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Biomedical subjects

J E Fischer

Publications and source records attributed to J E Fischer.

At least 271 records · Page 15Linked to original sources
PubMed1987

Effect of insulin on amino acid uptake and protein turnover in skeletal muscle from septic rats. Evidence for insulin resistance of protein breakdown.

We investigated the effect of different concentrations of insulin (0, 10, 1 X 10(2), 1 X 10(3), 1 X 10(4), and 1 X 10(5) mU/L [0, 70, 7 X 10(2), 7 X 10(3), 7 X 10(4), and 7 X 10(5) pmol/L]) on amino acid (alpha-aminoisobutyric acid) uptake and protein synthesis and breakdown in incubated extensor digitorum longus (EDL) and soleus muscles of rats. We studied three groups: untreated, fed rats; sham-operated rats; and septic rats. Sepsis was induced by cecal ligation and puncture. The alpha-aminoisobutyric acid uptake was increased by insulin in all three groups. Protein synthesis was maximally stimulated by 30% to 40% by 1 X 10(2) mU/L (7 X 10(2) pmol/L) of insulin in all three groups. Protein degradation in soleus muscle was not affected by insulin. In EDL muscles from untreated and sham-operated rats, protein breakdown was reduced by 15% to 20% by 1 X 10(2) mU/L (7 X 10(2) pmol/L) of insulin. In contrast, protein breakdown was not inhibited by insulin in septic EDL muscle until the concentration of the hormone was increased to 1 X 10(4) mU/L (7 X 10(4) pmol/L), at which concentration the hormonal effect was less than half that in nonseptic muscle. The results suggest a postreceptor insulin resistance of protein breakdown in septic muscle, while the response to the hormone of amino acid transport and protein synthesis was not altered in sepsis.

Aminobutyrates↗
PubMed1987

Superoxide dismutase in rats with sepsis. Effect on survival rate and amino acid transport.

In a recent study, administration of the free radical scavenger superoxide dismutase (SOD) improved survival in rats with sepsis when administered two hours before induction of sepsis. The present study was designed to determine whether free radical-induced membrane damage is involved in the pathogenesis of decreased muscle amino acid uptake, noted in sepsis. Additionally, the effect on survival rate of SOD given after the onset of sepsis was studied. Sepsis was induced by cecal ligation and puncture in rats. Amino acid transport in incubated soleus muscles was studied using tritiated alpha-aminoisobutyric acid. Amino acid uptake was significantly reduced in muscle from rats with sepsis. Administration of SOD before induction of sepsis or added in vitro to incubated muscles with sepsis had no effect on alpha-aminoisobutyric acid uptake. Survival rate was not increased when SOD was given two hours after cecal ligation and puncture. The results suggest that free radical-induced membrane damage is not the mechanism of inhibited muscle amino acid transport in sepsis. Since survival was not improved by SOD administered after induction of sepsis, the role of the enzyme in the treatment of sepsis may be questioned.

Amino Acids↗
PubMed1987

Resting energy expenditure of host and tumor is similar in rats with methylcholanthrene-induced sarcoma.

In the present study we assessed the resting energy expenditure of 30 free-feeding control and methylcholanthrene-induced sarcoma-bearing rats prior to and following surgical removal of the tumor. Tumor-bearing rats demonstrated carcass wasting and massive tumor growth. The resting energy expenditure data in our model suggest that neither the presence and growth of a tumor nor its removal significantly change resting energy expenditure beyond the normal range for non-tumor-bearing rats. We suggest that in the partition of energy costs between host and tumor, both carry a similar input, proportional to their relative weight, into the total combined resting energy expenditure of host and tumor.

Animals↗
PubMed1987

Early total parenteral nutrition in acute pancreatitis: lack of beneficial effects.

To determine the effect of early aggressive parenteral support in pancreatitis, 54 patients with acute pancreatitis were randomized to receive either conventional therapy (control group) or conventional therapy plus the institution of total parenteral nutrition within 24 hours. The two groups were similar demographically. The total parenteral nutrition group had a significantly higher rate of catheter-related sepsis than did an additional group of contemporaneous patients without pancreatitis who received total parental nutrition (10.5 percent and 1.47 percent, respectively; p less than 0.01). There was no advantage to the use of early total parenteral nutrition; that is, there was no difference in the number of days to oral intake, total hospital stay, or number of complications of pancreatitis. Patients with zero or one Ranson's criterion on admission were more likely to be eating by the seventh hospital day than were those with two or more Ranson's criteria (80 percent and 54 percent, respectively; p less than 0.05). The early institution of total parenteral nutrition in patients with acute pancreatitis did not appear to improve the outcome. Its use should be limited to prolonged periods of no oral intake or treatment of a specific complication, such as a pseudocyst.

Acute Disease↗
PubMed1987

Effect of sepsis and starvation on amino acid uptake in skeletal muscle.

Sepsis and starvation are catabolic conditions often occurring simultaneously. We recently found that uptake of the nonmetabolized amino acid analog, alpha-aminoisobutyrate (AIB), was reduced in skeletal muscle during sepsis, and data were presented suggesting that this reduction was caused by a factor present in septic plasma. The purpose of the present study was to determine the effect of starvation on amino acid uptake and to investigate possible interactions between sepsis and starvation regarding effects on muscle amino acid uptake. Soleus muscles were removed intact from rats fasted for 0, 24, 48, or 72 hr. Muscles were incubated for 2 hr in Krebs-Henseleit bicarbonate buffer (pH 7.4) and glucose (5 mM) with or without 0.25 ml of septic plasma (total volume 3 ml). Muscle AIB uptake progressively decreased by approximately 50% during the first 48 hr of starvation, with no further decrease at 72 hr. Addition of septic plasma in vitro reduced AIB uptake in muscles from fed rats and from rats which had been fasted for 24 hr, but did not further reduce uptake after longer periods of starvation. The results suggest that starvation reduces amino acid uptake in skeletal muscle and that the nutritional status of muscle is an important component of the response to the factor(s) in septic plasma capable of inhibiting amino acid uptake.

Aminoisobutyric Acids↗
PubMed1987

Effect of catabolic hormone infusion on organ amino acid uptake.

Elevated plasma levels of the so-called catabolic hormones (glucocorticoid, epinephrine, glucagon) have been observed in severely injured patients, and infusion of these hormones to normal subjects has reportedly simulated several metabolic aberrations characteristic of severe trauma and sepsis. We recently reported that amino acid uptake was reduced in soleus muscle, heart, and diaphragm, and increased in the liver, of septic rats. The purpose of the present study was to investigate organ amino acid uptake in nonseptic rats infused with catabolic hormones. Central venous catheters were placed in male Sprague-Dawley rats (100-150 g) and after 24 hr hormones (glucagon 5 micrograms/kg/hr, epinephrine 6 micrograms/kg/hr, corticosterone 4.2 mg/kg/hr) or vehicle (saline, ascorbic acid 1 mg/ml, albumin 3 mg/ml) was infused for 72 hr. Animals were housed in metabolic cages and allowed food and water ad lib. One hour prior to sacrifice, alpha-[3H]aminoisobutyric acid (AIB) (2.5 microCi), a nonmetabolized amino acid analog mainly transported by system-A, was injected intravenously. Animals were killed and organs were removed, weighed, and dissolved in tissue solubilizer for measurement of radioactivity. AIB uptake was significantly elevated in all organs of catabolic hormone-infused animals studied. The results suggest that catabolic hormones may be involved in the pathogenesis of increased amino acid uptake in the liver during sepsis. Inhibited amino acid uptake in skeletal muscle during sepsis, however, is probably not primarily mediated by catabolic hormones.

Aminoisobutyric Acids↗
PubMed1987

Aggressive surgical approach for drug-free remission from myasthenia gravis.

A series of 27 patients with generalized myasthenia gravis is presented. All patients were treated by a sternal split and extended thymectomy and radical mediastinal dissection. The overall drug-free remission rate was 63%, although three additional patients are likely to achieve drug-free remission in the near future, with the total drug-free remission rate then being 74%. Of the remaining patients, all but three improved and require decreased medication, for an improvement rate of approximately 90%. One patient who has not improved had an invasive malignant thymoma. Drug-free remission was achieved in 46% of the male patients and in 82% of the female patients despite that the mean duration of disease was greater than 3.5 years. There was one serious complication, that of sterile sternal dehiscence. There was no mortality. The results suggest that an aggressive, radical surgical approach to myasthenia gravis, even in a group of patients considered somewhat less favorable because of a relatively long duration of disease, can result in a high percentage of drug-free remissions. Radical surgery for myasthenia gravis appears to be the treatment of choice, with medical therapy being reserved for those patients who are not likely to survive operation.

Adolescent↗
PubMed1987

Studies on the possible role of thyroid hormone in altered muscle protein turnover during sepsis.

Five days after thyroidectomy (Tx) or sham-Tx in young male Sprague-Dawley rats, sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent laparotomy and manipulation of the cecum without ligation or puncture. Sixteen hours after CLP or laparotomy, protein synthesis and degradation were measured in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles by determining rate of 14C-phenylalanine incorporation into protein and tyrosine release into incubation medium, respectively. Triiodothyronine (T3) was measured in serum and muscle tissue. Protein synthesis was reduced by 39% and 22% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx rats. The response to sepsis of protein synthesis was abolished in Tx rats. Protein breakdown was increased by 113% and 68% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx animals. The increase in muscle proteolysis during sepsis was blunted in hypothyroid animals and was 42% and 49% in EDL and SOL, respectively. T3 in serum was reduced by sepsis, both in Tx and sham-Tx rats. T3 in muscle, however, was maintained or increased during sepsis. Abolished or blunted response of muscle protein turnover after CLP in hypothyroid animals may reflect a role of thyroid hormones in altered muscle protein metabolism during sepsis. Reduced serum levels of T3, but maintained or increased muscle concentrations of the hormone, suggests that increased T3 uptake by muscle may be one mechanism of low T3 syndrome in sepsis, further supporting the concept of a role for thyroid hormone in metabolic alterations in muscle during sepsis.

Animals↗
PubMed1987

Burn-induced alterations in feeding, energy expenditure, and brain amine neurotransmitters in rats.

A 30% body surface area, open-flame, full-thickness burn of adult rats induced a 4-day period of anorexia that was followed by hyperphagia beginning on postburn day 10. The hyperphagic burned rats also exhibited increased resting energy expenditure and no gain in body weight, suggesting hypermetabolism. Plasma levels of immunoreactive insulin and albumin were decreased in both groups of burned rats; immunoreactive pancreatic glucagon concentrations were elevated only in the anorectic burned rats. Plasma levels of epinephrine were elevated in the hyperphagic burned rats. In the brain, dopamine metabolism appeared to be increased in the corpus striatum, nucleus accumbens, and amygdala of anorectic burned rats; norepinephrine levels were elevated in the hypothalamus and nucleus accumbens of the hyperphagic-hypermetabolic rats. These data indicate that this animal model of major burn trauma exhibits anorexia, hyperphagia, catabolism, and hypermetabolism. Furthermore, elevated dopamine metabolism appears to be associated with the anorexia, while the hyperphagia-hypermetabolism may be mediated by norepinephrine.

Animals↗
PubMed1987

Acivicin reduces tumor growth during total parenteral nutrition (TPN).

Glutamine appears to be an important substrate for tumor growth. Since tumor growth rate may be stimulated by total parenteral nutrition (TPN), we investigated the effect of the glutamine antimetabolite, acivicin, on methylcholanthrene sarcoma growth in rats maintained on TPN or on rat chow. Acivicin treatment significantly reduced tumor growth by 67% in rats receiving TPN and by 71% in rats maintained on chow. Carcass weights were significantly increased by TPN in both acivicin-treated and saline solution-treated tumor-bearing rats. Tumor-carcass ratios were significantly decreased in both groups of acivicin-treated tumor-bearing rats. Acivicin treatment or a similar approach may therefore be useful for stabilizing tumor growth in patients receiving TPN.

Animals↗
PubMed1987

The value of hepatobiliary scans in fasted patients receiving total parenteral nutrition.

Hepatobiliary scanning is considered to be a highly accurate method for the diagnosis of acute cholecystitis. False-positive scans (failure to visualize the gallbladder in the absence of cholecystitis) have been reported to occur in fasted patients receiving total parenteral nutrition (TPN). To determine the prevalence of false-positive scans in this patient population and identify factors that might be associated with scan outcome, hepatobiliary imaging was performed in fasted patients receiving TPN and without clinical evidence of acute cholecystitis. Gallbladder nonvisualization occurred in 18 of 50 (36%) patients. In the group whose gallbladders did not visualize, a significantly higher male to female ratio (15:3 versus 17:15; p = 0.016), alkaline phosphatase (346 +/- 84 IU/L versus 212 +/- 32 IU/L, p less than 0.04), total bilirubin (1.7 +/- 0.3 mg/dl versus 1.0 +/- 0.2 mg/dl, p less than 0.02), and lower serum albumin (2.4 +/- 0.01 gm/dl versus 2.8 +/- 0.2 gm/dl, p less than 0.02) levels were noted. In 18 patients, gallbladder ultrasonography was also performed, and the presence of sludge or a thickened gallbladder wall did not correlate with scan outcome. The prevalence of false-positive hepatobiliary scans in fasted patients receiving TPN is significant and does not always correlate with a syndrome of acute gallbladder inflammation. The results of such scans must therefore be interpreted with caution in these patients.

Adult↗
PubMed1987

Synthesis of neuropeptide Y.

Neuropeptide Y (NPY), a hexatriacontapeptide amide, was synthesized on benzhydrylamine resin. The peptide product obtained by HF treatment contained 63% of the target peptide, NPY. A comparison of the chemical, immunochemical and biological properties of the synthetic peptide with natural NPY indicated that they were identical.

Amino Acid Sequence↗
PubMed1986

Regional brain amino acid and neurotransmitter derangements during abdominal sepsis and septic encephalopathy in the rat. The effect of amino acid infusions.

Regional amino acids and brain neurotransmitters were studied in 33 normal and 32 rats with sepsis (induced by cecal ligation and puncture) infused with different amino acid formulations. The brain amino acid pattern during sepsis showed increased concentrations of most essential and six of the nonessential amino acids. The most consistent finding was the accumulation of indoleamines in all six brain regions studied during sepsis; increased brain tryptophan levels presumably resulted in enhanced metabolism of serotonin (5HT), increased production of 5-hydroxyindoleacetic acid (5HIAA), and a high 5HT/5HIAA ratio. Infusion of branched-chain amino acid-enriched formulas restored brain amino acid and neurotransmitter profiles, decreasing levels of tryptophan, tyrosine, 5HIAA, and 5HT/5HIAA ratios while increasing norepinephrine levels in some regions. These alterations in brain neurotransmitter metabolism may be at least partially responsible for the development of septic encephalopathy.

Amino Acids↗
PubMed1986

Clinical use of branched-chain amino acids in liver disease, sepsis, trauma, and burns.

The branched-chain amino acids (BCAAs)--leucine, isoleucine, and valine--share unique biochemical properties that may make them useful in altered physiologic states. They can be metabolized independently of liver function to provide energy, other amino acids, or small nitrogenous compounds. This unique ability makes the BCAAs a desirable supplement in liver disease with encephalopathy and, to a lesser extent, in sepsis with hepatic dysfunction. Furthermore, the BCAAs play a role in the regulation of protein synthesis, suggesting beneficial effects in catabolic states such as postoperative stress, trauma, renal failure, and burns. However, initial studies in these areas have presented equivocal results.

Amino Acids, Branched-Chain↗
PubMed1986

Protein metabolism in different types of skeletal muscle during early and late sepsis in rats.

Protein synthesis and degradation rates were measured in incubated soleus (SOL) and extensor digitorum longus (EDL) muscles 4, 8, and 16 hours following cecal ligation and puncture (CLP) in rats. No significant differences in protein synthesis between septic and control rats were found. The proteolytic rate in SOL muscle was increased by 36% eight hours after CLP and by 42% 16 hours after CLP. In EDL muscle, protein breakdown was not significantly increased until 16 hours after CLP, at which time it was 53% above the control value. The plasma amino acid pattern became increasingly deranged during the course of the study, and at 16 hours almost all individual amino acid levels were significantly different in septic rats compared with control rats. There was a significant positive correlation between plasma concentrations of phenylalanine, histidine, and ornithine and the proteolytic rate in EDL and SOL muscles, with the best correlation being found between phenylalanine concentration and proteolytic rate in SOL muscle. These results suggest that muscle wasting during sepsis is caused by increased protein breakdown, not by decreased protein synthesis, and that accelerated muscle proteolysis is an early phenomenon in sepsis.

Amino Acids↗
PubMed1986

Postoperative enteral vs parenteral nutrition. A randomized controlled trial.

Twenty patients undergoing major upper-gastrointestinal-tract or pancreaticobiliary surgery were randomized to receive postoperative nutritional support by total parenteral nutrition (TPN) or elemental diet administered by needle-catheter jejunostomy (NCJ). Both routes of administration provided adequate nutritional support. No unexpected complications were encountered. The NCJ group compared favorably with the TPN group at the end of the seven-day trial. The NCJ group provided significant cost efficiency while maintaining adequate nutritional support.

Adult↗
PubMed1986

The effect of indomethacin on muscle and liver protein synthesis and on whole-body protein degradation during abdominal sepsis in the rat.

It has been recently suggested that increased muscle protein degradation during injury or infection is at least partially mediated by the increased production of prostaglandin E2 in muscle, and some have suggested that cyclooxygenase inhibitors might decrease protein loss in injured or septic patients. In these experiments, fractional synthesis rates of mixed muscle and liver protein and whole-body tyrosine flux were measured by constant intravenous infusion of tyrosine labeled with carbon 14 in 17 rats with sham operations and 15 severely septic rats with or without indomethacin treatment (20 mg/kg/d). Fractional synthesis rates in muscle and liver were decreased in late sepsis and were lowest in the septic group receiving indomethacin. Unlike the fractional synthesis rate, which was affected by indomethacin in septic rats only, tyrosine flux was significantly lower in indomethacin-treated rats with sham operations and those with sepsis. Although indomethacin reduced total-body protein breakdown during sepsis, it was also associated with lower plasma albumin levels and with decreased protein synthesis in muscle and liver at a time when the survival of the septic host may be dependent on its ability to produce new protein for a variety of vital functions. These results do not support the use of indomethacin in sepsis.

Abdomen↗