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Biomedical subjects

B M Wolfe

Publications and source records attributed to B M Wolfe.

At least 109 records · Page 6Linked to original sources

Experience with home parenteral nutrition.

Twenty-nine patients underwent courses of home parenteral nutrition therapy ranging from 1.5 to 52 months (mean 14.5 months). The primary diagnoses responsible for the requirement of home parenteral nutrition were radiation enteritis in seven patients, short bowel syndrome secondary to resection in seven, Crohn's disease in two, malabsorption states in six, and other reasons in seven. Seventeen patients (57 percent) had at least one complication. Nine patients had intravenous catheter complications and nine had metabolic complications. Nine patients have died, 11 have been successfully weaned from home parenteral nutrition, and 9 continue to receive home parenteral nutrition. Home parenteral nutrition is useful in a variety of catastrophic clinical situations, including preparation for subsequent operative therapy, temporary malabsorption, and permanent disability of the gastrointestinal tract. Complications are frequent and may be life-threatening.

Adolescent↗

Norethindrone acetate inhibition of triglyceride synthesis and release by rat hepatocytes.

The progestin, norethindrone acetate has been widely administered to patients in the form of oral contraceptives; however, its hypolipemic action has received little study. This report describes the effects of conventional doses of norethindrone acetate (100 micrograms/day.kg body weight 0.75) on rat plasma lipid levels in vivo as well as the mechanism of action on triglyceride metabolism in isolated hepatocytes in vitro. Norethindrone acetate administration led to significant and proportional reductions of the concentrations of triglycerides, cholesterol and phospholipids of plasma lipoproteins of density less than 1.006 of rats fed a high carbohydrate diet. Norethindrone acetate (0.1 mM) also significantly inhibited the incorporation of both [9,10(-3)H] palmitate and [U-14C]glycerol into triglycerides of isolated hepatocytes from fed rats, by 11 to 16% (P less than 0.001). Release of labeled triglycerides from the isolated hepatocytes was similarly inhibited, 21% and 46%, respectively (P less than 0.05). At the higher concentration of 1.0 mM, norethindrone acetate inhibited the incorporation of [2(-3)H]glycerol into hepatocytic triglycerides by 35-39% (P less than 0.05). The present findings suggest that inhibition of hepatic triglyceride synthesis can account for the reduction of hepatic triglyceride secretion and for at least part of the lowering of plasma VLDL levels which occurs during administration of norethindrone acetate in the rat.

Animals↗

Effects of dietary substitution of mixed amino acids for glucose on the splanchnic metabolism of plasma triglycerides, cholesterol, carbohydrates, and amino acids in conscious fed baboons.

Splanchnic metabolism was studied in the fed state during prolonged constant intravenous administration of tracer amounts of [9,10]-3H palmitic acid and the calculated isocaloric intraduodenal administration (13 mg/min X kg body wt0.75) of either (1) glucose, (2) 15% mixed amino acids and 85% glucose or (3) 45% mixed amino acids and 55% glucose to conscious, restrained female baboons that had been maintained on a similar diet (supplemented in essential nutrients) for the previous 9 days. Secretion of plasma triglycerides from the splanchnic region was quantified from splanchnic flow and radiochemical measurements of transsplanchnic gradients of 3H-labeled free fatty acids and triglycerides. Mean splanchnic secretion of plasma triglycerides increased significantly as the proportion of dietary calories derived from amino acids was varied from 0 to 15 to 45% (mean values 1.1 +/- 0.1, 2.6 +/- 0.2 and 4.2 +/- 0.3 mumol/min kg body wt0.75, respectively, p less than 0.05). Increased triglyceride secretion was attributable to both significantly higher rates of esterification of free fatty acids taken up in the splanchnic region to triglycerides released into hepatic venous blood plasma (mean values 10 +/- 1, 16 +/- 2 and 34 +/- 5%, respectively) and to significantly higher rates of secretion of triglycerides derived from precursors other than free fatty acids. Higher intake of amino acids was also associated with both higher plasma concentrations of cholesterol and higher values for hepatic oxidation of cholesterol to bile acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Comparison of Intralipid 10% and Intralipid 20% as a source of energy and essential fatty acids--a multicenter study.

A multicenter clinical study was done which directly compared efficacy and safety of Intralipid 10% and Intralipid 20%. Twenty-nine patients received the 10% concentration, 30 patients received the 20% concentration. Both groups of patients received equivalent amounts of calories, amino acids, dextrose and fat for seven day study periods. Analysis of nitrogen balance data showed that the two preparations were equally effective in maintaining nitrogen balance. Both concentrations of fat emulsion were effective in reversing or correcting the changes of essential fatty acid deficiency. Analysis of clinical laboratory data indicated that both preparations were equally well tolerated by the patients. No adverse effects attributed to the fat emulsions were observed.

Adult↗

Long-term venous access in rhesus monkeys.

Long-term, intermittent, intravenous infusion of substances, such as amphotericin B, with a high potential for causing peripheral vein thrombophlebitis was feasible by means of a subcutaneously implanted silastic reservoir catheter device, which gave access to the central venous compartment. The implanted reservoirs withstood at least 100 percutaneous entries with a 27-gauge needle; injections were carried out by using an infusion pump. With precautions taken to prevent infection, clotting, or the formation of precipitates in the catheter, the device permitted easy intravenous injection and was well tolerated.

Animals↗

Energy sources, stores, and hormonal controls.

Energy is required by humans for such vital activities as metabolic processes and muscular contraction. The support of protein synthesis is critical in clinical nutritional support; approximately 25 per cent of energy expenditure is devoted to the support of protein synthesis. Energy is stored as carbohydrate, fat, and protein. Stored carbohydrate is rapidly exhausted, and the utilization of protein for energy is detrimental. Fat storage is usually abundant but cannot be mobilized and oxidized sufficiently to meet energy requirements, particularly in injured or septic patients. The provision of energy sources with amino acids in clinical nutrition permits the most efficient use of amino acids for protein synthesis. The majority of non-protein calories may be provided as either glucose or fat emulsion in patients with mild to moderate degrees of stress, but fat emulsion may be ineffective in severely stressed patients. A reliance on fat emulsion for energy may allow the use of peripheral venous infusion but is more expensive then glucose.

Carbohydrate Metabolism↗

Acute suppurative cholangitis.

Acute suppurative cholangitis is characterized by obstruction, inflammation, and pyogenic infection of the biliary tract associated with the clinical pentad of fever (and chills), jaundice, pain, shock, and central nervous system depression. The disease occurs most commonly in the elderly who have a history of calculous biliary tract disease. The disease represents a true surgical emergency. Appropriate antibiotic therapy and immediate surgical decompression of the biliary tract are essential and carry a mortality rate of approximately 33 per cent. Nonoperative management is uniformly fatal. If inadequately treated or untreated, the disease follows a fulminant course of progressive systemic sepsis, hepatic abscess formation, and heptic failure leading ultimately to death. Acute suppurative cholangitis, the most serious sequela of calculous biliary tract disease, is preventable by early elective surgical treatment for benign biliary tract disease.

Acute Disease↗

Effects of intravenous versus intragastric glucose pretreatment on triglyceride secretion by perfused livers of fed rats.

The effects of the route of administration of 450 mg [U-14C]glucose to 250-g fed rats in vivo on the subsequent release of triglycerides from the perfused liver was studied. Livers were perfused for 180 min using a nonrecycling medium containing 10 mM glucose, 2 mM lactate, 0.2 mM pyruvate, and 100 microunits/mL porcine insulin. Biopsies were obtained at the beginning and end of the perfusions. The perfusate was collected and the secreted triglycerides were analyzed. Slower absorption of the intragastric glucose load contrasted with the rapid entry of the intravenous load; however, the total liver counts were not significantly affected by the route of glucose delivery. Hepatic glycogen concentration was also not significantly different, but the percent of total liver counts which was present in glycogen was significantly higher after intravenous glucose. The majority of the radioactivity in the livers of both groups of rats was present in water-soluble metabolites, with lesser amounts in triglycerides and phospholipids. Radioactivity in hepatic triglycerides declined significantly during perfusion only in the rats which had received glucose intravenously. The mean rate of triglyceride secretion from the livers of rats receiving the glucose intravenously was significantly lower than that of the rats receiving glucose intragastrically (0.21 +/- 0.05 vs. 0.97 +/- 0.28 mg/g liver per 180 min, p less than 0.05). The route of glucose administration affects both entry of glucose into the blood and subsequent hepatic triglyceride metabolism and secretion.

Absorption↗

Evaluation of the results of external choledochoduodenostomy for retained, recurrent, or primary common duct stones.

Twenty-five patients were treated for retained, recurrent, or primary common duct stones by permanent drainage of the biliary tract with external choledochoduodenostomy. Twenty-one patients had common duct stones which became evident two to fifty years after the initial biliary tract procedure and which may represent stones formed in the common duct. Three recent patients had a clinical history of primary common duct stones, had stones which were soluble in chloroform-methanol solution, and had hepatic bile which was lithogenic as determined by evaluating the molar percentage of cholesterol, phospholipid, and bile salt in bile samples obtained at the time of choledochoduodenostomy. These data suggest that further stone formation is possible and that permanent bypass of the sphincter of Oddi is indicated to prevent recurrent bile duct obstruction. Long-term evaluation of the results of external choledochoduodenostomy indicates that the procedure is safe and effective in the prevention of recurrent biliary tract calculi.

Adult↗

Evaluation and management of nutritional status before surgery.

Preoperative evaluation of all patients should include evaluation of nutritional status. Factors of greatest clinical usefulness are nutritional history correlated with the clinical situation, and measures of body height and weight, serum albumin concentration, and muscle mass. Depressed immune function suggested by a lack of skin test reactivity to standard antigens may correlate with the risk of postoperative complications and death, but further studies are required to determine the specific relation of nutrient deficiencies and immune function. Micronutrient deficiencies must be identified and corrected rapidly. Nutritional support in patients with nutritional deficiencies should be started preoperatively either by enteral or intravenous techniques and continued postoperatively.

Anthropometry↗

Glucose promotes whole-body protein synthesis from infused aminoacids in fasting man. Isotopic demonstration.

15N-glycine constant infusion, with plateau urea enrichment as the endpoint, demonstrated a clear increase in whole-body protein synthesis when glucose was added to aminoacid infusion in fasting men. Whole-body protein-breakdown rates remained unchanged. There was an unexpected fall in whole-body nitrogen turnover when the subjects were changed from an oral intake to either of the intravenous programmes: this finding, not previously reported, may be due to the decrease in gastrointestinal enzyme synthesis and intestinal-lining cell-turnover when oral intake is replaced by total parenteral nutrition.

Administration, Oral↗

The effects of glucagon on protein metabolism in normal man.

Plasma glucagon rises after major injury and could act to increase gluconeogenesis and ureagenesis in the post-traumatic state. This study documents the effect of prolonged glucagon infusion on ureagenesis and nitrogen excretion, as well as possible sources of the increased ureagenesis, in normal man. Four healthy men fasted for 6 days during intravenous infusion of glucose (750 gmday), establishing a steady state of minimal ureagenesis. Glucagon (1 mg/day) then was added to the infusion for 5 days. Glucose alone was given for the final 2 days. Forearm muscle flux of metabolites was determined by standard arterial-deep venous sampling and capacitance plethysmography. Glucagon concentration was suppressed during glucose infusion (11 +/- 13 pg/ml) and rose to levels seen in subjects with major trauma during glucagon infusion (669 +/- 138 pg/ml). Glucose infusion stabilized urine nitrogen excretion at 1.54 +/- 0.42 gm of N/sq m/day. Nitrogen excretion increased to 2.40 +/- 0.53 gm of N/sq m/day with glucagon infusion, with urea accounting for the increased excretion. Excretion of 3-methylhistidine was unchanged. Plasma amino acid concentration was strikingly reduced on the first day of glucagon infusion, where it stabilized. Forearm flux showed a slight net release of amino acid nitrogen during glucose infusion. Addition of glucagon to the glucose infusion resulted in a net uptake of nitrogen by forearm skeletal muscle. These evidences strong suggest that glucagon infusion in normal man increases ureagenesis, not only at the expense of the free amino acid pool, but by the hydrolysis of visceral protein as well, with muscle protein being maintained.

Amino Acids↗

Norethindrone acetate inhibition of splanchnic triglyceride secretion in conscious glucose-fed siwne.

The effects of conventional doses of two synthetic contraceptive steroids on the concentration and rate of secretion of plasma triglycerides from the splanchnic region were investigated. Studies were undertaken in miniature swine under steady state conditions produced by prolonged constant hypercaloric intravenous infusions of glucose. The steroids, alone or in combination, were administered with the high carbohydrate diet for at least 2 weeks prior to study of splanchnic metabolism and were also infused intravenously during the studies. Splanchnic triglyceride secretion was determined from measurements of plasma flow and transsplanchnic radiochemical gradients of plasma triglycerides. Compared with studies in the untreated animal, norethindrone acetate significantly reduced the arterial concentration (1.1 +/- 0.1 vs. 0.7 +/- 0.1 mM) and rate of splanchnic secretion of plasma triglyceride fatty acids (2.0 +/- 0.4 vs. 0.8 +/- 0.1 micro mol/min.kg body wt(0.75)) and decreased the percent of free fatty acids entering the splanchnic region that was converted to plasma triglycerides (22 +/- 5 vs. 13 +/- 3%, P < 0.05). Ethynylestradiol, in the dose employed, had no significant effect on these variables; however, ethynylestradiol and norethindrone acetate together gave responses similar to norethindrone acetate alone. When the glucose was given intraduodenally vs. intravenously, values for splanchnic metabolism of triglycerides were unchanged. The hypolipemic effect of norethindrone acetate in glucose-fed swine was attributable to inhibition of hepatic triglyceride secretion.-Wolfe, B. M., and D. M. Grace. Norethindrone acetate inhibition of splanchnic triglyceride secretion in conscious glucose-fed swine.

Animals↗