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Biomedical subjects

R L Varco

Publications and source records attributed to R L Varco.

At least 19 recordsLinked to original sources
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↗
PubMed1979

Increased hepatic cholesterol synthesis in normal rats by cross-circulation with ileal bypassed partners.

Aortic cross-circulation between Holtzman rat littermates was employed to investigate the possible role of a blood-borne factor from the small intestine in the regulation of hepatic cholesterol synthesis. Experimental pairs, consisting of a normal rat and a distal 50% small bowel excluded partner, demonstrated significantly increased combined hepatic cholesterol synthesis when compared to control pairs, consisting of two normal rats, both at 3 and 5 days following parabiosis. This difference was accounted for by increased hepatic cholesterol synthesis in the normal rat in each experimental pair. Neither weight loss nor differences in dietary intake contributed to this effect. Whole blood cholesterol in the common circulation of both experimental and control pairs was lowered; while hepatic cholesterol content was transiently increased, at 3 but not 5 days following parabiosis. Thus, the intestinal bypassed rat stimulates, or releases inhibition of, hepatic cholesterol synthesis in a non-bypassed parabiotic partner. The mechanism for this phenomenon has yet to be defined.

Acetates↗
PubMed1979

Plasma lipoproteins and coronary arteriography in subjects in the program on the surgical control of the hyperlipidemias. Preliminary report.

Coronary arteriographic findings, plasma lipid and lipoprotein levels, and cigarette smoking history are reported for the first 101 male post myocardial infarction survivors who have been entered into the POSCH clinical trial. Estimates of the extent of stenosis in the major coronary arteries were made using 4 models ranging from a simple determination of the number of the 3 major vessels having significant (i.e. 50% or greater stenosis) disease to more complex methods of determining overall extent of disease in 14 major segments of the coronary arteries. Age was shown to be an important factor in the extent of vessel disease. When controlling for age, plasma cholesterol and LDL-cholesterol levels were shown to be related to the extent of disease, especially in Type II hyperlipoproteinemia subjects. Multiple linear regression analysis demonstrated that age and LDL-cholesterol had positive associations and HDL-cholesterol had an inverse association with the coronary artery disease indices. In this comparatively "healthy" subgroup of the overall population of first MI survivors the major CHD risk factors are limited to plasma lipids and cigarette smoking. This preliminary report of 10% of the recruitment objective of the project supports the currently held views of the lipid--atherosclerosis hypothesis regarding the effects of age-total plasma cholesterol, LDL--cholesterol, and HDL--cholesterol on the extent of coronary atherosclerotic plaques, as determined by coronary arteriography.

Adult↗
PubMed1979

Control of blood glucose in experimental diabetes by means of a totally implantable insulin infusion device.

Near-normal glucose tolerance tests in diabetic dogs were obtained during basal rate insulin infusions in restrained animals by use of extracorporeal infusion pumps and in conscious, unrestrained animals by means of implanted infusion pumps. Even better regulation of blood glucose in diabetic animals was obtained by the addition of predetermined pulses of insulin at higher flow rates than the basal flow rate, accomplished by use of a transcutaneously activated valve mechanism attached to the implanted infusion pump. We conclude that near-normal blood glucose concentrations can be maintained throughout the day in the dog by these means and that similar approaches, using implantable infusion pumps, in man may lead to better long-term control of diabetes than is currently available.

Animals↗
PubMed1979

Cholesterol pool sizes and turnover following portacaval shunt in the dog.

Portacaval shunt has been shown to be effective in lowering the plasma cholesterol level of both man and experimental animal. However, the primary mechanism which effects this reduction is unclear. We have measured the rapidly, and the slowly, miscible cholesterol pool sizes and the cholesterol production rate in mongrel dogs, with the animals in the cholesterol steady state, using 14C-cholesterol plasma decay curve analysis. Five control animals and three one year postoperative portacaval shunt animals with a 50 per cent plasma cholesterol level reduction were studied. No differences were demonstrated in either the cholesterol pool sizes or the production rate. These data have led us to postulate two hypotheses to explain the mechanism of the hypocholesterolemic effect of the portacaval shunt.

Animals↗
PubMed1978

Urolithiasis in patients with a jejunoileal bypass.

Five hundred and seventeen patients who had a jejunoileal bypass performed at the University of Minnesota Hospitals were studied with regard to the formation of urinary calculi postoperatively. A 9 per cent incidence of stones was found in the 365 patients for whom complete data were available. Men were affected more commonly than women. Of particular note was the correlation between long term oral supplementation of calcium postoperatively and a delay in the onset of symptomatic urolithiasis. A group of 91 recent patients who have been maintained on orally administered calcium are stone-free as long as 12 months after operation, again suggesting that supplementation of calcium may help prevent urolithiasis in patients who have had a bypass procedure.

Adult↗
PubMed1977

Vitamin B12 absorption following human intestinal bypass surgery.

Adaptation of vitamin B12 absorption by small intestine has been suggested by experimental and clinical studies. Five partial ileal bypass patients and ten jejunoileal bypass patients were studied for adaptation of B12 absorption following surgery. Adaptation of vitamin B12 absorption could not be demonstrated in either group. Few of the patients on an individual basis demonstrated adaptation. Parenteral B12 should be given to all patients who undergo bypass surgery unless evidence of persistent normal B12 absorption has been obtained.

Adaptation, Physiological↗
PubMed1977

Maximum lipid reduction by partial ileal bypass: a test of the lipid-atherosclerosis hypothesis.

Atherosclerosis is the process responsible for our national epidemic of coronary heart disease. A primary and proven atherosclerotic risk factor is the plasma cholesterol concentration. Yet, proof that a reduction in plasma cholesterol level results in a reduction in the incidence or severity of atherosclerosis and atherosclerotic cardiovascular disease still requires conclusive documentation. The controversial methods of operation and inconclusive results of concluded first and second generation trials are reviewed. These data clearly demonstrate that a definitive test of the lipid hypothesis has not been reported. Evidence is presented to show that the partial ileal bypass operation most nearly fulfills the six features of an "ideal" lipid lowering trial modality: maximum effectiveness (50% cholesterol reduction); known mechanism of action; no response "escape" or "rebound"; obligatory effect without patient cooperation; minimal side effects; and relative safety. The basic design and protocol of the National Heart and Lung Institute Program on Surgical Control of the Hyperlipidemias, a secondary intervention trial using a combination of diet therapy and partial ileal bypass surgery, are outlined.

Arteriosclerosis↗
PubMed1977

Significance of pneumatosis cystoides intestinalis after jejunoileal bypass.

In 148 radiographs taken two weeks to twenty-seven months postoperatively in a series of 402 jejunoileal bypass patients at the University of Minnesota, twenty-four patients demonstrated roentgen evidence for pneumatosis intestinalis on twenty-eight separate episodes. This primarily involved the right colon. Clinical signs and symptoms were reviewed in association with the roentgen findings. Symptoms of nausea, vomiting, fever, and abdominal stress were noted but were not universal. Six patients had no significant change in abdominal complaints at the time the pneumatosis was seen and seven patients had similar clinical findings without roentgen evidence for pneumatosis. Thus, the radiographic findings of pneumatosis intestinalis do not represent a specific sign for bypass enteritis.

Adult↗
PubMed1977

The effect of continuous heparin infusion for one year on serum cholesterol and triglyceride concentrations in the dog.

Fourteen normal dogs received continuous infusions of intravenous heparin for one year by means of an implantable infusion pump. Heparin wad admistered at an overall mean rate of 666 units/kg/day, a dose sufficient to prolong the Lee-White clotting time to greater than twice normal. Eight control, animals, under the same dietary and activity regimen, received continuous infusions of bacteriostatic water for one year by means of implanted pumps. Serum cholesterol concentrations rose to 50% above control values after one month of heparin infusion, and remained significantly (P less than 0.05) elevated at this level for the remaining 11 months. Serum triglyceride levels were unchanged. A possible mechanism for this elevation resides in the known effect of heparin to increase plasma free fatty acid concentrations by its activation of lipoprotein lipase. These results may have implications for the long-term use of heparin anticoagulation in the treatment of atherosclerotic states in man.

Animals↗
PubMed1977

The treatment of esophageal perforation with delayed recognition and continuing sepsis.

Five patients, recently treated for esophageal ruptures, provided a spectrum of "late" perforations. Treatment was individualized for each patient and ranged from suture closure of the perforation to esophagectomy. Four of the 5 patients survived and now have no dietary restrictions. The goals of treatment should be: (1) elimination of sources of chemical and bacterial soilage; (2) drainage of infected areas; (3) augmentation of host defenses by antibiotics; and (4) provision of adequate nutrition. Several treatment adjuncts, alone or in combination, may be used to accomplish these goals. The selection of treatment methods should be influenced by the site of perforation, the extent of local inflammation, the status of the residual esophagus, the overall status of the patient, and the chronicity of the perforation. As the risk of uncontrolled sepsis increases, the surgeon should take more aggressive and definitive steps, up to and including esophagectomy in certain cases, to prevent further soilage.

Anti-Bacterial Agents↗
PubMed1977

Small bowel length in hyperlipidemia and massive obesity.

Small bowel length has been measured during intestinal bypass surgery in 272 morbidly obese patients undergoing jejunoileal bypass and 121 nonobese patients undergoing partial ileal bypass for hyperlipidemia. There was no statistically significant difference in small bowel length between the obese and the nonobese patients. Small bowel length was not correlated with the degree of obesity expressed as the percentage of ideal weight. The only statistically significant correlation determined was between sex and bowel length in the obese subjects, where a greater length of small intestine was found in the males.

Adult↗