribed for either infected ulcers or severe RP symptoms.
There was no apparent effect on the estimated tricuspid gradient. Health status
was not affected by quinapril, and one-half of the patients who believed they had
benefited from the trial treatment were in the placebo arm. Quinapril was not
tolerated by one-fifth of the patients, with dry cough being the most frequent
side effect. CONCLUSION: Administration of quinapril for up to 3 years had no
demonstrable effects on the occurrence of upper limb digital ulcers or on other
vascular manifestations of lcSSc in this patient population.

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

PMID: 17968938 [PubMed - indexed for MEDLINE]

35: Curr Opin Rheumatol. 2007 Nov;19(6):611-8.

Current drug therapy for scleroderma and secondary Raynaud's phenomenon:
evidence-based review.

Henness S, Wigley FM.

Wolters Kluwer Health | Adis, Auckland, New Zealand.

(1) Scleroderma and secondary Raynaud's phenomenon are frequently associated with
increased morbidity for which no specific standardised treatment guidelines
exist. (2) Current therapies for scleroderma target the immune system, with the
goal of reducing inflammation and secondary tissue injury and fibrosis. Therapy
targeting underlying vascular disease is designed to improve the symptoms of
Raynaud's phenomenon and to reduce ischemic injury to involved organs. (3) Few
controlled trials of therapy used for scleroderma are completed, and current
treatments are largely based on organ-specific therapy and uncontrolled case
series suggesting disease modification. (4) Recent randomised, controlled trials 
in scleroderma demonstrate promising results in the treatment of interstitial
lung disease with cyclophosphamide, and vascular disease of the lungs and digits 
with endothelin receptor antagonists, the phosphodiesterase inhibitor sildenafil 
and prostacyclins, while trials with methotrexate show only modest benefit in
controlling scleroderma-associated skin disease. (5) Prostacyclins are a
therapeutic option in patients with secondary Raynaud's phenomenon. Modest
benefits have also been shown with alpha1-antagonists and calcium channel
blockers, while the effect of ACE inhibitors has been variable. Some data suggest
some benefits to the use of the phosphodiesterase inhibitor sildenafil, the
serotonin uptake inhibitor fluoxetine and the angiotensin receptor inhibitor
losartan.

Publication Types: 
    Review

PMID: 17917543 [PubMed - indexed for MEDLINE]

36: Clin Rheumatol. 2008 Mar;27(3):345-51. Epub 2007 Sep 2.

Lupus nephritis and Raynaud's phenomenon are significant risk factors for
vascular thrombosis in SLE patients with positive antiphospholipid antibodies.

Choojitarom K, Verasertniyom O, Totemchokchyakarn K, Nantiruj K, Sumethkul V,
Janwityanujit S.

Division of Allergy-Immunology-Rheumatology, Department of Medicine, Ramathibodi 
Hospital, 270 Rama6 Road, Bangkok, 10400, Thailand.

This study is aimed to determine the predictors of nongravid vascular thrombosis 
in systemic lupus erythematosus (SLE) patients with positive antiphospholipid
antibodies (SLE-aPL). A cohort of 67 SLE-aPL patients who had at least one
positive test for lupus anticoagulant (LA), anticardiolipin (aCL), or
anti-beta2glycoprotein-1(B2) was examined. Main outcome was the presence of
vascular thrombosis. Association between thrombosis and risk factors was examined
by contingency table. The odds ratio (OR) of significant predictors was
determined by logistic regression. Three percent of patients were LA(+), 6% were 
aCL(+), 31% were B2(+), 3% were aCL(+)LA(+), 35.8% were aCL(+)B2(+), 7.5% were
LA(+)B2(+), and 13.4% were positive for all tests. As for clinical
manifestations, 79% had lymphopenia, 76% had lupus nephritis (LN), 41.8% had
autoimmune hemolytic anemia, 34.3% had thrombocytopenia, 20.9% had abortion, and 
19.4% had Raynaud's phenomenon (RP). Thrombosis occurred in 26 patients. The
prevalence of thrombosis for SLE-aPL was 38.8%. Thrombosis was observed more
frequently in patients with LA(+) (12 of 18) than the others (14 of 49; p =
0.01). Two-by-two table showed that oral contraceptive and LN were significantly 
associated with increased risk of thrombosis, while lymphopenia and antimalarials
were significantly associated with decreased risk of thrombosis. Multivariate
analysis confirmed that LN and RP were associated with increased risk of
thrombosis (OR = 6.2 and 3.2; p = 0.005 and 0.008), while lymphopenia and
antimalarials were associated with decreased risk of thrombosis (OR = 0.86 and
0.18; p = 0.02 and 0.034). LA is the strongest test to determine the risk of
thrombosis in SLE-aPL. The presence of LN and RP strongly predicts thrombosis,
while lymphopenia and antimalarials are protective. These findings help to
identify patients who may benefit from prophylactic therapy.

PMID: 17805483 [PubMed - indexed for MEDLINE]

37: J Physiol Anthropol. 2007 Jun;26(4):449-57.

Perception of foot temperature in young women with cold constitution: analysis of
skin temperature and warm and cold sensation thresholds.

Sadakata M, Yamada Y.

School of Health Sciences, Faculty of Medicine, Niigata University, Niigata,
Niigata 951-8518, Japan. atom@clg.niigata-u.ac.jp

To examine the disease state of cold constitution, physiological measurements of 
the foot were conducted by investigating thermal sensations under an
environmental condition of 25 degrees C-26 degrees C (neutral temperature) in 29 
young women with and without cold constitution. The subjects were classified into
3 groups according to their experiences with cold constitution: cold
constitution, intermediate, and normal groups. Foot skin temperature was measured
by thermography. Thermal sensations were measured on the dorsum of the left foot 
using a thermal stimulator. Cold and warm spots on the dorsum of the right foot
were ascertained. Thermal stimulation was delivered by a copper probe. No
significant differences in foot skin temperature among these 3 groups were
identified as measured in a laboratory under neutral temperature conditions.
However, the mean warm sensation threshold was +6.3+/-1.09 degrees C (mean+/-SEM)
for the cold constitution group (n=14), +3.4+/-2.10 degrees C (mean+/-SEM) for
the intermediate group (n=7), and -0.25+/-1.96 degrees C (mean+/-SEM) for the
normal group (n=6). The difference was significant between the cold constitution 
and normal groups. No significant differences among the 3 groups were found in
the cold sensation threshold. This may be attributable to the distribution of
thermal receptors and to chronically reduced blood flow in subcutaneous tissues, 
where the skin temperature receptors responsible for temperature sensation are
located.

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

PMID: 17704623 [PubMed - indexed for MEDLINE]

38: Lupus. 2007;16(7):505-8.

Comment in:
    Lupus. 2008;17(4):355.

Raynaud's phenomenon is correlated with elevated systolic pulmonary arterial
pressure in patients with systemic lupus erythematosus.

Kasparian A, Floros A, Gialafos E, Kanakis M, Tassiopoulos S, Kafasi N,
Vaiopoulos G.

Department of Cardiology, Laikon General Hospital, Univ. of Athens, School of
Medicine, Athens, Greece.

In patients with Systemic lupus erythematosus (SLE), Raynaud phenomenon (RP) is
frequently present and associated with pulmonary hypertension (PHT). Elevated
pulmonary artery systolic pressure (PASP) is an indicator of PHT and can be
estimated noninvasively. We attempt to explore the significance of RP in SLE and 
to correlate it with clinical and serological parameters of the disease.The study
population consisted of 34 patients (age, sex and disease duration matched) who
fulfilled the revised SLE criteria of the American College of Rheumatology, and
were categorized into two groups: Group 1 had patients having SLE and RP (2
males/15 females, mean age 45 +/- 18 years) and group 2 had patients with SLE but
without RP (3 males/14 females, mean age 40 +/- 14 years. Detailed cardiac
ultrasound was performed including measurement of PASP, while clinical and
serological features of both groups were collected and correlated. Significant
differences were shown in the presence of arterial hypertension (P < 0.05),
arthralgias (P < 0.005), arthritis (P < 0.05), myalgias (P < 0.05), alopecia (P <
0.05) and PASP (P < 0.0001). No difference was observed among the cardiac
ultrasound indices and the ejection fraction between the two groups. PASP was
significantly correlated with RP, while no correlation was observed regarding the
disease duration.In patients with SLE, the presence of RP was associated with
elevation in PASP. Further investigation is needed to clarify the significance of
this relation.

PMID: 17670849 [PubMed - indexed for MEDLINE]

39: Folia Med (Plovdiv). 2006;48(3-4):22-8.

Raynaud's phenomenon in common rheumatic diseases.

Lambova SN, Kuzmanova SI.

Clinic of Rheumatology, Medical University, Plovdiv, Bulgaria.

Raynaud's phenomenon (RP) is caused by a reversible spasm of the smallest
arteries and the arterioles of the fingers and toes. Two forms of RP have been
described: primary and secondary. Secondary RP is often present in patients with 
rheumatic diseases. This review presents the characteristics of the clinical
pattern, the immunological profile and the capillaroscopic pattern in patients
with primary and secondary RP in common rheumatic diseases. Attention is paid to 
standard examinations usually used in RP patients. Primary RP appears to be more 
common in women beginning usually at puberty. This disorder is caused by
vasospasm; no abnormalities of the endothelium are observed. Primary RP shows
benign progression. Laboratory tests - erythrocyte sedimentation rate (ESR) and
antinuclear antibody test (ANA) - are normal. Capillaroscopy is normal too.
Secondary RP tends to begin later in life. Of the rheumatic diseases, scleroderma
is the one that is the most often associated with RP (in 90-95% of all cases).
The pathogenesis of secondary RP in scleroderma is explained with abnormalities
of the endothelium through different mechanisms. Motor ulcerations are frequently
observed. Anticentromeric and antitopoizomeric antibodies get positive.
Capillaroscopy appears to be very important for the early diagnosis and prognosis
of scleroderma. The capillaroscopic pattern is abnormal - enlarged capillaries,
hemorrhages and avascular areas are observed. Part of the patients with systemic 
lupus erythematosus, Sjogren's syndrome and polymyositis / dermatomyositis
develops secondary RP and it usually shows benign progression. RP is the main
symptom in mixed connective tissue disease and trophic abnormalities of the
fingers are frequently observed. Elevated anti-U1-RNP antibody titers and an
abnormal capillaroscopic pattern are specific for the condition. In older
patients isolated RP may represent a paraneoplastic manifestation. RP is
frequently found in the rheumatologic practice. The differentiation of the
primary form from the secondary one is essential because of the differences
concerning the heaviness of the disorder, the prognosis and the therapeutic
approach.

Publication Types: 
    Review

PMID: 17668693 [PubMed - indexed for MEDLINE]

40: Ann Pharmacother. 2007 Sep;41(9):1544-7. Epub 2007 Jul 31.

Effect of clonazepam on Raynaud's phenomenon and fingertip ulcers in scleroderma.

Colakoğlu M, Cobankara V, Akpolat T.

Departmen of Nephrology, School of Medicine, Pamukkale University, Denizli,
Turkey. murcol@mynet.com

OBJECTIVE: To report the novel finding of a significant improvement in Raynaud's 
phenomenon symptoms with clonazepam in a patient with systemic sclerosis. CASE
SUMMARY: A 45-year-old female with limited scleroderma and chronic renal failure 
was admitted to our hospital due to hyponatremia (sodium 103 mEq/L). Her
hyponatremia was treated by intravenous infusion of NaCl 3%. Clonazepam, which
had been prescribed previously for anxiety and insomnia, was discontinued. Three 
weeks after she was discharged from the hospital, the patient presented with the 
complaint of increased severity of Raynaud's phenomenon and digital ulcers. She
told us that her fingertip ulcers had been healed while she was taking clonazepam
and that episodes of Raynaud's phenomenon had increased after discontinuation of 
the drug. Clonazepam 1 mg twice daily was restarted, and Raynaud's phenomenon and
fingertip ulcers resolved within a month. On 2 occasions after that time, we
discontinued clonazepam and replaced it with alprazolam, as the patient believed 
alprazolam was more beneficial in alleviating anxiety. Episodes of Raynaud's
phenomenon and new digital ulcers recurred on both of these occasions, and
clonazepam was restarted. At the time of writing, no severe episodes of Raynaud's
phenomenon or fingertip ulcers have occurred with clonazepam treatment.
DISCUSSION: Raynaud's phenomenon and recurrent digital ulcers are a manifestation
of vascular disease in patients with systemic sclerosis and lead to pain,
impaired function, and tissue loss. Few drugs have previously been shown to
affect digital ulcers in the setting of scleroderma. Our patient experienced a
significant and sustained improvement in Raynaud's phenomenon and digital ulcers 
following the initiation of clonazepam. To our knowledge, as of March 2007, this 
is the first reported use of clonazepam in Raynaud's phenomenon and digital
ulcer. While its therapeutic mechanism remains unclear, clonazepam may offer some
advantages compared with current agents. CONCLUSIONS: We report a case of
Raynaud's phenomenon and digital ulcers responding to clonazepam. Further
research is warranted to test the robustness of this preliminary finding.

Publication Types: 
    Case Reports

PMID: 17666574 [PubMed - indexed for MEDLINE]

41: Br J Dermatol. 2007 Oct;157(4):690-7. Epub 2007 Jul 19.

Assessment of abnormal blood flow and efficacy of treatment in patients with
systemic sclerosis using a newly developed microwireless laser Doppler flowmeter 
and arm-raising test.

Kido M, Takeuchi S, Hayashida S, Urabe K, Sawada R, Furue M.

Department of Dermatology, Graduate School of Medical Sciences, Kyushu
University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
macky@dermatol.med.kyushu-u.ac.jp

Background Patients with systemic sclerosis (SSc) frequently suffer from
recalcitrant digital ulceration because of impaired cutaneous blood flow (CBF). A
simple and accurate CBF measurement would be helpful to evaluate the disease
status and efficacy of treatment in such patients. Objectives To examine the
feasibility of a newly developed, micromachined integrated laser blood flowmeter 
(MILBF) for evaluation of abnormal CBF responses in patients with SSc. Methods
CBF of finger pulp was measured in eight patients with SSc and in six healthy
controls using MILBF. CBF in the steady state and the responses to the
arm-raising test and cold provocation were assessed. The therapeutic efficacy of 
a single and an intensive prostaglandin E(1) (PGE(1)) infusion treatment was also
evaluated in some of the SSc patients. Results The patients with SSc showed
significantly lower steady-state CBF than controls. The rate of blood flow with
cold provocation and the velocity of blood flow recovery after cold provocation
(VR-CP) tended to be lower in patients with SSc. Augmentation of amplitude of the
digital pulse wave by arm raising (AA-AR) was observed in controls, but not in
patients with SSc. We also found that VR-CP and AA-AR may be good markers for
evaluating the efficacy of vasodilatory treatment. It should be noted that the
examined patients did not complain of any pain and/or distress during the
arm-raising test, as opposed to during cold provocation. Conclusions CBF
assessment using MILBF and an arm-raising test is accurate, noninvasive and well 
tolerated and thus the combination may be a better alternative method to evaluate
abnormal CBF and efficacy of treatment in patients with SSc.

Publication Types: 
    Evaluation Studies

PMID: 17640308 [PubMed - indexed for MEDLINE]

42: Int J Eat Disord. 2007 Dec;40(8):762-5.

Anorexia nervosa and Raynaud's phenomenon: a case report.

Yucel B, Uzum AK, Ozbey N, Kamali S, Yager J.

Department of Psychiatry, Istanbul Faculty of Medicine, Istanbul University,
Istanbul, Turkey. byucel@superonline.com

OBJECTIVE: To describe and discuss potential relationships between anorexia
nervosa (AN) and Raynaud's phenomenon, the course and concurrent treatment of
these two disorders as they appeared simultaneously, and a potential treatment
modification entailed in such concurrent therapies. BACKGROUND: Although
Raynaud's phenomenon has been described during the course of AN, the associations
and interactions between these two conditions are not clear. METHOD: We report
the medical workup, treatment, and outcomes in a 19-year old female patient who
developed Raynaud's phenomenon following the onset of AN. RESULTS: After
treatment with nutritional rehabilitation, counseling, and individual and group
therapy, the patient's weight, eating disorder-related behaviors, and attitudes
improved significantly. Raynaud's related symptoms improved, following treatment 
with a calcium channel blocker and antiaggregant therapy. In conjunction with
nutritional efforts to treat the patient's long-standing amenorrhea and
osteopenia, the treatment team elected to also administer estrogen hormone in
addition to oral calcium and vitamin D supplementation. Since oral contraceptives
are to be avoided in patients with Raynaud's phenomenon who show clinical
findings suggesting connective tissue disorder, the treatment team elected to
treat this patient with transdermal hormone replacement therapy. CONCLUSION: The 
co-occurrence of AN and Raynaud's phenomenon merits close and persistent
follow-up by a multidisciplinary team and may lead to alterations of usual
therapeutic approaches. (c) 2007 by Wiley Periodicals, Inc.

Publication Types: 
    Case Reports

PMID: 17607716 [PubMed - indexed for MEDLINE]

43: Int Heart J. 2007 May;48(3):417-22.

Combination therapy with oral sildenafil and beraprost for pulmonary arterial
hypertension associated with CREST syndrome.

Miwa K, Matsubara T, Uno Y, Yasuda T, Sakata K, Tsuda T, Kanaya H.

Department of Cardiology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan.

Pulmonary arterial hypertension (PAH) is commonly associated with CREST
(Calcinosis, Raynaud phenomenon, Esophageal motility disorders, Sclerodactyly,
and Telangiectasia) syndrome. Sildenafil, an oral phosphodiesterase type-5
inhibitor, may offer benefits in the pharmacological management of PAH. However, 
little is known about the long-term hemodynamic effects of sildenafil, and the
potential role of sildenafil in long-term combination with beraprost, an oral
prostacyclin analogue, remains unclear. We therefore examined the hemodynamic
effect of oral sildenafil alone and when coadministered with beraprost in a
patient with PAH associated with CREST syndrome. Traces of the acute hemodynamic 
effects of beraprost (20 microg) disappeared after 2 hours. In contrast, the
acute hemodynamic effects of sildenafil (50 mg) produced a greater reduction in
PAP (31%) and PVR (40%), and these effects also disappeared after 5 hours. After 
1 month of combination therapy of sildenafil (25 mg) twice daily and beraprost
(20 microg) 3 times daily, the fall in pulmonary artery pressure and pulmonary
vascular resistance was sustained (31% in both). Furthermore, the patient had
significantly improved her 3-minute walk test and NYHA function class without
significant adverse effects at the reported doses. The findings indicate that
oral sildenafil is a potent pulmonary vasodilator that appears to act
synergistically with oral beraprost to cause sustained pulmonary vasodilatation
in a patient with PAH associated with CREST syndrome.

Publication Types: 
    Case Reports

PMID: 17592207 [PubMed - indexed for MEDLINE]

44: Pain Pract. 2007 Jun;7(2):143-6.

Treatment of refractory ischemic pain from chemotherapy-induced Raynaud's
syndrome with spinal cord stimulation.

Ting JC, Fukshansky M, Burton AW.

University of Texas M.D. Anderson Cancer Center, Department of Anesthesiology and
Pain Medicine, Houston, Texas 77030, USA.

We report the successful treatment of refractory ischemic pain from
cisplatin-induced Raynaud's syndrome with spinal cord stimulation after failed
pharmacologic management and surgical sympathectomy. Case Report: A 48-year-old
man developed ischemic pain of the hands while undergoing cisplatin and
gemcitabine chemotherapy for metastatic pancreatic carcinoma. After extensive
pharmacologic management and surgical sympathectomy failed to provide adequate
analgesia, the patient underwent a percutaneous spinal cord stimulation trial
followed by permanent implantation and received significant pain relief prior to 
succumbing to his illness. Spinal cord stimulation provided effective therapy for
refractory ischemic pain, even after failed sympathectomy.

Publication Types: 
    Case Reports

PMID: 17559484 [PubMed - indexed for MEDLINE]

45: P R Health Sci J. 2006 Dec;25(4):307-13.

Clinical manifestations and vascular events in patients with lupus erythematosus 
anticardiolipin antibodies and raynaud's phenomenon.

Rodriguez VE, Gonzalez-Pares EN, Rivera C.

Rheumatology Section, Department of Internal Medicine, University of Puerto Rico 
School of Medicine, Sun Juan 00936-5067. varodriguez@rcm.upr.edu

BACKGROUND: Raynaud's phenomenon (RP) and anticardiolipin antibodies (ACL) are
two common clinical manifestations in patients with systemic lupus erythematosus 
(SLE). RP may lead to digital or limb loss. ACL are associated to thrombotic
episodes. It is not yet clear if there is an association between RP and the
presence of ACL in patients with SLE. OBJECTIVES: To study if the presence of
both RP and ACL in patients with SLE may be associated with certain clinical
manifestations or thrombotic events compared to SLE patients without RP or ACL.
METHODS: SLE patients from two lupus clinics were recruited. The patients were
divided into 4 groups. Patients with RP and positive ACL (RP+ ACL+), patients
with RP but negative ACL (RP+ ACL-), patients with negative RP and positive ACL
(RP- ACL+), and patients that were negative for RP and ACL (RP- ACL-) used as the
control group. Demographic data, diagnostic criteria, clinical manifestations,
history of arterial thrombosis, venous thrombosis and abortions were recorded. A 
physical examination was done. Anticardiolipin antibodies IgG and IgM were done
in the rheumatology laboratory at the University of Puerto Rico School of
Medicine. Descriptive statistics as well as analysis of variances (ANOVA), and
polytomous logistic regression were used. RESULTS: 236 patients with SLE were
studied. There was a tendency toward an increase in arterial thrombosis (p-value 
= 0.094) and venous thrombosis (p-value = 0.067) in the group that were positive 
for RP and ACL (RP+ ACL+). Although it was not statistical significant, when
polytomous logistic regression was used, both arterial and venous thrombosis had 
an increase in relative risk 3.21 for arterial and 3.11 for venous thrombosis.
Abortions were not increased in any of the four groups. Clinical manifestations
from SLE did not differ among the four groups. CONCLUSIONS: Patients with both RP
and ACL seem to be at an increase risk for both arterial and venous thrombotic
events; these patients may benefit from an antiplatelet medication to prevent
these events to occur.

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

PMID: 17550096 [PubMed - indexed for MEDLINE]

46: J Vasc Surg. 2007 Jun;45(6):1259-61.

Unusual etiology of upper extremity ischemia in a scleroderma patient: thoracic
outlet syndrome with arterial embolization.

Hugl B, Oldenburg WA, Hakaim AG, Persellin ST.

Section of Vascular Surgery, Department of Rheumatology, Mayo Clinic
Jacksonville, Jacksonville, FL 32224, USA. beate.hugl@i-med.ac.at

Although the causes of digital ischemia and necrosis are diverse in women, the
most common etiology is connective tissue disease. We describe a patient with
scleroderma who presented with arm ischemia secondary to arterial embolization
from thoracic outlet syndrome. Her sublavian artery was compressed by the
anterior scalene muscle and a cervical rib, leading to a stenosis with
poststenotic dilation of the artery. Within the aneurysmal formation was a
thrombus, which was probably the source of the distal embolization. The patient
underwent surgical resection of the cervical and first rib. The abnormal portion 
of the subclavian artery was resected and replaced with an interposition graft.

Publication Types: 
    Case Reports

PMID: 17543693 [PubMed - indexed for MEDLINE]

47: J Thorac Cardiovasc Surg. 2007 Jun;133(6):1428-33.

Long-term effects of thoracic sympathectomy on microcirculation in the hands of
patients with primary Raynaud disease.

Maga P, Kuzdzał J, Nizankowski R, Szczeklik A, Sładek K.

Department of Medicine, Jagiellonian University, Kraków, Poland. p.maga@chello.pl

OBJECTIVE: Videothoracoscopic sympathecomy is a widely used treatment modality in
patients with severe Raynaud disease, but the reported late results are less than
favorable. There have been no direct studies of the long-term effect of
sympathectomy on microcirculation in the hands of these patients. METHODS: In 25 
patients with Raynaud disease treated with videothoracoscopic Th2-Th4
sympathectomy, we performed basal laser-Doppler flowmetry and measured the
maximal refilling time after 1-minute occlusion measurements preoperatively and
at 1 week, 6 months, and 1, 2, 3, and 5 years after the sympathectomy. The
results were compared with the same measurements obtained in the group of 50
healthy individuals. RESULTS: The patients' symptom severity was assessed by
using the visual analogue scale. The basal capillary flow and the maximal
refilling time improved after the sympathectomy to a level not different from
that seen in the healthy population, and the effect was maintained during the
5-year follow-up period. The patients' symptom severity scores diminished to zero
in the early postoperative period and increased to 28% of their initial value 5
years after the operation. CONCLUSIONS: The videothoracoscopic Th2-Th4
sympathectomy produces excellent and long-lasting improvement of microcirculation
function in patients with Raynaud disease. The mild return of symptoms might be
due to factors other than the capillary blood flow alterations.

PMID: 17532934 [PubMed - indexed for MEDLINE]

48: Pain Physician. 2007 May;10(3):473-8.

A case of spinal cord stimulation in Raynaud's Phenomenon: can subthreshold
sensory stimulation have an effect?

Benyamin R, Kramer J, Vallejo R.

Millennium Pain Center, Bloomington, IL 61701, USA.
benyamin@millenniumpaincenter.com

Spinal cord stimulation is currently used to treat a variety of chronic
intractable painful conditions. We report a case of severe Raynaud's phenomenon
in the hands refractory to conservative treatment and responsive to diagnostic
stellate ganglion block that was effectively treated with a spinal cord
stimulator placed in the cervical epidural space. After capturing the affected
areas with paresthesias, blood flow in the left hand and fingers significantly
improved as evidenced by an increase in skin temperature, a change from cyanotic 
to pink appearance and concomitant reduction in pain. Moreover, the patient
reported that limb ischemia and pain could be managed overnight with stimulation 
intensities that were below sensory perception thresholds. Thus it seems, at
least in the overnight period, paresthesias were not required to maintain pain
relief. This case presents a potential divergence between a requirement for
paresthesias and pain relief in spinal cord stimulation therapy for the treatment
of Raynaud's phenomenon. The possible role of the sympathetic nervous system in
this relationship is also discussed.

Publication Types: 
    Case Reports

PMID: 17525782 [PubMed - indexed for MEDLINE]

49: Med Sci Monit. 2007 May;13 Suppl 1:121-8.

Comparison of thermography and Doppler sonography in the evaluation of the cold
immersion test in women with excessive vasospastic reaction.

Stefańczyk L, Woźniakowski B, Pietrzak P, Majos A, Grzelak P.

Department of Radiology and Diagnostic Imaging, Medical University of ?ódź, ?ódź,
Poland. stefanczyk_l@wp.pl <stefanczyk_l@wp.pl>

BACKGROUND: Determining the predisposition to vasospastic reactions in a function
test is important at the earliest possible stage of diagnosis. Thermography is an
acknowledged procedure for monitoring function tests; however, its availability
is limited. The aim of this study was to compare the progression of the cold
immersion test in a thermal picture and an US-CD examination with the flow
assessment of the small blood vessels of the hand. MATERIAL/METHODS: A group of
16 women declaring high cold tolerance of their hands was compared with a group
of 24 women reporting hand complaints when exposed to the cold. The subjects
underwent a test in which they immersed their right hand in ice-cold water (0
degrees C). Then images of the temperature distribution in the hand were recorded
with a thermovisory camera. At the same time, spectral waveforms were registered 
in the proper palmar digital artery and in the radial artery at specified time
intervals. RESULTS: Data analysis comprised temperature measurements at the level
of the nail plate of the middle finger and at the wrist. There were differences
between the groups at all the stages of the immersion test (efficient return of
temperature to initial values in the reference group, delayed return in subjects 
with low tolerance to thermal stimuli). Flow resistance analysis using the
Doppler method in the studied arteries revealed similar differences between the
groups (swift flow normalization and efficient reperfusion in the reference
group, higher flow resistance and low reperfusion in subjects with low tolerance 
to thermal stimuli). CONCLUSIONS: Changes in the parameters of hand warmth during
the immersion test assessed by thermography and changes in the flow parameters
observed by Doppler sonography demonstrated similar progression, which suggests
the equivalence of both methods. Doppler sonography may thus serve as a method of
monitoring function tests to establish a predisposition to vasospasm.

Publication Types: 
    Evaluation Studies

PMID: 17507897 [PubMed - indexed for MEDLINE]

50: Ann Thorac Cardiovasc Surg. 2007 Apr;13(2):118-21.

Ectopic cystic thymoma associated with Raynaud's phenomenon.

Nomura T, Kawasaki T, Tanabe T, Azuma A, Matsubara H.

Department of Cardiovascular Medicine, Kyoto Prefectural University School of
Medicine, Kyoto, Japan.

Mediastinal cystic tumors are well-marginated round lesions that comprise 12% to 
18% of all mediastinal masses. These lesions include a variety of diseases with
overlapping radiologic appearances and variable prognoses. Pathological
examinations are almost always required for differential diagnosis. We
encountered a case of anterior mediastinal tumor discovered in the process of
investigation of Raynaud's phenomenon. Taking into account the tumor location, a 
pericardial cyst was initially suspected. However, the tumor was surgically
resected and histopathological examinations demonstrated thymus-like tissue in
the cyst walls. Raynaud's phenomenon greatly improved after surgery. These
findings suggested that cystic thymoma originated from ectopic thymic tissue and 
is accompanied by paraneoplastic syndrome.

Publication Types: 
    Case Reports

PMID: 17505420 [PubMed - indexed for MEDLINE]

51: J Hum Lact. 2007 May;23(2):191-3.

Raynaud's phenomenon of the nipples: an elusive diagnosis.

Morino C, Winn SM.

Saint Luke's South Hospital, Overland Park, KS 66213, USA.

Pain and throbbing of the nipples associated with Raynaud's phenomenon often
mimics yeast or fungal infections. Breastfeeding mothers with Raynaud's of the
nipples are often treated inappropriately for organisms such as Candida Albicans 
with topical or systemic antifungal agents. This case report describes the
eventual diagnosis of Raynaud's phenomenon of the nipples in a breastfeeding
mother who was initially treated for yeast.

Publication Types: 
    Case Reports

PMID: 17478872 [PubMed - indexed for MEDLINE]

52: Blood Coagul Fibrinolysis. 2007 Jun;18(4):297-302.

Increased circulating platelet-leucocyte complexes in patients with primary
Raynaud's phenomenon and Raynaud's phenomenon secondary to systemic sclerosis: a 
comparative study.

Pamuk GE, Turgut B, Pamuk ON, Vural O, Demir M, Cakir N.

Department of Hematology, Trakya University Medical Faculty, Edirne, Turkey.
gepamuk@yahoo.com

Platelet activation and circulating platelet-leucocyte complexes increase in
vascular ischemic events and autoimmune inflammatory diseases. Platelet
activation markers and platelet-leucocyte complexes were evaluated in primary
Raynaud's phenomenon (RP) and in RP secondary to systemic sclerosis (SSc).
Whole-blood flow cytometry was utilized to quantify CD62P, platelet
microparticles (PMP), platelet-monocyte complexes (PMC) and platelet-neutrophil
complexes (PNC) in primary RP and in SSc patients with secondary RP. SSc patients
with secondary RP had significantly higher platelet CD62P expression than primary
RP patients and controls (P = 0.017 and 0.004, respectively). Primary and
secondary RP patients had higher mean PMC and PNC levels than controls (all P <
or = 0.001). PMP level in SSc patients with pulmonary hypertension was
significantly higher than in others (P = 0.048). All parameters were similar in
SSc patients with and without digital ulcers, aspirin-users and nonusers (P >
0.05). CD62P level decreased significantly after iloprost administration in four 
patients with digital ulcers (16.1 +/- 17.4 vs 7.4 +/- 3.8%, P = 0.03). Our
results suggest there is platelet-leucocyte complex formation in RP, and, despite
antithrombotic therapy, platelet activation and platelet-leucocyte interaction
are ongoing in SSc. This is important as it might have potential therapeutic
implications with respect to using antiplatelet drugs in SSc.

Publication Types: 
    Comparative Study

PMID: 17473568 [PubMed - indexed for MEDLINE]

53: Anesth Analg. 2007 May;104(5):1034-6, tables of contents.

Cerebral oxygen desaturation after cardiopulmonary bypass in a patient with
raynaud's phenomenon detected by near-infrared cerebral oximetry.

Aron JH, Fink GW, Swartz MF, Ford B, Hauser MC, O'Leary CE, Puskas F.

Department of Anesthesiology, SUNY Upstate Medical University, Syracuse, New
York, USA.

Raynaud's phenomenon is characterized by episodes of arterial vasospasm
precipitated by cold stress, usually affecting the digits of the hands. There is 
controversy about the occurrence of vasospasm in internal organ systems. In this 
report, we present a case of Raynaud's peripheral vasospasm accompanied by
cerebral oxygen desaturation as detected by near infrared cerebral oximetry after
separation from cardiopulmonary bypass.

Publication Types: 
    Case Reports

PMID: 17456649 [PubMed - indexed for MEDLINE]

54: Clin Rev Allergy Immunol. 2007 Feb;32(1):47-56.

Increased prevalence of anti-third generation cyclic citrullinated peptide
antibodies in patients with rheumatoid arthritis and CREST syndrome.

Wu R, Shovman O, Zhang Y, Gilburd B, Zandman-Goddard G, Shoenfeld Y.

Pathway Diagnostics Inc., Malibu, CA, USA.

To investigate the prevalence of anti-third generation cyclic citrullinated
peptide antibodies (anti-CCP3) in patients with systemic connective tissue
diseases, we assembled a training set consisting of 115 patients with rheumatoid 
arthritis (RA), 52 with Calcinosis, Raynaud's phenomenon, oesophageal
dysmotility, sclerodactyly, telangiectasia (CREST) syndrome, 21 with scleroderma,
20 with ankylosing spondylitis, 18 with reactive arthritis, 25 with juvenile
rheumatoid arthritis (RA), 51 with osteoarthritis, 26 with mixed connective
tissue disease, 23 with primary Sjogren's syndrome, 74 with systemic lupus
erythematosus, 49 with Polymyalgia rheumatica, and 39 with
polymyositis/dermatomyositis. The commercial enzyme-linked immunosorbent assay
(ELISA) was used to detect anti-CCP antibodies, including anti-CCP2 (regular,
second generation of CCP antigen) and anti-CCP3 (third generation of CCP antigen)
in disease-related specimens and normal controls. These serum samples were also
evaluated for anti-centomere antibodies by anti-centromere ELISA kit. The higher 
frequencies of anti-CCP3 and anti-CCP2 were detected in 75.6 and 70.4% patients
with RA, respectively. At the same time, anti-CCP3 (not anti-CCP2) was
significantly increased in samples isolated from patients with CREST syndrome.
The clinical sensitivity of IgG anti-CCP3 for the patients with CREST syndrome
was 29% (15 of 52) and the specificity was 96% (384 of 397), with the exception
of the RA group. The anti-centromere antibodies were significantly higher in
patients with CREST only. The results of our study suggest that compared to
anti-CCP2 assay, the new anti-CCP3 assay can enhance the clinical sensitivity for
diagnosis of RA and, as an associate marker combined with anticentromere, can
distinguish CREST syndrome from other systemic connective tissue diseases,
especially RA. The clinical specificity of anti-CCP3 was lower than anti-CCP2
assay in diagnosis of RA because of the crossreaction to the patients with CREST 
syndrome.

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

PMID: 17426360 [PubMed - indexed for MEDLINE]

55: Clin Rheumatol. 2007 Sep;26(9):1517-21. Epub 2007 Mar 31.

Antioxidant status after iloprost treatment in patients with Raynaud's phenomenon
secondary to systemic sclerosis.

Balbir-Gurman A, Braun-Moscovici Y, Livshitz V, Schapira D, Markovits D, Rozin A,
Boikaner T, Nahir AM.

B. Shine Department of Rheumatology, Rambam Health Care Campus, Haifa, Israel.
a_balbir@rambam.health.gov.il

Oxidative stress is involved in pathogenesis of Raynaud's phenomenon (RP), a
hallmark of systemic sclerosis (SSc). Frequent episodes of ischemia-reperfusion
may lead to release of free radicals and enhanced lipid peroxidation reflected by
elevated levels of malondialdehyde (MDA). The failure of native antioxidants
(Catalase [CAT], Superoxide dismutase [SOD], and Ceruloplasmin [CP]) might be
crucial in endothelial cells damage in RP. Iloprost (IL) synthetic prostacyclin
analogue is currently used in the treatment of SSc patients with RP. The
objectives of this study were to compare the serum levels of MDA and CP, CAT and 
SOD activity in red blood cells hemolysate in SSc patients compared to healthy
controls; and to study the effect of 5-days IL infusions on MDA and CP levels,
and CAT and SOD activity in SSc patients with RP. Twelve SSc patients were
treated with 50 mug IL for 5 days. Blood samples were taken before and after day 
1st and after day 5th of IL infusions. Levels of CAT were measured according to
the Aebi's method; SOD, according to the Misra and Fridovich method; MDA,
according to Slater's method; and CP, according to Ravin's method. Activities of 
CAT (p < 0.001) and SOD (p < 0.04) were significantly reduced; levels of CP (p < 
0.006) and MDA (p < 0.06) were raised in SSc compared to controls. IL infusions
caused reduction in MDA (p < 0.0001) levels and enhanced production of SOD (p <
0.006) and CAT (p < 0.003). The levels of CP did not change (p = 0.48). Oxidant
status in SSc patients with RP is impaired. Therapy with IL led to normalization 
of antioxidant activity. We suggest that CAT may be a sensitive and reliable
laboratory marker of oxidative stress severity in RP. We found that IL, in
addition to its vasoactive properties, has a potential to activate inner
antioxidant system. Activation of inner antioxidant activity may explain
long-term effect of IL instead of its very short half-life time.

Publication Types: 
    Clinical Trial

PMID: 17401513 [PubMed - indexed for MEDLINE]

56: Br J Dermatol. 2007 May;156(5):892-8. Epub 2007 Mar 28.

Assessment of nailfold capillaroscopy by x 30 digital epiluminescence
(dermoscopy) in patients with Raynaud phenomenon.

Beltrán E, Toll A, Pros A, Carbonell J, Pujol RM.

Department of Rheumatology, Hospital del Mar, Passeig Maritim 25-29, Barcelona,
Spain.

BACKGROUND: Dermoscopy is a useful tool for dermatologists to study melanocytic
lesions. Its possible usefulness in the assessment of capillary nailfold
morphological changes (capillaroscopy) has recently been advocated. OBJECTIVES:
To assess the practical utility of digital epiluminescence microscopy as a
capillaroscopic instrument in patients with Raynaud phenomenon (RP). To compare
the sensitivity and specificity rates obtained by epiluminescence microscopy with
those previously reported with conventional capillaroscopic devices. METHODS:
Fifty-six consecutive patients with primary RP (PRP; n = 5) or secondary RP (SRP;
n = 51) (11 men and 45 women in total) were included in the study. A control
group of 10 healthy subjects was also evaluated. Twenty-six patients (46%) had
systemic sclerosis (SS), 12 (21%) presystemic sclerosis (pre-SS), one (2%)
dermatopolymyositis-SS, one (2%) mixed connective tissue disease, two (4%)
Sjögren syndrome, two (4%) an overlap syndrome, one (2%) rheumatoid arthritis and
six (11%) other connective tissue diseases. Capillary nailfold changes were
studied using a nonportable digital epiluminescence device (magnification x 30). 
Following a systematized protocol, capillary nailfold morphology, density and
distribution were evaluated. Several capillaroscopic patterns were identified
(normal, sclerodermic, nonspecific, nondiagnostic) as previously defined. A
possible relationship between capillary nailfold changes and the intensity of RP 
or the presence of associated autoimmune diseases was assessed. RESULTS: The
sclerodermic pattern showed a sensitivity of 76.9% and a specificity of 90.9% in 
SS. A typical capillaroscopic SS pattern was observed in 73% of cases of limited 
SS and in 82% of cases of diffuse SS. Patients with Sjögren syndrome and
dermatopolymyositis-SS showed a nonspecific capillaroscopic pattern. All patients
with PRP presented a normal capillaroscopic pattern. A normal capillaroscopic
pattern was also observed in 11 of 12 patients with pre-SS. In one of two
patients presenting severe sclerodactyly and in all patients showing hand oedema 
(three of 56), capillaroscopic changes could not be evaluated. Avascular areas
correlated significantly with severe RP (P < 0.002), bone resorption (P < 0.007) 
and diffuse SS (P < 0.008). CONCLUSIONS: Digital epiluminescence seems to be a
useful and reliable technique in the evaluation of capillary nailfold
morphological changes. This technical variation allows the identification of
specific capillaroscopic patterns associated with connective tissue diseases. It 
also permits us to differentiate PRP from SRP. The results obtained with this
technique are similar to those previously reported using standard capillaroscopy 
devices.

Publication Types: 
    Evaluation Studies

PMID: 17388920 [PubMed - indexed for MEDLINE]

57: Drugs. 2007;67(4):517-25.

The diagnosis and treatment of Raynaud's phenomenon: a practical approach.

Pope JE.

Department of Medicine, Division of Rheumatology, London, Ontario, Canada.
janet.pope@sjhc.london.on.ca

Raynaud's phenomenon is a common disorder with vasospasm of the digital arteries 
causing pallor with cyanosis and/or rubor. It can be primary (idiopathic), where 
it is not associated with other diseases, or secondary to several diseases or
conditions, including connective tissue diseases, such as scleroderma and
systemic lupus erythematosus. Raynaud's is often mild enough to not require
treatment; however, with secondary Raynaud's there is not only vasospasm but also
fixed blood vessel defects so the ischaemia can be more severe. Complications can
include digital ulcers and could, rarely, lead to amputation. Treatment is often 
non-pharmacological including avoiding cold and smoking cessation. Calcium
channel antagonists, such as nifedipine, are often considered when treatment is
needed; however, adverse effects of these drugs can include hypotension,
vasodilatation, peripheral oedema and headaches. Other treatments have been
studied in randomised, controlled trials including classes of drugs, such as
angiotensin II inhibitors, selective serotonin reuptake inhibitors,
phosphodiesterase-5 inhibitors (e.g. sildenafil), nitrates (topical or oral; the 
latter can be limited by adverse effects, such as flushing, headache and
hypotension), and for more serious Raynaud's or its complications prostacyclin
agonists may be used. There are two large studies that demonstrate that
endothelin receptor blockade with bosentan can reduce the number of new digital
ulcers in scleroderma patients. However, it does not affect the healing period.
Thus, Raynaud's is common and often requires non-pharmacological treatment. When 
secondary Raynaud's is suspected, such as Raynaud's with an older age at onset or
other features of connective tissue disease, then an appropriate history,
physical examination and laboratory tests may be indicated to reach an
appropriate diagnosis. There have been advances in pharmacological treatment, but
some of the treatments are limited by adverse effects.

Publication Types: 
    Review

PMID: 17352512 [PubMed - indexed for MEDLINE]

58: Am J Med. 2007 Mar;120(3):264-71.

Smoking, alcohol consumption, and Raynaud's phenomenon in middle age.

Suter LG, Murabito JM, Felson DT, Fraenkel L.

VA Connecticut Healthcare System, West Haven, Conn, USA. lisa.suter@yale.edu

BACKGROUND: Data suggest Raynaud's phenomenon shares risk factors with
cardiovascular disease. Studies of smoking, alcohol consumption, and Raynaud's
have produced conflicting results and were limited by small sample size and
failure to adjust for confounders. Our objective was to determine whether smoking
and alcohol are independently associated with Raynaud's in a large,
community-based cohort. METHODS: By using a validated survey to classify
Raynaud's in the Framingham Heart Study Offspring Cohort, we performed
sex-specific analyses of Raynaud's status by smoking and alcohol consumption in
1840 women and 1602 men. Multivariable logistic regression analyses were used to 
examine the relationship of Raynaud's to smoking and alcohol consumption.
RESULTS: Current smoking was not associated with Raynaud's in women but was
associated with increased risk in men (adjusted odds ratio [OR] 2.59, 95%
confidence interval [CI], 1.11-6.04). Heavy alcohol consumption in women was
associated with increased risk of Raynaud's (adjusted OR 1.69, 95% CI,
1.02-2.82), whereas moderate alcohol consumption in men was associated with
reduced risk (adjusted OR 0.51, 95% CI, 0.29-0.89). In both genders, red wine
consumption was associated with a reduced risk of Raynaud's (adjusted OR 0.59,
95% CI, 0.36-0.96 in women and adjusted OR 0.30, 95% CI, 0.15-0.62 in men).
CONCLUSIONS: Our data suggest that middle-aged women and men may have distinct
physiologic mechanisms underlying their Raynaud's, and thus sex-specific
therapeutic approaches may be appropriate. Our data also support the possibility 
that moderate red wine consumption may protect against Raynaud's.

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: 17349450 [PubMed - indexed for MEDLINE]

59: Clin Pharmacol Ther. 2007 Apr;81(4):503-9. Epub 2007 Feb 14.

The effects of tadalafil on cold-induced vasoconstriction in patients with
Raynaud's phenomenon.

Friedman EA, Harris PA, Wood AJ, Stein CM, Kurnik D.

1Division of Clinical Pharmacology, Department of Medicine,Vanderbilt University 
School of Medicine, Nashville, Tennessee, USA.

Raynaud's phenomenon (RP) is a disorder characterized by episodic periods of
vasoconstriction typically provoked by exposure to cold. Phosphodiesterase 5
(PDE5) inhibitors may improve digital blood flow and clinical symptoms in
patients with RP, but the mechanisms are unknown. We examined the hypothesis that
a PDE5 inhibitor, tadalafil, attenuates cold-induced vasoconstriction.
Additionally, we examined whether tadalafil reduced vascular dysfunction
following ischemia, thus altering the response to repeated cooling. We conducted 
a double-blind, placebo-controlled crossover study in 20 subjects with RP on two 
separate study days, when subjects received either placebo or tadalafil (10 mg). 
Digital blood flow (flux) was measured by laser Doppler flowmetry at rest and
during two graduated local heat and cold exposure cycles. Temperature-response
curves were evaluated by E(max) (maximal flux during heating), E(min) (minimal
flux during cooling), and ET(50) and ET(90) (the local temperature at which flux 
decreased by 50% and 90% of E(max)-E(min), respectively). Tadalafil did not
increase baseline flux (81.0+/-73.0 vs 91.3+/-114.0 arbitrary unit (AU), P=0.57),
E(max) (280.0+/-107.6 vs 279.5+/-119.8 AU, P=0.94), ET(50) (25.4+/-4.4 vs
26.6+/-5.7 degrees C, P=0.62), or ET(90) (21.2+/-3.9 vs 21.8+/-5.0 degrees C,
P=0.78), (cycle 1 values presented). There were no differences between cycles on 
either study day. In conclusion, in patients with RP, single-dose tadalafil does 
not increase digital blood flow at baseline or in response to heating, nor does
it attenuate cold-induced vasoconstriction. Furthermore, it does not precondition
the endothelium to resist a second cooling challenge. The clinical benefit in
patients with RP treated with PDE5 inhibitors probably involves mechanisms other 
than acute inhibition of cold-induced vasoconstriction.

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

PMID: 17301734 [PubMed - indexed for MEDLINE]

60: J Endod. 2007 Feb;33(2):187-90.

A case report of a patient with Raynaud's phenomenon undergoing multiple
endodontic procedures.

Rankin CH.

Department of Endodontics, Tufts University, School of Dental Medicine, Boston,
Massachusetts 02111, USA. charles.rankin@tufts.edu

The pulp represents a terminal circulation. This fact, in addition to other
anatomical limitations such as a large volume of pulp: blood supply ratio and the
inability of pulp tissue to swell because of its dentinal confines, all may
contribute to the susceptibility of the pulp to infection and necrosis. Raynaud's
disease primarily affects the terminal vasculature of the fingers, toes or nose. 
Is there a relationship between patients with Raynaud's disease and the status of
the terminal vasculature of their dental pulps? The presented case opens up the
question and possibly makes a correlation between peripheral vascular disease and
pulpal disease.

Publication Types: 
    Case Reports

PMID: 17258642 [PubMed - indexed for MEDLINE]

61: Skin Res Technol. 2007 Feb;13(1):91-4.

In vivo study of skin mechanical properties in Raynaud's phenomenon.

Dobrev H.

Department of Dermatology and Venereology, Medical University, Plovdiv, Bulgaria.
hristo_dobrev@hotmail.com

BACKGROUND/AIM: Raynaud's phenomenon (RP) is usually the first symptom in
patients with systemic sclerosis (SS) and may precede skin changes by several
months or years. Non-invasive measurements of skin elasticity are very sensitive 
and appropriate for objective and quantitative evaluation of sclerodermatous
skin. The aim of this study was to investigate and compare the mechanical
properties of the skin in patients with primary, secondary, and suspected
secondary RP. MATERIALS/METHODS: A total of 63 patients were studied. They were
classified as having scleroderma-type nailfold capillary abnormalities--17 with
indurative phase of scleroderma (group 1), nine with edematous phase of
scleroderma (group 2), 18 with suspected secondary RP (group 3) and as having
RP-type nailfold capillary abnormalities, 19 with primary RP (group 4).
Thirty-nine sex- and age-matched healthy individuals with normal nailfold
capillaroscopy pattern were also studied as controls. Mechanical properties of
the skin were evaluated using a non-invasive suction device (Cutometer) equipped 
with a 2 mm probe. Measurements were performed over five anatomic regions:
cheeks, volar forearms, wrists, hands, and proximal phalanx of the fingers. The
skin mechanical parameters analyzed were distensibility (Uf), elasticity (Ua/Uf) 
and viscoelasticity (Uv/Ue). RESULTS: Most demonstrative changes were observed
over volar forearms. Patients included in groups 1-3 were characterized by
significantly lower Uf and higher Uv/Ue compared with patient group 4 and
controls. Patient groups 1 and 2 showed significantly lower Ua/Uf, as well. There
were no significant differences in skin mechanical parameters between patient
group 4 and control group. CONCLUSION: Mechanical properties of the skin in
patients with suspected secondary RP significantly differ from these in patients 
with primary RP and resemble those in patients with edematous phase of
scleroderma. Our findings suggest that the non-invasive measurements of skin
elasticity could be helpful in identifying patients with RP at risk of developing
SS.

PMID: 17250538 [PubMed - indexed for MEDLINE]

62: Australas J Dermatol. 2007 Feb;48(1):37-9.

Unilateral limited scleroderma-like changes following formation of an
arteriovenous fistula.

Roberts H, Curnow PA.

Department of Dermatology, Alfred Hospital, Prahran, Victoria, Australia.
hughroberts1@bigpond.com

A 55-year-old man presented with a 1-year history of progressive skin thickening 
involving the right hand associated with Raynaud's phenomenon, sclerodactyly and 
painful cutaneous ulcers. An arteriovenous fistula for haemodialysis had been
formed on the same arm 2 years previously. There were no symptoms or signs of
systemic sclerosis or involvement of the contralateral arm. The limb was
clinically ischaemic, attributed to a vascular steal phenomenon from the
arteriovenous fistula, superimposed on occlusive arterial disease. A
revascularization procedure was performed, which resulted in substantial
improvement in the sclerodactyly, Raynaud's phenomenon and hand function. Tissue 
hypoxia is believed to be a contributing factor in the pathogenesis of
scleroderma, and this case demonstrates scleroderma-like changes in the setting
of limb ischaemia.

Publication Types: 
    Case Reports

PMID: 17222301 [PubMed - indexed for MEDLINE]

63: Joint Bone Spine. 2007 Jan;74(1):e1-8. Epub 2006 Dec 4.

Raynaud's phenomenon.

Gayraud M.

Internal Medicine Department, Institut Mutualiste Motnsouris, 42 boulevard
Jourdan, 75014 Paris, France. martine.gayraud@imm.fr

Vascular acrosyndromes constitute a common reason for physician visits. They are 
associated with connective tissue disease; for example, 90% of patients with
scleroderma experience Raynaud's phenomenon. The rheumatologist must strive to
establish the diagnosis, to identify a potential underlying cause, and to
prescribe effective treatment when the symptoms are incapacitating. Raynaud's
phenomenon is the acrosyndrome most commonly encountered by rheumatologists. The 
diagnosis of Raynaud's phenomenon rests on clinical grounds. Nailfold
capillaroscopy and immunological tests are useful chiefly for determining the
cause. Calcium-channel antagonists are the treatment of reference for Raynaud's
phenomenon. Drugs introduced over the last few years for severe refractory forms 
include prostacyclin and its derivatives, endothelin receptor antagonists, and
phosphodiesterase inhibitors. These drugs were developed as a result of new
knowledge on the pathogenesis of Raynaud's phenomenon. Acrocyanosis, which is
extremely common, and erythromelalgia are the other main vascular acrosyndromes.

Publication Types: 
    Review

PMID: 17218139 [PubMed - indexed for MEDLINE]

64: J Dermatol Sci. 2007 Feb;45(2):113-20. Epub 2006 Dec 13.

A cold-response index for the assessment of Raynaud's phenomenon.

Foerster J, Kuerth A, Niederstrasser E, Krautwald E, Pauli R, Paulat R, Eweleit
M, Riemekasten G, Worm M.

Klinik für Dermatologie, Charité, Charitéplatz 1, 10117 Berlin, Germany.
john.foerster@charite.de

BACKGROUND: Quantification of Raynaud's phenomenon (RP) is a prerequisite in the 
evaluation of novel therapeutic strategies. Fingertip rewarming in response to
local cold provocation has been used in many studies but not been systematically 
validated. We have previously described the time elapsed before 63% of
pre-cooling temperature is reached as a RP activity index. OBJECTIVE: A
comprehensive evaluation of fingertip rewarming in primary and
scleroderma-associated RP. METHODS: We defined a cold-response index (CRI) as the
log transformation of the 63% rewarming time upon cold challenge. RESULTS: The
CRI shows high intra-individual reproducibility. The mean CRI values were
(mean+/-S.D.): 2.4+/-0.3 in controls (n=53) versus 2.7+/-0.3 in RP (n=50,
p<0.0001 versus controls), and 2.7+/-0.3 in scleroderma patients (n=46,
p<0.0001). In addition, baseline fingertip temperature was also found to be
significantly reduced both in primary as well as scleroderma-associated RP.
Kinetic analysis of rewarming temperature curves demonstrates that the CRI is
independent of individual rewarming patterns. Finally, the CRI decreases
significantly upon a single low-level systemic hyperthermia treatment in
scleroderma patients (2.68+/-0.28 before versus 2.45+/-0.33 after, p=0.0003),
while the extent of cooling remained unchanged, thus demonstrating sensitivity to
change. CONCLUSION: Our results provide a solid basis for using the cold-response
assay as an endpoint in addition to clinical activity scores in RP treatment
trials.

Publication Types: 
    Controlled Clinical Trial

PMID: 17169532 [PubMed - indexed for MEDLINE]

65: J Dermatol. 2006 Dec;33(12):884-6.

Calcinosis cutis of the fingertip associated with Raynaud's phenomenon.

Yang JH, Kim JW, Park HS, Jang SJ, Choi JC.

Department of Dermatology, Sanggye Paik Hospital, Inje University College of
Medicine, Seoul, Korea.

Cutaneous calcification may be divided into four major categories: (i)
dystrophic; (ii) metastatic; (iii) idiopathic; and (iv) iatrogenic. Dystrophic
calcification is the most common type of calcinosis cutis and is associated with 
a variety of diseases. It most notably occurs in connective tissue diseases.
Diffuse and limited cutaneous systemic sclerosis is an example of connective
tissue diseases that frequently show calcinosis. We experienced a case of
fingertip calcinosis cutis associated with Raynaud's phenomenon. The patient had 
no previous trauma, skin lesion or systemic connective tissue disease. We propose
that calcinosis cutis of the fingertip may result from chronic ischemic injury
caused by Raynaud's phenomenon.

Publication Types: 
    Case Reports

PMID: 17169096 [PubMed - indexed for MEDLINE]

66: JAAPA. 2006 Nov;19(11):34-8.

The patient with cold hands: understanding Raynaud's disease.

Jackson CM.

Internal Medicine Associates, Crozer-Chester Medical Center, Upland, PA, USA.

The availability of new treatments for Raynaud's disease, as with any medical
condition, depends on how convincing the results of clinical research prove to
be. The validity and reliability of research in Raynaud's disease is subject to
two major constraints: the seasonal and intermittent nature of the condition
limits the amount of time patients can be studied continuously, and researchers
have failed to agree on objective outcome measures. Vascular physiology is, and
no doubt is destined to remain, a dynamic and technology-driven clinical realm.
Despite the wide array of promising treatments, the best and most basic
management of Raynaud's disease seems to be behavioral and at least partly
pharmaceutical. The two biggest behavioral factors are nicotine use and exposure 
to cold environments. Giving up nicotine can be a daunting challenge for
long-term smokers and chewing-tobacco users. Avoiding cold environments may be
easier said than done, especially for patients who work outdoors or in
air-conditioned spaces. Perhaps the best treatment for Raynaud's disease is a
reliable diagnosis and the positive prognosis that comes with it. Most patients
have a stable course, and nearly half will actually improve with time and steady 
reassurance.

PMID: 17124789 [PubMed - indexed for MEDLINE]

67: Lupus. 2006;15(10):671-4.

Headache, Raynaud's syndrome and serotonin receptor agonists in systemic lupus
erythematosus.

Bernatsky S, Pineau CA, Lee JL, Clarke AE.

Division of Clinical Epidemiology, Montreal General Hospital, Montreal, PQ,
Canada.

There are potential concerns regarding serotonin receptor agonists in SLE
patients with migraine, particularly patients with concomitant Raynaud's
syndrome. We estimated the prevalence of lupus-related headache and Raynaud's
syndrome in the Montreal General Hospital SLE clinic cohort and evaluated the
relationship between these two variables in multivariable logistic regression
models, controlling for age, sex, race, SLE duration and the presence of lupus
anticoagulant and antibodies to cardiolipin and beta2 glycoprotein I. We also
assessed, through chart review in those individuals with both Raynaud's syndrome 
and migraine, a history of serotonin receptor agonist use, and any associated
worsening vasospasm. Based on Systemic Lupus Activity Measure (SLAM) scores, the 
cumulative incidence of lupus-related headache in our sample (n = 391) was 46.1%;
the prevalence of Raynaud's syndrome was 49.4%. The adjusted odds ratio (OR) for 
lupus-related headache and Raynaud's syndrome was 1.7 (95% CI 1.1, 2.5). In
addition, there was a strong independent relationship between headache and
anti-beta2 glycoprotein I antibodies (adjusted OR 5.6 [95% CI 1.8, 17.0]). The
data from our chart review suggest that careful use of serotonin receptor
agonists in patients with both Raynaud's syndrome and migraines may be
undertaken, although caution would necessitate that these agents not be used in
individuals with very severe Raynaud's (eg, digital ulcerations, and so on).

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

PMID: 17120594 [PubMed - indexed for MEDLINE]

68: Kaohsiung J Med Sci. 2006 Oct;22(10):491-9.

Peripheral sympathectomy for Raynaud's phenomenon: a salvage procedure.

Wang WH, Lai CS, Chang KP, Lee SS, Yang CC, Lin SD, Liu CM.

Division of Plastic and Reconstructive Surgery, Department of Surgery, Kaohsiung 
Medical University Hospital, Kaohsiung, Taiwan.

We retrospectively reviewed the effectiveness of peripheral sympathectomy for
severe Raynaud's phenomenon. In this study, a total of 14 digits from six
patients with chronic digital ischemic change were included. All patients had
pain, ulcer, or gangrenous change in the affected digits and were unresponsive to
pharmacologic or other nonsurgical therapies. In all cases, angiography showed
multifocal arterial lesions, so microvascular reconstruction was unfeasible.
Peripheral sympathectomy was performed as a salvage procedure to prevent digit
amputation. The results were analyzed according to reduction of pain, healing of 
ulcers, and prevention of amputation. In 12 of the 14 digits, the ulcers healed
and amputation was avoided. In the other two digits, the ulcers improved and
progressive gangrene was limited. As a salvage procedure for Raynaud's phenomenon
recalcitrant to conservative treatment, peripheral sympathectomy improves
perfusion to ischemic digits and enables amputation to be avoided.

Publication Types: 
    Case Reports

PMID: 17098681 [PubMed - indexed for MEDLINE]

69: J Vasc Surg. 2006 Nov;44(5):1023-8.

Incidence and natural history of Raynaud phenomenon: A long-term follow-up (14
years) of a random sample from the general population.

Carpentier PH, Satger B, Poensin D, Maricq HR.

Centre de Recherche Universitaire, La Léchère, France.
patrick.carpentier@ujf-grenoble.fr

BACKGROUND: Because the natural history of primary Raynaud phenomenon (RP) is
unclear, we undertook this long-term (14 years) follow-up of an epidemiologic
study on RP to investigate the incidence, remittance rate, and transition rate
toward systemic sclerosis and other scleroderma spectrum disorders in a
population-based sample of subjects. METHODS: In 1988 and 1989, 296 subjects
obtained from a random sample of the general population of the Alpine valley of
Tarentaise (southeast France) completed a cross-sectional study on RP. Of these, 
78 met the diagnostic criteria for RP (RP+). From April 2002 to March 2003, we
were able to get follow-up information on 292 people (dropout rate, 1.4%).
Eighteen subjects (6.1%) had died, and the remaining 274 were successfully
contacted. They were first evaluated by a standardized phone interview regarding 
their cold sensitivity, digital color changes, and RP. If any significant medical
changes related to RP and/or suggesting scleroderma were reported, these subjects
were invited for a medical evaluation. RESULTS: Mortality was similar in RP+ and 
RP- subjects, and no death was due to an RP-related condition. Seven cases of new
RP were diagnosed in the RP- group, which corresponds to an annual incidence rate
of 0.25%. Among the 72 RP+ subjects and the 7 subjects with a new RP available
for follow-up, none developed clinical features of scleroderma. A disappearance
of RP attacks for 2 winters or more was reported by 24 RP+ subjects (33%).
CONCLUSIONS: These results show that, in the general population, RP is most often
a benign condition and may disappear in a substantial proportion of subjects.

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

PMID: 17098538 [PubMed - indexed for MEDLINE]

70: Rheumatology (Oxford). 2007 Mar;46(3):533-8. Epub 2006 Oct 2.

The 'distal-dorsal difference': a thermographic parameter by which to
differentiate between primary and secondary Raynaud's phenomenon.

Anderson ME, Moore TL, Lunt M, Herrick AL.

University of Liverpool Adademic Rheumatology Unit, University Hospital Aintree, 
Liverpool, UK.

OBJECTIVE: To test the hypothesis that in a patient with Raynaud's phenomenon
(RP), a difference of >1 degrees C between the fingertips and the dorsum of the
hand ['distal-dorsal difference' (DDD), fingers cooler] is specific for
underlying structural vascular disease as occurs in systemic sclerosis (SSc), and
to evaluate other thermographic parameters in the separation of secondary from
primary RP. METHODS: A retrospective analysis of the case notes and thermography 
results of patients attending thermography, primarily over a 2-yr period.
Multinomial logistic regression was used to ascertain whether thermography
variables differed between groups with primary RP (56 patients), undifferentiated
connective tissue disease (21 patients) and SSc (45 patients), with adjustment
for age, sex and smoking. RESULTS: A DDD >1 degrees C in any finger at 30 degrees
C had a positive predictive value of 70%, and a negative predictive value of 82%,
in identifying the patient with RP secondary to SSc. From the results of the
multinomial logistic regression, a score was derived incorporating age, number of
fingers with DDD >1 degrees C at 30 degrees C and maximum rewarming gradient.
This score (with a suitable cut-off) was 82% sensitive and 82% specific in
identifying RP secondary to SSc, with a positive predictive value of 73% and a
negative predictive value of 89%. CONCLUSION: Parameters derived from
thermography (incorporating both a heat and cold challenge) aid in the prediction
of SSc in patients with RP.

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

PMID: 17018538 [PubMed - indexed for MEDLINE]

71: Appl Psychophysiol Biofeedback. 2006 Sep;31(3):203-16.

Thermal biofeedback for primary Raynaud's phenomenon: a review of the literature.

Karavidas MK, Tsai PS, Yucha C, McGrady A, Lehrer PM.

University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical
School, Piscataway, New Jersey, USA. karavima@umdnj.edu

The clinical presentation of primary Raynaud's phenomenon (RP) derives from
various pathogenic triggers. The use of thermal biofeedback (TBF) may be of
benefit in reducing the severity and frequency of attacks. This article
summarizes the relevant research regarding the pathophysiology of primary RP and 
mechanism of TBF for RP. Systematic reviews of the efficacy of TBF for RP and
treatment guidelines for clinicians are provided. The panel concludes that the
level of evidence for TBF efficacy is categorized as Level IV: efficacious. The
rationale, based on three randomized controlled trials conducted in independent
laboratories, demonstrated "superiority or equivalence" of treatments that
include TBF. However, randomly controlled trials (RCT) with positive clinical
outcomes tended to be small. A large RCT with negative results did not
effectively teach handwarming skills. Procedures for reviewing and rating of the 
levels of evidence of efficacy of studies was based on the Template for
Developing Guidelines for the Evaluation of the Clinical Efficacy of
Psychophysiological Interventions developed by the joint task force of the AAPB
and the Society for Neuronal Regulation (SNR).

Publication Types: 
    Review

PMID: 17016765 [PubMed - indexed for MEDLINE]

72: Pediatr Dermatol. 2006 Sep-Oct;23(5):437-42.

The prognostic value of nailfold capillary changes for the development of
connective tissue disease in children and adolescents with primary raynaud
phenomenon: a follow-up study of 250 patients.

Pavlov-Dolijanović S, Damjanov N, Ostojić P, Susić G, Stojanović R, Gacić D,
Grdinić A.

Institute of Rheumatology-Belgrade, Resavska, Belgrade, Serbia and Montenegro.
dolijan@agrifaculty.bg.ac.yu

To assess the prognostic value of capillaroscopy findings for the development of 
connective tissue disease in children and adolescents with Raynaud phenomenon, we
followed up a group of 250 (mean age 15 years) for 1 to 6 years after the first
capillaroscopy was performed. Every 6 months they were screened for signs and
symptoms of connective tissue disease. Analysis was performed on capillary
changes registered 6 months before the development of connective tissue disease. 
Capillary changes were classified into three types: normal, nonspecific, and
sclerodermatous. At the end of the follow-up period, 191 (76%) subjects had
primary Raynaud phenomenon, 27 (10.8%) were diagnosed as having undifferentiated 
connective tissue disease, and 32 (12.8%) fulfilled the criteria for a diagnosis 
of a specific connective tissue disease. Systemic lupus erythematosus was found
in nine (3.6%) patients, rheumatoid arthritis in 10 (4%) patients (six of them
with juvenile onset rheumatoid arthritis), and scleroderma spectrum disorders in 
13 (5.2%). The mean time for the evolution of Raynaud phenomenon into
undifferentiated connective tissue disease or a form of the disease was 2 years. 
Most of the subjects with primary Raynaud phenomenon (173/191, 91%),
undifferentiated connective tissue disease (22/27, 81%), juvenile onset
rheumatoid arthritis/rheumatoid arthritis (7/10, 70%), and systemic lupus
erythematosus (6/9, 67%) had normal capillary findings. Nonspecific capillary
changes occurred in 3 of 10 (30%) patients with rheumatoid arthritis, 2 of 9
(22%) with systemic lupus erythematosus, 4 of 27 (15%) with undifferentiated
connective tissue disease, and 18 of 191 (9%) with primary Raynaud phenomenon. Of
all the subjects, only 10 (4%) showed sclerodermatous disease type capillary
changes 6 months before the expression of a particular disease: eight (62%) of
these developed scleroderma spectrum disorders, one expressed systemic lupus
erythematosus, and one had undifferentiated connective tissue disease. We
concluded that there were no specific capillary changes predictive for future
development of systemic lupus erythematosus, juvenile onset rheumatoid
arthritis/rheumatoid arthritis, and undifferentiated connective tissue disease in
children and adolescents with Raynaud phenomenon. Most of our study subjects with
Raynaud phenomenon who developed these diseases had normal capillary findings or 
nonspecific changes. Children and adolescents who developed scleroderma spectrum 
disorders showed a sclerodermatous type of capillary changes 6 months before the 
expression of the disease, indicating that this type of capillary changes in
children and adolescents with Raynaud phenomenon highly correlated with further
development of scleroderma spectrum disorders.

PMID: 17014637 [PubMed - indexed for MEDLINE]

73: Ann Pharmacother. 2006 Nov;40(11):1998-2002. Epub 2006 Sep 26.

Renin-angiotensin system mediators and Raynaud's phenomenon.

Wood HM, Ernst ME.

College of Pharmacy, The University of Iowa, Iowa City, IA 52242-1009, USA.

OBJECTIVE: To review the use of angiotensin-converting enzyme (ACE) inhibitors
and angiotensin II receptor blockers (ARBs) in the treatment of Raynaud's
phenomenon (RP). DATA SOURCES: Biomedical literature was accessed through July
2006 via PubMed, the Iowa Drug Information System (IDIS), and Cumulative Index to
Nursing and Allied Health Literature (CINAHL) Plus. PubMed database terms
included Raynaud's disease, angiotensin-converting enzyme inhibitors, and
angiotensin II type 1 receptor blockers [pharmacological action]; IDIS terms
included hypotensive agents-ace inhib 24080200, raynaud's syndrome 443.0, and
hypotensive agents-angioten II 24080400; and CINAHL Plus terms included Raynaud's
disease, angiotensin-converting enzyme inhibitors, losartan, and irbesartan.
STUDY SELECTION AND DATA EXTRACTION: All clinical trials published in English
that reported both subjective and objective outcomes of efficacy were reviewed.
DATA SYNTHESIS: Several small, short-term studies have evaluated captopril,
enalapril, and losartan in the treatment of RP. The studies of ACE inhibitors
have found conflicting results in their ability to improve digit blood flow and
reduce both frequency and severity of RP attacks. Two studies have focused on the
use of losartan for RP treatment, with both finding a statistically significant
reduction in attacks and one showing improvement in symptoms of RP in comparison 
with the commonly utilized calcium-channel blocker, nifedipine. Most of the
studies were short term (< or =12 wk) and included a limited number of patients
(<60). CONCLUSIONS: ACE inhibitors and ARBs may provide some minor benefits in
the relief of RP, although no definite evidence exists to suggest that they are
superior to traditionally used treatments such as calcium-channel blockers.
Larger, randomized controlled trials of longer duration are needed to compare the
effectiveness of ACE inhibitors and ARBs with conventional treatment.

Publication Types: 
    Review

PMID: 17003081 [PubMed - indexed for MEDLINE]

74: Rheumatology (Oxford). 2006 Oct;45 Suppl 3:iii45-8.

Erratum in:
    Rheumatology (Oxford). 2008 Feb;47(2):234-5.

Successful treatment of patients with severe secondary Raynaud's phenomenon with 
the endothelin receptor antagonist bosentan.

Selenko-Gebauer N, Duschek N, Minimair G, Stingl G, Karlhofer F.

Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of
Dermatology, Medical University of Vienna, Vienna General Hospital, Austria.

Secondary Raynaud's phenomenon (RP) in patients with systemic sclerosis (SSc) and
other collagen vascular diseases is a serious manifestation of microvascular
damage that may precede the onset of visceral and/or cutaneous sclerosis for
years. Recent studies have demonstrated that the endothelin receptor antagonist
bosentan prevents the development of new digital ulcers in SSc. We investigated
the potential benefits of bosentan in patients with secondary RP associated with 
pre-scleroderma and with SSc, independent of digital ulcers. Three patients with 
secondary RP received bosentan 62.5 mg twice daily for 4 weeks followed by 125 mg
twice daily for 12 weeks during the winter season. Pain (visual analogue scale), 
Raynaud's disease activity (Scleroderma Health Assessment Questionnaire), number 
and severity of daily Raynaud's attacks (diary) and peripheral thermoregulation
(thermography) were assessed during treatment periods. Pain, Raynaud's disease
activity, number and severity of Raynaud's attacks significantly decreased during
treatment periods. Thermography after 16-week treatment demonstrated improved
peripheral thermoregulation. Although this is a small observational study,
treatment with bosentan appears to measurably reduce the daily impact of
Raynaud's disease and improve peripheral thermoregulation in patients with
secondary RP, independent of digital ulcers.

Publication Types: 
    Clinical Trial

PMID: 16987835 [PubMed - indexed for MEDLINE]

75: Rheumatology (Oxford). 2006 Oct;45 Suppl 3:iii33-5.

Erratum in:
    Rheumatology (Oxford). 2008 Feb;47(2):234-5.

Pathophysiology and clinical consequences of Raynaud's phenomenon related to
systemic sclerosis.

Sunderkötter C, Riemekasten G.

Department of Dermatology and Venereology, University Hospital Münster,
von-Esmarch-Str. 58, 48149 Münster, Germany. cord.sunderkoetter@ukmunster.de

According to the so-called vascular hypothesis, Raynaud's phenomenon (RP) is one 
initial event in the pathophysiological cascade leading to sclerosis in systemic 
sclerosis (SSc). It is characterized by recurrent, reversible spasms of small
arterioles and digital arteries, usually triggered by cold and emotional stress. 
Clinical signs of RP are a sudden pallor of single digits of fingers followed by 
reactive hyperaemia and in severe cases also by cyanosis. Besides imbalances
between vasoconstrictive and vasodilatory processes, structural alterations of
the involved vessels are fundamental to secondary RP in SSc. The latter is the
reason why secondary RP in SSc, in contrast to primary RP, often leads to
ischaemia and re-perfusion injuries. New insights into the pathophysiology of RP 
feature a special role for alpha2c-adrenoreceptors, Rho-kinase signalling
pathways and soluble mediators. They have resulted in promising therapeutic
options, including antagonism of endothelin receptors, inhibition of
phosphodiesterases or selective blockade of alpha2c-adrenoreceptors. They should 
also have a positive impact on the course of SSc in general.

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

PMID: 16987831 [PubMed - indexed for MEDLINE]

76: J Rheumatol. 2006 Oct;33(10):2085-7. Epub 2006 Sep 15.

Anakinra prevents symptoms of familial cold autoinflammatory syndrome and
Raynaud's disease.

Metyas SK, Hoffman HM.

Division of Rheumatology, University of Southern California, Los Angeles,
California 90033, USA. metyas@usc.edu

OBJECTIVE: Familial cold autoinflammatory syndrome (FCAS) is a rare, hereditary
disorder characterized by cold-induced inflammation. We describe the successful
longterm treatment of a patient with FCAS with anakinra, an interleukin 1
receptor antagonist (IL-1Ra). The remarkable response of FCAS and associated
Raynaud's disease in this patient suggests that IL-1 is an important mediator of 
these inflammatory diseases. Our report supports increasing evidence that
anakinra plays an important role in the treatment of select chronic inflammatory 
diseases.

Publication Types: 
    Case Reports

PMID: 16981288 [PubMed - indexed for MEDLINE]

77: J Hum Genet. 2006;51(10):879-86. Epub 2006 Sep 15.

Glutathione S-transferase M1 and GST T1 genetic polymorphisms and Raynaud's
phenomenon in French vinyl chloride monomer-exposed workers.

Fontana L, Marion MJ, Ughetto S, Catilina P.

Institut de Médecine du Travail, Faculté de Médecine, UFR Médecine, Univ Clermont
1, 28 place Henri Dunant, 63001, Clermont-Ferrand, France.
Luc.FONTANA@u-clermont1.fr

Occupational vinyl chloride monomer (VCM) exposure can induce Raynaud's
phenomenon (RP). However, not all VCM workers developed RP, which suggests an
underlying genetic susceptibility. Genetic polymorphisms of glutathione
S-transferases (GSTs), involved in VCM metabolism, have been shown to influence
certain VCM-related health effects. We have conducted a case-control study of 58 
subjects with RP along with 247 subjects without RP, from a population of 305
French workers exposed or formerly exposed to VCM, to assess any association
between GST M1 and GST T1 gene polymorphisms, either separately or in
combination, and the presence of RP. None of the GST M1 or GST T1 genotypes were 
significantly associated with the presence of RP among studied VCM workers. A
combination of positive genotypes for both GST M1 and GST T1 was significantly
associated with RP presence, compared to the other combinations of genotypes
(OR=2.1, 95% CI=1.1-3.8). OR adjusted for age, smoking status, alcohol
consumption and history of treated hypertension did not reach significance
(OR=2.0, 95% CI=0.9-5.2). None of the GST M1 and GST T1 genotypes seem to
contribute separately to the presence of RP, suggesting that they are not, when
taken alone, a major determinant of interindividual variability for VCM-induced
PR. However, the combination of both positive GST M1 and GST T1 genotypes appears
to contribute slightly to susceptibility to RP in VCM-exposed subjects.
Nevertheless, our study-the first to examine the role of a genetic component in
the occurrence of RP secondary to occupational exposure to a
chemical-corroborates the previous considerations that interaction between the
genetic constitution and environmental factors is of importance in determining
the health-adverse effects of VCM exposure.

PMID: 16977343 [PubMed - indexed for MEDLINE]

78: Occup Med (Lond). 2006 Oct;56(7):507-9. Epub 2006 Aug 11.

Thenar hammer syndrome: a case report.

Youakim S.

WorkSafeBC, Workers' Compensation Board of British Columbia, Canada.
syouakim@telusplanet.net

BACKGROUND: Raynaud's phenomenon occurs among automobile mechanics secondary to
long-term use of vibrating hand-held tools. It can also occur from traumatic
injury to the upper extremity. AIM: This report describes a case of single digit 
Raynaud's phenomenon in an automobile mechanic due to focal arterial impact
trauma. CASE REPORT: A 38-year-old right-handed transmission mechanic complained 
of paraesthesia and blanching of the right index finger on exposure to cold and
eventually developed a transient necrotic ulcer at the tip of the digit. He had a
long history of occupational exposure to vibrating hand-held power tools.
Evaluation for common causes of Raymond's phenomenon was negative. The diagnosis 
of hand-arm vibration syndrome (HAVS) was rejected because of the rapidity of
progression and severity of the symptoms restricted only to the index finger
without corresponding symptoms of the other digits of the right hand as would be 
expected. Angiography revealed an obstructive lesion of the distal right radial
artery at the wrist and he was diagnosed with thenar hammer syndrome. This
uncommon condition was due to focal injury of the distal radial artery caused by 
repeated slamming of transmission parts on a work table. CONCLUSIONS: Not all
cases of Raynaud's phenomenon in workers using vibrating hand-held tools are due 
to HAVS. Alternative aetiologies should be considered especially if symptoms are 
asymmetrical and unilateral.

Publication Types: 
    Case Reports

PMID: 16905623 [PubMed - indexed for MEDLINE]

79: Rheumatol Int. 2006 Dec;27(2):175-7. Epub 2006 Jul 27.

Scleroderma and chronic myeloid leukemia: a sheer coincidence, a consequence of
long lasting D-penicillamine therapy or a plausible relationship of both
diseases?

Kaşifoğlu T, Korkmaz C, Yaşar S, Gülbaş Z.

Division of Rheumatology, Department of Internal Medicine, Eskişehir Osmangazi
University Medical Faculty, Vişnelik Mah. Alifuat Güven C. Akasya Sok. 11/11,
26020 Eskişehir, Turkey.

Systemic sclerosis is a chronic multisystem disorder of unknown etiology
characterized by the involvement of skin and visceral organs caused by an
accumulation of collagen. It has been reported that the incidence of solid and
hematological malignancy increased in systemic sclerosis. Multiple myeloma and
chronic lymphocytic leukemia are the most common hematological malignancies seen 
in patients with systemic sclerosis. Chronic myeloid leukemia (CML) has only
rarely been reported so far. We here report a case with CREST (calcinosis,
Raynaud's phenomenon, esophageal dysfunction, sclerodactly, telangiectasia) who
developed CML 7 years after the onset of CREST. Ours is the second case with CML 
developing after the onset of CREST in the literature. We also briefly discuss
the possible tendency to hematological malignancy in systemic sclerosis.

Publication Types: 
    Case Reports

PMID: 16871407 [PubMed - indexed for MEDLINE]

80: Clin Exp Rheumatol. 2006 May-Jun;24(3):305-8.

Extra-articular manifestations of rheumatoid arthritis: results of a university
hospital of 526 patients in Turkey.

Calgüneri M, Ureten K, Akif Oztürk M, Onat AM, Ertenli I, Kiraz S, Akdogan A.

Hacettepe University Department of Rheumatology, Ankara, Turkey.

OBJECTIVE: Presence of extra-articular manifestations (EAM) in rheumatoid
arthritis (RA) is associated with more severe disease and increased mortality.
Prevalence of EAM may vary in different geographic areas and in different ethnic 
populations. In this study we investigated the frequency of EAM in 526 RA
patients from a single university hospital in Turkey. METHODS: The hospital
records of patients who had been diagnosed as RA in Hacettepe University
Department of Rheumatology between the years 1988 and 2003 were retrospectively
evaluated. There were 73 males and 453 females, and mean age of the patients was 
48.0 +/- 12.3 years. The mean follow-up period was 4.8 +/- 4.1 years. Three
hundred and fifty-nine patients were rheumatoid factor (RF) positive (68.3%).
RESULTS: The overall frequency of EAM was 38.4% (202 patients). The most common
EAM was rheumatoid nodules (18.1%). Sicca symptoms, pulmonary findings, Raynaud's
phenomenon, livedo reticularis, carpal tunnel syndrome, vasculitis, amyloidosis, 
and Felty syndrome were present in 11.4%, 4.8%, 3%, 4.8%, 2.8%, 1.3%, 1.1%, and
0.3% of the patients, respectively. Overall EAM and rheumatoid nodules were
significantly more common in RF positive patients than RF negative patients. The 
frequency of rheumatoid nodules was significantly higher in males than in
females. CONCLUSION: The prevalence of EAM in Turkey is higher than East Asia and
Africa, and lower than UK and North America. Excluding secondary Sjögren's
syndrome, our results are similar to other Mediterranean populations like Italy.

PMID: 16870099 [PubMed - indexed for MEDLINE]

81: Ann Agric Environ Med. 2006;13(1):33-8.

Influence on operator's health of hand-transmitted vibrations from handles of a
single-axle tractor.

Goglia V, Gospodaric Z, Filipovic D, Djukic I.

Faculty of Forestry, Svetosimunska 25, 10000 Zagreb, Croatia.
goglia@hrast.sumfak.hr

The operators of the single-axle tractors are especially exposed to hand-arm
transmitted vibrations. These vibrations can cause the complex of vascular,
neurological and musculoskeletal disorders, collectively named hand-arm vibration
syndrome. Among these, the most common disorder is vibration-induced white finger
(Raynaud's phenomenon). The vibration levels were measured in three tractor's
working conditions, namely idling, transportation and soil tillage. The vibration
level on the handles was measured and analysed and the frequency spectra for the 
chosen working conditions were obtained. The frequency-weighted acceleration,
given in m/s2, was calculated and the obtained values are graphically presented. 
The measured vibration levels are then discussed with regard to the operator's
daily exposure limits recommended by the ISO 5349. The vibration levels were much
higher in the x and y directions than the z-direction in all working conditions. 
The vibration total values in idling, transportation and soil tillage were 3.37, 
8.37 and 9.62 m/s2, respectively. Results showed that the 10% of workers are
exposed to a risk of vibration-induced white finger disorder of the hands after
relatively short periods (3-4 years), if the tractor is used 8 hour per day in
soil tillage and transportation at full load. Considering the criteria of the ISO
5349, the daily working time with the single-axle tractor should be limited in
order to protect the operator and work schedules should be arranged to include
vibration-free periods.

PMID: 16841869 [PubMed - indexed for MEDLINE]

82: Ann Pharmacother. 2006 Jul-Aug;40(7-8):1388-93. Epub 2006 Jul 11.

Phosphodiesterase inhibitors in Raynaud's phenomenon.

Levien TL.

Pharmacotherapy Department, College of Pharmacy, Washington State University
Spokane, 99210-1495, USA. Levient@wsu.edu

OBJECTIVE: To evaluate the efficacy of the phosphodiesterase type 5 (PDE5)
inhibitors in the treatment of Raynaud's phenomenon. DATA SOURCES: Searches of
MEDLINE (1966-March 2006) and Web of Science (1980-March 2006) were conducted;
search terms were sildenafil, tadalafil, vardenafil, phosphodiesterase, and
Raynaud. Studies and case reports published in English were retrieved. Additional
references were identified in bibliographic reviews. DATA SYNTHESIS: Several
small studies and a number of case reports have described the use of PDE5
inhibitors in patients with either primary or secondary Raynaud's phenomenon. The
data from the best designed study show a reduced attack frequency and duration,
reduced Raynaud Condition Score, and increased capillary blood flow in patients
with secondary Raynaud's phenomenon. CONCLUSIONS: Available evidence suggests
that sildenafil may be associated with improved microcirculation, symptomatic
relief, and ulcer healing in patients with secondary Raynaud's phenomenon.
Limited information suggests similar effects with tadalafil and vardenafil.
Improved blood flow and clinical improvements have also been observed in some
patients with primary Raynaud's phenomenon treated with PDE5 inhibitors; however,
studies have yielded conflicting results.

Publication Types: 
    Review

PMID: 16835313 [PubMed - indexed for MEDLINE]

83: Occup Med (Lond). 2006 Sep;56(6):422-5. Epub 2006 Jun 16.

Modification of the Stockholm Vascular Scale.

Poole K, Elms J, Mason H.

Health and Safety Laboratory, Harpur Hill, Buxton, Derbyshire SK17 9JN, UK.
kerry.poole@hsl.gov.uk

BACKGROUND: Staging hand-arm vibration syndrome (HAVS) depends upon accurate
reporting of the extent and frequency of blanching attacks. Reporting may not be 
repeatable and not all individuals classifiable using the Stockholm Workshop
Scale (SWS). For Department of Trade and Industry (Dti) coal miners' assessments,
the SWS was modified to include a blanching score. Further modifications, which
involve splitting Stage 2V into 'early' and 'late' have been proposed but the
impact of this on classification has not been investigated. AIM: To investigate
the impact of modifications in the SWS on HAVS classification. METHODS: Staging
of individuals with HAVS according to the SWS using two modified scales. Two
different cut-offs for defining 'frequent' blanching attacks (>or=3 or >or=7
attacks/week, respectively) were used. RESULTS: One hundred and sixty-five
individuals were staged. Using the SWS, 58 and 31% of the population were
unclassifiable using the two cut-offs, respectively. The modification splitting
Stage 2V reduced the proportions that were unclassifiable to 2 and 9%,
respectively, and increased those classified as Stage 2V. The cut-off for
frequent attacks used (3 or 7) affected the proportion of individuals falling
into the subdivisions of Stage 2 with 17 and 42% being classified as 2Vearly and 
45 and 20% as 2Vlate, respectively. CONCLUSIONS: Subdividing Stage 2V enables
more individuals to be classified, but the proportion falling into each category 
is susceptible to the cut-off used for defining frequent attacks. Caution may
need to be applied if this categorization is used to make decisions regarding
fitness to work.

PMID: 16782771 [PubMed - indexed for MEDLINE]

84: Int Angiol. 2006 Jun;25(2):221-7.

Comment in:
    Int Angiol. 2006 Dec;25(4):436.

The role of endothelin-1 and selected cytokines in the pathogenesis of Raynaud's 
phenomenon associated with systemic connective tissue diseases.

Rychlik-Golema W, Mastej K, Adamiec R.

Department and Clinic of Angiology, Hypertension and Diabetology, Medical
University of Wroclaw, Wroclaw, Poland.

AIM: In the pathogenesis of Raynaud's phenomenon humoral and immunoinflammatory
agents are involved. The aim of this study was the assessment of the level of
endothelin-1 (ET-1), tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6),
soluble IL-6 receptor (IL-6sR), von Willebrand's factor (vWF) and platelet factor
4 (PF-4) in patients with Raynaud's phenomenon associated with systemic
connective tissue diseases. METHODS: The examined group consisted of 32 patients 
(24 women and 8 men) with Raynaud's phenomenon associated with selected
connective tissue diseases, aged 28-50 years. A control group consisted of 13
healthy volunteers. Immediately after a cold provocation test venous blood was
taken in order to assess serum concentrations of: TNF-alpha, IL-6, IL-6sR, vWF,
PF-4, antinuclear antibodies (ANA), antineutrophil antibodies (c-ANCA). RESULTS: 
In the group of patients with Raynaud's phenomenon mean serum concentration of
ET-1, TNF-alpha, PF-4, and vWF was significantly greater than in the healthy
group. In contrast, serum IL-6 and IL-6sR concentrations did not differ
significantly between the diseased and healthy groups. In a subgroup of Raynaud's
phenomenon patients showing particularly high concentration of serum ET-1 (twice 
as much as mean control concentration), the increase in IL-6, IL-6sR, vWF and
c-ANCA concentration exhibited statistical significance in comparison with
patients with lower serum ET-1 concentration. The vWF concentration exhibited
positive correlation with time interval between the occurrence of clinical
symptoms and serum ANA antibodies concentration. The increase in ET-1 synthesis
in Raynaud's phenomenon patients is dependent on the increase in IL-6 level and
c-ANCA antibodies level. CONCLUSIONS: The patients with Raynaud's phenomenon show
an increase in ET-1 and TNF-alpha concentrations. An enhanced ET-1 synthesis is
dependent on the augmentation of serum c-ANCA antibodies and IL-6 concentrations.

Publication Types: 
    Comparative Study

PMID: 16763543 [PubMed - indexed for MEDLINE]

85: J Clin Microbiol. 2006 Jun;44(6):2295-7.

Fatal myocardial necrosis caused by Staphylococcus lugdunensis and
cytomegalovirus in a patient with scleroderma.

Pirilä L, Söderström KO, Hietarinta M, Jalava J, Kytö V, Toivanen A.

Department of Medicine, University of Turku, Turku, Finland.

A 42-year-old woman developed a rapidly progressing fatal heart failure. At the
autopsy extensive necrosis of the myocardium was seen, with an almost complete
absence of inflammatory cells and the presence of bacterial structures identified
as Staphylococcus lugdunensis by PCR. In addition, the cytomegalovirus genome was
found to be located inside the cardiomyocytes.

Publication Types: 
    Case Reports

PMID: 16757644 [PubMed - indexed for MEDLINE]

86: Clin Res Cardiol. 2006 Jun;95(6):344-8. Epub 2006 May 18.

Coronary vasospasm-induced acute diastolic dysfunction in a patient with
Raynaud's phenomenon.

Tschöpe C, Westermann D, Steendijk P, Kasner M, Rudwaleit M, Schwimmbeck PL,
Poller WC, Schultheiss HP.

Charitè-University Medicine Berlin, Campus Benjamin Franklin, Department of
Cardiology and Pneumology, Hindenburgdamm 30, 12200, Berlin, Germany.
Carsten.Tschoepe@charite.de

We present the case of a patient with severe dyspnea and Raynaud's phenomenon. We
could clarify, using invasive techniques including left ventricular conductance
catheterization and coronary ergonovine provocation, that isolated diastolic
dysfunction induced by coronary vasospasm were responsible for the symptoms.
Systolic function was not affected. Short-term infusions with the prostacyclin
analogue iloprost, known to act as a disease-modifying agent in patients
suffering from Raynaud's phenomenon, led to an improvement of cardiac function.
Thus, episodes of dyspnea in patients with Raynaud's phenomenon might be also
interpreted as a coronary ischemia equivalent, which may belong to a visceral
form of Raynaud's phenomenon and which are sensitive to iloprost infusions.

Publication Types: 
    Case Reports

PMID: 16741592 [PubMed - indexed for MEDLINE]

87: Arthritis Rheum. 2006 Jun;54(6):1974-81.

Comment in:
    Arthritis Rheum. 2007 Jun;56(6):2102-3; author reply 2103-4.    Perspect Vasc Surg Endovasc Ther. 2007 Sep;19(3):341-2.

Transition from primary Raynaud's phenomenon to secondary Raynaud's phenomenon
identified by diagnosis of an associated disease: results of ten years of
prospective surveillance.

Hirschl M, Hirschl K, Lenz M, Katzenschlager R, Hutter HP, Kundi M.

Hanuschkrankenhaus, Vienna, Austria. Mirko.Hirschl@wgkk.sozvers.at

OBJECTIVE: To assess the early signs, risk factors, and rate of transition from
primary Raynaud's phenomenon (primary RP) to secondary RP. METHODS: A clinical
sample of 307 consecutive patients with RP was included in a prospective followup
study. After an initial screening, 244 patients were classified as having primary
RP, of whom 236 were followed up for a mean +/- SD of 11.2 +/- 3.9 years.
Patients classified according to the screening as having suspected secondary RP
underwent an extended screening program annually until transition to secondary RP
occurred. RESULTS: The initial prevalence of secondary RP was 11%. The annual
incidence of transition to suspected secondary RP was 2%, and the annual
incidence of transition to secondary RP was 1%. Overall, 46 patients were
classified as having suspected secondary RP, and 23 of these later were
classified as having secondary RP. Older age at onset of RP (hazard ratio 2.59,
95% confidence interval [95% CI] 1.40-4.80), shorter duration of RP at enrollment
(hazard ratio 0.87, 95% CI 0.81-0.94), and abnormal findings on thoracic outlet
test (hazard ratio 2.69, 95% CI 1.12-6.48) were associated with an increased risk
for transition to secondary RP. Compared with patients with suspected secondary
RP, those diagnosed as having secondary RP had a higher number and earlier
occurrence of pathologic findings. Furthermore, antinuclear antibodies at a titer
of > or = 1:320 and positive findings in specific serologic subsets were
associated with a significantly increased risk for developing a connective tissue
disease. CONCLUSION: Patients diagnosed initially as having primary RP may
actually comprise 1 of 3 groups: those with idiopathic RP, those with a rather
benign disease course, and those with a more severe course of the disease.

PMID: 16732585 [PubMed - indexed for MEDLINE]

88: In Vivo. 2006 May-Jun;20(3):377-80.

Iloprost enhances portal flow velocity and volume in patients with systemic
sclerosis.

Zardi EM, Picardi A, Ambrosino G, Fazio VM, Dobrina A, Frego M, Afeltra A,
Lumachi F.

Interdisciplinary Center for Biomedical Research (CIR), Laboratory of Internal
Medicine and Hepatology and Campus Bio-Medico University, School of Medicine,
00155 Roma, Italy.

BACKGROUND: Iloprost, a prostacyclin analog, reduces hepatic microcirculatory
damage after ischemia-reperfusion injury in animal liver models. The objective of
this study was to evaluate whether the portal flow velocity changes after
Iloprost infusion in patients with systemic sclerosis and Raynaud's phenomenon,
who usually have increased risk of microvascular thrombosis and transient liver
disturbances. PATIENTS AND METHODS: Fifteen patients (3 males and 12 females,
median age 58 years, range 47-66 years), with systemic sclerosis and Raynaud's
phenomenon, were exclusively treated with an infusion of Iloprost (2 ng/kg/min, 6
h/day) for 5 days. In each subject, the portal flow velocity (PV, cm/sec) and
portal flow volume (PFV, mL/min) were obtained by using portal color Doppler
ultrasonography equipment. RESULTS: Iloprost administration significantly
(p<0.001) increased both the PV (23.6+/-3.4 cmlsec vs. 29.1+/-3.9 cm/sec) and PFV
(1748.8+/-310. 7 mL/min vs. 2254.9+/-404.1 mL/min) values. CONCLUSION: Hepatic
perfusion significantly improved after Iloprost administration, suggesting that
such treatment might be useful in preventing vascular complications in patients
with systemic sclerosis. Iloprost improves the portal hemodynamics, favoring
local microvascular patency, and its effectiveness may be safely monitored by
using portal color Doppler ultrasonography.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 16724674 [PubMed - indexed for MEDLINE]

89: Clin Rheumatol. 2007 Mar;26(3):349-54. Epub 2006 Apr 25.

The natural course of progressive systemic sclerosis patients with interstitial
lung involvement.

Benan M, Hande I, Gul O.

Department of Pulmonary Diseases, Cerrahpasa Medical Faculty, Istanbul
University, Istanbul, Turkey.

OBJECTIVE: The aim of the study is to assess the natural course of systemic
sclerosis (SSc) in patients with interstitial lung involvement and to evaluate
the effects of treatment. MATERIALS AND METHODS: Sixty SSc patients with
interstitial lung involvement were included in the study and history and
retrospective data records of the patients were reviewed. RESULTS: It was
observed that 47 patients (78.3%) had Raynaud's phenomenon, 7 patients (11.7%)
had skin involvement, 5 patients (8.3%) had joint involvement, and 1 patient
(1.7%) had gastrointestinal system involvement as the first manifestation of the 
disease. Lung involvement had developed on an average of 113 +/- 106 months after
the first manifestation of the disease and was apparent within the first year in 
10 patients (16.7%), between 1 and 2 years in 3 patients (5%), between 2 and 3
years in 2 patients (3.3%), between 3 and 4 years in 5 patients (8.3%), between 4
and 10 years in 21 patients (35%), and after 10 years in 19 patients (31.7%).
When the symptoms of lung involvement appeared, 37 patients (61.7%) were not
receiving treatment while 23 (38.3%) were using an immunosuppressive agent. The
time interval of lung involvement for the treated patients was 131 +/- 95 months 
while it was 101 +/- 112 months in untreated patients (p>0.05). CONCLUSION: In
SSc patients with interstitial pulmonary involvement, the disease frequently
starts with Raynaud's phenomenon and pulmonary symptoms tend to appear at a mean 
of 7 years after the onset of disease. The first sign of the disease, the
probability of interstitial pulmonary involvement, is highest during the first 15
years after. Although this probability decreases after 15 years, in up to 10% of 
the patients, interstitial pulmonary involvement can still occur even up to 40
years. Immunosuppressive treatment is not effective in preventing the development
of pulmonary involvement. However, it delays the manifestation of pulmonary
symptoms for nearly 4 years.

PMID: 16636936 [PubMed - indexed for MEDLINE]

90: Rheumatol Int. 2006 Sep;26(11):1014-8. Epub 2006 Apr 8.

Raynaud's syndrome: comparison of late and early onset forms using hand perfusion
scintigraphy.

Csiki Z, Galuska L, Garai I, Szabó N, Varga J, András C, Zeher M.

Third Department of Internal Medicine, University of Debrecen Medical and Health 
Science Center, Nagyerdei krt. 98, 4012 Debrecen, Hungary. csikiz@gmail.com

Primary Raynaud's disease is generally a disease of younger females; however,
there are cases where symptoms present over the age of 40. These cases are
described as late onset. In our current prospective study we compared the
characteristics of early and late onset types of primary Raynaud's in 127
patients. In addition to the collection of medical records, we performed
capillary-microscopy and hand perfusion scintigraphy using Tc-99 m DTPA to
evaluate the microcirculation of each patient's fingers. Regarding the spectrum
of the capillary-microscopic findings, we did not find any significant difference
between the early and late onset forms. However, in hand perfusion examinations
done using Tc-99 m DTPA, we measured a significantly lower finger/palm ratio
(FPR) in the early onset group of patients. We also observed a correlation
between the duration of the disease and the FPR, as well as between the age and
FPR. Longer disease duration resulted in a significantly lower FPR. On the basis 
of our results, we believe that late onset Raynaud's should be treated as a
separate entity. Due to its different characteristics found on examination and
follow-up of our patients, functional hand perfusion examination should be
recommended independently of the age-related characteristics of the disease.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 16604347 [PubMed - indexed for MEDLINE]

91: Eur J Vasc Endovasc Surg. 2006 Aug;32(2):198-202. Epub 2006 Mar 27.

Comment in:
    Eur J Vasc Endovasc Surg. 2007 Jan;33(1):133.

Thoracoscopic sympathectomy for Raynaud's phenomenon--a long term follow-up
study.

Thune TH, Ladegaard L, Licht PB.

Department of Cardiothoracic and Vascular Surgery, Odense University Hospital,
Odense, Denmark. tom@thune.nu

OBJECTIVES: To assess the long term results of thoracoscopic sympathectomy for
Raynaud's phenomenon. DESIGN, MATERIALS AND METHODS: A retrospective study of 34 
consecutive patients who were treated for Raynaud's phenomenon by thoracoscopic
sympathectomy from 1996 to 2005. Eight patients presented with ulcerations of the
digits and 10 had severe ischaemia without ulcerations. The hospital records were
retrieved and questionnaires were mailed to the patients for follow-up. RESULTS: 
The questionnaire was answered by 91% of patients after a median follow-up time
of 40 months. An immediate effect was seen in 83% of the patients but symptoms
recurred in 60% during the follow-up period. Compensatory sweating occurred in 63
and 30% reported gustatory sweating. Thirteen patients (43%) regretted having the
operation. CONCLUSION: The majority of patients with Raynaud's phenomenon have an
excellent immediate effect from thoracoscopic sympathectomy and one third achieve
a long lasting effect. Side effects are frequent. We now only use thoracoscopic
sympathectomy in severe cases of Raynaud's phenomenon.

PMID: 16564187 [PubMed - indexed for MEDLINE]

92: Clin Rheumatol. 2007 Apr;26(4):587-9. Epub 2006 Mar 15.

High resolution 3 Tesla contrast-enhanced MR angiography of the hands in
Raynaud's disease.

Walcher J, Strecker R, Goldacker S, Winterer J, Langer M, Bley TA.

Department of Diagnostic Radiology and Medical Physics, University Hospital
Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany.

Raynaud's disease is associated with disorders in blood circulation of the hands.
The gold standard to visualise pathology of digital arteries is catheter
angiography. Contrast-enhanced MR angiography (CE MRA) has developed even more as
an alternative non-invasive method to digital subtraction angiography, mostly for
pelvic or lower limb vessels. We report a case of primary Raynaud's disease with 
high-grade stenosis and an occlusion of the digital arteries. This case
illustrates the benefit and efficiency of CE MRA at high fields in depicting
location and extension of peripheral arterial alterations.

Publication Types: 
    Case Reports

PMID: 16538393 [PubMed - indexed for MEDLINE]

93: Can J Anaesth. 2006 Mar;53(3):258-62.

Bilateral pain relief after unilateral thoracic percutaneous sympathectomy.

Gofeld M, Faclier G.

Department of Anesthesia, Sunnybrook & Women's College Health Sciences Centre,
University of Toronto, Ontario M4N 3M5, Canada. mgofeld@rogers.com

PURPOSE: To present a case of unexpected bilateral pain relief following
unilateral thoracic percutaneous sympathectomy. CLINICAL FINDINGS: We present a
case report where severe ischemic pain due to paraneoplastic Raynaud's syndrome
with distal gangrene was successfully treated by means of percutaneous thoracic
sympathectomy. A unilateral T2, T3 radiofrequency sympathectomy combined with
small volume phenol injection resulted in unexpected bilateral pain relief.
CONCLUSION: Our observations from this case report suggest a possible crossover
of sympathetic innervation at the cervical and thoracic levels. Percutanenous
thoracic radiofrequency sympathectomy is a feasible option for the treatment of
refractory ischemic upper limb pain.

Publication Types: 
    Case Reports

PMID: 16527790 [PubMed - indexed for MEDLINE]

94: Pediatr Cardiol. 2006 Mar-Apr;27(2):297-300.

Carney complex presenting with Raynaud's phenomenon and erythematous macules of
the extremities.

Mirkinson LJ, Ratnayaka K, Sable CA, Gaskin PR.

Department of Rheumatology, George Washington University Medical Center,
Children's National Medical Center, Washington, DC 20010, USA.
mirkil@holycross-health.org

A 12-year-old male presented with a 6-week history of apparent digital vasculitis
with color changes of the distal fingers and erythematous macules of the palms
and soles. Physical examination revealed skin findings of Carney complex and an
abnormal cardiac examination. Echocardiography demonstrated a large left atrial
mass, which caused partial obstruction during diastole and moderate mitral valve 
insufficiency. Surgical excision and pathological examination of the mass
confirmed the presence of a large, peduculated myxoma. This case illustrates the 
presentation of Carney complex with left atrial myxoma as apparent vasculitis and
Raynaud's phenomenon.

Publication Types: 
    Case Reports

PMID: 16501880 [PubMed - indexed for MEDLINE]

95: Clin Rheumatol. 2007 Apr;26(4):596-600. Epub 2006 Feb 22.

Primary biliary cirrhosis (PBC)-CREST overlap syndrome with coexistence of
Sjögren's syndrome and thyroid dysfunction.

Nakamura T, Higashi S, Tomoda K, Tsukano M, Sugi K.

Section of Internal Medicine and Rheumatology, Kumamoto Center for Arthritis and 
Rheumatology, 1-15-7 Kuhonji, Kumamoto 862-0976, Japan.
naktrkme@koh.marutakai.or.jp

Calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly,
telangiectasia (CREST) syndrome, a limited form of systemic sclerosis, is
sometimes complicated by primary biliary cirrhosis (PBC). A 52- and 61-year-old
Japanese woman with PBC-CREST overlap syndrome accompanied by Sjögren's syndrome,
and Hashimoto's thyroiditis, and Graves' disease, respectively, are reported.
They had suffered from Raynaud's phenomena, sclerodactyly, morning stiffness,
arthralgia, and sicca symptoms during these several years. They exhibited an
increased level of alkaline phosphatase, gamma-glutamyl transpeptidase, positive 
antibodies against mitochondria and centromere, and hyperglobulinemia without any
cholestatic symptoms. Histological findings from liver biopsy specimens were
consistent with those of PBC. Clinically, they were diagnosed as both
asymptomatic PBC and incomplete CREST syndrome. Their human leukocyte antigen
typing showed both DR4 and DR8 positive. The association of the four autoimmune
conditions is clinically and etiologically important. Although a combination of
these diseases is rare, it is of importance to keep in mind that various
autoimmune diseases could occur simultaneously. Of critical importance is that an
active diagnostic attitude towards them is admirable, and that early diagnosis
and therapy are needed.

Publication Types: 
    Case Reports

PMID: 16496080 [PubMed - indexed for MEDLINE]

96: Rheumatology (Oxford). 2006 Aug;45(8):999-1004. Epub 2006 Feb 16.

Iloprost treatment in patients with Raynaud's phenomenon secondary to systemic
sclerosis and the quality of life: a new therapeutic protocol.

Milio G, Corrado E, Genova C, Amato C, Raimondi F, Almasio PL, Novo S.

Department of Internal Medicine and Cardiovascular Diseases, University of
Palermo, Palermo, Italy. glaucomilio@libero.it

OBJECTIVES: To evaluate the clinical efficacy and the effects on the quality of
life of iloprost, a prostacyclin analogue, used according to a new protocol in
patients with Raynaud's phenomenon secondary to systemic sclerosis. METHODS: In
this randomized study, we treated 30 patients with iloprost, given by intravenous
infusion, at progressively increasing doses (from 0.5 to 2 ng/kg/min) over a
period of 6 h each day for 10 days in two consecutive weeks, with repeated cycles
at regular intervals of 3 months for 18 months. The results were compared with
those obtained in 30 other patients who received the same drug but with different
dosing schemes. RESULTS: The total average daily duration of the attacks, the
average duration of a single attack and the average daily frequency of the
attacks were reduced significantly in all treatment groups, but the comparison
between the groups demonstrated significant differences between patients treated 
with the new protocol and the others at later times (12 and 18 months). The
effects on the quality of life in the group treated with the new protocol,
evaluated with the Short Form-36, demonstrated a marked improvement regarding
both the scale relating to the physical aspect of the illness and, especially,
the scale relating to the mental aspect. CONCLUSIONS: In patients with systemic
sclerosis, cyclic intravenous iloprost infusion is efficacious in the treatment
of Raynaud's phenomenon. The protocol that we used, compared with others, not
only has favourable clinical effects but also leads to a marked improvement in
the quality of life.

Publication Types: 
    Randomized Controlled Trial

PMID: 16484290 [PubMed - indexed for MEDLINE]

97: Microvasc Res. 2006 Mar;71(2):128-34. Epub 2006 Feb 13.

Exaggerated local hand sympathetic but not renin-angiotensin system activation in
patients with primary Raynaud's phenomenon.

Coppo M, Boddi M, Poggesi L, Bandinelli M, Abbate R, Gensini GF.

Cardiology 1, Department of Medical and Surgical Critical Care, University of
Florence, Florence, Italy. mcoppo@unifi.it

In Raynaud's disease (RD), an overactivity of sympathetic nervous system (SNS)
was hypothesized but only indirect proofs were obtained. Complex interactions
between the renin-angiotensin system (RAS) and SNS were reported without clear
demonstrations of a RAS involvement. Recently, the use of ACE inhibitors and AT1 
receptor antagonists in RD patients showed mixed results. The study of total and 
regional kinetics of tritiated noradrenaline (NA) and the measurements of local
Angiotensin (Ang) I and II arterial-venous gradient were performed in 10 RD
patients and 10 controls both in rest conditions and following a cold pressor
test (CPT). Hand blood flow (HBF) was measured by strain-gauge plethysmography.
Baseline HBF was slightly lower in patients than in controls, but during CPT, it 
significantly decreased only in RD patients (P < 0.01). Total (3H)-NA clearance
and spillover were similar in the two groups throughout the study. On the
contrary, baseline hand NA spillover was higher in RD patients than in controls
and the difference further increased during CPT. Hand NA spillover was linearly
related to HBF (P < 0.001). Arterial-venous Ang I and Ang II gradients were
positive without difference between controls and patients throughout the study.
In conclusion in RD patients, a pathological waste of NA from sympathetic nervous
endings of the hand region, exaggerated by sympathetic stimulation, occurs but an
enhanced local Ang II formation was not demonstrable.

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

PMID: 16476452 [PubMed - indexed for MEDLINE]

98: Vasc Med. 2005 Nov;10(4):293-307.

Mechanisms of Raynaud's disease.

Cooke JP, Marshall JM.

Section of Vascular Medicine, Stanford University School of Medicine, 300 Pasteur
Drive, Stanford, CA 94305-5406, USA. john.cooke@stanford.edu

Raynaud's phenomenon is due to transient cessation of blood flow to the digits of
the hands or feet. An attack of Raynaud's phenomenon is classically manifested as
triphasic color changes. The white phase is due to excessive vasoconstriction and
cessation of regional blood flow. This phase is followed by a cyanotic phase, as 
the residual blood in the finger desaturates. The red phase is due to hyperemia
as the attack subsides and blood flow is restored. An attack is frequently
associated with pain and/or paresthesia due to sensory nerve ischemia. Variants
of Raynaud's phenomenon include acrocyanosis and primary livedo reticularis, each
of which is associated with reduced skin blood flow, exacerbated by cold or
emotional upset. Raynaud's phenomenon in the absence of other disorders is
primary Raynaud's phenomenon, or Raynaud's disease. The mechanisms of Raynaud's
disease include increased activation of the sympathetic nerves, in response to
cold or emotion; an impaired habituation of the cardiovascular response to stress
may contribute. In addition, there appears to be a local fault, which is likely
multifactorial. This local fault is due to an alteration in vascular function
rather than vascular structure. The alteration in vascular function may be
related to increased sensitivity to cold of the adrenergic receptors on the
digital artery vascular smooth muscle. In some cases, locally released or
systemically circulating vasoconstrictors may participate, including endothelin, 
5-hydroxytryptamine and thromboxane. A deficiency or increased degradation of
nitric oxide, possibly due to increased oxidative stress, may be involved in some
cases. These recent pathophysiological insights may lead to new therapeutic
options.

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

PMID: 16444858 [PubMed - indexed for MEDLINE]

99: Arch Intern Med. 2006 Jan 23;166(2):231-3.

Phosphodiesterase type 5 inhibition is a novel therapeutic option in Raynaud
disease.

Caglayan E, Huntgeburth M, Karasch T, Weihrauch J, Hunzelmann N, Krieg T, Erdmann
E, Rosenkranz S.

Klinik III für Innere Medizin, Universität zu Köln, Köln, Germany.

BACKGROUND: Raynaud disease (RD) is a common disorder affecting 3% to 5% of the
healthy population, and occurs in more than 90% of patients with connective
tissue diseases. The therapeutic options remain limited, particularly in patients
with secondary RD due to connective tissue disease. Theoretical considerations
lead to the expectation that phosphodiesterase type 5 inhibitors may improve
clinical symptoms and digital blood flow in patients with RD. METHODS: We
conducted an open-label pilot study in 40 patients with RD, 33 (82%) of whom had 
secondary and 7 (18%) of whom had primary RD. Digital blood flow was measured by 
laser-Doppler flowmetry at room temperature and during the cold-exposure test
before medical treatment, 1 hour after the initial intake, and after 2 weeks of
continuous treatment (10 mg twice a day) with the novel phosphodiesterase type 5 
inhibitor vardenafil. Clinical symptoms were recorded by a patient questionnaire 
and summarized as the Raynaud condition score. RESULTS: Laser-Doppler flowmetry
revealed that vardenafil improved digital blood flow in 28 (70%) patients,
whereas 12 (30%) did not respond. In individuals responding, digital blood flow
significantly increased by a mean +/- SEM of 21.0% +/- 4.9% and 30.0% +/- 5.7% at
1 hour and 2 weeks of treatment at room temperature, respectively, and by 18.8%
+/- 4.4% and 35.1% +/- 7.5% at 1 hour and 2 weeks during the cold-exposure test, 
respectively (P < .01 for all). Consistently, clinical symptoms improved in 27
(68%) of the 40 patients, and the Raynaud condition score declined from a mean
+/- SEM of 5.05 +/- 0.38 to 3.54 +/- 0.31 (P < .001). CONCLUSION: Our data
indicate that phosphodiesterase type 5 inhibition significantly improves
peripheral blood flow and clinical symptoms in a large subset of patients with RD
and, thus, may provide a novel therapeutic approach in such individuals.

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

PMID: 16432094 [PubMed - indexed for MEDLINE]

100: Acta Paediatr. 2005 Dec;94(12):1860-2.

Raynaud phenomena and migraine in two children: inclusion within a family of
related disorders.

Besser RE, Stern CM.

Department of Paediatrics, St. Thomas' Hospital, London, United Kingdom.

We report a case of two siblings with Raynaud phenomena and migraine, whose
symptoms were successfully treated with pizotifen. CONCLUSION: To our knowledge, 
this is the first case documenting the association between Raynaud phenomena and 
migraine in two siblings with a family history of Raynaud phenomena and ischaemic
heart disease.

Publication Types: 
    Case Reports

PMID: 16421056 [PubMed - indexed for MEDLINE]

101: Clin Exp Rheumatol. 2005 Nov-Dec;23(6):801-8.

Survey of Raynaud's phenomenon and systemic sclerosis based on a representative
study of 10,000 south-Transdanubian Hungarian inhabitants.

Czirják L, Kiss CG, Lövei C, Süto G, Varjú C, Füzesi Z, Illés T, Nagy Z.

Department of Immunology and Rheumatology, Medical School, Hungarian Brothers of 
St. John of God and University of Pécs, Hungary. laszlo.czirjak@aok.pte.hu

OBJECTIVES: To assess the prevalence of Raynaud's phenomenon (RP) and of RP
associated systemic sclerosis (SSc) in a large regional representative study.
METHODS: Ten thousand individuals aged between 14-65 years participated in
face-to-face interviews. The stratified sample of the South-West Hungarian
population was representative for age, sex and urban or rural residence.
Individuals reporting complaints suggesting the presence of "clinically
significant" RP were asked to undergo a clinical investigation. Patients showing 
complaints provoked by taking something out of the freezer (-20 degrees C)
compartment of the refrigerator and/or whether they had experienced digital
ulcers were sorted into this category. RESULTS: The overall prevalence of RP was 
at least 578.9/10,000, and the prevalence of "clinically significant" RP could be
calculated as at least 87.7/10,000 inhabitants. In this latter group 17.2% of the
cases had either established SSc or anticentromere antibody or scleroderma
capillary pattern on nailfold capillaroscopy. SSc with "clinically significant"
RP and/or ulcers was identified in a prevalence of 9.1/10.000 individuals, whilst
there was a prevalence of 14.7/10,000 of RP with either anticentromere antibody
or scleroderma capillary pattern. CONCLUSIONS: "Clinically significant" RP
affects almost 1% of the population. We identified cases with early stages of
scleroderma spectrum disorder showing either anticentromere autoantibody or
scleroderma capillary pattern. The prevalence of SSc was found to be higher than 
expected. It is reasonable to screen "clinically significant" RP cases for
scleroderma-related symptoms because this approach makes it possible to identify 
patients with both SSc and early scleroderma related symptoms.

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

PMID: 16396698 [PubMed - indexed for MEDLINE]

102: Clin Rheumatol. 2006 Nov;25(6):814-8. Epub 2006 Jan 4.

The usefulness of power Doppler ultrasonography in differentiating primary and
secondary Raynaud's phenomenon.

Lee SI, Lee SY, Yoo WH.

Division of Rheumatology, Department of Internal Medicine, Chonbuk National
University Medical School, and Research Institute of Clinical Medicine, San 2-20,
Geumam-dong, Deokjin-gu, Jeonju, Jeonbuk, 561-180, Republic of Korea.
goldgu@chonbuk.ac.kr

The objectives of this study were to assess a usefulness of power Doppler
ultrasonography (PDU) and compare the diagnostic value of PDU to nailfold
capillaroscopy (NFC) in the patients with clinically diagnosed Raynaud's
phenomenon (RP) and healthy controls. Forty-one patients with primary (n=19),
secondary RP (n=22), and ten healthy controls underwent PDU and NFC examinations 
on the same day. Microvascularity was evaluated using PDU before and after cold
challenges, and the PDU signals were qualitatively graded on a scale of 1-4.
According to the change of microvascularity before and after cold challenges, the
findings of PDU were classified into three groups: (1) 'pattern I' (normal
microvascularity over grade 3 both before and after cold challenges), (2)
'pattern II' (decreased microvascularity to grade 1 or 2 only after cold
challenge), and (3) 'pattern III' (decreased microvascularity of grade 1 or 2
both before and after cold challenges). PDU confirmed the presence of RP in all
patients with clinically diagnosed RP and yielded a correct classification in
88.9% of the all persons analyzed (normal=100%, primary RP=89.5%, secondary
RP=77.3%). The analysis was performed to assess the degree of agreement between
the final diagnoses obtained by PDU and NFC. A good correlation rate was observed
between PDU and NFC examinations in differentiating primary from secondary RP
(Kappa=0.658, p<0.01). In conclusion, PDU examination with a cold challenge is a 
useful and reliable method to diagnose RP and discriminate between primary and
secondary RP.

Publication Types: 
    Controlled Clinical Trial

PMID: 16391889 [PubMed - indexed for MEDLINE]

103: Int J Immunopathol Pharmacol. 2005 Oct-Dec;18(4):761-70.

Significant changes of peripheral perfusion and plasma adrenomedullin levels in
N-acetylcysteine long term treatment of patients with sclerodermic Raynauds
phenomenon.

Salsano F, Letizia C, Proietti M, Rossi C, Proietti AR, Rosato E, Pisarri S.

Department of Clinical Medicine, U.O.C Clinical Immunology and Allergology,
University of Rome, La Sapienza, Italy. felice.salsano@uniroma1.it

The unclear pathogenesis of scleroderma vascular lesions makes treatment of
Raynaud's phenomenon (RP) in Systemic Sclerosis (SSc) patients very difficult and
a new effective treatment is requested. Recently, a powerful antioxidant agent,
the N-acetylcysteine (NAC) has been shown to decrease the frequency and severity 
of RP in SSc patients. Subsequently, using functional infrared imaging, we showed
that a single 1-hour NAC infusion in these patients caused a significant increase
of skin temperature. The aim of this study was to demonstrate the efficacy of
long term therapy with NAC in an open clinical trial evaluating clinical,
instrumental and laboratory parameters. Patients started the treatment receiving 
for two years, from October to May, intravenous NAC infusions of 15 mg/kg per
hour each, for 5 consecutive hours, every two weeks. Before and after each
infusion, patients underwent both Laser Doppler perfusion Imaging (LDPI) for the 
evaluation of the digital perfusion and a blood test to ascertain the plasma
adrenomedullin (AM) levels. The NAC infusion increased global hands perfusion and
induced a significant decreasing of plasma AM concentrations. Side effects were
negligible, easy to control and reversible. Reduction of frequency and severity
of RP attacks was recorded. In conclusion, NAC seems to act as an effective
vasodilatator in the treatment of RP secondary to SSc and, in addition, it
induced significant changes in plasma levels of AM, a potent vasodilator
endothelial-derived peptide.

Publication Types: 
    Clinical Trial

PMID: 16388726 [PubMed - indexed for MEDLINE]

104: Vasa. 2005 Nov;34(4):243-9.

The response of skin perfusion and of rheological and immunological variables to 
intravenous prostanoid administration in Raynaud's phenomenon secondary to
collagenosis.

Drinda S, Neumann T, Pöhlmann G, Vogelsang H, Stein G, Wolf G, Hein G.

Division of Rheumatology and Osteology, Department of Clinical Medicine III,
Friedrich Schiller University Jena, Germany. stefan.drinda@med.uni-jena.de

BACKGROUND: Prostanoids are used in the treatment of Raynaud's phenomenon and
acral perfusion disorders secondary to collagenosis. In subjective terms,
intravenous administration of these agents produces success in more than 50% of
patients. The therapeutic outcome of clinical administration of alprostadil or
iloprost may vary from individual to individual. PATIENTS AND METHODS: The
following variables were analysed in a cross-over study in 27 patients with
collagenosis and Raynaud's phenomenon: plasma viscosity and erythrocyte
aggregation (rheological variables), partial pressure of oxygen and laser Doppler
flowmetry in the finger region, and lymphocyte phenotyping and interleukin (IL)
determinations (immunological variables). RESULTS: Laser Doppler flowmetry
revealed significant differences between patients with secondary Raynaud's
phenomenon and a control group of 25 healthy subjects. Laser Doppler readings did
not change significantly as a result of the treatments. Therapy with iloprost
produced a reduction in IL-1beta, L-selectin (CD 62 L) and IL-6. CONCLUSION: The 
change in immunological variables due to iloprost may explain the long-term
effects of prostaglandins in the treatment of Raynaud's phenomenon. From our
results it is not possible to infer any preference for iloprost or alprostadil.

Publication Types: 
    Clinical Trial

PMID: 16363279 [PubMed - indexed for MEDLINE]

105: Clin Exp Dermatol. 2006 Jan;31(1):6-12.

Infrared-monitored cold response in the assessment of Raynaud's phenomenon.

Foerster J, Wittstock S, Fleischanderl S, Storch A, Riemekasten G, Hochmuth O,
Meffert B, Meffert H, Worm M.

Clinic for Dermatology, Charité, Berlin, Germany. john.foerster@charite.de

BACKGROUND: Evaluation of treatments for Raynaud's phenomenon (RP) requires
objective response parameters in addition to clinical activity scores.
Thermographic monitoring of fingertip re-warming after cold challenge has been
widely used but usually requires sophisticated equipment. We have previously
shown that fingertip re-warming after cold challenge follows a first-order
transient response curve that can be described by a single variable, designated
tau. OBJECTIVES: Here, we describe a novel device termed a duosensor, which
records the tau value upon cold challenge in an automated manner. METHODS: We
determined tau values in healthy probands, patients with primary or secondary RP 
associated with autoimmune disease and patients with scleroderma-associated RP
following cold challenge, to determine assay variability, sensitivity and
specificity. RESULTS: Duosensor-based thermography exhibited low intraindividual 
variability in healthy probands. As expected, tau values in RP patients were
significantly increased compared with controls (8.08 +/- 3.65 min vs. 3.23 +/-
1.65 min). The duosensor-determined tau value yielded a specificity of 94.6% and 
predictive value of 95.3% for the presence of RP in a retrospective analysis of
139 patients. Furthermore, in a cohort of scleroderma patients with RP, patient
self-assessment of RP severity correlated with tau values. CONCLUSIONS: Taken
together, the present data suggest that tau value determination provides a
suitable outcome measure for clinical studies of novel RP treatments. As the
duosensor is a simple stand-alone device requiring no supporting equipment and
minimal personnel attention, it should allow RP activity monitoring even in
clinical settings with minimal technical infrastructure.

PMID: 16309469 [PubMed - indexed for MEDLINE]

106: Ann Rheum Dis. 2006 Jul;65(7):952-4. Epub 2005 Nov 24.

Low plasma protein nitrotyrosine levels distinguish primary Raynaud's phenomenon 
from scleroderma.

Kingdon EJ, Mani AR, Frost MT, Denton CP, Powis SH, Black CM, Moore KP.

Royal Free and University College Medical School, University College London
(UCL), Rowland Hill Street, London NW3 2PF, UK.

OBJECTIVE: To investigate the hypothesis that increased formation of reactive
nitrogen species may contribute to the vascular pathology that develops in
patients with connective tissue disease such as scleroderma. PATIENTS AND
METHODS: The level of protein-bound nitrotyrosine in plasma was measured by
stable isotope dilution gas chromatography/negative ion chemical ionisation mass 
spectrometry in 11 patients with primary Raynaud's phenomenon, 37 with
scleroderma, 13 with chronic renal impairment, and in 23 healthy controls.
RESULTS: Plasma protein-bound nitrotyrosine was markedly decreased in patients
with primary Raynaud's phenomenon (mean (SEM) 0.60 (0.06) ng/mg dry protein)
compared with patients with scleroderma (1.78 (0.21) ng/mg protein), chronic
renal impairment (1.42 (0.17) ng/mg protein) or healthy controls (1.63+/-0.15
ng/mg protein, ANOVA p<0.001). CONCLUSION: These data suggest that there is
decreased nitration of plasma proteins, or increased degradation of nitrated
proteins from the circulation of patients with primary but not secondary
Raynaud's phenomenon.

Publication Types: 
    Comparative Study

PMID: 16308344 [PubMed - indexed for MEDLINE]

107: Cephalalgia. 2005 Dec;25(12):1168-72.

The 3p21.1-p21.3 hereditary vascular retinopathy locus increases the risk for
Raynaud's phenomenon and migraine.

Hottenga JJ, Vanmolkot KR, Kors EE, Kheradmand Kia S, de Jong PT, Haan J,
Terwindt GM, Frants RR, Ferrari MD, van den Maagdenberg AM.

Department of Human Genetics, Leiden University Medical Centre, Leiden, and
Department of Neurology, Rijnland Hospital, Leiderdorp, The Netherlands.

Previously, we described a large Dutch family with hereditary vascular
retinopathy (HVR), Raynaud's phenomenon and migraine. A locus for HVR was mapped 
on chromosome 3p21.1-p21.3, but the gene has not yet been identified. The fact
that all three disorders share a vascular aetiology prompted us to study whether 
the HVR haplotype also contributed to Raynaud's phenomenon and migraine in this
family. Whereas the parent-child transmission disequilibrium test (TDT) did not
reach significance, the sibling TDT revealed that the HVR haplotype harbours a
susceptibility factor for Raynaud's phenomenon and migraine. Identification of
the HVR gene will improve the understanding of the pathophysiology of HVR,
Raynaud's phenomenon and migraine.

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

PMID: 16305605 [PubMed - indexed for MEDLINE]

108: Clin Rheumatol. 2006 Jul;25(4):506-10. Epub 2005 Nov 15.

Raynaud's phenomenon: prevalence in an Italian population sample.

De Angelis R, Salaffi F, Grassi W.

Clinica Reumatologica, Ospedale "Augusto Murri", via dei Colli, 52, 60035, Jesi, 
(AN), Italy. rossella.deangelis@asl5.marche.it

To estimate the prevalence of Raynaud's phenomenon (RP) in an Italian population 
aged 18 years and above, a validated questionnaire was mailed to a random sample 
of 3,664 subjects. Sociodemographic data and data regarding the prevalence of RP 
symptoms were collected. Trained rheumatologists carried out a subsequent
standardized clinical examination to confirm diagnosis of RP and to detect
associated diseases. The subjects (2,155) completed the questionnaire, with 45
reporting RP [prevalence rate 2.1%, 95% confidence intervals (CI) 1.8-2.4]. The
mean age [standard deviation (SD)] was 57.5 (12.7), and 40 (88.8%) were women.
Prevalence was found higher in women (3.4%, 95% CI 2.8-4.1) than in men (0.5%,
95% CI 0.2-0.9) (p<0.0001). A connective tissue disease was diagnosed in six
(0.28%) subjects, three of the participants (0.14%) were identified as having RP 
associated to an idiopathic carpal tunnel syndrome, and 36 (1.67%) were diagnosed
as having primary RP. Our study has found a lower prevalence of RP than others
have reported. There is thought to be an association with climate and ethnic
factors. No relationship was found regarding factors that are thought to be among
the most relevant triggering factors for RP, e.g., occupational exposure.
Differences with previous studies may be related to the current characteristics
of the population surveyed.

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

PMID: 16292469 [PubMed - indexed for MEDLINE]

109: J Dtsch Dermatol Ges. 2004 Sep;2(9):758-62.

Is there a vasospasmolytic effect of acupuncture in patients with secondary
Raynaud phenomenon?

Hahn M, Steins A, Möhrle M, Blum A, Jünger M.

Kreiskrankenhaus Rottweil, Dept. of Dermatology, Germany.
martin.hahn@hautpraxis.com

BACKGROUND: Raynaud phenomenon (RP) is a vasospastic disorder of the digital
arteries. Severe forms are found in patients with connective tissue diseases.
Vasospasmolytic therapies are often limited by side effects such as orthostatic
hypotension. PATIENTS/METHODS: We investigated therefore the effect of
acupuncture in a double blind, placebo-controlled, randomized trial in patients
with secondary RP. The study was performed during the winter season by licensed
acupuncturists weekly for 8 weeks (points chosen for the verum group: L.I.4,
S.J.5, St.36, P.6, Du.20, Ex.28). RESULTS: An improvement was detected in both
groups but there was no significant effect on clinical symptoms - based on
patient diaries (average number of attacks before and after treatment: verum 1.9 
+/- 2.0 vs. 1.4 +/- 1.7 attacks/ day and placebo 2.8 +/- 1.8 vs. 1.9 +/- 1.1;
duration of attacks: verum 15 +/- 12 vs. 12 +/- 9 min. and placebo 31 +/- 17 vs. 
16 +/- 6; n.s.) or on skin microcirculation, measured by local cold testing.
CONCLUSIONS: A specific vasospasmolytic effect of acupuncture could not be
proven. This may be due to minor morphologic changes of supplying arteries or a
severe local defect in endothelial function rather than a neurological
disturbance which might be influenced by acupuncture. Much larger studies would
be needed to identify the possible small benefit from acupuncture. If long-term
relief is not obtained, it is unlikely to be cost-effective.

Publication Types: 
    Randomized Controlled Trial

PMID: 16279219 [PubMed - indexed for MEDLINE]

110: Circulation. 2005 Nov 8;112(19):2980-5.

Comment in:
    Circulation. 2005 Nov 8;112(19):2894-5.

Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory
therapy.

Fries R, Shariat K, von Wilmowsky H, Böhm M.

Klinik für Innere Medizin III (Kardiologie, Angiologie, Internistische
Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
r.fries@gotthard-schettler-klinik.de

BACKGROUND: Vasodilatory therapy of Raynaud's phenomenon represents a difficult
clinical problem because treatment often remains inefficient and may be not
tolerated because of side effects. METHODS AND RESULTS: To investigate the
effects of sildenafil on symptoms and capillary perfusion in patients with
Raynaud's phenomenon, we performed a double-blinded, placebo-controlled,
fixed-dose, crossover study in 16 patients with symptomatic secondary Raynaud's
phenomenon resistant to vasodilatory therapy. Patients were treated with 50 mg
sildenafil or placebo twice daily for 4 weeks. Symptoms were assessed by diary
cards including a 10-point Raynaud's Condition Score. Capillary flow velocity was
measured in digital nailfold capillaries by means of a laser Doppler anemometer. 
While taking sildenafil, the mean frequency of Raynaud attacks was significantly 
lower (35+/-14 versus 52+/-18, P=0.0064), the cumulative attack duration was
significantly shorter (581+/-133 versus 1046+/-245 minutes, P=0.0038), and the
mean Raynaud's Condition Score was significantly lower (2.2+/-0.4 versus
3.0+/-0.5, P=0.0386). Capillary blood flow velocity increased in each individual 
patient, and the mean capillary flow velocity of all patients more than
quadrupled after treatment with sildenafil (0.53+/-0.09 versus 0.13+/-0.02 mm/s, 
P=0.0004). Two patients reported side effects leading to discontinuation of the
study drug. CONCLUSIONS: Sildenafil is an effective and well-tolerated treatment 
in patients with Raynaud's phenomenon.

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

PMID: 16275885 [PubMed - indexed for MEDLINE]

111: J Am Acad Dermatol. 2005 Nov;53(5 Suppl 1):S263-5.

Treatment of cutaneous calcinosis in CREST syndrome by extracorporeal shock wave 
lithotripsy.

Sparsa A, Lesaux N, Kessler E, Bonnetblanc JM, Blaise S, Lebrun-Ly V, Colombeau
P, Vidal E, Bédane C.

Department of Dermatology, Dupuytren University Hospital, Limoges, France.
a.sparsa@free.fr

We describe the unusual case of a 78-year-old woman consulting for extensive and 
painful wound leg ulcerations and calcifications secondary to CREST syndrome that
was treated by extracorporeal shock wave lithotripsy. This treatment was
considered because of the severity of our patient's symptoms and her failure to
respond to various medical and surgical treatment.

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

PMID: 16227105 [PubMed - indexed for MEDLINE]

112: Curr Opin Rheumatol. 2005 Nov;17(6):752-60.

Understanding, assessing and treating Raynaud's phenomenon.

Boin F, Wigley FM.

Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore,
Maryland 21224, USA.

PURPOSE OF REVIEW: New insights in the pathophysiology and molecular mechanisms
implicated in cutaneous vasomotor response to cooling are emerging from recent
literature. These advances are introducing significant changes in the management 
of Raynaud's phenomenon. In this review, we outline how these new findings are
leading to novel methods of assessment and new opportunities for specific
targeted therapy. RECENT FINDINGS: New potential targets for treatment of
Raynaud's phenomenon derive from experimental observations. Increased protein
tyrosine kinase activity and tyrosine phosphorylation have been described in
vascular smooth muscle cells in response to cooling and are linked to excessive
alpha2-adrenergic response. Activation of Rho/Rho kinase pathway is triggered by 
increase of reactive oxygen species and up-regulates alpha2c-adrenergic receptors
on the surface of vascular smooth muscle cells, thus determining an excessive
vasoconstrictive response to cooling. This observation generated pilot trials
testing rho-kinase inhibitors and alpha2c-adrenergic receptors antagonists in
vasospastic conditions with encouraging results. Therapies already in use for
pulmonary hypertension are also showing an effect in Raynaud's phenomenon.
Studies evaluating anti-endothelin-1 (bosentan), phosphodiesterases inhibitors
(sildenafil), and prostanoids (given for critical digital ischemia) in the
treatment of Raynaud's phenomenon all determined improvement of symptoms and/or
digital ischemic lesions. Novel techniques for better visualization and
quantification of cutaneous microvascular defects are under development. The hope
is that these new tools will allow earlier discrimination between primary and
secondary Raynaud's phenomenon as well as a better way to predict outcome and
response to therapy. SUMMARY: Remarkable progress towards a rational approach to 
the management and treatment of Raynaud's phenomenon is emerging.

Publication Types: 
    Review

PMID: 16224254 [PubMed - indexed for MEDLINE]

113: Clin Rheumatol. 2006 May;25(3):325-8. Epub 2005 Oct 12.

Incidence and clinical correlation of anticentromere antibody in Thai patients.

Pakunpanya K, Verasertniyom O, Vanichapuntu M, Pisitkun P, Totemchokchyakarn K,
Nantiruj K, Janwityanujit S.

Division of Allergy, Immunology and Rheumatology, Faculty of Medicine,
Ramathibodi Hospital, Rama 6 Road, Bangkok 10400, Thailand. rasjw@mahidol.ac.th

Anticentromere antibodies (ACA) are useful in assessing and classifying patients 
with mild variant of systemic sclerosis called calcinosis, Raynaud's phenomenon, 
esophageal dysmotility, sclerodactyly, telangiectasias (CREST) syndrome. From
their prognostic significance, we are interested in the prevalence and disease
correlation in Thai patients. A total of 3,233 serum samples of patients with any
musculoskeletal symptoms were sent for antinuclear antibody determination at
Ramathibodi Immunology Laboratory Service between the years 1998 and 2001. Forty 
sera (1.23%) were ACA positive. These sera were from 27 patients with autoimmune 
diseases and 13 with nonautoimmune diseases. Among autoimmune group, scleroderma 
was the most common diagnosis (33.3%) with limited sclerosis being the most
frequent variant. The percentages of autoimmune disease were almost the same
among the low-titer (1:40) and the high-titer (1:640) groups. The study suggests 
that the prevalence of ACA in Thai patients is low. The presence of ACA detected 
in patients with vague musculoskeletal symptoms does not suggest a diagnosis of
CREST syndrome. Even high-titer ACA can be found in nonautoimmune diseases.

PMID: 16220222 [PubMed - indexed for MEDLINE]

114: Arthritis Res Ther. 2005;7(5):R1103-12. Epub 2005 Jul 19.

Local hyperemia to heating is impaired in secondary Raynaud's phenomenon.

Boignard A, Salvat-Melis M, Carpentier PH, Minson CT, Grange L, Duc C,
Sarrot-Reynauld F, Cracowski JL.

Laboratory HP2, EA 3745 Inserm ESPRI, Grenoble Medical School, France.

Accurate and sensitive measurement techniques are a key issue in the
quantification of the microvascular and endothelial dysfunction in systemic
sclerosis (SSc). Thermal hyperemia comprises two separate mechanisms: an initial 
peak that is axon reflex mediated; and a sustained plateau phase that is nitric
oxide dependent. The main objective of our study was to test whether thermal
hyperemia in patients with SSc differed from that in patients with primary
Raynaud's phenomenon (RP) and healthy controls. In a first study, we enrolled 20 
patients suffering from SSc, 20 patients with primary RP and 20 healthy
volunteers. All subjects were in a fasting state. Post-occlusive hyperemia, 0.4
mg sublingual nitroglycerin challenge and thermal hyperemia were performed using 
laser Doppler flowmetry on the distal pad of the third left finger. In a second
study, thermal hyperemia was performed in 10 patients with rheumatoid arthritis
and 10 patients with primary RP. The thermal hyperemia was dramatically altered
in terms of amplitude and kinetics in patients with SSc. Whereas 19 healthy
volunteers and 18 patients with primary RP exhibited the classic response,
including an initial peak within the first 10 minutes followed by a nadir and a
second peak, this occurred only in four of the SSc patients (p < 0.0001). The 10 
minutes thermal peak was 43.4 (23.2 to 63), 42.6 (31 to 80.7) and 27 (14.7 to
51.4) mV/mm Hg in the healthy volunteers, primary RP and SSc groups, respectively
(p = 0.01), while the 44 degrees C thermal peak was 43.1 (21.3 to 62.1), 42.6
(31.6 to 74.3) and 25.4 (15 to 52.4) mV/mm Hg, respectively (p = 0.01). Thermal
hyperemia was more sensitive and specific than post-occlusive hyperhemia for
differentiating SSc from primary RP. In patients with rheumatoid arthritis,
thermal hyperemia was also altered in terms of amplitude. Thermal hyperemia is
dramatically altered in patients with secondary RP in comparison with subjects
with primary RP. Further studies are required to determine the mechanisms of this
altered response, and whether it may provide additional information in a clinical
setting.

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

PMID: 16207327 [PubMed - indexed for MEDLINE]

115: J Eur Acad Dermatol Venereol. 2005 Sep;19(5):617-20.

Scleroderma with type III glomerulonephritis and MPO-ANCA antibodies in the
serum.

Herrera-Esparza R, Aguilar JL, Saucedo A, González I, López-Robles E, Avalos-Díaz
E.

Department of Immunology, Centro de Biología Experimental, Universidad Autónoma
de Zacatecas, and Department of Internal Medicine, HGZ1 IMSS, Zacatecas, México. 
herreraavalos@prodigy.net.mx

Scleroderma is an autoimmune disease characterized by early inflammatory
infiltrates followed by fibrosis in the skin and internal organs. CREST is a
relatively benign cutaneous variant of scleroderma that features calcinosis,
Raynaud's phenomenon, oesophageal dysfunction, sclerodactyly and telangiectases. 
Glomerulonephritis is a rare association of CREST. We are reporting a patient
with CREST who developed glomerulonephritis and had anticentromere and
antineutrophil cytoplasmic autoantibodies (ANCA) in her serum.

Publication Types: 
    Case Reports

PMID: 16164722 [PubMed - indexed for MEDLINE]

116: Int Surg. 2005 Apr-Jun;90(2):88-92.

Microsurgical distal sympathectomy in chronic vasospastic syndromes of the hand.

Ortensi A, Salsano F, Trinchi S, D'orazi V, Pisarri S.

Microsurgery Unit, Department of Surgical Sciences, and Department of Clinical
Medicine, Immunology and Allergology, University of Rome, La Sapienza, Italy.

The authors propose a microsurgical technique to treat upper limb chronic digital
ischemia that is resistant to medical therapy. The adventitiectomy technique on
digital arteries is used here to remove the fibrous tissue and the
vasoconstrictor sympathetic nervous fibers contained in it. This operation is a
valid alternative to traditional proximal sympathectomy.

PMID: 16119712 [PubMed - indexed for MEDLINE]

117: Rheum Dis Clin North Am. 2005 Aug;31(3):465-81, vi.

Raynaud's phenomenon in mixed connective tissue disease.

Grader-Beck T, Wigley FM.

Division of Rheumatology, Johns Hopkins School of Medicine, 5200 Eastern Avenue, 
Suite 4100, Baltimore, MD 21224, USA.

Raynaud's phenomenon affects most patients who have mixed connective tissue
disease (MCTD) and frequently represents the initial manifestation of the
disease. It is the cutaneous symptom of a systemic vasculopathy that is
characterized by intimal fibrosis and blood vessel obliteration that frequently
leads to visceral involvement, particularly pulmonary hypertension. An
association between Raynaud's phenomenon and the characteristic autoantibody in
MCTD, anti-U1-RNP (ribonucleoprotein), is found across the spectrum of rheumatic 
diseases, including undifferentiated connective tissue disease, scleroderma, and 
systemic lupus erythematosus. Capillary nailfold examination represents a
valuable tool to identify patients who are at risk for MCTD. The goal in the
therapy of Raynaud's phenomenon in MCTD is to decrease the frequency of attacks, 
to prevent digital ulceration, and to limit progressive vascular damage.
Therapeutic regimens include the traditional use of calcium channel blockers and 
novel vascular therapies.

Publication Types: 
    Review

PMID: 16084319 [PubMed - indexed for MEDLINE]

118: Am J Nurs. 2005 Aug;105(8):56-65; quiz 65-6.

Raynaud phenomenon.

Reilly A, Snyder B.

Union Carbide Corporation, a subsidiary of the Dow Chemical Company, Piscataway, 
NJ, USA. reillyam@dow.com

Raynaud phenomenon, a vascular disorder triggered by cold or emotional stress,
results from an exaggerated vasoconstriction and vasospasm of the digital
arteries and arterioles. The fingers, and, less often, the toes, are affected;
ear lobes, lips, nose, and nipples may also be involved. This article describes
the difference between primary and secondary Raynaud phenomenon and reviews
etiology, diagnosis, prevention, and management of symptoms.

Publication Types: 
    Review

PMID: 16062060 [PubMed - indexed for MEDLINE]

119: Vasa. 2005 May;34(2):93-100.

Microcirculatory and clinical effects of serial percutaneous application of
carbon dioxide in primary and secondary Raynaud's phenomenon.

Schmidt J, Monnet P, Normand B, Fabry R.

Thérapeutique, Faculté de Medecine, Clermont-Ferrand, France.

BACKGROUND: A randomized double-blind monocentric trial was conducted at the spa 
of Royat, France, in patients with mild Raynaud's phenomenon (one or two attacks 
a day during the autumn and winter months). Hemodynamic changes were quantified
by laser Doppler flow (LDF) and computerized chronothermometric test (CT) during 
local application of CO2 and compared with the usual clinical parameters.
PATIENTS AND METHODS: Patients were randomized to 18 days of CO2 (group 1) or 9
days of air + 9 days of CO2 (group 2). The gas was applied at a constant
temperature to previously humidified skin on the forearm. Effects of the active
treatment were measured by LDF and continuing benefits by computerized
chronothermometric test (CT test). Clinical assessment was made on four occasions
(before, in the middle and at the end of treatment, and three months afterwards) 
on the basis of the number of daily attacks and the duration and severity of the 
attacks. RESULTS: LDF showed a significant increase in digital blood flow (+ 41%)
and in vasomotion (+ 42%) during CO2 treatment but no change on placebo
treatment. CT test showed a comparable response to cold in the two groups during 
treatment. Three months later, however, warming time was significantly decreased 
(by 7 minutes: 25%) and warming rate increased (+ 22.4%) in group 1 (intergroup
difference: p = 0.02). There was no difference between groups in the weekly
number of attacks during treatment periods. In contrast there was a moderate
increase in both groups in the winter months. There was no increase in the
severity of the attacks nor in their duration. CONCLUSION: In this clinical
trial, LDF evidenced positive effects of percutaneous application of natural CO2 
gas on vasomotricity and vasomotion while CT test showed that patients who had
received 18 days of CO2 adapted more easily to exposure to cold. Clinical
improvement seems to be masked by winter weather conditions.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15968890 [PubMed - indexed for MEDLINE]

120: Clin Rheumatol. 2006 Mar;25(2):153-8. Epub 2005 Jun 11.

Predictive value of nailfold capillaroscopy in patients with Raynaud's
phenomenon.

Meli M, Gitzelmann G, Koppensteiner R, Amann-Vesti BR.

Division of Angiology, Department of Internal Medicine, University Hospital,
Ramistrasse 100, 8091 Zurich, Switzerland.

The objective of this study was to evaluate the long-term follow-up of patients
with Raynaud's phenomenon (RP) and pathological nailfold capillaroscopy (NC) in
order to analyse the predictive value of specific features of capillaroscopy for 
the development of a connective tissue disease (CTD). From 1992 to 2002, NC alone
or combined with fluorescence videomicroscopy with sodium fluorescein (NaF) was
performed in 1024 consecutive patients because of RP. We analysed the follow-up
and pathological features of NC in all patients who had neither clinical nor
serological signs of a CTD at the time of NC. Of 308 patients with neither
serological findings nor clinical signs of CTD but with RP and pathological
features in NC suspicious for CTD, follow-up data were available for 133
patients. An additional NaF test had been performed in 51 (38.4%) patients. After
a mean follow-up of 6.5 years (range: 1-15 years), 109 patients had developed a
CTD and 24 patients did not show any clinical signs or serological markers for a 
CTD after a mean follow-up of 8.5 years (range: 2-15 years). There were no
differences in age, duration of RP or of follow-up in patients who developed a
CTD compared to patients who did not. Significantly more giant capillaries
(p=0.0001), avascular fields (p=0.02) and irregular architecture (p=0.0001) had
been observed in patients who had developed a CTD during the follow-up of 6.5
years. The presence of giant capillaries, avascular fields and irregular
architecture of nailfold capillaries is predictive for the development of a CTD
in patients with RP.

PMID: 15951918 [PubMed - indexed for MEDLINE]

121: Best Pract Res Clin Rheumatol. 2005 Jun;19(3):437-52.

Capillaroscopy.

Cutolo M, Pizzorni C, Sulli A.

Research Laboratory and Division of Rheumatology, Department of Internal
Medicine, University of Genova, Viale Benedetto XV, 6, 16132 Genova, Italy.
mcutolo@unige.it

Raynaud's phenomenon (RP) is the most common and significant clinical condition
with an indication for a microvascular analysis to be carried out as soon as
possible. Microvascular involvement is a key feature of RP and several rheumatic 
diseases are characterised by the presence of RP. Nailfold capillary microscopy
shows an impressive cost/effectiveness ratio: it is simple, non-invasive and
inexpensive. Well recognised nailfold videocapillaroscopic patterns (NVC) have
been described mainly in systemic sclerosis (SSc) patients with secondary RP. The
peripheral microvascular damage in SSc is characterised by increasing structural 
alterations of the capillaries (giant capillaries and microhaemorrhagies) with a 
progressive decrease in their density. The detection of the scleroderma NVC
pattern allows an early distinction between the primary RP (functional, not
disease associated) and the secondary RP (disease associated). Other major NVC
patterns have been described in the field of rheumatic diseases. Interestingly,
correlations are evident between the NVC and the clinical symptoms, severity of
the disease and the laboratory findings.

Publication Types: 
    Review

PMID: 15939368 [PubMed - indexed for MEDLINE]

122: Clin Rheumatol. 2005 Aug;24(4):365-9. Epub 2005 May 20.

Raynaud's phenomenon in a healthy Turkish population.

Onbaşi K, Sahin I, Onbaşi O, Ustün Y, Koca D.

Department of Internal Medicine, Yüzüncü Yil University School of Medicine, Van, 
Turkey. kevseronbasi@yahoo.com

Raynaud's phenomenon (RP) is a vasospastic disease and is characterized by
ischemia of the digits, nose, and ears. The vasospasm can be triggered by cold
weather, cold water, or emotional stress and is followed by triphasic color
changes. First white color (ischemia), then blue color (congestion and cyanosis),
and finally red color change (reactive hyperemia) can be observed. The prevalence
is reported to be between 0.5 and 20% in different studies and is dependent on
genetic, occupational, and environmental factors. The purpose of our study was to
determine the prevalence of RP in an eastern part of Turkey among healthy
subjects. A total of 768 people were included in the study. This cross-sectional 
study was conducted between April 2003 and October 2003 at the University
Hospital and at the State Hospital in Van, Turkey. The participants were
interviewed and examined to diagnose RP and a questionnaire and color charts were
used. Of these 768 patients, 25 women and 20 men were diagnosed to have RP. A
female predominance (25/20) was observed. Their mean age was 24.78 +/- 5.71
years. The prevalence of RP was 5.9% in our study population.

Publication Types: 
    Comparative Study

PMID: 15906111 [PubMed - indexed for MEDLINE]

123: Microvasc Res. 2005 May;69(3):178-9.

Use of tadalafil in a patient with a secondary Raynaud's phenomenon not
responding to sildenafil.

Baumhaekel M, Scheffler P, Boehm M.

Department of Cardiology and Angiology, University Hospital of the Saarland,
Kirrbergerstr., 66421 Homburg/Saar, Germany. magnus@baumhaekel.de

The Raynaud's phenomenon often accompanies systemic rheumatic diseases and is
also known as a vascular side effect of chemotherapy. Therapy of the Raynaud's
phenomenon with nitrates or calcium-channel-blockers is rarely beneficial. In
contrast, the PDE-V-inhibitor sildenafil seems to be effective in these patients.
For the first time we report on a patient with Raynaud's phenomenon due to
chemotherapy not responding to sildenafil but to the new PDE-V-inhibitor
tadalafil in an equivalent dosage. Measurement with a laser Doppler revealed an
increased blood flow and a reduction of symptoms. Therefore, therapy of Raynaud's
phenomenon with the new PDE-V-inhibitor tadalafil seems to be an effective
treatment option in patients not responding to sildenafil.

Publication Types: 
    Case Reports

PMID: 15896360 [PubMed - indexed for MEDLINE]

124: J Rheumatol. 2005 May;32(5):841-8.

Computerized nailfold video capillaroscopy--a new tool for assessment of
Raynaud's phenomenon.

Anderson ME, Allen PD, Moore T, Hillier V, Taylor CJ, Herrick AL.

University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford, UK.

OBJECTIVE: To develop a computer based nailfold video capillaroscopy system with 
enhanced image quality and to assess its disease-subgroup resolving power in
patients with primary and secondary Raynaud's phenomenon (RP). METHODS: Using
frame registration software, digitized video images from the microscope were
combined to form a panoramic mosaic of the nailfold. Capillary dimensions (apex, 
arterial, venous, and total width) and density were measured onscreen.
Significantly, the new system could guarantee analysis of the same set of
capillaries by 2 observers. Forty-eight healthy control subjects, 21 patients
with primary RP, 40 patients with limited cutaneous systemic sclerosis (lcSSc),
and 11 patients with diffuse cutaneous SSc (dcSSc) were studied. Intra- and
interobserver variability were calculated in a subset of 30 subjects. RESULTS:
The number of loops/mm was significantly lower, and all 4 capillary dimensions
significantly greater, in SSc patients versus controls plus primary RP patients
(p < 0.001 for all measures). When comparing control (+ primary RP) patients with
SSc patients (lcSSc + dcSSc) the most powerful discriminator was found to be the 
number of loops/mm. Results for intra- and interobserver reproducibility showed
that the limits of agreement were closer when both observers measured the same
capillaries. CONCLUSION: The key feature of the newly developed system is that it
improves reproducibility of nailfold capillary measurements by allowing
reidentification of the same capillaries by different observers. By allowing
access to previous measurements, the new system should improve reliability in
longitudinal studies, and therefore has the potential of being a valuable outcome
measure of microvessel disease/involvement in clinical trials of scleroderma
spectrum disorders.

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

PMID: 15868619 [PubMed - indexed for MEDLINE]

125: Int Arch Occup Environ Health. 2005 Apr;78(3):218-22. Epub 2005 Mar 15.

Thermoregulation and rheological properties of blood in primary Raynaud's
phenomenon and the vibration-induced white-finger syndrome.

Ziegler S, Zöch C, Gschwandtner M, Eckhardt G, Windberger U, Minar E, Rüdiger H, 
Osterode W.

Division of Angiology, Clinic for Internal Medicine II, University Medical School
of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
sophie.ziegler@meduniwien.ac.at

OBJECTIVE: Frequent use of vibrating tools may lead to typical attacks of
Raynaud's phenomenon (RP). The present study assesses the feasibility of the use 
of thermographic measurements of blood rheometry in the diagnosis of
vibration-induced white-finger (VWF) syndrome. SUBJECTS AND METHODS: We studied
38 patients that were suffering from RP (primary RP, n=29; VWF, n=9) and 13
controls (six men and 45 women; mean age 49.1+/-11.6 years). Superficial finger
skin blood flow was assessed with an infrared thermocamera before and after
exposure to heat and cold. Fibrinogen, whole-blood viscosity and erythrocyte
aggregation at different shear rates and plasma viscosity were measured. MAIN
RESULTS: In patients with RP finger temperatures after re-warming were lower than
those in controls [right hand digit (DIG) I P<0.02; DIG II-V P<0.01; left hand
DIG I P<0.01; DIG II-V p<0.02], male patients with primary RP had higher
Fg-values (P<0.02) and a trend to higher plasma viscosity. Patients with VWF had 
a trend to lower plasma viscosity than controls. Whole-blood viscosity at each
shear rate was highest in patients with VWF. CONCLUSION: Provocation manoeuvres
are essential in the diagnosis of RP. We speculate that the decreased plasma
viscosity in VWF is a compensatory physiological mechanism, probably
counteracting the chronic effects of vasospasm. The rise in whole-blood viscosity
could be due to endothelial injury or to a reduction in the venous blood pH
level. The abnormal cold reactivity of patients with RP may be partly related to 
rheological factors.

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

PMID: 15838713 [PubMed - indexed for MEDLINE]

126: Arthritis Rheum. 2005 Apr;52(4):1259-63.

The incidence and natural history of Raynaud's phenomenon in the community.

Suter LG, Murabito JM, Felson DT, Fraenkel L.

Yale University School of Medicine, New Haven, Connecticut 06520-8088, USA.
lisa.suter@yale.edu

OBJECTIVE: Raynaud's phenomenon (RP) is a common disorder, yet its incidence and 
natural history are unknown. Our objective was to determine the incidence and
natural history of RP not associated with a connective tissue disease in a large,
community-based population. METHODS: Using serial examinations of the Framingham 
Heart Study offspring cohort, we collected data regarding RP symptoms for 717
women and 641 men over a 7-year period. We used validated criteria for RP
classification and categorized participants as having incident, persistent, or
remitted RP. We performed sex-specific analyses of RP status by age, body mass
index, vibratory tool use, season of examination, state of residence, use of
antihypertensive medications, and smoking status. RESULTS: The mean +/- SD age of
participants was 53.5 +/- 10 years. The incidence of RP was 2.2% in women (n =
14) and 1.5% in men (n = 9). Of the 78 women and 50 men who had RP at baseline,
36% of women (n = 28) and 36% of men (n = 18) had persistent RP. RP remitted in
64% of women (n = 50) and 64% of men (n = 32), with 41 women and 25 men meeting
no or only 1 RP criterion at followup. RP episodes were infrequent and rarely
interfered with daily activities. CONCLUSION: This is the first prospective study
to determine the incidence and natural history of RP in a community-based cohort.
Our data demonstrate that RP not associated with a connective tissue disease is
frequently a transient phenomenon and rarely interferes with daily activities.

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

PMID: 15818710 [PubMed - indexed for MEDLINE]

127: J Rheumatol. 2005 Apr;32(4):656-64.

Effect of granulocyte macrophage-colony stimulating factor on extracellular
matrix deposition by dermal fibroblasts from patients with scleroderma.

Postiglione L, Ladogana P, Montagnani S, di Spigna G, Castaldo C, Turano M, Bruno
EM, Di Meglio F, Riccio A, Rossi G.

Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli
Studi Federico II, Naples, Italy. lorposti@unima.it

OBJECTIVE:. To investigate the in vitro effect of granulocyte macrophage-colony
stimulating factor (GM-CSF) on the deposition of extracellular matrix (ECM) in
fibroblasts obtained from the skin of patients with systemic sclerosis (Ssc),
compared to healthy controls. METHODS: Dermal fibroblasts obtained from 14
patients with SSc (7 with the diffuse form and 7 with CREST syndrome) and from 7 
controls were studied. Both SSc and normal skin fibroblast cultures were
stimulated for 4 and 8 days with 100 ng/ml GM-CFS. GM-CSF receptor (GM-CSFR)
expression was determined by Western blot of cell lysates. Immunofluorescence was
used to determine GM-CSFR expression and to investigate the deposition of ECM
(type I collagen, fibronectin, and tenascin). Quantitative analysis of ECM was
performed by ELISA. Expression of type I collagen and metalloproteinase 1 (MMP-1)
mRNA was determined by real-time quantitative PCR. RESULTS: Deposition of ECM by 
normal fibroblasts appeared not to be influenced by stimulation with GM-CSF; in
contrast, after stimulation with GM-CSF SSc fibroblasts showed increased
deposition of fibronectin and tenascin, while type I collagen production was
decreased; these results were found with both immunofluorescence and ELISA.
Quantitative PCR revealed that GM-CSF inhibited the expression of mRNA type I
collagen in SSc fibroblasts but not in normal fibroblasts, whereas levels of the 
main collagenolytic enzyme, MMP-1, were not affected. CONCLUSION: These results
suggest that in SSc fibroblasts GM-CSF exerts a blocking effect on the deposition
of type I collagen, through an inhibitory action on mRNA, while the production of
other components of ECM such as fibronectin and tenascin is increased by
stimulation with this cytokine.

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

PMID: 15801021 [PubMed - indexed for MEDLINE]

128: Acta Anaesthesiol Scand. 2005 Apr;49(4):576-8.

Unilateral recurrent laryngeal nerve neuropraxia following placement of a ProSeal
laryngeal mask airway in a patient with CREST syndrome.

Kawauchi Y, Nakazawa K, Ishibashi S, Kaneko Y, Ishikawa S, Makita K.

Department of Anesthesiology and Critical Care Medicine, Tokyo Medical and Dental
University, Tokyo, Japan. kajunyakko@yahoo.co.jp

We report a severe unilateral recurrent laryngeal nerve neuropraxia following use
of the ProSeal laryngeal mask airway (PLMA) in a 71-year-old female patient with 
CREST syndrome. She required amputation of the 5th phalanx of foot because of
gangrene due to Raynaud's syndrome. Anesthesia was induced with propofol, and a
size 3 PLMA was inserted. Anesthesia was maintained with sevoflurane and nitrous 
oxide for 2 h and the operation was performed uneventfully. On removal of PLMA,
the cuff volume was measured to 40 ml. The patient did not complain of
respiratory discomfort shortly after PLMA removal. However, the next day she
developed dysphagia and hoarseness. Laryngoscopic examination revealed unilateral
vocal cord paralysis. Cricothyrotomy was required because of suspected silent
aspiration pneumonia. The pharyngolaryngeal complications improved with a mobile 
vocal cord but slight hoarseness after 2 months. We considered the patient's
CREST syndrome with a potential of tissue ischemia, and the high intracuff
pressure of the PLMA due to nitrous oxide influx, to be the cause of severe
recurrent laryngeal nerve neuropraxia in this case.

Publication Types: 
    Case Reports

PMID: 15777310 [PubMed - indexed for MEDLINE]

129: Clin Sci (Lond). 2005 Jul;109(1):45-54.

Contribution of prostanoids to endothelium-dependent vasodilatation in the
digital circulation of women with primary Raynaud's disease.

Easter MJ, Marshall JM.

Department of Physiology, The Medical School, University of Birmingham, Vincent
Drive, Edgbaston, Birmingham B15 2TT, UK.

In 15 women with PR (primary Raynaud's) disease and in 15 matched control women, 
ACh (acetylcholine) was delivered by iontophoresis to the dorsum of the finger
(seven 20 s pulses of 0.1 mA, followed by one 20 s pulse of 0.2 mA, applied at 60
s intervals). Cutaneous RCF (red cell flux) was recorded from the same site by
the laser Doppler technique. ACh evoked progressive increases in RCF that were
comparable in pre- and post-menopausal women with PR [maxima of 294+/-113 and
259+/-59 pu (perfusion units) respectively, n = 7 and 8 respectively], and in
pre-menopausal controls (225+/-92 pu, n = 7), but smaller in post-menopausal
controls (140+/-63 pu, n = 8; P < 0.05). Aspirin (600 mg, orally), a COX
(cyclo-oxygenase) inhibitor, potentiated the ACh-evoked dilator responses in pre-
and post-menopausal women with PR (343+/-129 and 311+/-48 pu respectively) and
post-menopausal controls (277+/-124 pu; P < 0.05), but had no effect in
pre-menopausal controls (225+/-92 pu). These results suggest that vasoconstrictor
COX products limit ACh-evoked endothelium-dependent cutaneous dilatation in the
digits in pre- and post-menopausal women with PR and in post-menopausal, but not 
pre-menopausal, control women. We propose that PR disease is associated with
abnormality in the ability of oestrogen to modulate the synthesis of
endothelium-dependent vasodilator and/or vasoconstrictor COX products.

PMID: 15769250 [PubMed - indexed for MEDLINE]

130: Mayo Clin Proc. 2005 Mar;80(3):416-8.

Axillary vein thrombosis as a manifestation of rapidly progressive neuropathic
arthropathy of the shoulder associated with syringomyelia.

Tristano AG, Willson ML, Montes de Oca I.

Department of Internal Medicine, Hospital Dr. Domingo Luciani, Caracas,
Venezuela. mjtristano@cantv.net

Neuropathic arthropathy is a destructive joint disease associated frequently with
loss of proprioception. Syringomyelia (with or without Arnold-Chiari
malformation) is characterized by slow progression over many years; the joints
involved most frequently are the shoulders and elbows. Neuropathic arthropathy of
the hand is rare, and clinical features are vasomotor problems, digital ulcers,
thickening of the fingers, and painless subluxation of the finger joints. We
report an unusual case of neuropathic arthropathy of the shoulder and hands,
associated with syringomyelia without Arnold-Chiari malformation. Neuropathic
arthropathy of the shoulder was rapidly progressive, and axillary vein thrombosis
was the first manifestation; however, neuropathic arthropathy of the hands was
unrecognized for 7 years, and painless ulceration of the fingers with spontaneous
amputation of the terminal phalanx and Raynaud phenomenon were the initial
manifestations. To our knowledge, this is the first report of a patient with this
constellation of findings.

Publication Types: 
    Case Reports

PMID: 15757024 [PubMed - indexed for MEDLINE]

131: Nurs Times. 2005 Feb 22-28;101(8):30-1.

Raising awareness of Raynaud's phenomenon and scleroderma.

Mawdsley AH, Brown SJ.

Raynaud's and Scleroderma Association, Alsager, Cheshire.

The 2005 Raynaud's and scleroderma awareness campaign aims to highlight Raynaud's
phenomenon, a common episodic circulatory disorder in which the small blood
vessels in the extremities are oversensitive to changes in temperature. For a
small number of people, Raynaud's is one of the earliest symptoms of scleroderma,
so people with Raynaud's require prompt assessment and diagnosis.

PMID: 15754937 [PubMed - indexed for MEDLINE]

132: Lupus. 2005;14(2):113-9.

Impact of external quality assessment on antinuclear antibody detection
performance.

Pham BN, Albarede S, Guyard A, Burg E, Maisonneuve P.

Service d'Hématologie et Immunologie, Hôpital Beaujon, France.
bn.pham@bjn.ap-hop-paris.fr

Our objective was to evaluate performance of the clinical laboratories for the
detection of antinuclear antibodies (ANA) by using indirect immunofluorescence
method (IIF), in France. A national external quality assessment (EQA) on ANA
detection was organized by the French health products safety agency once a year
since 1998. Between 606 to 687 laboratories together with six university
reference laboratories experienced in performing tests in autoimmunity
participated in the six-year consecutive survey. Each laboratory had to answer to
methodological procedures and give coded responses. Variability in IIF
methodological procedure was observed. Use of inappropriate microscope
magnifications for reading slides or nonconventional cutoff dilution of serum
were pointed out to concerned laboratories. Concerning ANA measurement, the rate 
of good responses ranged from 92.7% to 99.5% of the laboratories when the samples
contained ANA. A wide dispersion of ANA titers obtained on a same sample was
repeatly observed every year. Misinterpretation of particular fluorescence
pattern was noticed. On ANA negative sample, the rate of good responses was
94.3%. In conclusion, ANA detection in routine practice is far from being
standardized. However, EQA may have an impact on ANA detection performance when
it is conducted on several consecutive year surveys, by providing advice for
participating laboratories to limit inter laboratory variations related to
methodological procedures.

PMID: 15751815 [PubMed - indexed for MEDLINE]

133: Dermatol Online J. 2005 Mar 1;11(1):28.

Videodermatoscopy: a useful tool for diagnosing cutaneous dystrophic
calcifications.

Strumia R.

A suspected diagnosis of cutaneous calcification is based on the presence of
slightly elevated or ulcerated firm, white papules and plaques; these lesions
often extrude white, chalky material. In clinical practice, however, a biopsy is 
required to confirm clinical suspicions. We attempted to demonstrate cutaneous
calcinosis in vivo by using Raman spectroscopy, a nondestructive analytical
method based on the analysis of light scattered from the investigated material.
We used digital videodermatoscopy to improve the detection of cutaneous
calcifications in vivo in two patients with CREST syndrome. A characteristic
flower-like arrangement was observed at x-50 magnification. We believe this
pattern may be highly indicative of cutaneous dystrophic calcinosis.

Publication Types: 
    Case Reports
    Letter

PMID: 15748569 [PubMed - indexed for MEDLINE]

134: Rheumatology (Oxford). 2005 May;44(5):587-96. Epub 2005 Mar 1.

Pathogenesis of Raynaud's phenomenon.

Herrick AL.

University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford, UK.
aherrick@fs1.ho.man.ac.uk

The pathogenesis of Raynaud's phenomenon is not fully understood. However, the
last 20 yr have witnessed enormous increases in our understanding of different
mechanisms which, singly or in combination, may contribute. A key point is that
Raynaud's phenomenon can be either primary (idiopathic) or secondary to a number 
of underlying conditions, and that the pathogenesis and pathophysiology vary
between these conditions. This review concentrates upon those subtypes of
Raynaud's phenomenon of most interest to rheumatologists: systemic
sclerosis-related Raynaud's phenomenon, primary Raynaud's phenomenon and
Raynaud's phenomenon secondary to hand-arm vibration syndrome. In this review, I 
shall discuss the main mechanisms thought to be important in pathophysiology
under the three broad headings of 'vascular', 'neural' and 'intravascular'. While
these are false distinctions because all interrelate, they facilitate discussion 
of the key elements: the blood vessel wall (particularly the endothelium), the
neural control of vascular tone, and the many circulating factors which can
impair blood flow and/or cause endothelial injury. Vascular abnormalities include
those of both structure and function. Neural abnormalities include deficiency of 
the vasodilator calcitonin gene-related peptide (released from sensory
afferents), alpha(2)-adrenoreceptor activation (possibly with up-regulation of
the normally 'silent' alpha(2C)-adrenoreceptor) and a central nervous system
component. Intravascular abnormalities include platelet activation, impaired
fibrinolysis, increased viscosity and probably oxidant stress. As our
understanding of the pathophysiology of Raynaud's phenomenon increases, so do our
possibilities for identifying effective treatments.

Publication Types: 
    Review

PMID: 15741200 [PubMed - indexed for MEDLINE]

135: Nuklearmedizin. 2005 Feb;44(1):29-32.

Microcirculation of the fingers in Raynaud's syndrome: (99m)Tc-DTPA imaging.

Csiki Z, Garai I, Varga J, Szücs G, Galajda Z, András C, Zeher M, Galuska L.

3th Department of Internal Medicine University of Debrecen Medical and Health
Science Center, Móricz Zs. krt. 22, 4004 Debrecen, Hungary. csiki@iiibel.dote.hu

AIM: We investigated the circulatory characteristics of patients suffering of
primary and secondary Raynaud's syndrome. PATIENTS, METHODS: We examined 106
patients presenting with the classical symptoms of Raynaud's syndrom (47 primary,
59 secondary) by hand perfusion scintigraphy developed by our Department of
Nuclear Medicine. After visual evaluation we analyzed the images
semiquantitatively, using the finger to palm ratio. We statistically compared the
patients with primary and those with secondary Raynaud's syndrome. RESULTS: By
visual evaluation we constated regional perfusion disturbances in 42 from 59
patients with secondary Raynaud's syndrome. However, this was observed in only 3 
from 47 patients with the primary form of this disease. This difference was
statistically significant (p<0.001). Semiquantitative analysis showed that the
finger/palm ratios (FPR) were significantly lower (p<0.05) for the patients with 
primary Raynaud's syndrome. No differences in the FPR values concerning sex or
right and left side. CONCLUSION: The hand perfusion scintigraphy with
(99m)Tc-DTPA is a noninvasive, cost effective diagnostic tool, which objectively 
reflects the global and regional microcirculatory abnormalities of the hands, and
provides quantitative data for follow-up.

PMID: 15711726 [PubMed - indexed for MEDLINE]

136: Rheumatology (Oxford). 2005 Apr;44(4):488-94. Epub 2005 Feb 3.

Cooling-induced contraction and protein tyrosine kinase activity of isolated
arterioles in secondary Raynaud's phenomenon.

Furspan PB, Chatterjee S, Mayes MD, Freedman RR.

Department of Psychiatry and Behavioral Neurosciences, Wayne State University,
Detroit, MI 48201, USA. aa1985@wayne.edu

OBJECTIVE: To investigate the response of skin arterioles from control subjects
and patients with scleroderma and Raynaud's phenomenon (RP/SSc) to cooling and
modulators of protein tyrosine kinase (PTK) activity. METHODS: We used the
microvessel perfusion technique to characterize the response of isolated dermal
arterioles (100-200 microm, outside diameter) from normal (n = 17) and RP/SSc (n 
= 17) subjects to cooling from 37 degrees to 31 degrees C. Fluorescent
immunohistochemistry was used to measure tyrosine phosphorylation. RESULTS:
Arterioles from control subjects exhibited dilation in response to cooling from
37 to 31 degrees C whereas those from RP/SSc subjects contracted (+4.3 +/- 1.7 vs
-16.7 +/- 3.1%, P < 0.05, n = 6). In the presence of the protein tyrosine
phosphatase inhibitor sodium orthovanadate (SOV, 10 microM), the response of
arterioles from control subjects did not change; however, arterioles from RP/SSC 
subjects exhibited a significantly greater contraction (-72.6 +/- 19.7%; P <
0.05, n = 6). Tyrosine phosphorylation of arterioles at 37 degrees C from control
and RP/SSc subjects was similar. In response to cooling to 31 degrees C, however,
arterioles from RP/SSc subjects exhibited a significantly greater increase in
tyrosine phosphorylation compared with those from control subjects (43 +/- 7.0%
vs 10 +/- 3.8%; P < 0.01). SOV increased tyrosine phosphorylation in arterioles
from both groups (73 +/- 11.6% vs 42 +/- 5.6%; P < 0.05, n = 5). Arterioles from 
RP/SSC subjects precontracted with norepinephrine exhibited greatly attenuated
relaxation to acetylcholine compared with those from control subjects.
CONCLUSION: The results of this study support the view that the hallmark of
Raynaud's phenomenon associated with scleroderma, cooling-induced vasospasm,
appears to be mediated by an increase in PTK activity possibly exacerbated by
impaired endothelium-dependent vasodilation.

Publication Types: 
    In Vitro
    Research Support, U.S. Gov't, P.H.S.

PMID: 15695304 [PubMed - indexed for MEDLINE]

137: Rheum Dis Clin North Am. 2005 Feb;31(1):177-86, x-xi.

Estrogens and neuropeptides in Raynaud's phenomenon.

Generini S, Seibold JR, Matucci-Cerinic M.

Division of Medicine I, II, and Rheumatology, Department of Medicine and Surgery,
University of Florence, Villa Monna Tessa, Viale Pieraccini 18, 50139 Florence,
Italy.

Raynaud's phenomenon (RP) is characterized by ischemia and reperfusion of the
extremities. Vasomotor instability is due to a microcirculatory disturbance that 
may be linked to different events involving the endothelium or peripheral nerve
terminals. Endothelium and nerve endings "sense" the modifications of the
microenvironment and both of them release factors that contribute to find a
balance between vasolidation and vasoconstriction. Moreover, estrogens may
contribute to control vascular tone regulating finger skin circulation. A loss of
neuropeptides has been shown in secondary RP where supplementation with factors
derived from nerve endings has been demonstrated to induce a potent vasolidation.
Estrogen administration improved endothelial dysfunction in secondary RP.
Neuropeptides and estrogens thus share the endothelial-dependent pathway, usually
mediated by nitric oxide, in inducing vasolidation. The network directed by the
endothelium is in reality controlled by a neuro-hormonal axis composed by
neuropeptides and estrogens. This delicate balance keeps the vascular tone, and
its dysfunction may lead to a dysregulation of vascular tone, manifest in clinics
as a primary or secondary RP.

Publication Types: 
    Review

PMID: 15639062 [PubMed - indexed for MEDLINE]

138: Appl Ergon. 2005 Jan;36(1):55-60. Epub 2004 Oct 31.

Vascular and nerve damage in workers exposed to vibrating tools. The importance
of objective measurements of exposure time.

Gerhardsson L, Balogh I, Hambert PA, Hjortsberg U, Karlsson JE.

Department of Occupational and Environmental Medicine, Sahlgrenska University
Hospital, St Sigfridsgatan 85, SE-412 66 Göteborg, Sweden.
lars.gerhardsson@ymk.gu.se

The aim of the present study was to compare the development of vibration white
fingers (VWF) in workers in relation to different ways of exposure estimation,
and their relationship to the standard ISO 5349, annex A. Nineteen vibration
exposed (grinding machines) male workers completed a questionnaire followed by a 
structured interview including questions regarding their estimated hand-held
vibration exposure. Neurophysiological tests such as fractionated nerve
conduction velocity in hands and arms, vibrotactile perception thresholds and
temperature thresholds were determined. The subjective estimation of the mean
daily exposure-time to vibrating tools was 192 min (range 18-480 min) among the
workers. The estimated mean exposure time calculated from the consumption of
grinding wheels was 42 min (range 18-60 min), approximately a four-fold
overestimation (Wilcoxon's signed ranks test, p<0.001). Thus, objective
measurements of the exposure time, related to the standard ISO 5349, which in
this case were based on the consumption of grinding wheels, will in most cases
give a better basis for adequate risk assessment than self-exposure assessment.

PMID: 15627422 [PubMed - indexed for MEDLINE]

139: Eur J Haematol. 2005 Jan;74(1):75-6.

Bone marrow necrosis successfully treated with corticosteroid.

Santana AN, Ramos RG, Zanandrea EF, Brandão-Neto RA.

Pulmonary Division, University of São Paulo Medical School, São Paulo, Brazil.
alfredonicodemos@hotmail.com

A 60-yr-old white woman with CREST syndrome (calcinosis cutis, Raynaud's
phenomenon, esophageal involvement, sclerodactyly, telangectasia), idiophatic
portal hypertension and esophageal varices presented with a 2-month history of
bone pain and severe anemia, requiring erythrocyte transfusion every 5-7 d.
Initial laboratory findings were hemoglobin (Hb) 4.4 g/dL, platelets 15 x
10(9)/L, white blood cell count (WBC) 2.7 x 10(9)/L. Bone marrow biopsy showed
large areas of BMN, and cultures of bone marrow aspirate were negative. The
patient was started on intravenous pulse methylprednisolone (1000 mg/d for 3 d)
followed by oral prednisone (1 mg/kg/d), and did not require erythrocyte
transfusion thereafter. On the 40th day, our patient had Hb 11.6 g/dL, platelets 
120 x 10(9)/L, WBC 6.2 x 10(9)/L. Here, we describe the first report of BMN in a 
patient with CREST syndrome, the first description of successful treatment with
intravenous pulse corticosteroid and discuss the possible immune mechanisms
involved in the present case.

Publication Types: 
    Case Reports

PMID: 15613112 [PubMed - indexed for MEDLINE]

140: Acta Ophthalmol Scand. 2004 Dec;82(6):738-40.

Reduced thirst in patients with a vasospastic syndrome.

Teuchner B, Orgül S, Ulmer H, Haufschild T, Flammer J.

University Eye Clinic, Basel, Switzerland.

PURPOSE: To compare thirst, drinking behaviour, and endothelin-1 (ET-1) plasma
levels between vasospastic and non-vasospastic subjects. METHODS: We compared 67 
subjects with a primary vasospastic syndrome with 64 age- and sex-matched
non-vasospastic control subjects. A detailed medical history was recorded,
including a questionnaire containing queries about thirst and drinking behaviour,
history of migraine or unspecific headache, history of episodes of low blood
pressure, and smoking habits. Body mass index (BMI) was calculated and blood
samples were drawn for ET-1 measurements. RESULTS: Subjects with a vasospastic
syndrome reported a reduced desire to drink and a lower estimated quantity of
daily fluid intake, more often forgot to drink, more often had both migraine and 
unspecific headache, more often had episodes of low blood pressure, and had an
increased plasma level of ET-1. These features differed statistically
significantly between the two groups. There was also a non-significant trend
among vasospastic subjects to smoke less and to have a smaller BMI. CONCLUSION: A
reduced desire to drink is found frequently among vasospastic subjects.

Publication Types: 
    Comparative Study

PMID: 15606473 [PubMed - indexed for MEDLINE]

141: Z Rheumatol. 2004 Dec;63(6):457-62.

Nailfold video-capillaroscopy in systemic sclerosis.

Cutolo M, Pizzorni C, Sulli A.

Department of Internal Medicine, University of Genova, Viale Benedetto xv,6,
16132 Genova, Italy. mcutolo@unige.it

The Raynaud's phenomenon (RP) is the most common and significant clinical
condition supporting microvascular analysis as soon as possible. Microvascular
involvement is a key feature of RP, and several rheumatic diseases are
characterized by the presence of the RP. Nailfold capillary microscopy shows an
impressive cost/effectiveness ratio: it is simple, noninvasive and
inexpensive.Well-recognized videocapillaroscopic patterns (NVC) have been
described mainly in scleroderma (SSc) patients complaining of a secondary RP. The
peripheral microvascular damage in SSc is characterized by increasing structural 
alterations of the capillaries (giant capillaries and microhemorrhages) with
progressive decrease of their density. The detection of the scleroderma NCV
allows early differentiation between primary RP (functional, not disease
associated), and secondary RP (disease associated). Other major NVC patterns have
been described in the field of rheumatic diseases. Interestingly, correlations
are evident between the NCV and the clinical symptoms, severity of the disease
and the laboratory findings. Further clinical and epidemiological studies, as
well as a standardized and computerized quantitation of the observed damages are 
required.

Publication Types: 
    Review

PMID: 15605209 [PubMed - indexed for MEDLINE]

142: Arthritis Rheum. 2004 Dec;50(12):3994-4001.

Efficacy and tolerability of a selective alpha(2C)-adrenergic receptor blocker in
recovery from cold-induced vasospasm in scleroderma patients: a single-center,
double-blind, placebo-controlled, randomized crossover study.

Wise RA, Wigley FM, White B, Leatherman G, Zhong J, Krasa H, Kambayashi J,
Orlandi C, Czerwiec FS.

Johns Hopkins School of Medicine, Baltimore, Maryland 21224, USA.

OBJECTIVE: OPC-28326 is a selective alpha-adrenergic antagonist with preferential
binding to the alpha(2C)-adrenergic receptor (alpha(2C)-AR) subtype. This study
observed the effect of OPC-28326 on skin temperature and digital blood flow
following an acute cold challenge in patients with Raynaud's phenomenon secondary
to scleroderma. METHODS: The study was designed as a single-center, double-blind,
placebo-controlled, randomized, 3-period crossover study of OPC-28326 (oral doses
of 10 mg or 40 mg) or placebo. The primary outcome measures were the time to
recover 50% and 70% of the fall (induced by cold challenge) in baseline digital
skin temperature. RESULTS: Twelve of 13 enrolled patients completed the study.
The mean time to achieve 50% and 70% recovery of the change in prechallenge
digital skin temperature was shorter after the OPC-28326 40-mg dose than after
placebo (50% recovery at 5.8 minutes versus 10.0 minutes [P = 0.02]; 70% recovery
at 13.8 minutes versus 19.5 minutes [P = 0.01]). These recovery times tended to
be shorter in the 10 mg OPC-28326 group as well, but the difference versus
placebo was not significant (50% recovery at 9.0 minutes versus 10.0 minutes [P =
0.65]; 70% recovery at 15.3 minutes versus 19.5 minutes [P = 0.07]). Total
digital blood flow tended to be lower prior to the cold challenge and after
administration of 40 mg OPC-28326, as compared with that after placebo, but the
difference was not significant. Symptoms that were potentially drug-related were 
reported more frequently with 40 mg OPC-28326 than with 10 mg OPC-28326 or with
placebo, but none were serious or sustained. CONCLUSION: OPC-28326 at doses of 10
mg and 40 mg was well tolerated during this study. The shorter time to skin
temperature recovery after 40 mg OPC-28326 suggests that selective alpha(2C)-AR
blockade improves digital skin perfusion during recovery from cooling in patients
with Raynaud's phenomenon secondary to scleroderma.

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

PMID: 15593189 [PubMed - indexed for MEDLINE]

143: Onkologie. 2005 Jan;28(1):41-3.

Acral necrosis after inadequate excessive administration of bleomycin in a
testicular cancer patient.

Grünwald V, Bolte O, Wiebe S, Ganser A, Schöffski P.

Abteilung für Hämatologie, Hämostaseologie und Onkologie, Medizinische Hochschule
Hannover, Germany. Gruenwald.Viktor@mh-hannover.de

BACKGROUND: Testicular cancer has a favorable prognosis in the majority of
patients due to the excellent susceptibility to chemotherapy with cisplatin,
etoposide and bleomycin (BEP), which is commonly administered over 3-4 cycles of 
treatment. CASE REPORT: A 22-year-old male failed to achieve complete response
after unconventional treatment with 6 courses of BEP for intermediate-risk
metastasized testicular cancer. The patient developed chemotherapy-induced
digital necrosis and substantial loss of digital function after this excessive
treatment. This condition resolved with infusional alprostadil combined with oral
clonidin and pentoxifyllin. RESULT: Infusional alprostadil adds substantial
clinical benefit to combined vasoactive therapy in chemotherapy-induced vascular 
toxicity, even after the onset of digital necrosis.

Publication Types: 
    Case Reports

PMID: 15591723 [PubMed - indexed for MEDLINE]

144: Curr Opin Rheumatol. 2004 Nov;16(6):718-22.

Raynaud phenomenon and the vascular disease in scleroderma.

Kahaleh MB.

Division of Rheumatology, Department of Medicine, Medical College of Ohio, 1321
Glendale Avenue, Toledo, OH 43617, USA. bkahaleh@mco.edu

PURPOSE OF REVIEW: Raynaud phenomenon is the earliest and most common clinical
manifestations of scleroderma (systemic sclerosis). Therefore, Raynaud phenomenon
offers the best window into the investigation of the early steps in the
pathogenesis of systemic sclerosis. This review focuses on the differential
diagnosis of Raynaud phenomenon, the transition of Raynaud phenomenon to systemic
sclerosis, mechanisms and consequences of vascular injury and dysfunction in
systemic sclerosis, and therapeutic options. RECENT FINDINGS: Careful clinical
evaluation using a simple definition of Raynaud phenomenon is the most reliable
and reproducible method in the diagnosis. Although the assessment of vascular
function by noninvasive methods is still not sensitive enough for the evaluation 
and follow-up of individual patients, it helps in the differential diagnosis and 
in population studies. Progressive deficiency in vasodilatory capacity of the
vessels is proposed as a mechanism of Raynaud phenomenon, particularly in
systemic sclerosis. In addition, decreased fibrinolysis and enhanced coagulation 
pathways undoubtedly contribute to vascular dysfunction. The mechanism of
endothelial injury is still elusive, yet endothelial apoptosis mediated by
antiendothelial antibodies is the most attractive hypothesis now. Therapies
directed at the vascular disease continue to focus on the alleviation of vascular
spasm. However, immunosuppressive therapy may influence the levels of vascular
injury markers and thus may have an effect on the vascular disease itself.
SUMMARY: Continued progress in the investigation of the vascular aspects of
scleroderma is described in this review. Immune involvement in the early stages
of the disease and mechanism of vascular repair in advance cases are some of the 
highlights of last year's progress.

Publication Types: 
    Review

PMID: 15577610 [PubMed - indexed for MEDLINE]

145: J Rheumatol. 2004 Dec;31(12):2408-12.

Low level laser therapy in primary Raynaud's phenomenon--results of a placebo
controlled, double blind intervention study.

Hirschl M, Katzenschlager R, Francesconi C, Kundi M.

Department of Angiology, Hanusch Hospital, Heinrich Collinstrasse 30, A-1140
Vienna, Austria. Mirko.Hirsch@wgkk.sozvers.at

OBJECTIVE: To assess the efficacy of low level laser therapy in patients with
primary Raynaud's phenomenon and predict the success of laser therapy by clinical
characteristics. METHODS: Forty-eight patients were included in a randomized
placebo controlled, double blind crossover study. Laser and sham therapy each
were applied 5 days a week for 3 weeks. Clinical symptoms, exposure to triggers, 
and frequency and intensity of attacks were recorded in diaries. Results of
infrared thermography before onset and at the end of both irradiation sequences
were evaluated. Primary endpoint was the average intensity of attacks; secondary 
endpoints were average number of attacks and thermography results. Age, sex,
duration of symptoms, age at onset of symptoms, evoking conditions other than
cold, maximum temperature drop after cold provocation, and rewarming time after
cold provocation were tested as potential predictors. RESULTS: Number of attacks 
and their intensity were significantly reduced during laser therapy compared to
sham treatment. Thermographic parameters did not reach statistical significance. 
In a stepwise multiple regression analysis, evoking conditions other than cold
(stress, wetness as additional triggers), rewarming time, and temperature
decrease after cold provocation were significant predictors of therapeutic
efficacy. CONCLUSION: Low level laser therapy reduces frequency and severity of
Raynaud attacks. The effect is most pronounced in patients with signs of
decreased threshold for vasospasm and less effective in patients with delayed
hyperemia.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15570642 [PubMed - indexed for MEDLINE]

146: Auton Neurosci. 2004 Nov 30;116(1-2):62-8.

Laser Doppler-recorded venoarteriolar reflex in Raynaud's phenomenon.

Stoyneva Z.

Laboratory of Clinical Neurovegetology, University Hospital St. Ivan Rilsky, 15
Acad. Ivan Geshov Str., 1431 Sofia, Bulgaria. zlatka_stoyneva@yahoo.com

The aim of the study was to assess whether Laser Doppler-recorded venoarteriolar 
reflex (VAR) response to hand lowering can contribute to differentiate primary
from secondary Raynaud's phenomena. MATERIALS AND METHODS: Skin fingerpulp
perfusion (PU) of each hand of 60 persons was investigated: 15 healthy controls; 
15 primary Raynaud's phenomenon (RP) patients; 15 patients with Raynaud's
phenomenon secondary to systemic sclerosis (SSc); 15 patients with Raynaud's
phenomenon secondary to vibration exposure. Blood perfusion was monitored by
Laser Doppler flowmetry (LDF) as initial values and at a temperature of 32
degrees C with hands on the sternum (PUh) and in dependency (PUd). VAR indices
were analyzed: delta VAR (DeltaVAR) calculated as (PUd-PUh); percent change of
perfusion--[(DeltaVAR/PUh) x 100]; and vasoconstriction response--(PUd/PUh).
RESULTS: Initial mean superficial skin temperatures and perfusions in Raynaud's
phenomenon groups were significantly lower compared to healthy controls but with 
wide overlap of the values in individual cases. Venoarteriolar indices were
significantly different between secondary Raynaud's phenomenon groups and healthy
controls and between secondary and primary Raynaud's phenomenon groups. Percent
changes were significantly higher in control and primary RP groups compared to
secondary RP groups. Vasoconstriction indices between primary and secondary RP
patients (p<0.0001) and between controls and secondary RP patients (p<0.0001)
also differed. A loss of venoarteriolar reflex (DeltaPU>or=0) was established in 
10.0% of primary, 53.3% of sclerodermic, and 36.7% of vibration-induced Raynaud's
phenomenon patients. The significantly higher prevalence rate of impaired
venoarteriolar reflex in secondary Raynaud's phenomenon patients proves local
vasomotor dysfunction and reflects either postganglionar sympathetic
insufficiency with vascular tone failure or altered smooth muscle cells'
responses. CONCLUSIONS: Laser Doppler flowmetry is a valuable noninvasive method 
for investigation of the very early skin venoarteriolar dysfunctions, for
evaluation of focal autonomic dysregulation and skin vasomotor abnormalities in
RP patients. Laser Doppler-recorded venoarteriolar reflex testing is a simple
procedure and an adequate additional diagnostic tool, which contributes to
diagnose RP and differentiate primary from secondary RP.

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

PMID: 15556839 [PubMed - indexed for MEDLINE]

147: Rheumatology (Oxford). 2005 Feb;44(2):145-50. Epub 2004 Nov 16.

Calcium channel blockers for primary Raynaud's phenomenon: a meta-analysis.

Thompson AE, Pope JE.

Mary Pack Arthritis Centre, University of British Columbia, Vancouver, Canada.

BACKGROUND: To determine the efficacy of calcium channel blockers (CCBs) for
primary Raynaud's phenomenon (RP). Primary outcomes were frequency and severity
of RP attacks. METHODS: A meta-analysis was conducted using primary data sources:
Medline, Current Contents and the Cochrane Controlled Trials Register. Inclusion 
criteria were randomized controlled trials (RCTs) of >2 days' duration with <35% 
dropouts. Eighteen of 31 trials were eligible for inclusion [13 nifedipine vs
placebo; five other CCBs vs placebo (n = 361)]. The main reasons for trial
exclusion were: subset data (primary RP) not provided (n = 10); data published
more than once (n = 1); lack of control group (n = 1); and lack of randomization 
(n = 1). Data were abstracted independently and a weighted mean difference (WMD) 
was calculated for the outcomes. RESULTS: The WMD (95% confidence interval) of
all CCBs vs placebo for reduction in the frequency of attacks (n = 17) over 1
week was -5.00 (-9.02, -0.99) (P = 0.01) or -2.80 (-3.90, -1.70) when
heterogeneity was considered, and -6.05 (-11.19,-0.19) (P = 0.04) for nifedipine 
alone (n = 10). The WMD of all CCBs vs placebo (n = 8) for reduction in severity 
of attacks (assessed with a 10-cm visual analogue scale) was -1.39 (-2.20, -0.58)
(P = 0.0007) and -1.81 (-3.08, -0.54) (P = 0.005) for nifedipine alone (n = 5).
CONCLUSIONS: Several small RCTs of CCBs for primary RP have been conducted and
have yielded clinical improvement in the frequency and severity of ischaemic
attacks. Most trials were crossover trials in which order effect was not studied;
this may have introduced bias. The effect size may have been small because of low
dosing in studies. The efficacy of CCBs for reducing severity and frequency of
ischaemic attacks in primary RP is small (average of 2.8 to 5.0 fewer attacks per
week and a 33% reduction in severity).

Publication Types: 
    Meta-Analysis
    Review

PMID: 15546967 [PubMed - indexed for MEDLINE]

148: J Pediatr Hematol Oncol. 2004 Nov;26(11):768-9.

First report of a vincristine dose-related Raynaud's phenomenon in an adolescent 
with malignant brain tumor.

Gottschling S, Meyer S, Reinhard H, Krenn T, Graf N.

Department of Pediatric Hematology and Oncology, University Children's Hospital, 
Homburg/Saar, Germany. kisgot@uniklinik-saarland.de

The authors report a case of a vincristine-induced, reproducible dose-related
Raynaud's phenomenon. It occurred in a 14-year-old boy with a malignant brain
tumor who received repeated vincristine injections. The authors describe how they
handled this severe secondary Raynaud's phenomenon with acral cutaneous tissue
necrosis. Reducing the dose of the vinca-alkaloid injections, together with an
additional medication with a calcium-channel blocking agent, was a successful
strategy in this patient. There are few case reports of secondary Raynaud's
phenomenon in adult oncologic patients receiving certain anticancer drugs
(including vincristine, bleomycin, and cisplatin), and to the authors' knowledge 
this kind of vincristine toxicity has not previously been described in either
adults or children.

Publication Types: 
    Case Reports

PMID: 15543016 [PubMed - indexed for MEDLINE]

149: J Neurosurg. 2004 Nov;101(5):854-7.

Association of an irregularly shaped anterior choroidal aneurysm with CREST
syndrome. Case report.

Zoumalan RA, Bendok BR, Parkinson RJ, Sorin J, Burke AM, Batjer HH.

Department of Neurological Surgery, Northwestern University Feinberg School of
Medicine, Chicago, Illinois 60611, USA.

The authors present the case of a 50-year-old woman with a history of CREST
syndrome (calcinosis, Raynaud phenomenon, esophageal motility disorders,
sclerodactyly, and telangiectasia), a variant of scleroderma, who was
incidentally found to have an irregular intracranial aneurysm. The patient
presented with migraine headaches. A magnetic resonance image of the brain
obtained during the headache workup revealed a right posterior carotid artery
wall aneurysm in the region of the anterior choroidal artery (AChA). On digital
subtraction angiograms, the lesion measured 3.5 mm at its largest diameter.
Because of the irregular shape of the aneurysm, the patient's relatively young
age, and the potential for further aneurysm growth due to collagen disease,
surgical clip application was recommended following a discussion of available
treatment options. At surgery, the aneurysm was identified as bilobed and broad
based, and the AChA was found to be associated with the aneurysm neck.
Satisfactory clipping of the aneurysm was achieved with preservation of the
parent vessels. An association of CREST syndrome with intracranial aneurysms has 
only been reported once before. This case is presented to draw attention to the
possibility of a pathophysiological connection between CREST syndrome and
intracranial aneurysms and to postulate a possible mechanism whereby this
condition may result in aneurysm formation. The association of aneurysms with
other pathological collagen-related conditions is well known, and literature
relevant to a possible connection between CREST syndrome and aneurysms is
reviewed and discussed.

Publication Types: 
    Case Reports

PMID: 15540926 [PubMed - indexed for MEDLINE]

150: Microvasc Res. 2004 Nov;68(3):203-8.

Laser Doppler anemometry distinguishes primary Raynaud phenomenon from VWF
syndrome.

Ziegler S, Gschwandtner M, Zöch C, Barth A, Minar E, Rüdiger H, Osterode W.

Division of Angiology, Clinic for Internal Medicine II, University of Vienna of
the Vienna General Hospital, Währinger Gürtel, Vienna, Austria.
sophie.ziegler@akh-wien.ac.at

OBJECTIVES: We evaluated two microcirculatory function-tests, the Laser Doppler
(LD)-Anemometry and the Laser Doppler Imager (LDI)-Flowmetry in their value to
further elucidate functional behavior of the "Vibration-induced white finger
syndrome" (VWF) and to distinguish between Raynaud's phenomenon (RP) of
idiopathic or vibration origin. PARTICIPANTS AND METHODS: Ninety-four patients,
suffering from RP were studied (78 patients with primary RP and 16 patients with 
VWF). Measurement of blood cell velocity (BCV) before and after provocation was
obtained by nailfold capillary microscopy and an included Laser detector
("Anemometry"). Digital blood flux was recorded by LDI-Flowmetry during a
standardized cooling and rewarming thermal challenge. RESULTS: "Time to peak" of 
BCV, a measure of maximal reactive hyperemia was longer in VWF in comparison to
primary RP (30.37 versus 19.29 sec P < 0.02), respectively. CONCLUSION: Based on 
the fact, that prolongation of reactive hyperemia, an indicator of impaired
endothelium-dependent vasodilation is also frequently found in peripheral
arterial occlusive disease, it is hypothesized that VWF is not only a
microcirculatory vasospastic disorder, but may also be related to
atherosclerosis. Anemometry, in association with an appropriate provocation-test,
could represent a useful non-invasive method for objectifying diagnosis of VWF in
patients with RP.

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

PMID: 15501239 [PubMed - indexed for MEDLINE]

151: Kidney Blood Press Res. 2005;28(1):27-31. Epub 2004 Sep 23.

Raynaud's phenomenon and endothelial dysfunction in end-stage renal disease
patients treated with hemodialysis.

Czupryniak A, Kałuzyńska A, Nowicki M, Wiecek B, Bald E, Owczarek D.

Department of Nephrology and Dialysis, Polish Mother's Memorial Hospital Research
Institute, ?ódz, Poland. aczupryniak@wp.pl

BACKGROUND/AIMS: Steal syndrome is a well-known complication of arteriovenous
shunt placement. Increased frequency of Raynaud's phenomenon (RP) especially
concerning shunt limb is reported among hemodialysis (HD) patients. The aim of
the study was to assess the relation of impairment of peripheral circulation
diagnosed with cold stress test (CST) and thermography to the AV shunt location
and markers of endothelial dysfunction in HD patients. METHODS: The study group
comprised 21 patients (6 male, 15 female, mean age 32.6 +/- 15.0 years) treated
with HD for a mean of 69 +/- 54 months. 10 healthy individuals (4 male, 6 female,
mean age 38.6 +/- 14.7 years) served as controls. The diagnosis of RP was made
upon the results of thermographic measurements during CST. Von Willebrand factor 
activity and antigen, endothelin-1 and plasma total homocysteine (tHcy) were
measured in all subjects. RESULTS: RP was found significantly more often in HD
patients than in controls: 11/21 vs. 1/10 (p = 0.04). RP occurred in both hands
in 7/11 (64%) patients. tHcy was higher in HD patients than in the controls (31.7
+/- 13.9 vs. 10.9 +/- 3.2 microg/l, p < 0.0001). tHcy and von Willebrand factor
antigen were significantly higher in the RP-positive than RP-negative patients or
controls. CONCLUSION: Small vessel dysfunction diagnosed as positive RP is a
frequent finding in HD patients. It seems that endothelial injury rather than AV 
shunt steal syndrome is responsible for development of RP in HD patients.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 15452382 [PubMed - indexed for MEDLINE]

152: Scand J Rheumatol. 2004;33(4):253-6.

Comparison between iloprost and alprostadil in the treatment of Raynaud's
phenomenon.

Marasini B, Massarotti M, Bottasso B, Coppola R, Papa ND, Maglione W, Comina DP, 
Maioli C.

Department of Medicine, Surgery and Dentistry, San Paolo Hospital, University of 
Milan, Italy. bianca.marasini@unimi.it

OBJECTIVE: The prostanoids iloprost and alprostadil are widely used to treat
ischaemic changes in patients with Raynaud's phenomenon (RP), but the optimal
regimen is poorly defined. We evaluated whether there are differences between
iloprost and alprostadil, in terms of either clinical efficacy or of laboratory
data, with the aim of assisting in the treatment of connective tissue disease
(CTD)-associated RP. METHODS: Twenty-one women with CTD-associated RP were given 
intravenous iloprost (11 patients) or alprostadil (10 patients) cyclically (5
consecutive days, followed by 1 day every 30 days). Clinical efficacy (RP
symptoms, skin score, digital ulcers) and circulating levels of von Willebrand
factor (VWf), tissue plasminogen activator (tPA), thrombomodulin (TM) and Type
III procollagen N-terminal propeptide (PIIINP) were evaluated by enzyme-linked
immunoassay at different intervals. RESULTS: The overall benefits of iloprost and
alprostadil were similar. RP improved in 45% versus 90% of patients; ulcers in
60% versus 40% of patients (iloprost versus alprostadil). Skin score did not
significantly change with either drug. Circulating VWf decreased with either drug
(iloprost -6.2%, alprostadil -9.4%), while tPA, TM, and PIIINP remained
unchanged. Side effects were only minor and less frequent with alprostadil.
CONCLUSION: Iloprost and alprostadil were both of benefit in CTD-associated RP,
without significant differences in either clinical efficacy or circulating
markers. However, ease of handling and the lower price favours alprostadil.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15370722 [PubMed - indexed for MEDLINE]

153: Eur J Dermatol. 2004 Sep-Oct;14(5):327-31.

Chromosome aberrations in Raynaud's phenomenon.

Porciello G, Scarpato R, Storino F, Migliore L, Ferri C, Cagetti F, Morozzi G,
Bellisai F, Marcolongo R, Galeazzi M.

Servizio di Reumatologia Ospedale Misericordia e Dolce di Prato, Italy
g.porciello@katamail.com

We evaluated the occurrence of spontaneous chromosome damage in cultured
peripheral lymphocytes of subjects with idiopathic and pre-scleroderma Raynaud's 
phenomenon, by means of molecular cytogenetic analysis. Using the micronucleus
assay as a marker of chromosome alteration, we studied 30 patients with
pre-scleroderma Raynaud's phenomenon, 30 patients with idiopathic Raynaud's
phenomenon and 30 healthy subjects. All subjects were classified as ANA-, ACA+ or
Scl 70+. To identify the mechanism of micronucleus formation, fluorescence in
situ hybridisation analysis was also performed. Pre-scleroderma Raynaud's
phenomenon subjects showed significantly higher micronucleus frequencies than
idiopathic Raynaud's phenomenon subjects and controls (37.0 +/- 11.5 vs. 11.1 +/-
3.2 and 10.7 +/- 2.7 respectively p < 0.0001). Interestingly, subjects with
idiopathic Raynaud's phenomenon displayed micronucleus frequency comparable to
that of healthy controls. Furthermore, ACA+ subjects showed the highest
micronucleus frequencies (41.0 +/- 7.6) as compared to subjects with Scl 70+
antibody (25.0 +/- 3.5). Our results show that circulating lymphocytes of only
pre-scleroderma Raynaud's phenomenon subjects undergo chromosomal damage, as
detected by the micronucleus assay, at a higher rate than expected. No prevalence
of aneuploidogenic or clastogenic events in micronucleus formation is revealed by
fluorescence in situ hybridisation analysis.

PMID: 15358572 [PubMed - indexed for MEDLINE]

154: Clin Rheumatol. 2005 Apr;24(2):145-51. Epub 2004 Sep 4.

Raynaud's phenomenon in undifferentiated connective tissue disease (UCTD).

De Angelis R, Cerioni A, Del Medico P, Blasetti P.

Dipartimento di Patologia Molecolare e Terapie Innovative, Cattedra di
Reumatologia, Università Politecnica delle Marche, Ancona, Italy.
rossella.deangelis@asl5.marche.it

The aim of this study was to ascertain which clinical and immunological factors
are associated with Raynaud's phenomenon (RP) in patients with undifferentiated
connective tissue disease (UCTD) and to investigate microvascular involvement. A 
total of 78 patients were evaluated. They all showed symptoms suggestive of a
connective tissue disorder (CTD), but did not fulfil the criteria for any of the 
defined CTDs. They all had a disease duration of at least 1 year. Nailfold
capillaroscopy (NC) was performed using a computerised videomicroscope. We
diagnosed RP in 52.5% of our patients. Patients with RP showed a higher
occurrence of oesophageal dysmotility (p=0.001) and anti-ribonucleoprotein (RNP) 
antibodies (p=0.004) than those without RP. The distinguishing capillaroscopic
characteristics of UCTD patients with RP were widened and irregularly enlarged
loops (75 and 55%, respectively), giant capillaries (35%), and less than two
haemorrhages per finger (40%). The combination of features indicative of a 'slow'
scleroderma pattern was present in 18 of 40 patients with UCTD and RP (p=0.0003).
Only 3 of the original 78 patients (3.8%) developed a definite CTD. In none of
our patients did we observe avascular areas or changes from the original
capillaroscopic pattern during follow-up examination. Our study indicates that
patients with UCTD would seem to have a benign form of RP, since they show the
absence of cutaneous complications, the existence of a mild microvascular damage 
and a stable nailfold capillary pattern. Further examinations of these patients
will be required in order to confirm our findings.

PMID: 15351873 [PubMed - indexed for MEDLINE]

155: Vasa. 2004 May;33(2):87-8.

Vasospasm of the scrotum--a manifestation of Raynaud's phenomenon?

al-Awami M, Schillinger M, Minar E.

Department of Medical Angiology, University of Vienna, Austria.
mahdi.al-awami@akh-wien.ac.at

Raynaud's phenomenon (RP) is characterized by local artery vasoconstriction in
response to cold exposure or emotional stress. RP appears as attacks of blanching
or cyanosis of digits, or both, followed by a hyperaemic phase. Usually the
digits of the hands or less commonly of the feet are affected. Other sites such
as nose, ears could also be affected. We report a patient who has been suffering 
for long time of cold induced sensitivity associated with well demarcated pallor 
of the scrotum.

Publication Types: 
    Case Reports

PMID: 15224461 [PubMed - indexed for MEDLINE]

156: Intern Med. 2004 May;43(5):397-9.

Successful long-term treatment with cyclosporin A in protein losing
gastroenteropathy.

Sunagawa T, Kinjo F, Gakiya I, Hokama A, Kugai Y, Matayoshi R, Yonamine Y,
Tomiyama R, Saito A.

First Department of Internal Medicine, Faculty of Medicine, University of the
Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215.

Protein-losing gastroenteropathy (PLG) can occur as a manifestation of various
diseases including autoimmune disorders, and optimal therapy of these underlying 
diseases may be the only effective remedy for PLG. In the present report, we
describe a case of a 54-year-old woman with PLG associated with an autoimmune
disease, presumably CREST syndrome. She failed to respond to steroid treatment.
Subsequently, cyclosporine was initiated, which resulted in a rapid recovery. The
patient was successfully treated with low-dose cyclosporine for five years. There
has not been, to our knowledge, any report of PLG successfully treated with
cyclosporine. Cyclosporine therapy may be effective not only in inducing but also
in maintaining complete remission in patients with autoimmune-associated PLG,
especially refractory or intolerable to steroids and/or immunosuppressive
therapies.

Publication Types: 
    Case Reports

PMID: 15206552 [PubMed - indexed for MEDLINE]

157: Rheumatology (Oxford). 2004 Aug;43(8):986-91. Epub 2004 Jun 15.

Digital iontophoresis of vasoactive substances as measured by laser Doppler
imaging--a non-invasive technique by which to measure microvascular dysfunction
in Raynaud's phenomenon.

Anderson ME, Moore TL, Lunt M, Herrick AL.

University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford, UK.

OBJECTIVE: To test the hypothesis that microvascular vasodilation is impaired in 
patients with systemic sclerosis (SSc) compared with patients with primary
Raynaud's phenomenon (PRP) and healthy controls, using the technique of laser
Doppler imaging to quantify blood flow responses to iontophoresis of vasoactive
agents. METHODS: Microvascular blood flow was measured by laser Doppler imaging
before, during and after 120 s iontophoresis (30 microA) of 1% acetylcholine
chloride (ACh, endothelium-dependent) and 1% sodium nitroprusside (NaNP,
endothelium-independent). Two adjacent fingers of the left hand were studied, and
the procedure then repeated on the right. Ten patients with limited cutaneous SSc
(LCSSc), 10 patients with PRP and 11 healthy control subjects were studied.
RESULTS: Vasodilation in response to both ACh and NaNP iontophoresis, as measured
by 'area under the blood flow.time curve' (AUC), normalized for baseline flux,
was similar in the control and PRP groups, but was diminished in the LCSSc group 
compared with both control and PRP groups (ACh results: control vs LCSSc P =
0.028, PRP vs LCSSc P = 0.005; NaNP results: control vs LCSSc P = 0.004, PRP vs
LCSSc P = 0.005). There were no differences between groups in baseline flux
values nor in voltages required to drive the 30 microA current. CONCLUSIONS: Both
endothelium-dependent and endothelium-independent vasodilation are impaired in
patients with LCSSc. Vasodilatory responses in patients with PRP are similar to
those in controls. If reproducibility is confirmed to be satisfactory, then these
techniques could be used to examine disease progression over time and
responsiveness to vasoactive treatment, thus facilitating clinical trials.

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

PMID: 15199217 [PubMed - indexed for MEDLINE]

158: Cell Cycle. 2004 Jul;3(7):923-30. Epub 2004 Jul 27.

Human ninein is a centrosomal autoantigen recognized by CREST patient sera and
plays a regulatory role in microtubule nucleation.

Stillwell EE, Zhou J, Joshi HC.

Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia
30322, USA.

Centrosome is the major microtubule organizing center in mammalian cells that
plays a critical role in a variety of cellular events by the microtubule arrays
emanating from it. Despite its significance, the molecular mechanisms underlying 
the structure and function of the centrosome are still not clear. Herein we
describe the identification of three isotypes of human ninein by expression
library screening with autoimmune sera from CREST patients. All three ninein
isotypes exhibit centrosomal localization throughout the cell cycle when
GFP-tagged fusion proteins are expressed transiently in mammalian cells.
Construction of serial deletions of GFP-tagged ninein reveals that a stretch of
three leucine zippers with a flanking sequence is required and sufficient for
centrosomal targeting. Overexpression of ninein results in mislocalization of
gamma-tubulin, recruiting it to ectopic (noncentrosomal) ninein-containing sites 
which are not active in nucleating microtubules. In these cells, nucleation of
microtubules from the centrosome is also inhibited. These results thus suggest a 
regulatory role for ninein in microtubule nucleation.

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

PMID: 15190203 [PubMed - indexed for MEDLINE]

159: Nucl Med Commun. 2004 Feb;25(2):207-11.

Comment in:
    Nucl Med Commun. 2005 Mar;26(3):269-70.

Assessment of digital ischaemia and evaluation of response to therapy by 99mTc
sestamibi limb scintigraphy after local cooling of the hands in patients with
vasospastic Raynaud's syndrome.

Sarikaya A, Ege T, Firat MF, Duran E.

Department of Nuclear Medicine, Trakya University Hospital, Edirne, Turkey.
alisar_2000@yahoo.com

AIM: Cold induced arteriolar constriction in patients with vasospastic Raynaud's 
syndrome (VRS) produces temporary digital ischaemia. The aim of this study was to
ascertain whether 99mTc sestamibi scintigraphy is useful in the diagnosis and the
monitoring of treatment in VRS. METHODS: Fifteen patients with VRS and 20 matched
normal controls underwent examination. Twelve patients with VRS received therapy.
For each patient, one hand was immersed in iced water for 30s while the other
hand served as a control. Ten minutes after cooling, 99mTc sestamibi was injected
and imaging was performed 60min later. The per cent decrease of the perfusion
(%DP) was calculated by semiquantitative analysis to determine the severity of
hypoperfusion. RESULTS: In all patients with VRS, moderate or marked
hypoperfusion were seen in 99mTc sestamibi images after exposure to the iced
water, while there was minimal or mild hypoperfusion in the control groups.
Values for %DP were 46.86 +/- 19.04 and 7.85 +/- 4.53 for the VRS group and
normal subjects, respectively. The difference between both groups was
statistically significant (P = 0.0000). In 12 treated patients with VRS,
pre-treatment and post-treatment %DP values were 51.16 +/- 18.42 and 33.58 +/-
17.83, respectively, and a significant difference was seen between both values (P
= 0.001). However, there was still a statistically significant difference between
control subjects and post-therapy values (7.85 +/- 4.53 vs. 33.58 +/- 17.83, P = 
0.0000). The +/- 95% confidence interval of DP for control subjects was 5.7-10%
(chi-squared, P = 0.000). When a DP of 10% was used as a cut-off point,
sensitivity, specificity and diagnostic accuracy were 100%, 70% and 83%,
respectively, for the 99mTc sestamibi scan. There was also a strong correlation
between %DP and the duration of the disease (r = 0.80, P = 0.0003). CONCLUSION:
The results of this study indicate that a 99mTc sestamibi scan is a valuable
imaging method for the determination of digital ischaemia in vasospastic
Raynaud's syndrome, and may play a role in evaluating the response to therapy.

Publication Types: 
    Clinical Trial

PMID: 15154713 [PubMed - indexed for MEDLINE]

160: Arthritis Rheum. 2004 May;50(5):1578-85.

Increased tyrosine phosphorylation mediates the cooling-induced contraction and
increased vascular reactivity of Raynaud's disease.

Furspan PB, Chatterjee S, Freedman RR.

C.S. Mott Center, Wayne State University, 275 East Hancock Avenue, Detroit, MI
48201, USA. aa1985@wayne.edu

OBJECTIVE: Increased levels of protein tyrosine kinase (PTK) are mechanistically 
associated with increased contractile responsiveness to cooling. This study tests
the hypothesis that increased PTK activity mediates the increased vascular
reactivity to agonists and cooling associated with primary Raynaud's disease
(RD). METHODS: The response of dermal arterioles isolated from control (n = 29)
and RD (n = 29) subjects to contractile and dilatory agents at 37 degrees C and
31 degrees C was characterized using the microvessel perfusion technique.
Fluorescence immunohistochemistry was used to measure tyrosine phosphorylation.
RESULTS: At 37 degrees C, arteries from RD patients exhibited similar sensitivity
to the specific alpha(2)-adrenergic agonist UK 14,304, to serotonin, and to
angiotensin II. At 31 degrees C, however, the response to all 3 agonists was
greater in the arterioles from the RD patients than in those from the control
subjects. Agonist-induced contraction at both temperatures was reversed by
cumulative addition of the PTK inhibitors genistein (1-30 microM) and tyrphostin 
47 (0.1-10 microM). All arterioles from control subjects relaxed slightly in
response to cooling, whereas more than half of those from RD patients contracted.
This cooling-induced contraction was reversed by the cumulative addition of
genistein. The 3 agonists elicited large increases in tyrosine phosphorylation
only in arterial segments from RD patients at 31 degrees C. Cooling from 37
degrees C to 31 degrees C elicited a large increase in tyrosine phosphorylation
in arterioles from RD patients, but not those from control subjects. All
increases in tyrosine phosphorylation could be prevented by genistein.
CONCLUSION: Increased tyrosine phosphorylation mediates cooling-induced
contraction and the increased vascular reactivity of skin arterioles from
individuals with RD.

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

PMID: 15146428 [PubMed - indexed for MEDLINE]

161: Med Sci Monit. 2004 May;10(5):CR202-8. Epub 2004 Apr 28.

Duration of Raynaud's phenomenon is negatively correlated with serum levels of
interleukin 10 (IL-10), soluble receptor of interleukin 2 (sIL2R), and sFas in
systemic sclerosis patients.

Dziankowska-Bartkowiak B, Zalewska A, Sysa-Jedrzejowska A.

Department of Dermatology, Medical University of ?ódź, Lodz, Poland.
anuciazalewska@hotmail.com

BACKGROUND: Dysfunction of blood vessels and endothelial cells is regarded as a
primary triggering factor of the development of autoimmunological processes in
systemic sclerosis (scleroderma, SSc). Literature data suggest that the duration 
of Raynaud's phenomenon may correlate with disease severity. MATERIAL/METHODS:
The study comprised 34 patients with SSc, 19 with limited SSc (lSSc) and 15 with 
diffuse SSc (dSSc). The duration of Raynaud's phenomenon (before skin fibrosis
development) was correlated with the serum levels of selected markers, measured
by ELISA, reflecting disturbances in autoimmunological processes, angiogenesis,
apoptosis, and fibrosis. RESULTS: A shorter duration of Raynaud's phenomenon was 
shown to correlate with higher serum levels of interleukin-10 (IL-10) in the
whole SSc group and of aminoterminal propeptide of collagen III (PIIINP) in the
lSSc subgroup (p<0.05). It also correlated with higher serum levels of soluble
interleukin 2 receptor (sIL2R) and the soluble protein sFas in the whole SSc
group and the lSSc subgroup (p<0.05). CONCLUSIONS: The results obtained confirm
the importance of vasomotor disturbance duration in triggering fibrosis in the
course of systemic sclerosis.

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

PMID: 15114270 [PubMed - indexed for MEDLINE]

162: Scand J Rheumatol. 2003;32(6):343-7.

Long-term outcome of primary Raynaud's phenomenon and its conversion to
connective tissue disease: a 12-year retrospective patient analysis.

Ziegler S, Brunner M, Eigenbauer E, Minar E.

Division of Angiology, Clinic for Internal Medicine II, University Hospital
School of Medicine, Vienna, Austria. sophie.ziegler@akh-wien.ac.at

OBJECTIVES: To determine the frequency of development of connective tissue
disease (CTD) in patients considered to have idiopathic Raynaud's phenomenon (RP)
> 10 years. PATIENTS AND METHODS: Based on initial evaluation, 113 women and 29
men were divided into either 'primary RP' (n=109) or 'possible secondary RP'
(n=33) groups and were re-evaluated after a median follow-up period of 12.4
years. RESULTS: Overall 20 patients (14.1%) progressed to a definite CTD; 10 from
'primary RP' (9.2%) and 10 from possible secondary RP' (30.3%). Initial presence 
of antinuclear antibodies, thickening of fingers, higher age at onset of RP, and 
female sex seemed to be important determinants for a possible transition to a
CTD. CONCLUSION: In RP-patients, who are at risk of development of a CTD, serial 
clinical and laboratory controls are warranted for the decision to initiate
therapy early.

Publication Types: 
    Comparative Study

PMID: 15080265 [PubMed - indexed for MEDLINE]

163: J Int Med Res. 2004 Mar-Apr;32(2):222-31.

A new tactile skin sensor for measuring skin hardness in patients with systemic
sclerosis and autoimmune Raynaud's phenomenon.

Takei M, Shiraiwa H, Omata S, Motooka N, Mitamura K, Horie T, Ookubo T, Sawada S.

First Division of Internal Medicine, Department of Medicine, Nihon University
School of Medicine, Tokyo, Japan.

We used a new tactile sensor to measure the elastic properties of skin in
patients with systemic sclerosis or Raynaud's phenomenon. The sensor consists of 
a piezoelectric vibrator with vibration pickup to measure frequency changes when 
the sensor is placed on the skin. The mean frequency change at the skin surface
of the proximol third phalanx in patients with systemic sclerosis was
significantly lower than in age- and sex-matched controls. The results in
systemic sclerosis patients were statistically correlated to the Modified Rodnan 
Skin Thickness Score. This technique was also used to measure the therapeutic
efficacy of salpogrelate, a new specific serotonin receptor antagonist. A greater
mean frequency change was seen after treatment. We conclude that this new tactile
sensor is useful for quantitatively measuring skin sclerosis and may help
determine the efficacy of therapeutic treatments.

PMID: 15080028 [PubMed - indexed for MEDLINE]

164: Vasa. 2004 Feb;33(1):25-9.

Low level laser therapy for treatment of primary and secondary Raynaud's
phenomenon.

al-Awami M, Schillinger M, Maca T, Pollanz S, Minar E.

Department of Medical Angiology, University of Vienna, Austria.
mahdi.al-awami@akh-wien.ac.at

BACKGROUND: We recently performed a pilot study which suggested that clinical and
thermographic improvements occurred in patients with primary and secondary
Raynaud's phenomenon (RP) following treatment with low level laser irradiation
(LLLI). In view of these findings, we have proceeded with a double blind,
placebo-controlled study. METHODS: Forty seven patients suffering from primary or
secondary RP were randomly assigned in a double-blind manner to receive either 10
sessions of distant LLLI (16 f, 8 m, median age 45 years) or placebo irradiation 
(21 f, 2 m, median age 46 years) during winter months. The attack frequency of RP
was measured by a diary count; its severity was assessed by means of visual
analogue scale. Response to cold challenge test before and after LLL or placebo
treatment was assessed by infrared thermography. RESULT: Overall a significant
reduction of the frequency as well as the severity of RP in patients with either 
LLLI (frequency p < 0.0001, severity p < 0.0001) or placebo treatment (frequency 
p < 0.0001, severity p = 0.02) was found, but patients in the LLLI group
exhibited a statistically more significant improvement of the frequency at 6
weeks p = 0.007 and 3 months p = 0.02 and the severity p = 0.02, p = 0.04 of RP. 
Thermographic response to cold challenge improved only in patients treated with
LLL but not in those treated with placebo. CONCLUSION: LLLI significantly lowers 
the frequency and severity of Raynaud's attacks in patients with primary and
secondary RP. Since this therapeutic modality is a safe, and non-invasive
treatment, it might be considered as an alternative to existing therapeutic
regimes.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15061044 [PubMed - indexed for MEDLINE]

165: Pediatrics. 2004 Apr;113(4):e360-4.

Raynaud's phenomenon of the nipple: a treatable cause of painful breastfeeding.

Anderson JE, Held N, Wright K.

Department of Pediatrics, University of California, San Francisco, California
94115, USA. jane.anderson@ucsfmedctr.org

Maurice Raynaud first described the vasospasm of arterioles in 1862, and
Raynaud's phenomenon is now felt to be common, affecting up to 20% of women of
childbearing age. Raynaud's phenomenon has been reported to affect the nipples of
breastfeeding mothers and is recognized by many lactation experts as a treatable 
cause of painful breastfeeding. In 1997, Lawlor-Smith and Lawlor-Smith reported 5
women with Raynaud's phenomenon associated with breastfeeding, but there are few 
other case reports, and none report the possible relationship between Raynaud's
phenomenon of the nipple and previous breast surgery. We report 12 women who
breastfed 14 infants, all of whom were seen in 1 pediatric practice and 1
lactation consultation center in San Francisco, California, within the past 3
years. Of the 12 women, 11 were seen between June 2002 and May 2003. All women
suffered from extremely painful breastfeeding, with symptoms precipitated by cold
temperatures and associated with blanching of the nipple followed by cyanosis
and/or erythema. Poor positioning and poor attachment or latch may cause
blanching of the nipple and pain during breastfeeding, but 10 of the 12 mothers
were evaluated by experienced lactation consultations, who were sure that
inappropriate breastfeeding techniques were not contributing factors. Because the
breast pain associated with Raynaud's phenomenon is so severe and throbbing, it
is often mistaken for Candida albicans infection. It is not unusual for mothers
who have Raynaud's phenomenon of the nipple to be treated inappropriately and
often repeatedly for C albicans infections with topical or systemic antifungal
agents. Eight of our 12 mothers and their infants received multiple courses of
antifungal therapy without relief before the diagnosis was made. To diagnose
Raynaud's phenomenon accurately, additional symptoms such as precipitation by
cold stimulus, occurrence of symptoms during pregnancy or when not breastfeeding,
and biphasic or triphasic color changes must be present. All our mothers
experienced precipitation of symptoms by cold stimuli and demonstrated biphasic
or triphasic color changes, and 6 of the 12 experienced symptoms during
pregnancy. Interestingly 3 of 12 mothers also reported a history of breast
surgery, including 1 mother who had a fibroadenoma removed and 2 who had
breast-reduction surgery. The association between breast surgery/implants and
autoimmune disease, including Raynaud's phenomenon, has been discussed
extensively, but the association of Raynaud's phenomenon of the nipple during
breastfeeding has not been reported previously. Given the small numbers in the
study, it is uncertain as to whether this may be a precipitating factor in
developing Raynaud's phenomenon. Treatment options include methods to prevent or 
decrease cold exposure, avoidance of vasoconstrictive drugs/nicotine that could
precipitate symptoms, and pharmacologic measures. There are reports in the lay
press of the use of herbal medicines, aerobic exercise, and dietary supplements, 
but because most women with painful breastfeeding require immediate relief of the
pain to continue breastfeeding successfully, it is important to offer a treatment
plan that will alleviate the pain quickly. Nifedipine, a calcium channel blocker,
has been used to treat Raynaud's phenomenon because of its vasodilatory effects. 
Very little of the medication can be demonstrated in breast milk and thus is safe
to use in breastfeeding mothers. Of the 12 mothers in our series, 6 chose to use 
nifedipine, and all had prompt relief of pain. Only 1 mother developed side
effects from nifedipine. Pediatricians and lactation consultants should be aware 
of this treatable cause of painful breastfeeding and should specifically question
their patients, because most mothers will not provide this information to the
breastfeeding consultant. Prompt treatment will allow mothers to continue to
breastfeed pain free while avoiding unnecessary antifungal therapy.

Publication Types: 
    Case Reports

PMID: 15060268 [PubMed - indexed for MEDLINE]

166: Tenn Med. 2004 Mar;97(3):117-9.

Cranial nerve VIII involvement in a patient with progressive systemic sclerosis.

Iskandar SB, Loyd S, Roy TM.

Department of Internal Medicine, James H. Quillen College of Medicine, East
Tennessee State University, Johnson City, USA.

Systemic sclerosis is a multisystem disorder characterized by abundant fibrosis
of the skin, blood vessels, and visceral organs. Cranial nerve involvement is an 
uncommon feature of this connective tissue disorder, and when it occurs it is the
trigeminal nerve that is primarily affected. We report an elderly woman who
presented with sensorineural hearing loss and was then diagnosed with the CREST
syndrome of progressive systemic sclerosis (calcinosis cutis, Raynaud's
phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia).
Involvement of the eighth cranial nerve with scleroderma and CREST syndrome is
rare, but appears to be the cause of sensorineural hearing loss in our patient.

Publication Types: 
    Case Reports

PMID: 15054944 [PubMed - indexed for MEDLINE]

167: Eur J Vasc Endovasc Surg. 2004 Apr;27(4):414-6.

Laser Doppler skin perfusion pressure in the assessment of Raynaud's phenomenon.

Kanetaka T, Komiyama T, Onozuka A, Miyata T, Shigematsu H.

Division of Vascular Surgery, Department of Surgery, University of Tokyo, Tokyo, 
Japan.

OBJECTIVES: In the assessment of Raynaud's phenomenon, objective evaluation of
digital microcirculatory flow is important, and so we investigated whether the
measurement of laser Doppler skin perfusion pressure could be of use. MATERIALS
AND METHODS: Ten fingers of five patients with secondary Raynaud's phenomenon due
to systemic sclerosis, 22 fingers of 11 patients with primary Raynaud's
phenomenon and 10 fingers of five control patients were examined. Skin perfusion 
pressure was measured on the third finger of both hands at rest, and then again 3
min after local cold exposure. RESULTS: Laser Doppler skin perfusion pressure at 
rest in patients with secondary Raynaud's phenomenon was significantly lower than
that in patients with primary Raynaud's phenomenon and the control patients
(p<0.05). Skin perfusion pressure decreased significantly in both patient groups 
upon local cold exposure (p=0.005). There were significant differences in
perfusion pressure after cold exposure among both groups (p<0.05). CONCLUSIONS:
The low skin perfusion pressure at rest in patients with secondary Raynaud's
phenomenon suggested the presence of obstructive arterial lesions. The marked
pressure decrease in all Raynaud's patients after local cold exposure might be
due to vasospasm of the microvasculature in the digits. These results indicate
that the measurement of laser Doppler skin perfusion pressure is valuable in the 
diagnosis of Raynaud's phenomenon.

PMID: 15015193 [PubMed - indexed for MEDLINE]

168: Ann Occup Hyg. 2004 Mar;48(2):129-37.

Skin cooling on contact with cold materials: the effect of blood flow during
short-term exposures.

Jay O, Havenith G.

Human Thermal Environments Laboratory, Department of Human Sciences, Loughborough
University, Leicestershire LE11 3TU, UK.

This study investigates the effect of blood flow upon the short-term (<180 s)
skin contact cooling response in order to ascertain whether sufferers of
circulatory disorders, such as the vasospastic disorder Raynaud's disease, are at
a greater risk of cold injury than people with a normal rate of blood flow. Eight
female volunteers participated, touching blocks of stainless steel and nylon with
a finger contact force of 2.9 N at a surface temperature of -5 degrees C under
occluded and vasodilated conditions. Contact temperature (Tc) of the finger pad
was measured over time using a T-type thermocouple. Forearm blood flow was
measured using strain gauge plethysmography. Contact cooling responses were
analysed by fitting a modified Newtonian cooling curve. A significant difference 
was found between the starting skin temperatures for the two blood flow
conditions (P<0.001). However, no effect of blood flow was found upon any of the 
derived cooling curve parameters characterizing the skin cooling response
(P>0.05). It is hypothesized that the finger contact force used (2.9 N) and the
resultant pressure upon the tissue of the contact finger pad restricted the blood
supply to the contact area under both blood flow conditions; therefore, no effect
of blood flow was found upon the parameters describing the contact cooling
response. Whilst the findings of this study are sufficient to draw a conclusion
for those in a working environment, i.e. contact forces below 2.9 N will seldom
be encountered, a further study will be required to ascertain conclusively
whether blood flow does affect the contact cooling response at a finger contact
force low enough to allow unrestricted blood flow to the finger pad. Further
protocol improvements are also recommended.

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

PMID: 14990434 [PubMed - indexed for MEDLINE]

169: J Am Acad Dermatol. 2004 Mar;50(3):456-60.

Coexistence of erythromelalgia and Raynaud's phenomenon.

Berlin AL, Pehr K.

Department of Dermatology, College of Medicine, University of Illinois at
Chicago, Chicago, IL, USA.

Erythromelalgia is characterized by spontaneous recurrent episodes of redness,
heat, and pain of the extremities that can be triggered or worsened by heat.
Raynaud's phenomenon occurs in response to cold exposure and presents as pallor
of the fingers or toes, often followed by cyanosis and rubor. Although the 2
conditions may appear to be opposites in symptomatology and clinical
presentation, there are very rare reports of their coexistence. A case of
coexistent erythromelalgia and Raynaud's phenomenon is presented. The
pathophysiology is reviewed to elucidate a common mechanism underlying some cases
of the 2 seemingly opposite conditions. A review of the literature indicates that
causative and pathophysiologic similarities between the 2 conditions may exist in
some cases. Rare reports of coexistence of the 2 disease processes further
strengthen such research findings.

Publication Types: 
    Case Reports
    Review

PMID: 14988692 [PubMed - indexed for MEDLINE]

170: Clin Hemorheol Microcirc. 2004;30(1):17-24.

Association between capillaroscopy, haemorheological variables and plasma
proteins in patients bearing Raynaud's phenomenon.

Spengler MI, Svetaz MJ, Leroux MB, Leiva ML, Bottai HM.

Departamento de Ciencias Fisiológicas, Cátedra de Física Biológica, Facultad de
Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, CP 2000,
Rosario, Argentina.

Raynaud's phenomenon is a paroxysmal and reversible vasospasm affecting generally
the acral circulatory regions. The relevance of the haemorheological alterations 
in these patients, as a source of ischemic events has been neglected. The
objective of the present work was to evaluate and correlate the rheological blood
properties, some biochemical parameters, e.g., plasma fibrinogen and
immunoglobulin levels, and periungual capillaroscopy. The explicative variables
considered were: blood viscosity, plasma viscosity, erythrocyte rigidity index,
plasma fibrinogen, erythrocyte sedimentation rate, erythrocyte aggregate size,
erythrocyte aggregation rate and serum immunoglobulin (IgG and IgM). The response
variable was the nailfold capillary pattern categorised as either normal or
pathological. Fibrinogen, erythrocyte aggregation rate and IgM are significantly 
higher in patients with a pathological pattern in comparison with patients
bearing a normal one. The statistical analysis enabled us the modelling of the
pathological pattern occurrence probability in function of plasma fibrinogen.
Consequently, 100 mg/dl plasma fibrinogen increase, increases twice the
probability of presenting a pathological pattern. Therefore, we can conclude that
high levels of fibrinogen in Raynaud's phenomenon patients are associated with
impaired skin microcirculation assessed by periungual capillaroscopy.

PMID: 14967879 [PubMed - indexed for MEDLINE]

171: J Eur Acad Dermatol Venereol. 2004 Jan;18(1):62-8.

Nailfold digital capillaroscopy in 447 patients with connective tissue disease
and Raynaud's disease.

Nagy Z, Czirják L.

Hungarian Brothers of St John of Good and University of Pécs, Faculty of
Medicine, Department of Immunology and Rheumatology, H-7621, Pécs, Irgalmasok u. 
1, Hungary.

The presence of megacapillaries and a decreased capillary density are the
hallmarks of the scleroderma capillary pattern, which can be detected by nailfold
capillarmicroscopy. One hundred and eighty-six patients with Raynaud's
phenomenon, 65 cases with undifferentiated connective tissue disease (UCTD), 47
patients with systemic lupus erythematosus (SLE), 26 patients with
dermato/polymyositis, 14 with rheumatoid arthritis, seven cases with primary
Sjögren's syndrome and 102 patients with systemic sclerosis (SSc) were
investigated. Of the 16 patients with diffuse cutaneous SSc and the 86 limited
cutaneous SSc cases, 14 (87.5%) and 53 (61.6%) showed the scleroderma capillary
pattern, respectively. Nine of the 65 (13.8%) cases with UCTD and 24 of the 186
(12.9%) cases with Raynaud's phenomenon also exhibited the same pattern. Four of 
the 47 (8.5%) with SLE and seven of the 26 (26.9%) with dermato/polymyositis, and
no patients with rheumatoid arthritis or Sjögren's syndrome, exhibited the
scleroderma capillary pattern. The conclusion is that the scleroderma capillary
pattern is often present in SSc and dermato/polymyositis. Furthermore, patients
with Raynaud's phenomenon and UCTD may also occasionally exhibit this pattern.
Therefore, capillarmicroscopy seems to be a useful tool for the early selection
of those patients who are potential candidates for developing scleroderma
spectrum disorders.

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

PMID: 14678534 [PubMed - indexed for MEDLINE]

172: J Rheumatol. 2003 Nov;30(11):2503-5.

Severe Raynaud's phenomenon with yohimbine therapy for erectile dysfunction.

Johnson S, Iazzetta J, Dewar C.

Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada.

Yohimbine is a selective alpha-2 adrenergic antagonist that has been used in the 
pharmacologic management of erectile dysfunction (ED). We describe a patient with
CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysfunction,
sclerodactyly, and telangiectasia) who paradoxically experienced worsening of
Raynaud's phenomenon when using yohimbine for ED.

Publication Types: 
    Case Reports

PMID: 14677199 [PubMed - indexed for MEDLINE]

173: Arthritis Rheum. 2003 Dec;48(12):3518-21.

Occurrence of Raynaud's phenomenon in children ages 12-15 years: prevalence and
association with other common symptoms.

Jones GT, Herrick AL, Woodham SE, Baildam EM, Macfarlane GJ, Silman AJ.

University of Manchester, Manchester, UK.

OBJECTIVE: Although Raynaud's phenomenon (RP) in adults is frequently reported as
having been present since childhood, there have been no studies on the prevalence
of RP in children. This study was undertaken to ascertain the prevalence of RP in
children ages 12-15 years and to determine whether, as with other commonly
reported symptoms, there were any associations with adverse psychosocial factors.
METHODS: A previously validated self-administered RP questionnaire was
distributed to 903 children ages 12-15 years, from 28 schools. The questionnaire 
also included questions on other common childhood symptoms and on adverse
psychosocial factors. RESULTS: Seven hundred twenty children responded (80%), in 
whom the prevalence of RP was 15%. This was higher in girls (18% versus 12%) and 
increased with age. After adjustment for age and sex, there was an association
with reporting of current pain, both in the arm/shoulder region and elsewhere in 
the body. There were no associations with psychosocial variables. CONCLUSION: RP 
is frequent in children ages 12-15 years. Unlike other common childhood symptoms,
RP showed no association with psychosocial factors in this study.

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

PMID: 14674003 [PubMed - indexed for MEDLINE]

174: Am J Cardiol. 2003 Dec 1;92(11):1310-5.

Effects of cilostazol in patients with Raynaud's syndrome.

Rajagopalan S, Pfenninger D, Somers E, Kehrer C, Chakrabarti A, Mukherjee D,
Brook R, Kaplan MJ.

Division of Cardiology, Department of Internal Medicine, University of Michigan
School of Medicine, Ann Arbor, Michigan, USA. srajagop@umich.edu

Raynaud's syndrome (RS), which is characterized by recurrent episodes of
vasospasm with exposure to cold, may occur alone (primary RS) or in association
with connective tissue diseases or other underlying conditions (secondary RS). We
investigated the effect of cilostazol on vessel wall responses in RS. Patients
were diagnosed (primary or secondary RS associated with connective tissue
diseases) and randomized to placebo or cilostazol 100 mg twice daily for 6 weeks 
in a double-blind manner. Brachial artery vasoreactivity, laser Doppler
fluxmetry, and cold pressor testing (CPT) were performed at study initiation and 
completion. Symptoms were assessed using standardized questionnaires. Forty
subjects completed the study (19 with primary RS and 21 with secondary RS).
Cilostazol significantly increased the mean brachial artery diameter at 6 weeks
(primary RS, p = 0.006; secondary RS, p = 0.06). There was no change in median
flow-mediated dilation (FMD) with cilostazol in primary RS (25th, 75th
percentiles) (4.06% [2.5, 6.1] to -0.77% [-2.4, 3.4] or secondary RS (2.2% [0.05,
6.3] to 2.95% [1.7, 7.4]). There were no changes in nitroglycerin-mediated
dilation or microvascular flow indexes in either cohort. In patients with primary
RS, cilostazol treatment yielded a positive change in the slope of brachial
responsiveness to CPT (increase of 0.32 mm/min; p = 0.002 vs placebo). Cilostazol
treatment remained significantly associated with increased brachial artery
diameter when controlling for baseline values (p = 0.018). Cilostazol increased
conduit vessel diameter in patients with primary and secondary RS, with a
favorable impact on conduit vessel responsiveness to cold in patients with
primary RS without affecting microvascular flow or symptoms.

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

PMID: 14636909 [PubMed - indexed for MEDLINE]

175: Occup Environ Med. 2003 Dec;60(12):962-8.

Skin temperature recovery from cold provocation in workers exposed to vibration: 
a longitudinal study.

Cherniack M, Brammer A, Meyer J, Morse T, Peterson D, Fu R.

University of Connecticut Health Center, Farmington, CT 06030-6210, USA.

BACKGROUND: Vibration white finger (VWF) is characterised by arterial
hyperresponsiveness and vasoconstriction following cold provocation. Several
years after of removal from exposure, most subjects show improved finger systolic
blood pressure (FSBP) under conditions of cold challenge, but continue to report 
cold hands and finger blanching. AIMS: To assess the underlying reasons for the
persistence of cold symptoms. METHODS: A total of 204 former users of pneumatic
tools with cold related hand symptoms were evaluated and then re-evaluated a year
later. Symptoms were evaluated using the Stockholm Workshop Scale. Finger
systolic blood pressure per cent (FSBP%) was assessed by comparing digital blood 
pressure in a cold provoked and normalised state. Fingertip skin temperature was 
measured during cooling and occlusion and during rewarming and recovery. RESULTS:
There were dramatic improvements in FSBP% (14.3 mm Hg %), modest improvement in
recovered skin temperature (0.86 degrees C), and no change in symptom stage. When
the most symptomatic subjects (n = 75) were compared with the less symptomatic
subjects (n = 129), there were similar inter-test improvements in FSBP%. Skin
temperature recovery improved in the less symptomatic (+1.49 degrees C), but did 
not change in the most symptomatic group (-0.12 degrees C). However, the more
symptomatic group had higher temperatures at the initial test, thus qualifying
the result. CONCLUSIONS: Skin temperature recovery after cold challenge in
subjects with VWF remains reduced in the symptomatic subjects several years after
exposure removal. This is evident even when blood pressure has increased in the
setting of cold provocation. Results suggest that in VWF, the dermal circulation 
remains impaired, even after the restoration of arterial blood pressure in the
digits.

PMID: 14634190 [PubMed - indexed for MEDLINE]

176: Int Angiol. 2003 Sep;22(3):243-9.

Blood endothelin-1 and cold-induced vasodilation in patients with primary
Raynauld's phenomenon and workers with vibration-induced white finger.

Nakamura H, Matsuzaki I, Hatta K, Nagase H, Nobokuni Y, Kambayashi Y, Ogino K.

Department of Environmental and Preventive Medicine, Graduate School of Medical
Science, Kanazawa, Japan. hiro-n@po.incl.ne.jp

AIM: Cold water-immersion induces vasoconstriction with an elevation of blood
endothelin-1, which is a potent vasoconstrictor peptide, in patients with primary
Raynaud's phenomenon (PRP). However, physiological involvement of endothelin-1 in
cold-induced vasodilation (CIVD) remains to be elucidated. METHODS: We monitored 
changes of finger blood flow during cold water (10 degrees C) immersion and
assayed blood endothelin-1 in 7 PRP patients and 7 workers with vibration-induced
white finger (VWF) and in the respective control subjects. RESULTS: While
significant reductions in finger blood flow at 2 min after the immersion were
observed in PRP patients and VWF workers, its elevation at 4 min, which was
considered to reflect CIVD, was recognized only in PRP patients. In healthy
controls, blood endothelin-1 increased at 4 min and returned to the basal level
immediately after the immersion. The increase in blood endothelin-1 at 4 min in
PRP patients was greater than that in controls, and continued even after the
immersion. Conversely, the increase neither at 4 min nor after immersion was seen
in VWF workers. Local vascular changes produced by repetitive vibration may be
responsible for the attenuated CIVD and unchanged blood endothelin-1 during cold 
water-immersion in VWF workers. CONCLUSION: Our results showing elevated blood
endothelin-1 during and after immersion in PRP contrast with that in VWF
suggesting that endothelin-1 is related to sympathetic hyperactivity which is
more involved in PRP rather than VWF. It seems unlikely that endothelin-1 is
functionally or directly associated with CIVD.

PMID: 14612851 [PubMed - indexed for MEDLINE]

177: Clin Rheumatol. 2003 Oct;22(4-5):279-84.

Raynaud's phenomenon: clinical spectrum of 118 patients.

De Angelis R, Del Medico P, Blasetti P, Cervini C.

Department of Rheumatology, University of Ancona, Italy. deaross65@libero.it

OBJECTIVES: To establish the prevalence of the associated secondary diseases in
patients with Raynaud's phenomenon (RP) attending a rheumatology specialty centre
and to determine the frequency with which a secondary illness develops in those
having RP, in absence of a well-defined secondary cause. METHODS: 118 consecutive
patients were evaluated. Medical history, physical and laboratory investigations 
entered into a database. Patients with primary RP and patients with RP who did
not fulfil any diagnostic criteria for inclusion in a secondary form were
followed up over a three-year period. RESULTS: 63 RP patients were found with
related conditions. 35 patients met criteria for inclusion in a primary RP group,
20 patients had 'unclassifiable' RP, of which two (10%) developed a well-defined 
disease. None of the primary RP patients developed a secondary disease.
CONCLUSIONS: This study shows that less than 50% of patients with RP attending a 
rheumatology specialty centre have a connective tissue disease. Patients with
isolated RP appear to have a benign disease, since primary RP remains as such,
and only a small percentage of patients with 'unclassifiable' RP evolve into a
well-defined CTD.

Publication Types: 
    Comparative Study

PMID: 14576990 [PubMed - indexed for MEDLINE]

178: Clin Rheumatol. 2003 Sep;22(3):196-202.

Vascular damage and lack of angiogenesis in systemic sclerosis skin.

Konttinen YT, Mackiewicz Z, Ruuttila P, Ceponis A, Sukura A, Povilenaite D,
Hukkanen M, Virtanen I.

Department of Medicine, Orton Research Institute and the Orthopaedic Hospital of 
the Invalid Foundation, Helsinki, Finland. yrjo.konttinen@helsinki.fi

The aim of this study was to analyse microvascular damage and compensatory
angiogenesis in skin from patients with systemic sclerosis (SSc) compared with
systemic lupus erythematosus (SLE), Raynaud's phenomenon (RP) and healthy
controls. Immunohistochemistry was used for skin biopsies (9 SSc, 10 SLE, 9 RP
and 12 healthy controls) using von Willebrand factor and beta3 integrin subunit
specific antibodies, TechMate immunostaining robot and biotin-streptavidin
protocol. In the early stages of SSc, vWF was found in the perivascular space and
interstitial matrix in papillary but not in the reticular dermis, in particular
around small oedematous blood vessels infiltrated by mononuclear cells. The
extravascular release of vWF in SSc specimens was associated with weak or even a 
total lack of immunoreactivity within the associated endothelial cells. Late
stages of SSc were characterised by loss of the dermal papillae, subepidermal
fibrosis, hypovascularity and strong endothelial vWF expression without
extravascular leakage. In all SSc patients studied only a few vascular profiles
were weakly immunostained for beta3 integrin subunit. This work demonstrates that
vWF is not only released into the systemic circulation, but is also leaked to the
perivascular space/matrix. This local release and deposition of vWF is probably a
sensitive and early marker of microvascular involvement in SSc pathogenesis.
Local vWF release may play a role in platelet adhesion, aggregation,
thrombogenesis and dermal connective tissue remodelling. In spite of some
attempts towards compensatory angiogenesis in SSc, as evidenced by beta3 integrin
subunit expression, it was evident that the angiogenic response was not able to
prevent the development of hypovascularity during the advanced stages of the
disease.

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

PMID: 14505210 [PubMed - indexed for MEDLINE]

179: Ann Rheum Dis. 2003 Oct;62(10):1003-5.

Raynaud's phenomenon and antiphospholipid antibodies in systemic lupus
erythematosus: is there an association?

Caccavo D, Del Porto F, Garzia P, Mitterhofer AP, Galluzzo S, Rigon A, Vadacca M,
Navajas MF, Amoroso A, Afeltra A.

Department of Clinical Medicine, Immunology, and Infectious Diseases, University 
of Bari, Bari, Italy.

OBJECTIVE: To evaluate the association of IgG and IgM antibodies directed against
different negatively charged phospholipids (that is, anticardiolipin (aCL),
antiphosphatidylinositol, antiphosphatidylserine, and antiphosphatidic acid) and 
anti-beta(2)-glycoprotein I (abeta(2)GPI), with Raynaud's phenomenon in patients 
with systemic lupus erythematosus (SLE). METHODS: Ninety three patients with SLE 
(81 female), 40 with and 53 without Raynaud's phenomenon, were included in the
study. IgG and IgM antiphospholipid antibodies and abeta(2)GPI were determined by
enzyme linked immunosorbent assay (ELISA). RESULTS: Fifty patients (54%) were
positive for IgG and/or IgM antibodies to one or more phospholipid antigens or to
beta(2)GPI. The prevalence of all autoantibodies evaluated, either IgG or IgM,
was higher in patients without than in those with Raynaud's phenomenon. A
negative association was found between IgG aCL and Raynaud's phenomenon
(p=0.038), whereas autoantibodies other than aCL were not significantly
associated with Raynaud's phenomenon. CONCLUSION: Our results demonstrate no
positive association between antiphospholipid antibodies and Raynaud's phenomenon
in SLE and indicate that measurement of anti-negatively charged phospholipid
antibodies other than aCL is not useful as a serological marker predictive for
Raynaud's phenomenon.

Publication Types: 
    Comparative Study

PMID: 12972482 [PubMed - indexed for MEDLINE]

180: Vasa. 2003 May;32(2):83-6.

Systemic scleroderma patients have improved skin perfusion after the transdermal 
application of PGE1 ethyl ester.

Schlez A, Häfner HM, Kittel M, Braun S, Diehm C, Jünger M.

Universitäts-Hautklinik, Eberhard-Karls-Universität, Tübingen.

BACKGROUND: Patients with systemic scleroderma exhibit a noticeable slowing of
blood cell velocities or even stasis in the capillaries of the skin. In this
study the effects of transdermally applied prostaglandin PGE1 ethyl ester on
nutritive cutaneous perfusion and on Raynaud's symptoms were investigated.
PATIENTS AND METHODS: 24 patients with systemic scleroderma were treated
transdermally over a period of 14 days with prostaglandin E1 ethyl ester patches.
The response of blood cell velocity in the nailfold capillaries to cold exposure 
was tested in 20 patients, and all of the patients recorded the number of
Raynaud's episodes in a journal over a period of two weeks. RESULTS: After the
transdermal application of prostaglandin E1 ethyl ester there was an increase in 
blood cell velocity in the nutritive capillaries of systemic scleroderma patients
(increase from 0.35 +/- 0.14 mm/s to 0.47 +/- 0.11 mm/s, (p < 0.05)). At the same
time there was a decrease in the number of Raynaud's episodes (2.9 +/- 2.4 per
day to 2.6 +/- 2.0 per day (p < 0.05)). CONCLUSION: The transdermal application
of prostaglandin E1 ethyl ester was shown to have a favourable effect on
nutritive blood flow in the capillaries of the skin in systemic scleroderma
patients.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 12945100 [PubMed - indexed for MEDLINE]

181: Vasa. 2003 May;32(2):69-73.

Lack of seasonal variation in flow-mediated dilatation of the brachial artery in 
women with primary Raynaud's phenomenon and healthy controls.

Klein-Weigel P, Krall K, Falkensammer J, Heinz-Erian P, Ulmer H, Fraedrich G.

Department of Vascular Surgery, University of Innsbruck, Austria.
p.klein-weigel@ruppiner-kliniken.de

BACKGROUND: The aim of this study was to examine endothelium function and
seasonal variations of endothelium function in women with primary Raynaud's
phenomenon (RP) and healthy controls. PATIENTS AND METHODS: After a fast of at
least 8 hours we studied 21 patients with primary RP (mean age 31.1 years, mean
duration of RP 9.1 years) and 22 controls (mean age 27.8 years) by use of high
resolution brachial artery sonography in winter (December/January 2000) and
summer (July/August 2001). To exclude circadian variations all examinations were 
performed in the late afternoon only. All subjects were non-smokers. Confounding 
factors like serum glucose, HbAlc, and lipid concentrations were analyzed
immediately before the investigations. Nicotine contamination was randomly
analyzed in hair samples in 8 subjects of each study group. Flow mediated
dilatation (FMD%) and nitroglycerin induced dilatation (NID%) were calculated by 
putting the basal vessel diameter as 100%. RESULTS: Basal, flow-mediated, and
nitroglycerin-induced absolute diameters of the brachial artery did not differ
significantly between the study groups (p = 0.85). The test conditions (basal,
postocclusive, nitroglycerin-induced) always let to the same vessel response in
winter and summer (p = 0.61) and there was no significant influence between these
test conditions and the study groups (p = 0.07). Compared to patients FMD% was
slightly reduced in controls in summer (p = 0.09). Analysis of variance excluded 
a significant relation between study group and season (p = 0.43). For NID% too,
no statistically significant differences were found. CONCLUSIONS: We were not
able to show impaired or seasonally variant flow-mediated or
nitroglycerin-induced dilatation of the brachial artery in patients with primary 
RP. Our results argue against the presence of a more generalized endothelium
dysfunction detectable with high resolution ultrasound of the brachial artery in 
patients with primary RP.

PMID: 12945098 [PubMed - indexed for MEDLINE]

182: Reg Anesth Pain Med. 2003 Jul-Aug;28(4):354-8.

Continuous regional anesthesia before surgical peripheral sympathectomy in a
patient with severe digital necrosis associated with Raynaud's phenomenon and
scleroderma.

Greengrass RA, Feinglass NG, Murray PM, Trigg SD.

Department of Anesthesiology, Mayo Clinic, Jacksonville, Florida, USA.

BACKGROUND AND OBJECTIVE: Digital ischemia and necrosis caused by Raynaud's
phenomenon in patients with connective tissue diseases may not respond to medical
therapy and may have major adverse effects on quality of life. We describe the
use of continuous ambulatory regional anesthesia for diagnosis and treatment
before peripheral sympathectomy in a patient with secondary Raynaud's phenomenon.
CASE REPORT: A 55-year-old man with progressive systemic sclerosis and secondary 
Raynaud's phenomenon presented with severe pain and digital necrosis that were
refractory to maximal medical treatment and thoracic sympathectomy. Continuous
ambulatory regional analgesia increased digital temperature from 32.3 degrees C
at baseline to 34.4 degrees C after 80 minutes. An increase in digital flow was
documented by Doppler ultrasound measurements made ventrally at the point of
greatest pulsation of the radial artery. Subsequent peripheral sympathectomy
resulted in restoration of nutrient flow with healing of ulcers and alleviation
of pain. CONCLUSIONS: Continuous ambulatory regional anesthesia appears effective
as a treatment bridge for vasospasm and ischemia associated with secondary
Raynaud's phenomenon. The enhancement of peripheral blood flow achieved with the 
regional anesthetic technique suggests that surgical peripheral sympathectomy may
provide long-term benefits.

Publication Types: 
    Case Reports

PMID: 12945033 [PubMed - indexed for MEDLINE]

183: Clin Exp Rheumatol. 2003 Jul-Aug;21(4):445-50.

The outcome of angiography in patients with Raynaud's phenomenon: an unexpected
role for atherosclerosis and hypercholesterolemia.

van Vugt RM, Kater L, Dijkstra PF, Schardijn GH, Kastelein JJ, Bijlsma JW.

Department of Rheumatology and Clinical Immunology, Slotervaart Hospital,
Amsterdam, The Netherlands.

OBJECTIVE: Upper extremity angiography can make an important contribution to the 
diagnosis in vasculopathy. The present study was designed to assess the
diagnostic role of upper extremity angiography in patients with disturbed
circulation of the hand, according to a standardised protocol. METHODS: The study
was carried out in an outpatient setting in 103 patients suffering from bilateral
Raynaud's phenomenon without any obvious underlying disease and who were
unresponsive to nifedipine and aspirin. All patients had angiographies taken
according to a standardized technique using vasodilating medication, and reviewed
according to a standardised protocol that covered all the known characteristics
of angiopathy such as diminished flow, stops, tortuosity, irregularity of the
wall, tapering, collaterals and blushing. RESULTS: Standardised angiograms showed
vasculopathy compatible with primary vasospasm in 42 patients [all women; mean
age 35.1 years], atherosclerotic vascular disease in 44 patients [M/F 9/35; mean 
age 46.7 years], peripheral embolism in 8 patients [M/F 4/4; mean age 38.4
years], vasculitis in 3 patients [3 women; mean age 38 years] and Buerger's
disease in 3 patients [3 men; mean age 47 years]. Inter-observer differences were
present in 4 cases, but consensus could be reached through open discussion. An
unexpected 47% of patients with atherosclerotic vascular disease had
dyslipidemia, frequently of familial origin. CONCLUSIONS: The standardised
angiography protocol proved to be helpful in the assessment of upper extremity
angiography. Surprisingly, a high prevalence of angiographic abnormalities
compatible with atherosclerotic vascular disease could already be diagnosed in
relatively young patients with Raynaud's phenomenon, of whom 47% showed
hypercholesterolemia.

Publication Types: 
    Comparative Study

PMID: 12942695 [PubMed - indexed for MEDLINE]

184: Dermatol Surg. 2003 Sep;29(9):968-70.

Successful palliation and significant remission of cutaneous calcinosis in CREST 
syndrome with carbon dioxide laser.

Chamberlain AJ, Walker NP.

Department of Dermatology, The Churchill, Oxford Radcliffe Hospitals, Old Road,
Headington, Oxford OX3 7LJ, United Kingdom. alex_chamberlain@hotmail.com

BACKGROUND: There are few satisfactory medical or surgical therapies for
cutaneous calcinosis in connective tissue disorders. OBJECTIVE: Carbon dioxide
laser vaporization allows precise ablation of superficial dystrophic
calcification. This treatment modality was considered because of the severity of 
our patient's symptoms and failure to respond to various medical therapies.
METHODS: Over a 5-year period, six affected digits received a single treatment
with carbon dioxide laser vaporization. RESULTS: Treated digits healed over a
6-week period and led to a significant remission in symptoms. The average
remission time for affected digits to date is at least 3 years and has allowed
our patient to remain in full-time employment. CONCLUSION: Carbon dioxide laser
vaporization may offer effective remission of symptoms in cutaneous calcinosis of
CREST syndrome (including cutaneous calcinosis, Raynaud's phenomenon,
sclerodactyly, and telangiectasia).

Publication Types: 
    Case Reports

PMID: 12930342 [PubMed - indexed for MEDLINE]

185: Arch Dermatol. 2003 Aug;139(8):1027-30.

Comment in:
    Arch Dermatol. 2004 May;140(5):617.

The handheld dermatoscope as a nail-fold capillaroscopic instrument.

Bergman R, Sharony L, Schapira D, Nahir MA, Balbir-Gurman A.

Departments of Dermatology and Rheumatology, Rambam Medical Center and the Bruce 
Rappaport Faculty of Medicine, Haifa, Israel. r_bergman@Rambam.health.gov.il

BACKGROUND: The presence of nail-fold capillary abnormalities may be useful in
diagnosing several connective tissue disorders, including scleroderma,
dermatomyositis, and mixed connective tissue disease, and in differentiating
primary Raynaud phenomenon from Raynaud phenomenon due to scleroderma and mixed
connective tissue disease. Capillaroscopy, however, usually requires special
equipment and may be time consuming.Purpose To investigate the potential use of
the unmodified common handheld dermatoscope as a capillaroscopic
instrument.Subjects The study included 106 patients who were consecutively
referred and a control group of 170 healthy subjects or patients with unrelated
skin disorders. METHODS: A nail-fold capillaroscopic examination using a standard
handheld dermatoscope was performed on all fingers of each subject. A
scleroderma-dermatomyositis pattern was defined as the presence of 2 or more of
the following findings in at least 2 nail folds: enlargement of capillary loops, 
loss of capillaries, disorganization of the normal distribution of capillaries,
"budding" ("bushy") capillaries, twisted enlarged capillaries, and capillary
hemorrhages (extravasates). RESULTS: A scleroderma-dermatomyositis pattern was
found in 19 (70.4%) of 27, 7 (63.6%) of 11, and 4 (50%) of 8 patients with
scleroderma, dermatomyositis, and mixed connective tissue disease, respectively. 
These frequencies were statistically significantly higher than a null percentage 
of scleroderma-dermatomyositis pattern in the control group (P<.001) and a
scleroderma-dermatomyositis pattern in only 1 (4.5%) of 22 patients with systemic
lupus erythematosus as well as in 2 (5.3%) of 38 patients with Raynaud phenomenon
but without evidence of a connective tissue disorder (P<.01). CONCLUSIONS: The
capillaroscopic results obtained with the dermatoscope are comparable to those
described with other instruments. Therefore, the unmodified hand-held
dermatoscope may be used as a capillaroscopic instrument to detect a
scleroderma-dermatomyositis pattern and to help the dermatologist in the clinical
diagnosis of connective tissue disorders.

Publication Types: 
    Evaluation Studies

PMID: 12925391 [PubMed - indexed for MEDLINE]

186: Arthritis Rheum. 2003 Jul;48(7):1992-2000.

Increased asymmetric dimethylarginine and endothelin 1 levels in secondary
Raynaud's phenomenon: implications for vascular dysfunction and progression of
disease.

Rajagopalan S, Pfenninger D, Kehrer C, Chakrabarti A, Somers E, Pavlic R,
Mukherjee D, Brook R, D'Alecy LG, Kaplan MJ.

Department of Internal Medicine, University of Michigan Medical School, Ann
Arbor, MI 48109-0273, USA. srajagop@umich.edu

OBJECTIVE: To compare microvascular and macrovascular functions in a cohort of
patients with primary and secondary Raynaud's phenomenon (RP) who were matched
for demographic, risk factor, and severity profiles. METHODS: Forty patients with
primary or secondary RP matched for vascular risk factors and severity scores
underwent testing of endothelial function and cold pressor responsiveness of the 
brachial artery. Microvascular perfusion of the digital vasculature was assessed 
using laser Doppler fluxmetry in response to reactive hyperemia. Plasma was
assayed for endothelin 1 (ET-1), asymmetric dimethylarginine (ADMA),
intercellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1),
and monocyte chemoattractant protein 1 (MCP-1). RESULTS: Patients with RP had
abnormal vasoconstrictor responses to cold pressor tests (CPT) that were similar 
in primary and secondary RP. There were no differences in median flow-mediated
and nitroglycerin-mediated dilation or CPT of the brachial artery in the 2
populations. Patients with secondary RP were characterized by abnormalities in
microvascular responses to reactive hyperemia, with a reduction in area under the
curve adjusted for baseline perfusion, but not in time to peak response or peak
perfusion ratio. Plasma ET-1, ADMA, VCAM-1, and MCP-1 levels were significantly
elevated in secondary RP compared with primary RP. There was a significant
negative correlation between ET-1 and ADMA values and measures of microvascular
perfusion but not macrovascular endothelial function. CONCLUSION: Secondary RP is
characterized by elevations in plasma ET-1 and ADMA levels that may contribute to
alterations in cutaneous microvascular function.

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

PMID: 12847693 [PubMed - indexed for MEDLINE]

187: Rheum Dis Clin North Am. 2003 May;29(2):293-313.

Management of Raynaud's phenomenon and digital ischemic lesions in scleroderma.

Hummers LK, Wigley FM.

Division of Rheumatology, Johns Hopkins University, Baltimore, MD 21205, USA.

Raynaud's phenomenon is a challenging problem in patients who have scleroderma.
It causes a great deal of morbidity with recurrent painful attacks and frequent
digital ischemic lesions. The strategy to treat the vascular disease must
consider treatment for the vasospasm and the intrinsic vascular disease with
intimal proliferation and vessel occlusion. Vasodilator therapy remains the main 
method to treat Raynaud's phenomenon, but new understanding of the pathobiology
of scleroderma vascular disease is providing novel treatment options. We need
more investigations into these vasoactive drugs before routine use can be
recommended. Critical ischemia can cause deep tissue injury and digital loss. An 
aggressive approach to reversing an ischemic crisis is essential for preventing
these severe events.

Publication Types: 
    Review

PMID: 12841296 [PubMed - indexed for MEDLINE]

188: Rheum Dis Clin North Am. 2003 May;29(2):275-91, vi.

The vasculopathy of Raynaud's phenomenon and scleroderma.

Flavahan NA, Flavahan S, Mitra S, Chotani MA.

Heart and Lung Research Institute, Ohio State University, 473 West 12th Avenue,
Columbus OH 43210, USA. flavahan.1@osu.edu

The scleroderma (SSc) disease process involves dramatic dysfunction in acute and 
chronic vascular regulatory mechanisms; it presents initially with heightened
vasoconstrictor or vasospastic activity and progresses to structural derangement 
or vasculopathy of the microcirculation. This article discusses the regulatory
mechanisms that contribute to this dysfunction and the vascular changes in the
context of the other aspects of the SSc disease process in a novel attempt to
integrate the individual pathologies of the disease process.

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

PMID: 12841295 [PubMed - indexed for MEDLINE]

189: Microvasc Res. 2003 Jul;66(1):73-6.

Comparison of thermography and laser Doppler imaging in the assessment of
Raynaud's phenomenon.

Clark S, Dunn G, Moore T, Jayson M 4th, King TA, Herrick AL.

University of Manchester Rheumatic Diseases Centre, Hope Hospital, M6 8HD,
Salford, UK.

The main objective of the study was to compare the techniques of thermographic
and laser Doppler imaging in the assessment of digital blood flow. Thermography
measures surface temperature; laser Doppler measures microciculatory flow.
Seventeen healthy control subjects and 40 patients with Raynaud's phenomenon (7
primary, 33 secondary to systemic sclerosis) underwent a 20-min acclimatization
period at 23 degrees C. Thermographic and then laser Doppler images were taken of
the dorsal aspect of both hands, and the procedure was repeated at a room
temperature of 30 degrees C. Three regions/values of interest from each hand were
chosen for analysis: the dorsum of the hand, the tip of the middle finger, and
the "gradient" between these. Thermographic and laser Doppler results correlated 
poorly. For example, correlations between techniques for the gradient value were 
as follows: left hand 23 degrees C, r = 0.61; right hand 23 degrees C, r = 0.64; 
left hand 30 degrees C, r = 0.47; right hand 30 degrees C, r = 0.48. One
explanation for these findings is that laser Doppler imaging is more sensitive to
blood flow changes and therefore more likely to show inhomogeneities than the
highly damped temperature response. Therefore one technique cannot substitute for
another.

PMID: 12826077 [PubMed - indexed for MEDLINE]

190: J Rheumatol. 2003 Jun;30(6):1244-7.

Spontaneous chromosome damage (micronuclei) in systemic sclerosis and Raynaud's
phenomenon.

Porciello G, Scarpato R, Ferri C, Storino F, Cagetti F, Morozzi G, Bellisai F,
Migliore L, Marcolongo R, Galeazzi M.

Istituto di Reumatologia, University of Siena, Italy. g.porciello@katamail.com

OBJECTIVE: To evaluate the prevalence of spontaneous chromosome damage in
cultured peripheral lymphocytes of patients with systemic sclerosis (SSc),
idiopathic Raynaud's phenomenon (RP), and suspected secondary RP, by means of
molecular cytogenetic analysis. METHODS: We studied 43 patients with SSc, 13 with
idiopathic RP, and 16 with suspected secondary RP and 25 healthy controls. As a
marker of chromosome alteration we used the micronucleus (MN) assay. All subjects
were also classified for antinuclear antibodies, anticentromere antibodies (ACA),
or Scl70. To identify the mechanism of MN formation, we also performed MN
fluorescence in situ hybridization (FISH) analysis using a pancentromeric DNA
probe. RESULTS: Patients with SSc and subjects with RP showed significantly
higher MN frequencies than controls (25.9 +/- 1.7 and 19.1 +/- 2.15,
respectively, vs 9.4 +/- 2.2; p < 0.001). Subjects with suspected secondary RP
displayed MN frequency (23.5 +/- 2.7) comparable to that of SSc patients, while
spontaneous MN level in idiopathic RP subjects (13.6 +/- 3.0) did not differ
significantly from controls (9.4 +/- 2.2). ACA positive subjects showed the
highest MN frequencies (32.8 +/- 1.7) compared to subjects with a different
antibody pattern (18.3 +/- 1.6). CONCLUSION: Our results show the presence of
higher levels of micronuclei in circulating lymphocytes of patients with SSc and 
subjects with suspected secondary RP. They also suggest a possible role of ACA in
determining cytogenetic anomalies. FISH analysis indicated that both
aneuploidogenic and clastogenic events contributed to the formation of MN
observed in SSc patients and subjects with suspected secondary RP.

PMID: 12784397 [PubMed - indexed for MEDLINE]

191: Int Angiol. 2003 Mar;22(1):95-7.

Hypereosinophilia-induced digital necrosis in a smoking patient.

Stephan D, Lipsker D, Sens P, Hassani S, Welsch M.

Vascular Diseases and Hypertension, University Hospital of Strasbourg,
Strasbourg, France. Dominique.Stephan@chru-strasbourg.fr

Raynaud's phenomenon and digital necrosis of the fingers are rare complications
of hypereosinophilia. We report a case of a smoking male who developed Raynaud's 
phenomenon and digital necrosis of the fingers associated with idiopathic
hypereosinophilia with angiographically documented occlusion of small and medium 
arteries of the extremities. The eosinophils may play a thrombotic role in
vascular pathology and eosinophil blood count should be checked when
investigating patients with digital gangrene.

Publication Types: 
    Case Reports

PMID: 12771865 [PubMed - indexed for MEDLINE]

192: Vasc Med. 2002;7(4):265-7.

The use of Ginkgo biloba in Raynaud's disease: a double-blind placebo-controlled 
trial.

Muir AH, Robb R, McLaren M, Daly F, Belch JJ.

Peripheral Vascular Diseases Research Unit, University Department of Medicine,
Ninewells Hospital & Medical School, Dundee, UK. a.h.muir@dundee.ac.uk

Raynaud's phenomenon (RP) is a common and painful condition characterized by
episodic digital ischaemia produced by emotion and cold. Treatment of RP is
notoriously difficult because of the high incidence of side effects. The aim of
our study was to investigate the clinical efficacy of a standardized Ginkgo
biloba extract (Seredrin) in the treatment of RP in patients with no apparent,
associated condition such as systemic sclerosis. A two-week assessment period was
done during which patients were asked to record frequency, severity and duration 
of attacks in diaries. Subjects were then randomized independently of the study
centre to receive either active or placebo treatment for 10 weeks, during which
time the same data were recorded in their diaries. Patients were seen after two
and four weeks of treatment and at the end of the 10-week treatment phase. Blood 
samples pre- and post-treatment were taken for haemorrheology. Only in the number
of attacks per day was there a significant effect of treatment over placebo. The 
number of attacks per week prior to treatment with Seredrin was 13.2 +/- 16.5
reducing to 5.8 +/- 8.3, a reduction of 56%, whereas placebo reduced the number
by only 27% (p < or = 0.00001). There were no significant differences in
haamorrheology between the two groups. Ginkgo biloba phytosome may be effective
in reducing the number of Raynaud's attacks per week in patients suffering from
Raynaud's disease.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12710841 [PubMed - indexed for MEDLINE]

193: Mol Cell Biochem. 2003 Feb;244(1-2):139-41.

Oral L-arginine can reverse digital necrosis in Raynaud's phenomenon.

Rembold CM, Ayers CR.

Cardiovascular Division, Department of Internal Medicine, University of Virginia 
Health System, Charlottesville, VA 22908-0146, USA. crembold@virginia.edu

Raynaud's phenomenon is characterized by transient reduction in blood supply
through the small arteries in the hands and feet. Severe Raynaud's phenomenon can
cause digital necrosis. It has been hypothesized that nitric oxide may have a
role in Raynaud's phenomenon. We report two cases in which oral L-arginine
reversed digital necrosis in Raynaud's phenomenon and two additional cases in
which the symptoms of severe Raynaud's phenomenon were improved with oral
L-arginine. These reports suggest that a defect in nitric oxide synthesis or
metabolism is present in Raynaud's phenomenon. They also suggest a potential role
for oral L-arginine therapy in Raynaud's phenomenon, especially in Raynaud's
phenomenon with digital necrosis.

Publication Types: 
    Case Reports

PMID: 12701823 [PubMed - indexed for MEDLINE]

194: Postgrad Med J. 2003 Mar;79(929):176-7.

Raynaud's phenomenon after radical radiotherapy for tumours of the head and neck.

Westbury CB, Harrington KJ, Rhys-Evans P, Archer DJ, Searle AE, Henk JM, Black
CM, Nutting CM.

Head and Neck Unit, Royal Marsden Hospital NHS Trust, London, UK.

Endothelial cell injury is implicated in the development of radiation induced
tissue damage and may also be involved in the pathophysiology of secondary
Raynaud's phenomenon. Two patients are presented in whom the typical symptoms and
signs of Raynaud's phenomenon developed as a late complication of radical
radiotherapy. One had Raynaud's of the tongue and one of the lip. Both patients
had a prior history of primary Raynaud's phenomenon and in each case the symptoms
were repeatedly precipitated by sudden cold exposure. The possible pathogenesis
of radiation induced Raynaud's phenomenon in the head and neck region is
discussed.

Publication Types: 
    Case Reports

PMID: 12697923 [PubMed - indexed for MEDLINE]

195: Int J Vitam Nutr Res. 2003 Feb;73(1):3-7.

Ascorbic acid does not improve endothelium-dependent flow-mediated dilatation of 
the brachial artery in patients with Raynaud's phenomenon secondary to systemic
sclerosis.

Mavrikakis ME, Lekakis JP, Papamichael CM, Stamatelopoulos KS, Kostopoulos ChC,
Stamatelopoulos SF.

Department of Clinical Therapeutic, Alexandra University Hospital, Athens,
Greece.

Previous studies have shown that patients with Raynaud's phenomenon secondary to 
systemic sclerosis present abnormal endothelial function; the mechanisms
responsible for the endothelial dysfunction are unknown but increased vascular
oxidative stress could be a possible cause. The hypothesis that a potent
water-soluble antioxidant can reverse endothelial dysfunction in these patients
was tested in the present study. We examined 11 female patients with Raynaud's
phenomenon secondary to systemic sclerosis and ten healthy control women by
ultrasound imaging of the brachial artery to assess flow-mediated
(endothelium-dependent) and nitrate-induced (endothelium-independent)
vasodilatation. Flow-mediated dilatation and nitrate-induced dilatation were
significantly reduced in patients with Raynaud's phenomenon, indicating abnormal 
endothelial and smooth muscle cell function. Patients with Raynaud's phenomenon
entered a double-blind, randomized, crossover placebo-controlled trial and
received orally 2 g of ascorbic acid or placebo; vascular studies were repeated
two hours after ascorbic acid or placebo administration. Flow-mediated dilatation
did not improve after ascorbic acid (1.6 +/- 2.2% to 2.2 +/- 2.5%, ns) or placebo
administration (1.2 +/- 1.9% to 1.7 +/- 1.4%, ns); also nitrate-induced
dilatation was similar after ascorbic acid or placebo (16 +/- 7.4% vs 17 +/- 8%, 
ns), suggesting no effect of ascorbic acid on endothelial and vascular smooth
muscle function. In conclusion, ascorbic acid does not reverse endothelial
vasomotor dysfunction in the brachial circulation of patients with Raynaud's
phenomenon secondary to systemic sclerosis. The use of different antioxidants or 
different dosing of ascorbic acid may be required to show a beneficial effect on 
endothelial vasodilator function.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12690904 [PubMed - indexed for MEDLINE]

196: Clin Exp Rheumatol. 2003 Jan-Feb;21(1):99-102.

Open label trial of tamoxifen in scleroderma.

Thomas-Golbanov CK, Wilke WS, Fessler BJ, Hoffman GS.

Department of Rheumatologic and Immunologic Diseases, Cleveland Clinic
Foundation, Desk A50, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.

BACKGROUND: Previous reports have suggested that treatment with the selective
estrogen antagonist tamoxifen may be effective in diminishing primary and
secondary Raynaud's vasospasm, including cases occurring in the setting of
scleroderma. Tamoxifen treatment has also been associated with improvement of
retroperitoneal fibrosis and desmoid tumors, conditions also associated with
abnormal fibroblast proliferation. Tamoxifen increases production of the
immunosuppressive cytokine TGF beta which modulates fibroblast activity. The
potential effect of tamoxifen on vascular reactivity and fibrotic lesions raised 
questions about its utility as a therapeutic agent in scleroderma. OBJECTIVE: To 
determine the utility of tamoxifen therapy in scleroderma. METHODS: Open label
preliminary, prospective, proof of concept study of tamoxifen. RESULTS: Fifteen
patients (3 male, 12 female) with scleroderma were enrolled (10 diffuse disease, 
5 CREST). Mean age was 55 (34-75) years. Mean duration of scleroderma was 9.3
(1-25) years. Two patients were excluded. For 13 patients, mean duration of
treatment was 7 (1.5-32) months. Two of 13 patients treated with tamoxifen
experienced transient improvement. They did not appear to have clinical features 
that identified them as a unique subset. Both patients subsequently relapsed, in 
one case 12 months, and in the other 24 months after treatment. CONCLUSION: Based
on these results, we would not recommend tamoxifen for further large scale
studies in scleroderma.

Publication Types: 
    Clinical Trial

PMID: 12673898 [PubMed - indexed for MEDLINE]

197: J Rheumatol. 2003 Apr;30(4):720-2.

Use of thermographic criteria to identify Raynaud's phenomenon in a population
setting.

Cherkas LF, Carter L, Spector TD, Howell KJ, Black CM, MacGregor AJ.

Twin Research and Genetic Epidemiology Unit, St. Thomas' Hospital, London,
England.

OBJECTIVE: To assess the value of thermographic measurements of digital skin
temperature after cold challenge in classifying Raynaud's phenomenon (RP) in a
healthy population. METHODS: One hundred seventy-five patients with RP and 404
controls were subjected to a 15 degrees C, 60 s cold challenge test. All
participants were women. Digital temperature measurements were taken at baseline,
immediately postimmersion, and 10 min after immersion using a portable
radiometer. RESULTS: Baseline skin temperature was a significant predictor of RP;
however, the fall in temperature on immersion and the subsequent rewarming rate
provided no additional information. CONCLUSION: Baseline skin temperature can
help to predict the occurrence of RP in patients drawn from the general
population, but has relatively low discriminatory power. The cold challenge test 
itself is of limited additional value for classification. Although objective
temperature measurements show little power overall to discriminate between RP and
non-RP patients, detecting low baseline digital temperature may be a useful
adjunct to clinical history in classifying the disease.

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

PMID: 12672189 [PubMed - indexed for MEDLINE]

198: Pediatrics. 2003 Apr;111(4 Pt 1):715-21.

Raynaud's phenomenon in children: a retrospective review of 123 patients.

Nigrovic PA, Fuhlbrigge RC, Sundel RP.

Division of Immunology, Program in Rheumatology, Children's Hospital and
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115,
USA. peter.nigrovic@tch.harvard.edu

OBJECTIVE: To examine the clinical presentation and disease associations of
Raynaud's phenomenon (RP) in children and adolescents. METHODS: A systematic
retrospective chart review was conducted of 123 cases drawn from 2 computerized
databases at the Children's Hospital of Boston. Participants aged <19 years with 
episodic reversible color changes in the extremities were examined. Case records 
were analyzed for clinical presentation, disease associations, and physical
examination and laboratory findings. RESULTS: In contrast to the findings of
smaller pediatric series reported to date, the large majority of our
patients-approximately 70%-did not have a recognized underlying connective tissue
disease. For both primary and secondary RP, approximately 80% of patients were
female, and mean age of onset was similar in the 2 groups. Biphasic or triphasic 
color changes were less common than monophasic changes and were no more common in
secondary than primary RP. Findings predictive of secondary RP were limited to
the presence of antinuclear antibodies and abnormal nailfold capillaries.
Antiphospholipid antibodies were found at some time in at least 21% of patients
with both primary and secondary RP. CONCLUSIONS: RP in children, as in adults,
principally affects girls and is frequently free of association with connective
tissue disease. Antinuclear antibody positivity and abnormal nailfold capillaries
correlate with secondary disease. Antiphospholipid antibodies are surprisingly
common, a new finding of uncertain implications.

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

PMID: 12671102 [PubMed - indexed for MEDLINE]

199: Occup Environ Med. 2003 Apr;60(4):287-94.

Hand-arm vibration syndrome in Swedish car mechanics.

Barregard L, Ehrenström L, Marcus K.

Department of Occupational and Environmental Medicine, Sahlgrenska Academy,
Göteborg University, Sweden. lars.barregard@ymk.gu.se

AIMS: To assess the occurrence of hand-arm vibration syndrome (HAVS) in Swedish
car mechanics, and the relation between HAVS and duration of exposure. METHODS: A
total of 806 mechanics answered a questionnaire on vascular and neurological
symptoms, and exposure to vibrations. Mechanics with symptoms, and some mechanics
without symptoms, were invited to a clinical examination, including also a timed 
Allen test. Vascular and neurological symptoms were classified using the
Stockholm Workshop scales. The mean daily exposure (mainly using nut-runners) was
14 minutes and the mean exposure duration, 12 years. Published data have shown
vibration levels in nut-runners of about 3.5 m/s(2). RESULTS: In the
questionnaire, 24% reported cold induced white finger (WF), 25% persistent
numbness, and 13%, reduced grip force. The clinical examination showed a
prevalence of vibration induced white finger (VWF) of about 15%, mainly in stage 
2, and after 20 years, of 25%. A survival analysis showed similar results. We
found that the International Organisation for Standardisation (ISO) model
underestimates the risk of VWF. The incidence after 1975 was 19 cases per 1000
person-years. Slow refill times in the timed Allen test were common (15% had a
refill time of >20 seconds), and associated with the presence of VWF. The
clinical examination revealed neurological symptoms in the hands in about 25% of 
subjects, mainly at stage 2. After 20 years, the prevalence was 40%. The
questionnaire items on WF and numbness both showed likelihood ratios of 13.
CONCLUSION: HAVS is common among Swedish car mechanics in spite of short daily
exposure times. This underlines the need for preventive measures.

PMID: 12660377 [PubMed - indexed for MEDLINE]

200: Eur J Vasc Endovasc Surg. 2003 Apr;25(4):336-41.

Differentiation of primary and secondary Raynaud's disease by carotid arterial
stiffness.

Cheng KS, Tiwari A, Boutin A, Denton CP, Black CM, Morris R, Seifalian AM,
Hamilton G.

University Department of Primary Care and Population Sciences, Royal Free and
University College Medical School, University College London and The Royal Free
Hospital, London, NW3 2QG, UK.

INTRODUCTION: primary Raynaud's disease may be difficult to differentiate
clinically from the secondary form with an underlying connective tissue,
haematological, neurovascular or drug-induced disorder. We undertook a study to
determine the elastic carotid and muscular femoral arterial biomechanical
properties and intima-media thickness (IMT) in subjects with primary and
secondary Raynaud's disease, to assess whether these parameters could
differentiate the two conditions. METHODS: twenty patients with primary Raynaud's
disease and 53 subjects with secondary Raynaud's associated with scleroderma
(systemic sclerosis, SSc) had measurements of their carotid and femoral wall
mechanics with a duplex scanner coupled to a Wall Track system. Their age,
gender, body mass index, heart rate, systolic and diastolic blood pressures,
presumed cardiovascular load, plasma creatinine, fasting cholesterol,
triglyceride and glucose concentrations were also measured. RESULTS: the carotid 
elastic properties [mean (SD): elastic modulus: 560 (180) vs 1204 (558) mmHg,p
<0.001 and stiffness index: 5.69 (1.35) vs 11.92 (6.4), p<0.001 for primary and
secondary Raynaud's respectively] were significantly impaired in patients with
secondary Raynaud's disease even after adjustment for potentially influencing
physiological and biochemical variables. There were no statistical differences in
the femoral elastic properties or the carotid and femoral IMTs between the two
groups. CONCLUSION: Duplex determination of the carotid elasticity or stiffness
is different in primary Raynaud's phenomenon compared with secondary Raynaud's
associated with SSc. This may be a useful non-invasive tool, in addition to
autoantibody markers and nail-fold capillaroscopy, to differentiate between the
two forms of Raynaud's phenomenon.

Publication Types: 
    Evaluation Studies

PMID: 12651172 [PubMed - indexed for MEDLINE]

201: Curr Rheumatol Rep. 2003 Apr;5(2):168-74.

Treatment of Raynaud's phenomenon: new insights and developments.

Herrick AL.

University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford M6
8HD, UK. aherrick@fs1.ho.man.ac.uk

Although certain broad principles of treatment apply to all patients with
Raynaud's phenomenon, the exact approach will vary depending on the nature and
severity of the underlying digital vascular problem. Advances in the
understanding of the pathophysiology of Raynaud's phenomenon are directing new
lines of therapy. This review considers general (nonpharmacologic) measures, the 
different types of drug therapy, and the role of surgery. Recent advances in the 
use of more conventional treatments, such as calcium channel blockers, are
discussed and also newer agents that are currently being researched, for example,
endothelin-1 receptor antagonists and nitric oxide donors. The necessity of
prompt assessment and treatment of acute digital ischemia, which is a medical
emergency, is highlighted.

PMID: 12628049 [PubMed - indexed for MEDLINE]

202: Cardiovasc Res. 2003 Mar;57(3):615-24.

Current pathophysiological views on vibration-induced Raynaud's phenomenon.

Stoyneva Z, Lyapina M, Tzvetkov D, Vodenicharov E.

Centre of Occupational Diseases, University Hospital St Ivan Rilsky, Sofia,
Bulgaria. zlatka_stoyneva@yahoo.com

This review attempts to summarize and discuss contemporary pathogenetic views on 
vibration-induced Raynaud's phenomenon assuming its multifactorial etiology. An
increase in central and peripheral sympathetic nervous activity is discussed
based on different physiological indicators of autonomic dysfunction and
sympathetic hyperactivity. Local acral vasodysregulation is considered. Receptor 
and nerve endings dysfunction presented with predominance of alpha(2)-receptor
function in the digital arteries and neuronal loss in those digital cutaneous
perivascular nerves containing calcitonin gene-related peptide result in
deficiency of endogenous release of this powerful vasodilator. Endothelial damage
and dysregulation induced by vibration and increased shear stresses are
demonstrated by the elevated plasma level of thrombomodulin and of von Willebrand
factor and reduced endothelium-dependent vasodilator responses. The
concentrations of endothelin-1 are high, the highest being in most advanced
stages. Decreased plasma thiol level, indicating increased production and
activity of free radicals, contribute to vasospastic paroxysms in vibration white
finger patients. Dysbalance of local vasoactive factors with opposing effects on 
vascular smooth muscle like endothelin and nitric oxide, endothelin and
calcitonin gene-related peptide, nitric oxide and superoxide anion are discussed.
Disturbed smooth muscle response is supposed. Changes in hemostasis, fibrinolysis
and hemorrheology, activation of blood cells with erythrocyte hyperaggregation
and red cell hypodeformability, platelet aggregation with increased release of
vasoconstricting thromboxane A(2) and serotonin as well as leukocyte activation, 
entrapment within capillaries and post-capillary venules and increased reactive
oxygen species and lysosomal lytic enzymes release might also contribute to
digital vasospasms and tissue damage. Elevated soluble intercellular adhesion
molecule-1 levels involved in the adherence of leukocytes to endothelium and to
other leukocytes have been found in patients with hand-arm vibration syndrome.

Publication Types: 
    Review

PMID: 12618223 [PubMed - indexed for MEDLINE]

203: Pediatr Infect Dis J. 2003 Feb;22(2):195-7.

Severe Raynaud's phenomenon with chronic hepatis C disease treated with
interferon.

Iorio R, Spagnuolo MI, Sepe A, Zoccali S, Alessio M, Vegnente A.

Department of Pediatrics, University of Naples Federico II, Italy.
riorio@unina.it

Severe Raynaud's phenomenon developed in a 5-year-old girl with chronic hepatitis
C infection at the fifth month of interferon therapy in the absence of
cryoglobulinemia and other conditions commonly associated with secondary
Raynaud's phenomenon. Although interferon therapy was promptly discontinued,
Raynaud's phenomenon persisted for 4 months with appearance of necrotic-ulcerous 
lesions at the tips of fingers.

Publication Types: 
    Case Reports

PMID: 12613457 [PubMed - indexed for MEDLINE]

204: Med Hypotheses. 2003 Mar;60(3):391-7.

7-oxo-DHEA and Raynaud's phenomenon.

Ihler G, Chami-Stemmann H.

Department of Medical Biochemistry and Medical Genetics, Texas A&M College of
Medicine, College Station 77843, USA. gmihler@tamu.edu

Patients with Raynaud's phenomenon have abnormal digital vasoconstriction in
response to cold. The pathogenesis remains unknown but may involve a local
neurovascular defect leading to vasoconstriction. Diagnosis of primary Raynaud's 
phenomenon is based on typical symptomatology coupled with normal physical
examination, normal laboratory studies and lack of observable pathology by nail
fold capillaroscopy. Secondary Raynaud's phenomenon is known to occur associated 
with several connective tissue diseases, vascular injury due to repeated
vibrational trauma, and other causes which produce demonstrable vascular and
microcirculatory damage. Treatment of Raynaud's symptoms is conservative and
aimed at prevention of attacks. Patients are advised to remain warm and, if
possible, to live in warm climates. We suggest that an ergogenic (thermogenic)
steroid, 7-oxo-DHEA (3-acetoxyandrost-5-ene-7,17-dione), which is available
without prescription as the trademarked 7-keto DHEA, may be very helpful in
prevention of primary Raynaud's attacks by increasing the basal metabolic rate
and inhibiting vasospasm.

PMID: 12581618 [PubMed - indexed for MEDLINE]

205: Am J Clin Oncol. 2003 Feb;26(1):26-9.

Paraneoplastic Raynaud phenomenon and idiopathic thrombocytopenic purpura in
non-small-cell lung cancer.

Wong AS, Hon Yoon K.

Department of Hematology Oncology, National University Hospital, Singapore.
wongsg@nuh.com.sg

The association of Raynaud phenomenon with malignancy has rarely been reported.
Idiopathic thrombocytopenic purpura is also an infrequent complication of solid
tumors. We report a 62-year-old man who sought treatment for severe Raynaud
phenomenon requiring medical therapy and was subsequently diagnosed to have
non-small-cell lung cancer. After chemotherapy and radiotherapy, his cancer was
in complete remission and the Raynaud phenomenon resolved. Severe
thrombocytopenia later developed for which no apparent cause was found, and which
was responsive to steroid therapy. This heralded relapse of his lung cancer. This
is a case of lung cancer with two rare paraneoplastic syndromes.

Publication Types: 
    Case Reports

PMID: 12576920 [PubMed - indexed for MEDLINE]

206: Semin Arthritis Rheum. 2002 Dec;32(3):157-62.

Interferon-induced Raynaud's syndrome.

Schapira D, Nahir AM, Hadad N.

B. Shine Department of Rheumatology, Department of Hematology, Rambam Medical
Center and Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, 
Israel.

OBJECTIVE: To review the clinical features, diagnosis, treatment, and outcome of 
interferon-induced Raynaud's phenomenon. METHODS: The medical literature was
reviewed from 1967 to November 2001 with the assistance of a MEDLINE search using
the key words: Raynaud, Interferon, ischemia, thrombosis and necrosis. A
qualitative review was performed after the articles were abstracted and the
relevant information was summarized. RESULTS: Twenty-four cases of
interferon-induced Raynaud's phenomenon (including our patient) are described.
Interpheron-alpha was the most common causative agent (14 cases). The symptoms
appeared weeks to years after beginning treatment and varied from mild vasospasm 
to occlusion of digital arteries and tissue necrosis (14 cases), sometimes
necessitating finger amputation (6 patients). Digital plethysmography,
arteriography and capillaroscopy were valuable diagnostic tools. In 4 cases,
cardiac, ophthalmic, or central nervous system drug-induced ischemia accompanied 
the peripheral Raynaud's phenomenon. Of the 15 cases with a documented outcome,
withdrawal of the drug alone resulted in complete (6 patients) or partial (1
patient) recovery. In the others, supportive therapy was needed. The recovery
period lasted from 2 weeks to 3 months. In 2 patients, continuation of treatment 
was possible. CONCLUSIONS: Raynaud's phenomenon and related complications must be
recognized as possible side effects of interferon therapy. Early diagnosis and
withdrawal of the drug may prevent unnecessary morbidity and disability.
Copyright 2002, Elsevier Science (USA). All rights reserved.

Publication Types: 
    Case Reports
    Review

PMID: 12528080 [PubMed - indexed for MEDLINE]

207: Vasa. 2002 Nov;31(4):274-5.

Digital arterial occlusive disease and parvovirus B19 infection.

Kern P.

phkern@bluewin.ch

We report a case of a 37-year-old white woman, who presented with digital
arterial occlusions associated with parvovirus B19 infection. Two other member of
the family presented acute febrile illness, polyarthralgia (husband), and
erythema infectiosum (son) during the same month. This new report gives weight to
the concept that acute human parvovirus infection could become part of the
differential diagnosis of acute digital occlusive arteriopathy.

Publication Types: 
    Case Reports

PMID: 12510554 [PubMed - indexed for MEDLINE]

208: Arch Med Res. 2002 Nov-Dec;33(6):531-5.

Diabetes mellitus vs. Raynaud disease: different lung vascular bed disorders.

Boulbou MS, Gourgoulianis KI, Krommydas GC, Klisiaris VK, Arseniou AA, Dafopoulos
KC, Molyvdas PA.

Department of Respiratory Medicine, University Hospital of Larissa, Greece.

BACKGROUND: In type II diabetes mellitus there are few data concerning pulmonary 
function abnormalities. In normal subjects and in patients with primary Raynaud
phenomenon, cold pressor test induces a decrease in carbon monoxide single-breath
diffusing capacity (DL,co) but not in secondary Raynaud phenomenon. Our objective
was to assess evaluation of lung diffusion capacity postural changes in diabetes 
mellitus and in secondary Raynaud phenomenon, two diseases with different
pulmonary capillaries functional disorders. METHODS: Twenty-five patients with
type II diabetes mellitus (mean age 52.24 years), 17 patients with secondary
Raynaud phenomenon (mean age 47.06 years), non-smokers without pulmonary or heart
disease, and 26 healthy matched subjects (mean age 47.50 years) underwent lung
diffusion capacity measurements by single-breath method also corrected by
alveolar volume (DL,co) in sitting and supine positions. RESULTS: Patients with
diabetes mellitus exhibited lower values of DL,co and DL,co/VA measurements in
comparison with subjects with Raynaud phenomenon and control group (p <0.01).
Additionally, they had a significant decrease in DL,co in supine compared to
sitting position (83.88 +/- 16.53 vs. 89.68 +/- 18.03, p = 0.023). To the
contrary, supine position in secondary Raynaud phenomenon and in control group
after cold pressor test showed a significant increase in DL,co/VA (120.93 vs.
109.78 in Raynaud and 114.36 vs. 99.47 in control group, p <0.001). CONCLUSIONS: 
Postural changes of lung diffusion capacity could be used as a simple,
non-invasive method to detect vascular disease resulting from different
pathophysiologic mechanisms such as diabetes mellitus and Raynaud phenomenon.

Publication Types: 
    Comparative Study

PMID: 12505097 [PubMed - indexed for MEDLINE]

209: Occup Environ Med. 2003 Jan;60(1):16-26.

Dose-response patterns for vibration-induced white finger.

Griffin MJ, Bovenzi M, Nelson CM.

Human Factors Research Unit, Institute of Sound and Vibration Research,
University of Southampton, Southampton SO17 1BJ, UK. M.J.Griffin@soton.ac.uk

AIMS: To investigate alternative relations between cumulative exposures to
hand-transmitted vibration (taking account of vibration magnitude, lifetime
exposure duration, and frequency of vibration) and the development of white
finger (Raynaud's phenomenon). METHODS: Three previous studies have been combined
to provide a group of 1557 users of powered vibratory tools in seven occupational
subgroups: stone grinders, stone carvers, quarry drillers, dockyard caulkers,
dockyard boilermakers, dockyard painters, and forest workers. The estimated total
operating duration in hours was thus obtained for each subject, for each tool,
and for all tools combined. From the vibration magnitudes and exposure durations,
seven alternative measurements of cumulative exposure were calculated for each
subject, using expressions of the form: dose = summation operator a(m)(i)t(i),
where a(i) is the acceleration magnitude on tool i, t(i) is the lifetime exposure
duration for tool i, and m = 0, 1, 2, or 4. RESULTS: For all seven alternative
dose measures, an increase in dose was associated with a significant increase in 
the occurrence of vibration-induced white finger, after adjustment for age and
smoking. However, dose measures with high powers of acceleration (m > 1) faired
less well than measures in which the weighted or unweighted acceleration, and
lifetime exposure duration, were given equal weight (m = 1). Dose determined
solely by the lifetime exposure duration (without consideration of the vibration 
magnitude) gave better predictions than measures with m greater than unity. All
measures of dose calculated from the unweighted acceleration gave better
predictions than the equivalent dose measures using acceleration
frequency-weighted according to current standards. CONCLUSIONS: Since the total
duration of exposure does not discriminate between exposures accumulated over the
day and those accumulated over years, a linear relation between vibration
magnitude and exposure duration seems appropriate for predicting the occurrence
of vibration-induced white finger. Poorer predictions were obtained when the
currently recommended frequency weighting was employed than when accelerations at
all frequencies were given equal weight. Findings suggest that improvements are
possible to both the frequency weighting and the time dependency used to predict 
the development of vibration-induced white finger in current standards.

PMID: 12499452 [PubMed - indexed for MEDLINE]

210: Postgrad Med J. 2002 Nov;78(925):682-4.

Thoracoscopic sympathectomy for palmar hyperhidrosis and Raynaud's phenomenon of 
the upper limb and excessive facial blushing: a five year experience.

Rajesh YS, Pratap CP, Woodyer AB.

Royal Liverpool University Hospital, UK. rajyag@hotmail.com

Primary hyperhidrosis of the palms, face, and axillae has a strong negative
impact on social and professional life. A retrospective analysis of 40
laparoscopic transaxillary thoracic sympathectomies performed in a district
general hospital over a five year period was undertaken in order to determine the
effectiveness of this procedure. A postal questionnaire was sent to all patients 
to assess the benefit from the operation; postoperative pain and time off work
were collated. Immediate failure was noted in three patients, of whom two later
underwent successful reoperation. Recurrence was noted in three patients (8%).
Though immediate complications were minimal, the major long term postoperative
morbidity was compensatory hyperhidrosis on the back, chest, and thigh (77%)
along with gustatory sweating over the face (22%). Thoracoscopic sympathectomy is
a safe, effective, and minimally invasive surgical treatment for hyperhidrosis,
Raynaud's phenomenon of the upper limb, and excessive facial blushing; however,
the chance of long term compensatory hyperhidrosis is high.

PMID: 12496327 [PubMed - indexed for MEDLINE]

211: Joint Bone Spine. 2002 Oct;69(5):515-8.

Bronchiectasis in a patient with CREST syndrome.

Lavie F, Rozenberg S, Coutaux A, Koeger AC, Bourgeois P, Fautrel B.

Department of Rheumatology School of Medicine Pitié-Salpêtrière and University
Pierre & Marie Curie, Paris VI, Pitié-Salpêtrière Teaching Hospital, 83,
boulevard de l'Hĵpital, 75651 Paris cedex 13, France.

Bronchiectasis is an uncommon pulmonary manifestation of systemic sclerosis
(SSc). We report the case of a 70-year-old woman with CREST syndrome and
vasculitis who developed multifocal symptomatic bronchiectasis. The
bronchiectasis and immunosuppressive therapy precipitated severe lower
respiratory tract infection, which was fatal within a few months. The concomitant
occurrence of bronchiectasis and SSc raises the possibility of a
pathophysiological relationship. Several hypotheses can be put forward to explain
the occurrence of bronchial wall damage leading to bronchiectasis. Whatever the
mechanism, cases of bronchiectasis in patients with SSc should be reported to
make physicians aware of the substantial risk associated with this combination.

Publication Types: 
    Case Reports

PMID: 12477240 [PubMed - indexed for MEDLINE]

212: J Hand Surg [Am]. 2002 Nov;27(6):1073-80.

Adventitial stripping of the radial and ulnar arteries in Raynaud's disease.

Balogh B, Mayer W, Vesely M, Mayer S, Partsch H, Piza-Katzer H.

Department of Plastic and Reconstructive Surgery, KH Lainz, Wien, Austria.

Adventitial stripping of the palmar arch, the palmar common digital arteries, or 
the proper digital arteries is a last resort in the treatment of refractory
primary or secondary Raynaud's phenomenon. Seven patients who had adventitial
stripping of the ulnar and radial arteries proximal to the wrist and resection of
the nerve of Henle, if identifiable, are presented. All of them were evaluated by
telethermography, acral rheography, and a questionnaire before and after surgery.
All were asymptomatic after surgery with satisfactory healing of the ulcers at
the fingertips. None of them relapsed during the follow-up time of 1.5 years.

PMID: 12457360 [PubMed - indexed for MEDLINE]

213: J Hum Lact. 2002 Nov;18(4):382-5.

Nipple vasospasms, Raynaud's syndrome, and nifedipine.

Garrison CP.

Magee-Women's Hospital, Pittsburgh, Pennsylvania, USA.

This case report describes a situation in which a mother who experienced
prolonged nipple pain with her first child sought help from a lactation
consultant at the birth of her second child. Despite being very attentive to
positioning and latch, similar pain was experienced from the first feeding with
the second baby. The mother's history and symptoms were explored, and nipple
vasospasms related to Raynaud's syndrome were suspected. After reviewing the
literature and consulting with her personal obstetrician, the mother (a
pediatrician) chose to treat with nifedipine. The mother was pain free after a
2-week course and nursing without difficulty at 4 months postpartum.

Publication Types: 
    Case Reports

PMID: 12449056 [PubMed - indexed for MEDLINE]

214: J Eur Acad Dermatol Venereol. 2002 Sep;16(5):526-8.

Comment in:
    J Eur Acad Dermatol Venereol. 2002 Sep;16(5):433-5.

Transdermal application of prostaglandin E1 ethyl ester for the treatment of
trophic acral skin lesions in a patient with systemic scleroderma.

Schlez A, Kittel M, Scheurle B, Diehm C, Jünger M.

Department of Dermatology, University Tübingen, Germany.
anja.schlez@med.uni-tuebingen.de

An early dinical symptom in scleroderma patients is Raynaud's phenomenon. Later
cutaneous manifestations of the disease include oedematous swelling in the
extremities and in more extreme cases often very painful, refractory acral
necroses. We report on a 56-year-old female patient who participated in a
prospective, double-blind, multicentre comparative pilot study because of her
severe Raynaud symptoms, with dystrophic skin lesions on both hands. The goal of 
the study was to evaluate the efficacy and safety of prostaglandin E1 ethyl ester
in a transdermal drug delivery system compared with placebo in patients with
secondary Raynaud's phenomenon associated with systemic scleroderma or mixed
connective tissue disease. After 2 weeks of verum treatment the patient
experienced a marked improvement of Raynaud's attacks, with increased capillary
flow velocity, reduced blood stasis and dinical healing of the acral trophic
lesions. For this patient the transdermal application of prostaglandin E1 ethyl
ester in the form of a medicated patch proved to be a simple and effective
therapy for the acral trophic skin lesions associated with systemic scleroderma.

Publication Types: 
    Case Reports

PMID: 12428854 [PubMed - indexed for MEDLINE]

215: Clin Exp Rheumatol. 2002 Sep-Oct;20(5):641-6.

Increased but imbalanced expression of VEGF and its receptors has no positive
effect on angiogenesis in systemic sclerosis skin.

Mackiewicz Z, Sukura A, Povilenaité D, Ceponis A, Virtanen I, Hukkanen M,
Konttinen YT.

Institute of Experimental and Clinical Medicine, Vilnius, Lithuania.

OBJECTIVE: To investigate the expression of vascular endothelial growth factor
(VEGF) and its vascular and lymphatic receptors in skin in systemic sclerosis
(SSc) compared to systemic lupus erythematosus (SLE), Raynaud's phenomenon (RP)
and normal healthy control skin. METHODS: Staining was performed using rabbit
anti-human antibodies in DAKO TechMate Horizon staining robot programmed for the 
biotin-streptavidin protocol. RESULTS: VEGF was sporadically and weakly expressed
in normal skin, but in spite of vascular damage in diseased skin, VEGF expression
was only slightly upregulated. In contrast, its vascular receptors VEGFR-1
(Flt-1) and VEGFR-2 (Flk-1), were clearly upregulated. Finally, the lymphatic
VEGFR-3 (Flt-4) receptor was also upregulated in diseased skin and ectopically
expressed also in blood vessels. Negative staining and positive sample controls
confirmed the specificity of the staining. CONCLUSION: The imbalanced expression 
of VEGF and its vascular receptors suggest that the compensatory efforts to
angiogenesis fail in SSc, in part due to insufficient local production of VEGF,
which was low compared to VEGFR expression. This is compatible with the recent
observations on the lack of alpha V beta 3+ newly formed blood vessels in SSc
skin. Since microvascular angiogenic stimuli normally induce first VEGF and then 
VEGFR, these findings also suggest that the angiogenic cascade is turned on, but 
there is a defect in the finalization of its effects. Normalization of angiogenic
cascade in SSc could provide a future therapeutic target.

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

PMID: 12412194 [PubMed - indexed for MEDLINE]

216: South Med J. 2002 Sep;95(9):1058-9.

Primary biliary cirrhosis accompanied by CREST syndrome.

Kouraklis G, Glinavou A, Karatzas G.

Second Department of Propedeutic Surgery, Medical School University of Athens,
Greece.

CREST syndrome, a relatively benign, slowly progressive variant of systemic
scleroderma consists of calcinosis, Raynaud's phenomenon, esophageal dysfunction,
sclerodactyly, and telangiectasia. Although the association of this syndrome with
primary biliary cirrhosis (PBC) is recognized in women, it has never been
described in a man. We report the rare case of a male patient with CREST syndrome
accompanied by PBC, manifested by acute cholecystitis and mild jaundice. The
association of the two conditions is clinically and etiologically important.
Clinicians must be aware of this association, sincethe clinical features of CREST
syndrome may be mild and may be thought to be complications of the underlying
liver disease.

Publication Types: 
    Case Reports

PMID: 12356109 [PubMed - indexed for MEDLINE]

217: Arthritis Rheum. 2002 Sep;46(9):2410-20.

Measuring disease activity and functional status in patients with scleroderma and
Raynaud's phenomenon.

Merkel PA, Herlyn K, Martin RW, Anderson JJ, Mayes MD, Bell P, Korn JH, Simms RW,
Csuka ME, Medsger TA Jr, Rothfield NF, Ellman MH, Collier DH, Weinstein A, Furst 
DE, Jiménez SA, White B, Seibold JR, Wigley FM; Scleroderma Clinical Trials
Consortium.

Harvard Medical School, Boston, Massachusetts, USA. pmerkel@bu.edu

OBJECTIVE: To document disease activity and functional status in patients with
scleroderma (systemic sclerosis [SSc]) and Raynaud's phenomenon (RP) and to
determine the sensitivity to change, reliability, ease of use, and validity of
various outcome measures in these patients. METHODS: Patients with SSc and
moderate-to-severe RP participating in a multicenter RP treatment trial completed
daily diaries documenting the frequency and duration of RP attacks and recorded a
daily Raynaud's Condition Score (RCS). Mean scores for the 2-week periods prior
to baseline (week 0), end of trial (week 6), and posttrial followup (week 12)
were calculated. At weeks 0, 6, and 12, physicians completed 3 global assessment 
scales and performed clinical assessments of digital ulcers and infarcts;
patients completed the Health Assessment Questionnaire (HAQ), the Arthritis
Impact Measurement Scales 2 (AIMS2) mood and tension subscales, 5 specific
SSc/RP-related visual analog scales (VAS), and 3 other VAS global assessments. We
used these measures to document baseline disease activity and to assess their
construct validity, sensitivity to change, and reliability in trial data.
RESULTS: Two hundred eighty-one patients (248 women, 33 men; mean age 50.4 years 
[range 18-82 years]) from 14 centers participated. Forty-eight percent had
limited cutaneous SSc; 52% had diffuse cutaneous SSc. Fifty-nine patients (21%)
had digital ulcers at baseline. Patients had 3.89 +/- 2.33 (mean +/- SD) daily RP
attacks (range 0.8-14.6), with a duration of 82.1 +/- 91.6 minutes/attack. RCS
for RP activity (possible range 0-10) was 4.30 +/- 1.92. HAQ scores (0-3 scale)
indicated substantial disability at baseline (total disability 0.86, pain 1.19), 
especially among the subscales pertaining to hand function (grip, eating,
dressing). AIMS2 mood and tension scores were fairly high, as were many of the
VAS scores. Patients with digital ulcers had worse RCS, pain, HAQ disability
(overall, grip, eating, and dressing), physician's global assessment, and
tension, but no significant difference in the frequency of RP, duration of RP,
patient's global assessment, or mood, compared with patients without digital
ulcers. VAS scores for digital ulcers as rated by the patients were not
consistent with the physician's ratings. Factor analysis of the 18 measures
showed strong associations among variables in 4 distinct domains: disease
activity, RP measures, digital ulcer measures, and mood/tension. Reliability of
the RCS, HAQ pain and disability scales, and AIMS2 mood and tension subscales was
high. The RP measures demonstrated good sensitivity to change (effect sizes
0.33-0.76). CONCLUSION: Our findings demonstrate that the significant activity,
disability, pain, and psychological impact of RP and digital ulcers in SSc can be
measured by a small set of valid and reliable outcome measures. These outcome
measures provide information beyond the quantitative metrics of RP attacks. We
propose a core set of measures for use in clinical trials of RP in SSc patients
that includes the RCS, patient and physician VAS ratings of RP activity, a
digital ulcer/infarct measure, measures of disability and pain (HAQ), and
measures of psychological function (AIMS2).

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

PMID: 12355489 [PubMed - indexed for MEDLINE]

218: Occup Environ Med. 2002 Sep;59(9):640-2.

Raynaud's phenomenon, vibration induced white finger, and difficulties in
hearing.

Palmer KT, Griffin MJ, Syddall HE, Pannett B, Cooper C, Coggon D.

MRC Environmental Epidemiology Unit, Community Clinical Sciences, Southhampton
General Hospital, University of Southampton, SO16 6YD, UK. ktp@mrc.soton.ac.uk

BACKGROUND: An association has previously been reported between finger blanching 
and hearing difficulties, but only in workers with exposure to noise and hand
transmitted vibration (HTV). AIMS: To explore the association in a community
sample, including cases who lacked occupational exposure to noise or HTV. METHOD:
A questionnaire was mailed to 12 606 subjects aged 35-64 years, chosen at random 
from the age-sex registers of 34 British general practices. Inquiry was made
about years of employment in noisy jobs, lifetime exposure to HTV, hearing
difficulties and tinnitus, and lifetime history of cold induced finger blanching.
Subjects were classed as having severe hearing difficulty if they used a hearing 
aid or found it difficult or impossible to hear conversation in a quiet room.
Associations of finger blanching with hearing difficulties and tinnitus were
analysed by logistic regression. RESULTS: Among 8193 respondents were 185 who
reported severe hearing difficulty and 1151 who reported finger blanching. After 
adjustment for age and years of work in noisy jobs, hearing difficulty was about 
twice as common in men and women who reported finger blanching, including those
who had never been importantly exposed to noise and in those never exposed to
HTV. CONCLUSIONS: These data support an association between finger blanching and 
hearing loss, which is not explained by confounding occupational exposure to
noise, and suggest that it may extend to causes of blanching other than vibration
induced white finger. Further investigations are warranted to confirm the
association and explore possible mechanisms, such as sympathetic vasoconstriction
in the cochlea.

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

PMID: 12205240 [PubMed - indexed for MEDLINE]

219: Altern Med Rev. 2002 Aug;7(4):328-35.

Effect of ceramic-impregnated "thermoflow" gloves on patients with Raynaud's
syndrome: randomized, placebo-controlled study.

Ko GD, Berbrayer D.

Alternative Medicine Research, Department of Rehabilitation Medicine, Sunnybrook 
and Women's College Health Sciences Centre, University of Toronto, Ontario,
Canada. gordon.ko@swchsc.on.ca

OBJECTIVE: To determine the efficacy of ceramic impregnated gloves in the
treatment of Raynaud's syndrome. DESIGN: Double-blind, placebo-controlled study. 
SETTING: Teaching hospital outpatient clinic. PARTICIPANTS: Ninety-three patients
meeting the "Pal" criteria for Raynaud's syndrome. INTERVENTIONS: Treatment
period of three months with use of ceramic-impregnated gloves. MAIN OUTCOME
MEASURES: Primary end points: Pain visual analogue scale ratings and diary;
Disabilities of the Arm, Shoulder, Hand questionnaire; Jamar grip strength;
Purdue board test of hand dexterity. Secondary end points: Infrared skin
temperature measurements; seven-point Likert scale rating of treatment. RESULTS: 
In 60 participants with complete data, improvements were noted in the visual
analogue scale rating (p=0.001), DASH score (p=0.001), Jamar grip strength
(p=0.002), infrared skin fingertip temperature (p=0.003), Purdue hand dexterity
test (p=0.0001) and the Likert scale (p=0.001) with ceramic gloves over the
placebo cotton gloves. CONCLUSION: The ceramic-impregnated "thermoflow" gloves
have a clinically important effect in Raynaud's syndrome.

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

PMID: 12197784 [PubMed - indexed for MEDLINE]

220: Ear Nose Throat J. 2002 Jul;81(7):467-9.

Raynaud's phenomenon in radial forearm free-tissue transfer.

Teknos TN, Myers LL, Chepeha DB.

Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann
Arbor, USA. teknos@umich.edu

During 1998, 69 patients underwent either fasciocutaneous or osteofasciocutaneous
radial forearm free-tissue transfers at our institution. Three of these patients 
(4.3%), who had undergone a total of four transfers, had Raynaud's phenomenon.
Three of the four transfers survived without perioperative incident. The one flap
that failed had been well vascularized until postoperative day 3. Then,
coincident with a decrease in ambient room temperature, the patient's extremities
and his flap became cyanotic. A salvage procedure was unsuccessful. In this
article, we discuss the perioperative course, proposed pathophysiology, and
treatment strategies aimed at optimizing hand and flap outcomes in patients with 
Raynaud's phenomenon.

Publication Types: 
    Case Reports

PMID: 12149844 [PubMed - indexed for MEDLINE]

221: Ind Health. 2002 Jul;40(3):254-9.

Autonomic nervous activity during hand immersion in cold water in patients with
vibration-induced white finger.

Sakakibara H, Luo J, Zhu SK, Hirata M, Abe M.

Nagoya University School of Health Sciences, Japan.

Autonomic nervous function in response to cold was investigated in 21 patients
with vibration-induced white finger (VWF) and 17 healthy controls of similar age,
using power spectral analysis of heart rate variability. In a supine position,
electrocardiogram and skin temperature of both index fingers were measured during
immersion of right hand in cold water at 10 degrees C for 10 minutes. Autonomic
nervous activity was evaluated from the power of the low-frequency component (LF:
0.02-0.15 Hz), the high-frequency component (HF: 0.15-0.40 Hz) and the ratio of
the LF to the HF power (LF/HF ratio). The LF/HF ratio, an index of sympathetic
nervous activity, significantly increased during the immersion in the VWF
patients, but did not significantly increase in the controls. The LF/HF ratio was
then significantly greater in the patients than in the controls during the first 
1-2 minutes of the immersion. The HF power related to parasympathetic nervous
activity did not change significantly in either group. Finger skin temperature of
the immersed right hand was significantly lower in the VWF patients than in the
controls during the last five minutes of the immersion and in the recovery
period. The present results indicate that sympathetic nervous response to cold is
significantly enhanced in VWF patients. The exaggerated sympathetic response to
cold in these patients is considered to contribute to the enhanced
vasoconstriction of their extremities.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 12141373 [PubMed - indexed for MEDLINE]

222: J Rheumatol. 2002 Jul;29(7):1401-3.

Determination of fingertip lacticemy before and after cold stimulus in patients
with primary Raynaud's phenomenon and systemic sclerosis.

Pucinelli ML, Fontenelle S, Andrade LE.

OBJECTIVE: Establishing a cold stimulus test based on the measurement of finger
tip lacticemy (FTL) in Raynaud's phenomenon (RP). METHODS: Twenty-seven controls 
and 79 patients with RP [30 systemic sclerosis (SSc) and 49 isolated RP] were
studied. The latter were further classified into probable primary RP (PPRP) and
probable secondary RP (PSRP). FTL was determined before (pre-CS) and after
(post-CS) a cold stimulus and the percentage difference was designated ACS-FTL.
RESULTS: Pre-CS-FTL was marginally higher in SSc patients than in isolated RP and
controls. Post-CS-FFL was significantly higher in SSc and PSRP than in PPRP and
controls. SSc and PSRP patients had higher post-CS-FTL than pre-CS-FTL (positive 
ACS-FTL) while controls presented a negative ACS-FTL. Post-CS-FTL had a
heterogeneous behavior in patients with PPRP. CONCLUSION: CS-FTL test was shown
to be an easy method for evaluation of fingertip effective perfusion before and
after a cold stimulus. Further studies are warranted to test its possible
clinical application in discriminating between patients with SSc and controls, as
well as between patients with PPRP and PSRP.

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

PMID: 12136896 [PubMed - indexed for MEDLINE]

223: Foot Ankle Clin. 2001 Dec;6(4):699-713.

Medical and surgical considerations in patients with vasculitis and Raynaud's
syndrome.

Pederson WC.

Department of Surgery and Orthopaedic Surgery, University of Texas Health Science
Center, San Antonio, USA. microl@ix.netcom.com

Vascular problems in the foot are certainly common when one considers only
arteriosclerosis on the macrovascular scale. The primary cause of ischemia of the
foot undoubtedly is primary arteriosclerosis, whether related to smoking,
diabetes, renal failure, or other causes. Vasculitis and vasospasm, in their many
forms, are distinctly unusual as a cause of ischemia of the foot. These entities,
nonetheless, can cause significant problems from the standpoint of symptoms and
even ulceration or gangrene of the foot. This article addresses the
pathophysiology of vasculitis and vasospastic problems in the foot and their
management.

Publication Types: 
    Review

PMID: 12134579 [PubMed - indexed for MEDLINE]

224: Arthritis Rheum. 2002 May;46(5):1319-23.

Increased urinary F2-isoprostanes in systemic sclerosis, but not in primary
Raynaud's phenomenon: effect of cold exposure.

Cracowski JL, Carpentier PH, Imbert B, Cachot S, Stanke-Labesque F, Bessard J,
Bessard G.

Grenoble University Hospital, Grenoble, France. Cracowski@ujf-grenoble.fr

OBJECTIVE: F2-isoprostanes are free radical-dependent arachidonic acid
metabolites that are used as clinical markers of lipid peroxidation in systemic
sclerosis (SSc) and other microvascular diseases. The objectives of this study
were to determine whether the basal urinary levels of F2-isoprostane in SSc
patients differ from those in patients with primary Raynaud's phenomenon (RP) and
to investigate whether F2-isoprostane formation correlates with the cutaneous
microvascular perfusion decrease following cold exposure in SSc patients,
patients with primary RP, and healthy controls. METHODS: Eleven women with RP
secondary to SSc, 11 women with primary RP, and 11 healthy women were exposed to 
decreasing room temperature, from 25 degrees C to 15 degrees C, for 40 minutes.
Urine samples were obtained before and after the test for gas
chromatography/electronic impact mass spectrometry quantification of
15-F(2t)-isoprostane (15-F(2t)-IsoP; also called isoprostaglandin F(2alpha) type 
III). Cutaneous blood flow was monitored using a laser Doppler perfusion imager. 
RESULTS: The mean +/- SEM urinary 15-F(2t)-IsoP levels at baseline in SSc
patients (178 +/- 32 pmoles/mmole of creatinine) were 1.9 times higher than those
in healthy controls (95 +/- 11 pmoles/mmole of creatinine) and 1.7 times higher
than those in patients with primary RP (107 +/- 19 pmoles/mmole of creatinine) (P
< 0.05 for controls and patients with primary RP versus SSc patients). No
significant correlation was found between basal urinary 15-F(2t)-IsoP levels and 
the temperature or cutaneous blood flow decrease in response to the whole-body
cooling. Furthermore, the 15-F(2t)-IsoP response to the cooling test was not
correlated with the cutaneous blood flow decrease. CONCLUSION: Lipid peroxidation
is increased in SSc patients, but not in patients with primary RP. Cold exposure 
leads to a significant but small increase in 15-F(2t)-IsoP levels that is
independent of the cutaneous blood flow decrease. F2-isoprostane quantification
may be an interesting pharmacologic tool for monitoring responses to antioxidant 
treatment in SSc patients.

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

PMID: 12115239 [PubMed - indexed for MEDLINE]

225: Clin Rheumatol. 2002 Jun;21(3):251-4.

Elevated homocysteine levels in patients with Raynaud's phenomenon secondary to
systemic lupus erythematosus.

Cheng TT, Chiu CK.

Chang Gung Memorial Hospital, 123 Ta Pei Road, Niao Sung Hsian, Kaohsiung Hsien
83305, Taiwan, ROC. tiantsai@ms2.hinet.net

The objective of this study was to analyse the association between serum
homocysteine (Hcy) levels and the presence of Raynaud's phenomenon (RP) in a
cohort of systemic lupus erythematosus (SLE) patients. We enrolled premenopausal,
disease-inactive SLE patients ( n = 34) with RP (group I, n = 11) or without RP
(group II, n = 23), and age-matched healthy premenopausal women as controls
(group III, n = 20). Fasting Hcy levels were determined for all these subjects.
The results reveal that group I patients exhibited significantly greater serum
Hcy levels (11.68+/-2.98 mmol/l) than group II patients (8.29+/-2.89 mmol/l) ( P 
= 0.003), and group III healthy subjects (8.00+/-1.50 mmol/l) ( P = 0.001);
however, in this regard there was no significant difference between group II and 
group III patients ( P = 0.927). In conclusion, elevated serum Hcy levels were
noted for this cohort of SLE patients with RP compared to those not evidencing RP
and healthy controls. Although the pathogenesis of RP still remains obscure, this
study suggests that Hcy may play a role in the aetiopathogenesis of SLE patients 
with RP.

PMID: 12111632 [PubMed - indexed for MEDLINE]

226: Vasa. 2002 May;31(2):91-4.

Erratum in:
    Vasa 2002 Nov;31(4):280.

Double-blind, randomised, placebo controlled low level laser therapy study in
patients with primary Raynaud's phenomenon.

Hirschl M, Katzenschlager R, Ammer K, Melnizky P, Rathkolb O, Kundi M.

Angiologische Ambulanz und Tagesklinik, Hanuschkrankenhaus Wien.
mirko.hirschl@wgkk.sozvers.at

BACKGROUND: No causal treatment of primary Raynaud's phenomenon is available due 
to its unclear aetiology. Low level laser therapy (LLLT) is applied in a
multitude of medical conditions often without sufficient evidence of efficacy and
established mechanisms. To asses the effect of this therapy in patients with
primary Raynaud's phenomenon a randomised, double blind, placebo controlled cross
over study was designed. PATIENTS AND METHODS: Absolute and relative frequency
and intensity of vasospastic attacks during three weeks of either LLLT or placebo
therapy and results of infrared thermography before onset and at the end of both 
therapy sequences were evaluated in 15 patients with primary Raynaud's
phenomenon. RESULTS: Frequency of Raynaud's attacks was not significantly
affected by low level laser therapy. Compared to placebo a significantly lower
intensity of attacks during laser irradiation was observed, but no transfer
effect occurred. Additionally the mean temperature gradient after cold exposure
was reduced after laser irradiation, while the number of fingers showing
prolonged rewarming was unaffected. CONCLUSION: Though further studies are
necessary to confirm these results we could demonstrate for the first time in a
double blind placebo controlled clinical trial that low laser therapy is a
potential candidate for an effective therapy of Raynaud's phenomenon, although
effects seem to be of short duration.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12099151 [PubMed - indexed for MEDLINE]

227: Vasa. 2002 May;31(2):87-90.

Homocysteine levels in patients with Raynaud's phenomenon.

al-Awami M, Schillinger M, Maca T, Gschwandtner M, Bieglmayer C, Wagner O, Minar 
E.

Department of Medical Angiology, Clinical Institute for Medical Laboratory
Diagnostics, University of Vienna, Austria. mahdi.alawami@akh-wien.ac.at

BACKGROUND: Patients with Raynaud's phenomenon (RP) have vasomotor dysregulation,
mainly cause by dysfunction of the endothelium. Since homocysteine has been found
to be damaging to endothelial cells, we investigated the concentrations of plasma
homocysteine, folate and vitamin B12 in patients with primary or secondary RP
compared to healthy individuals. PATIENTS AND METHODS: We measured the
concentrations of plasma fasting homocysteine, folate and vitamin B12 in a group 
of healthy individuals (n = 45) and in patients with primary (n = 26) or
secondary RP (n = 42). RESULTS: Median homocysteine levels in healthy controls
and in patients with primary RP, secondary RP were 7.9 (IQR 4.1 to 11.8) 9.8 (IQR
5.1 to 14.4), and 10.6 (6.0 to 15.3) mumol/L, respectively. Patients with primary
and secondary RP had significantly higher homocysteine concentration compared to 
healthy controls (Kruskal Wallis p = 0.01). After matching for age and sex,
patients with either primary or secondary RP showed significantly higher
homocysteine levels (Wilcoxon p < 0.0001). No significant differences between the
three groups were found concerning serum levels of vitamin B12 (p = 0.9) and
serum folate levels (p = 0.2). CONCLUSION: These data demonstrate that patients
with RP have higher plasma levels of homocysteine. No significant differences in 
folate and vitamin B12 levels were found between patients with primary RP,
secondary RP, and healthy individuals. These data suggest that homocysteine may
play a role in RP and may provide new clues in understanding of the vasomotor
dysregulation.

PMID: 12099150 [PubMed - indexed for MEDLINE]

228: Cent Eur J Public Health. 2002 Jun;10(1-2):16-20.

Pathophysiology of vibration-induced white fingers--current opinion: a review.

Liapina M, Tzvetkov D, Vodenitcharov E.

Department of Hygiene and Ecology, Medical University, Dimitar Nestorov 15 Blvd.,
1431 Sofia, Bulgaria.

Vibration-induced white finger (VWF) is secondary Raynaud's phenomenon caused by 
vibrating hand tools. Initially described in 1911 by Loriga, the pathophysiology 
of VWF remains unclear. This review attempts to summarize the current common and 
the most modern theories of the pathogenesis of VWF and propose a model of
multifactorial etiology. The role of vasoregulatory abnormalities--autonomic
dysfunction, local vasoregulatory abnormalities, of the endothelial cell control,
of hemostasis, fibrinolysis and hemorrheology, of the leukocyte activation and
the levels cell adhesion molecules and pro-inflammatory cytokines have been
reviewed.

Publication Types: 
    Review

PMID: 12096677 [PubMed - indexed for MEDLINE]

229: J Vasc Surg. 2002 Jul;36(1):57-61.

Endoscopic thoracic sympathicotomy for Raynaud's phenomenon.

Matsumoto Y, Ueyama T, Endo M, Sasaki H, Kasashima F, Abe Y, Kosugi I.

Department of Cardiovascular Surgery, National Kanazawa Hospital, Japan.
matumoto@kinbyou.hosp.go.jp

PURPOSE: For many years, thoracic sympathectomy via open surgery was not used to 
treat Raynaud's phenomenon because of the invasiveness of this procedure and the 
poor long-term outcomes associated with it. However, with the introduction of
endoscopic surgery, thoracic sympathectomy (or sympathicotomy) has been performed
by some surgeons as a less invasive surgical option for patients with Raynaud's
phenomenon. The less invasive procedure has the possibility of emphasizing merits
of sympathectomy. The purpose of this study was to reevaluate the efficacy of
sympathicotomy for Raynaud's phenomenon with endoscopic technique and its range
of applicability. METHODS: Between December 1992 and August 2001, endoscopic
thoracic sympathicotomy (ETS) was performed in 28 patients with Raynaud's
phenomenon (of a total of 502 patients with autonomic disorders who underwent
ETS) at National Kanazawa Hospital. We considered indications for surgical
treatment of Raynaud's phenomenon to include severe chronic symptoms or
nonhealing digital ulceration refractory to intensive medical therapy. All
patients were mailed a self-assessment questionnaire after surgery to determine
the immediate and long-term results of the procedure. Data from both initial and 
long-term follow-up examinations were obtained. RESULTS: Fifty-four ETS
procedures were performed in 28 patients. No operative mortality was seen, and no
occurrence of major complications necessitated open surgery. Initial resolution
or improvement of symptoms was achieved in 26 of 28 patients (92.9%). However,
later in the postoperative period, symptoms recurred in 23 of 28 patients
(82.1%), although no recurrence of digital ulceration was seen throughout our
observation. At the final follow-up examination (median follow-up period, 62.5
months), 25 patients (89.3%) reported overall improvement of the frequency and
severity of their symptoms. CONCLUSION: Despite the high rate of recurrence, ETS 
clearly produced a high rate of initial relief. ETS did indeed promote healing of
digital ulcers, and the procedure shows potential for reducing the severity of
refractory symptoms. We consider ETS to be the method of choice for treatment of 
severe or refractory Raynaud's phenomenon, and especially for Raynaud's involving
digital ulcer, because of its safety and efficacy.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 12096258 [PubMed - indexed for MEDLINE]

230: Neoplasma. 2002;49(2):91-4.

Immune-mediated complications during interferon alpha therapy in chronic
myelogenous leukemia.

Tóthová E, Kafková A, Stecová N, Fricová M, Guman T, Svorcová E.

Department of Hematology, Medical Faculty Hospital and UPJS Kosice, Slovak
Republic. etothova@post.sk

Several prospective randomized studies have shown that the treatment of chronic
myeloid leukemia with interferon alpha (IFNalpha) prolongs the survival by
comparison with conventional chemotherapy. However, long-term treatment with
Interferon alpha can produce or exacerbate immune-mediated complications (IMC).
The purpose of this study was to analyze the experience with IMC in patients with
chronic myelogenous leukemia (CML) undergoing IFNalpha treatment. The occurrence 
of IMC was evaluated in 76 patients (47 male; 29 female) with Philadelphia
chromosome (Ph)-positive CML. Diagnostic criteria of IMC were performed in
patients with symptoms suggestive of particular disorders. Well-documented and
clinically evident complications developed in 7 patients after a median of 19
months (range 1-84) of IFNalpha treatment. These included 9.2% patients with
Ph-positive CML treated with IFNalpha-containing regimens. Hypothyroidism (H)
occurred in 1 patient (1.3%), immune-mediated hemolysis (HEM) in 2 patients
(2.6%) and connective tissue disorders (CTD) in 4 patients (5.3%) (2 systemic
lupus erythematosus--SLE, 1 Raynaud's phenomena and 1 mixed connective tissue
disease--MCTD). IFNalpha was discontinued in 3 patients and the dose was reduced 
in 2 patients. Five of 7 patients (75%) with immune-mediated complications had
some degree of cytogenetic response at the time of the event. The association
with female sex was strong and significant (86% vs 33.6%, x2; 48; p = 0.02). The 
frequency of IMC of clinical relevance with interferon alpha therapy in CML
increased (long-term therapy). The patients treated with interferon alpha should 
be monitored for signs and symptoms of autoimmunity.

PMID: 12088112 [PubMed - indexed for MEDLINE]

231: Int Arch Occup Environ Health. 2002 Mar;75(3):179-85.

The relationship between hand-arm vibration and lower extremity clinical
manifestations: a review of the literature.

Schweigert M.

Occupational Health Services Program, St Michael's Hospital, University of
Toronto, Canada. m.schweigert@utoronto.ca

OBJECTIVE: To assess the current literature supporting a relationship between
hand-arm vibration (HAV) and lower extremity clinical effects. METHODS: An
initial review of the literature identified lower extremity vascular and
neurological effects reported in association with HAV. A second literature review
was performed with explicit search and evaluation strategies. It focused on
analytical studies and looked for epidemiological evidence supporting the
relationship between HAV and lower extremity effects. RESULTS: Eight analytical
studies which met all of the initial inclusion/exclusion criteria were
identified. All of these had serious validity deficiencies with respect to
selection bias, response rates and lack of examination of confounders.
CONCLUSIONS: There was consistency with respect to an association between those
exposed who were diagnosed with hand-arm vibration syndrome (HAVS) and vascular
symptoms in the lower extremities. There was no evidence that hand-held vibration
exposure independent of the diagnosis of HAVS was associated with lower extremity
vascular symptoms. There was no evidence to suggest that HAV was associated with 
clinically significant lower extremity neurological symptoms.

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

PMID: 11954985 [PubMed - indexed for MEDLINE]

232: J Rheumatol. 2002 Apr;29(4):726-30.

Raynaud's phenomenon in primary Sjögren's syndrome. Prevalence and clinical
characteristics in a series of 320 patients.

García-Carrasco M, Sisó A, Ramos-Casals M, Rosas J, de la Red G, Gil V, Lasterra 
S, Cervera R, Font J, Ingelmo M.

Department of Systemic Autoimmune Diseases, Hospital Clinic, Barcelona, Spain.

OBJECTIVE: To determine the prevalence of Raynaud's phenomenon (RP) in a large
series of patients with primary Sjögren's syndrome (SS) and to identify the
clinical and immunological features related to its presence. METHODS: In a cross 
sectional study, we investigated 320 consecutive patients with primary SS (294
women, 26 men; mean age at onset 60 yrs, range 16-87 yrs). All patients fulfilled
4 or more of the diagnostic criteria for SS proposed by the European Community
Study Group in 1993. Diagnosis of RP in patients with SS was defined as
intermittent attacks of digital pallor and/or cyanosis in the absence of any
other associated disease or anatomical abnormalities. RESULTS: RP was present in 
40 (13%) patients. All were women, with a mean age of 57 yrs (range 18-78). RP
preceded onset of sicca symptomatology in 18 (45%) patients. The main triggering 
factor was exposure to cold, which induced RP in all patients, while emotional
stress was a factor in 12 patients, as was job related predisposition in 2.
Fifteen (38%) patients required pharmacological treatment with calcium channel
blockers (12 patients) or angiotensin converting enzyme inhibitors (2 patients)
during colder months, and one patient required treatment with intravenous
prostacyclin for ischemic complications. Compared with SS patients without RP,
those with RP showed a higher prevalence of articular involvement (50 vs 31%; p =
0.031), cutaneous vasculitis (30 vs 11%; p = 0.003), antinuclear antibodies (95
vs 65%; p < 0.001), anti-Ro/SSA (59 vs 31%; p < 0.001) and anti-La/SSB antibodies
(44 vs 20%, p = 0.003). CONCLUSION: We found RP in 13% of patients with primary
SS, in almost half of whom RP was the first autoimmune symptomatology. These
patients constituted a subset of SS with a higher frequency of some
extraglandular features and positive immunological markers. The clinical course
of RP seems to be milder in patients with primary SS than in those with other
systemic autoimmune diseases such as systemic sclerosis, with no vascular
complications and pharmacological treatment needed in only 40% of patients.

PMID: 11950013 [PubMed - indexed for MEDLINE]

233: Rheumatology (Oxford). 2002 Mar;41(3):324-8.

Digital vascular response to topical glyceryl trinitrate, as measured by laser
Doppler imaging, in primary Raynaud's phenomenon and systemic sclerosis.

Anderson ME, Moore TL, Hollis S, Jayson MI, King TA, Herrick AL.

University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford M6
8HD, UK.

OBJECTIVE: To investigate digital microvascular responses to topical glyceryl
trinitrate (GTN) in patients with primary Raynaud's phenomenon (PRP), limited
cutaneous systemic sclerosis (LCSSc) and healthy control subjects, using laser
Doppler imaging. METHODS: Ten patients with PRP, 13 with LCSSc and 10 control
subjects were studied. Baseline skin microvascular blood flow of the dorsum of
the index, middle and ring fingers of the non-dominant hand was measured using
scanning laser Doppler imaging. After the initial image, 2% GTN ointment was
rubbed on the dorsum of one finger for 1 min; placebo ointment was rubbed on the 
dorsum of a second finger for 1 min, and the third finger remained untreated.
Further laser Doppler scanning of these three fingers was conducted immediately, 
10 and 20 min after ointment application. RESULTS: There was increased blood flow
response to placebo compared with no treatment (P<0.001) and to GTN compared with
placebo (P=0.004). The change in blood flow over time differed significantly
between placebo and GTN (P<0.001), but not between placebo and no ointment
application: blood flow increased with GTN and decreased with placebo/no
treatment at 10 and 20 min. There were no differences in initial baseline blood
flow or response between the subject groups. CONCLUSIONS: An exogenous supply of 
nitric oxide by topical GTN ointment causes local endothelial-independent
vasodilatory responses in PRP, LCSSc patients and control subjects. As well as
demonstrating the effectiveness of topical GTN in patients with PRP and LCSSc,
this study illustrates the ability of laser Doppler imaging to quantify local
vasodilatory effects.

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

PMID: 11934971 [PubMed - indexed for MEDLINE]

234: Headache. 2002 Mar;42(3):227-9.

Migraine and Raynaud phenomenon: possible late complications of Kawasaki disease.

Constantinescu CS.

Division of Clinical Neurology, University Hospital, Queen's Medical Centre,
Nottingham, UK.

Migraine and Raynaud phenomenon often coexist and may reflect similar vascular
reactions. Both have been associated with vascular endothelial cell dysfunction. 
Kawasaki disease is a systemic vasculitis of unknown etiology that affects
children and may lead to the formation of coronary artery aneurysms. Endothelial 
cell dysfunction has been demonstrated late in Kawasaki disease and is not
restricted to coronary vessels. We report the case of a patient who developed
typical migraine with aura and Raynaud phenomenon at the age of 14, 12 years
after onset of Kawasaki disease. His migraine responded well to pizotifen, and
both migraine and Raynaud phenomenon improved after initiation of treatment with 
valproic acid. We postulate that both migraine and Raynaud phenomenon in this
case represent late consequences of Kawasaki disease and result from
extracoronary endothelial dysfunction.

Publication Types: 
    Case Reports

PMID: 11903548 [PubMed - indexed for MEDLINE]

235: Lupus. 2002;11(1):35-41.

Scleroderma-like nailfold capillaroscopic abnormalities are associated with
anti-U1-RNP antibodies and Raynaud's phenomenon in SLE patients.

Furtado RN, Pucinelli ML, Cristo VV, Andrade LE, Sato EI.

Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São
Paulo, Brazil.

This study aimed to evaluate the association between nailfold capillary
abnormalities and the presence of Raynaud's phenomenon (RP), anti-U1-RNP, and
anti-cardiolipin (aCL) antibodies in SLE patients. One-hundred SLE patients were 
studied. Widefield nailfold capillaroscopy was considered abnormal according to
five criteria. Intercapillary distance, capillary width and capillary length were
registered by videomorphometry in two fingers in 100 patients and in four fingers
in 40 of these patients. Both the presence of alterated capillaroscopy and the
presence of scleroderma-pattern (SD-pattern), characterized by the presence of
avascular areas and enlarged or giant loops, were associated with the isolated
presence of RP (P < 0.001) or anti-U1-RNP antibodies (P < 0.01), as well as with 
the simultaneous presence of RP and anti-U1RNP antibodies (P < 0.001). There was 
a negative association between the presence of aCL antibodies and SD-pattern (P <
0.05). Higher figures for the videomorphometric parameters capillary width,
intercapillary distance and capillary length (measured on four fingers) were
observed in patients with RP. Patients presenting both RP and anti-U1-RNP
antibodies showed higher figures for intercapillary distance and capillary width.
This study demonstrated significant association between nailfold capillaroscopic 
abnormalities and either RP or anti-U1-RNP antibodies in SLE patients. The
association of RP, anti-U1-RNP antibodies, and 'scleroderma-like' findings on
nailfold capillaroscopy (SD-pattern) in patients with SLE may suggest a new SLE
subset with subclinical features of systemic sclerosis.

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

PMID: 11899953 [PubMed - indexed for MEDLINE]

236: Int Arch Occup Environ Health. 2002 Jan;75(1-2):6-13.

Diagnostic aspects of vibration-induced white finger.

Olsen N.

Department of Clinical Physiology and Nuclear Medicine, Aarhus University
Hospital, Denmark.

Vibration-induced white finger (VWF) is a secondary type of Raynaud's phenomenon 
(RP) caused by exposure to hand-arm vibration. The present review concerns the
cold-provoked attack of RP in vasospastic VWF. It concentrates on the most common
clinical and laboratory methods used to diagnose RP in vibration-exposed
subjects. Some physiological aspects of the attack of RP are mentioned to
elucidate the diagnostic principles of the tests. Anamnestic diagnostics by
medical interviews and questionnaires as well as cold-provocation tests with
detection of finger colour, finger systolic blood pressure (FSP), recovery time
of finger skin temperature and recovery time of normal nail colour after nail
compression are mentioned. The discriminative capacity and the reproducibility of
the tests are discussed. Cold-provocation tests with detection of finger colour
or zero FSP during cooling are recommended to be used if an attack of RP has to
be registered for diagnostic or medico-legal purposes in individual cases. An
abnormal reduction in FSP during cooling makes a history of RP very probable and 
is a suitable laboratory test for groups of subjects. Both recovery tests may be 
useful screening tests in field studies of vibration-exposed subject groups.

Publication Types: 
    Review

PMID: 11898878 [PubMed - indexed for MEDLINE]

237: Int Arch Occup Environ Health. 2002 Jan;75(1-2):37-42.

Use of questionnaire screening for vibration white finger in a high risk
industrial population.

Allen JA, McGrann S, McKenna KM.

Department of Physiology, The Queen's University of Belfast, Medical Biology
Centre, N Ireland. j.allen@qub.ac.uk

OBJECTIVES: To compare the results of questionnaire screening with those of
objective testing in the identification of vibration white finger (VWF) in a high
risk population. METHODS: Three groups of men (79 riveters, 52 healthy controls
and 79 compensation claimants) were assessed for VWF by a detailed questionnaire 
covering occupational and general medical history and incorporating specific
questions related to the presence or absence of relevant symptoms in their hands.
Each then underwent provocative cold testing under controlled conditions using
established protocols. The presence or absence of digital vasospasm following
cooling was determined by finger systolic pressure measurements using laser
Doppler flowmetry. The test protocols used have been evaluated in patients with a
clear clinical diagnosis of non-occupational Raynaud's syndrome. RESULTS: 6.3% of
the riveters and 83.5% of the claimants reported specific Raynaud's syndrome
symptoms but 30.4% of the riveters and only 19% of the claimants tested positive 
for vasospasm after middle phalangeal cooling to 10 degrees C for 5 min. Using a 
more severe cooling protocol provoked vasospasm in 46.8% of the claimants. Lack
of sensitivity or specificity of the objective testing could not explain the
large discrepancies between the findings in the riveters and in the claimants.
CONCLUSIONS: Questionnaire responses concerning VWF symptoms can be influenced by
the context in which they are recorded. It is important to employ more objective 
methods in assessing all workers at risk of developing VWF.

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

PMID: 11898875 [PubMed - indexed for MEDLINE]

238: Int Arch Occup Environ Health. 2002 Jan;75(1-2):29-36.

The clinical grading of Raynaud's phenomenon and vibration-induced white finger: 
relationship between finger blanching and difficulties in using the upper limb.

Palmer KT, Griffin MJ, Syddall H, Cooper C, Coggon D.

MRC Environmental Epidemiology Unit, Community Clinical Sciences, University of
Southampton, UK. ktp@mrc.soton.ac.uk

OBJECTIVES: To investigate the association between functional difficulties in
using the upper limb and extent and frequency of finger blanching, and the merits
of these markers in grading the severity of Raynaud's phenomenon (RP) and
vibration-induced white finger (VWF). METHODS: A questionnaire was mailed to a
randomly selected community sample of 22,194 working-aged adults. Information was
collected on cold-induced finger blanching--including the extent and frequency of
attacks in the past year, and on difficulty in using the upper limb in several
everyday activities (e.g. doing up buttons, opening a tight screwtop jar, and
pouring from a jug). Associations were examined by logistic regression with the
resultant odds ratios converted into prevalence ratios (PRs) and 95% confidence
intervals (95% CI). RESULTS: Among 12,907 respondents were 1,359 who reported
finger blanching and provided details of its extent and frequency. Of these, 7.4%
reported frequent attacks (50 or more over the year), and 12% reported extensive 
blanching (affecting nine or ten digits). After adjustment for potential
confounders, subjects with finger blanching reported an excess of difficulties in
using the limb. Thus, in men with blanching the PR for difficulty with buttons
was 4.7 (95% CI 3.9-5.8), and that for pouring from a jug was 3.8 (3.0-4.9) in
comparison with men who had never had blanching. Similar associations were found 
in women and in those men with exposure to hand-transmitted vibration. The risk
of reporting difficulties increased markedly with frequency of blanching--up to
four- or fivefold in those with 50 or more attacks in the past year compared with
those who had none; but differences by extent were less marked, with PRs < or =
1.6 in those with nine to ten digits affected compared with one to two digits.
CONCLUSIONS: RP and VWF are both associated with difficulties in using the upper 
limb in everyday tasks. Further investigation of potential reporting biases is
warranted, but if the associations are causal, frequency of attacks influences
impairment more than extent of disease. More account may need to be taken of
frequency of blanching episodes in assessing and in compensating subjects with
VWF.

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

PMID: 11898874 [PubMed - indexed for MEDLINE]

239: Int Arch Occup Environ Health. 2002 Jan;75(1-2):20-8.

Finger systolic blood pressure indices for the diagnosis of vibration-induced
white finger.

Bovenzi M.

Department of Public Health Sciences, Trieste General Hospitals, University of
Trieste, Italy. bovenzi@univ.trieste.it

OBJECTIVES: To compare the accuracy of several finger systolic blood pressure
indices (FSBPIs) for the diagnosis of cold-induced Raynaud's phenomenon in
vibration-exposed worker groups with different prevalences of vibration-induced
white finger (VWF). METHODS: The finger systolic blood pressure (FSBP) in a test 
finger at 10 degrees C as a percentage of the pressure at 30 degrees C, corrected
for the change in systolic blood pressure in a reference finger [FSBPI(A)] or the
arm [FSBPI(B)], was measured in 455 healthy controls and 874 workers exposed to
hand-transmitted vibration (HTV). The following FSBPIs were also calculated:
FSBPI(C), as the ratio between FSBP in the test finger at 10 degrees C and FSBP
in the same finger at 30 degrees C; and FSBPI(D), as the ratio of FSBP to arm
systolic blood pressure during finger cooling to 10 degrees C. The finding of
zero systolic blood pressure, FSBP(0), in the cooled finger was taken as an
objective sign of Raynaud's attack with complete closure of the digital arteries.
RESULTS: On a group basis, all FSBPIs could discriminate between the controls and
the HTV workers. In the vibration-exposed worker population, the FSBPIs were
significantly lower in the subjects affected with VWF than in those without
vasospastic symptoms. The lower normal limits of FSBPIs were derived from the
results of the cold test in the controls and were found to vary from 50% to 60%. 
The FSBPI(A) showed the best sensitivity for the detection of cold-induced
digital arterial hyper-responsiveness in both the total sample of HTV workers
(sensitivity 87%) and most of the vibration-exposed groups with different
prevalence of VWF (sensitivity from 79% to 100%). The results of the receiver
operating characteristic analysis suggested a higher diagnostic accuracy of
FSBPI(A) when compared with the global performance of the other FSBPIs. In the
whole sample of HTV workers, the predictive value of a positive cold test varied 
from 73% [FSBPI(D)] to 89% [FSBP(0)] and that of a negative test ranged between
89% [FSBP(0)] and 97% [FSBPI(A)]. CONCLUSIONS: The findings of this investigation
and clinical experience suggest that a discriminating threshold of FSBPI(A) <60% 
during finger cooling to 10 degrees C is an appropriate diagnostic criterion for 
the detection of abnormal cold response in the digital arteries of most
vibration-exposed workers with a true history of symptoms of finger whiteness at 
the medical interview.

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

PMID: 11898873 [PubMed - indexed for MEDLINE]

240: Arch Ophthalmol. 2002 Mar;120(3):302-7.

Vascular dysregulation in the choroid of subjects with acral vasospasm.

Hasler PW, Orgül S, Gugleta K, Vogten H, Zhao X, Gherghel D, Flammer J.

University Eye Clinic Basel, Mittlere Strasse 92, PO Box 4012, Basel,
Switzerland.

OBJECTIVE: To assess the relationship between ocular perfusion pressure and blood
flow in the choroid in subjects with acral vasospasm. PATIENTS AND METHODS:
Twenty otherwise healthy subjects with acral vascular dysregulation and 55
age-matched nonvasospastic healthy volunteers were recruited. After a 20-minute
rest in a sitting position, intraocular pressure and choroidal blood flow were
determined by means of applanation tonometry and choroidal laser Doppler
flowmetry, respectively. The laser Doppler flowmetry variables velocity, volume, 
and flux were assessed. The correlations between mean ocular perfusion pressure
([23 x [(23 x diastolic blood pressure) + (13 x systolic blood pressure)]]
-intraocular pressure) and blood flow measures were determined by means of the
Pearson linear correlation factor. The t test was used to evaluate differences
between normal subjects and patients with vasospasm. RESULTS: Apart from a slight
difference in systolic blood pressure (mean +/- SD, 113.70 +/- 11.88 mm Hg in the
vasospastic group and 121.09 +/- 14.58 mm Hg in the control group; P =.05), the 2
study groups were completely comparable. Velocity and flux correlated
significantly with the mean ocular perfusion pressure (r = 0.76, P<.001; r =
0.64, P =.002, respectively) in vasospastic subjects. Such correlations did not
occur in the control group, and the difference between vasospastic patients and
control subjects with regard to these correlations was statistically significant 
(P<.001 and P =.003, respectively). CONCLUSIONS: Choroidal blood flow seems, to
some degree, to be independent of perfusion pressure, but not in subjects with
acral vasospasm.

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

PMID: 11879133 [PubMed - indexed for MEDLINE]

241: Curr Rheumatol Rep. 2002 Apr;4(2):123-8.

Raynaud's phenomenon: epidemiology and risk factors.

Fraenkel L.

Yale University, Department of Internal Medicine, Section of Rheumatology, PO Box
208031, 333 Cedar Street, New Haven, CT 06520-8031, USA.
liana.fraenkel@med.va.gov

Although originally described more than 100 years ago, the pathophysiology of
Raynaud's phenomenon (RP) remains incompletely understood. Epidemiologic studies 
have the potential to improve our understanding of the pathogenesis of RP and to 
identify potential targets for therapeutic interventions. Such studies require
standardized instruments to accurately identify subjects with RP. Dr. Maricq was 
the first to develop and validate a standardized instrument to classify patients 
with this disorder. Her work has facilitated many of the epidemiologic studies of
RP that are discussed in this review.

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

PMID: 11890877 [PubMed - indexed for MEDLINE]

242: Joint Bone Spine. 2002 Jan;69(1):72-5.

Dermatomyositis sine myositis and antisynthetase syndrome.

Climent-Albaladejo A, Saiz-Cuenca E, Rosique-Roman J, Caballero-Rodriguez J,
Galvez-Munoz J.

Rheumatology unit, Hospital General Universitario Morales Meseguer, Murcia,
Spain. Zuniga@um.es

We describe a 66-year-old woman with cutaneous lesions typical of classic
dermatomyositis, clinical evidence of antisynthetase syndrome (arthritis,
Raynaud's phenomenon, mechanic's hands and interstitial lung disease with
anti-Jo-1 autoantibody) and lack of muscle disease after a full muscle evaluation
that included clinical, enzymatic, electromyographic, magnetic resonance imaging 
and histological studies. The patient did not develop myositis after 9 years of
clinical disease. The association of dermatomyositis sine myositis with
antisynthetase antibodies suggests that the characteristic skin lesions are
closely linked with dermatomyositis on the basis of the similar clinical and
serological features of both dermatomyositis sine myositis and classic
dermatomyositis.

Publication Types: 
    Case Reports

PMID: 11858361 [PubMed - indexed for MEDLINE]

243: Chest. 2002 Feb;121(2):656-9.

Pulmonary edema caused by inhaled nitric oxide therapy in two patients with
pulmonary hypertension associated with the CREST syndrome.

Preston IR, Klinger JR, Houtchens J, Nelson D, Mehta S, Hill NS.

Division of Pulmonary, Critical Care and Sleep Medicine, Rhode Island Hospital
and Brown University School of Medicine, Providence, RI 02903, USA.

Pulmonary arterial hypertension (PAH) is commonly associated with the CREST
(calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly,
telangiectasia) syndrome. Inhaled nitric oxide (iNO) is often used to assess
acute vasoresponsiveness in patients with PAH, and reports of adverse reactions
have been infrequent. We describe two of nine patients with PAH and CREST
syndrome who had pulmonary edema develop during acute iNO testing. This
complication was not encountered in the 46 patients with other forms of PAH
tested with iNO. We suggest that iNO should be used with caution, if at all, to
test acute vasoreactivity in patients with CREST syndrome.

Publication Types: 
    Case Reports
    Research Support, U.S. Gov't, P.H.S.

PMID: 11834688 [PubMed - indexed for MEDLINE]

244: J Rheumatol. 2002 Jan;29(1):94-101.

Enhanced expression of the receptor for granulocyte macrophage colony stimulating
factor on dermal fibroblasts from scleroderma patients.

Postiglione L, Montagnani S, Riccio A, Montuori N, Sciorio S, Ladogana P, Spigna 
GD, Castaldo C, Rossi G.

Dip. di Biologia e Patologia Molecolare e Cellulare, Università degli Studi
Federico, Napoli, Italia.

OBJECTIVE: To elucidate events that initiate the involvement and stimulation of
fibroblasts in systemic sclerosis (SSc). METHODS: We examined 15 patients with
SSc diffuse form, 15 with CREST syndrome, and 5 healthy subjects. Cultured
fibroblasts obtained from skin biopsies in SSc involved and non-involved areas
and norrmal skin fibroblasts were cultured with different doses of granulocyte
macrophage colony stimulating factor (GM-CSF) to study the effects of this factor
on the expression of GM-CSF receptor (GM-CSFR) on fibroblast proliferation and
cellular adhesion structures. RESULTS: Cultured fibroblasts obtained from
biopsies of normal and SSc skin areas express GM-CSFR and such expression is
increased in SSc fibroblasts. GM-CSF stimulation in vitro did not increase SSc
fibroblast growth, in spite of a strongly increased expression of the GM-CSFR.
The adhesion structures are always more abundant in SSc fibroblasts as compared
to healthy cells and GM-CSF seems able to increase cell adhesion plaques.
CONCLUSION: We suggest that shift of fibroblasts toward a more adhesive
differentiated pattern, due to or accompanied by an increased expression of
GM-CSFR, may be an important event in the pathogenesis of SSc.

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

PMID: 11824978 [PubMed - indexed for MEDLINE]

245: J Rheumatol. 2002 Jan;29(1):102-6.

Ulnar artery involvement in systemic sclerosis (scleroderma).

Taylor MH, McFadden JA, Bolster MB, Silver RM.

Department of Medicine, Medical University of South Carolina, Charleston 29425,
USA.

OBJECTIVE: Microvascular disease is one of the hallmarks of systemic sclerosis
(SSc, scleroderma), but macrovascular involvement also exists in some patients.
Patients with SSc may have severe Raynaud's phenomenon (RP) characterized by
refractory digital ulcerations. We investigated if large artery involvement, that
is, ulnar artery occlusion, has a role in the development of refractory digital
ulcerations, and if both screening for this involvement and revascularization of 
the ulnar artery occlusive disease may improve digital ulcer healing. METHODS: A 
retrospective chart review was performed of 15 patients with SSc, all of whom had
severe RP and digital ulceration, together with a positive Allen test and ulnar
artery occlusive disease documented by angiography. RESULTS: Women outnumbered
men 2:1, with limited disease predominating (7), 5 patients having diffuse
cutaneous disease and 3 overlap syndromes. All patients had positive antinuclear 
antibody and capillary microscopy findings consistent with SSc. Antiphospholipid 
antibodies were present in 4 of 6 patients tested. Tobacco use was seen in 5
patients, only 2 of whom were current smokers. All patients failed conventional
medical therapy (nitrates, calcium channel blockers, antiplatelet agents) for RP 
and digital ulceration. Only 1/8 patients improved with stellate ganglion block, 
and one patient had no improvement following digital sympathectomy. Eight
patients underwent ulnar artery revascularization combined with digital
sympathectomy, and 8 experienced dramatic improvement in RP and healing of
digital ulcers. CONCLUSION: An Allen test should be performed routinely on all
SSc patients with severe RP and refractory digital ulceration to investigate the 
possibility of ulnar artery occlusive disease. If suspected ulnar artery
occlusion is confirmed by angiography or ultrasonography, ulnar artery
revascularization with or without digital sympathectomy should be considered in
patients who fail conventional medical therapy.

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

PMID: 11824945 [PubMed - indexed for MEDLINE]

246: Appl Psychophysiol Biofeedback. 2001 Dec;26(4):251-78.

The Raynaud's Treatment Study: biofeedback protocols and acquisition of
temperature biofeedback skills.

Middaugh SJ, Haythornthwaite JA, Thompson B, Hill R, Brown KM, Freedman RR,
Attanasio V, Jacob RG, Scheier M, Smith EA.

Department of Anesthesiology and Perioperative Surgery, Medical University of
South Carolina, 165 Ashley Avenue, Suite 525, P.O. Box 250912, Charleston, South 
Carolina 29425, USA. middaugs@musc.edu

The Raynaud's Treatment Study (RTS) compared temperature biofeedback training and
a behavioral control procedure (frontalis EMG biofeedback) with nifedipine-XL and
a medication placebo for treatment of primary Raynaud's phenomenon (RP) in a
large (N = 313) multicenter trial. The present study describes the RTS
biofeedback protocols and presents data on the acquisition of digital skin
temperature and frontalis EMG responses in the RTS. The findings point to
substantial problems with acquisition of physiological self-regulation skills in 
the RTS. Only 34.6% of the Temperature Biofeedback group (N = 81) and 55.4% of
the EMG Biofeedback group (N = 74) successfully learned the desired physiological
response. In contrast, 67.4% of a Normal Temperature Biofeedback group (N = 46)
learned hand warming. Multivariate analysis found that coping strategies,
anxiety, gender, and clinic site predicted acquisition of hand-warming skills
whereas variables related to RP disease severity did not. Physiological data
showed vasoconstriction in response to the onset of biofeedback and also found
that performance in the initial sessions was critical for successful acquisition.
These findings indicate that attention to the emotional and cognitive aspects of 
biofeedback training, and a degree of success in the initial biofeedback
sessions, are important for acquisition.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 11802676 [PubMed - indexed for MEDLINE]

247: Clin Exp Rheumatol. 2001 Nov-Dec;19(6):647-54.

Lymphocyte-endothelium interaction in systemic sclerosis and Raynaud's
phenomenon.

Della Bella S, Molteni M, Mocellin C, Fumagalli S, Bonara P, Scorza R.

Department of Internal Medicine, University of Milan, IRCCS Ospedale Maggiore di 
Milano, Italy. silvia.dellabella@unimi.it

OBJECTIVE: To investigate interactions of immune cells with vascular endothelium 
in patients with systemic sclerosis (SSc) and in patients with idiopathic or
autoimmune Raynaud's phenomenon (RP). METHODS: Lymphocytes obtained from 11
patients with SSc, 9 with RP and 14 control subjects were pre-stimulated in vitro
with alloantigens and cultured together with human umbilical vein endothelial
cells (HUVECs). Lymphocyte adhesion and induction of endothelial HLA-class 11
molecules were measured by flow cytometry. Lymphocyte cytotoxicity against HUVECs
was also evaluated. In some cases cells were cultured under experimental
conditions of hypoxia and reoxygenation. RESULTS: Lymphocyte adhesion and
induction of endothelial cell expression of HLA-DR molecules were similar in
controls and SSc patients, but significantly lower in RP (p < 0.05 and p < 0.03, 
respectively). Cytotoxic activity of lymphoblasts against endothelial cells was
negligible in all patient groups. Under experimental conditions of hypoxia and
reoxygenation lymphocyte adhesion was significantly greater than in normoxic
conditions in SSc patients, while it was similar to normoxia in control subjects 
and RP patients. CONCLUSION: These results suggest that in RP patients there may 
be regulatory mechanisms of lymphocyte response able to control the processes
that lead to lymphocyte adhesion and endothelial HLA-DR molecule induction. These
mechanisms could play an important role in RP, and might possibly be lost in
clinically evident SSc.

PMID: 11791635 [PubMed - indexed for MEDLINE]

248: Int Angiol. 2001 Dec;20(4):307-13.

Raynaud's phenomenon (primary or secondary to systemic sclerosis). The usefulness
of laser-Doppler flowmetry in the diagnosis.

Del Bianco E, Magini B, Muscarella G, Cappugi P, Lotti T.

Department of Dermatological Science, University of Florence, Florence, Italy.
e.delbianco@dfc.unifi.it

BACKGROUND: Raynaud's phenomenon (RP) consists of painful vascular spasms of the 
extremities stressed by cold exposure. It is often a symptom, in many cases the
onset, of systemic sclerosis (SSc). The aim of this study was to evaluate the
role that laser-Doppler flowmetry (LDF) could have in the differential diagnosis 
of these disorders and to characterize the functional behaviour of the
microvessels in RP. METHODS: In this study we examined 52 patients (five males
and 47 females, aged 17-57) affected by primary RP, 21 patients (three males and 
18 females, aged 31-63) affected by RP secondary to SSc as defined by Wouda in
1987 and 20 healthy subjects (three males and 17 females, aged 26-58) by means of
LDF with an appropriate cold-test (11 degrees C for 2 min). RESULTS: We show that
the cold test applied at hand level can distinguish RP patients from healthy
subjects. Data show that basal blood flow of patients affected by SSc is
diminished in its medium value and presents a typical tracing without vasomotion 
in comparison to healthy subjects and also to patients affected by primary RP. On
the basis of our data among the primary RP patients we can also distinguish a
group that show basal blood flow tracing very similar to that of sclerodermic
patients. These subjects should be carefully followed-up. CONCLUSIONS: In
conclusion, it could be stimulating for the future to introduce LDF as a
complementary method for the diagnosis of RP and possibly for early
discrimination between the primary disease and that secondary to SSc.

PMID: 11782697 [PubMed - indexed for MEDLINE]

249: Vasa. 2001 Nov;30(4):281-4.

Low level laser treatment of primary and secondary Raynaud's phenomenon.

al-Awami M, Schillinger M, Gschwandtner ME, Maca T, Haumer M, Minar E.

Department of Medical Angiology, University of Vienna, Austria.
Salawama1@akh-wien.ac.at

BACKGROUND: Patients who had been treated with low level laser (LLL) for their
digital ulcers reported an impressive improvement of their symptoms of episodic
digital ischaemia. Therefore this pilot study was performed to evaluate the
efficacy of LLL as a new non-drug non-invasive treatment for patients with
primary and secondary Raynaud's phenomenon (RP). PATIENTS AND METHODS: Forty
patients (29 female, 11 male, mean age 51 years) with active primary (28%) and
secondary (72%) Raynaud's phenomenon received 10 sessions of LLL distant
irradiation during winter months. Assessment of subjective and objective
parameters was performed at baseline, one week after the last session and three
months later. Variations of subjective parameters as number of daily acute
episodes and severity of discomfort were assessed by a coloured visual analogue
scale. A standardised cold challenge test using computed thermography of
continuous temperature recordings by means of infrared telethermography was used 
to assess the digital blood flow. RESULTS: A significant improvement was noticed 
clinically and thermographically after 6 weeks and 3 months, respectively (p <
0.0001). CONCLUSIONS: These data suggest that LLL treatment has a good short and 
medium term effectiveness in patients with Raynaud's phenomenon.

Publication Types: 
    Evaluation Studies

PMID: 11771213 [PubMed - indexed for MEDLINE]

250: Rheumatology (Oxford). 2001 Dec;40(12):1384-7.

The use of portable radiometry to assess Raynaud's phenomenon: a practical
alternative to thermal imaging.

Cherkas LF, Howell K, Carter L, Black CM, MacGregor AJ.

Twin Research and Genetic Epidemiology Unit, St Thomas' Hospital, London, UK.

OBJECTIVES: To compare the performance of a portable radiometer with thermal
imaging and to assess the potential for radiometry to provide a practical
alternative for assessing vascular responsiveness in Raynaud's phenomenon (RP).
METHODS: Subjects comprised 18 patients with diagnosed RP and 19 non-RP subjects.
A thermal imager (Starsight) and a portable radiometer (Cyclops) measured digital
temperature at baseline and the subsequent drop and rise in temperature following
a cold challenge test. RESULTS: The intra-class correlations between the two
instruments for all three measures exceeded 80%. The overall performance of each 
instrument was almost the same, the Starsight thermal imager correctly
classifying 84% of subjects as RP or non-RP and the Cyclops portable radiometer
correctly classifying 86% of subjects. The sensitivity of the thermal imager was 
83%, compared with 89% for the portable radiometer; the specificity of both
instruments was 84%. The positive and negative predictive values of the thermal
imager were 83 and 84% respectively, and those for the portable radiometer were
84 and 89%. CONCLUSIONS: The two instruments performed equally well and the
differences between them in their absolute measurements did not influence their
ability to detect RP. Portable radiometry provides a practical, cheap, accurate
and reliable alternative to thermal imaging and has the potential to be used in
range of clinical and epidemiological settings.

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

PMID: 11752509 [PubMed - indexed for MEDLINE]

251: Am Surg. 2001 Nov;67(11):1096-7.

Clinical and objective data on spinal cord stimulation for the treatment of
severe Raynaud's phenomenon.

Neuhauser B, Perkmann R, Klingler PJ, Giacomuzzi S, Kofler A, Fraedrich G.

Department of Vascular Surgery, University Hospital Innsbruck, Austria.

Ischemic vascular disease of the upper extremity represents a difficult
therapeutic problem wherein medical treatment often fails. Epidural spinal cord
stimulation has been shown to be an effective alternative in severe peripheral
arterial disease. Although this method has been used for nearly two decades only 
limited experience exists in Raynaud's phenomenon of the upper limbs. In addition
objective parameters to prove therapeutic success are not well defined. Herein we
describe a patient with severe primary Raynaud's phenomenon over several years
who had significant pain relief and complete healing of ischemic digital
ulcerations after spinal cord stimulation. Pain level was evaluated using a
visual rating scale before and after surgery. Microcirculatory parameters were
assessed before and after spinal cord stimulation by capillary microscopy and
laser Doppler anemometry. Significant improvement of red blood cell velocity,
capillary density, and capillary permeability was demonstrated. At follow-up 18
months after surgery the patient had no complaints and all ulcerations of her
fingertips had healed. Spinal cord stimulation appears to be an effective
treatment in severe cases of Raynaud's phenomenon and we recommend its use in the
case of failed medical therapy. Pain rating and capillary microscopy enable one
to assess and visualize the effects of spinal cord stimulation.

Publication Types: 
    Case Reports

PMID: 11730228 [PubMed - indexed for MEDLINE]

252: Heart Dis. 2000 Jan-Feb;2(1):62-74.

Drug treatment of peripheral vascular disease.

Eberhardt RT, Coffman JD.

Department of Vascular Medicine, Boston University School of Medicine, Boston, MA
02118, USA.

There are a limited number of clinically effective pharmacotherapeutic agents for
treatment of peripheral vascular disorders. Pentoxifylline and cilostazol are
available for the symptomatic treatment of intermittent claudication. Analogs of 
carnitine and L-arginine are being evaluated for treatment of the symptoms of
intermittent claudication, and prostaglandins and growth factors are being
evaluated for critical limb ischemia. Calcium channel blockers remain the
treatment of choice for Raynaud's phenomenon. Alternative vasodilators may be
used selectively to treat individuals with Raynaud's phenomenon who are
intolerant of calcium channel blockers or in whom such therapy has been
unsuccessful. Prostaglandins have been evaluated in patients with refractory
Raynaud's phenomenon who also have digital ulceration. The mainstay of short-term
treatment (and prophylaxis) of deep vein thrombosis (DVT) has been unfractionated
heparin, but now the use of low molecular weight heparin (LMWH) has emerged.
Newer agents, such as heparinoids and direct thrombin inhibitors, hold promise
for the prevention and treatment of DVT. Prolonged treatment with warfarin is
still required to prevent recurrent thrombosis, although the duration of
treatment has come under debate.

Publication Types: 
    Review

PMID: 11728242 [PubMed - indexed for MEDLINE]

253: Scand J Rheumatol. 2001;30(5):290-6.

Relative roles of endothelial cell damage and platelet activation in primary
Raynaud's phenomenon (RP) and RP secondary to systemic sclerosis.

Silveri F, De Angelis R, Poggi A, Muti S, Bonapace G, Argentati F, Cervini C.

Department of Rheumatology, Ancona University, Ospedale A. Murri, Jesi, Italy.
fesilve@tin.it

OBJECTIVE: To evaluate the relative roles of endothelium and platelets in the
pathogenesis of primary RP and RP secondary to SSc. METHODS: Endothelial derived 
ET-1, t-PA, PAI-1, and platelet derived beta-TG, PDGF, TGF-beta were measured in 
36 patients with primary RP, 14 patients with RP secondary to SSc and 30 age and 
sex matched controls. RESULTS: A significative increase of ET-1, t-PA, PAI-1,
TGF-beta, and beta-TG were the most relevant changes in patients with RP
secondary to SSc with respect to the controls. Less relevant increases of t-PA,
PAI-1, PDGF, and beta-TG levels were observed in patients with primary RP vs
controls. CONCLUSIONS: These data seem to confirm the involvement of endothelial 
cells and platelets in the pathogenesis of RP, with mild changes in primary RP
and more relevant changes in RP secondary to SSc.

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

PMID: 11727844 [PubMed - indexed for MEDLINE]

254: Am J Clin Dermatol. 2001;2(5):315-25.

Treatment of systemic sclerosis.

Steen VD.

Department of Medicine, Georgetown University, Washington, DC, USA.
steenv@georgetown.edu

Systemic sclerosis is an extremely variable disease in its manifestations and
consequently, treatment needs to be individualized depending on the specific
problems that each patient has. Limited scleroderma patients have a prolonged
duration of Raynaud's phenomenon and puffy fingers before they develop any skin
thickening, digital ulcers or gastrointestinal symptoms. They are likely to
present with all the classic manifestations of scleroderma. Diffuse scleroderma
patients have a much more acute systemic onset with marked whole hand swelling
and may initially have only subtle skin thickening. A good understanding of the
differences between the natural history of limited and diffuse scleroderma will
enable the physician to treat present problems and anticipate future ones more
effectively. One should determine which major subset and organ systems are
involved before deciding on the appropriate therapy. Advances in organ-specific
therapy, particularly calcium channel antagonists in Raynaud's phenomenon, proton
pump inhibitors in esophageal reflux, intravenous iloprost and endothelin
receptor antagonists in pulmonary hypertension, and ACE inhibitors in renal
crisis, have decreased morbidity and mortality in patients with scleroderma.
Studies of aggressive therapies to prevent or improve pulmonary fibrosis are in
progress. Further clinical experience in wound healing, gastrointestinal
malabsorption and physical therapy for loss of motion has helped patients to have
a more comfortable life. In recent years, a significant number of controlled
clinical trials have been performed and there has been improved understanding of 
the best way to perform studies and of which patients are most likely to respond 
to therapy. Penicillamine, methotrexate, photopheresis, relaxin, interferons, and
cyclosporine have all been studied in controlled trials with variable outcomes.
Although an overall remittive therapy has not yet been determined, new,
potentially useful agents are being investigated.

Publication Types: 
    Review

PMID: 11721650 [PubMed - indexed for MEDLINE]

255: Acta Derm Venereol. 2001 Aug-Sep;81(4):294-7.

Systemic sclerosis-related Raynaud's phenomenon: effects of iloprost infusion
therapy on serum cytokine, growth factor and soluble adhesion molecule levels.

Mittag M, Beckheinrich P, Haustein UF.

Department of Dermatology, University of Leipzig, Germany.

Microvascular damage occurs in systemic sclerosis and is associated with
increased serum levels of endothelial adhesion molecules and
endothelium-associated cytokines, including vascular cell adhesion molecule-1
(VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, endothelin-1
and vascular endothelial growth factor (VEGF). Iloprost, a prostacyclin analogue,
induces clinical benefit in patients suffering from scleroderma-related Raynaud's
phenomenon. This study was performed to investigate the effect of iloprost
infusions on endothelium activation. Serum samples from 12 patients with systemic
sclerosis were examined using specific enzyme-linked immunoassays. The serum
levels of sICAM-1, sVCAM-1 and soluble E-selectin were initially elevated and
significantly reduced after iloprost infusions. The serum concentrations of VEGF 
and endothelin-1 revealed decreased levels after therapy too. These results
indicate that the well-known clinical benefit of iloprost infusions on Raynaud's 
phenomenon is serologically detectable by a reduction of serum levels of
endothelium-associated adhesion molecules, cytokines and growth factors
reflecting an improvement in endothelial function.

PMID: 11720181 [PubMed - indexed for MEDLINE]

256: Br J Dermatol. 2001 Oct;145(4):646-9.

The diagnostic quandary of hereditary haemorrhagic telangiectasia vs. CREST
syndrome.

Lee JB, Ben-Aviv D, Covello SP.

Ameripath Laboratory, 10th Floor, 145 East 32nd Street, New York, NY 10016, USA. 
jboklee@netscape.net

The distribution and clinical appearance of the telangiectasia in the CREST
syndrome (calcinosis, Raynaud's phenomenon, oesophageal involvement,
sclerodactyly, telangiectasia) and hereditary haemorrhagic telangiectasia (HHT)
are very similar. Several previously reported cases of the CREST syndrome
simulating HHT illustrate this diagnostic quandary. We report a patient who met
the diagnostic criteria for both the CREST syndrome and HHT, and discuss the
distinguishing features of the two diseases, including the distinctive
histopathological findings of telangiectasia in HHT.

Publication Types: 
    Case Reports

PMID: 11703295 [PubMed - indexed for MEDLINE]

257: Intern Med. 2001 Oct;40(10):1059-63.

Progressive interstitial renal fibrosis due to Chinese herbs in a patient with
calcinosis Raynaud esophageal sclerodactyly telangiectasia (CREST) syndrome.

Nishimagi E, Kawaguchi Y, Terai C, Kajiyama H, Hara M, Kamatani N.

Institute of Rheumatology and Aoyama Hospital, Tokyo Women's Medical University
School of Medicine.

A 58-year-old woman with calcinosis Raynaud esophageal sclerodactyly
telangiectasia (CREST) syndrome presented with slowly progressive renal
dysfunction. She was normotensive with normal plasma renin activity and lacking
symptoms of vasculitis. Mild proteinuria was of tubular origin, but serological
tests and an absence of sicca symptoms excluded the possibility of Sjögren's
syndrome. Light microscopic study of renal biopsy showed interstitial fibrosis
with ectasia and degeneration of proximal tubule and lymphocyte infiltration.
There were no remarkable changes in the glomeruli. Chromatographic analysis of
the Chinese herbs regimen that she had been taking for several years demonstrated
aristolochic acid. She was diagnosed as Chinese herbs nephropathy. Therapy with
oral prednisolone was markedly effective in improving renal function and anemia. 
To our knowledge, this is the first report of Chinese herbs nephropathy
complicating connective tissue disease. It is important to consider the
possibility of Chinese herbs nephropathy when patients treated with Chinese herbs
develop renal dysfunction.

Publication Types: 
    Review

PMID: 11688835 [PubMed - indexed for MEDLINE]

258: J Rheumatol. 2001 Oct;28(10):2263-8.

Effect of temperature and modulators of protein tyrosine kinase activity on the
reactivity of isolated venules in secondary Raynaud's phenomenon.

Furspan PB, Mayes MD, Freedman RR.

Department of Psychiatry, Internal Medicine, Wayne State University Detroit,
Michigan 48201, USA. aa1985@wayne.edu

OBJECTIVE: To investigate the response of skin venules from healthy controls and 
scleroderma patients with Raynaud's phenomenon (RP/SSc) to cooling and to
modulators of protein tyrosine kinase (PTK) activity at normal and reduced
temperature. METHODS: We used the microvessel perfusion technique to characterize
the response of isolated dermal venules (200-400 microm outside diameter) from
normal (n = 10) and RP/SSc (n = 8) subjects to cooling and to contractile agents 
at 37 and 31 degrees C. RESULTS. The response to clonidine at 37 degrees C was
less in venules from patients with RP/SSc compared to controls; the contraction
to serotonin was greater in venules from RP/SSc patients versus controls; at 31
degrees C, venules from RP/SSc patients contracted to both clonidine and
serotonin to a greater extent versus controls; and contraction to these agonists 
was reversed by cumulative addition of genistein (1-100 microM). Venules from
controls and patients with RP/SSc exhibited slight vasodilation to cooling from
37 to 31 degrees C. In the presence of the protein tyrosine phosphatase inhibitor
sodium orthovanadate (10 microM), venules from controls now exhibited a small
contraction (-5.1 +/- 3.2%) and venules from RP/SSC subjects a significantly
greater contraction (-38.7 +/- 9.0%; p < 0.05). CONCLUSION: Our study supports
the view that RP/SSc is the result of defects in the peripheral vasculature.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 11669167 [PubMed - indexed for MEDLINE]

259: J Rheumatol. 2001 Oct;28(10):2257-62.

Intravenous N-acetylcysteine for treatment of Raynaud's phenomenon secondary to
systemic sclerosis: a pilot study.

Sambo P, Amico D, Giacomelli R, Matucci-Cerinic M, Salsano F, Valentini G,
Gabrielli A.

Istituto di Clinica Medica Generale, Ematologia ed Immunologia Clinica,
University of Ancona, Italy.

OBJECTIVE: To assess the efficacy and tolerability of N-acetylcysteine (NAC) in
patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis
(scleroderma; SSc). METHODS: Twenty-two patients with RP secondary to SSc were
enrolled in a multicenter, open clinical trial lasting 11 weeks and conducted in 
winter. Primary outcome measures were frequency and severity of RP attacks, and
number of digital ulcers. Secondary outcome measure was improvement in digital
cold challenge test assessed by photoelectric plethysmography. Patients received 
a continuous 5 day intravenous infusion of NAC starting with a 2 h loading dose
of 150 mg/kg subsequently adjusted to 15 mg/kg/h. RESULTS: All 22 patients
completed the 5 day infusion and 20 of them the posttreatment followup. Both
frequency and severity of RP attacks decreased significantly compared to
pretreatment values. Active ulcers were significantly less numerous at all
followup visits (25.18% of baseline count on Day 33 from the beginning of
infusion). In the cold challenge test mean recovery time fell by 69.56%, 67.70%, 
71.42%, and 71.05% on Days 12, 19. 33, and 61 from the beginning of treatment.
Side effects were minor, easily controlled, and reversible. CONCLUSION:
N-acetylcysteine appears to be safe for the treatment of RP secondary to SSc.
These preliminary data warrant further controlled studies.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 11669166 [PubMed - indexed for MEDLINE]

260: J Rheumatol. 2001 Oct;28(10):2252-6.

Aerosolized iloprost in CREST syndrome related pulmonary hypertension.

Launay D, Hachulla E, Hatron PY, Goullard L, Onimus T, Robin S, Fauchais AL,
Queyrel V, Michon-Pasturel U, Hebbar M, Saulnier F, Devulder B.

Department of Internal Medicine, Functional Cardiac Exploration, Regional
University Hospital, Lille, France.

OBJECTIVE: To assess the outcome of patients with CREST syndrome associated
severe pulmonary hypertension treated by aerosolized iloprost in a noncomparative
study. METHODS: Five patients with CREST syndrome associated severe pulmonary
hypertension were treated with 100 microg/day of aerosolized iloprost. New York
Heart Association functional class and exercise tolerance (6 min walk test) were 
assessed at baseline, after one month, and then every 6 months. A right heart
catheterization was performed at baseline in all but one patient. Systolic
pulmonary artery pressure (PAP) was measured with Doppler echocardiography after 
one month and every 6 months. RESULTS: The mean followup was 13.2 +/- 8.8 months 
(median 6, range 6-24). Subjective quality of life improved in all patients. NYHA
functional class decreased from Class III to II in 3 patients, from Class III to 
I in one patient, and from Class IV to III in one patient. At 6 months, the
distance walked in 6 min had increased from 352 +/- 48 to 437 +/- 56 m (p =
0.06). At one month the mean systolic PAP was 58 +/- 13 vs 81 +/- 9 mm Hg at
baseline (p = 0.04). At 6 months the mean systolic PAP was 57 +/- 13 mm Hg (p =
0.06). The improvement of both clinical and hemodynamic status was maintained in 
the 2 patients treated for 2 years. Neither adverse effects nor need to increase 
the daily dose of iloprost were observed. One patient died of right heart failure
and one patient did not experience any improvement of exercise tolerance and
hemodynamics. CONCLUSION: Aerosolized iloprost might be potentially useful as
treatment for CREST syndrome associated pulmonary hypertension. However, patients
who could benefit from this treatment will probably have to undergo careful
criteria selection.

Publication Types: 
    Clinical Trial

PMID: 11669165 [PubMed - indexed for MEDLINE]

261: Clin Rheumatol. 2001;20(5):376-8.

Cocaine-Induced raynaud's phenomenon and ischaemic finger necrosis.

Balbir-Gurman A, Braun-Moscovici Y, Nahir AM.

B. Shine Department of Rheumatology, Rambam Medical Center, The Bruce Rappaport
Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
nahir@rambam.health.gov.il

A 37-year-old man with ischaemic finger necrosis and recent-onset Raynaud's
phenomenon associated with cocaine abuse is reported. Initial therapy with
systemic vasodilators, low-molecular-weight heparin and aspirin failed.
Resolution of the ischaemia and ulcer healing was rapidly achieved with
intravenous infusions of the prostacyclin analogue iloprost. The mechanism of
vascular ischaemic injury and the development of secondary Raynaud's phenomenon
due to cocaine use is discussed.

Publication Types: 
    Case Reports

PMID: 11642523 [PubMed - indexed for MEDLINE]

262: Occup Med (Lond). 2001 Sep;51(6):401-9.

Hand-arm vibration syndrome from exposure to high-pressure hoses.

Cooke R, House R, Lawson IJ, Pelmear PL, Wills M.

The Exeter Nuffield Hospital, Exeter, UK.

Hand-arm vibration syndrome has been reported in the literature to occur
following exposure to vibration from the use of many tools, but to date there
have been no case reports of its occurrence in workers who have used
high-pressure hoses, alone or with other tools. To remedy this, the case
histories of nine subjects (two without mixed exposure) examined in the UK and
Canada are presented, together with their severity classified according to the
Stockholm scales. Attention is drawn to the need to use multiple diagnostic tests
to establish the diagnosis and the need to implement vibration isolation and
damping methodologies, as and when feasible, with respect to hose nozzles in
order to minimize the hazard. The ultimate goal for tool manufacturers,
hygienists and engineers should be to reduce workplace vibration levels to meet
national and international guidelines and legislation, including UK Health &
Safety Executive guidelines and European Economic Community directives. The
respective risk levels are presented, together with vibration measurements on
hoses used by some of the cases.

Publication Types: 
    Case Reports

PMID: 11584120 [PubMed - indexed for MEDLINE]

263: Intern Med. 2001 Sep;40(9):905-10.

Primary pulmonary hypertension with severe systemic hypertension, Raynaud's
phenomenon and relative polycythemia.

Murata M, Kuroda T, Nakajima K, Fujikawa H, Shimada K.

Department of Cardiology, Jichi Medical School, Tochigi.

A 32-year-old Japanese man was hospitalized for evaluation of unconsciousness. He
was diagnosed as having primary pulmonary hypertension (PPH) with severe systemic
hypertension, Raynaud's phenomenon and relative polycythemia. Hemostatic studies 
revealed increased coagulation and decreased fibrinolysis, similar to findings of
chronic disseminated intravascular coagulation (DIC). Although activation of
coagulation and systemic hypertension were improved after treatment with
phlebotomy and administration of nifedipine, enerapril and warfarin, pulmonary
hypertension was unchanged, suggesting that irreversible change had already
occurred in the pulmonary arteries. Those complications could modify the process 
of pulmonary hypertension by inducing a hyperviscosity state.

Publication Types: 
    Case Reports

PMID: 11579954 [PubMed - indexed for MEDLINE]

264: Clin Exp Rheumatol. 2001 Sep-Oct;19(5):503-8.

Effects of long-term cyclic iloprost therapy in systemic sclerosis with Raynaud's
phenomenon. A randomized, controlled study.

Scorza R, Caronni M, Mascagni B, Berruti V, Bazzi S, Micallef E, Arpaia G,
Sardina M, Origgi L, Vanoli M.

Clinical Immunology and Allergy, University of Milan, IRCCS Ospedale Maggiore,
Milan, Italy. raffaella.scorza@unimi.it

OBJECTIVE: Iloprost is a stable prostacyclin analogue which has been shown to be 
effective in the short-term symptomatic treatment of Raynaud's phenomenon (RP)
secondary to systemic sclerosis (SSc). The aim of this study was to evaluate the 
effects of long-term cyclic therapy with iloprost in comparison with nifedipine
on the skin score, pulmonary function and Raynaud's severity score in patients
with SSc and RP. METHODS: We conducted a 12-month prospective, randomised,
parallel-group, blind-observer trial to compare the effects of intravenously
infused iloprost (2 ng/kg/min on 5 consecutive days over a period of 8 hours/day 
and subsequently for 8 hours on one day every 6 weeks) with those of conventional
vasodilating therapy with nifedipine (40 mg/day for os) in 46 patients with SSc
and RP. RESULTS: At 12 months, iloprost but not nifedipine reduced the skin score
(iloprost: from 13.26 +/- 2.05 to 9.26 +/- 1.32, p = 0.002; nifedipine: from
10.83 +/- 2.09 to 12.17 +/- 3.02, p = n.s.; iloprost vs nifedipine: p = 0.016)
and the RP severity score (iloprost: from 2.17 +/- 0.2 to 1.22 +/- 0.13, p = 0.02
vs baseline; nifedipine: from 2.08 +/- 0.34 to 1.33 +/- 0.22, p = n.s.). Carbon
monoxide diffusing capacity (DLCO), expressed as % of the predicted normal value,
worsened significantly in the nifedipine group (from 69.6 +/- 7.4% to 61.5 +/-
6.5%, p = 0.044) and remained stable in patients treated with iloprost (from 53.2
+/- 4.8 to 56.0 +/- 4.6%, iloprost vs nifedipine: p = 0.026). CONCLUSION: In SSc 
patients, cyclic intravenous iloprost infusion is able to control vasospastic
disease. Our results suggest that it might also act as a disease-modifying agent,
as it seems to improve the course of the disease. Further studies principally
focused on organ involvement and the natural history of the disease are needed to
confirm our results.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 11579708 [PubMed - indexed for MEDLINE]

265: Int Angiol. 2001 Sep;20(3):234-40.

A method for evaluating the thermal threshold in patients with Raynaud's syndrome
living in temperate areas. A report of three cases.

Luca S.

Ernest Cooke Clinical Microvascular Unit, St. Bartholomew's Hospital, London,
United Kingdom.

BACKGROUND: The concept of "thermal threshold" in Raynaud's syndrome was
theorized in 1990 by Pratesi as the ambient temperature below which an attack of 
vasospasm is more likely to be provoked, though so far it has not yet been proved
to be a reality. Our preliminary report of two cases, whose attacks were compared
with the daily maximum temperatures, showed results suggestive of the existence
of this parameter. METHODS: We asked a third female patient with Raynaud's
syndrome of the hands and feet to keep note of the time, days and modalities of
the phenomena, for at least three months including the summer. Data of six and
five months from Cases 1 and 2 respectively, not including the times at onset,
were reconsidered. The data available from all cases were compared to the true
daily mean temperature. The data of the new Case 3 were also compared with the
hourly temperatures on each day over the period of study. All calculations
referred to the estimated temperature to be expected from the difference in
altitude between the weather stations and the usual and temporary residences.
RESULTS: The mean thermal threshold was 17.166 degrees C in the less severe Case 
1 and 28.438 degrees C in Case 2 (complicated by gangrene). In Case 3, the mean
and hourly thresholds were 26.740 and 26.807 degrees C for the hands, and 25.092 
and 23.807 degrees C for the feet, respectively. CONCLUSIONS: This report is
suggestive, although not conclusively, of the existence of a thermal threshold,
which is higher in the more severe cases. Further research is required.

PMID: 11573058 [PubMed - indexed for MEDLINE]

266: Rheumatology (Oxford). 2001 Sep;40(9):1038-43.

Comment in:
    Rheumatology (Oxford). 2003 Apr;42(4):601-2.

Treatment of Raynaud's phenomenon with the selective serotonin reuptake inhibitor
fluoxetine.

Coleiro B, Marshall SE, Denton CP, Howell K, Blann A, Welsh KI, Black CM.

Centre for Rheumatology (Royal Free Campus), Royal Free and University College
School of Medicine, Rowland Hill Street, London, UK.

OBJECTIVE: To compare fluoxetine, a selective serotonin reuptake inhibitor, with 
nifedipine as treatment for primary or secondary Raynaud's phenomenon. METHODS:
Twenty-six patients with primary and 27 patients with secondary Raynaud's
phenomenon were assigned randomly to receive 6 weeks of treatment with fluoxetine
(20 mg daily) or nifedipine (40 mg daily). Following a 2-week washout period,
each group was crossed over to the other treatment arm. The primary outcome
variable was the frequency of attacks of Raynaud's phenomenon. Self-reported
attack severity, thermographic recovery from cold challenge and plasma levels of 
von Willebrand factor and soluble P-selectin were also measured. RESULTS: There
was a reduction in attack frequency and severity of Raynaud's phenomenon in
patients treated with either fluoxetine or nifedipine, but the effect was
statistically significant only in the fluoxetine-treated group (P=0.0002 for
attack severity and P=0.003 for attack frequency). Subgroup analysis showed that 
the greatest response was seen in females and in patients with primary Raynaud's 
phenomenon. A significant improvement in the thermographic response to cold
challenge was also seen in female patients with primary Raynaud's phenomenon
treated with fluoxetine but not in those treated with nifedipine. There was no
significant treatment effect on von Willebrand factor or soluble P-selectin. No
significant adverse effects occurred in the fluoxetine-treated group. CONCLUSION:
This pilot study confirms the tolerability of fluoxetine and suggests that it
would be effective as a novel treatment for Raynaud's phenomenon. Larger and
placebo-controlled trials are warranted to assess fluoxetine's therapeutic
potential further in this vasospastic condition.

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

PMID: 11561116 [PubMed - indexed for MEDLINE]

267: Acta Paediatr Taiwan. 2001 Jul-Aug;42(4):248-51.

Limited cutaneous systemic sclerosis: report of one case.

Lin MC, Fu LS, Huang KY, Tsen CF, Liou JM, Chi CS.

Department of Pediatrics, Veterans General Hospital, 160, Sec. 3, Taichung Harbor
Road, Taichung 407, Taiwan.

We report a case of systemic sclerosis, limited type, in a 5 year old boy in
Taiwan. He presented with erythema, tight skin over his face and digits,
subcutaneous calcification, telangiectasis, as well as Raynaud's phenomenon. The 
laboratory data showed weakly positive antinuclear antibody (ANA), and
Topoisomerase 1 antibody (anti-Scl-70) titers. However his esophagogram, CO
diffusion capacity, as well as cardiac and renal function were all normal. He
suffered from the skin change for 2 to 3 years before visiting our pediatric
clinic when he was 7 years old. We gave him Dipyridamole, D-penicillamine,
Colchicine, and Nifedipine. There was some remission of the scleroderma and
Raynaud's phenomenon after our treatment.

Publication Types: 
    Case Reports

PMID: 11550416 [PubMed - indexed for MEDLINE]

268: J Vasc Nurs. 2001 Sep;19(3):87-92; quiz 93-4.

Raynaud's phenomenon.

O'connor CM.

Barnes College of Nursing at the University of Missouri at St Louis, 63010, USA.

Many persons are affected by the phenomenon known as Raynaud's. Raynaud's is
classified in 2 ways-as Raynaud's disease or Raynaud's syndrome. Classification
is based on the presence of associated conditions. Raynaud's is characterized by 
vasospasm-induced color changes of the fingers, toes, and ears. The fingers are
most commonly affected. Studies involving cause, diagnosis, and treatment have
been instituted with varied results. Diagnosis is primarily based on clinical
symptoms involving digital color changes. Treatment is aimed at prevention of
attacks and includes medication, stress reduction, and avoidance of
vasoconstricting agents. Whether the phenomenon will develop into a more serious 
condition with which Raynaud's is associated is important. This article describes
the etiology, pathophysiology, diagnosis, treatment, and nursing implications
with regard to Raynaud's.

Publication Types: 
    Case Reports
    Review

PMID: 11533581 [PubMed - indexed for MEDLINE]

269: Microvasc Res. 2001 Sep;62(2):190-5.

Arteriolar resistance and hemorheological disorders related to Raynaud's
phenomenon.

Mchedlishvili G, Mantskava M, Pargalava N.

Microcirculation Research Center, I. Beritashvili Institute of Physiology, 14
Gotua St., Tbilisi, 380060, Georgia.

The functional condition of resistance arteries in human hands was monitored with
a noninvasive test. Blood flow velocity changes (Doppler flow meter) were
monitored in the radial artery before and after a 1-min stop flow in the hand
under conditions of stable systemic arterial pressure. In addition, the most
significant parameter of hemorheological disorders in microcirculation, RBC
aggregability, was investigated in the same patients' blood samples. The muscular
tone of the resistance arteries was found to be a mean of 35% higher during
Raynaud's phenomenon than in the healthy controls tested. The raised vascular
tone was not related to the patients' age and had a pronounced tendency to rise
with disease duration. RBC aggregability was a mean of 4% higher in the patients 
than in the healthy controls, and the difference was not reliable. We concluded
that, among principal pathogenic factors which might cause deficiency of the
blood supply to fingers, it is the enhanced tone of resistance arteries that is
primarily responsible for the development of Raynaud's phenomenon, while
hemorheological disorders are not, or are considerably less, involved in the
development of the principal symptom of the disease, deficient blood supply to
the fingers. Copyright 2001 Academic Press.

PMID: 11516248 [PubMed - indexed for MEDLINE]

270: Arthritis Rheum. 2001 Aug;44(8):1841-7.

Comment in:
    Arthritis Rheum. 2003 Jan;48(1):282-3; author reply 283.

Calcium-channel blockers for Raynaud's phenomenon in systemic sclerosis.

Thompson AE, Shea B, Welch V, Fenlon D, Pope JE.

University of Western Ontario, London, Canada.

OBJECTIVE: Most patients with systemic sclerosis (SSc) have Raynaud's phenomenon 
(RP), which is often more severe than idiopathic RP. This study was a
meta-analysis to determine the efficacy of calcium-channel blockers for the
treatment of RP in SSc. The primary outcome measures were frequency and severity 
of ischemic attacks, digital skin temperature, patient and physician global
assessments, and digital ulcers. METHODS: The Cochrane search strategy was used
to ascertain all trials in all languages. Primary data sources included Medline, 
Current Contents, and the Cochrane Controlled Trials Register. Studies that met
the inclusion criteria were randomized controlled trials of >2 days' duration
with a dropout rate of <35%. Twenty-nine studies were found, of which 8
randomized controlled trials were eligible for inclusion. The total number of
patients included was small (n = 109). Most trials included primary and secondary
RP, and the main reasons for trial exclusion were inability to extract subset
data on SSc patients (18 trials), data published previously (2 trials), and lack 
of a control group (1 trial). Data were abstracted independently by 2 reviewers, 
and either a weighted mean difference (WMD) or a standardized mean difference
(SMD) was calculated for all continuous outcomes; however, information was not
available for all outcomes within trials. RESULTS: The WMD of all calcium-channel
blockers versus placebo (6 trials) and of nifedipine alone versus placebo (5
trials) for the reduction in the frequency of ischemic attacks over a 2-week
period was -8.31 (95% confidence interval [95% CI] -15.71, -0.91) and -10.21 (95%
CI -20.09, -0.34), respectively. The SMD of all calcium-channel blockers versus
placebo (3 trials) and of nifedipine alone versus placebo (2 trials) for the
reduction in the severity of ischemic attacks was -0.69 (95% CI -1.21, -0.17) and
-0.99 (95% CI -1.74, -0.24), respectively. CONCLUSION: Calcium-channel blockers
for RP in SSc have been tested in several small clinical trials and appear to
lead to significant clinical improvement in both the frequency and the severity
of ischemic attacks. Most trials were crossover trials in which order effect was 
not studied. This could have introduced bias. The results of this study suggest
that the efficacy of calcium-channel blockers in reducing the severity and
frequency of ischemic attacks in RP secondary to SSc is moderate at best (mean
reduction of 8.3 attacks in 2 weeks and 35% less severity), and a further large, 
randomized controlled trial needs to be conducted.

Publication Types: 
    Comparative Study
    Meta-Analysis

PMID: 11508437 [PubMed - indexed for MEDLINE]

271: Ann Rheum Dis. 2001 Sep;60(9):846-51.

Serum TIMP-1, TIMP-2, and MMP-1 in patients with systemic sclerosis, primary
Raynaud's phenomenon, and in normal controls.

Young-Min SA, Beeton C, Laughton R, Plumpton T, Bartram S, Murphy G, Black C,
Cawston TE.

Department of Rheumatology, University of Newcastle-upon-Tyne, UK.
Steven.youngMin@ncl.ac.uk

BACKGROUND: Excess tissue matrix accumulates in systemic sclerosis (SSc),
accounting for both visceral and dermal fibrosis. It is suggested that decreased 
serum levels of matrix metalloproteinases (MMPs) or increased levels of tissue
inhibitors of matrix metalloproteinases (TIMPs) may account for this matrix
accumulation. OBJECTIVE: To measure serum levels of tissue inhibitors of
metalloproteinases, TIMP-1, TIMP-2, and collagenase-1 (MMP-1), in patients with
diffuse cutaneous systemic sclerosis (dcSSc), limited cutaneous systemic
sclerosis (lcSSc), primary Raynaud's phenomenon (RP), and in normal controls.
METHODS: Serum samples from patients with dcSSc (n=83), lcSSc (n=87), RP (n=80), 
and normal controls (n=98) were analysed using enzyme linked immunosorbent assays
(ELISAs) for total TIMP-1, TIMP-2, and MMP-1. Results from each assay were
analysed by the Kruskal-Wallis test. Dunn's multiple comparison post-test was
then applied between groups. RESULTS: TIMP-1 levels were significantly raised in 
dcSSc and lcSSc groups compared with the RP group and normal controls (p<0.01 to 
p<0.001). In the dcSSc group, TIMP-1 levels were significantly higher in early
disease (<2 years) than in late stage disease (>4 years) (p<0.05). This was not
found for the lcSSc group. Serum TIMP-2 and MMP-1 levels in dcSSc and lcSSc did
not differ significantly from those in normal controls. Increased levels of TIMPs
were not convincingly associated with organ disease. No assay result correlated
with autoantibody status (anti-topoisomerase 1 (anti-Scl-70), anticentromere
antibody, or anti-RNA polymerase). No significant differences in serum TIMP-1,
TIMP-2, or MMP-1 levels were shown in the RP group compared with normal controls.
CONCLUSIONS: Raised TIMP-1 levels in the SSc groups support the hypothesis that
matrix accumulation occurs in SSc at least in part owing to decreased
degradation. Moreover, the variation in TIMP-1 levels between the early and late 
disease stages of dcSSc seems to reflect the early progressive course of dermal
fibrosis seen clinically. The expected reduction in serum MMP-1 levels in the SSc
groups was not found. This suggests that tissue matrix accumulation is due to
increased inhibitors rather than to decreased MMPs.

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

PMID: 11502611 [PubMed - indexed for MEDLINE]

272: Skeletal Radiol. 2001 Aug;30(8):478-81.

Disproportionately severe calcinosis cutis in an 88-year-old patient with CREST
syndrome.

Buchowski JM, Ahn NU, Ahn UM, McCarthy EF, Mehta MB.

Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine,
601 N. Caroline Street, Baltimore, MD 21287, USA.

An 88-year-old woman with CREST syndrome (calcinosis, Raynaud's phenomenon,
esophageal dysmotility, sclerodactyly, and telangiectasias) presented with
hyperglycemia, intravascular depletion, and atrial fibrillation. The patient was 
found to have unusually severe calcinosis cutis in both legs extending from the
knees to the ankles bilaterally, as well as Raynaud's phenomenon, sclerodactyly, 
and telangiectasias. The patient was normocalcemic and normophosphatemic.
Although subcutaneous calcification is often seen with CREST syndrome, this case 
is unusual in that the area of involvement was much larger than previously
described. Furthermore, the amount of calcinosis was disproportionately severe
and was the major cause of symptoms and disability compared with the other
components of the syndrome.

Publication Types: 
    Case Reports

PMID: 11479756 [PubMed - indexed for MEDLINE]

273: Scand J Rheumatol. 2001;30(3):172-4.

Anti-cardiolipin antibodies, Raynaud's phenomenon with digital ischemia, and non 
small cell carcinoma of the lung.

Vaidya S, Logan JW.

Department of Internal Medicine, University of Arkansas for Medical Sciences,
Little Rock 72205-7199, USA. vaidyaswati@exchange.uams.edu

Raynaud's phenomenon, digital ischemia, antinuclear antibodies and
anticardiolipin antibodies are uncommon features of malignancy. The association
of all of these in a patient with malignancy has not previously been reported. We
describe a 52 year old woman with non small-cell carcinoma of the lung who also
had Raynaud's phenomenon, digital ischemia, anti-nuclear antibodies and
anticardiolipin antibodies.

Publication Types: 
    Case Reports

PMID: 11469530 [PubMed - indexed for MEDLINE]

274: Clin Hemorheol Microcirc. 2001;24(3):167-74.

Relevance of low titers of cryoglobulins and cold-agglutinins in patients with
isolated Raynaud phenomenon.

Kröger K, Billen T, Neuhaus G, Santosa F, Buss C, Kreuzfelder E,
Henneberg-Quester KB.

Klinik für Angiologie, University of Essen, Germany. knut.kroeger@uni-essen.de

INTRODUCTION: A Raynaud phenomenon can be associated with cold agglutinins or
cryoglobulins. Although cold agglutinins or cryoglobulins may lead to severe
acral gangrene the finding of relevant titers is rare. Low titers of cold
agglutinins or cryoglobulins are detected more frequently but are assumed to be
without any importance. OBJECTIVES: To prove a possible diagnostic or prognostic 
role of low titers of cold agglutinins or cryoglobulins in patients presenting an
isolated Raynaud phenomenon we did a retrospective analysis. SETTINGS AND
SUBJECTS: In 306 patients (40+/-16 years, range: 15-83 years) with a mean
duration of the history of an isolated Raynaud phenomenon of 48+/-73 months we
did a clinical examination, an analysis of antinuclear antibodies, extractable
antibodies, cold agglutinins, cryoglobulins, plasma and blood viscosity,
erythrocyte aggregation and a nail fold capillaroscopy. RESULTS: Low titers of
cold agglutinins were found in 49 patients and of cryoglobulins in 7 patients.
The finding of such low titers was not associated with extensive clinical
symptoms, duration of clinical symptoms, megacapillaries or haemorrhagies in
capillaroscopy, pathologic plasma and blood viscosity and erythrocyte
aggregation. The follow-up investigations (mean: 3.1+/-1.2 years, range: 3-7
years) revealed no development of a haematological, vasculitic or connective
tissue disease in the subgroup of patients who only had low titers of cold
agglutinins. CONCLUSION: The detection of low titers of cold agglutinins in
patients with isolated Raynaud phenomenon is of no diagnostic or prognostic
relevance.

Publication Types: 
    Comparative Study

PMID: 11455056 [PubMed - indexed for MEDLINE]

275: Br J Clin Pharmacol. 2001 Jul;52(1):17-23.

Seasonal differences in finger skin temperature and microvascular blood flow in
healthy men and women are exaggerated in women with primary Raynaud's phenomenon.

Gardner-Medwin JM, Macdonald IA, Taylor JY, Riley PH, Powell RJ.

Department of Rheumatology, University of Birmingham, Edgbaston, UK.
janet.gardner-medwin@virgin.net

AIMS: Patients with primary Raynaud's phenomenon (PRP) have more severe symptoms 
in the winter. The aetiology of this is more complex than simply increased
vasoconstriction in response to the immediate ambient temperature. The aim of
this study was to investigate differences in skin temperature (Tsk),
microvascular blood flow and responses to endothelium-dependent and independent
vasodilators in healthy controls, and women with PRP under identical
environmental temperatures but in different seasons. METHODS: Ten women with PRP 
were compared with age matched women (10) and men (10). Finger skin responses
were recorded immediately on arrival, after stabilizing in a temperature
regulated laboratory at 22-24 degrees C, and at matched warm (35 degrees C) and
cold (15 degrees C) Tsk in the winter and summer. Baseline red blood cell flux
(r.b.c. flux), and the change in flux in response to iontophoresis of
acetylcholine (ACh) and sodium nitroprusside (SNP) were recorded by laser Doppler
fluxmetry at the warm and cold Tsk. RESULTS: Arrival Tsk were significantly
cooler for all subjects during the winter (mean seasonal difference -2.6 degrees 
C, P < 0.0001), and markedly colder in subjects with PRP (mean seasonal
difference -3.5 degrees C, P < 0.0005). Statistically significant seasonal
differences persisted in all subjects at stable Tsk despite an identical
laboratory temperature (mean difference 1.3 degrees C, P < 0.0001). To achieve
comparable controlled finger Tsk a significantly colder local environment was
required for male controls (mean of -2.1 degrees C, P < 0.0001), and a
significantly warmer environment for subjects with PRP (mean of + 2.4 degrees C, 
P < 0.0001) compared with female controls. This needed to be warmer in the
winter, by a mean of 2.4 degrees C, than the summer for all subjects.
Vasodilatation in response to ACh, but not SNP, was significantly smaller (P <
0.0001) in the PRP group compared with the female controls for all visits, with
most of this difference arising in the winter visits (P < 0.01). CONCLUSIONS:
There is a seasonal and persistent influence on finger Tsk, and microvascular
blood flow in healthy men and women, which modifies the observed responses to
immediate changes in finger Tsk. The seasonal differences are greater in women
than men, and are further exaggerated in women with PRP, in whom this is
associated with reduced endothelium-dependent vasodilatation.

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

PMID: 11453886 [PubMed - indexed for MEDLINE]

276: Lancet. 2001 Jun 23;357(9273):2042-8.

Raynaud's phenomenon.

Block JA, Sequeira W.

Section of Rheumatology, Rush Medical College, Rush-Presbyterian-St Luke's
Medical Center, 1725 West Harrison Street, Chicago, IL 60612, USA.
jblock@rush.edu

Raynaud's phenomenon is characterised by episodic vasospasm of the fingers and
toes typically precipitated by exposure to cold. Mild Raynaud's is common and is 
not usually a harbinger of clinically important disability; its onset, however,
can be startling and uncomfortable for patients, and the well recognised
association in some cases with systemic rheumatic conditions often precipitates
aggressive assessments for underlying diseases. Advances in vascular physiology
have shed light on the role of the endothelium as well as endothelium-independent
mechanisms in the altered vasoregulation of Raynaud's. We review clinical aspects
of the disorder and new insights with respect to pathophysiology, and we discuss 
potential new therapeutics based on the disease mechanism, such as prostacyclin
analogues, serotonin antagonists, and calcitonin gene-related peptides.

Publication Types: 
    Review

PMID: 11438158 [PubMed - indexed for MEDLINE]

277: Pediatr Dermatol. 2001 May-Jun;18(3):249-51.

Raynaud phenomenon after treatment of verruca vulgaris of the sole with
intralesional injection of bleomycin.

Vanhooteghem O, Richert B, de la Brassinne M.

Department of Dermatology and Venereology, University Hospital, Liège, Belgium.

Intralesional injection of bleomycin (BLM) for the treatment of warts resistant
to all conventional therapies is of certain interest because of the drug's low
toxicity and its efficacy. However, delayed side effects may appear, particularly
Raynaud phenomenon. Accordingly, some precautions must be taken in patients with 
vascular or collagen diseases and, as a precaution, pregnant or lactating women
and infants should not be treated with this drug.

Publication Types: 
    Case Reports

PMID: 11438010 [PubMed - indexed for MEDLINE]

278: J Behav Med. 2001 Apr;24(2):137-53.

The effects of stress, anxiety, and outdoor temperature on the frequency and
severity of Raynaud's attacks: the Raynaud's Treatment Study.

Brown KM, Middaugh SJ, Haythornthwaite JA, Bielory L.

Clinical Trials and Surveys Corp., 350 West Quadrangle, Baltimore, Maryland
21210, USA.

It was expected that stress and anxiety would be related to Raynaud's phenomenon 
(RP) attack characteristics when mild outdoor temperatures produced partial or no
digital vasoconstriction. Hypotheses were that in warmer temperature categories, 
compared to those below 40 degrees F, higher stress or anxiety would be
associated with more frequent, severe, and painful attacks. The Raynaud's
Treatment Study recruited 313 participants with primary RP. Outcomes were attack 
rate, severity, and pain. Predictors were average daily outdoor temperature,
stress, anxiety, age, gender, and a stress-by-temperature or an
anxiety-by-temperature interaction. Outcomes were tested separately in multiple
linear regression models. Stress and anxiety were tested in separate models.
Stress was not a significant predictor of RP attack characteristics. Higher
anxiety was related to more frequent attacks above 60 degrees F. It was also
related to greater attack severity at all temperatures, and to greater pain above
60 degrees F and between 40 degrees and 49.9 degrees F.

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

PMID: 11392916 [PubMed - indexed for MEDLINE]

279: Microsurgery. 2001;21(3):75-9.

Surgery for ischemic pain and Raynaud's' phenomenon in scleroderma: a description
of treatment protocol and evaluation of results.

Tomaino MM, Goitz RJ, Medsger TA.

Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, 3471 
Fifth Avenue, Pittsburgh, PA 15213. tomainomm@msx.upmc.edu

Although the literature suggests that palmar sympathectomy (PS) with or without
vascular reconstruction may improve ischemic digital pain, fingertip ulceration, 
and cold intolerance in patients with scleroderma, the question regarding
long-term efficacy still remains. This retrospective study of six patients (eight
hands) operated on between 1995 and 1997 evaluates both early (6 months) and
long-term (average, 2.5 years) outcome after PS in combination with decompression
arteriolysis of the radial and ulnar arteries proximal to the wrist. When
preoperative digital blood flow was inadequate based on noninvasive vascular
studies and major inflow occlusion was present, vascular reconstruction was also 
performed when feasible. At early review, significant improvement in ischemic
digital pain and moderate improvement in cold intolerance resulted in eight
hands, and at final follow-up, this was sustained in seven hands. Preoperatively,
digital ulcerations were present in six hands. After digital debridement and/or
amputation, all wounds healed, but in one patient with bilateral disease who
continued to smoke, ulcerations recurred without the need for subsequent surgery.
Five of six patients were no longer dependent on narcotic analgesics, but use of 
vasodilator medication did not change. Five of six patients claimed significant
improvement in the quality of life after surgery and reported that they would
undergo the surgery again. PS in combination with radial and ulnar arteriolysis
appears to be efficacious at both early and long-term review. When major inflow
occlusion exists and digital blood flow is compromised, vascular reconstruction
is recommended if possible. We review our treatment protocol in this complex
population of patients. Copyright 2001 Wiley-Liss, Inc. Microsurgery 21:75-79
2001

PMID: 11372066 [PubMed - indexed for MEDLINE]

280: Clin Rheumatol. 2001;20(2):88-90.

Prevalence of Raynaud's phenomenon in general practice in the east of Spain.

Román Ivorra JA, Gonzálvez Perales JL, Fernández Carballido C, Graña J, Torres
MJ.

Rheumatology Unit, Hospital Universitario Dr Peset, Valencia, Spain.
roman_jan@gva.es

Our aim was to establish the prevalence of Raynaud's phenomenon in a general
practice in the east of Spain and compare our results with those of other studies
performed in geographical areas with similar climatic characteristics. Two
hundred and seventy-six subjects visiting their general practitioner for whatever
reason were randomly selected from a particular area of the city of Valencia.
Each was interviewed by their GP following the guidelines of a structured
questionnaire to establish whether they had Raynaud's phenomenon or not. There
were 205 women and 71 men. The mean age was 54.43, with a standard deviation of
18.22. Raynaud's phenomenon was present in nine subjects, two men and seven
women, with a prevalence of 2.8% and 3.4%, respectively. Of the nine positives
(mean age 60.56 years, standard deviation 16.38), two were diagnosed with
hypertension and two with migraine. None of them usually took Raynaud's
phenomenon-related drugs or performed physical exercise. No patient had a family 
history of Raynaud's phenomenon or had already been diagnosed with it. All the
positive males were affected only by the pallor stage. This study shows lower
prevalences than those of other studies performed in different geographical areas
with similar climatic conditions.

PMID: 11346237 [PubMed - indexed for MEDLINE]

281: J Rheumatol. 2001 Apr;28(4):786-94.

Treatment of Raynaud's phenomenon with intravenous prostaglandin
E1alpha-cyclodextrin improves endothelial cell injury in systemic sclerosis.

Gardinali M, Pozzi MR, Bernareggi M, Montani N, Allevi E, Catena L, Cugno M,
Bottasso B, Stabilini R.

Dipartimento di Medicina Interna, Ospedale San Gerardo, Monza, Italy.

OBJECTIVE: To evaluate the efficacy and safety of prostaglandin (PG)
E1alpha-cyclodextrin for Raynaud's phenomenon (RP) secondary to systemic
sclerosis (SSc) and its effect on variables of immune activation and endothelial 
injury in SSc such as tumor necrosis factor-alpha (TNF-alpha), soluble
interleukin 2 receptor (sIL-2R), circulating intercellular adhesion molecule-1
(cICAM-1), von Willebrand factor (vWF), and tissue-type plasminogen activator
(t-PA). METHODS: We studied 36 women with SSc, 24 of them given three 60 microg
intravenous PGE1alpha-cyclodextrin infusions on 5 consecutive days at 6 week
intervals during the winter. RP symptoms and healing of digital lesions were
evaluated. Twenty age matched healthy women were the controls. TNF-alpha, sIL-2R,
cICAM-1, vWF, and t-PA were measured after the first and last infusion of
PGEE1alpha-cyclodextrin and correlated with clinical features. RESULTS: RP
symptoms improved in 87% of the patients. The benefit of each 5 day cycle lasted 
4 or more weeks in 75%. PGE1alpha-cyclodextrin reduced the daily frequency of RP 
symptoms by 20% (p < 0.05), 41% (p < 0.005), and 53% (p < 0.0005) from baseline
after the 1st, 2nd, and 3rd infusions, respectively. The severity of the attacks 
was reduced to a limited degree. In 12 of the 14 patients with digital lesions,
these healed completely. Ten patients had mild side effects during treatment
(headache, increased intestinal motility, flushing). TNF-alpha, sIL-2R, cICAM-1, 
vWF, and t-PA plasma concentrations were significantly higher in patients with
SSc than controls (p < 0.05, p < 0.001). TNF-alpha, sIL-2R, and cICAM-1 were
higher in diffuse SSc and patients with lung involvement. The plasma levels of
cICAM-1 and t-PA were significantly reduced after the 1st infusion of
PGE1alpha-cyclodextrin (both p < 0.005) and further reduced after the last (p <
0.0005 and p < 0.005). CONCLUSION: PGE1alpha-cyclodextrin reduces RP symptoms and
plasma levels of the markers of endothelial injury in SSc, suggesting that an
improvement of endothelial dysfunction contributes to its prolonged therapeutic
effect.

PMID: 11327251 [PubMed - indexed for MEDLINE]

282: Comp Biochem Physiol A Mol Integr Physiol. 2001 Apr;128(4):749-57.

Effects of whole body cooling on sensory perception and manual performance in
subjects with Raynaud's phenomenon.

Rissanen S, Hassi J, Juopperi K, Rintamäki H.

Oulu Regional Institute of Occupational Health, Aapistie 1, FIN-90220, Oulu,
Finland. sirkka.rissanen@occuphealth.fi

Patients with Raynaud's phenomenon (RP) have abnormal digital vasoconstriction in
response to cold. The aim of the study was to investigate the effects of cooling 
on sensory perception and manual performance in healthy male subjects and
subjects with RP. There were two groups of subjects with primary RP: 12 subjects 
fulfilled the criteria of Lewis (L) and the other 12 the more critical criteria
of Maricq (M). Control group (C) consisted of 19 healthy men. Subjects were
exposed to 5 degrees C for 60 min. Skin temperatures were measured. Finger
dexterity, pinch strength, abduction/adduction of fingers, pressure perception
threshold and vibration perception threshold were tested during the exposure
every 15 min. At the beginning of the exposure the mean (S.E.) finger temperature
was 2.5 (1.2) degrees C (P<0.05) lower in M than in C. Manual performance and
sensory perception were impaired due to the cooling, the impairment being
significantly greater in M than in C. Responses of L were between those of M and 
C. In a given finger temperature vibration and pressure sensibility and manual
performance were lower in M and L than in C. In conclusion, cold exposure
decreased sensory perception and manual performance in the subjects with RP to a 
lower level than in the healthy subjects. Non-thermal factors may also decrease
performance in RP.

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

PMID: 11282318 [PubMed - indexed for MEDLINE]

283: Rheumatology (Oxford). 2001 Feb;40(2):140-6.

Increased urinary pyridinoline cross-link compounds of collagen in patients with 
systemic sclerosis and Raynaud's phenomenon.

Istok R, Czirják L, Lukác J, Stancíková M, Rovenský J.

Research Institute of Rheumatic Diseases, Piest'any, Slovak Republic.

OBJECTIVE: To study concentration changes in collagen degradation markers in
patients with diffuse and limited cutaneous systemic sclerosis and patients with 
scleroderma-related diseases. METHODS: Pyridinoline cross-link compounds were
analysed in urine samples using high-performance liquid chromatography. Samples
were analysed for pyridinoline (Pyr), deoxypyridinoline (Dpyr) and soft-tissue
pyridinoline (stPyr) in patients with diffuse cutaneous systemic sclerosis
(dcSSc, n=23) and limited cutaneous systemic sclerosis (lcSSc, n=48) and in
patients with scleroderma-related diseases such as primary Raynaud's phenomenon
(pRP, n=16) and secondary Raynaud's phenomenon (sRP, n=14). Healthy controls
(n=18) and patients with post-menopausal osteoporosis (OP, n=35) were also
investigated. RESULTS: Urinary Pyr, Dpyr and stPyr concentrations were
significantly higher in patients with Raynaud's phenomenon and systemic sclerosis
than in healthy controls. The highest concentrations (two to three times greater 
than in healthy controls) were found in patients with dcSSc. The stPyr
concentration was significantly higher in patients with dcSSc than in those with 
lcSSc, sRP and pRP. No significant difference in stPyr concentration was found
between the healthy controls and the OP group, suggesting that stPyr is derived
from soft tissues rather than bone. The extent and severity of skin involvement, 
measured as a skin score, significantly correlated with the concentrations of
stPyr and Pyr, whereas no such correlation was found for Dpyr. CONCLUSIONS:
Increased urinary concentrations of piridinoline cross-links reflect alterations 
in collagen turnover in both Raynaud's phenomenon and systemic sclerosis. The
close correlation between stPyr concentration and the extent of skin involvement 
in systemic sclerosis suggests that this parameter may be useful in monitoring
ongoing fibrosis in this disease.

PMID: 11257149 [PubMed - indexed for MEDLINE]

284: Ann Rheum Dis. 2001 Apr;60(4):407-9.

Differentiation between primary and secondary Raynaud's phenomenon: a prospective
study comparing nailfold capillaroscopy using an ophthalmoscope or
stereomicroscope.

Anders HJ, Sigl T, Schattenkirchner M.

Division of Rheumatology, Medizinische Poliklinik, Ludwig-Maximilians Universität
Munich, Germany. hjanders@clinbio.med.uni-muenchen.de

BACKGROUND: Nailfold capillary microscopy is a routine procedure in the
investigation of patients with Raynaud's phenomenon (RP). As a standard method,
nailfold capillary morphology is inspected with a stereomicroscope to look for
capillary abnormalities such as giant loops, avascular areas, and bushy
capillaries, which have all been found to be associated with certain connective
tissue diseases. AIM: To investigate prospectively whether nailfold capillary
inspection using an ophthalmoscope is of equivalent diagnostic value to standard 
nailfold capillary microscopy. METHOD: All the fingers of 26 patients with RP
were examined in a blinded fashion and compared with the final diagnosis one
month later. RESULTS: All giant loops, large avascular areas, and bushy
capillaries were identified by both methods. The correlation for moderate
avascular areas and crossed capillaries was 0.93 and 0.955 respectively. The
correlation for minor abnormalities that do not contribute to the differentiation
between primary and secondary RP was 0.837 and 0.861 respectively. All patients
were classified identically by the two methods. CONCLUSION: For the evaluation of
patients with RP, nailfold capillary morphology can reliably be assessed with an 
ophthalmoscope.

Publication Types: 
    Comparative Study

PMID: 11247874 [PubMed - indexed for MEDLINE]

285: Scand J Gastroenterol. 2000 Dec;35(12):1251-4.

No evidence of an association between Helicobacter pylori infection and Raynaud
phenomenon.

Savarino V, Sulli A, Zentilin P, Raffaella Mele M, Cutolo M.

Dipt di Medicina Intema e Specialità Mediche, Università Degli Studi di Genova,
Italy. vsavarin@unige.it

BACKGROUND: Raynaud phenomenon (RP) is a vasospastic condition that manifests
itself as cold-induced ischemic attacks of the fingers with skin color changes.
It may be classified as primary (PRP) or secondary (SRP), if associated to other 
diseases, mainly connective-tissue diseases. Recently, the association between
PRP and Helicobacter pylori infection has been reported. The aims of this study
were to evaluate the prevalence of gastric H. pylori infection in a large group
of patients affected by PRP and SRP and to assess whether it was more evident in 
patients with more recent onset of RP. METHODS: Ninety-eight consecutive patients
(93 F and 5 M), referring to our videocapillaroscopic service for the diagnosis
of vascular and connective-tissue diseases, were evaluated. Forty-nine of them
were affected by PRP and 49 by SRP. Patients were classified as having PRP on the
basis of normal serological and immunological findings, normal
videocapillaroscopic examination and exclusion of other conditions inducing RP.
H. pylori infection was diagnosed by 13C-urea breath test (UBT). Two groups of 49
age-and sex-matched controls, respectively, were also evaluated. RESULTS:
Patients with SRP resulted significantly older than those with PRP (P < 0.006).
UBT was found positive in 22/49 patients with PRP (45%) and in 29/49 patients
with SRP (59%). The positivity of the respective control groups was 36% and 53%
(P = NS). There was no higher prevalence of H. pylori infection in patients with 
RP lasting for less than 4 years. CONCLUSIONS: The results do not confirm the
previously reported high prevalence of H. pylori infection in patients with PRP. 
A high association was not even found between the presence of the microorganism
and SRP. There was no difference in the prevalence of H. pylori infection among
the subgroups with more recent onset of both PRP and SRP.

PMID: 11199362 [PubMed - indexed for MEDLINE]

286: J Rheumatol. 2001 Jan;28(1):119-21.

Abnormal responses to endothelial agonists in Raynaud's phenomenon and
scleroderma.

Freedman RR, Girgis R, Mayes MD.

Department of Psychiatry, Wayne State University School of Medicine, Detroit,
Michigan, USA. aa2613@wayne.edu

OBJECTIVE: To further specify the site of vascular dysfunction in patients with
Raynaud's phenomenon (RP) and scleroderma. METHODS: Ten patients with RP and
scleroderma and 11 healthy control subjects received brachial artery infusions of
sodium nitroprusside, an endothelium independent vasodilator, bradykinin, and
substance P while bilateral finger blood flow was measured with venous occlusion 
plethysmography. RESULTS: Both groups showed vasodilation to sodium
nitroprusside. However, in response to the endothelium dependent compounds
bradykinin and substance P, the controls showed vasodilation, whereas the
patients showed vasoconstriction. CONCLUSION: The vascular defect in RP and
scleroderma does not lie at the site of the muscarinic receptor, but possibly in 
a distal signaling mechanism.

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

PMID: 11196511 [PubMed - indexed for MEDLINE]

287: Br J Dermatol. 2001 Jan;144(1):182-5.

A case of porphyria cutanea tarda in association with idiopathic myelofibrosis
and CREST syndrome.

Lee SC, Yun SJ, Lee JB, Lee SS, Won YH.

Department of Dermatology, Chonnam National University Medical School, 8
Hak-dong, Dong-ku, Kwangju 501-757, Korea (South). schul@chonnam.chonnam.ac.kr

We report a 56-year-old Korean woman with porphyria cutanea tarda (PCT), showing 
multiple scarring bullae and hypertrichosis on sun-exposed areas of skin with
postinflammatory hyperpigmentation. Sclerodermoid changes were also found on both
hands, the face and neck. The patient had suffered from CREST syndrome,
manifesting with Raynaud's phenomenon and sclerodactyly, for more than 15 years. 
Anticentromere antibody was positive. She had presented with splenomegaly 3 years
before the development of PCT, and was diagnosed as having idiopathic
myelofibrosis, based on bone marrow biopsy. In summary, she had had CREST
syndrome for 15 years and later developed idiopathic myelofibrosis and PCT. This 
is the first reported case of PCT in association with idiopathic myelofibrosis
and CREST syndrome.

Publication Types: 
    Case Reports

PMID: 11167703 [PubMed - indexed for MEDLINE]

288: Rheumatology (Oxford). 2001 Jan;40(1):102-6.

Autoimmune hepatitis and systemic sclerosis: a new overlap syndrome?

Marie I, Levesque H, Tranvouez JL, François A, Riachi G, Cailleux N, Courtois H.

Department of Internal Medicine, Centre Hospitalier Universitaire de
Rouen-Boisguillaume, 76031 Rouen Cedex, France.

OBJECTIVE: We report the cases of two patients with the complete CREST variant
(calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly,
telangiectasia) of systemic sclerosis (SSc) who developed autoimmune hepatitis.
RESULTS: Our findings suggest that autoimmune hepatitis can be considered to be
one of the liver manifestations associated with SSc. Our data also indicate that,
because liver involvement may precede skin manifestations, evaluation for SSc is 
appropriate when autoimmune hepatitis is noted, and that the evaluation should
include clinical examination, testing for antinuclear antibodies (especially for 
anticentromere antibodies) and nailfold capillaroscopy. CONCLUSIONS: From a
practical point of view, our two cases emphasize that suspicion of autoimmune
hepatitis in SSc patients presenting with cytolytic hepatitis will help to
achieve both accurate diagnosis and optimal management.

Publication Types: 
    Case Reports

PMID: 11157149 [PubMed - indexed for MEDLINE]

289: Prostaglandins Other Lipid Mediat. 2000 Mar;60(4-6):153-60.

Pharmacokinetics of oral iloprost in patients with Raynaud's phenomenon secondary
to systemic sclerosis.

Janssena MC, Wollersheim H, Kraus C, Hildebrand M, Watson HR, Thien T.

Department of Medicine, Division of General Internal Medicine, University
Hospital Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.

Iloprost is a chemically stable, pharmacologically highly potent
prostacyclin-minietic. The therapeutic efficacy of the intravenous preparation
was proven in patients with peripheral arterial occlusive disease or with
Raynaud's phenomenon (RP). Recently, a sustained release oral preparation was
developed for outpatient therapy. The purpose of the current study was to
investigate whether the oral drug has a different pharmacokinetic profile in
patients with RP secondary to systemic sclerosis (SSc) in comparison with healthy
volunteers. Ten patients with RP secondary to SSc and 10 healthy volunteers
(matched for age and sex) participated. Oral iloprost 50 microg was given twice
daily for 8 days with dosing intervals of 5 h and plasma levels were taken over
10 h on Day 1 and 8. Plasma levels of iloprost were determined by a validated
specific and sensitive radio-immunoassay. Compared with healthy volunteers,
patients with SSc exhibited higher AUC values (by mean factors of 2. 1 and 2.0 on
Day 1 and 8) and maximum plasma levels (by mean factors of 1.6 and 1.8 on Day 1
and 8). The increased systemic iloprost exposure was observed after both daily
doses and on both monitored study days. Mean AUC values did not show accumulation
over the 8 days. These findings are in agreement with a reduced total clearance
of iloprost given by i.v. route in SSc patients compared to healthy volunteers,
although no participant with severe renal impairment was included. A weak but
significant correlation was found between individual creatinine clearance and AUC
values. In conclusion, RP secondary to SSc is associated with an increased
systemic iloprost exposure which is probably caused by changes of the metabolic
clearance of iloprost. These effects cannot be explained by changes of renal
function alone.

Publication Types: 
    Clinical Trial

PMID: 10751645 [PubMed - indexed for MEDLINE]

290: Ann Oncol. 2000 Nov;11(11):1501-2.

Interferon-alpha induced Raynaud's syndrome.

Kruit WH, Eggermont AM, Stoter G.

Department of Medical Oncology, Rotterdam Cancer Institute/University Hospital
Rotterdam, The Netherlands. kruit@onch.azr.nl

The cytokine interferon-alpha (IFN-alpha) is increasingly prescribed for a number
of indications, especially viral hepatitis and several malignancies. Two patients
are described who developed Raynaud's syndrome during treatment with IFN-alpha as
adjuvant therapy for high-risk melanoma. With a review of the available
literature the symptomatology, possible pathophysiologic mechanisms and treatment
options are discussed.

Publication Types: 
    Case Reports
    Review

PMID: 11142493 [PubMed - indexed for MEDLINE]

291: Angiology. 2000 Dec;51(12):985-98.

Quantitative assessment of peripheral arterial obstruction in Raynaud's
phenomenon: development of a predictive model of obstructive arterial
cross-sectional area and validation with a Doppler blood flow study.

Seitz WS, Kline HJ, McIlroy MB.

Cardiovascular Research Institute, University of California, School of Medicine, 
San Francisco, USA. imar@transbay.net

The objective of this study was to develop a method for the analytical assessment
of arterial obstruction in conditions of Raynaud's phenomenon capable of
providing diagnostic criteria. Numerous attempts have been made to determine and 
quantify arterial obstruction in terms of Doppler ultrasound measurements of
arterial blood velocity. Absent from these methods is a formulation that allows
an assessment of arterial obstruction based on the obstructed area as derived
from direct measurement. The authors used spectral analysis of velocity signals
from a pulsed, range-gated Doppler ultrasonic instrument to make quantitative
measurements of arterial blood flow velocity in hands of normal subjects and
persons with Raynaud's phenomenon. They measured the peak and mean velocity
during the cardiac cycle and the time integral of the velocity signal over the
cardiac cycle. These measurements for two distinct hemodynamic states induced by 
temperature changes allowed them to calculate the fractional change in arterial
cross-sectional area produced by the change in temperature through the
application of a hydraulic model of digital arterial circulation. They found an
equation expressing fractional obstructed area expressed as: dA/A = 2 (dD - taudv
- vtau)/(D + vdtau), where D is the time integral of the velocity signal; tau is 
the blood flow interval, v is the blood velocity; and dD, dtau and dv are the
differences in D, tau, and v at two different hemodynamic states produced by two 
different temperature states. Their findings suggest that over a temperature
range of 35 degrees-25 degrees C, normal subjects experience 0.05/ degrees C
reduction in cross-sectional area while Raynaud subjects experience a reduction
of 5.8%/degrees C. The results, based on findings in 13 subjects, suggest that
Doppler ultrasound can differentiate persons with Raynaud's phenomenon from
normal subjects. Additionally, the hydraulic model appears to offer the potential
of assessing relative stenotic area in other arterial obstructive diseases.

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

PMID: 11133000 [PubMed - indexed for MEDLINE]

292: Angiology. 2000 Dec;51(12):1003-6.

Circulating adhesion molecules in patients with vibration-induced white finger.

Kurozawa Y, Nasu Y.

Department of Public Health, Faculty of Medicine, Tottori University, and the
Vibration Syndrome Center, San-in Rosai Hospital, Yonago, Japan.
kurozawa@grape.med.tottori-u.ac.jp

We investigated whether a relationship existed between soluble adhesion molecules
and vascular damage from vibration-induced white finger. Thirty-five men exposed 
to vibration and 40 healthy control subjects were examined. Concentrations of
soluble E-selectin intercellular adhesion molecules, and vascular cell adhesion
molecules in serum were measured with sandwich enzyme-linked adhesion
immunosorbent assay. Neither E-selectin nor intercellular adhesion molecule
levels are elevated in men exposed to vibration with white finger compared to
levels in men exposed to vibration without white finger and control subjects. The
serum level of soluble vascular cell adhesion molecules is significantly
increased in patients with vibration-induced white finger.

PMID: 11132991 [PubMed - indexed for MEDLINE]

293: Ocul Immunol Inflamm. 2000 Sep;8(3):201-3.

Granulomatous anterior uveitis in a patient with CREST syndrome.

Akman A, Akova YA, Yücel E, Aydin P.

Department of Ophthalmology, Faculty of Medicine, Baskent University, Ankara,
Turkey. choroid@excite.com

The CREST syndrome is a variant form of progressive systemic sclerosis. Apart
from the occurrence of keratoconjunctivitis sicca, other types of ocular
involvement associated with this variant are quite rare. We present the case of a
73-year-old woman with the CREST variant of progressive systemic sclerosis who
developed unilateral granulomatous anterior uveitis. Systemic and laboratory
testing failed to suggest evidence for any other associated systemic disease as a
possible cause of the granulomatous uveitis. The inflammation was successfully
controlled with topical steroids and mydriatics. While a small number of cases of
uveitis have been reported in other variant forms of progressive systemic
sclerosis, to date there have been no descriptions of uveitis associated with the
CREST syndrome.

Publication Types: 
    Case Reports

PMID: 11120581 [PubMed - indexed for MEDLINE]

294: Pediatr Allergy Immunol. 2000 Nov;11(4):250-5.

Anti-centromere antibodies as a marker of Raynaud's phenomenon in pediatric
rheumatologic diseases.

Hossny E, Hady HA, Mabrouk R.

Department of Pediatrics, Ain Shams University, Cairo, Egypt. elhossny@yahoo.com

To examine the possible relationship between anti-centromere antibodies (ACA) and
pediatric rheumatologic diseases, we investigated the presence of ACA (using
enzyme immunoassay) in the sera of 45 children and adolescents with such diseases
and compared the results with a group of 42 age- and gender-matched healthy
subjects. ACA were present ( > or =10 U/ml) in three out of five patients (60%)
with scleroderma (SCD), in seven out of 16 (43.8%) patients with systemic lupus
erythematosus (SLE), in two out of five patients (40%) with mixed connective
tissue disease (MCTD), in one out of four patients (25%) with dermatomyositis
(DMS), and in two out of 14 patients (14.3%) with juvenile rheumatoid arthritis
(JRA). ACA were also detected in a single patient with anti-phospholipid syndrome
(APL) who had digital gangrene and hemiparesis, as well as in two healthy
subjects. ACA positivity was related to the presence of Raynaud's phenomenon in
the studied sample, as 86% of patients suffering from the phenomenon were ACA
positive. ACA positivity was associated with older age, high blood pressure and
high erythrocyte sedimentation rate (ESR) values, and lower hemoglobin and weight
and height percentile values. It was also higher among anti-nuclear
antibody-positive subjects. Raynaud's phenomenon and ACA positivity shared almost
the same clinical and laboratory associations in the studied patients. Thus, ACA 
are probably among the markers of Raynaud's phenomenon in pediatric rheumatologic
diseases. Their value as predictors of future development of the phenomenon needs
further evaluation.

PMID: 11110581 [PubMed - indexed for MEDLINE]

295: J Hand Surg [Br]. 2000 Dec;25(6):611-3.

Digital arterial occlusion in scleroderma: is there a role for digital arterial
reconstruction?

Tomaino MM.

Department of Orthopaedic Surgery, University of Pittsburgh Medical Center,
Pittsburgh 15213, USA. mtomaino@uoi.upmc.edu

A 47-year-old patient with Raynaud's phenomenon secondary to scleroderma
developed long finger ischaemic pain. This was successfully treated with a palmar
sympathectomy and a long finger digital artery reconstruction using a reversed
small calibre vein graft between a perforator from the deep palmar arch and the
radial digital artery at the level of the distal interphalangeal joint. Copyright
2000 The British Society for Surgery of the Hand.

Publication Types: 
    Case Reports

PMID: 11106531 [PubMed - indexed for MEDLINE]

296: Vasc Med. 2000;5(3):135-40.

Evaluation of treatment efficacy of Raynaud phenomenon by digital blood pressure 
response to cooling. Raynaud's Treatment Study Investigators.

Maricq HR, Jennings JR, Valter I, Frederick M, Thompson B, Smith EA, Hill R;
Raynaud's Treatment Study Investigators.

Department of Medicine, Medical University of South Carolina, Charleston 29425,
USA.

Our previous studies have suggested that digital blood pressure response to
cooling could provide a measure of the efficacy of treatments that are
administered to patients with Raynaud phenomenon (RP). This method was used on
158 primary RP patients participating in a multicenter, randomized clinical trial
that compared the efficacy of sustained-release nifedipine with temperature
biofeedback in the treatment of RP. A pill placebo and electromyography served as
controls. The response to local finger cooling was measured at 30 degrees, 20
degrees, 15 degrees and 10 degrees C in a temperature-controlled room under
standardized conditions. The results showed that, at the 15 degrees C and 10
degrees C local cooling temperatures, the patients in the nifedipine group had a 
higher mean digital systolic blood pressure, a higher relative digital systolic
blood pressure (RDSP), a smaller proportion of subjects with RDSP < 70% and a
smaller proportion of subjects with a zero reopening pressure than the patients
in the three other treatment groups. These results were statistically significant
at 10 degrees C, the nifedipine group being significantly different from all
others (p < 0.05); no significant difference was found between the three other
treatment groups.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 11104295 [PubMed - indexed for MEDLINE]

297: Neth J Med. 2000 Dec;57(6):229-32.

Pulmonary hypertension with limited cutaneous scleroderma (CREST syndrome).

Berends JC, Dompeling EC, van der Star JG, Hoorntje JC.

Isala Klinieken Locatie Weezenlanden, P.O. Box 10500, 8000 GM, Zwolle,
Netherlands. j.c.berends@int.azg.nl

A patient is described with a typical manifestation of pulmonary hypertension
associated with limited cutaneous scleroderma, also known as CREST syndrome. The 
patient was treated with a calcium antagonist, oral anticoagulation and, because 
of evidence for parenchymal inflammation of the lung, with low-dose prednisone
and cyclophosphamide. This treatment resulted in initial improvement of diffusion
capacity and exercise tolerance, however, 1 year after diagnosis the patient died
of progressive pulmonary hypertension.

Publication Types: 
    Case Reports

PMID: 11099792 [PubMed - indexed for MEDLINE]

298: J Rheumatol. 2000 Nov;27(11):2621-3.

Homocysteine concentration in primary and systemic sclerosis associated Raynaud's
phenomenon.

Marasini B, Casari S, Bestetti A, Maioli C, Cugno M, Zeni S, Turri O, Guagnellini
E, Biondi ML.

Department of Medicine, Surgery and Dentistry, Institute of Radiological
Sciences, San Paolo Hospital, Italy. bianca.marasini1@unimi.it

OBJECTIVE: To investigate whether patients with systemic sclerosis (SSc) have
raised homocysteine (Hcy) plasma levels, thought to be an independent risk factor
for vascular disease, and to study the relationship between Hcy and endothelial
damage, and between Hcy and methylene-tetrahydrofolate reductase (MTHFR)
genotypes, and patients' vitamin nutritional status, which are among the more
frequent causes of hyperhomocysteinemia. METHODS: We measured Hcy, von Willebrand
factor (vWF), folic acid, and vitamin B12 plasma levels and analyzed the
frequencies of MTHFR mutations in 30 patients with SSc and 12 patients with
primary Raynaud's phenomenon (RP); 29 healthy subjects served as controls.
RESULTS: Patients with SSc had higher Hcy and vWF concentrations than those with 
RP (p < 0.01 and p < 0.02, respectively) or controls (p < 0.02 and p < 0.0001,
respectively). Folic acid and vitamin B12 were lower in SSc than in RP (p < 0.01 
and p < 0.02, respectively) or controls (p < 0.05). MTHFR genotype did not
influence Hcy, folate, or vitamin B12 concentrations, but patients homozygous for
the mutant gene had higher vWF levels. CONCLUSION: Patients with SSc, but not
those with RP, had significantly higher Hcy and vWF plasma levels. Nutritional
rather than inherited factors seem to have a pathogenic role in SSc
hyperhomocysteinemia.

PMID: 11093443 [PubMed - indexed for MEDLINE]

299: J Dermatol. 2000 Oct;27(10):643-50.

Changes in plasma serotonin concentration and acceleration plethysmograms in
patients with Raynaud's phenomenon after long-term treatment with a 5-HT2
receptor antagonist.

Igarashi M, Okuda T, Oh-i T, Koga M.

Department of Dermatology, Tokyo Medical University, Japan.

High blood serotonin concentrations have been reported in patients with Raynaud's
phenomenon and a relationship has been suggested. Because of the difficulty in
evaluating Raynaud's phenomenon objectively, a possible correlation between blood
serotonin concentrations and clinical findings has not yet been evaluated. We
measured plasma serotonin concentrations and acceleration plethysmograms (APG)
before and one year after administration of a serotonin receptor antagonist.
Twenty-seven patients with either collagen disease or diseases associated with
Raynaud's phenomenon were given a combined 5-HT2 and serotonin receptor
antagonist, sarpogrelate hydrochloride. Plasma serotonin concentrations were
determined before and after administration and the APG d/a value was measured as 
an index of peripheral hemodynamics. These values were compared with the clinical
symptoms of the patients. After one year of treatment, the subjective symptoms
improved in 59.3% of patients who has Raynaud's phenomenon. The pretreatment
plasma serotonin concentrations of the study patients were significantly higher
than those of the normal controls, but became significantly decreased following
5-HT2 administration. However, there was no clear-cut relationship with the
clinical symptoms. The pre-treatment APG d/a value of the patients was
significantly lower than that of the normal controls, although there was no
significant difference after administration when analyzed as an entire group or
in a subset of patients whose symptoms did not subjectively improve or worsened
after one year of treatment. In the subset in whom the subjective symptoms
improved, however, the value significantly increased following administration,
suggesting an improvement in peripheral hemodynamics. These results suggest the
possibility that APG can be used as an objective index of peripheral
hemodynamics.

PMID: 11092268 [PubMed - indexed for MEDLINE]

300: Curr Opin Rheumatol. 2000 Nov;12(6):511-9.

Genetic factors in the etiology of systemic sclerosis and Raynaud phenomenon.

Tan FK, Arnett FC.

Division of Rheumatology and Clinical Immunogenetics, University of Texas,
Houston Medical School, 77030, USA. Filemon.K.Tan@uth.tmc.edu

There is increasing evidence that genetic factors play important roles in
susceptibility to and expression of systemic sclerosis (SSc), as well as primary 
Raynaud phenomenon. Familial aggregation for SSc, although infrequent (1.2%-1.5% 
of SSc families), has now been established, and when compared with population
prevalence represents a significant risk factor for the disease and lays a firmer
foundation for genetics in etiopathogenesis. Major histocompatibility complex
class II alleles increase disease risk in some populations but are more strongly 
correlated with specific autoantibody profiles. Microchimerism influenced by
human leukocyte antigen also remains an intriguing hypothesis. A variety of
extracellular matrix genes, including fibrillin-1, have become additional
candidates for contributing to what is likely a complex genetic disease. Reviewed
here is evidence relating to these concepts, especially new data reported over
the last year.

Publication Types: 
    Review

PMID: 11092201 [PubMed - indexed for MEDLINE]

301: Rheumatology (Oxford). 2000 Nov;39(11):1206-13.

Assessment of microvascular changes in Raynaud's phenomenon and connective tissue
disease using colour doppler ultrasound.

Keberle M, Tony HP, Jahns R, Hau M, Haerten R, Jenett M.

Institut für Röntgendiagnostik, University of Würzburg, Würzburg, Germany.

OBJECTIVE: We used colour Doppler ultrasound (CDU) to differentiate primary from 
secondary Raynaud's phenomenon (pRP and sRP, respectively) and to assess digital 
vascular damage in patients with connective tissue disease (CTD). METHODS:
Vascularity in the nailbeds of 15 healthy controls and 35 patients with CTD
(systemic sclerosis or systemic lupus erythematosus) was quantified using a
multi-D array transducer before and after cold and warm challenge, respectively. 
The results were compared with the clinically evaluated initial skin lesions.
Vascularity was compared similarly between 10 pRP and 22 sRP patients. RESULTS:
Vascularity at ambient temperature differed between healthy subjects and sRP
patients as well as between healthy subjects and CTD patients without initial
skin lesions. Patients with pRP had normal vascularity at ambient temperature but
differed from healthy controls in response to a dynamic temperature challenge.
CDU confirmed the clinical evaluation in 89.4% of the patients with RP and in
78.0% of the skin lesions. CONCLUSION: The novel CDU technique presented here
makes it possible to discriminate between pRP and sRP and to quantify vascular
changes in CTD patients.

PMID: 11085798 [PubMed - indexed for MEDLINE]

302: Proc AMIA Symp. 2000:903-7.

Text-based discovery in biomedicine: the architecture of the DAD-system.

Weeber M, Klein H, Aronson AR, Mork JG, de Jong-van den Berg LT, Vos R.

Social Pharmacy and Pharmacoepidemiology, Groningen University Institute for Drug
Exploration, Groningen, The Netherlands.

Current scientific research takes place in highly specialized contexts with poor 
communication between disciplines as a likely consequence. Knowledge from one
discipline may be useful for the other without researchers knowing it. As
scientific publications are a condensation of this knowledge, literature-based
discovery tools may help the individual scientist to explore new useful domains. 
We report on the development of the DAD-system, a concept-based Natural Language 
Processing system for PubMed citations that provides the biomedical researcher
such a tool. We describe the general architecture and illustrate its operation by
a simulation of a well-known text-based discovery: The favorable effects of fish 
oil on patients suffering from Raynaud's disease [1].

PMID: 11080015 [PubMed - indexed for MEDLINE]

303: Clin Rheumatol. 2000;19(5):378-80.

Systemic sclerosis: another rheumatic disease associated with hepatitis C virus
infection.

Abu-Shakra M, Sukenik S, Buskila D.

Department of Medicine and Rheumatic Diseases Unit, Soroka Medical Centre and
Ben-Gurion University, Beer-Sheva, Israel.

The first case of a patient with chronic infection with hepatitis C virus who
developed systemic sclerosis, manifested by severe Raynaud's phenomenon,
progressive skin thickening, painful fingertip ulcers, dysphagia and Sjogren's
syndrome, is described. The role of interferon therapy is discussed.

Publication Types: 
    Case Reports

PMID: 11055827 [PubMed - indexed for MEDLINE]

304: Ann Rheum Dis. 2000 Nov;59(11):870-4.

Digital vascular responses and serum endothelin-1 concentrations in primary and
secondary Raynaud's phenomenon.

Smyth AE, Bell AL, Bruce IN, McGrann S, Allen JA.

The Queen's University of Belfast, Musculoskeletal Education and Research Unit,
Musgrave Park Hospital, Stockmans Lane, Belfast BT9 7JB, UK.
anita.smyth@ntlworld.com

OBJECTIVE: To determine circulating endothelin-1 levels (ET-1) in patients with
primary or secondary associated Raynaud's phenomenon (RP) under resting
conditions and in response to cold provocation. METHODS: Patients were
categorised as primary RP (18) or scleroderma associated RP (14). Finger blood
flow was measured by venous occlusion plethysmography at finger temperatures of
32 degrees C and 24 degrees C. Vasospasm was detected as a finger systolic
pressure of 0 mm Hg after standardised provocative cooling. Severity of vasospasm
was assessed by the level of cooling required to provoke spasm. Plasma ET-1
levels were measured in antecubital blood withdrawn under baseline conditions
(finger 32 degrees C) and at the point of vasospasm. Measurements were also made 
in 19 matched control subjects. RESULTS: Finger blood flow was lower in patients 
with RP than in controls, with no difference between the two RP groups. Vasospasm
occurred in all patients with RP but not in any control subjects and a grading
system of severity was established. Baseline plasma ET-1 levels were similar in
patients with RP and controls. Increases in ET-1 levels at the point of vasospasm
in patients or corresponding timepoint in controls were also similar. There was
no significant difference between the ET-1 levels in the two RP subgroups when
the fingers were warm or when vasospasm was present. CONCLUSIONS: These results
do not support the hypothesis that ET-1 plays a part in the pathogenesis of RP.
Objective testing is a useful adjunct to the clinical diagnosis of RP and allows 
assignment of a severity grade.

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

PMID: 11053063 [PubMed - indexed for MEDLINE]

305: Int J Clin Lab Res. 2000;30(2):75-81.

Measurement of soluble adhesion molecules in primary Raynaud's phenomenon and in 
Raynaud's phenomenon secondary to connective tissue diseases.

Brevetti G, De Caterina M, Martone VD, Corrado S, Silvestro A, Spadaro G,
Scopacasa F.

Department of Medicine, University Federico II, Naples, Italy.

Adhesion molecules play a role in the inflammation and pathogenesis of vascular
diseases. In 13 patients with primary Raynaud's phenomenon, 19 with Raynaud's
phenomenon associated with connective tissue disease, and 16 control subjects, we
measured plasma levels of soluble forms of intercellular adhesion molecule-1,
vascular cell adhesion molecule-1, E-selectin, and von Willebrand factor.
Patients with secondary Raynaud's phenomenon had plasma levels of soluble forms
of intercellular adhesion molecule- 1, vascular cell adhesion molecule-1,
E-selectin, and von Willebrand factor which were significantly higher than in
those with primary Raynaud's phenomenon and controls, while no difference was
observed between patients with primary Raynaud's phenomenon and controls. Within 
the group with secondary Raynaud's phenomenon, the strongest correlations were
between soluble forms of intercellular adhesion molecule-1 and both E-selectin,
(r=0.67, P<0.001) and von Willebrand factor (r=0.58, P<0.01). In none of the
three groups were the levels of soluble adhesion molecules and von Willebrand
factor changed by exposure of hands to cold, although all patients had a definite
vasospasm. In conclusion, this study indicates that primary Raynaud's phenomenon 
is not associated with elevation of soluble adhesion molecules and von Willebrand
factor. Prospective studies are now required to investigate the role of these
molecules as predictors of secondary diseases.

PMID: 11043500 [PubMed - indexed for MEDLINE]

306: Rheumatology (Oxford). 2000 Oct;39(10):1132-8.

Effect of SR 49059, a V1a vasopressin receptor antagonist, in Raynaud's
phenomenon.

Hayoz D, Bizzini G, Noël B, Depairon M, Burnier M, Fauveau C, Rouillon A, Brouard
R, Brunner HR.

Division of Hypertension and Vascular Medicine, CHUV, Lausanne, Switzerland.

OBJECTIVE: To assess whether vasopressin V1a receptor blockade reduces the
abnormal vasoactive response to cold in patients suffering from Raynaud's
phenomenon (RP). METHODS: SR 49059, an orally active, non-peptidic vasopressin
V1a receptor antagonist, was given orally (300 mg once daily) to 20 patients with
RP in a single-centre, double-blind, placebo-controlled, randomized cross-over
study with two 7-day periods of treatment separated by 21 days of washout.
Bilateral finger systolic blood pressure and skin temperature were assessed
before and after immersion of the hand in cold water for 3 min (15 degrees C)
during the screening phase and three times (before and 2 and 4 h after drug
intake) on days 1 and 7 of each of the two treatment periods. Recovery of digital
pressure and skin temperature was measured 0, 10, 20 and 32 min after the end of 
the cold immersion test. RESULTS: SR 49059 significantly attenuated the
cold-induced fall in systolic pressure by 14.5% (95% confidence interval 0-29; P 
= 0.045) on the most affected hand on day 7 compared with placebo. Temperature
recovery after the end of the cold test showed a trend to enhancement 2 and 4 h
after SR 49059 on day 7 (P = 0.060 and P = 0.062 respectively). The beneficial
effects on finger pressure and temperature recovery were obtained without changes
in supine blood pressure or in heart rate. CONCLUSION: SR 49059 given orally once
a day for 7 days to patients with RP showed favourable effects compared with
placebo on finger systolic pressure and temperature recovery after cold
immersion, without inducing side-effects.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11035135 [PubMed - indexed for MEDLINE]

307: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000 Oct;90(4):456-9.

Painful trigeminal neuropathy caused by severe mandibular resorption and nerve
compression in a patient with systemic sclerosis: case report and literature
review.

Fischoff DK, Sirois D.

UMDNJ New Jersey Dental School, Division of Oral Medicine, Newark, NJ, USA.

Systemic sclerosis is a multi-system disorder characterized by abundant fibrosis 
of the skin, blood vessels, and visceral organs. Although resorption of the
mandible has been commonly observed and reported, we found no report of
resorption leading to a painful neuropathy of the inferior alveolar nerve. We
report a case of a patient with systemic sclerosis, severe resorption of the
angles, and inferior alveolar border of the mandible, resulting in a compression 
neuropathy of the inferior alveolar nerve. Diagnostic tests, medical treatment,
and surgical treatment are discussed, and the relevant literature is reviewed.

Publication Types: 
    Case Reports
    Review

PMID: 11027382 [PubMed - indexed for MEDLINE]

308: Panminerva Med. 2000 Mar;42(1):7-9.

Evaluation of haemostatic parameters and circadian variations of the haemostatic 
system in patients with systemic sclerosis and Raynaud's phenomenon.

Trifiletti A, Bartolone S, Scamardi R, Pizzoleo MA, Sottilotta G, Larosa D,
Barbera N.

Department of Internal Medicine, University of Messina, Italy.

BACKGROUND: Systemic sclerosis (SSc) is a multisystemic disease characterized by 
proliferation and swelling of endothelial cells and other disorders. Raynaud's
phenomenon (RP) is a disturbance, with unknown pathogenesis, that may be a
precursor to SSc. The aim of this study was to investigate possible alterations
in the haemostatic system and to examine whether there is a circadian variation
in haemostatic variables at the initial stage of SSc. METHODS: In 20 patients
with RP (in all patients secondary to SSc) and in 10 controls the levels of
thrombomodulin (TM), beta-thromboglobulin (beta-TG), D-dimer (DD), tissue-type
plasminogen activator (t-PA) and plasminogen activator-inhibitor (PAI-1) were
measured in venous plasma samples taken at 9.00 and 14.00. RESULTS: Only TM
levels were found to be higher in patients than in controls. Moreover the PAI-I
levels, in the patient group, showed a significant circadian rhythm (with peak
values at 9.00). No significant circadian variations for the other parameters
were detected. CONCLUSIONS: These data seem to indicate that in patients with RP 
there is an endothelial damage reflected by a significant elevation of the TM
plasma level and a circadian variation in plasma PAI-1, which was higher in the
morning. This observation may be an area worth exploring for its importance
potential in the knowledge of Raynaud's phenomenon.

PMID: 11019597 [PubMed - indexed for MEDLINE]

309: Pflugers Arch. 2000;440(5 Suppl):R137-8.

Possibilities for clinical use of prostacyclin in vascular disease.

Poredos P.

Department of Vascular Disease, University Medical Centre, Ljubljana, Slovenia.

Currently available drug therapies for patients suffering severe ischaemia with
rest pain and trophic lesions of the limbs remain unsatisfactory. Also vascular
reopening procedures are suitable in only about half of the patients. In
atherosclerotic disease when the vascular endothelium is damaged prostacyclin
synthesis is decreased and thromboxane A2 production increases. Prompted by this 
knowledge of the importance of prostacyclin in pathogenesis of atherosclerotic
disease an attempt was made to employ PGI2 clinically--for treatment of advanced 
forms of peripheral arterial atherosclerotic disease. Favourable effects of the
stable analogue of prostacyclin (Iloprost), were reported in various studies,
which included patients with peripheral atherosclerotic arterial disease,
thromboangiitis obliterans and Raynaud's phenomenon. The use of Iloprost resulted
in a significantly superior response than other drugs and placebo in terms of
alleviation of rest pain, ulcer healing and decrease of amputation rate of
ischaemic limbs. Therefore prostacyclin provides a therapeutic option in patients
with advanced forms of arterial disease--including critical ischaemia.

PMID: 11005643 [PubMed - indexed for MEDLINE]

310: J Am Acad Dermatol. 2000 Oct;43(4):631-4.

Raynaud's phenomenon, anticentromere antibodies, and digital necrosis without
sclerodactyly: an entity independent of scleroderma?

Sachsenberg-Studer EM, Prins C, Saurat JH, Salomon D.

Department of Dermatology, J-W Goethe University Hospital, Frankfurt, Germany.

We describe 4 women of 43, 73, 84, and 86 years with Raynaud's phenomenon, severe
digital necrosis, and high serum levels of anticentromere antibodies without skin
thickening or internal organ sclerosis. Investigations revealed no diabetes or
arterial vascular disease leading to arterial obstruction. Histologic examination
did not show any dermal sclerosis or calcinosis. The intravenous infusions of
prostaglandin reversed the ischemic lesions in 3 patients. These cases suggest
that the triad Raynaud's phenomenon, anticentromere antibodies and necrosis of
digits without sclerodactyly and sclerosis of internal organ should be considered
as an entity distinct from scleroderma with sclerosis. For this entity we propose
the name RACAND syndrome.

Publication Types: 
    Case Reports

PMID: 11004618 [PubMed - indexed for MEDLINE]

311: Cardiovasc Surg. 2000 Oct;8(6):457-62.

Clinical spectrum of Raynaud's phenomenon in patients referred to vascular
clinic.

Knapik-Kordecka M, Wysokinski WE.

Department and Clinic of Angiology, University Medical School of Wroclaw,
Poniatowski Street 2, 50-326, Wroclaw, Poland.

Difficulties to establish general characteristics of patients with Raynaud's
phenomenon, especially frequency, rates and predisposing factors of the evolution
of primary to secondary cases probably originate from substantial variation of
evaluated cohorts. We conducted a prospective study using standardised diagnostic
procedures in order to look for the specificity of patients referred to the
vascular centre; moreover, we assayed anticardiolipin antibodies in these
patients using double ELISA and compared its frequency to sex and age matched a
control group of 50 healthy individuals. 124 patients (20 men), mean age at onset
35.5 yr, range 9-69 yr, had confirmed diagnosis of Raynaud's phenomenon. Ninety
nine patients were found to have secondary phenomenon, 72% of them had trophic
changes of fingers and/or toes. Anticardiolipin antibodies assay was positive in 
seven patients and four healthy donors. Vascular diseases constituted about 20%, 
and connective tissue diseases 50% of secondary cases, but SLE (17 cases) not a
scleroderma (11 cases) was the most frequent clinical entity in the latter group.
There were only two patients with Buerger's disease and one with atherosclerosis 
as an underlying disease for vasospastic disorder. We concluded in the vascular
medicine centre that there were a lot of patients with ischemic necrosis or other
type of trophic changes, and very little primary, benign Raynaud's disease cases;
surprisingly, peripheral arterial occlusive disease was very seldom responsible
for vasospastic episodes. Primary or secondary antiphospholipid syndrome is not
associated with Raynaud's phenomenon.

PMID: 10996100 [PubMed - indexed for MEDLINE]

312: J Bone Joint Surg Br. 2000 Aug;82(6):818-9.

Raynaud's phenomenon in idiopathic carpal tunnel syndrome: postoperative
alteration in its prevalence.

Chung MS, Gong HS, Baek GH.

National University College of Medicine, Seoul, Korea.

In a previous study the prevalence of Raynaud's phenomenon (RP) in patients with 
idiopathic carpal tunnel syndrome (CTS) was found to be 60% which is much higher 
than that in the general population. We undertook a further study of the same
cohort of patients have both CTS and RP and who had an open release of the carpal
tunnel, to observe the effects of the operation on RP. We observed whether the
symptoms of RP improved, and repeated the cold provocation tests to see if the
arterial pulse which was decreased before operation would recover. We rated the
outcome as good when the patients showed both an improvement of the symptoms of
RP and a normal pulse amplitude after exposure to cold, fair when the pulse
amplitude recovered to more than two-thirds of that before exposure, and poor
when cold hypersensitivity was persistent or showed the same degree of decreased 
pulse amplitude as observed before operation. Of the 18 patients with both
conditions, ten (56%) had good and four (22%) fair results, with a mean recovery 
time of 4.2 months (6 weeks to 1 year) after operation. If the vasospasm seen in 
RP is an expression of vasomotor irritation in the carpal tunnel, these findings 
suggest that local compression of vasomotor fibres in the carpal tunnel can also 
be relieved by the release of this structure. Careful consideration, however, is 
still required in treating patients with both conditions since in some cases. RP 
may be superimposed or it may have other origins.

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

PMID: 10990303 [PubMed - indexed for MEDLINE]

313: Rheumatol Int. 2000;19(5):165-9.

Nerve conduction velocity study of the upper limb in Raynaud's phenomenon.

Mondelli M, Romano C, De Stefano R, Cioni R.

Serv. di EMG ASL, Siena, Italy. mondelli@unisi.it

A prospective study of upper limb nerve conduction velocity was performed in 39
subjects (9 males, 30 females, mean age 46.8 years) with idiopathic Raynaud's
phenomenon (RP) and 18 patients (3 males, 15 females, mean age 49.9 years) with
RP secondary to systemic sclerosis (SS). Five subjects with idiopathic RP (13%)
showed slowing of sensory conduction velocity (SCV) of the distal median nerve,
associated with delayed distal motor latency (DML) of the same nerve in three
patients, without clinical signs or symptoms of carpal tunnel syndrome (CTS).
Three patients with secondary RP (17%) had reduction of SCV of the distal median 
nerve, associated with increased DML of the same nerve in one and with clinically
silent slowing of SCV of the ulnar nerve in two (11%). Mean distal SCVs of the
median nerve were significantly lower and mean DMLs were significantly higher in 
both groups with respect to a control group. Mean distal conduction of the ulnar 
nerve was significantly slower only in the group with secondary RP. No slowing
was observed in the proximal part of any nerve. It seems likely that patients
with idiopathic RP have slowing of conduction in the distal part of the median
nerve, along the carpal tunnel. Since slowing does not occur in all parts of the 
nerves of the hand, it cannot be related to acral vasomotor disturbances, but to 
local or systemic factors. In contrast, patients with secondary RP had slowing of
median and ulnar nerve conduction velocity, presumably related to subclinical
distal peripheral neuropathy. A nerve conduction study of the hand could be
useful in cases of suspected secondary origin of RP. In idiopathic RP, slowing of
conduction may only affect the median nerve, whereas in secondary RP it may
affect other nerves of the hand.

PMID: 10984133 [PubMed - indexed for MEDLINE]

314: Clin Exp Dermatol. 2000 Jun;25(4):277-80.

Barraquer-Simons lipodystrophy, Raynaud's phenomenon and cutaneous vasculitis.

Porter WM, O'Gorman-Lalor O, Lane RJ, Francis N, Bunker CB.

Departments of Dermatology, Histopathology and Neurology, Charing Cross Hospital,
Imperial College School of Medicine, London, UK.

We report a 32-year-old man who presented with a 2-year history of unexplained
weight loss and symptoms of Raynaud's phenomenon. Clinical examination and
investigations were consistent with a diagnosis of acquired partial lipodystrophy
(Barraquer-Simons disease). This patient also exhibited an associated cutaneous
vasculitis and peripheral perniotic changes. He had normal renal function and
glucose tolerance and no immunological abnormality has been detected in his serum
to date. The absence of C3-nephritic factor in the presence of overt
lipodystrophy suggests that there may be another factor or immunological mediator
responsible for the subcutaneous changes seen in patients with lipodystrophy.

Publication Types: 
    Case Reports

PMID: 10971484 [PubMed - indexed for MEDLINE]

315: Br J Dermatol. 2000 Sep;143(3):641-4.

Comment in:
    Br J Dermatol. 2001 May;144(5):1087-90.

Hypereosinophilic syndrome presenting as cutaneous necrotizing eosinophilic
vasculitis and Raynaud's phenomenon complicated by digital gangrene.

Jang KA, Lim YS, Choi JH, Sung KJ, Moon KC, Koh JK.

Department of Dermatology, Paik Hospital, College of Medicine, Inje-University,
85, 2-Ga, Jur-Dong, Chung-Ku, Seoul 100-032, Korea. jang722@netsgo.com

Cutaneous necrotizing eosinophilic vasculitis is a recently identified type of
vasculitis that is characterized by an eosinophil-predominant necrotizing
vasculitis affecting small dermal vessels. Clinically, it presents with pruritic 
erythematous and purpuric papules and plaques, peripheral eosinophilia and a good
response to systemic steroid therapy. This vasculitis can be idiopathic or
associated with connective tissue diseases. Although the pathogenic roles of
eosinophil-derived granule proteins and interleukins have been documented in
diseases associated with eosinophilia, a role of CD40 (a glycoprotein of the
tumour necrosis factor receptor superfamily) has rarely been described. We
describe two patients with idiopathic hypereosinophilic syndrome (HES) presenting
with multiple erythematous patches and plaques on the lower extremities and
Raynaud's phenomenon. They satisfied the criteria for the diagnosis of HES by
clinical and laboratory investigations. Histopathology of the cutaneous lesions
revealed prominent eosinophilic infiltration with local fibrinoid change in
vessel walls in the dermis and subcutis. Immunohistochemical detection of CD3,
CD4, CD8 and CD40 was performed. Infiltrating eosinophils were strongly stained
by anti-CD40 monoclonal antibody. One patient improved with prednisolone,
pentoxifylline and nifedipine, without recurrence. The other patient initially
improved with steroids, but after self-withdrawal of steroid developed digital
ischaemia that evolved to severe necrosis and required amputation. Cutaneous
necrotizing eosinophilic vasculitis, Raynaud's phenomenon and digital gangrene
may develop as cutaneous manifestations of HES. CD40 may play a part in the
pathogenesis of eosinophilic vasculitis in HES.

Publication Types: 
    Case Reports

PMID: 10971345 [PubMed - indexed for MEDLINE]

316: Minerva Cardioangiol. 2000 Apr-May;48(4-5):137-46.

Considerations on pulsoplethysmographic changes in fingers due to iontophoresis
with methacholine in subjects with Raynaud's phenomenon.

[Article in English, Italian]

Taccola A, Zambelli M.

Fondazione Salvatore Maugeri IRCCS, Pavia.

This paper presents a study of plethysmographic changes induced by methacholine
(a derivative of acetylcholine) administered via iontophoresis in a population of
41 young women with apparently primary Raynaud's disease. All patients presented 
with a very clear statistically significant sphygmic increment, obviously
connected with the vasodilatation caused by methacholine. Moreover, in nearly
half of the 23 cases whose reaction to passive postural variations was
successively examined by plethysmography, the district circulatory response was
characterised by persistent neurogenous vasoconstriction due to methacholine or
by inadequate vasomotor EDRF mediated modulation. The authors believe that their 
findings serve as further evidence of the pathogenetic mechanisms of Raynaud's
disease. This is because they highlight the role played by "balance of vessel
motility" which would guarantee district circulatory homeostasis. Concrete proof 
thus corroborates well known indirect evidence that a pathological vasospasm can 
be triggered and persist when two fundamental conditions are met: a) intense
vasoconstriction initially of neurological origin and successively reinforced by 
biohumoural synergic stimuli; b) the breakdown of the capacity for EDRF mediated 
intrinsic vasomotor modulation. It is suggested that the prevalence of one or the
other factor would lead to a variety of clinical pictures denoting vascular
acrosyndromes of this type. The ability to single out such clinical pictures by
adding the iontophoresis test with methacholine to routine screening procedures
for the presence of Raynaud's disease, would allow physicians to make more
accurate diagnosis and improve therapy.

Publication Types: 
    Comparative Study

PMID: 10959150 [PubMed - indexed for MEDLINE]

317: Clin Exp Rheumatol. 2000 Jul-Aug;18(4):499-502.

Long-term low molecular weight heparin therapy for severe Raynaud's phenomenon: a
pilot study.

Denton CP, Howell K, Stratton RJ, Black CM.

Centre for Rheumatology (Royal Free Campus), Royal Free and University College
Medical School, London, UK.

OBJECTIVE: To investigate tolerability and efficacy of low molecular weight (LMW)
heparin therapy in patients with severe Raynaud's phenomenon. METHODS: A
prospective parallel group study comparing patients receiving regular
subcutaneous LMW heparin (n = 16) with a matched control group (n = 14).
Endpoints were change in Raynaud's attack severity, non-invasive vascular studies
or serum levels of circulating soluble adhesion molecules. RESULTS: There was
overall improvement in Raynaud's attack severity during heparin therapy (p =
0.0002). This was observed after 4 weeks, and was maximal by 20 weeks. Mean
finger blood flow recovery time improved, and serum levels of circulating ICAM-1,
VCAM-1 and E-selectin were lower at completion of heparin therapy, but changes
did not reach statistical significance. CONCLUSION: This study suggests that LMW 
heparin therapy is well tolerated, and potentially beneficial, in patients with
severe Raynaud's phenomenon, and justifies further evaluation.

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

PMID: 10949727 [PubMed - indexed for MEDLINE]

318: J Rheumatol. 2000 Jul;27(7):1686-92.

Severity of seropositive isolated Raynaud's phenomenon is associated with
serological profile.

Ihata A, Shirai A, Okubo T, Ohno S, Hagiwara E, Ishigatsubo Y.

First Department of Internal Medicine, Yokohama City, University of Medicine,
Yokohama City, Japan. ihata@pp.iij4u.or.jp

OBJECTIVE: To examine the relationship between the clinical severity of
seropositive isolated Raynaud's phenomenon (RP) and its serological background by
analyzing digital blood flow data obtained by laser Doppler flowmetry (LDF).
METHODS: We analyzed digital blood flow by LDF in 13 healthy volunteers, 55
patients with seropositive isolated RP, and 13 patients with anti-Scl-70 antibody
positive systemic sclerosis (SCL). The serological profiles of patients with RP
were as follows: 30 patients had the anti-centromere antibody (C) and 19 the
anti-RNP antibody (RNP). We designated the RP in each patient group as C-RP,
RNP-RP, and SCL-RP. We used an "arm-raising test" by which blood pressure could
be passively depressed, and the cold provocation test, which induced
vasoconstriction through the sympathetic reflex. We defined 2 variables, the
recovery velocity after cold exposure (RV-CE) and the increase in the amplitude
of the digital pulse wave during the arm-raising test (IA-AR), that are the most 
reliable and sensitive variables indicating the severity of RP. RESULTS: Both
RV-CE and IA-AR correlated significantly with the clinical severity of RP. In
IA-AR and RV-CE, there was a significant difference between C-RP and RNP-RP
(IA-AR 107.1 +/- 25.63 vs 37.4 +/- 17.25%; RV-CE 0.0667 +/- 0.010 vs 0.035 +/-
0.0096 V/s), showing that C-RP tended to be less severe than RNP-RP. CONCLUSION: 
We defined 2 variables that correlated with the clinical severity of RP; using
them we found that anti-centromere antibody positive RP is less severe than
RNP-RP

PMID: 10914852 [PubMed - indexed for MEDLINE]

319: Arthritis Rheum. 2000 Jul;43(7):1641-6.

A two-stage, genome-wide screen for susceptibility loci in primary Raynaud's
phenomenon.

Susol E, MacGregor AJ, Barrett JH, Wilson H, Black C, Welsh K, Silman A, Ollier
B, Worthington J.

ARC Epidemiology Research Unit, University of Manchester, UK.

OBJECTIVE: To identify chromosomal regions containing genes involved in the
susceptibility to primary Raynaud's phenomenon (RP). METHODS: Six extended
families with multiple individuals affected with primary RP (n = 37) were
examined for linkage in a 2-stage, whole-genome screen, using a total of 298
microsatellite markers. RESULTS: Multipoint, nonparametric linkage analysis
identified 5 areas of possible linkage, with a nominal level of significance of P
< or = 0.05. Analysis of a finer map of markers in these regions defined the
regions of linkage as 21.4 cM on 6q13-6q23.3 (D6S261; P = 0.0004), 10.2 cM on
7p22-7p15 (D7S664; P = 0.014), 1.6 cM on 9p23-9p22 (D9S156; P = 0.0075), 5.1 cM
on 17p13.1-17p12 (D17S1791; P = 0.036), and 11.8 cM on Xp11.4-Xp11.23 (DXS8054; P
= 0.006). Three potential candidate genes map to these regions: the beta subunit 
of the muscle acetylcholine receptor and the serotonin 1B and 1E receptors.
CONCLUSION: These results provide evidence of the presence and location of genes 
that are involved in the genetic susceptibility to primary RP.

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

PMID: 10902770 [PubMed - indexed for MEDLINE]

320: Baillieres Best Pract Res Clin Rheumatol. 2000 Mar;14(1):17-35.

Scleroderma and related disorders: therapeutic aspects.

Denton CP, Black CM.

Centre for Rheumatology, Royal Free and University College Medical School,
London, UK.

Improvements in management of systemic sclerosis have occurred through a growing 
understanding of pathogenic events accompanied by advances in diagnosis and
assessment, as well as developments in organ-based therapeutics. Unfortunately,
disease-modifying therapies of proven efficacy remain elusive and several agents 
in current use have been shown in well-controlled clinical trials to be of
questionable benefit. More positively, there have been advances in the treatment 
of major visceral complications such as renal crisis, pulmonary fibrosis,
pulmonary hypertension, gastrointestinal involvement and in the management of
scleroderma-associated Raynaud's phenomenon. Current approaches are reviewed,
evidence supporting or refuting the use of putative disease-modifying agents is
discussed, and new strategies are described that are currently being considered
for this fascinating but complex multisystem connective tissue disease.

Publication Types: 
    Review

PMID: 10882212 [PubMed - indexed for MEDLINE]

321: Occup Environ Med. 2000 Jul;57(7):448-52.

Comment in:
    Occup Environ Med. 2001 Apr;58(4):279-80.

Prevalence of Raynaud's phenomenon in Great Britain and its relation to hand
transmitted vibration: a national postal survey.

Palmer KT, Griffin MJ, Syddall H, Pannett B, Cooper C, Coggon D.

MRC Environmental Epidemiology Unit, Community Clinical Sciences, University of
Southampton, SO16 6YD, UK. krp@mrc.soton.ac.uk

OBJECTIVES: To assess the prevalence of Raynaud's phenomenon in the general
population of Great Britain and to estimate the proportion and number of cases
attributable to hand transmitted vibration (HTV). METHODS: A questionnaire was
posted to a random sample of 22,194 adults of working age. Information was
collected on the lifetime prevalence of finger blanching, smoking habits, and
occupational and leisure time exposures to HTV. Associations with risk factors
were explored by logistic regression, with odds ratios converted into prevalence 
ratios (PRs). RESULTS: Among the 12 907 respondents, 1835 (14.2%) reported finger
blanching at some time, including 1529 (11. 8%) in whom symptoms were induced by 
cold, and 597 (4.6%) in whom the blanched area was also clearly demarcated.
Prevalences were higher in women than men. Around one fifth of cases (2% of
respondents) had consulted a doctor about their symptoms. By comparison with men 
who had never been exposed to HTV, the PR for cold induced blanching in those
exposed only at work was 2.0 (95% CI 1.7 to 2.3), and in men exposed both at work
and in leisure it was 2. 5 (95% CI 2.1 to 3.1). Higher risks were found in men
who consulted a doctor about cold induced blanching, among whom 37.6% of cases
were estimated to arise from exposure to HTV. The estimated number of cases
attributable to HTV nationally was 222 000 in men who reported extensive
blanching (blanching affecting at least eight of the digits or 15 phalanges).
Similar patterns of risk were found in women, but the attributable proportion was
much lower (5.3% in cases consulting a doctor). CONCLUSIONS: Raynaud's phenomenon
is common in the general population. Many cases are attributable to HTV,
especially in men, emphasising the public health importance of this common
occupational hazard.

PMID: 10854496 [PubMed - indexed for MEDLINE]

322: Rheumatology (Oxford). 2000 May;39(5):506-12.

Quantitation of microcirculatory abnormalities in patients with primary Raynaud's
phenomenon and systemic sclerosis by video capillaroscopy.

Bukhari M, Hollis S, Moore T, Jayson MI, Herrick AL.

University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford M6
8HD, UK.

OBJECTIVE.: To assess nailfold capillary density and dimensions in patients with 
primary Raynaud's phenomenon (PRP), limited cutaneous systemic sclerosis (LSSc)
and diffuse cutaneous SSc (DSSc), and healthy control subjects. METHODS.: Using
the technique of nailfold video capillaroscopy, capillary density and dimensions 
were averaged from all visible capillaries in a 3 mm length of the nailfold from 
right and left ring fingers of each subject. Twenty healthy control subjects, 15 
patients with PRP, 13 patients with DSSc and 21 patients with LSSc were examined.
Intra-observer and inter-observer variability were calculated in 18 and 23
patients, respectively. RESULTS.: There were significant trends for capillary
density to fall and for all dimensions to rise across the four groups (P < 0.
0001 for density and all dimensions, order healthy controls, PRP, DSSc and LSSc).
Intra- and inter-observer reproducibility studies showed that although there was 
good correlation between and within observers, the limits of agreement were
between +/-25-50% indicating lack of reproducibility. CONCLUSIONS.:
Microcirculatory abnormalities can be quantified using the technique of video
capillaroscopy and were most marked in patients with LSSc.

Publication Types: 
    Comparative Study

PMID: 10852981 [PubMed - indexed for MEDLINE]

323: J Rheumatol. 2000 Jun;27(6):1403-7.

Clinical significance of anticentromere antibodies in patients with systemic
lupus erythematosus.

Nakano M, Ohuchi Y, Hasegawa H, Kuroda T, Ito S, Gejyo F.

Department of Medicine II, Niigata University School of Medicine, Japan.

OBJECTIVE: To clarify the clinical significance of anticentromere antibodies
(ACA) in patients with systemic lupus erythematosus (SLE). METHODS: Two hundred
sixteen patients with SLE who were treated in our department were surveyed cross 
sectionally for the presence of ACA using indirect immunofluorescence on HEp-2
cell lines. ACA were identified by their discrete speckled pattern. Antibodies to
the major centromere protein, CENP-B, were also studied with ELISA. Serial
determinations of anti-CENP-B were carried out using stored serum samples, if
available. RESULTS: ACA were recognized in 12 (5.6%) patients with SLE. All
patients were receiving steroid therapy, with a mean dose of prednisolone of 14.4
mg/day. These patients also tested positive for anti-CENP-B with high titers
despite the low serological disease activity in most. Three or more CREST
features were observed in 2 patients and 2 others had no such features. Both
patients without CREST features had a relatively short disease duration. The age 
at onset of SLE was significantly higher and Raynaud's phenomenon was more
frequent in patients with ACA than in patients without ACA. In 8 of 10 patients
tested, retrospective analysis using stored sera revealed no consistent change in
anti-CENP-B titers over time. CONCLUSION: The presence of ACA in patients with
SLE is apparently more frequent than previously believed. Patients with SLE with 
ACA may be a distinct subgroup. A longterm followup is warranted to fully
determine the clinical significance of ACA in patients with SLE.

PMID: 10852261 [PubMed - indexed for MEDLINE]

324: Intern Med. 2000 Jun;39(6):451-6.

Comment in:
    Intern Med. 2000 Jun;39(6):437.

Clinical, serological and genetic study in patients with CREST syndrome.

Akiyama Y, Tanaka M, Takeishi M, Adachi D, Mimori A, Suzuki T.

Department of Rheumatology, Saitama Medical School.

OBJECTIVE: To assess the clinical, serological and genetic features of Japanese
patients with CREST syndrome. PATIENTS AND METHODS: Clinical features,
autoantibodies and human histocompatibility leukocyte antigen (HLA) typing were
studied in thirty patients with CREST syndrome, including 29 females and one
male, with a mean age of 59.0 years (ranging from 40 to 76 years). RESULTS:
Interstitial pneumonia on chest X-ray and renal involvement were rare. Mitral
regurgitation and tricuspid regurgitation were present in 56.7% and 76.7%,
respectively. Sjören's syndrome (SS) and primary biliary cirrhosis (PBC) were
highly associated, however the positivity of the marker antibodies to those
syndromes, such as anti-SSA, anti-SSB, anti-mitochondrial (AMA) and anti-smooth
muscle autoantibodies were less frequent than that of primary SS and PBC without 
the other autoimmune diseases. The histological findings of PBC were all early
stages in Scheuer's classification. HLA-Cw6 were associated with CREST-PBC
overlap syndrome (p<0.05). However the HLA antigen was not correlated with CREST 
syndrome, and the frequency of HLA-DR2 between CREST syndrome with or without PBC
was significantly different (p<0.01). CONCLUSION: It was suggested that there was
a genetic difference between CREST syndrome alone and CREST-PBC overlap syndrome 
and there were differences (the positivity of AMA and the severity of bile duct
lesion) between PBC and CREST-PBC overlap syndrome.

PMID: 10852162 [PubMed - indexed for MEDLINE]

325: Anesth Analg. 2000 Jun;90(6):1417-8.

Acute vasospastic attack after extradural block in a patient with Raynaud's
disease.

Nay PG, O'Brien K.

Department of Anesthesiology, University of Michigan Medical Center, Ann Arbor,
Michigan 48109-0048, USA.

Implications: Raynaud's disease is an episodic and debilitating disease of the
circulation to the fingers and toes. This case report describes an acute
exacerbation of Raynaud's disease in a patient undergoing surgery with epidural
anesthesia. This potentially hazardous complication has not been previously
reported.

Publication Types: 
    Case Reports

PMID: 10825332 [PubMed - indexed for MEDLINE]

326: Br J Dermatol. 2000 May;142(5):1013-6.

Digital ulcers and necroses: novel manifestations of angiocentric lymphoma.

Ohtsuka T, Yamakage A, Yamazaki S.

Department of Dermatology, Dokkyo University School of Medicine, 880
Kitakobayashi, Mibu, Tochigi 321-0293, Japan. tohtsuka@dokkyomed.ac.jp

We describe a patient with angiocentric lymphoma whose presenting features were
multiple areas of digital ulceration and necrosis, including deep ulcers on both 
great toes. He lacked the lateral halves of both earlobes because of multiple
ulcers. Skin biopsy revealed a patchy and diffuse infiltrate of lymphoid cells
with nuclear atypia in the dermis and subcutaneous tissue. Angiocentric and
angiodestructive features of the lymphoid cells, a prominent histiocytic
infiltrate and some epithelioid cell granulomas were found. The results of
immunohistochemical staining showed a T-cell phenotype, and showed positive
staining for apoptosis. He died in July 1999. Peripheral vascular disturbances
including Raynaud's phenomenon, digital skin ulcers and necroses are novel
clinical symptoms in patients with angiocentric lymphoma, which should be added
to the differential diagnosis in patients with peripheral vascular disturbances.

Publication Types: 
    Case Reports

PMID: 10809864 [PubMed - indexed for MEDLINE]

327: Clin Nephrol. 2000 Apr;53(4):296-300.

A case of CREST syndrome and myeloperoxidase-specific anti-neutrophil cytoplasmic
autoantibody-associated glomerulonephritis.

Yamashita K, Yorioka N, Kyuden Y, Naito T, Tanji C, Ueda C, Usui K, Shigemoto K, 
Harada S, Yamakido M.

Ichiyokai Harada Hospital, Japan.

We report the first case of myeloperoxidase-specific anti-neutrophil cytoplasmic 
autoantibody (MPO-ANCA)-associated glomerulonephritis in a patient with CREST
syndrome. A 74-year-old Japanese man with CREST syndrome (calcinosis, Raynaud's
phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia) developed 
rapidly progressive renal failure without elevation of blood pressure. Renal
biopsy revealed glomerular sclerosis and fibrous crescents. The MPO-ANCA titer
was elevated to 145 EU/ml. When patients with collagen diseases develop rapidly
progressive glomerulonephritis, the possibility of MPO-ANCA-associated
glomerulonephritis should be kept in mind.

Publication Types: 
    Case Reports

PMID: 10809419 [PubMed - indexed for MEDLINE]

328: Cochrane Database Syst Rev. 2000;(2):CD000956.

Prazosin for Raynaud's phenomenon in progressive systemic sclerosis.

Pope J, Fenlon D, Thompson A, Shea B, Furst D, Wells G, Silman A.

Medicine (Division of Rheumatology), University of Western Ontario, LHSC-South
Campus, 375 South Street Room 309;Colborne Bldg., London, Ontario, Canada, N6A
4G5. jpope@julian.uwo.ca

OBJECTIVES: To determine the effects and toxicity of prazosin versus placebo
proposed for the treatment of Raynaud's phenomenon (RP) in scleroderma. SEARCH
STRATEGY: We searched the Cochrane Controlled Trials Register, and Medline up to 
December 1996 using the Cochrane Collaboration search strategy developed by
Dickersin et al.(1994). Key words included: Raynaud's or vasospasm, scleroderma
or progressive systemic sclerosis or connective tissue disease or autoimmune
disease. Current Contents were searched up to and including April 7, 1997. All
bibliographies of articles retrieved were searched and key experts in the area
were contacted for additional and unpublished data. The initial search strategy
included all languages. SELECTION CRITERIA: Randomized controlled trials
comparing prazosin versus placebo were eligible if they reported clinical
outcomes from the start of therapy. Trials with a greater than 35% dropout were
excluded. Trials were included if patients with diffuse or limited scleroderma
were the subjects. If patients with other connective tissue diseases or primary
Raynaud's were included, the trial was used if the data on the scleroderma
patients could be extracted from the paper. DATA COLLECTION AND ANALYSIS: All
data were abstracted by two independent and trained reviewers (DF, AT), and
verified by a third reviewer (JP). Each trial was assessed independently by the
same two reviewers for its quality using a validated quality assessment tool
(Jadad 1996). Peto's odds ratios were calculated for all dichotomous outcomes and
a weighted mean difference was carried out on all continuous outcomes. Fixed
effects and random effects model were used if the data was homogeneous or
heterogeneous, respectively. MAIN RESULTS: Two trials with a total of 40 patients
were included. Prazosin has been found in two randomized controlled cross-over
trials to be more effective than placebo in the treatment of Raynaud's secondary 
to scleroderma. However, the positive response is modest and side effects are not
rare in those taking prazosin. REVIEWER'S CONCLUSIONS: Prazosin is modestly
effective in the treatment of Raynaud's phenomenon secondary to scleroderma.

Publication Types: 
    Review

PMID: 10796398 [PubMed - indexed for MEDLINE]

329: Cochrane Database Syst Rev. 2000;(2):CD000955.

Cyclofenil for Raynaud's phenomenon in progressive systemic sclerosis.

Pope J, Fenlon D, Thompson A, Shea B, Furst D, Wells G, Silman A.

Medicine (Division of Rheumatology), University of Western Ontario, LHSC-South
Campus, 375 South Street Room 309;Colborne Bldg., London, Ontario, Canada, N6A
4G5. jpope@julian.uwo.ca

OBJECTIVES: To assess the effects and toxicity of Cyclofenil versus placebo for
the treatment of Raynaud's phenomenon (RP) in scleroderma. SEARCH STRATEGY: We
searched the Cochrane Controlled Trials Register, and Medline up to 1996 using
the Cochrane Collaboration search strategy developed by Dickersin et al.(1994).
Key words included: Raynaud's or Vasospasm, Scleroderma or Progressive Systematic
Sclerosis or Connective Tissue Disease or Autoimmune Disease. Current Contents
were searched up to and including April 7, 1997. All bibliographies of articles
retrieved were searched and key experts in the area were contacted for additional
and unpublished data. The initial search strategy included all languages.
SELECTION CRITERIA: All randomized trials comparing cyclofenil versus placebo
were eligible if they reported any clinical outcomes within the trial. DATA
COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers (DF,
AT). Peto's odds ratio (OR) was calculated for all dichotomous outcomes, and a
weighted mean difference was calculated for all continuous outcomes. A fixed
effects or random effects model was used if the data were homogeneous or
heterogeneous respectively. MAIN RESULTS: One trial with 38 patients was
included. There was a trend for Cyclofenil to demonstrate more improvement and
more dropouts compared to placebo, but there were no statistically significant
differences. REVIEWER'S CONCLUSIONS: Cyclofenil is not effective in the treatment
of Raynaud's phenomenon secondary to scleroderma.

Publication Types: 
    Review

PMID: 10796397 [PubMed - indexed for MEDLINE]

330: Cochrane Database Syst Rev. 2000;(2):CD000954.

Ketanserin for Raynaud's phenomenon in progressive systemic sclerosis.

Pope J, Fenlon D, Thompson A, Shea B, Furst D, Wells G, Silman A.

Medicine (Division of Rheumatology), University of Western Ontario, LHSC-South
Campus, 375 South Street Room 309;Colborne Bldg., London, Ontario, Canada, N6A
4G5. jpope@julian.uwo.ca

OBJECTIVES: To assess the effects and toxicity of the following agent: ketanserin
versus placebo proposed for the treatment of Raynaud's phenomenon (RP) in
scleroderma. SEARCH STRATEGY: We searched the Cochrane Controlled Trials
Register, and Medline up to 1996 using the Cochrane Collaboration search strategy
developed by Dickersin et al.(1994). Key words included: Raynaud's or vasospasm, 
scleroderma or progressive systematic sclerosis or connective tissue disease or
autoimmune disease. Current Contents were searched up to and including April 7,
1997. All bibliographies of articles retrieved were searched and key experts in
the area were contacted for additional and unpublished data. The initial search
strategy included all languages. SELECTION CRITERIA: All randomized controlled
trials comparing ketanserin versus placebo were eligible if they reported
clinical outcomes of interest. Trials with dropout rates greater than 35% were
excluded. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two
reviewers (DF, AT). Peto's odds ratios (OR) were calculated for all dichotomous
outcomes, and a weighted mean difference (WMD) was carried out on all continuous 
outcomes. A fixed effects or random effects model were used if the data was
homogeneous or heterogeneous, respectively. MAIN RESULTS: Three trials and 66
patients were included. The proportion improved was significantly better in the
group on ketanserin with an odds ratio (OR) of 4.80 (95% CI 1.33, 17.37).
However, when comparing ketanserin to placebo, the decrease in severity of RP
attacks favoured placebo but this was not statistically significant. Side effects
were significantly more common in the group using active treatment with an OR of 
5.96 (95% CI 1.61, 22.06). Frequency of attacks did not change, but the duration 
of attacks decreased significantly in the ketanserin group. REVIEWER'S
CONCLUSIONS: Ketanserin may have some efficacy in the treatment of Raynaud's
phenomenon secondary to scleroderma. Overall, ketanserin is not significantly
different from placebo for the treatment of Raynaud's phenomenon except for some 
decrease in the duration of attacks and more subjects improved on ketanserin
compared to placebo. However, there were more side effects. It can be concluded
that ketanserin treatment in Raynaud's phenomenon secondary to scleroderma is not
clinically beneficial.

Publication Types: 
    Review

PMID: 10796396 [PubMed - indexed for MEDLINE]

331: Cochrane Database Syst Rev. 2000;(2):CD000953.

Iloprost and cisaprost for Raynaud's phenomenon in progressive systemic
sclerosis.

Pope J, Fenlon D, Thompson A, Shea B, Furst D, Wells G, Silman A.

Medicine (Division of Rheumatology), University of Western Ontario, LHSC-South
Campus, 375 South Street Room 309;Colborne Bldg., London, Ontario, Canada, N6A
4G5. jpope@julian.uwo.ca

OBJECTIVES: To assess the effects and toxicity of the following
agents:Prostaglandin analogues together with other agents proposed for the
treatment of Raynaud's phenomenom (RP) in scleroderma. SEARCH STRATEGY: We
searched the Cochrane Controlled Trials Register, and Medline up to 1996 using
the Cochrane Collaboration search strategy developed by Dickersin et al.(1994).
Key words included: raynaud's or vasospasm, scleroderma or progressive systemic
sclerosis or connective tissue disease or autoimmune disease. Current Contents
were searched up to and including April 7, 1997. All bibliographies of articles
retrieved were searched and key experts in the area were contacted for additional
and unpublished data. The initial search strategy included all languages.
SELECTION CRITERIA: All randomized controlled trials comparing prostaglandin
analogues versus placebo were eligible if they reported clinical outcomes within 
the start of therapy, and if the dropout rate was less than 35%. DATA COLLECTION 
AND ANALYSIS: Data were abstracted independently by two reviewers (DF, AT).
Peto's odds ratios were calculated for all dichotomous outcomes and a weighted
mean difference was calculated for all continuous outcomes. A fixed effects or
random effects model was used if the data were homogeneous or heterogeneous,
respectively. MAIN RESULTS: Seven randomized trials and 332 patients were
included. Five of the seven trials were of parallel design. Five trials compared 
I.V. Iloprost and one trial studied p.o. Iloprost and another p.o. Cisaprost.
Some trials were dose finding trials so various doses of Iloprost were used. Due 
to different efficacies of I.V. Iloprost, oral Iloprost and oral Cisaprost, the
overall efficacy of these drugs was somewhat diluted. Intravenous Iloprost
appears to be effective in the treatment of secondary Raynaud's phenomenon.
REVIEWER'S CONCLUSIONS: Intravenous Iloprost is effective in the treatment of
Raynaud's phenomenon secondary to scleroderma at decreasing the frequency and
severity of attacks and preventing or healing digital ulcers. The effect seems to
be prolonged after the intravenous infusion is given. Oral Iloprost may have less
efficacy than intravenous Iloprost. However, Cisaprost has minimal or no efficacy
when given orally for the treatment of Raynaud's phenomenon secondary to
scleroderma.

Publication Types: 
    Review

PMID: 10796395 [PubMed - indexed for MEDLINE]

332: Arch Intern Med. 2000 Apr 24;160(8):1101-8.

Comparison of sustained-release nifedipine and temperature biofeedback for
treatment of primary Raynaud phenomenon. Results from a randomized clinical trial
with 1-year follow-up.

[No authors listed]

BACKGROUND: The efficacy and safety of sustained-release nifedipine for the
treatment of primary Raynaud phenomenon (RP) has not previously been demonstrated
by a randomized, controlled trial. Temperature biofeedback has been studied in
patients with primary RP but not in a large multicenter controlled trial or
compared with nifedipine therapy. OBJECTIVE: To evaluate and compare the
effectiveness of sustained-release nifedipine and temperature biofeedback for the
treatment of primary RP. PARTICIPANTS AND METHODS: This is a randomized,
controlled clinical trial, double-masked for drug and placebo but not masked for 
temperature and control biofeedback. It included 313 persons with primary RP as
defined by medical history, physical examination findings, normal nailfold
capillaries, and a history of 2 or more attacks per day during the previous cold 
season. Participants were randomized to 1 of 4 treatment groups: (1)
sustained-release nifedipine, (2) pill placebo, (3) temperature biofeedback, or
(4) control (electromyographic) biofeedback. The primary outcome measure was
self-reported, color chart-verified RP attacks during 1 winter month
approximately 1 year after initiation of treatment. Secondary outcome measures
included verified attacks at 2 months, all attacks at 2 months and 1 year, and
quality of life. RESULTS: Nifedipine-treated participants showed a 66% reduction 
in verified attacks compared with placebo recipients (P<.001); temperature
biofeedback training did not reduce attacks significantly compared with control
biofeedback (P = .37). Comparison of nifedipine and temperature biofeedback
treatments favored nifedipine use (P = .08); similar results were obtained for
the secondary end points. Adverse effects resulted in discontinuation of
nifedipine treatment in 15% of participants. CONCLUSIONS: Temperature biofeedback
is not better than its control treatment and is inferior to sustained-release
nifedipine for treating primary RP, whereas sustained-release nifedipine is a
safe and effective treatment for this disease.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 10789602 [PubMed - indexed for MEDLINE]

333: Int Arch Occup Environ Health. 2000 Apr;73(3):150-5.

Pathophysiology and classification of the vibration white finger.

Noël B.

Service de Dermatologie, Centre Hospitalier Universitaire Vaudois, Lausanne,
Switzerland. bernard.noel@chuv.hospvd.ch

Skin, arteries and nerves of the upper extremities can be affected by vibration
exposure. Recent advances in skin and vascular biology as well as new
investigative methods, have shown that neurovascular symptoms may be due to
different vascular and neurological disorders which should be differentiated if
proper management is to be evaluated. Three types of vascular disorder can be
observed in the vibration white finger: digital organic microangiopathy, a
digital vasospastic phenomenon and arterial thrombosis in the upper extremities. 
An imbalance between endothelin-1 and calcitonin-gene-related peptide is probably
responsible for the vasospastic phenomenon. Moreover, paresthesiae can be due to 
either a diffuse vibration neuropathy or a carpal tunnel syndrome. A precise
diagnosis is then necessary to adapt the treatment to individual cases. A
classification describing the type and severity of the vascular lesions is
presented. Asymptomatic lesions are included for adequate epidemiological studies
and risk assessment of vibrating tools. Monitoring of vibration exposed workers
should include not only a questionnaire about symptoms, but also a clinical
evaluation including diagnostic tests for the screening of early asymptomatic
neurovascular injuries.

Publication Types: 
    Review

PMID: 10787129 [PubMed - indexed for MEDLINE]

334: Jpn Circ J. 2000 Apr;64(4):239-42.

Prevalence of migraine and Raynaud's phenomenon in Japanese patients with
vasospastic angina.

Nakamura Y, Shinozaki N, Hirasawa M, Kato R, Shiraishi K, Kida H, Usuda K,
Ishikawa T.

Department of Cardiology, Kanazawa National Hospital, Japan. nakay@po.incl.ne.jp

The prevalence of migraine and Raynaud's phenomenon in Japanese patients with
vasospastic angina (group I) were compared with those in 2 control groups: one
with effort angina (group II) and the other group without known ischemic heart
disease (group III). There were no significant differences among the 3 groups
with respect to age and sex. The prevalence of migraine in group I was 23 of 100,
as compared with 4 of 100 in group II (p<0.01) and 11 of 100 in group III
(p<0.05). The prevalence of Raynaud's phenomenon in group I was 9 of 100, as
compared with 3 of 100 in group II and 4 of 100 in group III. Thus, in Japan, the
prevalence of migraine in patients with vasospastic angina was higher than those 
in the 2 control groups, whereas the prevalence of Raynaud's phenomenon did not
differ significantly among the 3 groups. The prevalence of Raynaud's phenomenon
in Japanese patients with vasospastic angina was different from that reported
from North America, although the prevalence of migraine was the same. This may be
partially explained by racial differences.

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

PMID: 10783043 [PubMed - indexed for MEDLINE]

335: J Am Acad Dermatol. 2000 May;42(5 Pt 1):787-90.

Quantitative nailfold capillary microscopy findings in patients with acrocyanosis
compared with patients having systemic sclerosis and control subjects.

Monticone G, Colonna L, Palermi G, Bono R, Puddu P.

Dipartimento di Immunodermatologia, Istituto Dermopatico dell'Immacolata I.D.I., 
IRCCS, Rome, Italy.

BACKGROUND: The morphologic capillary microscopy (capillaroscopy) pattern of
acrocyanosis is characterized by hemorrhages, pericapillary edema, and widened
capillaries. These findings can result in a difficult differential diagnosis with
systemic sclerosis (SSc). OBJECTIVE: We sought to quantify the characteristics of
the capillaroscopy pattern that distinguishes patients with acrocyanosis from
patients with SSc and control subjects. METHODS: A videomicroscope with
fiberoptic illumination and personal computer-based image processing was used to 
measure capillary density, giant capillaries, loop width, and arterial and venous
limbs in 10 patients with acrocyanosis, 10 patients with SSc, and 10 healthy
control subjects. RESULTS: Acrocyanotic patients differed in every quantitative
parameter both from control subjects and patients with SSc. In particular,
capillary density, which was reduced compared with that of control subjects, was 
much higher than that of patients with SSc: one giant capillary per finger was
observed in 2 patients with acrocyanosis, whereas more than 2 giant capillaries
per finger were observed in each patient with SSc. CONCLUSION: These differences 
may aid in making the distinction between the capillaroscopy patterns in
acrocyanosis and SSc.

Publication Types: 
    Comparative Study

PMID: 10775855 [PubMed - indexed for MEDLINE]

336: Occup Environ Med. 2000 May;57(5):341-7.

Vibration exposure, smoking, and vascular dysfunction.

Cherniack M, Clive J, Seidner A.

Department of Medicine, Division of Occupational and Environmental Medicine,
University of Connecticut Health Center, 263 Farmington Avenue-MC6210,
Farmington, Connecticut 06030-6210, USA.

OBJECTIVES: Vibration white finger (VWF), also known as "occupational Raynaud's
phenomenon", is marked by arterial hyperresponsiveness and vasoconstriction
during cold stimulation. The impact of tobacco use, and by extension stopping
smoking, on the long term course of the disease has been inconclusively
characterised. The objectives of this study included assessment of the impact of 
tobacco use on symptoms and on objective tests in shipyard workers exposed to
vibration, and in gauging the natural history of the disorder after stopping
exposure and changing smoking patterns. METHODS: In a cross sectional
investigation, 601 current and former users of pneumatic tools were evaluated
subjectively for cold related vascular symptoms, and tested by cold challenge
plethysmography. There was follow up and subsequent testing of 199 members of the
severely effected subgroup of smokers and non-smokers, many of whom had stopped
smoking in the interval between tests. Effects of smoking and stopping smoking on
symptoms and plethsymographic results were assessed. RESULTS: Symptoms and
measured abnormal vascular responses related to cold were more severe in smokers 
than in non-smokers. Follow up of 199 severely effected members of the cohort,
all removed from exposure for 2 years, indicated that smokers were almost twice
as likely to have more severe vasospasm (test finger/control finger systolic
blood pressure% (FSBP%) <30) than were non-smokers (-32.2% v 17.4%). 53 Subjects 
who stopped smoking during the interval between tests improved, and were
indistinguishable from non-smokers similarly exposed to vibration. Additional
physiological benefits of stopping smoking were still apparent at further follow 
up examination, 1 year later. Improvements evident on plethysmography were not
accompanied by improvements in symptoms, which were unaffected by smoking.
CONCLUSIONS: Smoking seems to delay physiological improvement in response to cold
challenge in workers with VWF, after the end of exposure to vibration. Symptoms
were less likely to improve over time than digital blood pressure, and were less 
affected by smoking.

PMID: 10769300 [PubMed - indexed for MEDLINE]

337: Arch Phys Med Rehabil. 2000 Apr;81(4):495-9.

Thermographic parameters in the diagnosis of secondary Raynaud's phenomenon.

Schuhfried O, Vacariu G, Lang T, Korpan M, Kiener HP, Fialka-Moser V.

Department of Physical Medicine and Rehabilitation, University of Vienna,
Austria.

OBJECTIVE: To determine the major infrared thermographic parameters in
discriminating between patients with and without secondary Raynaud's phenomenon. 
DESIGN: A cross-sectional study. SETTING: Outpatient clinic of a university
department of physical medicine and rehabilitation in Vienna. PATIENTS:
Consecutive sample of 86 patients (72 women, 14 men) referred from the Division
of Rheumatology for the clarification of a possible secondary Raynaud's
phenomenon. MAIN OUTCOME MEASURES: According to color changes induced by cold
exposure, clinical classification of Raynaud's phenomenon was performed as
follows: no, unlikely, probable, and definite Raynaud's phenomenon. The following
thermographic parameters were applied to a stepwise logistic regression analysis:
the absolute temperature of the fingertips before, 10, and 20 minutes after cold 
challenge (Tpre, T10, T20); the longitudinal temperature difference before, 10,
and 20 minutes after cold challenge (LTDpre, LTD10, LTD20); the mean area under
the rewarming curve of the fingertips; the recovery index 20 minutes after cold
challenge (RI20); and the most rapid phase of rewarming of the fingertips of both
hands (Gmax right, Gmax left). The sensitivity of thermographic classification
into the 4 groups of clinical evaluation was assessed by discriminant analysis
using significant parameters from logistic regression analysis. RESULTS: Only
LTDpre reached the level of significance (p < .0001). Using LTDpre, 22 of 23
subjects without clinical Raynaud's phenomenon and 20 of 26 patients with
definite clinical Raynaud's phenomenon were classified correctly. Patients with
unlikely or probable Raynaud's phenomenon were classified as no Raynaud's
phenomenon or definite Raynaud's phenomenon. CONCLUSION: LTDpre is the major
thermographic parameter to discriminate between patients with and without
definite Raynaud's phenomenon by clinical history.

PMID: 10768542 [PubMed - indexed for MEDLINE]

338: J Autoimmun. 2000 May;14(3):267-74.

Kinetics of anti-fibrillin-1 autoantibodies in MCTD and CREST syndrome.

Lundberg I, Antohi S, Takeuki K, Arnett F, Steiner G, Brumeanu TD, Klareskog L,
Bona C.

Department of Rheumatology, Karolinska Hospital, Stockholm, Sweden.

Using a highly sensitive Radioimmunoassay (RIA), the kinetics of synthesis of
anti-fibrillin (Fbn-1) autoantibodies were studied in 17 patients with mixed
connective tissue disease (MCTD) and two with CREST syndrome calcinosis,
Raynaud's oesophageal dismotility, sclerodectyly and teleangiectasis who were
found to be positive for this autoimmune response. IgG autoantibodies specific
for recombinant Fbn-1 (rFbn-1) (aa 369-425) were found in all patients excepting 
one with MCTD, multiple sclerosis, and dermatomyositis. IgM were found in fewer
cases. Several kinetics patterns of anti-Fbn-1 autoantibodies were observed: a)
long lasting persistence of IgG and IgM autoantibodies up to 14 years; b)
fluctuation of antibodies during various periods up to 16 years; c) disappearance
of antibody response after several years, and d) patients producing IgG but not
IgM autoantibodies. No differences in the synthesis of autoantibodies were
observed between MCTD patients with a stable disease, and those developing during
the course features of systemic sclerosis (SSc), Sjogren's syndrome, or
rheumatoid-like arthritis. In one patient displaying a lupus-like syndrome for 3 
years, the appearance of anti-Fbn-1 autoantibodies coincided with the occurrence 
of MCTD and scleroderma. While the detection of anti-Fbn-1 autoantibodies may be 
clinically useful in differential diagnosis or eventual prognosis of patients
with connective tissue diseases, their role in the pathogenesis of scleroderma
syndromes requires further investigation. Copyright 2000 Academic Press.

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

PMID: 10756089 [PubMed - indexed for MEDLINE]

339: Respirology. 2000 Mar;5(1):27-32.

Suppressive effect of saprogrelate hydrochloride on Raynaud's phenomenon and
respiratory failure in patients with systemic sclerosis.

Kato S, Kishiro I, Ohnuma N, Takasaki K, Okamoto S, Nakamoto A, Kaneko N,
Kumamoto H.

First Department of Internal Medicine, Dokkyo University School of Medicine
Tochigi, Japan.

OBJECTIVE: In seven patients with systemic sclerosis (SS), we evaluated the
clinical effectiveness of oral administration of saprogrelate hydrochloride (SH: 
300 mg/day) for 2 months on Raynaud's phenomenon (RP) and respiratory failure
estimated by Hugh-Jones classification. METHODOLOGY: We evaluated laboratory data
(arterial blood gas (pH, PaO2 and PaCO2), pulmonary function tests (%VC, FEV1/FVC
and %DL(CO)), mean pulmonary arterial pressure (mPAP), white blood cell count,
C-reactive protein and the plasma levels of fibrinopeptide A (FPA),
beta-thrombogloblin (beta-TG), platelet factor 4 (PF4) and thrombomodulin (TM))
before and after SH administration. RESULTS: The frequency and duration of RP, as
well as the coldness, numbness and pain of RP were significantly decreased after 
SH administration (P < 0.05, P < 0.01 and P < 0.001). Respiratory failure
estimated by Hugh-Jones classification was also significantly decreased after SH 
administration (P < 0.05), and the %DL(CO) was significantly increased (P <
0.01). The mPAP decreased significantly after SH administration (P < 0.05).
Plasma FPA, beta-TG and PF4 significantly decreased after administration (P <
0.05 and P < 0.01). CONCLUSIONS: SH therapy could prevent RP and respiratory
failure in patients with SS.

Publication Types: 
    Clinical Trial

PMID: 10728728 [PubMed - indexed for MEDLINE]

340: Clin Infect Dis. 2000 Mar;30(3):500-3.

Raynaud's phenomenon as a manifestation of parvovirus B19 infection: case reports
and review of parvovirus B19 rheumatic and vasculitic syndromes.

Harel L, Straussberg R, Rudich H, Cohen AH, Amir J.

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petah 
Tiqva 49 202, Israel. gvharel@netvision.net.il

Infection with human parvovirus B19 is manifested as erythema infectiosum,
transient aplastic crisis, or hydrops fetalis. Rheumatic manifestations include
arthropathy and various vasculitic syndromes. Isolated Raynaud's phenomenon due
to parvovirus B19 has never been described. We report on 2 previously healthy
sisters with new-onset Raynaud's phenomenon accompanied by severe generalized
polyarthralgia. A full workup was negative, except serology for parvovirus B19,
which was positive. All symptoms gradually subsided within 3-5 months, and no
recurrence has been noted during the 3 years since onset. We review all the
studies in the English-language literature on parvovirus B19-induced rheumatic
and vasculitic syndromes. We hypothesize that the pathogenesis of Raynaud's
phenomenon in our patients involved immune-mediated endothelial damage leading to
platelet activation and vasoconstriction. We recommend that in cases of
unexplained Raynaud's phenomenon, serology for parvovirus B19 be included in the 
evaluation.

Publication Types: 
    Case Reports
    Review

PMID: 10722434 [PubMed - indexed for MEDLINE]

341: Appl Occup Environ Hyg. 2000 Mar;15(3):291-302.

Review of occupational standards and guidelines for hand-arm (segmental)
vibration syndrome (HAVS).

Pelmear PL, Leong D.

St. Michael's Hospital, Toronto, Ontario.

This article reviews the health effects, treatment, prevention strategies, and
international standards for hand-arm vibration syndrome (HAVS). It draws
attention to the proposed International Standards Organization (ISO) 1998
revision requirement to base the assessment of vibration on the
root-sum-of-squares for all directions rather than the dominant direction; the
European Economic Commission (EEC) directives with their threshold, action, and
ceiling levels; and the intent of the EEC, United Kingdom, and Japanese
jurisdictions to propose action levels to prevent the incidence of
vibration-induced Raynaud's phenomenon (VWF) from exceeding the background level 
in their countries. Proposals for the revision of the American Conference of
Governmental Industrial Hygienists (ACGIH) Threshold Limit Values (TLVs) are
presented.

Publication Types: 
    Review

PMID: 10701292 [PubMed - indexed for MEDLINE]

342: Ann Rheum Dis. 2000 Mar;59(3):206-10.

Prevalence of Raynaud's phenomenon in a healthy Greek population.

Voulgari PV, Alamanos Y, Papazisi D, Christou K, Papanikolaou C, Drosos AA.

Department of Internal Medicine, Medical School, University of Ioannina, 451 10
Ioannina, Greece.

OBJECTIVE: Raynaud's phenomenon (RP) is comprised of repeated episodes of colour 
changes of the skin of digits on cold exposure or emotional stress. The
prevalence of RP in the general population is variable fluctuating between
4%-15%, among surveys. The aim of this study was to estimate the prevalence of RP
in a healthy working Greek population and to investigate the possible association
of RP with various demographic, social and other factors. METHODS: A total of 756
employees of the University Hospital of Ioannina was included in the study. They 
belong to the administrative (120 subjects), nursing and technical (a
representative sample of 418 and 218 subjects, respectively) personnel. Five
hundred subjects (111 men and 389 women) responded in a face to face interview
based on a specially conformed questionnaire. The study began in November 1997
and was completed in March 1998. RESULTS: Twenty six subjects with RP (1 man and 
25 women) were found. Their mean (SD) age was 32.73 (5.77) years. The prevalence 
of RP was 5.2% (0.9% in men and 6.4% in women). The sex ratio, male/female, was
1/7.1. An association between RP and migraine was found. However, there were no
significant correlations of RP with smoking, alcohol and coffee consumption,
dietary habits, occupational history and drug exposure. No social or other
demographic parameters associated to RP frequency were found. CONCLUSIONS: The
prevalence of RP (5.2%) in the population studied is relatively low compared with
previous studies. RP focuses on the fourth decade of life and affects mainly
women. There was no evidence of any correlation of RP with social, environmental 
or personal parameters while an association of RP with migraine was found.
Geographical or genetic factors, or both, may be responsible for these results.

PMID: 10700429 [PubMed - indexed for MEDLINE]

343: Eur J Dermatol. 2000 Jan-Feb;10(1):55-8.

Raynaud's phenomenon possibly induced by a compund drug of tegafur and uracil.

Seishima M, Izumi T, Kanoh H.

Department of Dermatology, Ogaki Municipal Hospital, Minaminokawa-cho 4-86, Ogaki
City, 503-8502, Japan. seimarik@gumail.cc.gifu-u.ac.jp.

We describe a 50-year-old woman who noted acral hyperpigmentation, sclerodactyly 
and Raynaud's phenomenon with 1:160 of antinuclear antibody titer after treatment
with a compound drug with tegafur and uracil. Histological findings of the finger
and palm included hyperkeratosis, vacuolar degeneration of basal cells, thickened
collagen fibers in the dermis, and dilatation of capillary vessels, perivascular 
mononuclear cell infiltration and melanophages in the upper dermis. IgG, IgA,
IgM, C3 and C1q were not deposited in the skin by direct immunofluorescence
study. After cessation of the drug, Raynaud's phenomenon and hyperpigmentation
disappeared within 1 month and 4 months, respectively, and antinuclear antibody
turned negative within 4 months. These observations suggest that tegafur may have
caused not only hyperpigmentation in the palms and soles, but also sclerodactyly 
and Raynaud's phenomenon in the present case.

Publication Types: 
    Case Reports

PMID: 10694301 [PubMed - indexed for MEDLINE]
