An imbalance in plasma prostanoids in patients with Raynaud's phenomenon and pulmonary vasospasm.
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Raynaud's phenomenon has been suggested as a predisposing factor for pulmonary vasospasm which may lead to pulmonary hypertension, but the occurrence of cold stimulus-induced pulmonary vasospasm has been inconsistent. Such inconsistent pulmonary vascular responses may be caused by differences in the production of endogenous vasodilators and vasoconstrictors among patients. Fourteen patients with Raynaud's phenomenon associated with mixed connective tissue disease (n=10) or systemic sclerosis (n=4) participated in the study. Right heart catheterization was performed before and after a cold pressor test, immersing a hand in cold water (15 degrees C) for 5 min. Plasma levels of 6-keto prostaglandin (PG)F1alpha, thromboxane (TX)B2 and endothelin (ET)-1 in the mixed venous blood were measured. Mean pulmonary artery pressure increased after the cold pressor test in five of 14 patients, and the patients were divided into those with pulmonary vasospasm (responders) and those without vasospasm (nonresponders). After the cold pressor test, levels of 6-keto PGF1alpha increased significantly in nonresponders (p<0.01) and decreased significantly in responders (p<0.05). The ratios of 6-keto PGF1alpha to TXB2 significantly increased in nonresponders (p<0.01) but not in responders and the difference between responders and nonresponders after the cold pressor test was also statistically significant (p<0.05). No significant change in plasma ET-1 levels occurred in either responders or nonresponders. The results suggest that an impaired production of prostaglandin I2 and an imbalance between prostaglandin I2 and thromboxane A2 are associated with the occurrence of pulmonary vasospasm induced by Raynaud's phenomenon. (+info)
Quantitation of microcirculatory abnormalities in patients with primary Raynaud's phenomenon and systemic sclerosis by video capillaroscopy.
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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. (+info)
Prevalence of Raynaud's phenomenon in Great Britain and its relation to hand transmitted vibration: a national postal survey.
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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. (+info)
A two-stage, genome-wide screen for susceptibility loci in primary Raynaud's phenomenon.
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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. (+info)
Raynaud's phenomenon in idiopathic carpal tunnel syndrome: postoperative alteration in its prevalence.
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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. (+info)
Hereditary deficiency of the seventh component of complement.
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Deficiency of the seventh component of complement has been found in the serum of a 42-yr-old Caucasian woman who has Raynaud's phenomenon, sclerodactyly, and telangiectasia. Partial deficiency was found in the serum of the patient's parents and children, indicating a pattern of inheritance of autosomal codominance. Transfusion experiments indicated that exogenous C7 had a 91-h halk-life in the patient. There was no evidence for C7 synthesis after transfusion. No C7 inhibitors were detected in the patient's serum. The patient's serum was found to support the activation of complement by both the classical and properdin pathways to the C7 stage. The addition of C7 to the patient's serum permitted it to support hemolytic reactions initiated by either pathway. No defects could be detected in plasma or whole blood coagulation. The patient's serum was deficient in opsonizing unsensitized yeast particles in serum and in the generation of chemotactic factor by antigen-antibody complexes and endotoxin. Both deficiencies were corrected by the addition of C7. These observations suggest a key role for C7 for in vitro yeast phagocytosis and chemotaxis generation. However, the patient's lack of infections indicates a relatively minor role for C7 in human resistance to infection. (+info)
Effect of SR 49059, a V1a vasopressin receptor antagonist, in Raynaud's phenomenon.
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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. (+info)
Digital vascular responses and serum endothelin-1 concentrations in primary and secondary Raynaud's phenomenon.
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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. (+info)