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Biomedical subjects

J E Fischer

Publications and source records attributed to J E Fischer.

At least 289 records · Page 16Linked to original sources
PubMed1986

Septic encephalopathy. Etiology and management.

There are widespread disturbances in hepatic and peripheral metabolism in sepsis. Prominent effects include elevated plasma concentrations of aromatic and sulfur-containing amino acids during sepsis, while BCAA are normal or reduced. These alterations probably in part reflect accelerated muscle protein breakdown and hepatic dysfunction. Concomitant with changes in plasma amino acids, altered brain levels of amino acids and neurotransmitters are observed. Increased brain concentrations of the serotoninergic and reduced levels of the catecholaminergic neurotransmitters, along with the occurrence of false neurotransmitters, may be important factors in the pathophysiology of septic encephalopathy. Although the main objective in the treatment of septic patients, of course, is to remove or drain the septic focus, recent studies have shown that administration of BCAA-enriched solutions may be beneficial in the improvement of metabolic derangements and septic encephalopathy. It should be emphasized that not a great deal of work has been done in this area, and the above results are preliminary and fragmentary. However, they do at least provide a working hypothesis for testing of another form of metabolic encephalopathy.

Amino Acids↗
PubMed1986

Liver resection. A comparison using the Nd-YAG laser, an ultrasonic surgical aspirator, or blunt dissection.

Before gaining wide acceptance, possible surgical tools should be compared with the standard ones. This study, therefore, compared the Nd-YAG laser and the CUSA with the standard blunt dissection technique for liver resection in 24 dogs (8 in each group). Using a noncontact technique, the Nd-YAG laser was used for cutting as well as coagulation. The Nd-YAG laser or the CUSA reduced the resection time, with the laser being the faster of the two, and was accompanied by a probable but not significant decrease in perioperative blood loss. The CUSA delineated the blood vessels and bile ducts and gave superior control. It also caused significantly less tissue damage on light and electron microscopic examination than the other two methods. Cultures taken 1 week after operation showed that the risk of bacterial infection correlated well with the extent of tissue necrosis and was significantly greater after use of the Nd-YAG laser than after use of the CUSA. The numbers of animals are small and the conclusions should be tempered by caution, but it appears that the CUSA, but not the Nd-YAG laser, may improve the results of elective liver resection.

Animals↗
PubMed1986

Effect of Intralipid on clearance and organ uptake of bacteria in intra-abdominal sepsis in rats.

Although infusion of Intralipid has been reported to block reticuloendothelial system (RES) function, it is unclear if this is true at rates used clinically. This study investigates the effect of Intralipid, infused at a rate providing about half of the non-protein caloric needs, on survival and bacterial clearance in septic rats. Continuous infusion of Intralipid (0.9 g/100 g bw/d) or saline (controls) was started immediately after induction of hyperdynamic intra-abdominal sepsis (bacterial agents: E. coli, B. thetaiotamicron). RES function was studied by means of intravenous injection of Selenium-labelled, viable E. coli after 24 or 48 h. Compared to the saline-treated controls, Intralipid did not cause any change in clearance from blood or localisation to liver, spleen or lungs. The 24 and 48 h survival rates were about 80 and 65%, respectively, and similar in the two groups. It is concluded that infusion of Intralipid at a rate close to that used clinically did not impair survival or bacterial clearance in rats with gram-negative sepsis.

Journal Article↗
PubMed1986

Lack of synergy between phagocytes and antimicrobials against Nocardia asteroides.

Previous observations suggested that synergy between antimicrobials and phagocytes may occur during Nocardia asteroides infection. We incubated N. asteroides with seven antimicrobials, and then exposed the nocardiae to phagocytes. Neutrophils and monocytes killed about half the nocardiae whether or not the nocardiae had been preincubated with antimicrobials. We also determined whether exposure to neutrophils led to increased susceptibility of nocardiae to antimicrobials, and it did not. We found no evidence for synergy between antimicrobials and phagocytes in host defence against this bacterium.

Adult↗
PubMed1986

Branched chain amino acid-enriched solutions in the septic patient. A randomized, prospective trial.

A prospective, randomized trial was undertaken to compare the nutritional efficacy in surgical stress of a standard amino acid solution and two branched chain-enriched amino acid solutions: one enriched primarily with valine, the other with leucine. The study comprised 37 patients in the surgical intensive care unit who received isocaloric, isonitrogenous parenteral nutrition started within 24 hours of the onset of major operation, injury, or sepsis. Nitrogen retention was marginally but statistically significantly better on days 5, 7, and 10 in both groups of patients receiving the branched chain-enriched solutions, but differences in cumulative nitrogen balance were not statistically significant. Amino acid composition appeared to be important in that the group receiving the leucine-enriched solution appeared to maintain hepatic protein synthesis better (as manifest by higher short-turnover plasma protein concentrations) and required less exogenous insulin to maintain euglycemia. Improved outcome was not seen in the groups receiving the branched chain-enriched solutions.

Adolescent↗
PubMed1986

Inhibited muscle amino acid uptake in sepsis.

Amino acid uptake in vivo was determined in soleus (SOL) muscle, diaphragm, heart, and liver following intravenous injection of [3H]-alpha-amino-isobutyric acid ([3H]-AIB) in rats made septic by cecal ligation and puncture (CLP) and in sham-operated controls. Muscle amino acid transport was also measured in vitro by determining uptake of [3H]-AIB in incubated extensor digitorum longus (EDL) and SOL muscles. Results were expressed as distribution ratio between [3H]-AIB in intracellular and extracellular fluid. AIB uptake in vivo was reduced by 90% in SOL and cardiac muscle and by 45% in diaphragm 16 hours after CLP. In contrast, AIB uptake by liver was almost four times higher in septic than in control animals. AIB uptake in vitro was reduced by 18% in EDL 8 hours after CLP but was not significantly altered in SOL at the same time point. Sixteen hours after CLP, AIB uptake was significantly reduced in both muscles, i.e., by 17% in EDL and by 65% in SOL. When muscles from untreated rats were incubated in the presence of plasma from septic animals (16 hours CLP) or from animals injected with endotoxin (2 mg/kg body weight), AIB uptake was reduced. Addition of endotoxin in vitro (2-200 micrograms/ml) to incubated muscles did not affect AIB uptake. The results suggest that sepsis leads to marked impairment of amino acid transport system A in muscle and that this impairment is mediated by a circulating factor that is not endotoxin. Reduced uptake of amino acids by skeletal muscle during sepsis may divert amino acids to the liver for increased gluconeogenesis and protein synthesis.

Amino Acids↗
PubMed1986

Anal continence following Soave procedure. Analysis of results in 100 patients.

The Soave procedure is an increasingly popular procedure for the definitive therapy of patients with ulcerative colitis. The authors present their experience with 100 patients in whom total proctocolectomy, rectal mucosal stripping, and ileoanal anastomosis (generally using an S-pouch) were carried out. The physiological and anatomical basis of continence is presented, and anastomosis at the top of the columns of Morgagni is recommended. Of the 100 patients in whom this procedure was performed, there was no mortality either in-hospital or later. Of the 12 patients in whom the anastomosis was done 1 cm above the top of the columns (and thus columnar epithelium was retained), six have recurrent anorectal disease, but all are continent both day and night. Three patients in whom the anastomosis was done at the dentate line have had difficulty with continence; two are now continent, but one, after being totally incontinent for 4 years, has required a permanent ileostomy. Of the 69 patients in whom the anastomosis was done at the top of the columns of Morgagni, five are incontinent at night only and two have seepage during both day and night. Thus, if the anastomosis is done at the level recommended, namely, at the top of the columns of Morgagni, retaining no columnar epithelium and anastomosing the ileal pouch to transitional epithelium (which the authors believe not to be subject to the disease of ulcerative colitis), daytime continence will be achieved in 97% and total day and night continence in 90%. The evidence presented suggests that a properly done pull-through procedure with ileoanal anastomosis is the procedure of choice for ulcerative colitis.

Adolescent↗
PubMed1986

Hepatic steatosis in total parenteral nutrition: failure of fatty infiltration to correlate with abnormal serum hepatic enzyme levels.

Total parenteral nutrition (TPN) is associated with hepatic biochemical and morphologic changes. Suggested causes include excessive glucose calories, fatty acid deficiency, and enterically derived hepatotoxins escaping atrophied bowel. Male Sprague-Dawley rats were cannulated or sham operated with internal jugular ligation. The cannulated groups received TPN with a 25% dextrose base, or TPN 12.5% dextrose and given nothing by mouth, or saline solution and allowed to eat ad lib. Sham animals ate ad lib. After 6 days the animals were killed and portal blood was assayed for endotoxin and cultured. Cultures were also taken of the liver. Serum hepatic enzyme concentration and hepatic fat were determined. All cultures and endotoxin assays were negative. Microscopy revealed nonlipid vacuolization in both TPN groups, a finding reproduced by direct portal infusion of endotoxin. There was significant hepatic steatosis in the 25% dextrose base TPN versus all other groups (28.6% liver weight versus 6.3% liver weight; p less than 0.05). This was correlated with caloric intake (28.7 calories/100 gm/day versus 21.2 calories/100 gm/day; p less than 0.05). Liver enzymes were not significantly different among groups. We conclude that hepatic steatosis in TPN is a result of overfeeding a glucose only substrate and that fatty infiltration is independent of changes in blood hepatic enzyme concentrations. Although other morphologic changes of hepatotoxin-induced injury were seen in the TPN group, portal endotoxemia to the level of 1 ng/ml could not be documented.

Animals↗
PubMed1986

Reduced muscle amino acid uptake in sepsis and the effects in vitro of septic plasma and interleukin-1.

Inhibited amino acid transport in skeletal muscle during sepsis has been demonstrated previously. In the present study we investigated the effects in vitro of plasma from septic animals or fractions of septic plasma that contain solutes with a molecular weight less than 30,000 daltons or less than 2000 to 3000 daltons on amino acid transport in incubated rat soleus (SOL) muscles. The influence of interleukin-1 (IL-1), prostaglandin E2 (PEG2), and the "catabolic" hormones corticosterone, glucagon, and epinephrine on muscle amino acid uptake was also investigated. Amino acid transport was studied with 3H-alpha-aminoisobutyric acid (AIB). Whole-septic plasma and the two low molecular-weight fractions of the septic plasma reduced muscle amino acid uptake by about 20%. IL-1 or PGE2 did not affect amino acid transport. When the catabolic hormones were added individually to incubated SOL muscles, no changes in AIB uptake were noticed. When glucagon or epinephrine was added in combination with corticosterone or when all three hormones were added together, amino acid transport was reduced by 10% to 15%. The results suggest that inhibited muscle amino acid uptake in sepsis is caused by a circulating factor(s) with a molecular weight less than 2000 to 3000 daltons. A synergistic action among the catabolic hormones may be one important factor for reduced muscle amino acid transport in sepsis.

Amino Acids↗
PubMed1986

Reversal of tumor-induced biochemical abnormalities by insulin treatment in rats.

In F344 rats bearing transplantable 3-methylcholanthrene (CAS: 56-49-5)-induced sarcomas, plasma concentrations of immunoreactive insulin were decreased following the development of mild or severe anorexia. Plasma levels of immunoreactive glucagon and lactate were elevated in severely anorectic tumor-bearing (TB) rats, while plasma glucose concentrations remained normal. Both groups of TB rats exhibited decreased plasma levels of serine, glutamine, citrulline, and tryptophan and increased concentrations of alanine. Plasma levels of proline and phenylalanine were also elevated in the severely anorectic TB rats. In a second experiment, 7 daily treatments with insulin corrected the anorexia for 6 days and increased body weights of TB rats. Plasma concentrations of lactate and immunoreactive glucagon were decreased, and the abnormal plasma concentrations of glutamine, proline, analine, and phenylalanine were altered toward normal following the insulin treatments. Therefore, these data are consistent with insulin treatments benefiting the TB host by increasing feeding, increasing body weight, reducing tumor glycolysis and metabolism, reducing gluconeogenesis, and reducing host catabolism, while not stimulating tumor growth. Thus insulin therapy may have potential benefits in cancer treatment by shifting glucose metabolism toward the host and away from the tumor.

Amino Acids↗
PubMed1985

Muscle prostaglandin production in the rat. Effect of abdominal sepsis and different amino acid formulations.

Recent in vitro studies attribute regulatory functions to prostaglandins (PGs) in muscle protein metabolism, particularly enhancing proteolysis. In the present study, the amount of muscle PG production from endogenous precursors was determined in control and septic animals (cecal ligation and puncture) that were infused with 5% dextrose or dextrose with three amino acid formulations differing in their branched-chain amino acid (BCAA) content. We could not detect any differences in prostaglandin E, 6-keto-prostaglandin F1 alpha, and thromboxane B2 production between control and septic animals. Furthermore, the infusion of BCAAs, which have previously been shown to be nitrogen sparing following injury, did not influence the production of any of the PGs studied in either control or septic muscle. It is likely that the effects of the BCAAs on muscle synthesis and degradation are independent of the PGs.

Abdomen↗
PubMed1985

Behavioral depression after intraventricular infusion of octopamine in rats.

The behavioral and neurochemical effects of four intraventricular infusions of octopamine (3,200 micrograms), tryptophan (800 micrograms), and octopamine plus tryptophan delivered over 6 hours was studied in rats after performing a portacaval anastomosis or a sham operation. After each infusion, each animal was rated for neurologic depression with a 17 point test battery. Although overt coma was not induced, octopamine infusions severely depressed neurologic function. Concentrations of norepinephrine, dopamine, and serotonin in the brain were significantly decreased after the infusion of octopamine. Levels of norepinephrine in the brain were significantly correlated with neurologic status and greater depletion of norepinephrine was associated with greater neurologic depression. These studies demonstrate that infusing large amounts of the trace amine octopamine depresses behavior in the rat and this depression is most closely associated with depletion of stores of norepinephrine in the brain.

Animals↗
PubMed1985

Postoperative enteral versus parenteral nutritional support in gastrointestinal surgery. A matched prospective study.

The effects of an elemental-enteral diet administered by a needle catheter jejunostomy or central total parenteral nutrition were prospectively studied in 15 patients undergoing abdominal operations. Infusions were started 1 day after operation and continued for 7 to 10 days. The two nutrient modalities were matched to deliver equal amounts of nitrogen and calories. Both promoted positive nitrogen balance and preserved body weight and serum proteins (albumin, transferrin, thyroxine-binding prealbumin, and retinol-binding protein). Both enteral and parenteral nitrogen caused a similar increase in plasma insulin levels. Pancreatic glucagon, total glucagon, gastrin, and pancreatic polypeptide were also maintained at similar levels in both groups. Plasma vasoactive intestinal polypeptide levels declined in patients receiving total parenteral nutrition but remained stable in the patients who were fed enterally. Both routes caused modest, inconsequential elevations in liver enzymes, but were otherwise equally safe. Patients tolerated total parenteral nutrition far better in the early postoperative period. Patients whose needs are great are probably better treated by total parenteral nutrition. Needle catheter jejunostomy feeding, however, is much less expensive. These studies do not support the commonly held belief that enteral nutrition is a more efficient route for administration of calories and protein.

Adult↗
PubMed1985

Use of a branched chain amino acid enriched solution in patients under metabolic stress.

The metabolic response to stress results in proteolysis, increased gluconeogenesis, and negative nitrogen balance. Infusion of BCAA has been shown experimentally to decrease protein degradation and stimulate protein synthesis. Such infusion may modify the response of patients to metabolic stress. An amino acid solution containing 45 percent BCAA as a component of central vein parenteral nutrition was infused into 20 moderately to severely stressed postoperative patients in a prospective, nonrandomized fashion. Infusion was begun within 24 hours postoperatively and continued for 7 to 14 days. Patients received 1.6 g protein equivalents per kg body weight daily and 30 kcal/kg body weight daily. Nutritional indexes as measured by albumin and transferrin values were maintained during the study period. Nitrogen balance became increasingly positive over the period of infusion without an increase in the urinary excretion of 3-methylhistidine. There were no serious clinical or biochemical side effects of the BCAA infusion, although a statistically significant increase in alkaline phosphatase was observed. These results suggest that central vein parenteral nutrition utilizing a 45 percent BCAA enriched solution can promote nitrogen retention without serious side effects in moderately to severely stressed patients.

Adolescent↗
PubMed1985

Effects of jejunoileal bypass on food intake, amino acid levels, and indoleamine metabolism in rats.

Adult rats were subjected to either a 90 to 95 percent jejunoileal bypass or a sham operation and were sacrificed 35 days after surgery. Rats with jejunoileal bypass lost 33 percent of their original weight, whereas the sham operated rats gained 14 percent. Food intake per 100 g body weight was significantly increased between postoperative days 14 and 35 in the jejunoileal bypass rats. Levels of tryptophan were significantly reduced in the cortex, hypothalamus, striatum, hippocampus, mesencephalon, diencephalon, pons-oblongata, and cerebellum, whereas serotonin concentrations were lowered in the diencephalon, pons-medulla, and cerebellum in jejunoileal rats compared with control rats. Levels of 5-HIAA were reduced in the hypothalamus, cortex, mesencephalon, and diencephalon. In the plasma of bypassed rats, concentrations of valine, leucine, isoleucine, tryptophan, methionine, threonine, and tyrosine were significantly lower than in the control rats. In the cerebral cortex, levels of phenylalanine, tyrosine, histidine, and glutamine were increased. The results suggest involvement of indoleamine metabolism in disrupted eating after jejunoileal bypass. The elevated brain levels of glutamine, phenylalanine, tyrosine, and histidine resemble similar changes seen after portosystemic shunting in rats.

Amino Acids↗
PubMed1985

The critical level for preservation of continence in the ileoanal anastomosis.

Mucosal proctectomy with ileoanal anastomosis was performed for 90 patients with ulcerative colitis or polyposis over the past 18 years. In three, the anastomosis was at the dentate line. All three had varying degrees of soilage necessitating permanent ileostomy in one. For 12 patients with the anastomosis 1.0 cm proximal to the top of the columns, all were totally continent, but six experienced recurrent disease. For 75 in the third group, the anastomosis was at the top of the columns. Five await ileostomy closure. Of the other 70, none experienced recurrent disease and three have mild nighttime soilage, two of which are less than 1 year following operation. We recommend that the transitional epithelium of the anorectal columns be preserved.

Anal Canal↗
PubMed1985

Release of secretin immunoreactivity from the ileum.

In the rat, about 80% of the intestinal content of secretin immunoreactivity is found distal to the duodenum with a peak in the ileum. This work therefore studied whether the secretin immunoreactivity in distal ileum could be released by substances normally found in the intestinal lumen. An isolated loop of ileum or duodenum was perfused with 100 mM HCl, 3 mM HCl, 50 mM taurocholate, 50 mM oleate, 308 mM glucose, 273 mM amino acids, or 308 mM NaCl in anesthetized rats. Release of secretin immunoreactivity was estimated by the integrated response above basal in portal blood. Substantial release of secretin immunoreactivity was seen after both ileal and duodenal perfusion with concentrated HCl and taurocholate, whereas perfusion with oleate was followed by a lesser response. The response to taurocholate was slower than that to HCl, but more likely represents a physiologic mechanism. The results show that the distal small intestine is capable of contributing to secretin immunoreactivity in the circulation and it is speculated that bile salts and secretin constitute parts of a negative feedback loop.

Animals↗