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Biomedical subjects

J E Fischer

Publications and source records attributed to J E Fischer.

At least 361 records · Page 20Linked to original sources
PubMed1981

Blood-brain barrier derangement in sepsis: cause of septic encephalopathy?

Patients with sepsis often manifest disorientation, somnolence, asterixis and coma, symptoms also seen in portasystemic encephalopathy. Altered plasma concentrations of the neutral amino acids and in creased blood-brain transport of these acids may play a role in portasystemic encephalopathy. Plasma amino acids and blood-brain barrier transport of neutral amino acids were investigated in a rat model of abdominal sepsis, cecal ligation and puncture. The blood-brain transport was studied by the technique of Oldendorf with carbon-14-amino acids 12 and 24 hours after the induction of sepsis. In similar groups of animals, isolation of brain capillaries was carried out by the technique of Hjelle and the capillaries were incubated with carbon-14-amino acids to study transport activity. Plasma and brain amino acids were deranged in a fashion similar to the derangements seen in portasystemic encephalopathy, with a decrease in plasma branched chain amino acids and an increase in most neutral amino acids in brain. The changes were most pronounced after 24 hours. The brain uptake of several neutral amino acids was increased in the septic rats, while the uptake of lysine, a basic amino acid, was normal. In the brain capillaries isolated from septic rats, tyrosine and leucine transport was also greater than in sham-operated animals. Elevated neutral amino acids may play a role in the encephalopathy encountered in septic patients similar to its role in patients with portasystemic encephalopathy, as similar mechanisms appear to be operating.

Abdomen↗
PubMed1981

Reduced tissue content of vasoactive intestinal peptide in aganglionic colon of Hirschsprung's disease.

The colonic tissue content of immunoreactive vasoactive intestinal peptide was measured in four children with histologically proven Hirschsprung's disease. The concentration of vasoactive intestinal peptide was lower in the aganglionic bowel than in nearby normal bowel. Similar results have been described for another gastrointestinal peptide: substance P. Abnormalities of peptidergic control may contribute to the motility disorder of congenital aganglionic colon.

Child↗
PubMed1981

Gastrin and gastric acid secretion in renal failure.

In 10 anephric patients awaiting transplantation, 15 patients with chronic renal failure and 30 patients with acute renal failure, daily basal plasma gastrin levels and basal and stimulated gastric acid secretion were measured. Significant elevated plasma gastrin levels were found in all of the anephric patients and in 50 percent of the patients with acute and 55 percent of those with chronic renal failure. Elevated plasma gastrin levels decreased to normal after kidney transplantation or when kidney function returned to normal in the patients with acute renal failure. Gastric acid secretion studies showed a consistent pattern in all three groups of patients with a low basal acid output, a high basal intragastric pH and a very significant peak acid output, perhaps secondary to elevated plasma gastrin levels due to inadequate renal inactivation of gastrin. This may partly explain the increased incidence of gastrointestinal bleeding and gastritis seen in patients with different degrees of renal failure.

Acute Kidney Injury↗
PubMed1981

Comparison of distal and proximal splenorenal shunts: a randomized prospective trial.

Controversy still surrounds the place of portalsystemic shunting in the therapy of bleeding esophageal varices. Recently, a selective shunt, the distal splenorenal shunt, has achieved some degree of popularity and, apparently, is associated with less chronic encephalopathy. Because of this, a trial was initiated at the Massachusetts General Hospital and continued at the University of Cincinnati Medical Center, prospectively randomizing central and distal splenorenal shunts in consecutive elective cases of patients with established variceal bleeding. Preoperative evaluation included endoscopic examination at the time of hemorrhage, angiography and upper gastrointestinal series, emphasis on mental function including EEG, amino acids, neurologic examination, as well as standard liver chemistries. Nineteen patients underwent central splenorenal shunts and 23 distal splenorenal shunt. There was one operative death from hemorrhagic pancreatitis in a Child's Class A patient with distal splenorenal shunt. Four late deaths, from gunshot wound, auto accident, overwhelming pneumonitis similar to postsplenectomy syndrome, and metastatic carcinoma (2.5 years after operation), have been recorded in the distal splenorenal shunt group, and none in the central splenorenal shunt group. On follow-up angiographic examination, six shunts have clotted, with three patients requiring reoperation, generally mesocaval shunt. There has been no chronic encephalopathy, three individual episodes of encephalopathy, two in the central splenorenal shunt group and one in the distal splenorenal shunt group, two associated with gastrointestinal bleeding and one with intercurrent infection and overdiuresis. Follow-up liver chemistries and amino acids which may be useful as an indicator of hepatic function suggest that although the distal shunt group had a better amino acid pattern before operation, branched-chain amino acids tend to become lower in the distal group while remaining the same in the central group. Aromatic amino acids increase post shunt, equally in the two groups. The results do not support the contention that distal splenorenal shunt is associated either with greater survival or freedom from encephalopathy than central splenorenal shunt, a small side-to-side shunt. Ascites seems better controlled by the central splenorenal shunt.

Adult↗
PubMed1981

Uptake of amino acids by brain microvessels isolated from rats after portacaval anastomosis.

The uptake of amino acids by microvessels isolated from brains of rats was studied. Previous studies have demonstrated alterations in blood-brain amino acid transport after portacaval shunt in rats. In order to elucidate whether such changes in the blood-brain barrier were located in the microvessels, brain microvessels were isolated from both rats with portacaval shunt and controls. Brain microvessels from rats 2 weeks after shunt operations took up significantly greater amounts of 14C-labeled neutral amino acids, but not of glutamic acid, lysine, or alpha-methylaminoisobutyric acid than microvessels from sham-operated controls. Measurement of uptake kinetics showed a higher Vmax for phenylalanine and leucine uptake and a lower Vmax for lysine uptake in microvessels from shunted rats compared with control, whereas the respective Km's of uptake were similar in both preparations. The results suggest that changes in brain microvessel transport activity account for altered brain neutral amino acid concentrations after portacaval shunt and that such changes can be studied in vitro in isolated microvessels.

Amino Acids↗
PubMed1981

Transport of neutral amino acids at the blood-brain barrier.

The movement of neutral amino acids across the blood-brain barrier is bidirectional, however, blood to brain transport is much better characterized than brain to blood transport. Available evidence points to the existence of a single transport system (system L) at the luminal capillary surface. The properties of this system place constraints on possible mechanisms of regulating blood-brain neutral amino acid transport activity. One property, mediation of exchange transport, suggests that amino acid influx is coupled to efflux, particularly efflux of glutamine, synthesized in glial astrocytes from ammonia and glutamic acid. Such a coupling could account for increased blood-brain neutral amino acid transport in liver disease and decreased transport activity after treatment with methionine sulfoximine, a glutamine synthetase inhibitor.

Amino Acids↗
PubMed1981

An increase in vasoactive intestinal peptide levels in canine endotoxin shock.

Some of the many metabolic and cardiovascular activities and effects of vasoactive intestinal peptide are quite similar to the changes observed in endotoxin shock. The changes occurring in plasma vasoactive intestinal peptide levels during canine endotoxin shock were studied. Vasoactive intestinal peptide levels were markedly and significantly elevated following the administration of endotoxin, corresponding well with the drop in systemic blood pressure. In the dogs surviving the experiment, plasma vasoactive intestinal peptide levels returned to normal levels after 24 hours, corresponding well with the restoration of normal hemodynamic values. Surviving dogs exhibited significantly lower vasoactive intestinal peptide levels than did nonsurvivors. Many of the biologic activities of vasoactive intestinal peptide make it suitable for counteracting endotoxemia, thus acting as the defense of the body against endotoxin. However, the lower vasoactive intestinal peptide levels in the surviving dogs rather points to vasoactive intestinal peptide as a causative factor in canine endotoxemia.

Animals↗
PubMed1981

Nitrogen-sparing mechanisms of singly administered branched-chain amino acids in the injured rat.

Previous studies have demonstrated that the in vivo nitrogen-conserving quality of amino acid solutions might be improved by increasing the percentage of branched-chain amino acids (BCAA) and that infusion of a solution consisting only of the three BCAA-valine, leucine, and isoleucine-in the postoperative period resulted in nitrogen equilibrium. To clarify which of the properties ascribed to the BCAA is responsible for the improved postoperative nitrogen conserving quality, we infused rats undergoing laparotomy and jugular vein cannulation with each of the BCAA or alanine separately. Twenty-four hours before the were killed 5 microCi 14C-tyrosine was added to the infusate to determine total body protein degradation and fractional synthesis rate in liver and muscle. All four amino acid-containing solutions conserved nitrogen as compared with 6.5% dextrose. Fractional synthesis of rate mixed liver protein was significantly increased in all groups receiving BCAA. Only the infusion of valine significantly increased muscle protein synthesis. Total body protein breakdown rate was similarly decreased in all groups receiving amino acids (alanine, valine, leucine, or isoleucine). Total body protein breakdown correlated significantly with the nitrogen balance. The protein-sparing mechanisms of the BCAA in the post-traumatic period are mediated through reduction in whole body protein breakdown, as well as by increasing protein synthesis in both liver and muscle protein. These results appear specific for the BCAA as isonitrogenous amounts of alanine do not give similar results.

Alanine↗
PubMed1980

Does intravenous fat spare nitrogen in the injured rat?

The role of glucose versus fat as a source of energy in parenteral nutrition is controversial, particularly when administered after trauma, injury or in sepsis. In the present series of experiments, rats undergoing laparotomy and jugular vein cannulation were infused with hypertonic glucose or Intralipid with and without amino acids. The results demonstrate that the combination of amino acids and glucose has a better nitrogen-conserving ability than amino acids and fat, lasting at least 4 days after injury. However, when infused without amino acids, fat had the same nitrogen-conserving quality as glucose. The authors attribute the improved nitrogen-conserving quality of amino acids and glucose to the specific carbohydrate influence on amino acid metabolism, an action which is specific in both protein-free and protein-containing meals but has only very limited effect in the absence of simultaneously infused or fed amino acids. In the moderately to severely injured rat, a glucose calorie is significantly more effective in sparing nitrogen than a fat calorie.

Amino Acids↗
PubMed1980

Plasma amino acid analysis in the differential diagnosis of jaundice.

Distinguishing between obstructive (surgical) and hepatocellular (medical) jaundice is sometimes impossible using the relatively simple diagnostic means of history, physical examination and liver function tests. In an attempt to reduce the number of jaundiced patients in need of complex and expensive diagnostic procedures, we investigated the use of the plasma amino acid pattern in the diagnosis of jaundice. Jaundiced rats with galactosamine-induced hepatitis and seven patients with acute onset hepatitis presented a plasma amino acid pattern in which most all amino acid levels were elevated except for arginine in the rat and branched chain amino acids in the patients. Rats jaundiced due to common bile duct ligation and seven patients with obstructive jaundice proved at surgery exhibited a near-normal amino acid pattern. These experimental and clinical data demonstrate very clear qualitative and quantitative differences in plasma amino acid patterns of hepatocellular and obstructive jaundice, with the latter exhibiting an almost-normal pattern. We suggest the use of the plasma amino acid pattern as a useful adjunct in the differential diagnosis of medical and surgical jaundice.

Adult↗