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Biomedical subjects

J E Fischer

Publications and source records attributed to J E Fischer.

At least 19 recordsLinked to original sources
PubMed1979

Hyperammonaemia, plasma aminoacid imbalance, and blood-brain aminoacid transport: a unified theory of portal-systemic encephalopathy.

It is proposed that hyperammonaemia in liver cirrhosis or after portacaval shunt contributes to plasma neutral aminoacid imbalance and to increased activity of the blood-brain neutral amino-acid transport system. Plasma neutral aminoacid concentrations are deranged, partly, but not completely, because ammonia stimulates glucagon secretion; a high rate of gluconeogenesis and hyperinsulinaemia follow. Brain uptake of neutral aminoacids rises because ammonia stimulates brain-glutamine synthesis, which results in rapid exchange of brain glutamine for plasma neutral aminoacids. Hyperammonaemia therefore contributes to encephalopathy indirectly, by raising the brain concentration of neutral aminoacids which after neurotransmitter metabolism, rather than directly, by toxic effects on neuronal metabolism.

Amino Acids, Branched-Chain↗
PubMed1979

Chronic hepatic encephalopathy. Long-term therapy with a branched-chain amino-acid-enriched elemental diet.

Therapy of chronic hepatic encephalopathy is often frustrating, limited as it is by the ability to adequately nourish such patients. Protein is needed for repair, but such patients are intolerant of protein. Previous work from this and other laboratories has suggested that the distorted plasma amino acid pattern may be causally related to hepatic encephalopathy. A single, well-studied, long-term patient received therapy with a branched-chain amino-acid-enriched elemental diet that not only enabled adequate nutrition with protein but resulted in improvement in hepatic function as well as reversal of some aspects of hepatic encephalopathy that heretofore have been deemed irreversible. The results confirm that branched-chain-enriched amino acid diets previously successful in the intravenous mode may be successfully used in chronic long-term support of patients with protein intolerance, with improvement in hepatic function secondary to improvement in nutrition.

Administration, Oral↗
PubMed1979

Chromium deficiency during total parenteral nutrition.

Chromium is required for maintenance of normal glucose tolerance. After complete bowel resection and five months of total parenteral nutrition, severe glucose intolerance, weight loss, and a metabolic encephalopathy-like confusional state developed in a patient. Serum chromium levels were at the lowest normal level. Supplementation of 150 microgram of chromium per day reversed the glucose intolerance, reduced insulin requirements, and resulted in weight gain and the disappearance of encephalopathy. The low levels of chromium and response to chromium supplementation suggest that chromium deficiency can arise in long-term total parenteral nutrition.

Blood Glucose↗
PubMed1979

Brain tryptophan and the neoplastic anorexia-cachexia syndrome.

The cause of anorexia associated with neoplasia is unknown, and some investigators have suggested a central mechanism. Recent neurophysiologic studies have revealed the possible role of serotoninergic system involving tryptophan (TRP) and its indole neurotransmitter metabolites in regulating particular aspects of feeding behavior. We therefore studied plasma and brain factors affecting TRP transport through the blood-brain barrier (plasma free and total TRP, albumin, nonesterified fatty acids, plasma neutral amino acids, brain uptake index [BUI] for TRP) and central serotonin metabolism (5-HT, 5-HIAA) in young, anorexic rats bearing the Walker-256 tumor injected intramuscularly. Plasma free TRP, but not plasma total TRP, and, more important, brain TRP and brain 5-HIAA were significantly higher in tumor-bearing rats than in pair-fed control animals. The results suggest an association between altered brain TRP metabolism and feeding behavior in tumor-related anorexia.

Animals↗
PubMed1979

Release of vasoactive intestinal peptide in the central nervous system in man.

Recent work has shown that vasoactive intestinal peptide (VIP), one of the many candidate hormones of the gut, also occurs widely in neurones. To determine whether the neuronal peptide may have a neurotransmitter function, we studied changes in immunoreactive VIP in dog plasma and human cerebrospinal fluid after the infusion of choline esterase inhibitors (neostigmine and physostigmine, respectively). Immunoreactive VIP was released in both situations. The systemic changes (in VIP levels) were enhanced five weeks after portacaval shunting in dogs. Our results demonstrate that the immunoreactive VIP level increases as a result of choline esterase inhibitors. The plasma "release" may originate either from peripheral peptidinergic nerve terminals or from APUD cells of the gastroenteropancreatic system. The increase in immunoreactive cerebrospinal fluid VIP may very well originate from central neurons, since the peptide does not apparently cross the blood-brain barrier.

Animals↗
PubMed1979

Hyperalimentation.

As widespread use of parenteral nutrition enters the second decade, it is obvious that a great deal of progress has been made, both as to increasing safety and developing new solutions. There are few hard data in this area, not surprising in so young a field. Prospective studies hopefully will yield definitive results in areas in which such knowledge is lacking. More importantly, better understanding of various disease states will undoubtedly result in the modification of existing solutions to allow for better treatment.

Ambulatory Care↗
PubMed1979

Infusion of the branched chain amino acids in postoperative patients. Anticatabolic properties.

Postinjury metabolism is characterized by breakdown of muscle protein as substrate for energy production and gluconeogenesis and by the resultant loss of lean body mass and weight loss. The branched chain amino acids (BCAAs) which are principally oxidized by the skeletal muscle have been implicated in recent in vitro and in vivo studies as having special anticatabolic and regulating effects in skeletal muscle. We studied the anticatabolic effects of the BCAAs in 35 patients undergoing operative injury of moderate severity. In a prospective randomized and blinded manner patients were infused for five days starting immediately after surgery with either 5% dextrose or 5% dextrose with an amino acid solution containing 22, 35 or 100% BCAAs. All patients survived and there were no major postoperative complications. Mean hospital stay was 17 days for patients receiving amino acids and 19 days for patients receiving 5% dextrose only (p = ns). All three groups receiving amino acid solutions were in nitrogen equilibrium or in a slight positive nitrogen balance, while the group receiving 5% dextrose only was in a mean negative nitrogen balance of 6.6 +/- 0.6 gN/day. The differences between the three groups receiving amino acids were slight and not significant. Weight loss was 2 +/- 0.7 kg in the 5% dextrose group, 1 +/- 0.7 kg in the 22% BCAAs group, 0.5 +/- 0.5 kg in the 35% BCAAs group and the 100% BCAAs group gained 0.4 +/- 1.8 kg. Blood chemistries in the different groups and during the study period remained within normal limits except for ammonia levels rising significantly in the 5% dextrose group and SGOT levels rising in the 22% and 35% BCAA groups. With mild variations the plasma amino acid patterns in all groups were similar to the normal pattern, even in the 100% BCAAs group receiving an unbalanced amino acid solution, suggesting the complete cessation of amino acid efflux from muscle, the muscle depending solely on the exogenous supply of BCAAs to satisfy its metabolic requirements. The results suggest that early nutritional suppport in the postoperative period will result in nitrogen equilibrium and that the infusion of the three BCAAs only in the postoperative state is as effective in preventing muscle catabolism as other more balanced amino acid solutions. In the postinjury state balanced amino acid solutions rich in BCAA may prove beneficial.

Adult↗
PubMed1979

Essential fatty acid deficiency in total parenteral nutrition. Detection by changes in intraocular pressure.

Essential fatty acid deficiency (EFAD) has been commonly and readily diagnosed during fat-free total parenteral nutrition (TPN), with only vague awareness of possible functional and clinical derangements secondary to essential fatty acid deficiency. Arachidonic acid is known to be a precursor for prostaglandin (PG) synthesis. Prostaglandins are known to be intermediaries between stimulus and cellular response in a variety of physiologic and pathologic processes; one would suspect therefore that EFAD would result in PG deficiency with resultant multiple derangements in functions regulated by PG. We tested this hypothesis by serially measuring intraocular pressure (IOP) in patients before and during fat-free TPN and after supplementing these patients with fat. In the eye as well as in various other organs PG are believed to act as mediators of adrenergic neurotransmission by a negative feedback mechanism. As catecholamines are potent ocular hypotensive agents, decreased levels of PG due to EFAD will cause increase in catecholamine turnover with a reduction in IOP. Two groups of patients matched as to their age, sex, nutritional status and diseases were studied. One group (control) was receiving a normal diet or fat-containing TPN while the other group was receiving fat-free TPN. IOP in the fat-free TPN group dropped from 13.7 +/- 0.4 mmHg pre-TPN to 9.3 +/- 0.5 mmHg during the first week of fat-free TPN. Within two weeks after supplementation of fat or return to normal oral diet IOP returned to 13.9 +/- 0.3 mmHg. Prostaglandin levels, which were 0.025 +/- 0.004 ng/ml pre-TPN or in control patients decreased to 0.012 +/- 0.002 ng/ml (p < 0.001) during fat-free TPN, to return to normal after fat was added to TPN regime or patients returned to normal oral diet. During fat-free TPN linoleic acid levels decreased to 40% of its initial value with a mild increase upon the addition of fat, while eicosatrienoic acid and the triene:tetraene ratio increased to 6.5 times their initial values. Arachidonic acid levels did not change during fat-free TPN or after repletion with fat. Intraocular pressure determination seem to be a simple, harmless, inexpensive, reliable and sensitive indicator of EFAD. Moreover, IOP determination represent a functional derangement which in a clinical setting lends functional credence to the biochemical changes of EFAD whose entire significance has not yet been determined. Similarly, serial IOP determinations are sensitive in detecting adequate functional repletion of EFAD. As PG are known to act as intermediaries in a variety of physiological processes it seems reasonable to assume that the change in IOP is only one of many different changes and derangements to occur as a result of PG and EFA deficiency.

Adult↗
PubMed1979

Review of 404 patients with gastrointestinal fistulas. Impact of parenteral nutrition.

This paper represents an extensive review, spanning 30 years of experience with 404 patients with gastrointestinal fistulas. It includes the first period (1945-1960) during the introduction of antibiotics, the second period (1960-1970) which saw rapid improvements in parasurgical care including, respiratory support, perfection of antibiotics, some introduction of nutritional support and improved monitoring, and the third period which saw the introduction of parenteral nutrition specifically central venous hyperalimentation using hypertonic glucose and amino acids (1970-1975) in the treatment of patients with fistulas. The principal causes for mortality in the historical sense were malnutrition, sepsis and electrolyte imbalance. Mortality among patients with gastrointestinal cutaneous fistulas decreased between the first and second periods from approximately 48 to 15%. Surprisingly, mortality did not decrease further in the "hyperalimentation period" although spontaneous closure of gastrointestinal fistulase increased. The results suggest that the improvement in mortality in patients with gastrointestinal cutaneous fistulas is mostly due to the introduction of improved parasurgical care. It is acknowledged that nutritional support was practiced in the 1960's although this was generally not in the form of hyperalimentation. The addition of hyperalimentation in large scale to the treatment of gastrointestinal cutaneous fistulas has improved spontaneous closure and is a valuable part of the armamentarium. The decrease in mortality however, cannot be attributed to parenteral nutrition.

Female↗
PubMed1979

Plasma amino acids as predictors of the severity and outcome of sepsis.

Sepsis is a major catabolic insult resulting in a peripheral energy deficit which is made up in part by increased breakdown of lean body mass and oxidation of amino acids, principally the branched chain amino acids. The prognosis in any given case of sepsis is difficult to predict, but should theoretically be related to the degree of disturbance in peripheral energy deficit, which may in turn, be related to plasma amino acid pattern. In order to study whether this hypothesis was correct, plasma amino acids and some of their metabolic byproducts, the beta-hydroxyphenylethanolamines, were studied in 25 septic patients, and were used as discriminant variables in a series of computer performed discriminant analyses and multiple regressions. The two functions tested were the degree of metabolic septic encephalopathy as a determinant of the severity of sepsis and the final outcome in the septic patient. Plasma amino acid patterns exhibited elevated levels of the aromatic and sulfur containing amino acids, phenylalanine, tryosine, tryptophan, methionine, cysteine, and taurine, normal concentrations of alanine, and low normal concentrations of the branched chain amino acids, valine, leucine and isoleucine. Arginine levels, as previously noted, were very low. Patients not surviving the septic episode exhibited higher concentrations of aromatic and sulfur containing amino acids, while patients surviving sepsis had higher concentrations of the branched chain amino acids and arginine. When the degree of encephalopathy as a determinant of the severity of sepsis and step wise discriminant analysis with multiple crescent techniques were used, the best discriminant function between patients with and without encephalopathy was found to result from the interaction of cysteine, methionine, phenylalanine, isoleucine, leucine, and valine. These amino acids gave a correct classification in 82% of patients with no encephalopathy, and 80% of patients with septic encephalopathy. When the same amino acids were used for the discriminant analysis for patients dying of sepsis and patients surviving, the best discriminant function was achieved by using plasma concentrations of alanine, cysteine, methionine, isoleucine, arginine, tyrosine and phenylalanine resulting in 91% of the nonsurvivors, and 79% of the survivors correctly classified. The results suggest a close and significant relationship between the deranged energy metabolism and muscle protein breakdown in sepsis, and the outcome. This further suggests a central role for certain amino acids in perhaps predicting the severity of sepsis and its outcome.

2-Hydroxyphenethylamine↗
PubMed1979

Effect of exercise on postoperative nitrogen balance.

This study was designed to investigate whether exercise, when used as an adjunct to parenteral nutrition, has any influence on postoperative muscle catabolism, amino acid metabolism, and nitrogen balance. Twenty male Sprague-Dawley rats were divided into two groups of exercised and nonexercised animals. All animals underwent laparotomy and jugular vein cannulation, were placed in metabolic cages, and were infused with a dextrose-protein solution at 15 kcal and 0.56 g amino acids/100 g body wt per 24 h for a total of 96 h. The exercised animals were run on a treadmill for 15 min/day for a total of 3 days. There was no difference in nitrogen balance and body weight change between exercised and nonexercised animals, as well as no difference between animals who experienced different degrees of exercise. Total and individual plasma amino acids in the exercised group were 15% lower than in the nonexercised group; the total and individual free amino acids in muscle of the exercised group were 66% higher than in the nonexercised group. This pattern of high levels of amino acids in the muscle, coupled with decreased plasma concentrations, is suggestive of increased amino acid turnover in the muscle of the exercised animals. We suggest that, in the postoperative or postinjury period, exercise has a stimulating effect on amino acid turnover in the skeletal muscle resulting from 1) amino acid (mainly the branched-chain amino acids) consumption for energg metabolism and gluconeogenesis, and 2) protein synthesis. The net balance of both results in nitrogen equilibrium similar to that of a nonexercised control group.

Amino Acids↗
PubMed1979

Disseminated intravascular coagulation with the peritoneovenous shunt.

Coagulation data were collected before and after peritoneovenous shunting for intractable ascites in 19 shunting procedures. After insertion of the shunts, changes consistent with disseminated intravascular coagulation developed in all cases in which good flow of ascitic fluid was obtained. In cases with temporary shunt function, the coagulation variables suggestive of disseminated intravascular coagulation returned toward normal when the flow of ascitic fluid ceased. A fall in the level of fibrinogen degradation products indicated that the shunt had clotted. Bleeding attributable to disseminated intravascular coagulation alone was uncommon. Clotting of the shunts was frequent. The use of heparin improved some of the coagulation variables but did not prevent shunt clotting or clinical bleeding. We conclude that the peritoneovenous shunt induces a moderate disseminated intravascular coagulation and that measurement of fibrinogen degradation products is useful in assessing shunt function.

Adult↗