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)

The objective of this study was to evaluate the safety and the effect of recombinant exogenous growth hormone (GH) on nitrogen production in patients with severe sepsis. It was designed as a prospective, randomized, placebo-controlled trial, and performed in the medical intensive care unit of a university hospital. Twenty patients admitted with septic shock and receiving standard parenteral nutrition served as subjects. Treatment consisted of GH 0.1 mg/kg/day or placebo administered as continuous intravenous infusion on the second, third, and fourth days after admission. The study period was eight days. During GH administration, nitrogen production decreased significantly in the GH group and increased in controls (p < 0.01). Nitrogen balance became slightly positive in the GH group during treatment: 1.2 +/- 6.4 versus controls -3.7 +/- 3.8 g/day (day 3) (p < 0.05). Within 24 hours after cessation of treatment, differences between GH and controls disappeared. 3-Methylhistidine excretion as a measure of absolute muscle breakdown declined during the study period, but did not differ between groups. The levels of insulin, insulinlike growth factor 1, glycerol, free fatty acids, and beta-hydroxybutyrate increased during treatment. Despite continuous intravenous administration, GH levels gradually declined during the 3 treatment days, indicating increased metabolic clearance. Side effects other than insulin resistance were not observed. Growth hormone administration reduces nitrogen production and improves nitrogen balance in patients with severe sepsis. These effects are not sustained after cessation of treatment.
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PMID:Effects of recombinant human growth hormone in patients with severe sepsis. 146 18

1. Patients suffering trauma and sepsis are insulin resistant, but no studies have specifically been made of patients suffering multiple organ failure. 2. We have studied exogenous glucose utilization in multiple organ failure using a combination of the hyperglycaemic glucose clamp and indirect calorimetry to quantify glucose utilization in multiple organ failure, partitioning it into oxidative and nonoxidative disposal (storage). 3. Fourteen septic patients with multiple organ failure were studied. APACHE II (Acute Physiological and Chronic Health Evaluation Mark II) scores on the day of the study ranged from 11 to 31 (median 16). Twenty percent D-glucose was infused and blood glucose was clamped at 12 mmol/l for 3 h. The results were compared with those obtained on seven healthy control subjects. 4. Glucose utilization and energy expenditure were similar in the two groups for the first 90 min of the clamp, after which glucose utilization and energy expenditure increased steadily in the control subjects but did not change in the patients. Respiratory exchange ratio rose in both groups; considered over the whole of the clamp period, respiratory exchange ratio was slightly lower in the patients than in the control subjects (P < 0.05) but not at any specific time point. Glucose oxidation rose in both groups but non-oxidative glucose disposal (storage) rose only in the control subjects. Glucose oxidation was slightly lower in the patients (P < 0.05) but not at any specific time point and there was no difference between the groups in the amount by which glucose oxidation increased. Non-oxidative disposal in the patients fell significantly (P < 0.01) over the course of the clamp and was significantly lower than in the control subjects (P < 0.01). 5. Growth hormone increased in response to glucose infusion in the patients but not in the control subjects. 6. Like patients suffering uncomplicated sepsis or trauma, patients with multiple organ failure are also insulin resistant. The defect appears to lie in an impairment of the ability to store glucose rather than oxidize it, and this may be due in part to the increase in growth hormone in patients with multiple organ failure.
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PMID:Septic patients in multiple organ failure can oxidize infused glucose, but non-oxidative disposal (storage) is impaired. 854 78

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1), especially the former, have immunoregulatory effects in addition to anabolic effects. The hormones may act to protect the host from lethal bacterial infection by promoting the maturation of myeloid cells, stimulating phagocyte migration, priming phagocytes for the production of superoxide anions and cytokines, and enhancing opsonic activity. GH administration may be beneficial for the prevention, as well as treatment, of severe sepsis in critical illness.
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PMID:Growth hormone and the immune response to bacterial infection. 874 19

Malnutrition is a critical predictor of mortality and morbidity in children with biliary atresia who undergo orthotopic liver transplantation. Growth hormone (GH) enhances nitrogen retention in patients with chronic obstructive lung disease, sepsis, and in fasted adult volunteers. The goal of this study was to assess the acute response to recombinant human GH (rhGH) treatment in children with biliary atresia to determine whether GH therapy was likely to improve pretransplant nutritional status. Five children, aged 10-32 months, with biliary atresia and persistent cholestasis despite surgical attempts to reestablish bile flow, were studied. All five children had portal hypertension, conjugated hyperbilirubinemia, and decreased serum albumin concentrations. Length, weight, and growth velocity were decreased in all five children. Despite adequate energy and protein intake, fat stores were depleted in all five subjects, and somatic protein stores were diminished in all except one child. Baseline serum concentrations of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) were low (8.4 +/- 2 ng/ml and 0.2 +/- 0.1 mg/l respectively). In the four children who completed the study, serum IGF-I and IGFBP-3 levels did not change after treatment with rhGH (0.1 mg/kg/day) for 4 days. Our findings indicate that children with biliary atresia awaiting liver transplantation are insensitive to GH and that treatment with GH is unlikely to promote anabolism. A rationale exists for examining the effect of treatment with IGF-I, which mediates the anabolic effects of GH.
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PMID:Growth hormone insensitivity in children with biliary atresia. 885 79

Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may be beneficial against the protein catabolism seen in injury and septicemia. Further understanding of their effects on carbohydrate metabolism is needed. In a septic porcine model receiving total parenteral nutrition, pretreatment with GH or IGF-1 (or no treatment in controls) was followed by an infusion of live Escherichia coli bacteria. Endogenous glucose production, carbohydrate oxidation, glucose and lactate fluxes over the liver, gastrointestinal organs, kidney, and hindleg were determined. Endogenous glucose production increased during septicemia in the GH group. The metabolic acidosis induced by septicemia was augmented by GH, but attenuated by IGF-1. The alanine and lactate levels were significantly higher in the GH- than in the IGF-1 treated animals during septicemia. IGF-1 pretreatment appeared to induce favorable effects while GH pretreatment might produce unfavorable effects on carbohydrate metabolism in septic piglets.
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PMID:Treatment with growth hormone and insulin-like growth factor-1 in septicemia: effects on carbohydrate metabolism. 956 41

Characteristic responses to surgery, trauma, and sepsis are catabolism and immunodepression. Nutritional therapy is important for managing patients with severe surgical stress. Conventional nutritional support, however, has not been successful in reducing morbidity and mortality rates. New nutritional support strategies have been aimed at enhancing protein metabolism and immunity. This review focuses on glutamine and growth hormone as nutritional support strategies for patients experiencing surgical stress. Glutamine is important in several key metabolic processes in critical illness. Exogenous glutamine also augments the functions of lymphocytes, macrophages, and neutrophils. Growth hormone has potent anabolic actions. Moreover, the peptides have immunostimulatory effects. These new modalities may be beneficial for the treatment of surgical patients.
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PMID:[Glutamine and growth hormone for the surgical nutritional support]. 961 98

Patients suffering severe burns have an accelerated catabolism with a highly negative nitrogen balance that may worsen their prognosis. Somatropin treatment has been shown to improve this balance in different hypercatabolic situations. Moreover, in children with extensive burns it also reduces the healing time of the skin graft donor site and shortens the hospital stay. In the existing literature there are no controlled prospective clinical trials in adult patients that confirm these data. Our aim was to demonstrate the efficacy of recombinant growth hormone (somatropin) in reducing the healing time of the skin graft donor sites and the length of stay in the burn unit in adult patients with severe burns. A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 adult patients with severe burns (more than 40% of the total body surface burned or more than 15% full-thickness burns). Patients received placebo (n = 11) or somatropin (n = 13) at a dosage of 0.15 mg/kg/day divided into two equal doses (every 12 hours) via intramuscular injection. Treatment was initiated the day the first autograft was performed and terminated the day the patient was discharged from the burn unit. The mean number (+/- SD) of skin grafts per patient was similar between the two groups (4.2 +/- 1.8 vs 3.4 +/- 1.8 in the placebo and somatropin groups, respectively). No reduction in the healing time of the skin graft donor site was observed in the somatropin group compared to the placebo group. Likewise, the time admitted to the burn unit was not significantly different, either in the absolute number of days (36.2 +/- 19.7 vs 30.1 +/- 16.8 days in the placebo and somatropin groups, respectively) or in relation to the percentage of the total body surface burned or the body surface with full-thickness burns. Growth hormone and insulin-like growth factor I (IGF-I) levels were three and five times higher, respectively, in the somatropin group than in the placebo group. Ten of the patients treated with somatropin experienced hyperglycemia, and seven of them required insulin treatment. No other adverse side effect was observed. One patient in the placebo group died as a result of sepsis and multiple organ failure. Somatropin, with the treatment regimen and dosage used in these studies, did not reduce the healing time of the skin graft donor sites or the length of hospitalization in the burn unit in adult patients with severe burns.
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PMID:Effects of human recombinant growth hormone on donor-site healing in burned adults. 1189 25

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are potent regulators of muscle mass. Transgenic mice that over-express these proteins exhibit dramatically enlarged skeletal muscles. In contrast, malnutrition, critical illness, sepsis, and aging are all associated with a dramatic reduction in muscle mass and function. The circulating concentration of IGF-I and the expression of IGF-I in skeletal muscle are also reduced during catabolic states. Consequently, GH has been used clinically to increase lean body mass in patients with muscle wasting. Likewise, delivery of IGF-I specifically into muscle has been proposed as a genetic therapy for muscle disorders. A better understanding of the regulation of IGF-I expression in skeletal muscle and muscle cells is therefore of importance. Yet, our knowledge in this area has been limited by a lack of GH responsive muscle cells. In addition the IGF-I gene spans over 90 kb of genomic DNA and it exhibits a very complex regulatory pattern. This review will summarize our knowledge of the control of muscle mass by GH, IGF-I, anabolic steroids, exercise and other growth enhancing hormones. We will also highlight recent advances in the regulation of IGF-I and signal transducers and activators of transcription (Stats) by GH. A special emphasis will be placed on the interaction of IGF-I and proinflammatory cytokines in skeletal muscle and muscle cells.
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PMID:Regulation of insulin-like growth factor-I in skeletal muscle and muscle cells. 1262 63

Growth hormone (GH) stimulates insulin-like growth factor I (IGF-I) synthesis in both liver and muscle. During sepsis, proinflammatory cytokines inhibit GH action in liver, but it is unknown whether sepsis also produces GH resistance in muscle. Sepsis was induced by cecal ligation and puncture, and 18 h later the effect of GH on signal transducer and activator of transcription (STAT) phosphorylation and IGF-I mRNA content was assessed in rat gastrocnemius and liver. The relative abundance of phosphorylated (p)STAT5a, pSTAT5b, pSTAT3, and pSTAT1 was increased in liver from control rats after GH. Sepsis alone also increased hepatic pSTAT5a, pSTAT3, and pSTAT1. Sepsis dramatically impaired the ability of GH to stimulate the phosphorylation of STAT5a and -5b, as well as to increase IGF-I mRNA in liver. In muscle from control rats, GH increased pSTAT5a and -5b, whereas content of pSTAT3 and pSTAT1 was not affected. Sepsis increased basal content of pSTAT3 but not pSTAT5a, pSTAT5b, or pSTAT1 in muscle. The GH-induced increase of pSTAT5a and -5b in muscle from septic rats was not inhibited, suggesting that muscle was not GH resistant. In contrast to these changes in pSTAT5, the ability of GH to increase IGF-I mRNA was completely absent in muscle from septic rats. Because the suppressor of cytokine signaling (SOCS) proteins may function as negative regulators of GH signaling, we examined the content of these proteins. Sepsis produced small (30-50%), albeit statistically significant, increases in SOCS-1, -2, and -3 protein in muscle. In contrast to muscle, the SOCS proteins in the liver did not change under the various experimental conditions, suggesting that these proteins are not responsible for the impaired phosphorylation of STAT5 by GH. In conclusion, sepsis produces GH resistance in both muscle and liver, with the locus of this impairment in muscle differing from that in liver and being independent of a defect in STAT5 phosphorylation.
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PMID:Sepsis-induced muscle growth hormone resistance occurs independently of STAT5 phosphorylation. 1264 50

Growth hormone (GH) has been used as anabolic therapy to treat catabolic patients. In a recent study, however, administration of high doses of GH to critically ill adults was associated with an increase in morbidity and mortality. Preponderance of septic shock and uncontrolled infections as causes of death in these patients suggests an immuno-modulatory effect of GH. Our hypothesis was that GH treatment may modulate the production of proinflammatory cytokines, which are implicated in sepsis. In our study, human monocytes in whole blood were activated with lipopolysaccaharide (LPS) (1-100 ng/ml) purified from a clinical isolate of group B Neisseria meningitidis in the presence of a high dose of GH (100 ng/ml). The subsequent proinflammatory cytokine response was analysed by intracellular cytokine staining and flow cytometry. Our results show that GH enhances IL1-alpha, IL-6 and TNF-alpha production by LPS activated monocytes in whole blood. The modulation of cytokines by GH may be responsible for the adverse consequences of GH in critically ill patients.
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PMID:Growth hormone enhances proinflammatory cytokine production by monocytes in whole blood. 1293 50


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