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Biomedical subjects

J E Fischer

Publications and source records attributed to J E Fischer.

At least 343 records · Page 19Linked to original sources

Delay of cancer anorexia following intraventricular injection of para-chlorophenylalanine.

Serotonergic mediation of cancer anorexia was investigated in immature female rats following the intraventricular injection of para-chlorophenylalanine (PCPA) or normal saline. Significant anorexia developed 6 days after the induction (IM) of Walker 256 carcinosarcomas in saline-treated rats. Although tumor-bearing rats treated with PCPA ate less than PCPA-injected controls by day 7, their feeding response was significantly greater than that of saline-treated tumor-bearing rats on days 5, 6 and 7. The PCPA treatment had no significant effect on food intake in nontumor-bearing rats. Biochemical analysis revealed significant elevations in plasma free tryptophan, brain tryptophan and brain 5-hydroxyindoleacetic acid in saline-treated tumor-bearing rats. Brain serotonin, 5-hydroxyindoleacetic acid and norepinephrine levels were decreased in PCPA-treated rats. Although these data may provide some support for a serotonergic mediation of cancer anorexia, additional mechanisms are clearly indicated.

Animals↗

Plasma and skeletal muscle amino acids following severe burn injury in patients and experimental animals.

This study describes and analyzes sequential changes in plasma and skeletal muscle free amino acids following severe burn injury. Plasma free amino acids were determined in children (n = 9) with burns averaging 60% total body surface area and were compared with laboratory beagles (n = 44) which received a flame burn totaling 30% of their body surface area. In addition, needle biopsy specimens were obtained from the semitendonosus muscle in the animals to determine free intracellular amino acids. In both patients and animals the amount of total free amino acids in plasma fell following burn, suggesting relative protein deficiency. This drop was primarily due to a 47% drop in nonessential amino acids. However, plasma phenylalanine was consistently higher than normal following burn, and was strongly associated with death and weight loss in both animals and patients, especially when analyzed as a ratio with tyrosine. This finding suggested excessive catabolism, hepatic dysfunction, or both. Plasma levels of several amino acids correlated significantly with weight loss. Alterations in muscle free amino acids generally were similar to plasma amino acids. Exceptions were muscle alanine and glycine which strongly correlated with weight loss. However, the determination of muscle free amino acid profiles did not yield clinically useful information not available from plasma profiles. Plasma levels of liver enzymes suggested progressive hepatic dysfunction. These studies show that the laboratory beagle is a good model for studying the metabolic alterations of amino acids that accompany burn injury, since they mimic humans in many parameters which appear to be most useful with respect to clinical evaluation.

Amino Acids↗

Infusion of branched-chain enriched amino acid solution in patients with hepatic encephalopathy.

Hospitalized patients with hepatic insufficiency often suffer from severe catabolic states and are in urgent need of nutritional support during their acute illness. Protein intolerence, however, remains a significant problem with respect to the provision of adequate nutrition, either enterally or parenterally. The following report is an anecdotal series of 63 consecutive patients in a large urban hospital treated prospectively with nutritional support using a prototype high branched-chain amino acid solution (FO80) given by technique of total parenteral nutrition by the subclavian or internal jugular route with hypertonic dextrose. Sixty-three patients, of which 42 had chronic liver disease (cirrhosis) with acute decompensation and 17 with acute hepatic injury as well as four with hepatorenal syndrome, are the subject of this report. All required intravenous nutritional support and were either intolerant to commercially available parenteral nutrition solutions or were in hepatic encephalopathy at the time they were initially seen. The cirrhotic patients had been hospitalized for a mean of 14.5 +/- 1.9 days before therapy, had a mean bilirubin of 13 mg/100 ml, and had been in coma for 4.8 +/- 0.7 days despite standard therapy. Patients with acute hepatitis had been in the hospital for 16.2 +/- 4.1 days before therapy, had a mean bilirubin of 25 mg/100 ml, and had been in coma 5.2 +/- 1.6 days before therapy. Routine tests of liver function, blood chemistries, amino acids, EEGs, and complex neurological testing including Reitan trailmaking tests were used in the evaluation of these patients. Up to 120 grams of synthetic amino acid solution with hypertonic dextrose was tolerated in these patients with improvement noted in encephalopathy of at least one grade in 87% of the patients with cirrhosis and 75% of the patients with hepatitis. Nitrogen balance was achieved when 75 to 80 grams of synthetic amino acids were administered. Survival was 45% in the cirrhotic group and 47% in the acute hepatitis group. Encephalopathy appeared to correlate with individual amino acids differentially in the various groups and with the ratio between the aromatic and the branched-chain amino acids. Ammonia did not correlate with either the degree of encephalopathy or improvement therefrom. In 24 Patients therapy for hepatic encephalopathy was limited to infusion of the branched-chain enriched amino acid solution only, with wake-up in 66% of this group. The results strongly suggest that in protein intolerant patients requiring nutritional support, infusion with branchedchain enriched amino acid solutions is well tolerated with either no worsening of or improvement in hepatic encephalopathy coincident with the achievement of nitrogen equilibrium and adequate nutritional support.

2-Hydroxyphenethylamine↗

The effect of parenteral and enteral nutrition on portal and systemic immunoreactivities of gastrin, glucagon and vasoactive intestinal polypeptide (VIP).

To compare the effect of parenteral with enteral nutrition on gastroentero-pancreatic hormones, hypercaloric and hypocaloric nutrient preparations, commonly used clinically, were administered to rats either through cannulae in the jugular vein or gastrostomies. Control rats were fed orally ad libitum. Portal and aortic plasma was collected for radioimmunoassay with antibodies to C-terminal regions of gastrin and glucagon and to N-terminal-to-central regions of glucagon and VIP. Levels of all immunoreactivities were significantly lower in aortic than portal plasma. Apparent clearance of glucagon and gastrin by liver or lung both was enhanced by administration of the hypercaloric nutrient intravenously. Only intragastric hypercaloric nutrition maintained levels of VIP immunoreactivity close to those of control rats. Intragastric administration of either preparation appeared to maintain adequate levels of gastrin. Differences in the levels of glucagon immunoreactivities may be related to the stimulatory effects of metabolites in the lower gut and pancreas.

Animals↗

Preservation of anorectal continence following total colectomy.

The search for continence in the surgical management of ulcerative colitis has resulted in the evolution of a method that has yielded gratifying results in the last 18 patients. The disease process is removed; all patients are continent; they have no postoperative perineal excoriation; the frequency of stools is not excessive and the patients are returning to work or to school within three weeks following ileostomy closure. Their ages were eight to 52 years. The procedure consists of a total of colectomy with mucosal proctectomy, ileoanal anastomosis and construction of a terminal ileal, pelvic reservoir. A proximal ileostomy diverts the fecal stream until healing is complete. The authors are now recommending the operation be considered for patients of all ages who require surgery for chronic ulcerative colitis as well as polyposis.

Adolescent↗

Analysis of brain indoleamines and catecholamines associated with burn-induced anorexia.

Guinea pigs subjected to a full-thickness 30% body surface flame burn significantly reduced food intake and lost weight for 5 days thereafter. Comparison of brain monoamine changes in burned, pair-fed control, and freely feeding control groups revealed normal levels of norepinephrine and elevated concentrations of dopamine in burned animals compared to the pair-fed control group. Levels of the serotonin precursor, tryptophan, and metabolite, 5-hydroxyindoleacetic acid, were also increased in burned compared to pair-fed animals, suggesting increased activity of indoleamine neurons. Although brain catecholamine levels were not correlated with food intake, significant negative correlations between food consumption and tryptophan, serotonin, and 5-hydroxyindoleacetic acid were observed. These data suggest that aberrations in indoleamine and possible catecholamine neurotransmitter systems may be involved in the mediation of burn-induced anorexia.

Amino Acids↗

Maternal fetal and placental gastrin concentrations.

The radioimmunoassay technique was used to measure maternal, placental and fetal serum gastrin levels. A progressive increase in gastrin levels occurred with the advance of pregnancy reaching mean peak levels of 62 (SEM 12) pg/ml during labour. Umbilical artery (74 pg/ml: SEM 7) or vein (73 pg/ml: SEM 7) gastrin concentration was higher than maternal gastrin levels. Placental gastrin concentration was 840 pg/g (SEM 96) and amniotic fluid contained 22 pg/ml (SEM 2). This study implies that one of the reasons for increased maternal gastric residue seen during pregnancy is due to an increased serum gastrin concentration. Also the advanced stage of development of gastrointestinal system of the newborn is in accord with high fetal gastrin concentration.

Adult↗

Effect of jejunoileal bypass on plasma and brain amino acids in the rat.

Liver failure and coma are serious complications of jejunoileal bypass (JIB) in man. Rats underwent either a 90-95% JIB or a sham operation. Six weeks later all animals were sacrificed, and plasma and brain amino acids were determined. In the plasma of rats with JIB compared with sham operation, the concentrations of valine, leucine, isoleucine, lysine, tryptophan, and tyrosine were significantly lower, while in the brain, phenylalanine, tyrosine, histidine, and glutamine were significantly higher. These changes in the brain are similar to those resulting from portalsystemic shunting in the rat.

Amino Acids↗

Total parenteral nutrition in a pregnant insulin-requiring diabetic.

A 28-year-old class F diabetic woman whose pregnancy was complicated by gastroparesis, hemorrhagic gastritis, narcotic addiction, intrauterine fetal growth retardation, and severe preeclampsia was supported with total parenteral nutrition (TPN) from the 27th to the 29th week or pregnancy. During this period there was adequate control of serum glucose, a positive nitrogen balance, and a normal amino acid profile. Unfortunately, a rapid deterioration in renal function and hypertensive disease occurred, requiring cesarean section at the 29th gestational week. TPN was continued for an additional 30 days postoperatively until the gastritis resolved and adequate oral nutrition could be reestablished. Wound healing was satisfactory.

Acute Kidney Injury↗

Hyperalimentation in cancer.

A growing body of work has been addressed to the hypothesis that because patients with cancer who have poor nutritional status have a worse prognosis, increased nutritional support in these patients will result in better tolerance of surgical interventions, chemotherapy and radiation therapy, and a better outcome from the cancer. Although the hypothesis is an attractive one, there is only a single well-conducted, randomized, prospective trial to date that shows that active nutritional support is of benefit in the therapy of patients with cancer. Based on this review of the literature, it is felt that though cachexia is clearly of negative import in patients with cancer, there is little evidence to support the hypotheses that any nutritional support changes the outcome or the course of therapy of patients with cancer. It seems reasonable to continue the nutritional support to cachectic patients with cancer concomitant with specific anticancer therapy, but supportive nutritional therapy alone with postponement of specific anticancer treatment, as in awaiting weight gain or anabolism, cannot be justified with the current state of the art.

Cachexia↗

Association between microorganism growth at the catheter insertion site and colonization of the catheter in patients receiving total parenteral nutrition.

Catheter-related sepsis is one of the major complications of total parenteral nutrition (TPN) therapy. The relationship between microbial colonization of the skin at the site of catheter insertion and colonization of the central venous catheter was investigated in 74 catheters used to administer TPN therapy in 53 patients. Semiquantitative culture specimens were obtained from the insertion site and intravascular and subcutaneous catheter segments at the time of catheter removal. Bacteria and/or fungi were recovered from 19 catheters and 19 insertion sites; of the 19 colonized catheters, 6 had sterile insertion sites. Organisms isolated from the remaining 13 catheters were isolated concurrently from the insertion site. Catheter-associated bacteremia or fungemia was observed in 10 of the 19 patients with colonized catheters. The association between colonization of catheters and the presence of more than 10(3) bacterial or fungal colony-forming units at the insertion site was significant (P less than 0.005). These results demonstrated that colonization of catheters by organisms present on the skin at the site of catheter insertion occurred twice as frequently as colonization by the hematogenous route. The results also suggested that colonization of catheters by organisms present at the insertion site occurred only after a threshold number of organisms was reached.

Adult↗

The effect of a new branched chain--enriched amino acid solution on postoperative catabolism.

Branched-chain amino acids (BCAAs) may regulate muscle amino acid flux. Metabolic studies of both experimental animals and humans utilizing comparatively large amounts of BCAAs infused with hypocaloric glucose have shown that catabolism and proteolysis can be blunted. These studies suggested that the nitrogen-sparing properties of amino acid solutions used in postoperative trauma or sepsis might be improved by increasing the amount of BCAAs. This hypothesis was tested on ten patients undergoing operations of moderate severity utilizing a peripheral amino acid mixture with a branched-chain:non-branched-chain ratio of 45:55% given in 5% dextrose. The patients received 1.7 gm of protein equivalent/kg of ideal body weight in 5% dextrose-crystalloid solution with a concentration of 3.5% amino acids for the first 5 postoperative days. Nitrogen balance, 3-methylhistidine excretion, blood chemistries, and plasma amino acid profile tests were done daily. The results showed that nitrogen equilibrium was maintained for 5 postoperative days without any untoward effects on patients, their surgical wounds, or hepatic function. Plasma amino acids showed no significant changes from baseline with the exception of elevations of the BCAAs. We conclude that this 45% BCAA-enriched solution may be safely administered to patients with postoperative traumatic injury and results in nitrogen equilibrium over a 5-day period.

Adolescent↗

Blood-brain barrier derangement in uremic encephalopathy.

A disturbance of cerebral neurotransmitters and an accumulation of octopamine, a putative false neurotransmitter, have been found in patients with uremic encephalopathy who manifest disorientation, somnolence, asterixis, and coma--symptoms also seen in portal systemic encephalopathy (PSE). Altered plasma concentrations of the neutral amino acids (NAAs) and increased blood-brain NAA transport may play a role in PSE, and in the present study plasma amino acid concentrations and blood-brain barrier NAA transport were investigated in rats with acute and chronic uremia. Acute uremia was produced by unilateral nephrectomy and occlusion of the renal artery of the remaining kidney for 70 minutes; the animals were studied 24 hours later. Chronic uremia was produced by unilateral nephrectomy and 70% to 80% devascularization of the remaining kidney; these animals were studied 2 weeks later. Brain uptake was studied with the technique of Oldendorf, and blood and brain amino acids (AAs) were measured. The blood urea nitrogen (BUN) level in rats with acute uremia increased to 108 mg/dl, in rats with chronic uremic 54 mg/dl, and in sham-operated rats 22 mg/dl. In both uremic groups there was a decrease in plasma branched-chain AAs. In the brain these AA levels were normal, while levels of phenylalanine, tyrosine, and histidine were increased in uremic rats.

Amino Acids↗

The use of amniotic fluid 3-methyl histidine to creatinine molar ratio for the diagnosis of intrauterine growth retardation.

To determine if the amniotic fluid 3-methyl histidine to creatinine molar ratio (3MH:CR) could prove useful for the antepartum detection of intrauterine growth retardation (IUGR), the 3MH:CR was determined retrospectively in 3 groups of human amniotic fluids. Group A consisted of amniotic fluids from pregnancies yielding IUGR fetuses whose birth weight was less than or equal to the tenth percentile for gestational age; group B consisted of amniotic fluid from pregnancies yielding infants whose birth weight was greater than the tenth but less than or equal to the 25th percentile for gestational age; group C consisted of amniotic fluids from pregnancies yielding infants whose birth weight was greater than the 25th but less than or equal to the 75th percentile for gestational age. The mean 3MH:CR x 10(-3) for groups A, B, and C were 15.9 +/- 1.9, 5.4 +/- 0.8, and 6.2 +/- 0.5, respectively. The mean 3MH:CR x 10(-3) was statistically different between groups A and B (P less than or equal to .001) and between groups A and C (P less than or equal to .001), but not statistically different between the 2 control groups. Employing an upper limit of normal of 8 for the 3MH:CR x 10(-3), 13 of 15 IUGR neonates were correctly identified as IUGR, and 23 of 27 neonates were correctly identified as being of normal birth weight for gestational age (sensitivity 86.7%, specificity 85.2%, incidence of correct diagnosis 85.7%). No consistent relationship was shown to exist between maternal serum and amniotic fluid 3-methyl histidine level. There was no statistically significant relationship between 3MH:CR x 10(-3) and gestational age. The comparison of the data generated in this study to that obtained with previously reported ultrasonic and biochemical techniques suggests that the amniotic fluid 3MH:CR ratio may prove helpful in establishing the antenatal diagnosis of IUGR, particularly in cases where the gestational age is uncertain.

Amniotic Fluid↗