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Biomedical subjects

F M Wigley

Publications and source records attributed to F M Wigley.

At least 55 records · Page 3Linked to original sources
PubMed1995

Acute effect of topical minoxidil on digital blood flow in patients with Raynaud's phenomenon.

OBJECTIVE: Raynaud's phenomenon is a relatively common disorder for which highly effective, well tolerated treatment has yet to be developed. Minoxidil, a potent vasodilator which, on a single application to the scalp causes significant local cutaneous vasodilation, was selected for study in primary Raynaud's phenomenon. METHODS: Ten subjects were enrolled in a randomized double blind, placebo controlled acute challenge crossover trial. Single applications of topical minoxidil 5% solution and placebo were made to each subject's fingers on 2 separate occasions, and measures of digital skin temperature, systolic blood pressure, and laser Doppler flow were obtained, before and after acute cold challenge. RESULTS: Digital skin temperature, systolic blood pressure, and laser Doppler flow both before and after cold challenge were not improved by pretreatment with topical minoxidil 5% solution. CONCLUSION: In individuals with primary Raynaud's phenomenon, a single application of minoxidil 5% solution to the fingers is not effective in improving baseline digital blood flow or cold tolerance.

Administration, Cutaneous↗
PubMed1994

Expansion of selected V delta 1+ gamma delta T cells in systemic sclerosis patients.

We have previously shown an increased percentage of gamma delta T cells expressing the TCR V delta 1 gene segment in the peripheral blood and bronchoalveolar lavage fluid of patients with systemic sclerosis (SSC). To estimate clonality of these V delta 1+ T cells, the diversity of V delta 1 junctional regions (V-D-J) was examined using a reverse transcriptase-PCR to amplify TCR delta-chain transcripts isolated from PBMC, lung, esophagus, stomach, or skin of patients and controls. Limited diversity of V delta 1-J delta junctional regions in SSC patients was demonstrated by comparing the size distribution of PCR-amplified junctional region cDNA from patients with that of controls. Sequence analyses confirmed that V delta 1-J delta junctional regions from the blood of SSc patients had less diversity than those from controls, in that a significantly higher proportion of sequences were repeated in patients (54.4 vs 19.4% in controls). Evidence for selection of the V delta 1+ T cells in the tissues of SSC patients came from the findings that the same V delta 1-J delta junctional sequences persisted in an individual patient over time and that identical junctional sequences were isolated from multiple sites. Analysis of deduced amino acid sequences revealed two clusters of similarities among the junctional regions from patients. These data suggest that expansion of V delta 1+ gamma delta T cells may be Ag driven in SSC patients.

Adult↗
PubMed1994

Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study.

OBJECTIVE: To evaluate the efficacy and safety of iloprost, a prostacyclin analog, administered intravenously in patients with Raynaud phenomenon secondary to systemic sclerosis. DESIGN: Multicenter, randomized, parallel placebo-controlled, double-blind study. SETTING: University medical centers. PATIENTS: 131 patients with systemic sclerosis (101 women, 30 men) ages 20 to 79 years. INTERVENTION: Patients were randomly assigned to receive one of two parallel treatments of five daily sequential, 6-hour intravenous infusions of iloprost (0.5 to 2.0 ng/kg per min) or to receive a similar volume of placebo. MEASUREMENTS: Frequency of Raynaud attacks, Raynaud severity score, physician's overall rating of treatment effect, and digital cutaneous lesion healing. RESULTS: Of the 131 patients enrolled, 126 completed the 5-day infusion and 114 (87%) completed at least 6 weeks of follow-up. Sixty-four patients were randomly assigned to receive iloprost and 67 patients, to receive placebo. The mean weekly number of Raynaud attacks decreased 39.1% with iloprost and 22.2% with placebo (P = 0.005). In addition, the mean percentage of improvement in a global Raynaud severity score during the entire 9-week follow-up was greater in patients given iloprost (34.8%) than in those receiving placebo (19.7%) (P = 0.011). The physician's overall rating of treatment effect showed greater improvement with iloprost than with placebo at week 6 (52.4% compared with 27.4%; P = 0.008) and week 9 (60.9% compared with 26.9%; P < 0.001). At week 3, 14.6% more patients receiving iloprost had 50% or more lesions heal compared with those given placebo (95% CI, 0.9% to 30%). During the infusion, 59 (92%) of the patients receiving iloprost had one or more side effects compared with 38 (57%) of the patients receiving placebo. CONCLUSION: Iloprost is effective for the short-term palliation of severe Raynaud phenomenon in patients with systemic sclerosis.

Adult↗
PubMed1994

Clinical aspects of systemic and localized scleroderma.

Continued efforts are being made to better define the clinical course, disease subsets, and predictors of outcome in scleroderma. Data suggest that the course of the skin disease is triphasic, with the most active thickening phase in the first 12 months of disease. The presence of specific autoantibodies may predict clinical course more precisely than any clinical feature. Antipolymerase I, II, and III antibodies seem specific for scleroderma and, if present, may predict aggressive disease. Early detection of lung involvement provides an opportunity to select patients who may be responsive to drug treatment. Renal crisis in scleroderma is still important and may occur in the absence of significant signs of cutaneous fibrosis. Renin plasma levels do not appear helpful in predicting renal crisis. Significant gastrointestinal reflux disease with delayed acid clearance and esophagitis is associated with aperistalsis of the lower esophagus. Evidence for widespread structural and functional abnormalities of the microvascular circulation have been reemphasized. The psychosocial impact of scleroderma has been studied, demonstrating both the importance of depression and the need for social support. The etiology of localized scleroderma remains unknown despite efforts to link these lesions to Borrelia burgdorferi infection.

Autoantibodies↗
PubMed1994

Foot and ankle problems in rheumatoid arthritis.

The purpose of this study was to examine the prevalence of foot and ankle problems in 99 patients with clinically proven rheumatoid arthritis. Patients were recruited from outpatient rheumatology clinics; no attempt was made to select patients on the basis of the severity of their disease, duration of disease, or symptom constellation. Each patient was examined by an investigator utilizing a predesigned protocol to assess their functional status, functional capacity, and overall joint involvement. Ninety-three of 99 patients had complaints referable to the foot or ankle at some time since diagnosis of rheumatoid arthritis. Ankle problems were paramount in 42%, forefoot difficulties in 28%, and equal ankle and forefoot problems in another 14%. Only four patients had had any treatment involving foot orthotic devices or special shoe wear. The prevalence of foot and ankle symptoms was related to the duration of systemic illness, but was present in > 50% of patients at any time after diagnosis of rheumatoid arthritis. Patients with longstanding rheumatoid arthritis have a high prevalence of foot and ankle symptoms. Unlike previous reports, the present study found a high prevalence of ankle and hindfoot symptoms, as opposed to forefoot complaints. Despite this finding, the patients had been treated infrequently by either conservative nonoperative management directed at accommodating footwear or surgical intervention to favorably alter their foot and ankle mechanics.

Activities of Daily Living↗
PubMed1994

Comparison of aminobenzoate potassium and placebo in the treatment of scleroderma.

OBJECTIVE: To determine the safety and efficacy of aminobenzoate potassium (KPAB) in treating the skin manifestations of scleroderma. METHODS: Via a 48-week prospective, randomized, double blind, placebo controlled trial we compared the efficacy of KPAB 12 g/day with matching placebo. Outcome measures included skin mobility and thickening scores, patient and physician global assessments and, measurements of maximal oral aperture and hand range of motion. RESULTS: Of 146 patients who entered the study, 76 (52%) completed. Demographics of the study population included age 49 +/- 13 years, 83% women, mean (range) disease duration was 104 (7-600) months. There were no differences in the demographics of the KPAB vs placebo nor the group that completed the study compared with the withdrawal group. There were no clinical or statistically significant differences between the KPAB and the placebo treated groups in any of the outcome measures. Subgroup analyses of skin mobility and skin thickening based on age, extent of disease, severity of disease, duration of disease and involved vs uninvolved skin were performed, but no differences were noted. The overall compliance to the medical regimen was > or = 75% in 93% of patients completing the study. Eighteen patients in the KPAB group and 6 placebo patients withdrew due to adverse drug reactions (ADR). The most common withdrawals for ADR were gastrointestinal intolerance and headaches. All ADR resolved following withdrawal of medication. CONCLUSION: KPAB did not alter the skin changes of scleroderma in a group of patients with relatively longstanding stable disease. KPAB was reasonably well tolerated in this group of patients.

4-Aminobenzoic Acid↗
PubMed1993

Raynaud's phenomenon.

The classification of Raynaud's phenomenon has been complicated by various confusing labels, including Raynaud's disease and Raynaud's syndrome. To improve clarity and to allow for uniformity in reporting, most investigators agree that only the terms primary and secondary Raynaud's phenomenon should be used for patient classification. The prevalence of Raynaud's phenomenon seems to vary among different populations and different climates, suggesting genetic and environmental influences on its expression. The concept that Raynaud's phenomenon is the manifestation of a generalized vasospastic disorder has been addressed by studies of migraine headaches, variant angina, and the pulmonary vascular circulation. Current data suggest that the pathophysiology of Raynaud's phenomenon is complex and multifactorial, involving the endothelium, neuroreceptor expression, and locally produced mediators that affect vascular responses. New and old diagnostic tools used to measure digital circulation continue to be tested in an effort to define a better method of evaluating patients. Occupational causes of Raynaud's phenomenon continue to be an important health problem despite efforts to control vibratory tool usage. The role of beta-blockers in the induction of Raynaud's phenomenon has been questioned, but the use of chemotherapeutic agents is a definite risk factor. A new radical surgical approach for severe refractory Raynaud's phenomenon was described. Intravenous prostaglandins continue to appear helpful in the treatment of severe Raynaud's phenomenon, and oral prostaglandins are beginning to be studied.

Humans↗
PubMed1993

Reliability of grading scales for individual radiographic features of osteoarthritis of the knee. The Baltimore longitudinal study of aging atlas of knee osteoarthritis.

RATIONALE AND OBJECTIVES: The authors present an atlas of individual radiographic features of osteoarthritis of the knee and evaluate the inter- and intra-reader reliability of trained readers using this atlas. METHODS: Four trained readers graded 30 standing anterior-posterior knee radiographs for eight selected features of osteoarthritis (medial and lateral osteophytes, joint space narrowing, and sclerosis; osteophytes of the tibial spines and chondrocalcinosis) as well as the Kellgren-Lawrence global scale. Inter- and intra-reader reliability were calculated using intraclass correlation coefficients. RESULTS: For all features except sclerosis and osteophytes of the tibial spines, inter-reader reliability ranged from 0.63 to 0.83, whereas intra-reader reliability ranged from 0.82 to 0.95. CONCLUSION: Using this atlas, trained readers are reliable in measuring the presence and severity of individual radiographic features of osteoarthritis of the knee. This atlas should be useful in clinical and epidemiologic studies of osteoarthritis of the knee.

Adult↗
PubMed1992

Interleukin-1, interleukin-2, interleukin-4, interleukin-6, tumor necrosis factor alpha, and interferon-gamma levels in sera from patients with scleroderma.

OBJECTIVE: To determine whether interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-4, interferon-gamma (IFN gamma), IL-6, and tumor necrosis factor alpha (TNF alpha) are detected more frequently in sera from scleroderma patients than in sera from controls. METHODS: Serum concentrations of these cytokines were measured in 78 scleroderma patients and 73 controls, using enzyme-linked immunosorbent assay, radioimmunoassay, and bioassay techniques. RESULTS: IL-2, IL-4, and IL-6 were each detected more frequently in sera from scleroderma patients than in sera from controls. TNF alpha and IL-1 alpha were found with equal frequency in patient and control sera. IL-1 beta and IFN gamma were not detected in any sera. CONCLUSION: IL-2, IL-4, and IL-6 may be among the cytokines that contribute to the disease process in scleroderma patients. To our knowledge, this is the first report of elevated serum IL-4 levels in human disease.

Adolescent↗
PubMed1992

Anticentromere antibody as a predictor of digital ischemic loss in patients with systemic sclerosis.

OBJECTIVE: To determine the clinical and serologic risk factors for digital ischemic events in patients with systemic sclerosis (SSc). METHODS: Retrospective review of clinical and laboratory data and review of current clinical status of 98 patients with SSc, seen between 1985 and 1990. RESULTS: Amputation of 1 or more digits due to ischemia occurred in 20.4% of the patients; 9.2% had multiple digit loss. Sclerodactyly alone and anticentromere antibody (ACA) were associated with loss of 1 or more digits. Age, smoking status, duration of disease, or duration of Raynaud's phenomenon were not predictive for loss of digits. CONCLUSION: Patients with limited SSc who are positive for ACA have an increased risk of major peripheral vascular occlusive disease.

Adult↗
PubMed1992

Increase in translaryngeal resistance during phonation in rheumatoid arthritis.

Laryngeal involvement by RA is a common finding, but there have been no studies of laryngeal function in RA patients. This study was undertaken to determine if patients with rheumatoid arthritis have functional abnormalities of the upper airway during phonation which may be the result of synovitis of the laryngeal joints caused by RA. Translaryngeal resistance was measured in six patients with RA and six matched control subjects using an interrupter method to measure PSG and V during vocalization. Patients with RA had a higher R (65.0 +/- 8.15 cm H2O/L/s) than control subjects (38.4 +/- 7.43 cm H2O/L/s [p less than 0.05]). This was the consequence of lower V rates during phonation at similar PSG. We conclude that abnormalities of the larynx in RA patients are common and cause measurable physiologic abnormalities.

Adult↗
PubMed1992

Intravenous iloprost treatment of Raynaud's phenomenon and ischemic ulcers secondary to systemic sclerosis.

OBJECTIVE: We conducted this study to assess the clinical usefulness and physiologic effects of intravenous iloprost in patients with Raynaud's phenomenon secondary to systemic sclerosis. METHODS: Thirty-five patients with Raynaud's phenomenon secondary to systemic sclerosis, including 11 with digital ischemic ulcerations, were enrolled in a double blind placebo controlled parallel study in 2 centers. Following a 2 week washout, subjects received intravenous iloprost (0.5-2.0 ng/kg/min) or saline by continuous infusion for 6 h on 5 consecutive days. Clinical assessments, status of digital ulcers, measures of in vivo platelet activation and detailed studies of peripheral vascular response to cold challenge, were performed at entry, at 5 days of therapy and at biweekly intervals for 10 weeks. RESULTS: Complete healing of all cutaneous lesions (ulcers, fissures, and paronychia) was observed 10 weeks after treatment in 6 of 7 patients receiving iloprost versus none of 4 receiving placebo (p = 0.015). Ischemic digital tip ulcers completely healed in all 4 patients with ulcers in the iloprost group, but none in the placebo group (p = 0.029). Patient diaries of frequency, duration and symptoms of Raynaud's phenomenon showed improvement in both groups. Critical ischemic temperature (finger temperature during controlled cold challenge at which Raynaud's or loss of detectable digital blood flow occurred) progressively decreased in the iloprost group from 21.3 +/- 7.3 degrees C at baseline to a minimum of 16.1 +/- 3.2 degrees C at 8 weeks after treatment (p = 0.076), whereas no consistent changes were observed in the placebo group. Treatment was associated with improvement in the rate of skin temperature recovery following cold challenge. No changes were noted in ambient digital skin temperature, total digital blood flow, finger systolic pressure or in measures of in vivo platelet activation. One subject dropped out with chest pain, but adverse effects of nausea, vomiting, headache and jaw pain were otherwise limited to the 5 days of drug infusion. CONCLUSION: Iloprost appears useful for the treatment of digital ulcers in systemic sclerosis and is associated with evidence of prolonged physiologic improvement although the mechanism of this effect remains unclear.

Adult↗
PubMed1992

Treatment of systemic sclerosis.

A new awareness of the challenges and pitfalls of clinical research in patients with systemic sclerosis has recently arisen. Several editorials discussed concern about the design of therapeutic trials and the need to use established scientific standards to find better markers of disease activity and better ways to measure improvement or deterioration of organ involvement, including the heart, lung, and gastrointestinal tract. This year, an uncontrolled experience in the use of D-penicillamine in the treatment of patients with rapidly progressive skin involvement was reported. In addition, a multicenter study of photopheresis demonstrated benefit compared with D-penicillamine. Several new prokinetic drugs demonstrated promise for the treatment of gastrointestinal disease in patients with systemic sclerosis. Although studies continue to demonstrate the benefit of intravenous prostaglandins in the treatment of Raynaud's phenomenon and digital ulcers in scleroderma, an initial report of oral prostaglandins was disappointing. Clinical researchers are now working together to design multicenter studies and to define new uniform standards of disease activity so that the appropriate treatment for systemic sclerosis can be determined.

Cyclosporine↗
PubMed1991

Factors associated with osteoarthritis of the hand in males: data from the Baltimore Longitudinal Study of Aging.

The association of metabolic and physiologic factors with hand osteoarthritis was studied in 888 Caucasian male subjects aged 17-102 years in the Baltimore Longitudinal Study of Aging. Left-hand radiographs taken between 1958 and 1975 were read by one investigator for grade of osteoarthritis using Kellgren-Lawrence scales. Possible risk factors, assessed at the same visit as the last radiograph during this interval, included age and measures of bone mass, body composition, muscle mass, and muscle strength. Results of bivariate analyses of these cross-sectional data showed that increasing grade of hand osteoarthritis was associated with increasing age; greater mean levels of waist/hip ratio and percentage of body fat; and lower mean levels of percentage of cortical area, grip strength, and forearm circumference. After adjustment for age using residuals from best-fit quadratic regression models, none of these independent variables remained significantly associated with grade of hand osteoarthritis. These data fail to support hypotheses that metabolic and physiologic factors are associated with hand osteoarthritis independent of their known age-related changes.

Adolescent↗
PubMed1991

Failure of vasoldilator infusion to alter pulmonary diffusing capacity in systemic sclerosis.

PURPOSE: Patients with systemic sclerosis (SSc) do not exhibit a normal increase in the diffusing capacity for carbon monoxide (DLCO) on assuming the supine position. We sought to determine whether a potent prostacyclin derivative and vasodilator, iloprost, would reverse this defect. PATIENTS AND METHODS: Fourteen patients with SSc were enrolled in a randomized, double-blind, placebo-controlled study of iloprost. Patients were tested before and during 3 days of iloprost or placebo infusion with both upright and supine pulmonary function studies. RESULTS: The results of baseline pulmonary function studies including DLCO were not significantly altered by iloprost. Furthermore, iloprost did not alter the abnormal postural DLCO response. CONCLUSION: These results suggest that the pulmonary vascular defects seen in this group of patients are not a consequence of reversible pulmonary vasospasm.

Adult↗
PubMed1991

Renal function predicts colchicine toxicity: guidelines for the prophylactic use of colchicine in gout.

In order to establish the degree of renal malfunction necessary for colchicine toxicity in patients receiving it daily for the prevention of recurrent acute gout, we obtained serum creatinine levels and measured or estimated creatinine clearances in a consecutive series of 17 patients with demonstrated colchicine myotoxicity. An estimate of creatinine clearance, based on ideal body weight and age, was nearly always 50 ml/min or less, and was the most practical predictor of the risk of toxicity. By comparison, patients with gout from the same clinical data base, but without myotoxicity, had normal renal function. The data yield clear guidelines for safe use of colchicine chronically.

Adult↗
PubMed1990

The longitudinal course of hand osteoarthritis in a male population.

In this prospective analysis of the natural history of osteoarthritis (OA) of the hand, the incidence and progression of various radiographic features of OA were examined in 177 men who participated in the Baltimore Longitudinal Study of Aging. Subjects who were less than 60 years old were selected based on the availability of at least 4 hand radiographs taken during at least 20 years of followup, while subjects who were age 60 or older were required to have had at least 4 hand radiographs taken during only 14 years of followup. Individual joints of the hands were graded for the presence and severity of 5 features of OA: osteophytes, joint space narrowing, subchondral sclerosis, lateral deformity, and cortical collapse. They were also graded according to the global Kellgren/Lawrence scale. The incidence and rate of progression of OA, as measured by all scales, increased in progressively older age groups. Cox's proportional hazards models showed that isolated doubtful osteophytes (Kellgren/Lawrence grade 1) and isolated joint space narrowing predicted the development of the radiographic features of OA. The rate of OA progression slowed as the severity increased. We conclude that, in men, the incidence of radiographic features of hand OA increases with age. Regardless of age, the earliest radiographic signs of OA are joint space narrowing and doubtful osteophytes.

Aging↗