Biomedical subjects
Publications and source records attributed to R D Smink.
Angiosarcoma of the breast is an uncommon entity, and the development of cutaneous angiosarcoma of the breast after segmental mastectomy and irradiation therapy is even less common. We report a case of cutaneous angiosarcoma that developed 4 1/2 years after segmental mastectomy (lumpectomy) with axillary dissection and irradiation therapy for infiltrating ductal carcinoma of the breast.
The entry characteristics of patients in the Program on the Surgical Control of the Hyperlipidemias (POSCH), a randomized, controlled, clinical trial, are described in this article. The primary objective addressed by POSCH was whether lowering total plasma cholesterol by partial ileal bypass surgery results in a reduction in mortality and morbidity in post-myocardial infarction patients. Between 1975 and 1983, 838 patients between the ages of 30 and 64 years were randomized into POSCH. The mean age at entry was 51 years, and 91% of the patients were men. The mean time between myocardial infarction and entry was 2.2 years. The mean baseline total plasma cholesterol was 251 mg/dl, with a mean LDL-cholesterol of 179 mg/dl and a mean HDL-cholesterol of 40 mg/dl. Significant disease (greater than or equal to 50% occlusion) of one or more major coronary arteries was found in 91% of the patients. In addition to a description of the POSCH patient population at entry, comparisons of the POSCH patient population to populations of participants in other lipid-lowering trials are presented to provide a perspective on how POSCH relates to these trials.
BACKGROUND AND METHODS: The Program on the Surgical Control of the Hyperlipidemias (POSCH), a randomized clinical trial, was designed to test whether cholesterol lowering induced by the partial ileal bypass operation would favorably affect overall mortality or mortality due to coronary heart disease. The study population consisted of 838 patients (417 in the control group and 421 in the surgery group), both men (90.7 percent) and women, with an average age of 51 years, who had survived a first myocardial infarction. The mean follow-up period was 9.7 years. RESULTS: When compared with the control group at five years, the surgery group had a total plasma cholesterol level 23.3 percent lower (4.71 +/- 0.91 vs. 6.14 +/- 0.89 mmol per liter [mean +/- SD]; P less than 0.0001), a low-density lipoprotein cholesterol level 37.7 percent lower (2.68 +/- 0.78 vs. 4.30 +/- 0.89 mmol per liter; P less than 0.0001), and a high-density lipoprotein cholesterol level 4.3 percent higher (1.08 +/- 0.26 vs. 1.04 +/- 0.25 mmol per liter; P = 0.02). Overall mortality and mortality due to coronary heart disease were reduced, but not significantly so (deaths overall [control vs. surgery], 62 vs. 49, P = 0.164; deaths due to coronary disease, 44 vs. 32, P = 0.113). The overall mortality in the surgery subgroup with an ejection fraction greater than or equal to 50 percent was 36 percent lower (control vs. surgery, 39 vs. 24; P = 0.021). The value for two end points combined--death due to coronary heart disease and confirmed nonfatal myocardial infarction--was 35 percent lower in the surgery group (125 vs. 82 events; P less than 0.001). During follow-up, 137 control-group and 52 surgery-group patients underwent coronary-artery bypass grafting (P less than 0.0001). A comparison of base-line coronary arteriograms with those obtained at 3, 5, 7, and 10 years consistently showed less disease progression in the surgery group (P less than 0.001). The most common side effect of partial ileal bypass was diarrhea; others included occasional kidney stones, gallstones, and intestinal obstruction. CONCLUSIONS: Partial ileal bypass produces sustained improvement in the blood lipid patterns of patients who have had a myocardial infarction and reduces their subsequent morbidity due to coronary heart disease. The role of this procedure in the management of hypercholesterolemia remains to be determined. These results provide strong evidence supporting the beneficial effects of lipid modification in the reduction of atherosclerosis progression.
The Program on the Surgical Control of the Hyperlipidemias (POSCH) is a prospective, randomized, controlled, multi-center, secondary, atherosclerosis intervention trial. POSCH addresses the therapeutic arm of the lipid-atherosclerosis theory, i.e. whether lowering of plasma cholesterol is directly related to a reduction in atherosclerosis risk. In this trial, lipid modification is accomplished by the partial ileal bypass operation. Between 1975 and 1983, 838 patients were randomized into this study. All patients were between 30 and 64 years of age, had survived one and only one electrocardiogram and enzyme-documented myocardial infarction, and had a total plasma cholesterol of at least 220 mg/dl or a low density lipoprotein (LDL)-cholesterol of at least 140 mg/dl if the total plasma cholesterol was between 200 and 219 mg/dl after a minimum of 6 weeks of dietary fat and cholesterol restriction. The primary response variable in POSCH is overall mortality. Secondary endpoints include fatal and non-fatal myocardial infarctions, serial electrocardiographic changes, and, most importantly, sequential coronary arteriography changes. The minimum follow-up is currently planned to be 7 years. Study analyses will be made primarily on the "intention to treat" basis. This paper is the first detailed presentation of POSCH design and methodology. Included are descriptions of study design, implementation, and data collection, including data processing, quality assurance/quality surveillance, and patient safety monitoring. POSCH seeks to demonstrate a significant reduction in overall mortality by lipid modification and to validate the use of coronary arteriographic change as a surrogate endpoint for change in coronary heart disease risk.
Abdominal hernias are noted with increasing frequency in association with peritoneal dialysis as this mode of dialysis becomes increasingly popular. These hernias often present as localized groin edema, without evidence of a mass, on physical examination. Diagnosis is more difficult when the edema encompasses both groins. Radionuclide imaging peritoneography offers a safe, simple, well-tolerated, highly accurate method of localizing peritoneal defects. We used this method to locate and lateralize inguinal hernias in three patients receiving continuous ambulatory peritoneal dialysis who presented with bilateral scrotal edema and who had unrevealing physical examination findings. All three had unilateral, indirect inguinal herniorrhaphies under local anesthesia and have returned successfully to peritoneal dialysis without complication.
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The Program on Surgical Control of the Hyperlipidemias (POSCH) is a multicentered secondary coronary heart disease intervention trial utilizing maximal plasma lipid reduction as achieved by the partial ileal bypass operation. With over 500 patients recruited into this trial at present, the 4-year sequential lipid changes are statistically highly significant and include an approximate 30% plasma total cholesterol and 40% low density lipoprotein (LDL)-cholesterol reduction, with a slight increase in the high density lipoprotein (HDL)-cholesterol and a marked increase in the HDL-cholesterol:LDL-cholesterol ratio of about 75% or higher. A definitive answer to the lipid-atherosclerosis theory corollary--whether a decrease in the plasma cholesterol engenders a reduction in the incidence or severity of atherosclerotic cardiovascular disease--can be expected from these marked lipid changes in POSCH.
The effect of saturated (beef tallow) and polyunsaturated (corn oil) fat diets on plasma cholesterol, bile flow and composition, and excretion of fecal steroids, was studied in 5 female and 6 male miniature swine. The animals were fitted with a modified Baldwin T-tube in the common bile duct for bile sampling and a catheter in the duodenum for reinfusion. Plasma cholesterol levels were increased by beef tallow and decreased by corn oil. Both fats caused an increase in the secretion of bile, biliary lipids and bile acid pool size. The increases were significant when the source of fat was corn oil. The fecal neutral steroid excretion measured in the male swine was increased by both fats. However, only the polyunsaturated fat diet caused a significant increase in the fecal acidic steroid excretion.
In order to evaluate the metabolic response of nutritionally deprived cancer patients to parenteral nutrition, metabolic parameters including glucose turnover, oxidation, and Cori cycle activity were measured in eight patients before and during short-term (5 to 10 days) i.v. nutrition, with solutions containing amino acids and hypertonic glucose. Before parenteral nutrition, five patients had essentially normal glucose turnover, oxidation, and Cori cycle activity, whereas three patients had moderately increased glucose turnover and markedly increased Cori cycle activity. In response to parenteral nutrition, plasma glucose, insulin, and venous lactate concentration increased and free fatty acid decreased. The percentage of respiratory CO2 from glucose oxidation and the rate of oxidation increased. CO2 production increased, whereas O2 consumption was essentially unchanged. Respiratory quotient rose to greater than 1.0. Endogenous glucose production and high basal Cori cycle activity were decreased. Total parenteral nutrition was judged clinically beneficial in five patients, whereas one patient was unchanged. Deleterious responses, including moderate lactic acidemia, occurred in two of three patients with elevated basal Cori cycle activity.
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Plasma free fatty acid (FFA) turnover and oxidation were determined by the primed continuous infusion of albumin bound (1-14C) palmitic acid in 2 patients after an overnight fast and during fat-free total parenteral nutrition (TPN), in 1 during fat-free TPN, and in another in whom one-third of calories were administered by the continuous infusion of Intralipid via a central venous catheter in conjunction with a standard glucose-amino acid solution. During TPN, plasma FFA concentrations in 2 patients were reduced from 0.7 to 0.11 and 0.08 mM, respectively, and their plasma FFA turnover during TPN was only 26% (3.86 and 2.68 mu mol/min/kg) of that prior TPN. In these subjects prior to TPN, 33 and 47% of the plasma FFA turnover was immediately oxidized, accounting for 58% of the CO2 output; however, during TPN only 16% of the plasma FFA turnover was oxidized, accounting for 10% of the caloric expenditure. The plasma FFA kinetics in the third patient were similar to those described for the first two. In contrast, the plasma FFA concentration of the fourth patient during Intralipid TPN was 0.4 mM. His plasma FFA production was 11.3 mu mol/min/kg, of which 18.4% was immediately oxidized, contributing 28% to the total CO2 output. These studies indicated that during fat-free TPN plasma FFA turnover is reduced and plasma FFA oxidation is a minor contributor to energy homeostasis; however, when one-third of the calories are supplied by fat emulsion, plasma FFA turnover is appreciable and the oxidation of plasma FFA is an important source of energy.