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Biomedical subjects

B Bistrian

Publications and source records attributed to B Bistrian.

18 recordsLinked to original sources
PubMed1999

Perioperative hyperglycemia, infection or risk?

This review covers the recent studies that have served to further our understanding of the nature of the relationship between perioperative hyperglycemia and nosocomial infection. On the one hand hyperglycemia can be a consequence of the systemic inflammatory response, and can serve as a marker of the severity of stress and the degree of immunocompetence resulting from infection or injury. Strong evidence is, however, emerging that hyperglycemia in the perioperative period can also be a significant risk factor for the development of nosocomial infection.

Blood Glucose↗
PubMed1998

Medium-chain triglyceride and n-3 polyunsaturated fatty acid-containing emulsions in intravenous nutrition.

Medium-chain triglycerides and n-3 polyunsaturated fatty acid emulsions as a physical mixture have attracted increasing interest for use in parenteral nutrition and may play an important role in the development of structured triglycerides in a future generation of new lipids. Over the past two decades, the clinical use of intravenous emulsion for the nutritional support of hospitalized patients has relied exclusively on long-chain triglycerides providing both a safe, calorically dense alternative to dextrose and a source of essential fatty acids needed for biological membranes and maintenance of the immune function. During the past decade, the development of new triglycerides (medium- and long-chain triglyceride emulsions and structured triglyceride emulsions) for parenteral use have provided useful advances and opportunities to enhance nutritional and metabolic support. Medium-chain triglycerides and n-3 polyunsaturated fatty acid emulsions possess unique physical, chemical, and metabolic properties that make them theoretically advantageous over the conventional long-chain triglycerides. The physical mixture of medium- and long-chain triglycerides have been used clinically in patients with critical illness, liver disease, immunosuppression, pulmonary disease, and in premature infants, with good tolerance and the avoidance of some of the problems encountered with long-chain triglycerides alone.

Animals↗
PubMed1994

A phase II multicenter, double-blind, randomized, placebo-controlled study of three dosages of an immunomodulator (PGG-glucan) in high-risk surgical patients.

OBJECTIVE: To examine the safety and efficacy of multiple doses of PGG-glucan (poly-[1-6]-B-D-glucopyranosyl-[1-3]-B-D-glucopyranose) in high-risk patients undergoing major thoracic or abdominal surgery. DESIGN: An interventional, multicenter, double-blind, randomized, placebo-controlled study. SETTING: Four university-affiliated medical centers. PATIENTS: Sixty-seven high-risk patients undergoing major thoracic or abdominal surgery. INTERVENTION: Patients were randomized in a 1:1:1:1 ratio to receive saline placebo or PGG-glucan at a dose of 0.1 mg/kg, 0.5 mg/kg, and 1.0 mg/kg or 2.0 mg/kg. One dose was administered before surgery and three doses were administered after surgery. MAIN OUTCOME MEASURES: To examine the safety and efficacy of PGG-glucan infusion and to identify potentially important factors for a planned phase III study. RESULTS: A dose-response trend with regard to infection incidence among patients who received PGG-glucan was observed. Serious infections occurred in four patients who received placebo and in three patients who received PGG-glucan at a dose of 0.1 mg/kg. However, only one patient who received PGG-glucan at a high dose had a serious infection. The incidence and severity of adverse events was comparable in all groups. CONCLUSIONS: PGG-glucan was generally safe and well tolerated, may decrease postoperative infection rates, and warrants further investigation in a planned phase III trial.

Adjuvants, Immunologic↗
PubMed1994

Randomized phase I/II trial of a macrophage-specific immunomodulator (PGG-glucan) in high-risk surgical patients.

OBJECTIVE: The safety and efficacy of PGG-glucan in surgical patients at high risk for postoperative infection who underwent major thoracic or abdominal surgery were determined. SUMMARY BACKGROUND DATA: Recent studies have reported a 25% to 27% infectious complication rate in patients undergoing major surgery with an average cost per infected patient of $12,000. The efficacy of PGG-glucan pretreatment in prevention of sepsis has been demonstrated in rodent models for gram-negative and gram-positive bacterial and yeast infections. In vitro studies have demonstrated enhanced microbial killing by monocytes and neutrophils in healthy volunteers after PGG-glucan administration. Thus, PGG-glucan may play a role in decreasing the infectious complication rate in patients undergoing major surgery. METHODS: A double-blind, placebo-controlled randomized study was performed in 34 high-risk patients undergoing major abdominal or thoracic surgery. RESULTS: There were no adverse drug experiences associated with PGG-glucan infusion. Patients who received PGG-glucan had significantly fewer infectious complications (3.4 infections per infected patient vs. 1.4 infections per infected patient, p = 0.05), decreased intravenous antibiotic requirement (10.3 days vs. 0.4 days, p = 0.04) and shorter intensive care unit length of stay (3.3 days vs. 0.1 days, p = 0.03). CONCLUSIONS: PGG-glucan is safe and appears to be effective in the further reduction of the morbidity and cost of major surgery.

Abdomen↗
PubMed1990

Abnormal liver function in malnourished patients receiving total parenteral nutrition: a prospective randomized study.

A prospective study was performed in clinically malnourished patients in which liver function was tested during a 4-week period of total parenteral nutrition (TPN). The purpose was to determine if concomitant intravenous lipid administration would reduce liver function abnormalities noted to occur frequently in patients receiving TPN. Twenty-five patients were randomly assigned to receive either daily infusions of 200 cc of a 20% lipid emulsion with TPN or TPN without lipid for the first week. In the subsequent 3 weeks all patients received daily intravenous lipid. The early lipid treatment group received 0.7 g lipid/kg BW/day and approximately 280 mg of choline/day from the lecithin emulsifier throughout the entire study period. Liver function tests were performed twice in the first week, then weekly thereafter. There were significant (p less than 0.05) elevations in liver function tests in the early lipid treatment group (for aspartate aminotransferase in weeks 1, 2, and 3, and lactic acid dehydrogenase in weeks 2 and 3). Alkaline phosphatase activity was elevated at weeks 2, 3, and 4 for the lipid-treatment group and at week 1 for the lipid-restricted group. The two groups had a similar elevation in gamma-glutamyltransferase activity. Analysis of covariance demonstrated that the overall duration of TPN, and not the presence or absence of intravenous lipid, was significantly related to the elevations in both alkaline phosphatase and gamma-glutamyltransferase (GGT) levels. In contrast, the early intravenous administration of lipid was significantly related to the increase in aspartate aminotransferase levels. The peak increase in AST was noted at day 7 in the lipid-administration group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Metabolic and nutritional aspects of weaning from mechanical ventilation.

Nutritional and metabolic support appears to be indicated for critically ill patients requiring mechanical ventilation. Feeding formulas should be adjusted according to the nutrient requirements and efficiency of gas exchange in the individual patient. Management of the complex weaning problem patient with limited respiratory reserve requires many principles common to muscle exercise training.

Humans↗
PubMed1989

Protein-restricted diets in diabetic nephropathy.

Low-protein diets in nondiabetic renal failure may slow the progressive loss of renal function in some patients, but few studies have detailed the nutritional consequences of these diets in patients with diabetic nephropathy. We studied 7 patients with insulin-dependent diabetes mellitus and chronic renal insufficiency [mean +/- SEM creatinine clearance (S, U): 28.3 +/- 6.5 ml/min (0.47 +/- 0.11 ml/s x 1.73/A)] for 15 weeks who were prescribed a diet of 0.6 g protein/kg ideal body weight. Midarm muscle circumference (24.1 +/- 1.8 at onset vs. 24.5 +/- 1.5 cm at completion), triceps skinfold thickness (21.6 +/- 3.1 vs. 21.0 +/- 1.5 mm), body weight (71.8 +/- 4.1 vs. 71.2 +/- 4.6 kg), and serum albumin [3.0 +/- 0.1 vs. 3.2 +/- 0.1 g/dl (30 +/- 1 vs. 32 +/- 1 g/l)] remained stable. Based on urinary nitrogen excretion, diet diaries overestimated the degree of dietary protein restriction; there was good adherence to the diet as evidenced by a reduction in urinary urea nitrogen (average 32%). Blood glucose control was maintained despite increased carbohydrate intake. On average, creatinine clearance did not change significantly, but proteinuria diminished slightly (1.8 +/- 0.2 vs. 1.5 +/- 0.6 g/day). These results indicate that 0.6 g/kg/day protein diets did not cause protein depletion in insulin-dependent diabetic patients. Longer-term studies are indicated to assess more fully the efficacy of these dietary regimens in reducing proteinuria or benefiting diabetic nephropathy.

Adult↗
PubMed1988

Enhanced survival to endotoxin in guinea pigs fed IV fish oil emulsion.

Improved survival to endotoxin has been demonstrated in rats pretreated with cyclooxygenase inhibitors or made essential fatty acid deficient, implying that excessive omega 6 fatty acids, possibly through their eicosanoid products, contribute to mortality. Following endotoxin administration, we also have shown improvement in survival with oral diets supplemented with fish oil. This study sought to explore whether parenteral fish oil ameliorates the adverse impact of endotoxin. Male Hartley-strain guinea pigs were obtained at a body weight of 500 g and fed a normal laboratory diet. Central venous lines through which the animals received either a 10% safflower oil emulsion (n = 11) or a 10% fish oil emulsion (n = 11) during two, 24-hr periods separated by two days were inserted. Two days after the second infusion, endotoxin (0.35 mg/100 g b.w.), was given intraperitoneally, and survival was noted. The animals received a total of 25.4 g of IV fat per kg b.w., including 5.3 g of eicosapentaenoic acid per kg b.w., for the fish oil group. From six hr after endotoxin through four days, there was better survival in the fish oil group (p less than .006). Final mortality showed 7/11 fish-fed vs 2/11 safflower-fed animals surviving. We conclude that the administration of parenteral fish oil, even for a brief time, can have a profound effect on subsequent survival to endotoxin.

Animals↗
PubMed1986

Acquired defect in interleukin-2 production in patients with type I diabetes mellitus.

Deficient production of interleukin-2 has been reported in Type I diabetes, but its cause has not been elucidated. We therefore measured interleukin-2 production in 27 patients with Type I diabetes, 20 patients with Type II diabetes (6 requiring insulin), 5 monozygotic twin pairs discordant for Type I diabetes, and 10 nondiabetic persons with islet-cell antibodies. Interleukin-2 production was decreased in patients with Type I diabetes as compared with controls (35.8 +/- 2.5 vs. 61.6 +/- 4.6 percent, P less than 0.001). Interleukin-2 production did not differ between patients with Type II diabetes and controls, regardless of whether the patients used insulin. Twins with Type I diabetes had decreased interleukin-2 production as compared with normal controls (33.2 +/- 5.4 vs. 61.6 +/- 4.6 percent, P less than 0.001) and with their nondiabetic twins (33.2 +/- 5.4 vs. 54.5 +/- 3.4 percent, P less than 0.005). Interleukin-2 production in nondiabetic twins and in nondiabetic persons with islet-cell antibodies was normal. There was no correlation between glycosylated hemoglobin levels and interleukin-2 production in any diabetic group. We conclude that patients with Type I diabetes have an acquired defect in interleukin-2 production, whereas patients with Type II diabetes do not, and that this defect is not correlated with an ongoing autoimmune process, with hyperglycemia, or with insulin administration or oral hypoglycemic therapy. Thus, the defect appears to be related to marked beta-cell destruction, although not to the metabolic consequences thereof or the responsible autoimmune process.

Adult↗
PubMed1986

Prophylaxis against central vein thrombosis with low-dose warfarin.

Low-dose warfarin was given to patients to prevent venous thrombosis. Patients at greatest risk for having thrombi adjacent to central venous catheters were detected by the von Kaulla assay. Patients with normal von Kaulla assays had one thrombus per 1844 days at risk while those with accelerated von Kaulla assays had one thrombus per 500 days at risk. Low-dose warfarin therapy given to patients at high risk reduced the incidence of venous thrombosis from one thrombus per 251 days to one thrombus per 1617 days. Thus low doses of warfarin that do not prolong the prothrombin time appear to offer prophylaxis against venous thrombosis in patients at high risk for developing venous thrombosis adjacent to the central venous catheters.

Adolescent↗
PubMed1983

Effects of low-dose warfarin on antithrombin III levels in morbidly obese patients.

Morbid obesity has been associated with increased risks for thrombotic diseases. Patients with morbid obesity are shown to have decreased activity and decreased concentration of antithrombin (AT) III. This deficit can be corrected by giving the patients low doses of the oral anticoagulant warfarin. The same beneficial effect was not observed in normal lean control volunteers in whom the levels of AT III were normal at all times. Thus, it may be possible to offer prophylactic protection against the effects of having depressed levels of AT III in patients at increased risk for thrombotic diseases without using full anticoagulant doses of warfarin, including morbidly obese patients.

Antithrombin III↗
PubMedDate not supplied

Recombinant human tumor necrosis factor and recombinant murine interleukin-1 alter the binding of Escherichia coli to intestine, mucin glycoprotein, and the HT29-C1 intestinal cell line.

Little is known about the effects of cytokines at the intestinal mucosal surface on the adherence of bacteria. We examined the effects of recombinant tumor necrosis factor (TNF) and interleukin-1 (IL-1) on the adherence of various strains of Escherichia coli to intestinal mucosa in vivo and in in vitro models. We studied the effects of TNF or IL-1 injected intraperitoneally on the ability of a rabbit enteric pathogen (RDEC-1) and a nonpathogenic E. coli (1392-) to colonize rabbit small bowel and found that there was a trend toward increased colonization by the RDEC-1 organisms in the TNF-treated rabbits, and a significant increase in colonization by the RDEC-1 organisms in the IL-1-treated animals (P < 0.01). Both TNF and IL-1 altered the density and the level of glycosylation of the small bowel mucus glcoprotein purified from the treated and untreated rabbits, and TNF treatment significantly increased the number of bacteria bound by this purified mucin (P < 0.01 for all strains). HT29-C1 intestinal cells in tissue culture were also grown in media with TNF or IL-1 and used in bacterial binding assays. The cells provided with media with 50 pg/mL of either cytokine bound significantly more of the three bacterial strains than cells in untreated media (P < 0.01 for all strains). The cytokines TNF and IL-1 have the potential to alter bacterial adherence to intestinal mucosa in vivo and in vitro; additional studies to clarify the role that these alterations in adherence may play in the clinical syndromes characterized by increased levels of intestinal cytokines are warranted.

Animals↗
PubMedDate not supplied

The role of cytokines in the catabolic consequences of infection and injury.

During infection and injury a series of metabolic events are activated that leads to a state of negative nitrogen balance and significant loss of lean body mass. This process is characterized by marked anorexia, net whole body protein breakdown, and liver anabolism. This host response initially is beneficial to the body because it helps it to fight disease and enhance healing. However, if such imbalance is maintained for long periods, it will invariably produce significant loss of lean body mass that may lead to a series of untoward clinical events. The role of the proximate cytokines, tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6) as well as glucocorticoids as important mediators of many pathophysiological manifestations of infection and injury has been studied extensively. However, the involvement of other mediators, at least in skeletal muscle proteolysis during sepsis has been hypothesized, because blockade of glucocorticoids, TNF, IL-1, and IL-6 reduces but does not normalize protein breakdown rates nor does the direct application of these mediators to skeletal muscle in vitro enhance proteolysis. Furthermore other studies have suggested that the lymphokine, interferon-gamma (IFN-gamma, type II interferon or immune interferon), produces fever and enhances thermogenesis, body weight loss, and skeletal muscle depletion in rodents in a manner similar to that seen with TNF and IL-1. Cytokines appear to be major components of the host metabolic response during infection and injury. However, neither all the cytokines involved nor the exact mechanisms underlying their metabolic effects are completely understood. The regulation of muscle protein synthesis and breakdown, which largely determines the development of cachexia, appears to depend on the delicate balance between a number of regulatory substances including cytokines, glucocorticoids, catecholamines, insulin, and insulin-like growth factors.

Anorexia↗