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Background: Relaxin is a pregnancy-related hormone that has tissue remodeling and antifibrotic effects. Systemic sclerosis (scleroderma) is characterized by fibrosis of the skin, vasculature, and internal organs.Objective: To assess the efficacy, safety, and dose-response effect of recombinant human relaxin in patients with scleroderma.Design: Multicenter, parallel-group, randomized, double-blind, placebo-controlled trial.Setting: Academic referral centers.Patients: 68 patients who had had stable, diffuse scleroderma (moderate to severe) for less than 5 years.Intervention: Recombinant human relaxin, 25 or 100 microg/kg of body weight per day, or placebo administered by continuous subcutaneous infusion over 24 weeks.Measurements: Modified Rodnan skin score was the primary efficacy measure. Secondary measurements were pulmonary function, the Health Assessment Questionnaire, and other measures of scleroderma that reflected fibrosis.Results: Patients who received 25 microg/kg of recombinant human relaxin per day had significantly lower skin scores than those who received placebo (mean change, -3.6 at 4 weeks [P = 0.021], -7.5 at 12 weeks [P < 0.001], and -8.7 at 24 weeks [P = 0.040]). Similar trends were noted in other outcome measures, including forced vital capacity, measures of oral aperture and hand extension, functional status, and global assessment. Patients who received 100 microg/kg of relaxin per day did not differ from those who received placebo. Drug-related adverse events included menometrorrhagia, reversible anemia, and complications of the subcutaneous drug administration system (site irritation and local infection).Conclusions: Twenty-four weeks of recombinant human relaxin, 25 microg/kg per day, is associated with reduced skin thickening, improved mobility, and improved function in patients with moderate to severe diffuse scleroderma. [ABSTRACT FROM AUTHOR]

Sera from 88 patients with progressive systemic sclerosis were examined for precipitating mitochondrial antibodies using sonicated rat liver mitochondrial fraction as an antigen source in immunodiffusion. Precipitin lines indicating the presence of anti-mitochondrial antibodies (AMA) in 22 patients were detected. Only six of 22 sera had, additionally, precipitating antibodies to nuclear antigens. Standardized reference sera containing antibodies lo mitochondrial antigens (M-A. M-B and M-C systems) were used to further characterize the type of mitochondrial antibodies. M-B antibody was most commonly detected (72.7%) either alone (eight patients) or in combination (eight patients) with M-A and M-C antibodies. M-A antibody was found in 12 patients (54.5%) and M-C antibody was present in three. The antigen related to M-B is DNAase and trypsin sensitive, In contrast to the resistant M-A antigen. AMA were detected in 21 of 22 patients by indirect immunofluorescence. When solid phase ELISA was used to detect AMA using mitochondria, fraction as antigen, a significant difference (P<0.005) was noted between sera with and without precipitating mitochondrial antibody. The antibody was frequently present in patients with progressive systemic sclerosis detected 2 or more years earlier (P<0.01). Three patients were found to have primary biliary cirrhosis and others had pruritus, hepatomegaly or abnormal liver function tests. The implication of the findings is discussed. [ABSTRACT FROM AUTHOR]

The known intestinal complications of systemic sclerosis (SSc) stem mainly from motor disturbances. Autopsy findings were studied to identify anatomic abnormalities that may be associated with this disease. Descriptions of intestinal organs at autopsy were compared in 16 patients with SSc and 18 patients with systemic lupus erythematosus (SLE), a related disease control. There was a high incidence of perforation in SSc (7 of 16 patients) compared to SLE (1 of 18 patients) (P < 0.05). In SSc, perforations involved all parts of the bowel: transmural esophageal fibrosis (after heater probe cautery), dehiscence of suture line after gastric resection, perforated duodenal ulcers (N = 2), terminal ileal ischemia, and diverticulitis (N = 2). Two of the perforations in SSc were silent and were discovered at autopsy. The one perforation in SLE was due to full-thickness necrosis from vasculitis. This study suggests that the intestinal walls of patients with SSc are inherently weak; the gastroenterologist should keep this in mind when performing invasive procedures. [ABSTRACT FROM AUTHOR]

An enzyme immunoassay was used to determine the prevalence of anti-IgE auto-antibodies in 66 patients with systemic sclerosis (scleroderma) stratified according to extent and duration of disease. Serum IgG anti-IgE antibodies were detected in 14 (21%) patients and IgM anti-IgE antibodies in nine (14%) patients. The overall prevalence of IgG or IgM isotypes was 21/66, (32%). Anti-IgE autoantibodies were not found in six patients with undifferentiated connective tissue disease or two patients with eosinophilic fasciitis. Attempts to demonstrate histamine release from basophils in vitro by using serum samples containing high titre anti-IgE antibody were unsuccessful. By multivariate analysis the presence of anti-IgE antibody was not associated with duration of systemic sclerosis; extent of scleroderma; specific visceral features, including heart, lung, renal, and gastrointestinal involvement; or mortality. [ABSTRACT FROM PUBLISHER]

Objectives: To evaluate the effect of selective blockade of type B cholecystokinin receptors on gall bladder contraction in normal humans and to compare methods for quantitative analysis of gall bladder contraction. Methods: L-365,260, a novel, nonpeptide cholecystokinin antagonist shown to be selective for type B cholecystokinin receptors, was administered every 6 h over a 5--7-day period. Plasma levels of L-365,260 were determined by high pressure liquid chromatography. Gallbladder contraction after a standardized fatty meal was measured by ultrasonography, and results were calculated by ellipsoid or sum of cylinders methods. Results: L-365,260 levels were comparable to levels in earlier studies demonstrating inhibition of pentagastrin-stimulated acid secretion in normal subjects and blockade of anxiogenic effects of cholecystokinin injections in patients with panic disorder. Regardless of the method used for estimating gallbladder size, none of the L-365,260 doses studied inhibited gallbladder contraction, gallbladder size was most consistently estimated by the ellipsoid method using measurements normalized to individual values for minimum and maximum gallbladder dimensions. Conclusions: Multiple oral doses of L-365,260 do not alter ultrasonographically assessed gallbladder contraction at doses shown to be clinically effective in earlier studies. Despite being more difficult to implement, the sum of cylinders method for estimating gall bladder size offers no advantage over the ellipsoid method. [ABSTRACT FROM AUTHOR]

Opportunities for third-party reimbursement, marriage and family therapy (MFT) legislation, and federal funding depend largely on evidence supporting the efficacy of specific family therapies in treating specific disorders. The following comprehensive review of literature attempts to answer this "specificity question." The article summarizes outcome research (1986-95) relating to the efficacy of specific modalities of MFT in treating certain disorders and updates the chart originally introduced by Gurman, Kniskern, and Pinsof (1986). Implications for clinical practice and research are discussed. [ABSTRACT FROM AUTHOR]