PubMed Health⌕ Search

Biomedical subjects

Virginia Steen

Publications and source records attributed to Virginia Steen.

8 recordsLinked to original sources
PubMed2006

Cyclophosphamide versus placebo in scleroderma lung disease.

BACKGROUND: We conducted a double-blind, randomized, placebo-controlled trial to determine the effects of oral cyclophosphamide on lung function and health-related symptoms in patients with evidence of active alveolitis and scleroderma-related interstitial lung disease. METHODS: At 13 clinical centers throughout the United States, we enrolled 158 patients with scleroderma, restrictive lung physiology, dyspnea, and evidence of inflammatory interstitial lung disease on examination of bronchoalveolar-lavage fluid, thoracic high-resolution computed tomography, or both. Patients received oral cyclophosphamide (< or =2 mg per kilogram of body weight per day) or matching placebo for one year and were followed for an additional year. Pulmonary function was assessed every three months during the first year, and the primary end point was the forced vital capacity (FVC, expressed as a percentage of the predicted value) at 12 months, after adjustment for the baseline FVC. RESULTS: Of 158 patients, 145 completed at least six months of treatment and were included in the analysis. The mean absolute difference in adjusted 12-month FVC percent predicted between the cyclophosphamide and placebo groups was 2.53 percent (95 percent confidence interval, 0.28 to 4.79 percent), favoring cyclophosphamide (P<0.03). There were also treatment-related differences in physiological and symptom outcomes, and the difference in FVC was maintained at 24 months. There was a greater frequency of adverse events in the cyclophosphamide group, but the difference between the two groups in the number of serious adverse events was not significant. CONCLUSIONS: One year of oral cyclophosphamide in patients with symptomatic scleroderma-related interstitial lung disease had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and the health-related quality of life. The effects on lung function were maintained through the 24 months of the study.

Administration, Oral↗
PubMed2005

Targeted therapy for systemic sclerosis.

Systemic sclerosis is a multisystem disease whose therapy is focused at pathogenic pathways causing variable types of damage in the individual organs. There are 3 major pathways that cause organ damage in scleroderma. First, t-cells, cytokines and inflammation are prominent very early in the disease. Early alveolitis which occurs before interestial fibrosis in the lungs is the best example of inflammation. Second, endothelial cell damage causes severe thickening of vessels and two of the most deadly complications in scleroderma, pulmonary arterial hypertension and renal crisis. Scleroderma renal crisis is now very treatable with angiotensin converting enzyme inhibitors. There are now treatments for pulmonary arterial hypertension which should improve outcome in these patients as well. Third, fibroblasts lead to severe cutaneous fibrosis or skin thickening that is the hallmark of the disease. No treatment is available but we are hopeful that new antagonists to the cytokine, TGF beta, will prove helpful. B cells and autoantibodies are not involved in the pathogenesis of the disease, but there are scleroderma specific antibodies that help in defining patient subsets. All of these factors are influenced by unknown inciting agents and the permissive genetic background.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

The heart in systemic sclerosis.

The heart is one of the major organs involved in scleroderma. Cardiac involvement can be manifested by myocardial disease, conduction system abnormalities, arrhythmias, or pericardial disease. Additionally, scleroderma renal crisis and pulmonary hypertension lead to significant cardiac dysfunction secondary to damage in the kidney and lung. This report summarizes the recent advances to further understand the types and mechanism of abnormalities in the heart in scleroderma. New cardiac technology shows significant frequencies of asymptomatic cardiac abnormalities. Further long-term studies are necessary to determine the outcome and the best approach to treatment of such abnormalities. Diastolic dysfunction has been carefully evaluated in scleroderma in recent years and appears to be more common than once realized. There is controversy as to whether this is a significant finding independent to other cardiopulmonary problems. More extensive evaluation of the conduction and the arrhythmia ablative therapy has helped manage these life-threatening complications.

Cardiovascular Diseases↗
PubMed2004

High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis trial: lessons learned.

OBJECTIVES: To review important findings, or lessons, that were learned about measures of response, design, conduct, and analysis of a randomized, controlled trial (RCT), even though the trial failed to demonstrate efficacy of d-penicillamine. METHODS: One hundred thirty-four patients with early (< or =18 months), diffuse systemic sclerosis (SSc) were entered into an RCT (high-dose [822 mg daily] vs low-dose [120 mg every other day] D-penicillamine) and were followed up regularly for up to 4 years. Because analysis failed to show efficacy for D-penicillamine in early diffuse SSc, all data were pooled for additional secondary analyses. RESULTS: This RCT showed that trials of potential disease-modifying interventions can be completed in SSc using the American College of Rheumatology guidelines. This RCT used an active control. After analysis, we were not able to tell whether either dose was effective or ineffective. That experience argues in favor of using placebo controls until such time as an active control can be found that truly modifies the disease. Skin score and the disability index of the Health Assessment Questionnaire (HAQ-DI) were valid predictors of outcome. Along with the physician global assessment, they also were valid measures of response. CONCLUSIONS: Even in studies that are therapeutically "negative," careful evaluation of the data can examine other hypotheses and thereby provide important insights into other aspects of trial design, outcome measures, patient function, and trial conduct.

Adult↗
PubMed2004

Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines.

Pulmonary arterial hypertension (PAH) occurs as an idiopathic process or as a component of a variety of disease processes, including chronic thromboembolic disease, connective tissue diseases, congenital heart disease, and exposure to exogenous factors including appetite suppressants or infectious agents such as HIV. This article reviews evidence for screening in susceptible patient groups and the approach to diagnosing PAH when it is suspected, and provides specific recommendations for applying this evidence to clinical practice.

Echocardiography↗
PubMed2003

Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement.

OBJECTIVE: To determine whether there are factors, such as the diffusing capacity for carbon monoxide (DLCO) or pulmonary artery pressure (PAP) on echocardiogram, that can predict the development of pulmonary hypertension (PHT) in patients with limited scleroderma. METHODS: Using the large Pittsburgh Scleroderma Databank, 106 patients who had the diagnosis of PHT after January 1, 1982, were matched with 106 controls by scleroderma subtype, age, sex, race, disease duration, and the mean time to the diagnosis of PHT after the initial Pittsburgh visit. Autoantibodies, vascular features, use of calcium channel blockers, extent of pulmonary function, and echocardiogram findings were determined at any time prior to the diagnosis of PHT (or prior to the matched time in controls). RESULTS: Patients with PHT had a mean DLCO of 52% of predicted at an average of 4.5 years prior to the diagnosis of PHT. This was markedly decreased compared with the values in controls, whose mean DLCO was 81% of predicted (P < 0.0001). The estimated mean PAP on echocardiogram was only slightly higher in the PHT patients compared with controls (34 mm Hg versus 29 mm Hg; P not significant). Nineteen PHT patients had 4 serial measurements of the DLCO during the 15 years prior to the diagnosis of PHT. The initial mean DLCO was 80% of predicted, which decreased in a linear manner to a mean of 35% of predicted at the time of diagnosis of PHT, whereas the value in controls remained at approximately 80% of predicted (P < 0.0001). PHT patients had more severe Raynaud's phenomenon and more severe digital tip ulcers, but they used calcium channel blockers significantly less frequently (37% versus 61% of controls; P < 0.01). The predominance of nucleolar autoantibodies and the absence of anti-Scl 70 antibody were associated with PHT. CONCLUSION: A decreasing DLCO is an excellent predictor of the subsequent development of isolated PHT in limited scleroderma. The DLCO may be significantly decreased for many years prior to the diagnosis of PHT. The presence of autoantibodies and the PAP may also be helpful predictors. The long-term use of calcium channel blockers may be protective, but newer agents that are more effective in treating PHT may also be helpful in altering the natural history of this serious complication in limited scleroderma.

Adult↗
PubMed2002

Predictors and outcomes of scleroderma renal crisis: the high-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis trial.

OBJECTIVE: The reported frequency of scleroderma M01-R renal crisis (SRC) in diffuse systemic sclerosis (SSc; scleroderma) is 15-20%. Early use of angiotensin-converting enzyme (ACE) inhibitors has markedly improved outcome. The present analysis reexamines the prognostic factors for and outcome of SRC in a prospective cohort of patients with early diffuse SSc. METHODS: We retrospectively evaluated the cohort of SSc patients who participated in the High-Dose Versus Low-Dose D-Penicillamine in Early Diffuse SSc trial. Patients with diffuse cutaneous scleroderma were enrolled if their disease duration was <18 months. Because the trial failed to show a difference between treatment groups, the data were pooled. RESULTS: One hundred thirty-four SSc patients entered the observation period a mean +/- SD of 0.8 +/- 0.3 years after onset of SSc. SRC occurred in 18 patients a mean +/- SD of 0.9 +/- 1.1 years after entry. During a mean +/- SD 4.0 +/- 1.1 years of followup after entry, 9 of the 18 patients died (mean +/- SD 0.6 +/- 0.9 years after SRC onset). Baseline characteristics that predicted SRC included a modified Rodnan skin thickness score of >or=20 (P < 0.01), enlarged cardiac silhouette on radiograph (P = 0.04), large joint contractures (wrist, elbow, knee) (P = 0.008), and prednisone use at entry (P = 0.01). Baseline characteristics that did not predict SRC included age, sex, race, Health Assessment Questionnaire score, fist closure, handspread, lung involvement, muscle weakness, erythrocyte sedimentation rate, and platelet count. In 5 of 10 subjects for whom at least 2 sequential skin scores were available, skin scores increased significantly (P = 0.012) in the 6 months before onset of SRC. CONCLUSION: SRC occurred in 13% of patients soon (mean 11 months) after entry into the cohort. Predictors of SRC identified in this study included higher than average skin score, prednisone use at study entry, large joint contractures, and heart enlargement. Our data suggest, however, that low-dose prednisone alone was not associated with the onset of SRC, except in the appropriate clinical setting. Although ACE inhibitors and dialysis are now readily available, SRC continues to be associated with poor survival (in this study, 50% of patients with SRC died).

Adult↗