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D Wilmore

Publications and source records attributed to D Wilmore.

16 recordsLinked to original sources
PubMed1999

Alteration in enterocyte gene expression may explain structural and functional changes following glutamine supplemented parenteral nutrition.

Following extensive bowel resection, the intestinal tract undergoes a variety of adaptive responses to enhance bowel function. The purpose of this study was to determine the effect of glutamine-supplemented parenteral nutrition on mucosal cellularity and gut function. In addition, enterocyte gene expression of two relevant systems was also characterized and related to the structural and functional changes that occurred. Male Wistar rats underwent a 60% small bowel resection and jugular vein catheterization and were randomized into two groups. The control group (n = 10) received a standard intravenous nutritional solution and the study group (n = 10) received a similar solution but enriched with alanylglutamine dipeptide. After 7 days blood was taken for amino acid analysis, and bowel was harvested to determine mucosal morphology and expression of mucosal cell glutaminase and IGF-I mRNA. Mesentery lymphnodes were cultured to determine the presence of bacteria and thus access bacteria translocation. Serum glutamine concentration and mucosal architecture were maintained in the study group compared to the controls. Seventy percent of lymphnodes were cultured positive in control vs. only 20% in the study group (P < 0.05). Jejunal mucosal glutaminase and ileum mucosal IGF-I mRNA increased twofold and threefold respectively compared to control animals. Parenteral nutrition supplemented with alanyl-glutamine dipeptide supports mucosal cellularity and regional immune function in rodents following intestinal resection, These alterations are associated with enhanced enterocyte expression of glutaminase and IGF-I. These changes may facilitate the structural and functional alterations which were observed in the glutamine treated animals.

Animals↗
PubMed1995

Bioelectric impedance detects fluid retention in patients undergoing cardiopulmonary bypass.

Excessive fluid accumulation is associated with increased morbidity and prolonged convalescence after cardiopulmonary bypass. However, water fluctuations are difficult to assess solely on the basis of changes in body weight and fluid balance. Bioelectric impedance analysis is a simple, rapid, noninvasive bedside technique that measures the resistance of the body to a weak alternating current (50 kHz). The change in resistance is inversely proportional to the change in total body water. To investigate the relationship between body weight, fluid balance, and resistance, 18 patients who had cardiopulmonary bypass (9 men, 9 women, aged 61 +/- 3 years, weighing 80 +/- 4 kg, with ejection fraction 54% +/- 3% and bypass time 113 +/- 8 minutes [mean plus or minus standard error of the mean]) were followed up for 7 postoperative days. Body weight, fluid balance, and whole body and regional resistance were determined at 24-hour intervals. In the immediate postoperative period, fluid retention was accurately detected by simultaneous measurements of weight gain and decreased resistance (p < 0.001). Both measurements detected the initiation of diuresis by postoperative day 2 (p < 0.01). Whole body resistance returned to baseline values by day 7 (p > 0.05), and body weight returned to baseline on day 4 (p > 0.05). Change in weight and change in whole body resistance were highly correlated with cumulative fluid balance (r = 0.84, p < 0.001, and r = -0.81, p < 0.001, respectively), and these two measures were also related to each other throughout the study (r = -0.89, p < 0.001). The initial change in resistance was the best measurement associated with postoperative outcome (p < or = 0.01). The data suggest that the measurement of electric resistance across the body can accurately detect acute changes in total body water and in fluid redistribution through the body. However, determining the relative day-to-day change in whole body resistance seems more appropriate than calculating absolute fluid changes over time. Bioelectric impedance offers a simple, rapid, noninvasive method to monitor serial changes in total body water. This technique can be useful in situations in which rapid alterations in water compartments occur, and it may be useful in predicting outcome after cardiopulmonary bypass.

Adult↗
PubMed1995

Increased survival after major thermal injury: the effect of growth hormone therapy in adults.

BACKGROUND: Advances in the management of patients with major thermal injury have resulted in a progressive increase in survival rates. We report preliminary data evaluating the safety and potential efficacy of human growth hormone (HGH) administration in a high-risk population of burned patients. METHODS: From 1989 to 1993, 69 patients sustaining major burns (defined as patient age plus percentage of body surface area with deep second- and third-degree burns > or = 90) were evaluated. Patients routinely received anti-inflammatory pharmacotherapy including antioxidants, an endotoxin binder, and cyclooxygenase blockade. Half of the 54 patients who survived more than 7 days received HGH to enhance wound healing. Injury severity, morbidity, and mortality for patients receiving HGH was compared to the 27 patients not receiving HGH. RESULTS: For the entire population (n = 69), average age was 56 +/- 23 years, body surface area burned was 58% +/- 24%, and 30% sustained smoke inhalation. Actual mortality was 41%, significantly less than the more than 70% mortality rate predicted from reported outcome data. Patients receiving HGH were well matched with the group not receiving HGH with respect to extent of injury, burn management, pharmacotherapy, and in-hospital morbidity. Mortality of the patients receiving HGH was 11%, significantly less than the 37% mortality rate of the patients without HGH (p = 0.027). CONCLUSION: Compared to standard predictors of burn mortality our small patient group appears to have an improved survival rate, suggesting that the use of anti-inflammatory agents appears safe and potentially beneficial. Patients receiving HGH exhibited minimal drug-related complications and mortality rates were improved when this population was compared with both predicted mortality rates and a well-matched control population of concurrently treated patients. Prospective blinded trials are now necessary to confirm these findings in a larger patient group.

Adolescent↗
PubMed1993

A comparison of medium-chain and long-chain triglycerides in surgical patients.

Available lipid emulsions made from soybean or safflower oil are classified as long-chain triglycerides (LCT). In contrast, medium-chain triglyceride (MCT) emulsions have different physical properties and are metabolized by other biochemical pathways. To compare the differences between these two fat emulsions, the authors studied 12 surgical patients and 6 volunteers. These subjects were randomly assigned to receive parenteral nutrition with MCT or LCT emulsion. Measurement of arterial and venous concentration differences across the forearm demonstrated that muscle utilization was significantly improved with MCT administration. There was also a trend toward improved nitrogen balance in the MCT group, and less weight loss in the postoperative period also was observed in this group. During the fat clearance test, the serum ketone concentrations were significantly higher in the MCT than the LCT group. The improvement in nitrogen retention may be associated with increasing ketone and insulin levels. Fat emulsions containing 50% MCT are safe for use in parenteral nutrition and may provide an alternate fuel that improves protein metabolism.

Drug Combinations↗
PubMed1991

Hepatic failure and coma after liver resection is reversed by manipulation of gut contents: the role of endotoxin.

Despite significant improvements in the surgical care of patients, hepatic failure after extensive liver resection continues to be associated with a high morbidity and death. We postulated that hepatic failure after liver resection was related to gut-derived endotoxemia. Rats were randomized to receive oral gavage twice daily with one of the following preparations: (1) 0.9% saline; (2) neomycin sulfate and cefazolin; (3) cholestyramine; (4) lactulose. After 7 days of gavage, animals underwent either a two-thirds partial hepatectomy or sham operation. At time 0 (preresection), 10, 20, and 30 hours after resection, aortic blood was obtained for determination of ammonia, glutamine, and endotoxin levels. In selected animals, portal vein or inferior caval blood was obtained simultaneously with the aortic sample to evaluate the glutamine and ammonia exchange across the intestine and hind limb. Germ-free rats also underwent a partial hepatectomy or sham operation, and blood was obtained for glutamine and ammonia exchange at 0 and 20 hours after resection. Hepatectomy in the saline-pretreated rats resulted in a sixfold increase in plasma glutamine, increased uptake of glutamine and release of ammonia by the gut, increased release of glutamine by the hind-limb, and a high mortality rate. Pretreatment with agents that altered gut contents reduced the endotoxemia, maintained normal glutamine and ammonia levels, and reduced the mortality rate. Germ-free rats had a similar response to that seen in treated animals. Altering the gut contents in this model reduced the level of endotoxemia, blunted the catabolic response, and enhanced survival.

Ammonia↗
PubMed1988

Recombinant human tumor necrosis factor administered as a 24-hour intravenous infusion. A phase I and pharmacologic study.

Recombinant human tumor necrosis factor (rH-TNF) is a cytokine with direct antitumor properties. In a phase I trial we continuously infused rH-TNF for 24 hours. We gave a total of 115 courses of therapy to 50 patients. Doses ranged from 4.5 to 645 micrograms of rH-TNF/m2. Systemic toxicity, including fever, chills, fatigue, and hypotension, increased with the dose of rH-TNF administered. Doses greater than 454 micrograms/m2 frequently caused severe lethargy and fatigue, which precluded hospital discharge of the patient at the completion of therapy. The dose-limiting toxicity was hypotension, and five patients treated at the two highest dose levels required dopamine treatment. Other organ-specific toxicity was modest and spontaneously resolved after 48 hours. The 24-hour infusions of rH-TNF were associated with significant decreases in serum cholesterol and high-density lipoprotein levels. Pharmacokinetic studies using an enzyme-linked immunosorbent assay demonstrated peak plasma rH-TNF levels of 90-900 pg/mL. Despite continuous infusion of rH-TNF, no steady-state level was achieved. The recommended phase II dose for rH-TNF as a 24-hour continuous infusion is 545 micrograms/m2.

Adolescent↗
PubMed1987

A single dose of endotoxin activates neutrophils without activating complement.

Both complement (C) and neutrophils (PMN) are activated in critically ill patients. To evaluate the role of endotoxin in this response, we studied C activation products and PMN cell surface receptors in seven normal subjects before and after endotoxin (USRef 20 U/kg) or saline solution administered on separate occasions. By 4 hours, with endotoxin only, all subjects had myalgia, headache, an increase in body temperature and heart rate, and leukocytosis that returned to normal by 24 hours. At the same time, PMN cell surface receptors for the complement opsonin C3b increased, as measured by indirect immunofluorescence, rising to 251 +/- 44% of baseline by 4 hours (p less than 0.01) and remaining elevated at 24 hours (237 +/- 16%, p less than 0.01). PMN receptors for iC3b increased to 308 +/- 49% of baseline by 4 hours (p less than 0.02) and returned to normal by 24 hours. There was no change in plasma of C3a desArg, C4a desArg, and C5a desArg (4 hours: mean C3a: 153.4 +/- 11.5 ng/ml versus 176.2 +/- 16.2 ng/ml for saline solution, p = ns; C4a: 159.6 +/- 32 ng/ml versus 151.4 +/- 21 ng/ml, p = ns; C5a: undetectable). To confirm the lack of C activation, we examined PMN chemotaxis (CTX) to C5a for any impairment caused by prior in vivo exposure to C5a. CTX to C5a was unaffected (4 hours: 109% +/- 22% of normal versus 114% +/- 10% for saline solution, p = ns). PMN CTX to formyl-methionyl-leucine-phenylalanine and PMN phagocytosis and killing of S. aureus were also unaffected by endotoxin. Thus, a single dose of endotoxin produced a subjective febrile illness and precipitated sustained PMN activation as indicated by increased PMN cell surface complement receptor number in the absence of C activation.

Adult↗
PubMed1987

High-dose combination alkylating agent preparative regimen with autologous bone marrow support: the Dana-Farber Cancer Institute/Beth Israel Hospital experience.

Fifty-nine patients received 61 courses of cyclophosphamide, cisplatin, and carmustine combined. The phase I study consisted of seven dose escalations. Dose levels 5 and 6 also included the attempted addition of melphalan at 40 and 80 mg/m2. The maximum tolerated dose for the three-drug combination was 5620 mg/m2 of cyclophosphamide, 165 mg/m2 of cisplatin, and 600 mg/m2 of carmustine. The dose-limiting toxic effect was fatal veno-occlusive disease of the liver in two of five patients treated at the highest dose level. Veno-occlusive disease of the liver was fatal in two of 40 patients treated at Dose level 4, the maximum tolerated dose. The median time to recovery of polymorphonuclear leukocyte counts to greater than 500/microliters and platelet counts to transfusion independence greater than 20,000/microliters was 19 and 22 days, respectively, after marrow reinfusion. Other toxic effects observed included postdischarge pulmonary toxicity, which appeared to respond to prednisone therapy. Thus, this combination of alkylating agents can be combined at close to the transplant dose of each individual agent. The response rate was high despite considerable prior treatment in most patients. Of 16 evaluable patients with breast cancer, 15 responded (six complete responses). Of six evaluable patients with sarcoma, six responded (one complete response). While patients with melanoma had had no prior treatment, 11 of 17 patients responded (65%). There are currently three patients who are disease-free. Two patients with melanoma were rendered disease-free by excisional biopsy of the only remaining nodule after good partial response, and a patient with metastatic breast cancer remains disease-free after a complete response at 36+ months.

Adult↗
PubMed1986

High-dose combination alkylating agents with autologous bone marrow support: a Phase 1 trial.

Twenty-nine patients were treated with 31 courses of high-dose combination cyclophosphamide, cisplatin, and carmustine (BCNU) with and without melphalan with autologous bone marrow support. Toxicity was dose related. The maximum tolerated dose for cyclophosphamide, cisplatin, and BCNU in this combination in mg/m2 was 5,625, 165, and 600, respectively. Further dose escalation was precluded by the development of multiple organ toxicity, including venoocclusive disease, refractory thrombocytopenia, and hypertension. Melphalan added to the three-drug combination produced excessive renal and gastrointestinal toxicity. Objective tumor regression occurred in 21 of 25 evaluable cases. The results suggest that selected alkylating agents can be combined in full or nearly full doses before nonmyelosuppressive dose-limiting toxicity precludes further escalation.

Adult↗