No abstract

Objective. To examine racial differences in disease onset, extent, manifestations, and survival among women with scleroderma.Methods. A retrospective cohort study of women with scleroderma, diagnosed in Michigan between 1980 and 1991, was conducted. Clinical, laboratory, and demographic data were abstracted from the patients' medical records.Results. A total of 514 women with scleroderma were identified: 117 (23%) were black and 397 (77%) were white. Among black women, the mean age at diagnosis was lower (44.5 years versus 51.5 years; P < 0.001) and diffuse disease was more common (49.6% versus 24.9%; P < 0.001) than among white women. The overall incidence of scleroderma was 14.1 per million per year: 22.5 per million per year in black women versus 12.8 per million per year in white women (P < 0.001). Pericarditis (P = 0.009), pulmonary hypertension (P < 0.001), pleural effusions (P = 0.01), myositis (P = 0.02), and an erythrocyte sedimentation rate >40 mmlhour (P < 0.001) were more frequent among black women, while white women were more likely to have digital infarctions (P < 0.001). Survival at 7 years from form October 25, 1996. diagnosis was 72.5% among black women and 77.6% among white women. Age-adjusted survival was significantly reduced among black women (P = 0.033), most likely because of increased diffuse involvement. Survival among those with renal or pulmonary involvement was also significantly reduced.Conclusion. Black women with scleroderma were significantly more likely than white women to develop diffuse disease, be diagnosed at a younger age, have a higher incidence of inflammatory features, and have a worse age-adjusted survival rate.Scleroderma is an uncommon connective tissue disease that is characterized by variable degrees of fibrosis within the skin and internal organs. Previous epidemiologic studies have provided estimates of incidence, prevalence, and mortality, and have identified the various clinical and laboratory manifestations that distinguish the diffuse and limited scleroderma subtypes (1,2). In addition, some investigators have suggested important differences between black and white women with regard to incidence, mortality, case fatality, and extent of disease manifestations (3-5). However, few studies have contained sufficient numbers of both black and white women to completely identify and confirm these observations.As part of a population-based case-control study to identify potential risk factors among women with scleroderma, we recruited a large, racially diverse cohort of women with scleroderma in Michigan (6). During review of their medical records, 74 clinical and laboratory parameters were recorded, as well as demographic information, date of diagnosis, and date of death or last followup examination. These data enabled us to examine racial differences in age at diagnosis, extent of disease, clinical manifestations, incidence of disease, and survival.

Blood flows to the major organs of the resting conscious dog were measured prior to and 30 and 90 min after feeding using the radioactive microsphere technique. Mean systemic arterial pressure, heart rate, and arterial PO2, PCO2, and pH, as well as blood flow to the brain, heart, adrenals, skeletal muscle, hepatic artery, and gastric antrum were not significantly changed following the meal. Pancreatic and duodenal and jejunal blood flows increased at both 30 and 90 min, whereas ileal blood flow increased only at 90 min after feeding. Flow to the gastric body increased in only half of the fed animals, but it increased in all of the animals treated with histamine. In all cases where there was an increase in total wall flow the increase was confined to the mucosa-submucosal layer. Blood flow to the colon was unchanged except for a decrease in the distal colon at 30 min. Thus, the cardiovascular response to feeding appears to be limited to those organs and tissues actively involved in digestion.

Postprandial intestinal hyperemia is a locally mediated vascular response to the presence of nutrients in the lumen. In this review we discuss the role of various constituents of chyme in the development of the hyperemia and possible mechanisms of action. The luminal contents that produce the hyperemia are digested products of food; undigested food or pancreatic enzymes have no effect. Micellar fatty acids are the most potent vasodilators, whereas amino acids at physiological concentrations have little effect on intestinal blood flow. However, by-products of protein digestion are as potent as those of carbohydrates in increasing the blood flow. Bile increases ileal but does not alter jejunal blood flow. In addition, bile enhances the glucose-induced hyperemia and renders fatty and amino acids vasoactive. The mechanisms by which bile exerts its effect on the vasoactivity of these nutrients are poorly understood. The intestinal hyperemic response to the presence of nutrients in the lumen is mediated by a variety of regulatory pathways that vary with the nutrient. Factors involved include tissue metabolic rate, metabolites, nutrient absorption, tissue osmolality, tissue oxygen tension, intestinal peptides such as neurotensin and vasoactive intestinal polypeptide, and paracrine substances such as prostaglandins and histamine. It is likely that the hyperemia results from the complex interplay of all these factors on the intestinal vascular smooth muscle. Extrinsic and intrinsic nerves play a minor role in nutrient-induced hyperemia.

The cyclic siloxane octamethylcyclotetrasiloxane (D4) and the linear siloxane hexamethyldisiloxane (HMDS) have numerous industrial and consumer applications and thus have the potential for human exposure. The present study was undertaken to examine potential estrogenic and antiestrogenic activities of D4 and HMDS. To address potential differences in sensitivity between rat strains the study used both Sprague-Dawley (SD) and Fischer 344 (F-344) rats. Estrogenicity of the test compounds was determined by measuring absolute and relative uterine weights in immature rats and by monitoring uterine epithelial cell height. In order to place the data obtained for D4 into perspective relative to strong and weak estrogenic compounds, the response produced by D4 at 0, 10, 50, 100, 250, 500, and 1000 mg/kg/day was compared to responses produced by ethinyl estradiol (EE) (1, 3, 10, or 30 microg/kg/day), diethylstilbestrol dipropionate (DES-DP) (0.5, 1.5, 5, 15 microg/kg/day), and coumestrol (CE) (10, 35, 75, 150 mg/kg/day). Antiestrogenic effects were evaluated by co-administering D4 (500 mg/kg/day) with EE at 1, 3, 10, and 30 microg /kg/day. All compounds were administered in sesame oil at a volume of 5 mL/kg by oral gavage. Beginning on postnatal day 18 (SD) or 21 (F-344) each pup (12 per group) received a single dose of test compound once a day for 4 consecutive days. The pups were euthanized the morning after the last treatment and their uteri removed, weighed, and processed for histological examination. EE and DES-DP produced a significant dose-dependent increase in absolute and relative uterine weights and uterine cell height. The maximum increase in uterine weight following EE exposure was approximately 350% relative to controls in both strains. The weak phytoestrogen CE also produced a dose-related increase in absolute and relative uterine weight and epithelial cell height, but the response occurred over a much higher range of doses. At the highest dose of CE, uterine weight was increased approximately 230% relative to controls. Following exposure to D4, absolute and relative uterine weights and uterine epithelial cell height were statistically significantly increased in both strains of rats at doses above 100 mg/kg/day. In terms of uterine weight, D4 was approximately 0.6 million times less potent than EE or DES-DP in SD pups and 3.8 million times less potent than EE or DES-DP in F-344 pups. The maximal increase in uterine weight, relative to controls, produced by D4 at 1000 mg/kg/day was approximately 160% in SD rats, while the maximum increase produced by D4 in F-344 rats was 86%. D4 co-administered over a wide range of EE doses, resulted in a significant reduction in uterine weight compared to EE alone. HMDS was evaluated in SD rats only. The response produced by HMDS (600 and 1200 mg/kg/day) was compared to EE (3 microg/kg/day). Antiestrogenic effects were evaluated by co-administering HMDS (1200 mg/kg/day) with EE at 3 microg/kg/day. HMDS had no measurable effect on uterine weight under the experimental condition...