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Virginia D Steen - One of the best experts on this subject based on the ideXlab platform.
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Kidney disease other than renal crisis in patients with Diffuse Scleroderma.
The Journal of rheumatology, 2005Co-Authors: Virginia D Steen, Aijaz Syzd, John P. Johnson, Arthur Greenberg, Thomas A MedsgerAbstract:OBJECTIVE: To determine the frequency and severity of kidney abnormalities in patients with Diffuse Scleroderma. METHODS: All patients with Diffuse Scleroderma seen at the University of Pittsburgh between 1972 and 1993 were included in the study. Kidney function tests were routinely obtained as part of the Pittsburgh Scleroderma Outcome Study. Additional kidney tests were obtained as part of the 1992 biannual outcome assessment. Patients who had kidney abnormalities including a serum creatinine > 1.2 mg/dl or proteinuria prior to 1993 were identified. The clinical setting and longterm outcome of kidney disease were evaluated. RESULTS: Renal crisis occurred in 129/675 (19.5%) patients. Kidney function abnormalities or proteinuria were present in 173 (26%); 48% had no abnormalities. Most patients had other explanations for the abnormality. Only 12 (2%) of the 675 patients with Diffuse Scleroderma had no explanation for the elevated creatinine level. Most patients with proteinuria had toxicity from D-penicillamine. No explanations for proteinuria were found in 16 (2%) of this cohort. Thus, a total of only 28 (4%) of these 675 patients had an unknown cause for their kidney dysfunction or proteinuria. None of these patients, who were followed for a mean of 10 years after onset of Scleroderma, have developed chronic renal insufficiency that progressed to dialysis. CONCLUSION: Patients with Diffuse Scleroderma without renal crisis rarely have significant increases in serum creatinine or proteinuria that cannot be explained by other etiologies. These patients with Scleroderma should be carefully evaluated for non-Scleroderma causes of kidney disease.
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severe organ involvement in systemic sclerosis with Diffuse Scleroderma
Arthritis & Rheumatism, 2000Co-Authors: Virginia D Steen, Thomas A MedsgerAbstract:Objective To determine the natural history and timing of severe involvement of the kidney, heart, lung, gastrointestinal (GI) tract, and skin in patients with systemic sclerosis (SSc) and Diffuse cutaneous involvement. Methods This study used the Pittsburgh Scleroderma Databank and included patients with Diffuse Scleroderma who were seen between January 1, 1972 and December 31, 1995. Patients had frequent followups, and a 95% accountability for these patients was maintained. Severe organ involvement was defined as the presence of any of the following: 1) in the kidney, Scleroderma “renal crisis”; 2) in the heart, cardiomyopathy, symptomatic pericarditis, or an arrhythmia requiring treatment; 3) in the lung, pulmonary fibrosis on chest radiograph and a forced vital capacity of 40. The timing from disease onset to survival for each case of severe organ involvement was determined. Results Of the 953 patients with Diffuse Scleroderma, kidney involvement developed in 177 (19%), heart involvement in 143 (15%), lung involvement in 151 (16%), GI tract involvement in 74 (8%), and skin involvement in 233 (24%). Severe skin and kidney involvement occurred during the first 3 years in 70% of those who ever developed these problems throughout a mean of 10 years of followup. Severe heart, lung, and GI tract involvement developed during the first 3 years in 45–55% of those who were ever affected. The survival of patients with severe organ involvement was poor. The 9-year cumulative survival rate of all patients with severe organ involvement was 38%, compared with 72% in patients without such involvement (P < 0.0001). Conclusion This study demonstrates that severe organ involvement in SSc patients with Diffuse Scleroderma most often occurs early in the course of the disease. Survival for patients with severe organ involvement is markedly reduced. Patients should therefore be monitored very closely during the first 3 years of disease for signs and symptoms that may signal the subsequent development of severe organ damage. Potential disease-modifying therapies must be initiated early to modify the natural history of SSc and to improve survival. Patients who survive the first few years without developing severe organ involvement are less likely to develop such life-threatening involvement later in the disease course.
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Recombinant Human Relaxin in the Treatment of Scleroderma
Annals of Internal Medicine, 2000Co-Authors: James R. Seibold, Virginia D Steen, P. J. Clements, Maureen D. Mayes, Robert W. Simms, Daniel E. Furst, Larry W Moreland, Joseph H. Korn, Naomi F. Rothfield, Michael H. WeismanAbstract:Twenty-four weeks of recombinant human relaxin therapy was associated with reduced skin thickening, improved mobility, and improved function in patients with moderate to severe Diffuse Scleroderma.
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Pregnancy in women with systemic sclerosis
Obstetrics and gynecology, 1999Co-Authors: Virginia D SteenAbstract:Abstract Objective: To determine pregnancy outcomes in women with systemic sclerosis. Methods: Women of childbearing age with systemic sclerosis seen at the University of Pittsburgh between 1987 and 1996 were observed prospectively. Pregnancy outcomes included abortion, miscarriage, preterm and term birth, and perinatal death. Complications of pregnancy and Scleroderma were determined during and after pregnancy. Results: Fifty-nine women with systemic sclerosis had 91 pregnancies during the 10-year period. No increase in the frequency of miscarriage was found, except in those with long-standing Diffuse Scleroderma. Preterm births occurred in 29% of pregnancies, and all but one of the infants survived. Symptoms related to Scleroderma, particularly Raynaud phenomenon, improved during pregnancy, but esophageal reflux became worse. After pregnancy, some women with Diffuse Scleroderma had increased skin thickening. There were three cases of renal crisis during pregnancy, all in women with early Diffuse Scleroderma. Four women had five healthy infants while taking angiotensin-converting-enzyme inhibitors. Conclusion: Women with systemic sclerosis can safely have healthy pregnancies. Those with early Diffuse Scleroderma should wait until their disease stabilizes before becoming pregnant to decrease the risk of renal crisis. High-risk pregnancy management should be standard for all Scleroderma pregnancies because of the high frequency of premature births.
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Clinical manifestations of systemic sclerosis.
Seminars in cutaneous medicine and surgery, 1998Co-Authors: Virginia D SteenAbstract:Systemic sclerosis is a multisystem disease characterized by inflammation and fibrosis of many organs. There are two major subsets, limited cutaneous (the old CREST syndrome) and Diffuse cutaneous Scleroderma. The major difference is the pace of disease. Limited Scleroderma patients often have a long history of Raynaud's phenomenon before other symptoms. They have skin thickening limited to hands and frequently have problems with digital ulcers and esophageal dysmotility. Although generally a milder form than Diffuse Scleroderma, they can have life-threatening complications from small intestine hypomotility and pulmonary hypertension. Diffuse Scleroderma patients have a much more acute onset, with many constitutional symptoms, arthritis, carpal tunnel syndrome, and marked swelling of hands and legs. They get widespread skin thickening, progressing from their fingers to their trunk. Internal organ problems, including gastrointestinal and pulmonary fibrosis, are common, but severe life-threatening involvement of the heart and kidneys occurs. Understanding the type of disease that occurs in these two subsets will enable the physician to anticipate problems, aggressively treat those that can be treated, and give the patient a better understanding of their disease.
Janet E. Pope - One of the best experts on this subject based on the ideXlab platform.
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Predicting improvement in Diffuse Scleroderma: lessons learnt
Annals of the rheumatic diseases, 2016Co-Authors: Janet E. PopeAbstract:Dobrota et al 1 have analysed the EUSTAR (EULAR Scleroderma Trials and Research) systemic sclerosis (SSc, Scleroderma) database using a subset of Diffuse cutaneous SSc (dcSSc) to determine predictors of skin improvement over 1 year in randomised trials. The idea is to enrol more informative patients in a randomised controlled trial (RCT), as incident dcSSc is rare. However, you could want patients who progress/worsen (if not on effective treatment) or those who regress/improve more when on treatment, or some of each subgroup in the sample studied. More than 900 patients were included in the EUSTAR early dcSSc study,1 and like a Bell curve, with a smaller tail, a quarter improved, two-thirds had no change and one-tenth worsened. In order to have a sample size that is enriched for patients who may improve with effective treatment compared with a control, or conversely may worsen without effective treatment, then more informative patients are included and the study size can be smaller. They found that by varying the baseline modified Rodnan skin score (mRSS), the proportion of those who regressed went from 13% to 19% if the mRSS was
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predicting improvement in Diffuse Scleroderma lessons learnt
Annals of the Rheumatic Diseases, 2016Co-Authors: Janet E. PopeAbstract:Dobrota et al 1 have analysed the EUSTAR (EULAR Scleroderma Trials and Research) systemic sclerosis (SSc, Scleroderma) database using a subset of Diffuse cutaneous SSc (dcSSc) to determine predictors of skin improvement over 1 year in randomised trials. The idea is to enrol more informative patients in a randomised controlled trial (RCT), as incident dcSSc is rare. However, you could want patients who progress/worsen (if not on effective treatment) or those who regress/improve more when on treatment, or some of each subgroup in the sample studied. More than 900 patients were included in the EUSTAR early dcSSc study,1 and like a Bell curve, with a smaller tail, a quarter improved, two-thirds had no change and one-tenth worsened. In order to have a sample size that is enriched for patients who may improve with effective treatment compared with a control, or conversely may worsen without effective treatment, then more informative patients are included and the study size can be smaller. They found that by varying the baseline modified Rodnan skin score (mRSS), the proportion of those who regressed went from 13% to 19% if the mRSS was <18 to 25, respectively. Therefore, the range of mRSS from 18 to 25 was most likely to enrich for those who would progress over an observation period. This can simply be that patients in mid-range skin scores in early dcSSc do not have as much of a floor or ceiling effect; that is, very low scores may worsen but are unlikely to improve and very high mRSS scores are unlikely to progress as they already have a high amount of skin involvement (ceiling). Conversely, they observed that 44% improved if the mRSS was more than 25. The mean mRSS was 16 at baseline in the EUSTAR analysis,1 so not all patients would …
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The health assessment questionnaire (HAQ) is strongly predictive of good outcome in early Diffuse Scleroderma: results from an analysis of two randomized controlled trials in early Diffuse Scleroderma
Rheumatology (Oxford England), 2003Co-Authors: N. Sultan, Janet E. Pope, P. J. Clements, D. E. Furst, J. R. Siebold, Weng Kee Wong, N. Bellamy, Maureen D. Mayes, M. Baron, Barbara WhiteAbstract:Objective. Scoring poorly on the health assessment questionnaire (HAQ) has recently been shown to be a strong predictor of morbidity and mortality in rheumatoid arthritis (RA), while a good HAQ score is predictive of a better outcome. In patients presenting with early Diffuse Scleroderma prognosis is variable. Our goal was to determine possible baseline predictors of future good outcomes. Methods. We used the raw data from two randomized controlled trials (RCTs) in early Diffuse Scleroderma: methotrexate (Pope et al.) and D-penicillamine (Clements et al.). Subjects in the methotrexate trial were divided into the following groups: (1) those with at least 20% improvement in the primary outcome measurements [patient global assessment, physician global assessment, UCLA skin tethering score, modified Rodnan skin score (MRSS), DLCO as % predicted and HAQ disability] at 1 yr vs (2) the others. Baseline factors (including age, gender, skin scores, physician and patient global assessments, HAQ disability and pain scores, DLCO and physical parameters) were analysed to find baseline variables strongly correlated with later improvement. These variables were explored in the D-penicillamine trial to determine if (in a separate trial) they were still predictive of improved outcome at 1 and 2 yr. Adjusted models were used to find baseline predictors of good outcome. The median HAQ-DI was 1.3 (methotrexate) and 1.0 (D-penicillamine). Results. A baseline HAQ disability score of less than the median was predictive of at least a 20% improvement at I and 2 yr with odds ratios of 1.77 to 5.05, in four of the five outcome measurements (in both groups); with strongly significant P values for 3 of 5 outcomes (UCLA skin score, MRSS, patient global skin score; P < 0.02) from the methotrexate study group. These three outcomes were strongly correlated with improvement (r between 0.25 and 0.35). Although data from the D-penicillamine trial were less convincing, in both trials the less than median HAQ-DI and HAQ pain scores showed a stronger association with improved outcome, more so than age, gender, skin score and baseline global assessment. Conclusion. A low baseline HAQ (defined as less than the median HAQ score) is predictive of improved outcome in Diffuse Scleroderma at 1 and 2 yr.
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a randomized controlled trial of methotrexate versus placebo in early Diffuse Scleroderma
Arthritis & Rheumatism, 2001Co-Authors: Janet E. Pope, James R. Seibold, Murray Baron, Michael H. Ellman, Simon Carette, Ian M. Chalmers, Paul Hong, N. Bellamy, Douglas C Smith, David P OhanlonAbstract:Objective. Early Diffuse Scleroderma (systemic sclerosis; SSc) has no proven treatment. This study was undertaken to examine the efficacy of methotrexate (MTX) in improving the skin and other disease parameters in early Diffuse SSc. Methods. Seventy-one patients with Diffuse SSc of <3 years' duration were enrolled in a multicenter, randomized, placebo-controlled, double-blind trial. Thirty-five patients were treated with MTX and 36 with placebo. Treatment was administered for 12 months. The primary outcome measures were skin score (as determined with 2 different indices) and physician global assessment. Results. At baseline, there were no statistically significant differences in skin scores, carbon monoxide diffusing capacity (DLco), physician global assessment, or other secondary outcome measurements between the 2 treatment groups. At study completion, results slightly favored the MTX group (mean SEM modified Rodnan skin score 21.4 +/- 2.8 in the MTX group versus 26.3 +/- 2.1 in the placebo group [P < 0.17]; UCLA skin score. 8.8 +/- 1.2 in the MTX group versus 11.0 +/- 0.9 in the placebo group [P < 0.15]; DLco in the MTX group 75.7 +/- 4.6 versus 61.8 +/- 3.4 in the placebo group [P < 0.2]). In addition, physician global assessment results favored MTX (P < 0.035), whereas patient global assessment did not differ significantly between groups. When between-group differences for changes in scores from baseline to 12 months were examined using intent-to-treat methodology, MTX appeared to have a favorable effect on skin scores (modified Rodnan score -4.3 in the MTX group versus 1.8 in the placebo group [P < 0.009]; UCLA score -1.2 in the MTX group versus 1.2 in the placebo group [P < 0.02]), but differences in the degree of change in the DLco and physician global assessment were not significant. For the UCLA skin score, these differences in results were not statistically significant after adjustment for baseline differences in sex distribution and steroid use. Dropout rates were similar in the 2 groups. Conclusion. Although results of this trial demonstrated a trend in favor of MTX versus placebo in the treatment of early Diffuse SSc, the between-group differences were small and the power to rule out false-negative results was only 50%. Our findings do not provide evidence that MTX is significantly effective in the treatment of early Diffuse SSc.
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A randomized, controlled trial of methotrexate versus placebo in early Diffuse Scleroderma
Arthritis and rheumatism, 2001Co-Authors: Janet E. Pope, Nicholas Bellamy, James R. Seibold, Murray Baron, Michael H. Ellman, Simon Carette, C. Douglas Smith, Ian M. Chalmers, Paul Hong, David P. O'hanlonAbstract:Objective. Early Diffuse Scleroderma (systemic sclerosis; SSc) has no proven treatment. This study was undertaken to examine the efficacy of methotrexate (MTX) in improving the skin and other disease parameters in early Diffuse SSc. Methods. Seventy-one patients with Diffuse SSc of
Carol M. Black - One of the best experts on this subject based on the ideXlab platform.
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Pilot study of anti‐thymocyte globulin plus mycophenolate mofetil in recent‐onset Diffuse Scleroderma
Rheumatology, 2001Co-Authors: Richard Stratton, H. Wilson, Carol M. BlackAbstract:OBJECTIVE: To assess the safety and efficacy of anti-thymocyte globulin (ATG) followed by mycophenolate mofetil (MMF) in the treatment of Diffuse Scleroderma. METHODS: A pilot study of 13 patients with recent-onset Diffuse Scleroderma was carried out. Patients received ATG for 5 days, followed by MMF for 12 months. We recorded adverse events, Scleroderma skin score, hand contractures, EuroQol score, Scleroderma functional assessment, pulmonary function studies, echocardiogram and plasma creatinine concentration. RESULTS: Mean skin score decreased during the study from 28 at baseline to 17 after 12 months of MMF (P
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pilot study of anti thymocyte globulin plus mycophenolate mofetil in recent onset Diffuse Scleroderma
Rheumatology, 2001Co-Authors: Richard Stratton, H. Wilson, Carol M. BlackAbstract:OBJECTIVE: To assess the safety and efficacy of anti-thymocyte globulin (ATG) followed by mycophenolate mofetil (MMF) in the treatment of Diffuse Scleroderma. METHODS: A pilot study of 13 patients with recent-onset Diffuse Scleroderma was carried out. Patients received ATG for 5 days, followed by MMF for 12 months. We recorded adverse events, Scleroderma skin score, hand contractures, EuroQol score, Scleroderma functional assessment, pulmonary function studies, echocardiogram and plasma creatinine concentration. RESULTS: Mean skin score decreased during the study from 28 at baseline to 17 after 12 months of MMF (P<0.01). Hand contractures worsened during the study. Mean measurements of systemic disease remained stable. One patient died after a Scleroderma renal crisis. Five patients developed serum sickness after ATG treatment, but this was controlled by corticosteroid therapy. MMF therapy was well tolerated. CONCLUSION: ATG and MMF appear safe in Scleroderma. The improvement in skin score and the apparent stability of systemic disease during the study period suggest that controlled studies of these agents are justified.
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Pilot study of anti‐thymocyte globulin plus mycophenolate mofetil in recent‐onset Diffuse Scleroderma
Rheumatology (Oxford England), 2001Co-Authors: Richard Stratton, H. Wilson, Carol M. BlackAbstract:Objective, To assess the safety and efficacy of anti-thymocyte globulin (ATG) followed by mycophenolate mofetil (MMF) in the treatment of Diffuse Scleroderma. Methods. A pilot study of 13 patients with recent-onset Diffuse Scleroderma was carried out. Patients received ATG for 5 days, followed by MM F for 12 months. We recorded adverse events, Scleroderma skin score, hand contractures, EuroQol score, Scleroderma functional assessment, pulmonary function studies, echocardiogram and plasma creatinine concentration. Results. Mean skin score decreased during the study from 28 at baseline to 17 after 12 months of MMF (P < 0.01). Hand contractures worsened during the study. Mean measurements of systemic disease remained stable. One patient died after a Scleroderma renal crisis. Five patients developed serum sickness after ATG treatment, but this was controlled by corticosteroid therapy. MMF therapy was well tolerated. Conclusion. ATG and MMF appear safe in Scleroderma. The improvement in skin score and the apparent stability of systemic disease during the study period suggest that controlled studies of these agents are justified.
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Different patterns of endothelial cell activation in renal and pulmonary vascular disease in Scleroderma.
QJM : monthly journal of the Association of Physicians, 1998Co-Authors: Richard Stratton, John G Coghlan, Jeremy D. Pearson, A Burns, P Sweny, David Abraham, Carol M. BlackAbstract:Abnormal endothelial cell function is implicated in the development of Scleroderma, and in major life-threatening complications of the disease. The nature of the stimulus leading to abnormal endothelial cell function in Scleroderma, Scleroderma renal crisis, and Scleroderma-associated pulmonary hypertension was investigated by measurement of soluble adhesion molecules, shed by activated endothelial cells, in sera from patients with these conditions. In Scleroderma renal crisis, mean levels of soluble E-selectin (p < 0.05 limited Scleroderma, p < 0.0001 Diffuse Scleroderma), sVCAM-1 (soluble vascular cell adhesion molecule-1) (p < 0.05 limited Scleroderma, p < 0.05 Diffuse Scleroderma), and sICAM-1 (soluble intercellular adhesion molecule-1) (p < 0.0001 limited Scleroderma, p < 0.0001 Diffuse Scleroderma) were raised, supporting a model of endothelial cell activation in this complication. Evidence for endothelial cell activation in Scleroderma-associated pulmonary hypertension was inconsistent, with normal sE-selectin and normal sVCAM-1 in sera from patients with limited Scleroderma and pulmonary hypertension. The endothelial cell phenotype in Scleroderma-associated pulmonary hypertension may resemble that of unstimulated cells. The pulmonary vascular and renal vascular lesions associated with Scleroderma may arise by distinct pathogenic mechanisms.
James R. Seibold - One of the best experts on this subject based on the ideXlab platform.
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Endothelial and fibroblastic activation in Scleroderma. The myth of the "uninvolved skin".
Arthritis and rheumatism, 2010Co-Authors: Henry N. Claman, Ralph C. Giorno, James R. SeiboldAbstract:We studied the immunohistochemistry of the skin of Scleroderma patients to determine the differences (if any) between clinically "affected" and "nonaffected" areas. We examined paired skin biopsy samples from clinically involved forearm skin ("affected") and clinically uninvolved proximal skin ("nonaffected") taken from 19 patients with Diffuse Scleroderma and from 15 normal control subjects. We stained the sections with antibodies to endothelial leukocyte-adherence molecule type 1 (ELAM-1; to detect endothelial activation) and to procollagen-1 (PC-1; to detect newly formed, unprocessed collagen). There was increased expression of ELAM-1 and PC-1 in Sclerodermatous skin as compared with the controls, but there was no difference between clinically affected and nonaffected skin samples. In 10 of 11 patients whose condition was getting worse, endothelial and fibroblast activation preceded fibrosis. Endothelial and fibroblast activation are more widespread in the skin of Scleroderma patients than is evident by inspection on physical examination. What appears to be "normal" skin in Diffuse Scleroderma is already pathologic, as shown by abnormal endothelial activation and procollagen production.
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a randomized controlled trial of methotrexate versus placebo in early Diffuse Scleroderma
Arthritis & Rheumatism, 2001Co-Authors: Janet E. Pope, James R. Seibold, Murray Baron, Michael H. Ellman, Simon Carette, Ian M. Chalmers, Paul Hong, N. Bellamy, Douglas C Smith, David P OhanlonAbstract:Objective. Early Diffuse Scleroderma (systemic sclerosis; SSc) has no proven treatment. This study was undertaken to examine the efficacy of methotrexate (MTX) in improving the skin and other disease parameters in early Diffuse SSc. Methods. Seventy-one patients with Diffuse SSc of <3 years' duration were enrolled in a multicenter, randomized, placebo-controlled, double-blind trial. Thirty-five patients were treated with MTX and 36 with placebo. Treatment was administered for 12 months. The primary outcome measures were skin score (as determined with 2 different indices) and physician global assessment. Results. At baseline, there were no statistically significant differences in skin scores, carbon monoxide diffusing capacity (DLco), physician global assessment, or other secondary outcome measurements between the 2 treatment groups. At study completion, results slightly favored the MTX group (mean SEM modified Rodnan skin score 21.4 +/- 2.8 in the MTX group versus 26.3 +/- 2.1 in the placebo group [P < 0.17]; UCLA skin score. 8.8 +/- 1.2 in the MTX group versus 11.0 +/- 0.9 in the placebo group [P < 0.15]; DLco in the MTX group 75.7 +/- 4.6 versus 61.8 +/- 3.4 in the placebo group [P < 0.2]). In addition, physician global assessment results favored MTX (P < 0.035), whereas patient global assessment did not differ significantly between groups. When between-group differences for changes in scores from baseline to 12 months were examined using intent-to-treat methodology, MTX appeared to have a favorable effect on skin scores (modified Rodnan score -4.3 in the MTX group versus 1.8 in the placebo group [P < 0.009]; UCLA score -1.2 in the MTX group versus 1.2 in the placebo group [P < 0.02]), but differences in the degree of change in the DLco and physician global assessment were not significant. For the UCLA skin score, these differences in results were not statistically significant after adjustment for baseline differences in sex distribution and steroid use. Dropout rates were similar in the 2 groups. Conclusion. Although results of this trial demonstrated a trend in favor of MTX versus placebo in the treatment of early Diffuse SSc, the between-group differences were small and the power to rule out false-negative results was only 50%. Our findings do not provide evidence that MTX is significantly effective in the treatment of early Diffuse SSc.
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A randomized, controlled trial of methotrexate versus placebo in early Diffuse Scleroderma
Arthritis and rheumatism, 2001Co-Authors: Janet E. Pope, Nicholas Bellamy, James R. Seibold, Murray Baron, Michael H. Ellman, Simon Carette, C. Douglas Smith, Ian M. Chalmers, Paul Hong, David P. O'hanlonAbstract:Objective. Early Diffuse Scleroderma (systemic sclerosis; SSc) has no proven treatment. This study was undertaken to examine the efficacy of methotrexate (MTX) in improving the skin and other disease parameters in early Diffuse SSc. Methods. Seventy-one patients with Diffuse SSc of
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Recombinant Human Relaxin in the Treatment of Scleroderma
Annals of Internal Medicine, 2000Co-Authors: James R. Seibold, Virginia D Steen, P. J. Clements, Maureen D. Mayes, Robert W. Simms, Daniel E. Furst, Larry W Moreland, Joseph H. Korn, Naomi F. Rothfield, Michael H. WeismanAbstract:Twenty-four weeks of recombinant human relaxin therapy was associated with reduced skin thickening, improved mobility, and improved function in patients with moderate to severe Diffuse Scleroderma.
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safety and pharmacokinetics of recombinant human relaxin in systemic sclerosis
The Journal of Rheumatology, 1998Co-Authors: James R. Seibold, Maureen D. Mayes, Barbara White, Philip J. Clements, Daniel E. Furst, Deborah A Mccloskey, Larry W Moreland, Fredrick M Wigley, Susan Rocco, Mark EriksonAbstract:OBJECTIVE: To investigate the safety and pharmacokinetics of a 28 day continuous subcutaneous infusion of recombinant human relaxin in patients with systemic sclerosis with Diffuse Scleroderma. METHODS: Thirty patients with stable Diffuse Scleroderma of moderate severity received recombinant human relaxin at 6, 12, 50, 100, and 200 microg/kg/day or placebo in a double blind, sequential panel, dose escalation study. RESULTS: All patients completed 28 days of study treatment. Steady state concentrations of serum relaxin were achieved by the 3rd day of infusion and were dose proportionate. Patients receiving 200 microg/kg/day achieved levels about 50-fold those of normal pregnancy. Pharmacokinetics of relaxin were nonlinear with hyperbolic increases of both t1/2 and volume of distribution and parallel decrease of elimination rate coefficient. An elimination transport system was suggested with saturation at serum relaxin concentration of 45 ng/ml. Adverse events included local infusion site rash and pain, minor bleeding episodes, and decreased hemoglobin concentration (mean reduction 1.1 g/dl). Standard measures of Scleroderma were unchanged, although global assessment favored relaxin over placebo. CONCLUSION: Recombinant human relaxin in the doses used was safe and well tolerated. Longer term controlled trials are warranted to define the potential efficacy of relaxin in patients with Diffuse Scleroderma.
Richard Stratton - One of the best experts on this subject based on the ideXlab platform.
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Pilot study of anti‐thymocyte globulin plus mycophenolate mofetil in recent‐onset Diffuse Scleroderma
Rheumatology, 2001Co-Authors: Richard Stratton, H. Wilson, Carol M. BlackAbstract:OBJECTIVE: To assess the safety and efficacy of anti-thymocyte globulin (ATG) followed by mycophenolate mofetil (MMF) in the treatment of Diffuse Scleroderma. METHODS: A pilot study of 13 patients with recent-onset Diffuse Scleroderma was carried out. Patients received ATG for 5 days, followed by MMF for 12 months. We recorded adverse events, Scleroderma skin score, hand contractures, EuroQol score, Scleroderma functional assessment, pulmonary function studies, echocardiogram and plasma creatinine concentration. RESULTS: Mean skin score decreased during the study from 28 at baseline to 17 after 12 months of MMF (P
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pilot study of anti thymocyte globulin plus mycophenolate mofetil in recent onset Diffuse Scleroderma
Rheumatology, 2001Co-Authors: Richard Stratton, H. Wilson, Carol M. BlackAbstract:OBJECTIVE: To assess the safety and efficacy of anti-thymocyte globulin (ATG) followed by mycophenolate mofetil (MMF) in the treatment of Diffuse Scleroderma. METHODS: A pilot study of 13 patients with recent-onset Diffuse Scleroderma was carried out. Patients received ATG for 5 days, followed by MMF for 12 months. We recorded adverse events, Scleroderma skin score, hand contractures, EuroQol score, Scleroderma functional assessment, pulmonary function studies, echocardiogram and plasma creatinine concentration. RESULTS: Mean skin score decreased during the study from 28 at baseline to 17 after 12 months of MMF (P<0.01). Hand contractures worsened during the study. Mean measurements of systemic disease remained stable. One patient died after a Scleroderma renal crisis. Five patients developed serum sickness after ATG treatment, but this was controlled by corticosteroid therapy. MMF therapy was well tolerated. CONCLUSION: ATG and MMF appear safe in Scleroderma. The improvement in skin score and the apparent stability of systemic disease during the study period suggest that controlled studies of these agents are justified.
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Pilot study of anti‐thymocyte globulin plus mycophenolate mofetil in recent‐onset Diffuse Scleroderma
Rheumatology (Oxford England), 2001Co-Authors: Richard Stratton, H. Wilson, Carol M. BlackAbstract:Objective, To assess the safety and efficacy of anti-thymocyte globulin (ATG) followed by mycophenolate mofetil (MMF) in the treatment of Diffuse Scleroderma. Methods. A pilot study of 13 patients with recent-onset Diffuse Scleroderma was carried out. Patients received ATG for 5 days, followed by MM F for 12 months. We recorded adverse events, Scleroderma skin score, hand contractures, EuroQol score, Scleroderma functional assessment, pulmonary function studies, echocardiogram and plasma creatinine concentration. Results. Mean skin score decreased during the study from 28 at baseline to 17 after 12 months of MMF (P < 0.01). Hand contractures worsened during the study. Mean measurements of systemic disease remained stable. One patient died after a Scleroderma renal crisis. Five patients developed serum sickness after ATG treatment, but this was controlled by corticosteroid therapy. MMF therapy was well tolerated. Conclusion. ATG and MMF appear safe in Scleroderma. The improvement in skin score and the apparent stability of systemic disease during the study period suggest that controlled studies of these agents are justified.
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Different patterns of endothelial cell activation in renal and pulmonary vascular disease in Scleroderma.
QJM : monthly journal of the Association of Physicians, 1998Co-Authors: Richard Stratton, John G Coghlan, Jeremy D. Pearson, A Burns, P Sweny, David Abraham, Carol M. BlackAbstract:Abnormal endothelial cell function is implicated in the development of Scleroderma, and in major life-threatening complications of the disease. The nature of the stimulus leading to abnormal endothelial cell function in Scleroderma, Scleroderma renal crisis, and Scleroderma-associated pulmonary hypertension was investigated by measurement of soluble adhesion molecules, shed by activated endothelial cells, in sera from patients with these conditions. In Scleroderma renal crisis, mean levels of soluble E-selectin (p < 0.05 limited Scleroderma, p < 0.0001 Diffuse Scleroderma), sVCAM-1 (soluble vascular cell adhesion molecule-1) (p < 0.05 limited Scleroderma, p < 0.05 Diffuse Scleroderma), and sICAM-1 (soluble intercellular adhesion molecule-1) (p < 0.0001 limited Scleroderma, p < 0.0001 Diffuse Scleroderma) were raised, supporting a model of endothelial cell activation in this complication. Evidence for endothelial cell activation in Scleroderma-associated pulmonary hypertension was inconsistent, with normal sE-selectin and normal sVCAM-1 in sera from patients with limited Scleroderma and pulmonary hypertension. The endothelial cell phenotype in Scleroderma-associated pulmonary hypertension may resemble that of unstimulated cells. The pulmonary vascular and renal vascular lesions associated with Scleroderma may arise by distinct pathogenic mechanisms.