Search PubMed⌕ Search

Biomedical subjects

D W Wilmore

Publications and source records attributed to D W Wilmore.

At least 37 records · Page 2Linked to original sources
PubMed1997

Metabolic support of the gastrointestinal tract: potential gut protection during intensive cytotoxic therapy.

BACKGROUND: Potentially curative options involving cytoablative therapies are now available for the treatment of almost all human tumors, but major toxicities represent the rate-limiting step in achieving a cure with these therapies. With successful hematoprotective strategies now in use, it is apparent that the gastrointestinal tract will be the rate-limiting organ system that prevents further dose escalation in many cancer patients. METHODS: A review of the English language literature was conducted. Paperchase, a computer-based application that reviews the data bases of the National Library of Medicine and the National Cancer Institute, was used to obtain pertinent literature. RESULTS: A variety of gut-protective nutrients and growth factors were identified. These substances may be useful in preventing dose-limiting gastrointestinal symptoms. Animal studies and some patient data suggest that the amino acid glutamine stimulates mucosal growth and promotes gut health. When nutrient administration is coupled with growth factors, such as growth hormone, insulin-like growth factor-1, glucagon-like peptide-2, and interleukin-11, a high level of bowel protection should be attained. CONCLUSIONS: Therapy is evolving that may be useful in protecting the intestinal mucosa and preventing dose-limiting gastrointestinal symptoms.

Animals↗
PubMed1997

Starvation enhances hepatic free radical release following endotoxemia.

Although it is well known that malnourished patients who become septic have an increased risk of organ failure and death compared to normally nourished individuals, the pathological processe(s) underlying this observation are unknown. To evaluate one possible explanation for this finding, we tested the hypothesis that malnutrition depresses hepatic antioxidant stores and accelerates hepatic release of oxygen free radicals in an animal model of sepsis. Male rats were either fasted (n = 14) or fed (n = 14) for 3 days prior to receiving lipopolysaccharide (LPS, 17 mg/kg intraperitoneally). Animals were weighed daily and then sacrificed 6 and 24 hr after LPS administration to determine hepatic superoxide anion (an oxygen free radical) release and liver glutathione (GSH, an antioxidant) content. Fasted rats were severely malnourished as indicated by a 23% decrease in body weight compared to fed rats, which gained 11% (P < 0.05). Liver GSH was depressed by 30% (P < 0.05) and 20% (P = 0.066) in the fasted compared to fed animals 6 and 24 hr after LPS administration. In addition, hepatic superoxide anion release was 210 and 75% higher in the fasted animals 6 and 24 hr after LPS injection (P < 0.05 at both time points). Liver superoxide anion release and GSH content were negatively correlated (P < 0.001, R = - 0.73) indicating that superoxide anion release increased as GSH content fell. Malnutrition leads to depletion of liver antioxidant stores with accelerated release of hepatic oxygen free radicals. Oxidant-mediated organ damage may be one cause of increased morbidity and mortality in malnourished, systemically infected patients.

Animals↗
PubMed1997

Metabolic responses to interleukin-1: centrally and peripherally mediated.

OBJECTIVE: The purpose of this study was to differentiate between the catabolic effects of interleukin-1 (IL-1) when infused into the central nervous system or into the periphery. SUMMARY BACKGROUND DATA: After injury and infection, IL-1 has been found in the central nervous system. Chronic intracerebrovascular infusion of IL-1 produces protein catabolism, anorexia, and fever. However, IL-1 may act directly on liver and bone marrow to elicit metabolic responses. Although IL-1 is thought to be involved in a number of metabolic responses associated with injury-inflammation, the sites of action are unclear. METHODS: Rats were implanted with chronic infusion pumps and received diluent or three doses of IL-1 infused subcutaneously for 6 days, and a variety of response variables were measured. In a second study, doses were adjusted so that similar systemic catabolic responses were obtained from peripheral and intracerebroventricular infusion of IL-1. The acute-phase responses then were compared in the two groups of animals receiving IL-1 by different routes. RESULT: Subcutaneously infused IL-1 elicited catabolic responses in a dose-response manner. Similar catabolic responses were achieved by infusing one tenth of the dose of IL-1 given subcutaneously into the central nervous system. Although similar systemic responses (protein catabolism, anorexia, fever, and weight loss) were observed with both routes of infusion, the subcutaneous infusion produced a much greater lymphocytosis, elevation in acute-phase reactants, and fall in serum iron and albumin. CONCLUSIONS: The IL-1 appears to have different effects depending on the site of production and site of action. Regionalization of signal proteins such as IL-1 should be taken into consideration when devising specific anticytokine treatment strategies.

Animals↗
PubMed1997

Factors predicting a successful outcome after pharmacologic bowel compensation.

OBJECTIVES: The authors determined those factors that predict a successful outcome in patients who receive pharmacologic agents to promote bowel absorption after massive intestinal resection. SUMMARY BACKGROUND DATA: Patients with the short bowel syndrome are maintained on long-term total parenteral nutrition (TPN) or more frequently considered for intestinal transplantation as part of their treatment program. The authors have administered a combination of trophic agents and a specialized diet to further enhance intestinal compensation and optimize nutrient absorption in patients with intestinal failure. METHODS: Forty-five TPN-dependent adults with a jejunal-ileal remnant < or = 50 cm and a portion of colon in continuity were treated with growth hormone, glutamine, and a modified diet for 4 weeks and observed for an average of 1.8 years. RESULTS: The average age of the patients was 43 years, the average jejunal-ileal length was 23 cm, and the average length of time the patient received TPN was 4.3 years. After 4 weeks of therapy, 26 (58%) were free of TPN support. Predictors of a favorable response included greater bowel length, lower body weight, and greater bowel length-body weight ratio. At follow-up, the percentage of patients who were not receiving TPN had fallen to 40%. CONCLUSIONS: Approximately half of a group of patients, thought to have absorptive surface area inadequate to be independent of TPN support, can maintain themselves on enteral feedings after this intestinal rehabilitation program. Because of the risk, costs, and alterations in lifestyle associated with long-term TPN or intestinal transplantation or both, it seems prudent to consider a program of bowel rehabilitation with an individual patient before embarking on another therapeutic plan.

Adult↗
PubMed1997

Superiority of blood over saline resuscitation from hemorrhagic shock: a 31P magnetic resonance spectroscopy study.

OBJECTIVE: To study the relation between blood and saline administration, postresuscitation hematocrit (Hct) level, and metabolic recovery after hemorrhagic shock. SUMMARY BACKGROUND DATA: It is generally believed that crystalloid can be substituted, in whole or in part, for blood during resuscitation of hemorrhagic shock. This is based on the belief that Hct can be safely reduced but should not fall below a critical level. METHODS: Male rats weighing 200 g were subjected to an isobaric hemorrhagic shock at a mean arterial pressure of 30 mmHg for 14 minutes, after which they were randomized to one of three resuscitation regimens. Control group (n = 36) were resuscitated by return of all shed blood. Mid-Hct (n = 39) and low-Hct (n = 60) groups were depleted of one third and one half of their circulating blood volumes, respectively, and were resuscitated with three times that volume of normal saline. Skeletal muscle intracellular energetics and pH were measured serially using 31P magnetic resonance spectroscopy at baseline, during shock, and after resuscitation. Arterial blood was sampled at the same time points. The number of surviving animals in each group at 24 hours was recorded. RESULTS: After resuscitation, surviving rats in the low-Hct group demonstrated a greater consumption of high-energy phosphocreatine stores than did the other groups (control = 0.479 +/- 0.003, mid-Hct = 0.465 +/- 0.004, low-Hct = 0.457 +/- 0.007, mean +/- standard error of the mean; p < 0.01 low-Hct vs. other groups by analysis of variance). The rats that received saline resuscitation developed a relative intracellular acidosis (control = 7.29 +/- 0.02, mid-Hct = 7.25 +/- 0.02, low-Hct = 7.23 +/- 0.02; p < 0.05 controls vs. other groups by analysis of variance). At 24 hours, the death rates were significantly different among the groups: control = 1 of 36 rats (2.8%), mid-Hct = 6 of 39 (15.4%), and low-Hct = 14 of 60 (23.3%) (p < 0.05 by chi square analysis). CONCLUSION: The oxygen-carrying capacity of resuscitation fluid has an important impact on intracellular metabolism and outcome.

Animals↗
PubMed1997

[Effect of recombinant growth hormone on amino acids metabolism in blood and urine after major operation].

To determine the effects of recombinant human growth hormone (GH) on postoperative amino acids metabolism, we performed a placebo-controlled randomized double-blind trial in 18 patients after elective gastrectomy or colectomy. The same amount of calories and amino acids were administered. Research group was daily injected growth hormone 0.15 IU/(kg.day) and control group was given placebo during the first postoperative week. All urine were analyzed for nitrogen balance and excretion of 3-methylhistidine. On the seventh postoperative day while the parenteral nutrients were being infused, amino acid exchange across the forearm was measured. On the seventh postoperative day all patients' amino acids in plasma were slightly increased by comparing with preoperative day but was not statistical significance. Forearm arterial-venous difference (A-V) measured on POD + 7 was markedly different between groups. There was continued release of amino acids from the forearm in the control subjects, while there was marked amino acid uptake in the GH patients (total amino acid nitrogen exchange was -398 +/- 158 mumol/L vs +165 +/- 61 mumol/L, P < 0.01). Excretion of urinary 3-methylhistidine in control group loss more than in GH group (7.3 +/- 1.0 mumol/(kg.24 h) vs 4.4 +/- 0.3 mumol/(kg.24 h), P < 0.05). The results demonstrated that GH can increase the uptake of amino acid from forearm and decrease the excreation of 3-methylhistidine in urine after operation, but did not disturb the balance of amino acids in plasma.

Amino Acids, Branched-Chain↗
PubMed1996

Glutamine-enriched total parenteral nutrition enhances plasma glutathione in the resting state.

Glutathione (GSH) is the major intracellular antioxidant and is essential to normal cell function and replication. Cysteine and other thiol compounds have been considered rate-limiting for GSH biosynthesis, but recent studies have demonstrated that glutamine (GLN) becomes essential during metabolic stress to replete tissue GSH levels which have become depleted. To determine the role of GLN supplementation in the resting, nonstressed state, we studied three groups of Wistar rats. The animals were catheterized and randomly assigned to one of three groups; (1) chow ad libitum group receiving iv saline (control), (2) standard total parenteral nutrition (STA-TPN) group, and (3) glutamine-enriched TPN (GLN-TPN) group. The intravenously fed animals received no rat chow. The infusions were administered at a rate of 2.2 ml/hr for 4 days and all animals were harvested on the fifth day of study. The GLN-TPN group had a significantly higher plasma GSH level than STA-TPN or control animals (P < 0.01). The hepatic concentration of GSH and the oxidized GSH/reduced GSH were similar in all groups. GLN-TPN had a significantly lower plasma ALT level than the control group (P < 0.05). The control group had a significantly higher ALP level than STA-TPN and GLN-TPN animals (P < 0.01). There were no significant differences in other measures of hepatic functions among the three groups. Our data demonstrate that in this model GLN-enriched TPN enhances plasma GSH concentrations, while maintaining hepatic GSH stores. This suggests that GSH turnover is altered during glutamine-enriched TPN, which may explain how dietary GLN supplementation enhances tissue antioxidant capacity.

Animals↗
PubMed1996

Glucocorticoid receptor antagonism by mifepristone alters phosphocreatine breakdown during sepsis.

OBJECTIVE: To determine the role of glucocorticoids in the regulation of myocellular energetics induced by sepsis by means of the glucocorticoid receptor antagonist mifepristone (RU 38486). DESIGN: Randomized controlled study. SETTING: University laboratories. PARTICIPANTS: Thirty-two adult male Wistar rats. METHODS: Animals were randomly assigned to 1 of 4 groups. In 2 groups, mifepristone (10 mg/kg) was administered by gavage feeding 2 hours before cecal ligation and single 18-gauge needle puncture or sham operation. The other 2 groups of animals received placebo gavage feedings 2 hours before their surgical procedures. Twenty-four hours after operation, high-energy phosphate ratios, intracellular pH, the forward rate constant for the creatine kinase reaction, and phosphocreatine breakdown rates were measured in the gastrocnemius muscle by in vivo phosphorus 31 magnetic resonance spectroscopy. Tissue and blood samples were collected to measure creatine and adenosine 5'-triphosphate concentrations, Na(+)-K+ adenosine triphosphatase activity, and circulating corticosterone levels. RESULTS: Circulating corticosterone levels were twice as high in septic animals as in sham-operation control rats (P < .01). Phosphocreatine breakdown rates and Na(+)-K+ adenosine triphosphatase activity were significantly higher (40% and 75%, respectively; P < .01) in placebo-treated septic rats than in sham-operation control rats. However, phosphocreatine breakdown rates and Na(+)-K+ adenosine triphosphatase activity in mifepristone-treated septic animals were not significantly elevated above control levels. CONCLUSION: Pretreatment with mifepristone reduces the demand for adenosine triphosphate production from phosphocreatine breakdown and downregulates Na(+)-K+ adenosine triphosphatase activity during sepsis.

Adenosine Triphosphate↗
PubMed1996

Does multifrequency bioelectrical impedance relate to body composition?

BACKGROUND: There is need for a rapid, noninvasive, inexpensive yet accurate bedside technique to measure body composition. Bioelectrical impedance analysis measures the resistance and conductance of a weak electrical current passed through the body. It has been suggested that multifrequency impedance analysis can determine the distribution of fluid between the extracellular and intracellular compartments. MATERIALS AND METHODS: The correlation between the resistance signals obtained from multifrequency bioelectrical impedance measurements and body composition was determined in normal rats ranging from 150 to 400 g in weight. Total body water, body fat, total body sodium, and total body potassium were measured using the carcass analysis technique, and extracellular water was derived from a dilutional marker using sodium bromide. Fat-free mass was calculated as the difference between body weight and body fat, and intracellular water was derived from total body water and extracellular water. Multifrequency bioelectrical impedance was measured at frequencies ranging from 3 to 300 kHz. Resistance at zero frequency and infinite frequency was calculated using the Cole and Cole equation. RESULTS: Resistance index (i.e., length of the animal2/resistance) was highly correlated with all body compartments (r = 0.879-0.996) at all frequencies. There was also a high correlation among all compartments of the body (r = 0.971--0.999). Because of this high intercorrelation among the body compartments, a specific relationship between the multifrequency bioelectrical impedance signal and a specific compartment was not identified. CONCLUSIONS: Resistance index at any frequency will be correlated with any body compartment in a normal population. The utility of this technique should be determined in situations where there is a disturbance in the relationship between various compartments of the body.

Animals↗
PubMed1996

The enhanced effect of parenteral nutrition on hepatotoxicity.

Recent studies have demonstrated that enteral feedings are associated with decreased morbidity and mortality when compared with parenteral feedings. In this study, we hypothesized that (1) route of feeding affects morbidity and mortality in a model of drug-induced hepatotoxicity and (2) glutamine and polymyxin B, which have been reported to reduce bacterial translocation, attenuate this effect when TPN is used. Male virus-free Wistar rats were divided into six groups receiving: (1) ad libitum chow infused with intravenous (IV) saline (Chow), (2) standard total parenteral nutrition solution administered via gastrostomy (Enteral), (3) standard total parenteral nutrition infused via a central catheter (TPN), (4) standard TPN containing polymyxin B (TPN-PolyB), and (5) glutamine-enriched TPN (TPN-GLN). A final group of animals was not manipulated but harvested at time 0 to serve as controls. The dose of polymyxin B used in this study has previously been shown to significantly reduce bacterial translocation. After 4 d of feeding, all rats received 5% dextrose infusion after an intraperitoneal (IP) injection of acetaminophen (ACM). Rats were sacrificed 0, 6, and 24 h after ACM administration. The TPN group had a lower liver glutathione level after 6 and 24 h, greater levels of liver enzymes after 24 h, and a lower survival rate after 24 h compared with Chow. The Enteral group had less morbidity than TPN but greater morbidity than Chow. Addition of polymyxin B or glutamine had a minimal effect on morbidity or mortality when compared to the TPN group. We conclude that rats receiving IV nutrition have greater morbidity and mortality following a standard hepatic insult than chow-fed rats. We speculate that alteration of microsomal cytochrome P-450 or drug clearance may be related to the benefits of providing nutrients by the gastrointestinal route.

Acetaminophen↗
PubMed1996

Use of growth hormone for postoperative respiratory failure.

BACKGROUND: The authors examined the efficacy of human growth hormone (HGH) in patients dependent on mechanical ventilation who were being weaned from the respirator. METHODS: A total of 53 patients were chosen by the primary surgical team in consultation with the critical care service to undergo HGH therapy. These patients had been receiving standard ICU support and had failed standard ventilator weaning protocols. As such, they were treated with HGH in an attempt to increase respiratory muscle strength and facilitate weaning from mechanical ventilation. RESULTS: General demographic information was recorded. Patients suffered from a high incidence of co-morbid conditions and infectious complications. The average duration of HGH therapy was 38 days, and 81% of the previously unweanable patients were eventually weaned from mechanical ventilation with an overall survival of 76%. Mortality as predicted by APACHE II Scores was significantly less than actual mortality (24% actual mortality vs. 42% predicted mortality, P < 0.05). CONCLUSIONS: This phase I study presents clinical evidence supporting the safety and efficacy of HGH in promoting respiratory independence in a selected group of surgical ICU patients. Randomized, blinded, controlled trials now seem warranted.

Aged↗
PubMed1996

Glutamine deficiency as a cause of human immunodeficiency virus wasting.

Tissue wasting often occurs during human immunodeficiency virus infection and acquired immune deficiency syndrome. While weight-loss in the human immunodeficiency virus-infected individual can be seen as an isolated symptom, catabolism during acquired immune deficiency syndrome is usually associated with complications such as diarrhea, malabsorption, fever and secondary infection. Glutamine is an amino acid central to many important metabolic pathways and recent findings suggest that glutamine depletion may explain the progression of tissue wasting during human immunodeficiency virus infection.

Animals↗
PubMed1996

Chronic central nervous system exposure to interleukin-1 beta causes catabolism in the rat.

Interleukin-1 (IL-1) and interleukin-6 (IL-6) are thought to play a role in mediating weight loss, net protein catabolism, anorexia, and fever after infection or injury. Because IL-1 and IL-6 can be synthesized in the brain and have been shown to be increased in central nervous system (CNS) infections, we investigated the metabolic consequences of prolonged CNS exposure to these cytokines. At equivalent doses, intracerebroventricular infusion of IL-1, but not IL-6, caused negative nitrogen balance, weight loss, and anorexia. Intracerebroventricular infusion of IL-1 also caused adrenocortical activation, as indicated by increased adrenal weight and plasma corticosterone, and decreased thymus weight. However, clamping plasma glucocorticoids at low levels by adrenalectomy and corticosterone pellet replacement did not attenuate IL-1-induced losses of body weight and nitrogen. We conclude that centrally produced IL-1 could play an important role in the metabolic alterations associated with CNS injury or infection and that these effects may not be solely attributable to increased secretion of glucocorticoids.

Adrenal Cortex↗