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Biomedical subjects

F B Cerra

Publications and source records attributed to F B Cerra.

At least 235 records · Page 13Linked to original sources
PubMedDate not supplied

Disease-specific amino acid infusion (F080) in hepatic encephalopathy: a prospective, randomized, double-blind, controlled trial.

Seventy-five patients with acute hepatic decompensation superimposed on chronic alcoholic cirrhosis were prospectively randomized for a blinded trial of the treatment of hepatic encephalopathy. The control group received 4 g of enteral neomycin daily along with 25% dextrose by a central venous catheter. The experimental group received a placebo resembling neomycin and isocaloric dextrose plus a modified amino acid mixture enriched with branched-chain amino acids to 36% and deficient in aromatic amino acids and methionine. Thirty patients in the F080 group and 29 in the control group completed the trial. The group receiving the modified amino acid mixture demonstrated a statistically significant improvement in encephalopathy as compared to the neomycin group, while maintaining nitrogen equilibrium. Survival and discharge from the hospital were statistically greater in the group treated with the modified amino acid solution and hypertonic dextrose. Treatment of hepatic encephalopathy in the presence of hepatic decompensation with an amino acid solution formulated for its treatment seems to produce faster, more complete recovery with improved capacity for nutritional support.

Adolescent↗
PubMedDate not supplied

Cardiac beta-adrenergic responsiveness is well preserved in moderate protein calorie malnutrition from semistarvation.

Twenty-one dogs underwent instrumentation of the left ventricle with ultrasonic dimension to study the effects of acute protein-calorie malnutrition on the adrenergic responsiveness of the heart. This study allowed a chronic and dynamic measurement of the major cardiac axes and the ventricular wall thickness, which in turn can be used to derive sophisticated measurements of global and intrinsic left ventricular function. Of the 21 dogs, 11 received a protein- and calorie-deficient diet designed to achieve a mean weight loss from a baseline of 20-25% over a 4-week period. The other 10 dogs received a normal diet. Dogs were also randomized to receive either acute propranolol beta-receptor blockade (n = 9) or acute isoproterenol beta-receptor stimulation (n = 12) during their baseline studies. Of the nine dogs given propranolol, five were subsequently malnourished and four served as controls. Of the 12 given isoproterenol, six were rendered malnourished and six were controls. All dogs were studied at both baseline and 4 weeks and received drugs in an identical fashion during both studies. The significant changes with malnutrition consisted of decreases in heart rate, cardiac mass, and left ventricular wall thickness. The degree of change in stroke volume, ejection fraction, cardiac output, dp/dt, and Emax (index of left ventricular contractility), with the administration of propranolol or isoproterenol was unaltered by malnutrition. These data support the contention that moderate protein-calorie malnutrition is well tolerated in instrumented, unstessed dogs and that the left ventricle's capacity to respond to beta-stimulation and to tolerate beta-blockade is largely unimpaired.

Animals↗
PubMedDate not supplied

Urinary urea nitrogen: too insensitive for calculating nitrogen balance studies in surgical clinical nutrition.

Urinary urea nitrogen (UUN) has been used as an estimate of total urinary nitrogen (TUN) when calculating nitrogen output for nitrogen balance (NB) studies. UUN is assumed to constitute 80 to 90% of the total nitrogen output; when estimating TUN from UUN, UUN values are multiplied by 1.25 to correct for non-urea nitrogen components. In order to evaluate the validity of estimating total urinary nitrogen output from measured UUN in a clinical setting, 491 UUN:TUN paired studies were performed on 24-hour urine collections in general surgical/trauma patients who had measured TUN outputs ranging from 0.04 to 54.0 g/d. Assessment of 315 NB studies was done to compare NB values of those calculated by using UUN as an estimate of TUN with those calculated from measured TUN. Patients in both studies were subdivided into four stress categories, using TUN/day as the index: less than 5 g, 5-10 g, 10-15 g, and greater than 15 g. On average, 80 to 90% of TUN is represented by the UUN. However, in our patient population the variability ranged from 12 to 112%. If these UUN values are used as estimates for TUN in calculating NB, variations of up to 12 g/d would result. Application of the correction factor of 1.25 is not consistent in correcting for nonurea nitrogen components in this clinical setting. The use of actual rather than estimated TUN may be a more accurate and appropriate method than UUN when calculating NB.

Adolescent↗
PubMedDate not supplied

Effect of a diet deficient in essential fatty acids on the translocation of intestinal bacteria.

Normal intestinal bacteria can initiate systemic disease by translocating out of the intestinal lumen to extraintestinal sites such as the mesenteric lymph nodes (MLN), liver, and spleen. To determine whether dietary essential fatty acids can affect the incidence of bacterial translocation, separate groups of mice were fed one of two diets for 8 days: an essential fatty acid-replete diet (EFA-R) containing a basal formula supplemented with arginine, yeast RNA, menhaden oil, and safflower oil, or an essential fatty acid-deficient diet (EFA-D) containing the same ingredients with the safflower oil replaced by menhaden oil. Mice were given either diet alone, diet plus 50 micrograms of intraperitoneal lipopolysaccharide (LPS), or diet plus 3 days of 4 mg of intramuscular metronidazole (MET) three times a day. (Both LPS and MET have been shown to increase the incidence of bacterial translocation to the MLN.) Within treatment groups there were no significant differences in the total numbers of viable ileal bacteria (separate quantitation of strict anaerobes, aerobic, and facultative Gram-positive results, and aerobic and facultative Gram-negative results). The incidence of bacterial translocation to the MLN was increased in mice fed EFA-D as compared with EFA-R in mice treated with diet alone (17% vs 0%; p less than .005) and in mice treated with diet plus LPS (71% vs 48%; p = .027). There was no difference in the incidence of bacterial translocation in mice fed EFA-D or EFA-R and treated with MET (83% vs 81%).

Animals↗
PubMedDate not supplied

Extracorporeal application of a gel-entrapment, bioartificial liver: demonstration of drug metabolism and other biochemical functions.

Metabolic activity of a gel-entrapment, hollow fiber, bioartificial liver was evaluated in vitro and during extracorporeal hemoperfusion in an anhepatic rabbit model. The bioartificial liver contained either 100 million rat hepatocytes (n = 12), fibroblasts (n = 3), or no cells (n = 7) during hemoperfusion of anhepatic rabbits. Eight other anhepatic rabbits were studied without hemoperfusion as anhepatic controls, and three sham rabbits served as normal controls. Albumin production rates (mean +/- SEM) were similar during in vitro (17.0 +/- 2.8 micrograms/h) and extracorporeal (18.0 +/- 4.0 micrograms/h) application of the hepatocyte bioartificial liver. Exogenous glucose requirements were reduced (p < 0.01) and euglycemia was prolonged (p < 0.001) in anhepatic rabbits treated with the hepatocyte bioartificial liver. The maximum rate of glucose production by the hepatocyte bioartificial liver ranged from 50-80 micrograms/h. Plasma concentrations of aromatic amino acids, proline, alanine, and ammonia were normalized in anhepatic rabbits during hepatocyte hemoperfusion. Gel-entrapped hepatocytes in the bioartifical liver performed sulfation and glucuronidation of 4-methylumbelliferone. P450 activity was demonstrated during both in vitro and extracorporeal application of the BAL device by the formation of 3-hydroxy-lidocaine, the major metabolite of lidocaine biotransformation by gel-entrapped rat hepatocytes. In summary, a gel-entrapment, bioartificial liver performed multiple hepatocyte-specific functions without adverse side effects during extracorporeal application in an anhepatic, small animal model. With its potential for short term support of acute liver failure, scale-up of the current bioartificial liver device is indicated for further investigations in large animal, preclinical trials.

Albumins↗
PubMedDate not supplied

Formation of porcine hepatocyte spheroids for use in a bioartificial liver.

Xenogeneic hepatocytes have recently been used in a bioartificial liver device as a potential short-term extracorporeal support of acute liver failure. Scaling up the system requires large quantities of viable and highly active cells. Hepatocytes grown as spheroids manifest higher metabolic activities for longer time periods as compared to those in monolayer cultures. Use of hepatocyte spheroids for application in a bioartificial liver can possibly alleviate the need of scaling up. Porcine hepatocytes when cultured under stirred conditions, from multicellular spheroids in a defined culture medium. Spheroids were formed 24 h after cell inoculation with an efficiency of 80-90% and a mean diameter of about 135 microns. Scanning electron microscopy revealed numerous microvilli projecting from the entire surface of the spheroids. Transmission electron microscopy revealed differentiated hepatocytes which displayed well-developed cytoplasmic structures separated by bile canaliculus-like structures. The morphological studies show a resemblance between cells in the spheroids and in the liver in vivo. Urea-genesis by spheroids was twice as active and was sustained for a longer culture period than that by hepatocytes cultured as monolayers. Preparation of porcine hepatocyte spheroids in an agitated vessel is simple efficient and reproducible. It will allow for preparation of large quantities of spheroids to be employed in a bioartificial liver device as well as in liver metabolism studies.

Animals↗
PubMedDate not supplied

Enhanced cytochrome P450 IA1 activity of self-assembled rat hepatocyte spheroids.

Primary rat hepatocytes can self-assemble to form multicellular spheroids when plated onto Primaria petri dishes. Spheroids have been observed to exhibit enhanced liver-specific functions and differentiated ultrastructure compared to monolayer cultures on dry collagen. With confocal scanning laser microscopy, CYP1A1 activity was evaluated in situ by detecting resorufin. This highly fluorescent molecule is the P450-mediated product of 7-ethoxyresorufin O-dealkylation (EROD). Significantly higher P450 activity was observed in spheroids compared to monolayers on collagen upon induction with 50 microM beta-naphthoflavone (BNF), a CYP1A inducer. This was confirmed by measuring microsomal EROD activity. The distribution of CYP1A1 activity within spheroids was heterogeneous, with higher activity localized to the hepatocytes in the interior. During the process of spheroid formation, cells were initially seen to attach and spread out as a monolayer. This stage was associated with relatively low CYP1A1 activity. As cells formed multicellular structures and aggregated into spheroids, the level of CYP1A1 activity increased over time. At least a fivefold higher fluorescence intensity was observed in spheroids compared to that of monolayers maintained on collagen. The higher P450 activity within spheroids may be associated with their ability to maintain a greater degree of differentiation compared to monolayers. These studies demonstrate the potential of hepatocyte spheroids as a model system for investigating drug metabolism, tissue engineering, and tissue self-assembly.

Animals↗
PubMedDate not supplied

Effect of fiber supplementation of liquid diet on cecal bacteria and bacterial translocation in mice.

Liquid Isosource was supplemented with soy fiber (Isosource-soy) or guar fiber (Isosource-guar) to study the effects of fiber supplementation of a liquid diet on the composition of mouse cecal flora and on the incidence of bacterial translocation, quantified as the number of mice with viable intestinal bacteria recovered from mesenteric lymph nodes. Mice fed chow, Isosource, Isosource-soy, or Isosource-guar had similar concentrations of cecal bacteria and similarly low incidences of bacterial translocation. In separate experiments, mice were given parenteral metronidazole or parenteral lipopolysaccharide (LPS) to induce cecal bacterial overgrowth and bacterial translocation. Compared with mice treated with diet alone, metronidazole- or LPS-treated mice had high numbers of cecal bacteria and high incidences of bacterial translocation. However, among the dietary groups of LPS-treated mice, the incidence of translocation was significantly less in mice fed Isosource-soy or Isosource-guar compared with mice fed unsupplemented Isosource. These results suggest that soy or guar supplementation of Isosource might be beneficial in some circumstances.

Animals↗
PubMedDate not supplied

Improvement in immune function in ICU patients by enteral nutrition supplemented with arginine, RNA, and menhaden oil is independent of nitrogen balance.

Hypermetabolism and multiple organ failure syndrome (MOFS) after trauma, surgery, or sepsis is associated with accelerated catabolism, the rapid onset of malnutrition, and immune system failure. Current nutritional support, enteral or parenteral, can achieve an acceptable nutritional response but appears unable to improve immune function. Nutrients such as arginine, refined menhaden oil, and RNA have been found to have immune-stimulating properties. This randomized blind prospective trial compared two nutritionally complete enteral formulas, one supplemented with arginine, menhaden oil, and RNA, on the disease-specific effects of anergy and suppression of in vitro tests of immune function in intensive-care patients and the nutritional outcome of nitrogen balance. After 7-10 days of enteral nutrition in patients with persistent sepsis syndrome, both formulas were associated with the achievement of net nitrogen retention and improved visceral protein status but with nonresolution of anergy. However, the supplemented formula was associated with marked stimulation of in vitro lymphocyte proliferative responses and a significant reduction in 3-methylhistidine excretion. Six and 12-mo follow-up data demonstrated no long-term effects. Nutrients targeted to effect the disease-induced in vitro suppression of immune function in MOFS appear to achieve that end independent of the nutritional outcome of nitrogen balance and without adverse clinical outcome.

Adult↗
PubMedDate not supplied

Effect of three liquid diets on cecal bacterial flora and bacterial translocation in mice.

Separate groups of mice were fed either standard rodent chow or one of three liquid diets (Impact, Isosource HN, Fibersource HN) for 14 days to determine the effects of these liquid diets on the cecal bacterial flora and on the incidence of bacterial translocation to the mesenteric lymph nodes. Liquid Isosource and liquid Fibersource had no noticeable effect on either the cecal bacterial flora or the incidence of bacterial translocation. Liquid Impact was associated with cecal bacterial overgrowth but had no effect on the incidence of bacterial translocation. Each of the liquid diets was then lyophilized and similarly fed to mice; none of the lyophilized diets had a noticeable effect on the cecal bacterial flora or the incidence of bacterial translocation. To test these liquid and lyophilized diets in stressed mice, separate groups of mice were again fed the various diets for 14 days but given parenteral Escherichia coli lipopolysaccharide (LPS) 24 h before being killed. None of the liquid or lyophilized diets had a noticeable effect on the cecal bacterial overgrowth noticed in LPS-treated chow-fed mice. Compared with chow-fed mice, the typically elevated LPS-induced bacterial translocation was even more elevated in mice fed liquid diet but was somewhat decreased in mice fed lyophilized diet. Thus, the modulatory effects of these liquid diets on the cecal flora and the incidence of bacterial translocation appeared to depend on the composition of the diet and on prior treatment with parenteral LPS.

Animals↗