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The objective of this study was to evaluate the effects of recombinant human growth hormone (GH) on cell immune function, intestinal barrier function, and outcome. A placebo-controlled randomized double-blind trial was performed, with 20 patients undergoing abdominal surgery enrolled in the study. The patients in the study group received GH (0.3 IU/kg/day) subcutaneously from day 3 before operation until day 7 after operation. The patients in the control group received placebo injections. All the patients were given isonitrogenic (0.15 g N/kg/day) and isocaloric (20 kcal/kg/day) parenteral nutrition from preoperative day 1 through postoperative day (POD) 6. The serum GH and insulin-like growth factor-1 (IGF-1) levels, intestinal permeability, peripheral CD4+/CD8+ lymphocyte subsets, and routine blood and biochemistry analyses were evaluated before and after GH treatment. In the study group a significant increase in serum levels of GH and IGF-1 was observed on PODs 3 and 7. A significant decrease in the CD4+ subset population and the CD4+/CD8+ ratio was observed in the control group on POD 7 compared with preoperative studies, whereas no change was observed in the study group. The lactulose/mannitol excretion (L/M) ratio in the control group was elevated significantly on POD 7 compared with that before operation (p = 0.01), whereas the L/M ratio in the study group did not change compared to preoperative values (p = 0.08). No adverse reactions were related to the administration. There were no differences observed in operation-related complications or postoperative hospital stays between the two groups. This small pilot study suggests that GH attenuated the depression in cellular immunity following surgical stress and possibly reduced the increase in intestinal permeability that occurs following operation. Further studies of a large group of patients are needed to determine if these changes can be translated into improved outcome in surgical patients. [ABSTRACT FROM AUTHOR]

Presents a symposium on glutamine. Difference between bone marrow transplant patients and critically ill patients; Problem on establishing safety in meta-analysis; Issue on designing a blutamine trial for critically ill patients; Discussion on what to use for controls in infusing glutamine.

The metabolic response to injury, whether a controlled elective surgical procedure or an accidental injury, is characterized by the breakdown of skeletal muscle protein and the translocation of the amino acids to visceral organs and the wound. At these sites, the substrate serves to enhance host defenses, and support vital organ function and wound repair. Glutamine (GLN) plays a major role in these processes, accounting for approximately one third of the translocated nitrogen. From available data, GLN-supplemented intravenous nutrition in patients undergoing elective surgery improves nitrogen balance, helps correct the decreased GLN concentration found in the free intracellular skeletal muscle amino acid pool and enhances net protein synthesis (particularly in skeletal muscle). Six randomized blind trials (two multicentered investigations) reported a decreased length in hospital stay in postoperative patients receiving GLN supplementation. After blunt trauma, GLN supplementation increased plasma concentrations, attenuated the immunosuppression commonly observed and decreased the rate of infection. Patients with burn injury have low GLN plasma and intramuscular concentrations; turnover and synthesis rate are accelerated, yet apparently inadequate to support normal concentrations. These data suggest that GLN supplementation has important effects in catabolic surgical patients, but the exact mechanisms to explain these events remain unknown, and more research is required to explain the apparent benefits of dietary GLN. [ABSTRACT FROM AUTHOR]

Discusses the importance of mitochondrial glutamine to the renal glutamine metabolism of rat. Discussion on renal glutamine metabolism; Significance of the maintenance of blood acid-base balance; Properties of the mitochondrial glutaminase.

Discusses advancements being made to improved surgery. Changes that have occurred in pain control management, with the introduction of techniques that reduce perioperative stress response and the use of minimally invasive operations; Definition of fast track surgery; Use of these techniques in day surgical units.

Growth factors enhance protein synthesis and thus reduce the catabolic response to injury. As a result of bioengineering and new manufacturing techniques several anabolic agents have become available for clinical use and have been evaluated in surgical patients with catabolic illness. Data support the anabolic effects of growth home in such patients, but its expense and possible deleterious effects during the acute phase of illness limit its use to selected patient groups. Insulin-like growth factor-1 has also been studied, but specific indications for its use have not been identified in catabolic patients. Testosterone and derivatives of this hormone exert anabolic effects, but few randomized trials include catabolic surgical patients, and higher doses of some derivative compounds are associated with hepatic dysfunction. Nonetheless, as we move into the future, studies will determine the specific doses for administration of these and other anabolic factors in specific patient groups. Anabolic therapy will shorten the length of therapy and improve the outcome in the future. [ABSTRACT FROM AUTHOR]

The short bowel syndrome is a symptom complex that occurs in adults who have less than 200 cm of jejunum-ileum remaining after intestinal resection. Similar symptoms are observed in infants and children following massive bowel resection or congenital anomalies and in individuals with longer segments of intestine with severe mucosal disease. Initial care should focus on a thorough excision of nonviable bowel, an exact measurement of the remaining viable bowel, placing all intestine in continuity at the initial or subsequent operation, and controlling initial food intake. With time, adaptation of the remnant intestine occurs, and absorptive function may be maximized by enhancing the enteral diet and minimizing parenteral nutrition. Growth factors and specialized nutrients may also enhance this process. Intestinal transplantation should be considered in selected individuals with the short bowel syndrome who fail intestinal rehabilitation protocols. [ABSTRACT FROM AUTHOR]

Severe surgical illness results in metabolic responses that mobilize substrate (amino acids and fatty acids) from body stores to support vital organs, enhance resistance to infection, and ensure wound healing. Central to this process is the redistribution of body protein, which moves from skeletal muscle to support the central viscera. If unsupported, this protein-wasting state could result in prolonged convalescence, diminished immunity, and poor wound healing. Present evidence suggests that the central nervous system plays a major role in regulating this protein catabolic response. Infusing exceedingly small quantities of the proinflammatory cytokines into the brain can mimic injury responses, and central cytokine blockade may be one therapeutic approach to attenuating these responses safely in the future. Additional evidence also demonstrates that the function of the hypothalamus and anterior pituitary is dampened during the later stages of severe surgical illness, and the possibility of hormonal replacement therapy needs to be explored. [ABSTRACT FROM AUTHOR]

Postoperative nitrogen sparing refers to a therapy that decreases net nitrogen loss from the body following an operation. Protein sparing has long been regarded as a surrogate marker for improved outcome, but a critical review of the evidence indicates that this relation is difficult to establish, especially in the short term. Thus, specific endpoints that evaluate outcome are needed to determine the efficacy of a specific therapy that spares protein. Cost effectiveness must also be considered. A variety of therapies were evaluated using protein-sparing, efficiency, and cost criteria. Evidence was reviewed for glucose, amino acids, parenteral nutrition, enteral nutrition, growth hormone, and glutamine administered during the perioperative period. Only three areas could be identified that spared nitrogen and provided efficacy: (1) preoperative total parenteral nutrition (TPN) for 7 to 10 days before operation in a depleted patient (≤15% body weight loss); (2) the use of growth hormone with nutritional support to promote wound healing (especially in burns) and possibly to enhance muscle strength (particularly in the elderly); and (3) the use of glutamine-supplemented TPN in severely ill surgical patients to decrease mortality. The issue of early tube feeding in trauma patients is still confusing. This therapy must be evaluated by an appropriate study in trauma patients that compares a tube-fed group with an unfed control group. Only by demonstrating improved outcomes and enhanced cost saving with our protein-sparing therapy can we continue to enhance the care of our surgical patients. [ABSTRACT FROM AUTHOR]

Interleukins (IL) -1 beta and -1 alpha and tumor necrosis factor (TNF-alpha) were measured by radioimmunoassay in plasma samples from 44 healthy individuals, 15 patients in septic shock, and 6 volunteers infused with endotoxin. Plasma IL-1 alpha levels were low (40 pg/ml) or undetectable in all situations. In 67% of the healthy subjects, plasma IL-1 beta levels were less than 70 pg/ml. Septic patients had higher plasma IL-1 beta levels (120 +/- 17 pg/ml, P = .001); those of surviving patients were higher than those of patients who died (P = .05). Plasma TNF-alpha concentrations in septic individuals were elevated (119 +/- 30 pg/ml) and correlated with severity of illness (r = .73, P = .003), but no correlation was observed between plasma IL-1 beta and TNF-alpha concentrations in individual samples. Infusion of endotoxin caused a twofold elevation of IL-1 beta, from a baseline of 35 +/- 5 pg/ml to a maximum of 69 +/- 27 pg/ml at 180 min (P less than .05). Peak TNF-alpha levels after endotoxin infusion were 15 times higher than IL-1 beta levels, were attained more rapidly (90 min), and as with the septic patients, did not correlate with IL-1 beta levels. These data support the concept that plasma IL-1 beta and TNF-alpha concentrations are regulated independently and are associated with different clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: To determine the effects of phosphocreatine (PCr) depletion on myocellular energetics. Design: Randomized controlled study. Setting: University laboratory. Materials: Thirty-eight adult male Wistar rats (110-121 g). Methods: The poorly metabolized creatine analogue β-guanidinopropionic acid, (β-GPA, 2% of a gel diet) was fed to the rats for 14 days to replace (75%) endogenous PCr stores before cecal ligation and puncture (CLP). Rats were randomized to receive sham operation and gel diet (sham-gel group [n=10]), sham operation and β-GPA diet (sham–β-GPA group [n=9]), CLP and gel diet (CLP-gel group [n=10]), and CLP and β-GPA diet (CLP–β-GPA group [n=9]). On day 14, all animals underwent operation. Twenty-four hours later, in vivo phosphorus 31–labeled magnetic resonance spectroscopy ([sup 31]P-MRS) of the gastrocnemius muscle was performed. Muscle samples were collected to determine enzyme activities of β-hydroxyacyl-CoA dehydrogenase, phosphofructokinase, citrate synthase, and the metabolites adenosine triphosphate (ATP), PCr, inorganic phosphate, and creatine. Free adenosine diphosphate levels, the phosphorylation potential, and free energy change of ATP hydrolysis were then calculated. Results: All animals undergoing CLP but no controls had positive results of blood cultures. Although sham–β-GPA animals had altered bioenergetics, CLP–β-GPA rats experienced a greater deterioration of energy state compared with CLP-gel controls. Glycolytic and oxidative enzyme activities were not significantly different between groups and therefore could not explain the observed differences. Conclusions: There is an overall decrease in energy availability during sepsis, which is worsened by PCr depletion. These changes support the contention that PCr plays an important role as an ATP buffer during systemic infection. [ABSTRACT FROM AUTHOR]

Adequate nutritional support for the critically ill patient has evolved over the past 150 years from a time when starvation was accepted practice for patients with fever. Three to four thousand calories and other essential nutrients can now be safely provided each day to patients with infection or other critical illness. Nutrients may be provided in meals, administered by specialized enteral feedings, or infused intravenously . Nutrient mixtures with a high proportion of carbohydrate and protein appear the best dietary therapy to maintain body protein and support other organ systems and cellular functions. New products and formulas offer the physician a wide variety of techniques for providing adequate nutrition to all patients with critical illness. [ABSTRACT FROM AUTHOR]

Objective: To determine whether glutamine-supplemented parenteral nutrition improves nitrogen retention and reduces hospital morbidity compared with standard parenteral nutrition after bone marrow transplantation.Design: Double-blind, randomized, controlled clinical trial.Setting: University teaching hospital.Patients: Forty-five adults receiving allogeneic bone marrow transplants for hematologic malignancies.Intervention: Parenteral nutrition was initiated the day after bone marrow transplantation (day 1). The experimental solution was supplemented with L-glutamine (0.57 g/kg body weight per day) and provided estimated requirements for energy and protein. The control solution was a standard, glutamine-free, isonitrogenous, isocaloric formula.Measurements: Nitrogen balance was determined between days 4 and 11 in the initial 23 patients. The incidence of clinical infection and microbial colonization, time until bone marrow engraftment, indices of clinical care, and other data related to hospital morbidity were recorded for all patients.Results: The glutamine-supplemented patients (n = 24) were clinically similar to the controls (n = 21) at entry. Nutrient intake was similar in both groups; however, nitrogen balance was improved in the glutamine-supplemented patients relative to the controls (-1.4 +/- 0.5 g/d compared with -4.2 +/- 1.2; P = 0.002). Fewer experimental patients developed clinical infection (three compared with nine in the control group; P = 0.041), and the incidence of microbial colonization was also significantly reduced. Hospital stay was shortened in patients receiving glutamine supplementation (29 +/- 1 d compared with 36 +/- 2 d; P = 0.017).Conclusion: Patients receiving glutamine-supplemented parenteral nutrition after bone marrow transplantation had improved nitrogen balance, a diminished incidence of clinical infection, lower rates of microbial colonization, and shortened hospital stay compared with patients receiving standard parenteral nutrition. These effects occurred despite no differences between groups in the incidence of fever, antibiotic requirements, or time to neutrophil engraftment. [ABSTRACT FROM AUTHOR]

Total leg blood flow was measured by venous occlusion plethysmography in five normals and 14 burned patients before and after 30 min of external heating. Leg surface temperatures were held constant, but rectal temperatures increased on the average of 0.4 to 0.5°C in all subjects following this heat load. Leg blood flow increased by 56.0% in the controls, 63.2% in five patients with essentially no leg bum (mean burn size = 1.5% leg surface), and 9.6% in nine patients with major leg injuries (mean bum size 55% leg surface). Failure of reflex vasodilatation in the burned leg was evident up to 107 days postinjury even when the wound was well-healed. All subjects sweated freely from the unburned skin. In two patients, where arm and leg blood flows were measured simultaneously, flow to the uninjured arm increased while that to the injured leg remained unchanged. This lack of reflex vasodilatation in the burned limbs suggests either that wound vessels are denervated or that they are so dilated in the basal state that further dilatation is limited. The bulk of this and other data would support the denervation concept. This physical or chemical denervation could occur at the time of injury, be localised to the area of the wound, and result in loss of both neurogenic vasoconstrictor tone and active reflex vasodilatation. [ABSTRACT FROM PUBLISHER]