Continuous single-rate long-term insulin infusion using a totally implantable pump.
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Biomedical subjects
Publications and source records attributed to H Buchwald.
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An exercise test may be characterized as positive because of the production of either electrocardiographic ST-segment depression or elevation. The relationship of exercise-induced ST-segment deviation to the specific motion abnormalities of the individual segments of the left ventricular wall was investigated. The first 280 subjects to enter the Program of Surgical Control of Hyperlipidemia were studied by treadmill exercise testing and left ventriculography. The results showed that exercise-induced ST-segment elevation could occur without evidence in the resting subject of either dyskinesia or aneurysm of the left ventricle, that the area of left ventricular damage was much greater in subjects with exercise-induced ST-segment elevation than in those with ST-segment depression, and that wall motion abnormalities were concentrated in the inferoposterior area in the group with ST-segment elevation, but were generally scattered throughout the left ventricular wall in the group with ST-segment depression.
We examined tissues of seven non-diabetic mongrel dogs and four diabetic beagle dogs treated with constant insulin infusion via totally implantable pumps for from 210 to 880 days. Kidney and skeletal muscle tissue from all dogs were stained with Congo Red and thioflavin-T and appropriately examined. Kidney tissues from the beagle dogs were examined by electron microscopy. No amyloid deposits were found in any of these tissues. Thus, we cannot confirm an earlier report of amyloid occurring in dogs given long-term intravenous insulin. It is concluded that amyloidosis is not a necessary complication of long-term intravenous insulin infusion in dogs.
Clinical documentation of atherosclerotic plaque regression has been difficult to obtain. This is a report of a patient with severe and early atherosclerotic cardiovascular disease with regression of at least three major atherosclerotic lesions demonstrated by coronary arteriography 10 years after partial ileal bypass operation. The patient's total plasma cholesterol was reduced over these 10 years, ranging from 40% to 23%, from the preoperative level of 757 mg/dl. Sequential arteriograms were assessed independently by several arteriographers and blindly by the Arteriography Review Panel of the Program on Surgical Control of the Hyperlipidemias (POSCH). The readings were analyzed by 4 grading methods. Unanimously, marked regression was read in the proximal left circumflex artery (70% leads to 20%), middle segment of the right coronary artery (45% leads to 20%), and in the distal right coronary artery (80% leads to 50%). Thus, by any and all of the methods used, there was significant regression of arteriographically demonstrated atherosclerotic lesions.
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We treated five patients with Type II diabetes by means of a subcutaneously implanted intravenous insulin pump and compared their metabolic response with that observed during conventional insulin therapy. The use of the pump improved control of glycemia, as manifested by reductions in mean plasma glucose (from 188 +/- 46 to 106 +/- 12 mg per deciliter [mean +/- S.D.]), fasting glucose (from 187 +/- 42 to 80 +/- 13 mg per deciliter), and postprandial glucose (from 287 +/- 74 to 182 +/- 29 mg per deciliter), together with a diminution of glycemic excursion and normalization of glycosylated hemoglobin A1 (from 12.1 +/- 2 to 8.0 +/- 1 per cent). At the end of the study the pumps had been in place for a mean of 7.0 months (range, 5.5 to 9.7 months) without mishap and with good patient acceptance. Our data suggest that improved blood glucose control can be achieved by means of a permanently implanted continuous insulin-infusion device in ambulatory patients with Type II diabetes who require insulin, and that the need for daily insulin injections can thereby be eliminated.
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This paper is a review of the scientific and economic (when possible) impact of 15 randomized clinical trials of lipid intervention for atherosclerotic cardiovascular disease. No effort has been made to be all-inclusive and certain smaller and first generation studies have been omitted. No effort has been made to offer detailed analyses of protocols; we have limited discussion to summaries of the salient features of each study presented. After stating the data, we introduce certain reflections and raise some of the more obvious questions that emerge.
Carefully age-matched, purebred male beagle dogs that underwent uninephrectomy one month after they were made diabetic with alloxan were used to establish a model of rapidly developing diabetic nephropathy in a large animal. The diabetic animals, all requiring insulin, were divided into two groups: one group with control by insulin injections permitting elevated fasting and postprandial serum glucose values and substantial glycosuria; the other with better control and with near-normal serum glucose levels and less glycosuria. By 1 year of diabetes both diabetic groups had renal lesions different from the uninephrectomized control animals but differing only slightly from one another. With light microscopy, diabetic dogs had increased mesangial thickening. With electron microscopic morphometry, glomeruli of diabetic subjects demonstrated increased fractional volumes of the total mesangium and of its cellular and matrix components and increased width of the GBM. These quantitative measures of diabetic nephropathy in the dog within 1 year of onset of the disease describe a model potentially useful in evaluating the efficacy of improved diabetic control in preventing or ameliorating diabetic nephropathy.
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.
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At the University of Minnesota, under the supervision of one staff surgeon, both the jejunoileal bypass (JIB) and gastric bypass (GIB) operations have been done for weight reduction in morbidly obese individuals. Over the past 11 years, end-to-end (40 to 4 cm) JIB performed for 727 patients. In addition, antecolic GIB was performed for 364 patients over the past 6 years. This report is based primarily on a comparison of 205 JIB and 106 GIB patients with surgery between July 1975 and July 1979. Adequate weight loss was seen in 75% of each group. The percentage of excess body weight loss was similar for the first year (65% for JIB and 62% for GIB); however, the JIB patients started at 214% of ideal weight and GIB patients at 197% of ideal weight. The operative mortality rate for either operation was well below 1%, and the immediate operative morbidity rate was low and only rarely delayed discharge from the hospital. The long-term complications for JIB were 37.7% arthralgia or arthritis, 7.1% oxalate urolithiasis, 5.6 incisional hernia, and 1.4% liver failure; complications of GIB were 10.2% nausea and/or vomiting, 1.9% reflux esophagitis, and 2.8% anastomotic problems. At 1 year, plasma cholesterol reductions for JIB patients averaged 42% (P less than 0.001), whereas for the GIB patients it ws only 14% (P less than 0.001). At 1 year after operation, 49% of 88 JIB patients showed progression of liver disease on sequential biopsies, with 31% unchanged and 20% improved. In 43 GIB patients, the biopsies showed improvement in 58%, an unchanged status in 30%, and worsening in 12%. The levels of serum glutamic oxaloacetic transaminase and alkaline phosphatase increased after JIB and eventually returned to normal, while GIB patients had only minor fluctuations of liver function tests. Comparable therapeutic weight results occurred with JIB and GIB; however, the GIB was associated with far fewer serious long-term complications and the JIB with a far greater cholesterol lowering. A percentage of the GIB patients showed progression of liver disease at 1 year after bypass.
Venous injection of alloxan monohydrate is a standard method to produce a canine model of diabetes. Others have reported mortalities greater than 45 per cent and yields of diabetic dogs of less than 36 per cent with this technique. In this study, a new method for alloxan diabetogenesis is reported upon: alloxan monohydrate is injected intravenously with protection of the renal arteries at the time of injection by a 7F, triple lumen double balloon catheter placed in the abdominal aorta. The balloons are inflated under fluoroscopic control to occlude the renal arteries at the time of injection. Forty-three age-matched beagle dogs were initially injected with 60 milligrams per kilogram of alloxan monohydrate: 26 or 61 per cent became diabetic-defined as persistently doubled fasting serum glucose and glucosuria; ten failed to become diabetic, 23 per cent, and seven died, 16 per cent. The ten initial failures were reinjected with 65 milligrams per kilogram of alloxan monohydrate: six or 60 per cent then became diabetic, three were persistent failures, 30 per cent, and one dog died, 10 per cent. Thus, the over-all yield of diabetic dogs was 74 per cent, with an 18 per cent mortality. Minimal renal damage occurred, as evidenced by creatinine clearance, blood urea nitrogen and renal biopsy studies. These results suggest a significantly improved method--a twofold improvement over standard success rates with a twofold less mortality--of producing diabetic dogs by alloxan injection.
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