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B R Bistrian

Publications and source records attributed to B R Bistrian.

At least 73 records · Page 4Linked to original sources

A proposed revision of current ICD-9-CM malnutrition code definitions.

Protein-energy malnutrition (PEM) is as common today in adult medical and surgical patients as it was when it was first identified more than 25 years ago. Under the current diagnosis-related group (DRG) payment system, malnutrition is considered a comorbidity or complicating condition. Thus, the identification and coding of malnutrition through the use of the International Classification of Diseases, ninth edition, Clinical Modification (ICD-9-CM) malnutrition codes can potentially change a patient's DRG and subsequently increase the amount of reimbursement a hospital receives. Unfortunately, the definitions for the current ICD-9-CM malnutrition diagnosis codes were developed principally in relation to clinical syndromes of primary PEM seen in pediatric age groups in less developed countries, rather than in relation to syndromes seen in hospitalized adult patients in industrialized societies. This discrepancy often leads to confusion and inconsistency when institutions attempt to code adult patients for malnutrition. Furthermore, inaccurate coding can result in inadequate reimbursement or rejection of a claim. Clearly, a separate description of the different forms of PEM seen in adults is needed not only for optimal application of nutrition support therapies but also for accurate medical records, quality assurance procedures, and reimbursement purposes. On the basis of 20 years of experience providing nutrition support to hospitalized adult patients, this article presents a schema developed at the Deaconess Hospital (Boston,Mass) that attempts to better define adult PEM using the ICD-9-CM malnutrition codes. The purpose of this article is to foster discussion and ultimately promote general agreement about a definition of adult PEM.

Aged↗

Determinants of plasma concentrations of insulin-like growth factor-I and albumin and their hepatic mRNAs: the role of dietary protein content and tumor necrosis factor in malnourished rats.

Protein restriction decreases plasma concentrations of albumin and insulin-like growth factor-I (IGF-I) by reducing their hepatic mRNA levels, whereas protein restriction increases IGF-I binding protein-2 (IGFBP-2) gene expression in the liver. Tumor necrosis factor (TNF), as an inducer of the injury response, decreases plasma albumin concentration and albumin mRNA in the liver. The present study was designed to evaluate the effects of protein repletion and TNF on plasma albumin and IGF-I and their mRNAs and IGFBP-2 mRNA in the liver of protein-restricted rats. After 2 weeks of feeding a 2% casein diet, rats were assigned to four groups according to either being refed with a 2% or 20% casein diet or receiving saline or TNF by intraperitoneal injection (50 microg/kg x d) for 4 days. Plasma IGF-I and albumin were assayed. Hepatic mRNAs of IGF-I, albumin, and IGFBP-2 were determined. Protein repletion increased plasma concentrations of IGF-I and albumin and their mRNA content in the liver, but decreased IGFBP-2 mRNA. TNF did not alter plasma IGF-I concentration but did increase hepatic IGF-I mRNA in protein-repleted animals, and plasma albumin concentration was significantly decreased with unaltered hepatic albumin mRNA. Thus, protein repletion of malnourished rats increased plasma IGF-I and albumin concentrations in association with increased expression of their mRNAs in the liver. However, plasma albumin but not IGF-I decreased following TNF in protein-restricted rats, whereas TNF increased hepatic IGF-I mRNA in protein-repleted rats. Thus, only plasma albumin concentration responds to both principal determinants, diet and injury, in the development of malnutrition.

Animals↗

Effect of iron-supplemented total parenteral nutrition in patients with iron deficiency anemia.

Iron deficiency anemia is common among hospitalized patients, and blood losses from diagnostic phlebotomy increase the likelihood of a negative iron balance. The role for iron supplementation of total parenteral nutrition (TPN) in these patients is unclear. Twenty-three patients with iron deficiency anemia were identified. Twelve patients were randomized to receive TPN without iron (group 1) and 11 received TPN supplemented with 10 mg of iron as iron dextran daily (group 2). Both groups were matched for age, serum iron studies, red cell indices, and hemogram. After a 7-d period, the mean serum iron in group 2 increased from 10 to 26 micrograms/dL, with an increased transferrin saturation from 7.3 to 15.3% (each, p < 0.05). No changes in total iron binding capacity, ferritin, reticulocyte count, hemoglobin, hematocrit, or mean corpuscular volume were observed in the two groups. The incidence of infectious complications was not different between both groups. We conclude that iron supplementation of TPN appears safe and is effective in increasing serum iron levels. The use of iron-supplemented short-term TPN needs to be further studied given no change in red cell indices, hemoglobin, hematocrit, or transfusion requirement.

Adult↗

Rapid modulation of lung and liver macrophage phospholipid fatty acids in endotoxemic rats by continuous enteral feeding with n-3 and gamma-linolenic fatty acids.

Dienoic eicosanoids derived from phospholipid arachidonic acid (AA) in lung and liver macrophages promote leukosequestration, thrombosis, and tissue injury. Current enteral diets (diet A) are enriched with linoleic acid (LA), a precursor of AA. Novel diets low in LA and containing eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) foster formation of less inflammatory eicosanoids. The study objective was to assess the rapidity and extent of LA and AA displacement in vivo from alveolar macrophage (AM phi), lung, and liver Kupffer and endothelial (KE) cell phospholipids in rats fed enterally with diets enriched with 5.3% (by wt) EPA and either 1.2% or 4.6% GLA (diets B and C, respectively). After surgical placement of catheters, the rats were fed enterally and co-infused intravenously with either endotoxin or vehicle continuously for 3 or 6 d. Rats given either diet B or C had significantly lower (P < 0.01) relative percentages of AA and LA within the AM phi, lung, and KE cell phospholipids, and concomitantly higher percentages of EPA compared with rats infused with diet A after 3 d of enteral feeding irrespective of endotoxin co-infusion. Incorporation of dihomo-gamma-linolenic acid (DHGLA), the metabolite of GLA, into lung and KE phospholipids was significant in rats given diet C. Most of the changes in fatty acid composition occurred by day 3. The polyunsaturated fatty acid composition of AM phi, lung, and KE cell phospholipids can be rapidly modified by continuous short-term enteral feeding with EPA- and GLA-enriched diets irrespective of concurrent endotoxemia.

Animals↗

Protein and lipid refeeding changes protein metabolism and colonic but not small intestinal morphology in protein-depleted rats.

In this study, we fed rats a 2% casein AIN 76 diet for 2 wk to produce protein malnutrition. We determined in these animals the effects of different concentrations of dietary protein refeeding (2% and 20% casein) on recovery and gut mucosal repletion and the potential role of type of dietary fat in the regulation of protein metabolism and mucosal growth by providing conventional long-chain triglyceride (LCT), a structured lipid composed of long-, medium- and short-chain fatty acids (SC/SL), or a physical mixture of the same components present in the structured lipid given as individual pure triglycerides (SC/PM) along with adequate amounts of protein and energy. The results confirmed that protein malnutrition can be reversed rapidly by protein refeeding, as indicated by an increase in body weight, positive nitrogen balance, liver growth and elevations in plasma concentrations of insulin-like growth factor-1, leucine and albumin. In the colon, crypt cell number, crypt depth and number of crypt cells in the rapidly proliferating fraction of the colon were greater in rats fed the higher protein diet. However, the general architecture of small intestinal mucosa, including duodenum, jejunum and ileum, was not affected by protein malnutrition. Although the number of colonic cells was similar with fat refeeding, there were significantly fewer displaying the proliferating cell nuclear antigen in the colonic epithelium when rats were fed SC/PM compared with SC/SL. Therefore, changes in colonic mucosal proliferation were only seen with repletion by adequate protein and by SC/SL feeding.

Absorption↗

Early enteral feeding in postsurgical cancer patients. Fish oil structured lipid-based polymeric formula versus a standard polymeric formula.

OBJECTIVES: The authors compared the safety, gastrointestinal tolerance, and clinical efficacy of feeding an enteral diet containing a fish oil/medium-chain triglyceride structured lipid (FOSL-HN) versus an isonitrogenous, isocaloric formula (O-HN) in patients undergoing major abdominal surgery for upper gastrointestinal malignancies. SUMMARY BACKGROUND DATA: Previous studies suggest that feeding with n-3 fatty acids from fish oil can alter eicosanoid and cytokine production, yielding an improved immunocompetence and a reduced inflammatory response to injury. The use of n-3 fatty acids as a structured lipid can improve long-chain fatty acid absorption. METHODS: This prospective, blinded, randomized trial was conducted in 50 adult patients who were jejunally fed either FOSL-HN or O-HN for 7 days. Serum chemistries, hematology, urinalysis, gastrointestinal complications, liver and renal function, plasma and erythrocyte fatty acid analysis, urinary prostaglandins, and outcome parameters were measured at baseline and on day 7. Comparisons were made in 18 and 17 evaluable patients based a priori on the ability to reach a tube feeding rate of 40 mL/hour. RESULTS: Patients receiving FOSL-HN experienced no untoward side effects, significant incorporation of eicosapentaenoic acid into plasma and erythrocyte phospholipids, and a 50% decline in the total number of gastrointestinal complications and infections compared with patients given O-HN. The data strongly suggest improved liver and renal function during the postoperative period in the FOSL-HN group. CONCLUSION: Early enteral feeding with FOSL-HN was safe and well tolerated. Results suggest that the use of such a formula during the postoperative period may reduce the number of infections and gastrointestinal complications per patient, as well as improve renal and liver function through modulation of urinary prostaglandin levels. Additional clinical trials to fully quantify clinical benefits and optimize nutritional support with FOSL-HN should be undertaken.

Adolescent↗

Metabolic changes in rats during a continuous infusion of recombinant interleukin-1.

The effects of recombinant interleukin-1 (IL-1), given as a continuous infusion for 6 days, on host responses were determined in rats. The development of fever, change in food intake and body weight, and key components of the acute-phase response in energy and protein metabolism were assessed. The effects of IL-1 were compared with those observed in a matched pair-fed group (semistarved), to distinguish the contribution from anorexia, and in a group that received IL-1 for 4 h acutely. IL-1 significantly increased core temperature, plasma levels of IL-6, and acute-phase protein production and decreased food intake and the circulating zinc level. The catabolic effects of IL-1 on nitrogen loss and muscle protein breakdown were independent of, and additive to those from malnutrition. The changes in energy expenditure, cumulative urinary nitrogen, and hydroxyproline excretion in the chronic IL-1 group were increased over semistarved animals. Finally, changes in muscle protein kinetics were only seen with chronic IL-1 infusion, and the changes in acute-phase protein were greater.

Acute-Phase Proteins↗

Growth hormone stimulates tyrosine phosphorylation of JAK2 and STAT5, but not insulin receptor substrate-1 or SHC proteins in liver and skeletal muscle of normal rats in vivo.

GH has been shown to stimulate tyrosine phosphorylation of JAK2, several STAT proteins, insulin receptor substrate-1 (IRS-1), and SHC proteins in cultured cells. The goal of this study was to determine GH effects on protein tyrosine phosphorylation in liver and skeletal muscle of normal rats in vivo. Nonfasted male Sprague-Dawley rats (225-250 g) were injected with GH iv, and tissues were obtained after 5, 15, 30, or 60 min. At a maximally effective GH dose (1.5 mg/kg body weight), phosphotyrosine antibody immunoblots demonstrated marked stimulation of the tyrosine phosphorylation of JAK2 (maximal at 5 min) and a 95,000 Mr protein (maximal at 15 min) in both liver and skeletal muscle. The 95,000 Mr protein was recognized and immunodepleted by STAT5 antibody, but not by other STAT protein antibodies. Although basal tyrosine phosphorylation of IRS-1 and SHC was evident, GH did not stimulate tyrosine phosphorylation of either of these proteins in liver or skeletal muscle. In conclusion, GH stimulates the tyrosine phosphorylation of JAK2 and STAT5, but not IRS-1, SHC, or other STAT proteins in liver and skeletal muscle of normal rats. These results differ from findings in cultured cells and support the concept that selectivity for tyrosine kinase substrates is an important determinant of postreceptor signaling specificity in vivo.

Adaptor Proteins, Signal Transducing↗

Physicochemical stability of total nutrient admixtures.

The effect of six independent factors on the stability of i.v. nutritional emulsions was studied. Forty-five i.v. nutritional admixtures were prepared, each containing the following: (1) amino acids (range, 2.5-7%), (2) hydrated glucose (range, 5-20%), (3) lipid emulsion (range, 2-5%), (4) monovalent cations (range, 0-150 meq/L), (5) divalent cations (range, 4-20 meq/L), and (6) trivalent cations (range, 0-10 mg of elemental iron/L). Stability assessments included particle-size analysis, pH determination, and visual inspection. Sizing and counting of fat particles was achieved by using light obscuration and dynamic light scatter methods. Light obscuration and visual assessments were performed at 0, 6, 12, 24, and 30 hours. Dynamic light scatter and pH determinations were performed at 0 and 30 hours. Multiple stepwise regression analysis revealed that trivalent cation concentration was the only variable that affected the stability of nutritional emulsions (p < 0.00001), accounting for approximately 60% of the potentially dangerous increases in fat particle sizes observed. In addition, a percentage of large fat particles (> 5 microns in diameter) greater than 0.4% was associated with unstable emulsions. However, this instability was visibly evident only 65% of the time. Changes in mean globule diameter, cream-layer thickness, and pH did not reveal instability in these emulsions. Emulsions in which > 0.4% of the initial fat concentration consists of particles of > 5 microns in diameter are likely to become unstable. Of the six factors studied, the trivalent cation in iron dextran was most disruptive to lipid-based parenteral nutrient admixtures.

Amino Acids↗

Insulin-like growth factor-1 is not mitogenic for the Walker-256 carcinosarcoma.

This study was designed to determine whether intravenous infusion of recombinant human insulin-like growth factor 1 (IGF-1) stimulates tumor growth. In order to determine the potential interaction between nutrition and IGF-1 administration the study was conducted in fasting rats and during continuous feeding by total parenteral nutrition. Tumor cell cycle kinetics including labeling index, DNA synthesis time, cell cycle time in Go/G1, and G2/M in the total cell cycle, and potential doubling time were determined by flow cytometry after in vivo pulse labeling the rats bearing the Walker-256 Carcinosarcoma with 5'-bromo-2'-deoxyuridine (BrdUrd). The results show that IGF-1 treatment has no significant effects on the proliferative characteristics of the tumor model regardless of the feeding status of the animal. This study provides preliminary cell-cycle kinetics data on the short-term effect of IGF-1 on tumor growth. Failure to show a significant effect of IGF-1 on the proliferative characteristics of the tumor suggests that IGF-1 may be given to cancer patients in amounts sufficient to promote weight gain without deleterious stimulation of tumor proliferation.

Animals↗

Fish oil feeding improves muscle glucose uptake in tumor necrosis factor-treated rats.

This study was conducted to characterize the effects of fish oil and sunflower oil on hepatic glucose production and peripheral glucose utilization during infusion of saline or tumor necrosis factor (TNF), using the euglycemic-hyperinsulinemic clamp technique combined with a primed-constant tracer infusion of high-performance liquid chromatography-purified 3H-3-glucose for estimation of whole-body glucose appearance and utilization rates. Insulin 10 mU/kg.min was infused to reach a plasma insulin level of 200 microU/mL. 14C-1-deoxyglucose (14C-DG) uptake was also measured in specific tissues following intravenous bolus administration. The results showed that during a hyperinsulinemic-euglycemic clamp, infusion of TNF 20 micrograms/kg for 3 hours resulted in a significant reduction of glucose infusion and a significant increase of hepatic glucose production in both dietary groups as compared with saline infusion, indicating a state of insulin resistance induced by TNF. The results also showed that TNF infusion significantly decreased the rate of 14C-DG uptake in muscle in the sunflower oil group but not in the fish oil group, suggesting that fish oil is able to restore to normal the glucose utilization impaired by TNF. These observations suggest that in hyperinsulinemic and euglycemic conditions, prefeeding with fish oil significantly improves glucose uptake in muscle tissue, but does not alter the increase in hepatic glucose production during TNF infusion.

Animals↗

IGF-I alters energy expenditure and protein metabolism during parenteral feeding in rats.

In this study, 20 micrograms.kg.-1.h-1 of recombinant human insulin-like growth factor I (IGF-I) was infused into normal healthy rats to examine the effects of IGF-I on glucose, protein, and energy metabolism in either overnight-fasting or parenteral-feeding states. The fed state was maintained by continuous intravenous feeding of a complete diet containing 838 kJ.kg-1.d-1, 2 g N.kg-1.d-1, and no fat. At each nutritional state, one-half of the animals received IGF-I infusion while the other half received saline as control. [14C-1]leucine and [3H-6]glucose were used to determine the effects of IGF-I on protein and glucose kinetics during fed and fasting states. The results showed that 1) infusion of IGF-I at this amount did not alter plasma glucose appearance and only marginally decreased plasma glucose concentrations in both nutritional states; 2) during fasting, IGF-I did not show anabolic effects on protein metabolism either at the whole-body level or in individual tissues. However, during feeding, IGF-I significantly stimulated exogenous nitrogen utilization by the whole body; and 3) IGF-I reduced the thermogenic effect of feeding. The results suggest that parenteral feeding may be an important variable in the response of protein anabolism to IGF-I in vivo.

Animals↗

Differential effects of interleukin-1 receptor antagonist in cytokine- and endotoxin-treated rats.

Previous studies have demonstrated that the administration of the cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF)(20 micrograms/kg) to rats in a fasting state can produce many and perhaps most of the metabolic alterations found in patients with sepsis and injury. The purposes of the present study were 1) to define the metabolic effects of IL-1 and TNF during a fed state provided by continuous intravenous feeding for 20 h and 2) to characterize the unique effects of IL-1 among the overall response to cytokines by using IL-1 receptor antagonist (IL-1RA; 5 mg/kg). The effects were also explored during the endotoxemic condition induced by infusion of 200 micrograms/kg of endotoxin into rats. The results showed that during feeding IL-1 is responsible for the increase in glucose flux and plasma insulin, the development of insulin resistance, and plasma zinc depression during condition mimicking sepsis and injury, similar to effects observed in the fasting state. The changes in energy expenditure have a more complex mechanism. The results also suggested that certain host responses to cytokines or endotoxin, particularly related to protein metabolism, differed between the fed and fasting states. These data may have a special clinical relevance for the insulin-resistant state that develops during severe infection, since using IL-1RA in conjunction with nutritional therapy may offer additional advantages in the treatment of these severe metabolic disorders.

Animals↗

Intestinal digestion, absorption, and transport of structured triglycerides and cholesterol in rats.

We compared the intestinal absorption of trilinolein (1,2,3-tri-[1-14C]linoleyl-sn-glycerol) with two different structured triglycerides containing one linoleic acid (C18:2) and two octanoic acids (C8:0), 1,3-dioctanoyl-2-[1-14C]linoleyl-sn-glycerol (2-linoleate) and 1,2-di[1-14C]octanoyl-3-linoleyl-sn-glycerol (1,2-octanoate), respectively. Lymphatic radioactive lipid output of 2-linoleate resembled that of trilinolein rats but remained significantly lower during the lipid infusion. Radioactive lipid was recovered along the entire small intestinal lumen, with a significantly higher amount of [14C]lipid recovered in the lower small intestine and cecum in the 2-linoleate group. Delayed uptake of radioactive 2-linoleate was not due to poor digestion. In contrast, 1,2-octanoate was efficiently digested, and both the free fatty acid (FFA) and the monoacylglycerol (MG) containing octanoate were rapidly absorbed. Irrespective of its position on the triglyceride molecule, 14C-labeled octanoate was poorly transported into lymph. In addition, intestinal luminal and mucosal recovery of [14C]octanoate was significantly lower in the 1,2-octanoate group compared with [14C]linoleate recovery in the 2-linoleate or trilinolein groups. Total recovery of infused radioactive lipid was significantly less in the 1,2-octanoate group than in the 2-linoleate or trilinolein groups. Thus radioactive octanoate in the form of FFA or 2-MG was rapidly absorbed and transported via the portal vein. The infusion of either 2-linoleate or 1,2-octanoate did not affect the absorption and lymphatic transport of cholesterol compared with trilinolein. In summary, the type of the fatty acid on the structured triglyceride molecule affects its digestion, absorption, and lymphatic transport. Structured triglycerides containing octanoic acid in the 1- and 3-positions and linoleic acid in the 2-position may not be advantageous to use as a sole source of dietary lipid, but should be supplemented with long-chain triglycerides.

Absorption↗

Host defenses and susceptibility to infection in patients with diabetes mellitus.

The recently completed Diabetes Control and Complications Trial (DCCT) provided compelling evidence that intensive treatment of people with insulin-dependent diabetes mellitus can delay or prevent diabetic microvascular complications. Although not studied in the DCCT, patients with noninsulin-dependent diabetes mellitus likely will benefit from near-normoglycemia. Although it is difficult to prove a similar causal relation between hyperglycemia and infection (this outcome was not looked for in the DCCT), there is substantial in vitro data and evolving clinical studies that support this hypothesis. This information is presented in this article following a review of the regulation of glucose levels.

Complement System Proteins↗

Influence of formalin fixation time and tissue processing method on immunoreactivity of monoclonal antibody PC10 for proliferating cell nuclear antigen.

Proliferating cell nuclear antigen (PCNA), an auxiliary protein of DNA polymerase-delta, has recently been proposed as a marker of proliferation that is detectable in formalin-fixed paraffin-embedded tissue. Fixation time has been known to influence protein immunoreactivity and therefore can significantly influence the results of a quantitative immunohistochemical assay. In this study, we investigate the relationship between formalin fixation time and immunoreactivity for PCNA in paraffin-embedded sections and examine the effect of postfixation tissue treatment with modified Bouin's solution. Samples of small and large intestine from two freshly sacrificed rats were fixed in 10% buffered formalin for 6, 30, 54, 174, 340, and 508 h. Standard histological processing was performed on paired specimens whose treatment differed only by predehydration immersion in a picric acid and mercuric chloride-containing solution. Paraffin sections were reacted with monoclonal antibody PC10 in a standard immunoperoxidase assay. Staining intensity for PCNA was scored on a scale of 0 to 10, and the mean number of PCNA-positive cells per crypt (10 crypts counted) was determined. No difference between animals was found. PCNA immunoreactivity was maximal in specimens fixed for 6 to 30 h, exponentially declining with longer fixation time. The rate of decline was mitigated in the treated sections. Fixation-time dependence of PCNA immunoreactivity has immediate implications for intra- and interlaboratory comparisons, especially in experimental studies in which specimens can be stored in formalin for variable times followed by batch processing. With regard to surgical pathology specimens, this study suggests that sample comparisons are valid, since routine fixation time is within the optimal rage for PCNA immunodetection.

Animals↗