Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred nineteen patients were entered onto a randomized trial of the role of intravenous hyperalimentation (IVH) in patients with small-cell lung cancer. IVH was given during the first 30 days of induction chemotherapy to 54 patients. IVH did not effect any improvement in response or survival from therapy. In view of the lack of benefits from IVH, an analysis was made of the toxicities suffered by the 54 patients receiving IVH as well as any effects IVH might have made on chemotherapy-induced toxicity. Toxicities observed included mechanical difficulties with the catheter leading to temporary or permanent discontinuation of the IVH (11 patients), subclavian vein thrombosis (one patient), sepsis in nine patients v none of the 62 control patients, fluid overload (27 patients), hyponatremia (25 patients), and hyperglycemia requiring insulin (13 patients). Patients receiving IVH had higher granulocyte counts on days 14 and 21 of the first cycle of chemotherapy. Analysis shows that this difference is likely caused by fever and infection associated with IVH rather than any nutritional effect on granulopoiesis. In this population of patients, IVH had significant complications but did not ameliorate chemotherapy-induced toxicity and it did not effect any clinical benefit. Future studies of adjunctive nutritional therapy must consider the significant risk in this older population and must limit IVH volume or exclude patients with even mild compromise in cardiovascular functions. Further, any new trial must have a significant rationale for adjunctive use to justify the potential risks.
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PMID:Effects of intravenous hyperalimentation during treatment in patients with small-cell lung cancer. 299 75

Suppression of an adrenocorticotropic hormone (ACTH) response to insulin hypoglycemia has been reported in ACTH-treated adults. There are no guidelines for withdrawal of ACTH treatment in children. After observing suppressed morning cortisol in several children, insulin tolerance tests were performed in five children within 48 hours after tapered withdrawal of ACTH treatment for myoclonic seizures. ACTH response, as determined by cortisol and beta-endorphin radioimmunoassay, was adequate in four of the children. One child showed low basal levels and minimal elevation during hypoglycemia for both beta-endorphin (0 to 3 pg/ml) and cortisol (3.6 to 4.4 micrograms/dL) on initial testing, but normal responses six weeks later. Measurement of beta-endorphin response supported a central basis for suppression in the child, who had had an adrenal hemorrhage during gram-negative sepsis while on ACTH. ACTH release is transiently suppressed in some children after exogenous ACTH treatment. Tapered withdrawal and stress coverage is recommended.
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PMID:Suppressed pituitary ACTH response after ACTH treatment of infantile spasms. 303 33

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.
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PMID:Branched chain amino acid-enriched solutions in the septic patient. A randomized, prospective trial. 307 94

The treatment of acute pancreatitis is primary conservative independent of the degree of severeness. The aim of our multimodal concept of therapy (stomach tube, catheterisation of urinary bladder, closed peritoneal dialysis, analgetics--peridural catheter-, substitution of volume-electrolytes, colloides, protein, plasma, blood-, antibiotics, heparin H2-receptor blocker, early artificial respiration, insulin, parenteral nutrition-glucose, amino acids, fat-, hemofiltration/-dialysis, percutaneous drainage of liquid formations) is to postpone or to avoid an operation. Only the erosion bleeding or a locally conditioned sepsis ask for an emergency operation. The lethality of the degrees II (n = 30) and III (n = 39) could be decreased to 20.3% in the last 7 years. The follow-up of 55 patients with severe pancreatitis was free of clinical symptoms in 80% with normal exocrine and endocrine function of pancreas. This confirms that the organ itself is mostly intact even in severe cases of pancreatitis, in hemorrhagic-necrotic pancreatitis.
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PMID:[Pancreatitis: conservative therapy]. 310 Aug 87

Although nutritional support is vital to treatment of severe sepsis, the septic patient does not respond normally to glucose infusion. We have used the hyperglycemic glucose clamp technique to investigate the initial hormonal and metabolic responses of the septic patient to glucose under controlled conditions. The plasma glucose concentration was raised to and maintained at 12 mmol/liter for 2 hr in 12 septic patients and 11 normal controls. Glucose utilization, assessed from the amount infused, was significantly depressed in the patients, despite similar plasma insulin concentrations in the two groups. Forearm glucose uptake was similarly impaired. Despite very similar plasma free fatty acid concentrations in the two groups, which were suppressed equally by the glucose infusion, whole-body fat oxidation was elevated in the patients compared with the controls, and suppressed to a lesser extent in response to glucose. Glycerol and ketone body concentrations were elevated in the patients in keeping with a picture of accelerated release, clearance, and oxidation of fatty acids. Plasma cortisol, epinephrine, and norepinephrine concentrations were elevated in the septic patients in a severity-related manner, but not to high levels compared with experimental work. Norepinephrine showed no response to the glucose infusion in either group. Plasma glucagon concentrations were not significantly elevated in the septic patients. We conclude that the hyperglycemic glucose clamp provides a useful model for studying glucose intolerance in sepsis. Impaired glucose utilization in septic patients is associated with increased fat oxidation, although the hormonal basis for these changes is still unclear.
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PMID:Hormonal and metabolic responses to glucose infusion in sepsis studied by the hyperglycemic glucose clamp technique. 311 25

Prostaglandin E2 (PGE2) reportedly increases protein break-down in skeletal muscle. The role of PGE2 for accelerated muscle proteolysis during sepsis, however, is controversial. In this study, the effect of the prostaglandin synthesis inhibitor indomethacin on PGE2 release and protein breakdown in skeletal muscle from nonseptic and septic rats was evaluated. Sepsis was induced in male Sprague-Dawley rats (40-60 g) by cecal ligation and puncture (CLP). After 16 hours the extensor digitorum longus (EDL) and soleus (SOL) muscles were dissected with intact tendons and incubated in an oxygenated medium, and the release of tyrosine (protein breakdown) and PGE2 into the incubation medium was determined. Paired muscles were incubated in the absence or presence of indomethacin (3 mumol/L or 6 mumol/L). In some experiments the effect of indomethacin was investigated in the presence of different concentrations of insulin (1, 10, or 100 mU/mL) since previous reports suggested an interaction between insulin and prostaglandins on protein turnover in skeletal muscle. In other experiments muscles were incubated in a flaccid or stretched state, which is known to influence the metabolic response to different substances. Protein breakdown rate was 0.210 +/- 0.013 and 0.492 +/- 0.025 mumol Tyr/g X 2 hours in EDL from nonseptic and septic rats, respectively (p less than 0.01). The corresponding values for SOL were 0.480 +/- 0.037 and 0.712 +/- 0.039 mumol Tyr/g X 2 hours (p less than 0.01). Addition of indomethacin to the incubation medium reduced PGE2 release from 29.1 +/- 3.1 to 6.8 +/- 0.7 ng/g X 2 hours in nonseptic SOL and from 50.6 +/- 10.4 to 5.6 +/- 0.7 ng/g X 2 hours in septic SOL. Protein breakdown rate in SOL and EDL from sham-operated or septic rats was unaffected by indomethacin, both when muscles were incubated in a flaccid or stretched state, and when they were incubated in the presence or absence of insulin. The present results do not suggest a role of PGE2 for accelerated muscle proteolysis in the present experimental septic model.
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PMID:Further evidence that accelerated muscle protein breakdown during sepsis is not mediated by prostaglandin E2. 316 71

The time course (12, 24 and 48 h) of changes in blood metabolites, and in gluconeogenesis and ketogenesis, in isolated hepatocytes from rats made septic by caecal ligation and puncture was measured. Blood glucose was not significantly different in septic rats, but lactate was increased at 12, 24 and 48 h; pyruvate and alanine were increased at 48 h. The blood ketone body concentrations were decreased at all times studied after induction of sepsis. These changes were accompanied by increased plasma insulin in the septic rats. The rate of hepatic lipogenesis in vivo was increased at 24 and 48 h. There were appreciable increases in the hepatic concentrations of alanine (200%), lactate (200%) and pyruvate (100%) as well as other intermediates in the gluconeogenic pathway. The hepatic concentrations of acetyl-CoA and ketone bodies were decreased. The rate of gluconeogenesis from added lactate, pyruvate, alanine and glutamine was depressed in isolated hepatocytes from septic rats at 24 and 48 h. The basal rate of ketogenesis or the rate from butyrate in isolated hepatocytes was not significantly altered by sepsis, whereas the rate from oleate was decreased at all time points. It is concluded that there is an impairment of the capacity for gluconeogenesis and ketogenesis in livers of septic rats. The latter may be due to decreased entry of long-chain acyl-CoA into the mitochondria for oxidation. The possibility that these changes are in part brought about by the hyperinsulinaemia associated with the sepsis is discussed.
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PMID:Time course of changes in hepatic metabolism in response to sepsis in the rat: impairment of gluconeogenesis and ketogenesis in vitro. 329 69

A 23-year-old insulin-dependent diabetic woman demonstrated increasing resistance to insulin administered by all routes, eventually requiring up to 20,000 units per day intravenously. Therapeutic trials of human and chemically modified insulin and of aprotinin were unsuccessful. Inappropriately low plasma free insulin levels (less than 60 mU/liter) during administration of extremely high insulin dosages (300 to 10,000 units per day) suggested that resistance was caused by rapid clearance of circulating insulin. There were several short periods of normal insulin sensitivity with hyperinsulinemia (more than 300 mU/liter) persisting long after intravenous insulin withdrawal, suggesting reentry to the circulation of intact, previously sequestered insulin. For four years, she has been treated with ambulatory continuous intravenous insulin infusion, which has been complicated by septicemia and central venous thrombosis. Her condition remains poorly controlled with documented intravenous insulin requirements of 2 to 20 units/hour.
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PMID:Massive insulin resistance apparently due to rapid clearance of circulating insulin. 330 Mar 7

Protein synthesis and degradation are particularly sensitive to malnutrition and catabolic states. Intracellular protein degradation is determined by the conformation, molecular weight, isoelectric point, and carbohydrate content of the proteins. ATP-stimulated endoproteases appear to catalyse the rate-limiting steps. In the liver, proteolysis is reduced by amino acids and/or insulin, whereas glucagon stimulates protein degradation, probably due to depletion of intracellular gluconeogenic amino acids. In the muscle, protein degradation is promoted by interleukin-1 and inhibited by Ep-475, which specifically inactivates cathepsin B,H, and L. Myofibrillar alkaline proteinase activity increases postoperatively and in patients suffering from malignant tumors, whereas normal proteinase values were observed in these patients following total parenteral nutrition. Increased alkaline proteinase activity is also observed in diabetes mellitus and is normalized by insulin. Extracellular proteolysis has been reported in patients with hypercatabolic acute renal failure and in patients with sepsis or acute pancreatitis. Plasma fractions obtained from hypercatabolic patients with postoperative acute renal failure were proteolytic. Plasma proteinase activity decreases during hemodialysis due to elimination of a metallo-proteinase. Plasma alpha 2-macroglobulin decreases in patients with acute renal failure and also during acute pancreatitis. Proteolytic degradation of parathyroid hormone by sera obtained from patients with acute pancreatitis has been observed. Also, there is a decrease of high molecular weight kininogen during experimental acute pancreatitis. Granulocyte elastase increases postoperatively, mainly in patients with sepsis. Sepsis also causes increased proteolytic activity in the urine. In conclusion, intracellular protein degradation can supply important precursors for hepatic and renal gluconeogenesis during malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proteinases in catabolism and malnutrition. 331

Decreased pyruvate dehydrogenase (PDH) activity in skeletal muscle has been observed during sepsis and may contribute to the altered glucose kinetics seen in this condition. The purpose of the present study was to determine if dichloroacetate (DCA), a known stimulator of PDH activity, could reverse the sepsis-induced increase in glucose metabolism. Hypermetabolic sepsis was produced in chronically catheterized rats by repeated subcutaneous injections of live Escherichia coli. Whole body glucose kinetics, assessed by a constant iv infusion of [6-3H and U-14C]-glucose, were determined in fasted septic and nonseptic rats before and for 4 hr after an injection of DCA (30 mg/100 g BW, iv). Sepsis produced hyperthermia (+1.6 degrees C) and increased the rates of glucose appearance (Ra; 95%), recycling (318%), metabolic clearance (MCR; 114%), and elevated plasma lactate levels (295%) compared to nonseptic controls. After injection of DCA into septic rats, glucose levels gradually fell, and the sepsis-induced hyperlactacidemia was completely reversed. Treatment of septic rats with DCA reversed the elevated glucose Ra; recycling, although reduced, was still elevated by 50% compared to control animals. DCA did not alter the hyperglucagonemia seen in septic animals, but it did reduce the plasma insulin levels by 60%. Hepatic and muscle PDH activities were not different in saline-treated septic and nonseptic animals. DCA elevated PDH activity in muscle from septic rats, but the increase was smaller than that seen in control animals. This may explain the smaller decline in glucose recycling and plasma lactate in septic animals. These results are consistent with DCA reducing the elevated glucose Ra in sepsis by partial activation of PDH, which reduces the elevated precursor (lactate) supply for gluconeogenesis. However, alterations in PDH activity did not appear to contribute to the underlying increase in glucose Ra and recycling observed in sepsis.
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PMID:Glucose kinetics and pyruvate dehydrogenase activity in septic rats treated with dichloroacetate. 331 89


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