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Biomedical subjects

H Buchwald

Publications and source records attributed to H Buchwald.

At least 127 records · Page 7Linked to original sources

Long-term, continuous intravenous heparin administration by an implantable infusion pump in ambulatory patients with recurrent venous thrombosis.

We studied the effect of long-term intravenous heparin infusion, delivered by a self-recycling, totally implantable infusion pump developed in our laboratory, in 21 patients with recurrent thromboembolic disease. Continuous infusions were maintained in these patients from 1 to 36 months, during which pumps were refilled by percutaneous needle injection at 4- to 8-week intervals. We maintained plasma heparin levels between 0.1 and 0.3 U/ml plasma. This regimen prevented thromboembolic phenomena in all except one patient, who apparently is refractory to heparin as well as oral anticoagulant drug therapy. Marked reduction of pain and improvement of mobility were reported by several patients with vena cava ligature syndrome. No spontaneous hemorrhagic complications occurred; however, several episodes of pump site hemorrhage were associated with pump refills. Bone mineral densities measured in eight subjects after 1 year of heparin infusion [1.00 +/- 0.06 (SE) gm/cm] were not significantly (P = 0.5) different from baseline values (0.98 +/- 0.08 gm/cm); however, osteoporosis did occur in one subject. Serum calcium, phosphorus, alkaline phosphatase, cholesterol, and triglycerides also remained unchanged in these subjects. These data suggest that continuous long-term heparin infusion is a viable therapeutic alternative in subjects with refractory thromboembolic disease.

Adult↗

The implantable infusion pump: a new concept in drug delivery.

Several of our most useful drugs cannot be administered orally. This paper is a summary of our work with a new drug delivery system: a totally implantable, continuous infusion pump, with a self-contained inexhaustible power source. Currently, after bench tests and animal experimentation, we have initiated clinical series utilizing this device to treat individuals with refractory thromboembolic conditions by intravenous heparin, and patients with localized solid tumors by intra-arterial chemotherapy. The use of this device for the infusion of insulin in the management of diabetes mellitus is yet in the laboratory stage of development. In addition to improving dy-today diabetic control and obviating the need for daily insulin injections, this pump offers an ideal opportunity to test whether optimal blood glucose control can significantly prevent or delay the onset of the crippling vascular complications of diabetes. The potential uses of this device, in many fields, are myriad.

Adult↗

Changes in body image and other psychological factors after intestinal bypass surgery for massive obesity.

A group of massively obese persons (predominantly women) was evaluated 6 months prior to intestinal bypass surgery and again while in the hospital awaiting surgery. A second follow-up group of massively obese persons was evaluated on the same measures in-hospital prior to surgery and then assessed periodically over the subsequent 1-year period. The 6-months-before-surgery group showed a general decline in concern with physical symptoms, anxiety, and social introversion at the in-hospital evaluation. The surgery follow-up group exhibited an increasing improvement, as weight loss progressed, in body image, feelings of physical and sexual attractiveness, and evaluation of one's personality. An improvement in mood also was seen. Body size estimation showed a realistic adjustment with weight loss. Both groups scored higher than average on a measure of the addictive personality. Follow-up of the nonresponders indicated that a substantial proportion of those persons had psychological or severe physical problems subsequent to surgery.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗