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Biomedical subjects

H Buchwald

Publications and source records attributed to H Buchwald.

At least 19 recordsLinked to original sources
PubMed1992

Changes in sequential coronary arteriograms and subsequent coronary events. Surgical Control of the Hyperlipidemias (POSCH) Group.

OBJECTIVE: Assessment of the relationship between changes in sequential coronary arteriograms and subsequent clinical coronary events. DESIGN: The Program on the Surgical Control of the Hyperlipidemias, a randomized secondary atherosclerosis intervention trial, obtained coronary arteriograms at baseline, 3, 5, and 7 or 10 years of follow-up. Assessments of changes between pairs of coronary arteriograms were made by two-member panels blinded to the patients' assigned treatment and to the temporal sequence of the films. The relationship of changes between the baseline and the 3-year follow-up arteriograms and subsequent clinical coronary events was examined. SETTING: Three university hospitals and one private primary care facility. PATIENTS: A total of 838 patients, with 417 patients randomized to the control group and 421 to the intervention group. Of all patients, 695 had baseline and 3-year arteriograms. INTERVENTION: The control group received American Heart Association Phase II diet instruction and the intervention group received identical dietary instruction plus a partial ileal bypass operation. MAIN OUTCOME MEASURE: The use of arteriographic changes as a predictor of subsequent clinical coronary events. RESULTS: Changes between the baseline and the 3-year coronary arteriographic overall disease assessment were significantly associated with subsequent overall and atherosclerotic coronary heart disease mortality (P less than .01). For the combined end point of atherosclerotic coronary heart disease mortality or confirmed nonfatal myocardial infarction, a significant relationship between the overall disease assessment and subsequent clinical events was found in the control group (P less than .0001) and in the surgery group (P = .04). For this combined end point, however, the control and the surgery groups were different with respect to clinical coronary events after 3 years, stratified by the baseline to 3-year overall disease assessment (P less than .001, unadjusted; P = .06, adjusted for 3-year clinical covariates). CONCLUSIONS: Coronary arteriographic changes can be used in atherosclerosis intervention trials as a limited surrogate end point for certain clinical coronary events. This relationship is statistically compelling for overall mortality and atherosclerotic coronary heart disease mortality. For an individual patient, changes in the severity of coronary atherosclerosis seen on sequential coronary arteriograms can serve as prognostic indicators for subsequent overall or atherosclerotic coronary heart disease mortality.

Adult↗
PubMed1992

Cholesterol inhibition, cancer, and chemotherapy.

An important feature of malignant transformation is loss of the cholesterol feedback inhibition mechanism that regulates cholesterol synthesis. Cancer cells seem to require an increase in the concentrations of cholesterol and of cholesterol precursors. Therefore, a reasonable assumption is that prevention of tumour-cell growth can be achieved by restricting either cholesterol availability or cholesterol synthesis. In-vivo and cell-culture experiments have shown that lowering the plasma cholesterol concentration or intervening in the mevalonate pathway with 3-hydroxy-3-methylglutaryl (HMG) CoA reductase inhibitors decreases tumour growth. Currently prescribed doses of HMG-CoA reductase inhibitors given orally or continuously by an implantable infusion pump could achieve tumour therapeutic tissue concentrations of these agents. My hypothesis is that cholesterol inhibition can inhibit tumour cell growth, can act as an adjuvant to cancer chemotherapy, and, possibly, can prevent carcinogenesis.

Adjuvants, Pharmaceutic↗
PubMed1992

Women in the POSCH trial. Effects of aggressive cholesterol modification in women with coronary heart disease. The POSCH Group. Program on the Surgical Control of the Hyperlipidemias.

The Program on the Surgical Control of the Hyperlipidemias (POSCH) provided the clearest and the most convincing evidence supporting the beneficial effects of cholesterol lowering in hypercholesterolemic survivors of a myocardial infarction. In POSCH, 78 of the 838 patients (9.3%) were women, with 32 randomized to the diet-control group and 46 to the diet plus partial ileal bypass surgery-intervention group. At 5 years, the mean per cent change from baseline was -23.9% for total plasma cholesterol (p < 0.0001), -36.1% for low-density lipoprotein cholesterol (p < 0.0001), and +8.5% for high-density lipoprotein cholesterol (p = not significant). Because of the small number of women, no statistically significant changes in clinical event rates were observed between the control and the surgery groups. A comparison of 162 coronary arteriography film pairs in the POSCH women, between baseline and 3, 5, 7, and 10 years, consistently showed less disease progression in the surgery group (p = 0.013 for combined assessments of the baseline to the longest follow-up film). Because the lipid and coronary arteriography findings in the POSCH women paralleled these findings in the total POSCH population and in the POSCH men, and because the arteriography changes in POSCH have previously been demonstrated to be statistically significant surrogate end points for certain clinical events and predictors of overall and atherosclerotic coronary heart disease mortality rates, we conclude that the lipid modification achieved in the POSCH women by partial ileal bypass reduced their atherosclerosis progression. The POSCH findings in women support the aggressive treatment of hyperlipidemia in the general management of atherosclerosis in women.

Coronary Angiography↗
PubMed1992

Partial ileal bypass in the treatment of hypercholesterolemia.

Partial ileal bypass is a surgical method of lowering circulating cholesterol levels. This article outlines the history of the partial ileal bypass operation and compares the efficacy, durability, compliance, safety, and cost of this operation with currently available diet and drug therapy for hypercholesterolemia. Partial ileal bypass patients have been followed for up to 26 years, and the procedure is employed currently throughout the United States and Europe. Partial ileal bypass has moved beyond the research stage and can be performed in community hospitals by competent general surgeons.

Anastomosis, Surgical↗
PubMed1991

Program on the Surgical Control of the Hyperlipidemias (POSCH): patient entry characteristics. The POSCH Group.

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.

Adult↗
PubMed1991

Pathogenesis of nephrolithiasis post-partial ileal bypass surgery: case-control study. The POSCH Group.

Between 1975 and 1983, 838 patients were randomized into the Program on the Surgical Control of Hyperlipidemias (POSCH) trial: 417 to standard medical care and 421 to partial ileal bypass (PIB) surgery. During the course of the trial, an increased incidence of kidney stone formation was found in the surgery group (4%/year) as compared to the control group (0.4%/year). A matched triplet case-control study was conducted to assess the possible causes for the increased incidence of kidney stones. Three groups were studied: PIB stone-formers (S); PIB non-stone formers (N); and non-PIB, non-stone formers in the control group (C). Initially, 162 patients (54 triplets) were selected. Ten percent of the patients declined to participate which resulted in a sample size of 146 patients. The PIB patients had statistically significant (P less than 0.05) lower levels of serum vitamin D metabolites; lower urine volume, pH, citrate, magnesium, carbon dioxide, and sulfate, and higher urinary oxalate, ammonia and relative supersaturation for calcium oxalate and uric acid than the control patients. Although S and N had similar results, those S with no prior history of stones had a higher calcium oxalate supersaturation than similar N with a negative prior history of stones (P less than 0.025). Based on these results, all PIB patients appear to be at risk for kidney stone formation. The combination of reduced urinary volume and calcium oxalate precipitation inhibitor substance with increased calcium oxalate relative supersaturation produced an increase in nephrolithiasis risk in the PIB groups.

Adult↗
PubMed1990

Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH)

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.

Adult↗
PubMed1990

Partial ileal bypass for hypercholesterolemia. 20- to 26-year follow-up of the first 57 consecutive cases.

Between 1963 and 1968, 57 patients underwent partial ileal bypass (PIB) at the University of Minnesota for primary hypercholesterolemia. Preoperative total plasma cholesterol (TC) was 363.3 +/- 136.8 mg/dL (mean +/- SD) in these patients. Baseline and follow-up TC results demonstrated highly significant (p less than or equal to 0.001) TC reduction, 34% (n = 48), 28% (n = 49), 35% (n = 26), 35% (n = 11), and 30% (n = 25) at 1, 2 to 5, 6 to 10, 11 to 15, and more than 20 years, respectively, after PIB. In 21 patients with baseline, 1-year, and more than 20-year results TC decreased 33% by 1 year and remained 29% less than baseline more than 20 years after surgery (p = NS versus 1 year). Plasma triglyceride results were available in fewer patients, and no statistically significant changes developed after PIB. Two patients (3.5%) underwent PIB reversal, one for intractable diarrhea and one for recurrent nephrolithiasis. In the 25 nonreversed, long-term survivors, no statistically significant weight change was noted. Twenty-four per cent had 0 to 2, 52% had 3 to 5, and 24% had more than 5 bowel movements per day. Subsequent cholecystectomy was required in eight patients, and nephrolithiasis developed in 10 (40%). During 20 to 26 years, most survivors developed clinically apparent atherosclerosis: angina (60%), myocardial infarction (16%), or coronary artery bypass (28%). Coronary heart disease was the predominant cause of death among nonsurvivors (80%). Overall survival rates were 95% 88%, 75%, 59%, 53%, and 41% at 1, 5, 10, 15, 20, and 25 years, respectively, after PIB. Partial ileal bypass leads to highly significant TC reduction, which is sustained, essentially unchanged, more than 20 years after operation. In comparison to available epidemiologic and clinical trial data, these results support the hypothesis that TC reduction has a beneficial effect in patients with hypercholesterolemia.

Adolescent↗
PubMed1990

Lipid results of partial ileal bypass in patients with heterozygous, type II-A hyperlipoproteinemia. Program on the Surgical Control of the Hyperlipidemias.

Although reduction in total plasma cholesterol has yet to be shown to have a beneficial effect on overall mortality, the weight of experimental and epidemiologic evidence supports efforts to lower total plasma cholesterol levels to reduce the risk of death from coronary heart disease (CHD). This is especially true in patients with heterozygous, type II-A hyperlipoproteinemia, whose total plasma cholesterol levels above the 90th percentile for age and sex place them at markedly increased risk of death from CHD. The lipid results of partial ileal bypass (PIB) were assessed in 110 patients with heterozygous, type II-A hyperlipoproteinemia in the Program on the Surgical Control of the Hyperlipidemias, a randomized, prospective clinical trial assessing the effects of cholesterol reduction on overall mortality and the course of CHD. Compared with dietary control (n = 52), PIB (n = 58) reduced total plasma cholesterol levels 24% +/- 2% (mean +/- SEM), reduced low-density lipoprotein (LDL) cholesterol levels 34% +/- 3%, and increased high-density lipoprotein (HDL) cholesterol levels 5% +/- 5% 5 years after surgery. Very low-density lipoprotein cholesterol levels were 28% +/- 21% higher and plasma triglyceride levels were 24% +/- 11% higher in the surgical group. The HDL cholesterol/total plasma cholesterol and HDL cholesterol/LDL cholesterol ratios were significantly higher after PIB. Apolipoprotein A-I and HDL subfraction 2 levels were significantly higher and apolipoprotein B-100 levels were significantly lower in the surgical group. PIB successfully lowered mean total plasma cholesterol and LDL cholesterol levels below the limits recommended by the National Cholesterol Education Program to minimize the risk of death from CHD. These results confirm the efficacy and support the role of PIB in the management of patients with marked hypercholesterolemia.

Adult↗
PubMed1989

Program on the Surgical Control of the Hyperlipidemias (POSCH): design and methodology. POSCH Group.

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.

Adult↗
PubMed1989

Dietary marine oil supplements fail to affect cholesterol metabolism or inhibit atherosclerosis in rabbits with diet-induced hypercholesterolemia.

Dietary marine oil supplements may protect against atherosclerosis, although their influence on plasma lipids, in vivo cholesterol metabolism, and aortic cholesterol accumulation remains uncertain. The effects of daily administration of marine oil--delivering 100 mg of eicosapentaenoic acid, 59 mg of docosahexaenoic acid, and 221 mg of omega-3 fatty acids per kilogram--were assessed in 33 New Zealand white rabbits. Six animals (group I) were immediately killed. In the remaining animals stable hypercholesterolemia was induced with a 0.25% cholesterol-enriched diet. After 7 weeks on this diet, six animals were killed (group II). Total plasma cholesterol had increased significantly (982 +/- 119 mg/dl vs. 55.6 +/- 7.1 mg/dl, mean +/- SEM, p less than 0.001). The remaining animals randomly received a tap-water placebo (group III, n = 12) or marine oil (group IV, n = 9) daily. After 3 months, total plasma cholesterol was similar (p = NS) among group II (982 +/- 119 mg/dl), group III (965 +/- 54 mg/dl), and group IV (913 +/- 46 mg/dl). No significant differences in HDL cholesterol, LDL cholesterol, VLDL cholesterol, or triglyceride levels developed between the placebo and marine oil groups. Two-hour, hepatic total lipid, neutral steroid, fatty acid, bile acid, and cholesterol synthesis rates were not significantly affected by marine oil treatment. Thoracic aortic cholesterol content increased during cholesterol feeding (5.7 +/- 0.9 mg/gm vs. 1.1 +/- 0.05 mg/gm, group II vs. group I, p less than 0.05). Marine oil supplementation had no effect on the progressive accumulation of cholesterol in the thoracic aorta (28.8 +/- 2.5 mg/gm vs. 29.4 +/- 1.8 mg/gm, group IV vs. group III, p = 0.84). The abdominal aortic cholesterol contents were also similar. These results do not support the use of dietary marine oil supplements for the amelioration of lipid metabolism or the prevention of atherosclerosis.

Animals↗
PubMed1989

Diverting cervical esophagostomy and construction and primary reconstitution of esophageal continuity.

A simple technique has been described herein that will allow the surgeon to construct a temporary, totally diverting, cervical esophagostomy, and then allow the surgeon to take down the esophagostomy with primary cervical esophageal reconstitution. Crucial to the success of this method is the careful preparation of the esophagus for a tension-free reconstruction at the time of the initial diversion procedure.

Anastomosis, Surgical↗
PubMed1988

Predictors of total and low-density lipoprotein cholesterol change after partial ileal bypass.

POSCH is a prospective, randomized secondary intervention trial examining the effect of maximal lipoprotein modification achieved by partial ileal bypass on overall mortality and the course of coronary heart disease. In the initial 189 surgical patients, total cholesterol levels decreased from 256.7 +/- 2.6 mg/dl to 166.6 +/- 2 mg/dl, and low-density lipoprotein cholesterol levels decreased from 181.5 +/- 2.7 mg/dl to 94.1 +/- 1.7 mg/dl 3 months after operation. These significant decreases were sustained through 5 years of follow-up (p less than 0.001). The total cholesterol level was 29.2 +/- 0.9 percent lower and the low-density lipoprotein cholesterol level was 43.2 +/- 1 percent lower at 5 years compared with the baseline level. Decreases of similar magnitude were seen in each of the common WHO lipoprotein phenotypes. The baseline total cholesterol level was the only significant independent preoperative predictor of the 5 year total cholesterol level (correlation coefficient 0.547; p less than 0.001), and the baseline low-density lipoprotein cholesterol level was the only significant independent preoperative determinant of the 5 year low-density lipoprotein cholesterol level (correlation coefficient 0.599; p less than 0.001). These relationships are expressed by the following equations: 5 year total cholesterol = 0.54 X baseline total cholesterol + 42.3, and 5 year low-density lipoprotein cholesterol = 0.455 X baseline low-density lipoprotein cholesterol + 19.2. The decrease in total and low-density lipoprotein cholesterol levels after partial ileal bypass are greater than reported by any trial of drug or diet intervention, including the Lipid Research Clinics Coronary Primary Prevention Trial which examined cholestyramine. Estimation of the change in total and low-density lipoprotein cholesterol levels after partial ileal bypass can be made based on preoperative lipid analysis and is essential in comparing different therapeutic modalities and assessing the role of partial ileal bypass among strategies aimed at lowering coronary heart disease risk.

Adult↗
PubMed1988

Low plasma lipid levels and increased cholesterol synthesis after partial ileal bypass plus lovastatin in hypercholesterolemic rabbits.

Partial ileal bypass (PIB) lowers the plasma total cholesterol (C) level, thereby increasing hepatic C synthesis to replenish bile acid and C stores. Lovastatin, a C synthesis inhibitor, may act as a potential adjuvant to PIB for lipid lowering. In this study, the effects of PIB and lovastatin, alone and in combination, were examined in plasma and tissue. For 14 weeks, 32 New Zealand White rabbits received a C-free, alfalfa-free, natural-ingredients diet previously shown to induce hypercholesterolemia. The rabbits were divided into control, lovastatin, PIB, and PIB plus lovastatin groups. Lovastatin was administered at a dose of 0.35 mg/kg twice daily. Compared with the control group, PIB alone decreased the plasma total C level by 75% (p less than 0.005), the low-density lipoprotein (LDL)-C level by 79% (p less than 0.025), and hepatic C content by 50% (p less than 0.05), while increasing hepatic C synthesis by 176% (p less than 0.05). Compared with the control group, lovastatin alone decreased the plasma total C value by 36% (p = NS), the LDL-C level by 35% (p = NS), hepatic C content by 29% (p = NS), and hepatic C synthesis by 52% (p = NS). Compared with the control group, the combination of PIB and lovastatin decreased the plasma total C level by 78% (p less than 0.005), the LDL-C level by 74% (p less than 0.025), and hepatic C content by 58% (p less than 0.05); however, the hepatic C synthesis increased by 490% (p less than 0.005) compared with the control group and by 110% (p less than 0.05) compared with PIB alone. This is the first demonstration of a metabolic reversal of the cholesterol synthesis inhibition engendered by lovastatin. We conclude that both PIB and lovastatin lower plasma total C and lipoprotein C fractions. Their combination has an additive C-lowering effect in plasma and decreases tissue C content by increasing cellular C demand. This latter effect overcomes the inhibitory effect of lovastatin on hepatic C synthesis, resulting in an augmented compensatory increase in hepatic C synthesis.

Animals↗