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Biomedical subjects

J Bhatia

Publications and source records attributed to J Bhatia.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of sodium metabisulfite on hydrogen peroxide production in light-exposed pediatric parenteral amino acid solutions.

The effect of sodium metabisulfite (MBS) on hydrogen peroxide (HP) production in model and commercial amino acid solutions exposed to phototherapy light was studied. Model and commercial pediatric amino acid solutions were prepared such that the amino acid concentration was 1%. MBS concentration, riboflavin concentration, and duration of exposure to phototherapy light were varied to determine the effect on HP production. Control solutions were kept in the dark. HP production was assayed in the model amino acid solutions by using potassium iodide in the presence of ammonium molybdate. In all experiments, HP production was measured at 360 nm in the presence and absence of catalase. In light-exposed solutions, HP production increased linearly for several hours and reached a plateau by eight hours. A mean maximum of 940 microM was produced (data pooled for all solutions). No detectable HP was generated in the solutions kept in the dark. After two hours of light exposure, it was necessary to add at least 10 times more MBS than is typically found in commercial total parenteral nutrient solutions to scavenge all the HP produced. An average of up to 940 microM of HP was produced in model and commercial pediatric parenteral 1% amino acid solutions in the presence of phototherapy light and clinically relevant concentrations of riboflavin and MBS. Light exposure decreased the antioxidant effect of MBS.

Amino Acids↗
PubMed1998

Exemplifying guidelines for preparation of recombinant DNA products in phase I trials in cancer: preparation of a genetically engineered anti-CEA single chain Fv antibody.

Products of recombinant DNA technology have potential for the diagnosis or treatment of cancer. There is a need to investigate whether they function by the intended mechanism in small phase I clinical trials before their suitability for more extensive studies can be assessed. Quality and safety of these products should be assured prior to their use in humans in a way which is appropriate to the preliminary nature of the trials but not inhibitory to progress. The Cancer Research Campaign control recommendations for products derived from recombinant DNA technology (Begent RHJ and associates. Eur J Cancer 1993, 29A, 13, 1907-1910) provide guidelines for the production of new biotechnology products in academic research units within a relatively short time, while ensuring appropriate quality and safety. The practical application of the guidelines requires that solutions are found for the quality and safety issues during the production of recombinant products. We describe an approach to the relevant quality and safety issues during and after the production and purification of a genetically engineered anti-carcinoembryonic antigen (CEA) single chain Fv (scFv) antibody for a phase I trial of radioimmunoguided surgery with the intention of providing a model for other products.

Biotechnology↗
PubMed1998

Neonatal pharyngeal pseudodiverticulum mimicking esophageal atresia.

Pseudodiverticulum of the hypopharynx is an infrequent but potentially serious complication of orogastric or nasogastric tube insertion and endotracheal intubation. We report two cases of injury to the hypopharynx resulting in a pseudodiverticulum of the hypopharynx that was initially diagnosed as esophageal atresia. Both cases were managed successfully by conservative therapy. We also review the literature regarding neonatal pharyngeal pseudodiverticulum.

Diagnosis, Differential↗
PubMed1996

Rhodopsin, Gq and phospholipase C activation in cephalopod photoreceptors.

We present characterization of the rhodopsin, Gq and phosphatidylinositol-specific phospholipase C (PLC) from the signal transduction pathway of cephalopod photoreceptors. Cephalopod rhodopsins are unique in possessing a C-terminal extension of proline-rich repeats, and they have a strong tendency to form ordered arrays. Two-dimensional arrays of a full-length and C-terminally-truncated cephalopod rhodopsin have been obtained. The C termini appear to cluster the rhodopsins into small groups. An AlF4(-)-activated Gq alpha subunit has been isolated and shown to activate a partially purified PLC beta. This 130 kDa PLC, isolated by absorption on heparin agarose, showed a specific activity of 195 nmol of phosphatidylinositol 4,5-bisphosphate hydrolysed per milligram of protein per minute in the presence of 1.6 microM free calcium.

Animals↗
PubMed1996

Pharmacokinetics of vancomycin in critically ill infants undergoing extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a widely used therapy for neonates with respiratory failure. Because of sepsis, many of these infants require antibiotics like vancomycin during ECMO treatment. ECMO transiently alters renal function and increases the circulating blood volume by 75%. Initial vancomycin pharmacokinetics were determined in 12 infants undergoing ECMO to determine an adequate drug administration regimen. Vancomycin dosage was based on current recommendations for weight and gestational age. Pharmacokinetic parameters were determined by fitting the data to a two compartment model. This study yielded a mean steady-state volume of distribution of 1.1 +/- 0.5 (range, 0.6 to 2.1) liters/kg and a mean vancomycin clearance of 0.78 +/- 0.19 (range, 0.49 to 1.07) ml/min/kg. The mean vancomycin half-life was 16.9 +/- 9.5 (range, 8.8 to 42.9) h. Nomogram-calculated creatinine clearance was a significant predictor of vancomycin terminal rate constant and clearance. These data suggest alterations in the pharmacokinetics of vancomycin in infants on ECMO. With the goal of achieving vancomycin concentrations in serum above the MIC for the offending pathogen while using the least amount of the drug necessary, new administration guidelines for term infants without renal impairment undergoing ECMO should be 20 mg of vancomycin per kg at an interval of 24 h. With significant renal impairment, the interval should be extended on the basis of concentrations in serum. In comparison with previously published data, the neonates undergoing ECMO in our study demonstrated a much larger volume of distribution, a lower clearance, and consequently a longer vancomycin half-life.

Anti-Bacterial Agents↗
PubMed1996

Effects of Carbicarb and sodium bicarbonate on hypoxic lactic acidosis in newborn pigs.

BACKGROUND: Use of sodium bicarbonate (NaHCO3) may result in intracellular acidosis due to the generation of CO2. Carbicarb, has been reported to be superior to sodium bicarbonate (NaHCO3) because of lesser generation of CO2. The present study was designed to investigate whether Carbicarb or NaHCO3 is superior to normal saline in the treatment of hypoxic lactic acidosis. METHODS: Hypoxia was induced by ventilation with 8% O(2) in 30 piglets with fixed ventilation. When the pH fell to < 7.2, hypoxia was reversed by placing the animals in 21% O2 (experiment 1) or 100% O(2) (experiment 2) and either saline, Carbicarb or NaHCO3 were given. Data were collected for 120 minutes after therapy. RESULTS: In both experiment 1 (severe acidosis, pH < or = 7.1) and 2 (moderate acidosis, pH < or = 7.2) use of Carbicarb and NaHCO3 increased the arterial carbon dioxide tension (pCO2) significantly (p < 0.05). With moderate acidosis: 1) use of alkalinizing agents compared to saline resulted in an initial improvement in arterial pH at 1 minute, but thereafter, the differences were not statistically significant; and 2) there were no differences in hemodynamic variables and plasma lactic acid concentration between the three groups. CONCLUSIONS: The data demonstrate that 1) both Carbicarb and NaHCO3 significantly increase arterial pCO2; and 2) use of either alkalinizing agent in moderate acidosis does not alter the course of acidosis.

Acid-Base Equilibrium↗
PubMed1995

A beta-subclass phosphatidylinositol-specific phospholipase C from squid (Loligo forbesi) photoreceptors exhibiting a truncated C-terminus.

A PCR-based strategy has been used to isolate a full length cDNA encoding a phosphatidylinositol-specific phospholipase C from a sized cDNA squid (Loligo forbesi) retinal library. The predicted protein sequence contains 875 amino acids, with calculated M(r) 98,181, and has marked similarity with PLC beta-isoforms, including conservation of the 'X' and 'Y' regions. It is unique in having a major C-terminal truncation. A major protein of apparent M(r) 120,000 estimated by SDS-PAGE has been isolated from squid photoreceptors and identified by partial protein sequence analysis to correspond to the protein sequence predicted from the cDNA clone. This protein has been shown to hydrolyse phosphatidylinositol 4,5-bisphosphate. It is not yet clear whether this represents the major light-activated PLC in squid vision.

Amino Acid Sequence↗
PubMed1994

Biliary glutathione and some amino acids are markedly diminished when biliary pressure is elevated.

We studied the effects of a transient elevation in biliary pressure on biliary glutathione and amino acids in rats. Other biliary solutes monitored were total bile salt, Pi, which is a putative marker of paracellular leakage, and glucose, which is reabsorbed from the biliary tract. Experiments were carried out on anesthetized rats intraduodenally infused with taurocholate to maintain bile flow during a 2-hr basal period, a 4-hr pressure period during which the bile duct cannula was elevated until bile flow decreased to 1/3 the basal rate, and a 2-hr period after release of hydrostatic biliary pressure. We found that pressure treatment caused biliary concentrations of glutathione to progressively decrease by 80%, while biliary Pi rapidly rose approximately 3- to 4-fold, bile salt gradually increased approximately 3-fold, and biliary glucose concentration progressively rose 15-fold. HPLC analysis of monobromobimane-derivatized biliary thiols indicated that the decline in biliary glutathione was not accompanied by an increase in its breakdown products, cysteine and cysteinylglycine. Pressure treatment led to four patterns of change in biliary amino acid concentrations: (1) increases of 29 to 76% for the basic amino acids lysine and arginine, which have very low bile/plasma ratios of about 0.1; (2) no change for the more water soluble amino acids with bile/plasma ratios close to 1.0, e.g., histidine and urea; (3) modest decreases of 16 to 48% for a variety of amino acids including serine, glutamate, and glycine; and (4) marked, progressive decreases of > 50% for aromatic and branched chain amino acids. By 2 hr after release of pressure, only the alterations in biliary glucose and some amino acids, particularly the branched chains, persisted. This is the first report of cholestasis-induced alterations in biliary amino acids.

Amino Acids↗
PubMed1993

Hydrogen peroxide generation in a model paediatric parenteral amino acid solution.

1. Parenteral amino acid solutions undergo photooxidation, which may be an important factor in total parenteral nutrition-associated hepatic dysfunction. Light-exposed parenteral solutions containing amino acids, in addition to vitamins and trace minerals, generate free radicals, which, in turn, may contribute to this type of injury. This study examined the characteristics of H2O2 production in a parenteral amino acid solution modelled on a commercially available paediatric parenteral amino acid solution. 2. The solution was exposed to light in the presence of riboflavin-5'-monophosphate (riboflavin), and peroxide formation in the presence and absence of catalase (H2O2 formation) was assayed using potassium iodide/molybdate. 3. Peak H2O2 production occurred at a light intensity of 8 microW cm-2 nm-1 in the 425-475 nm waveband and was linear to 2 h of light exposure. H2O2 production reached 500 mumol/l at 24 h. 4. H2O2 was directly related to a riboflavin concentration of up to 20 mumol/l and was maximal at 30 mumol/l. 5. H2O2 production was greatest in the amino acid/riboflavin solution at a pH of between 5 and 6. 6. Under the conditions of light exposure intensity, light exposure time, riboflavin concentration and pH found during the administration of parenteral nutrition in neonatal intensive care units, net H2O2 production occurs in solutions modelled on a paediatric parenteral amino acid preparation.

Amino Acids↗
PubMed1993

Feeding premature infants.

We have tried to offer a rational approach to the methods of premature infant feeding. Most of our information is incomplete, and many of the presumptions used in deciding feeding technique are not based on reliable scientific data. The calculations presented in this discussion are valuable as teaching methods in the nursery. The complexity of the questions about premature infant feeding makes it necessary for personnel in the neonatal unit to focus regularly on infant feeding and to allow for time dedicated to considering their suggestions.

Enteral Nutrition↗
PubMed1993

Total parenteral nutrition-associated alterations in hepatobiliary function and histology in rats: is light exposure a clue?

Light exposure of amino acids, especially in the presence of photosensitizers such as riboflavin, has been shown to result in photoproducts that are toxic both in vivo and in vitro. Provision of photooxidized single amino acids has been shown to result in hepatic dysfunction in both gerbils and rats. However, studies of the effects of light exposure of complete nutrient mixtures (glucose-amino acid-vitamins) on hepatobiliary responses are limited. These are important because, in clinical practice, total parenteral nutrition (TPN) solutions are continually exposed to light and because hepatic dysfunction is the most common metabolic aberration associated with TPN. Studies were conducted to compare the effects of TPN that had been exposed to light (+L) or protected from light (-L) on hepatobiliary function of rats. TPN solutions were either exposed to light or protected from light for 24 h and then infused into rats for 10 d. Data for enterally fed rats are also shown for comparison with parenterally fed animals. +L animals lost more weight and had lower bile flow, higher taurocholate output in bile, higher biliary osmolarity, and higher inorganic phosphate in bile. Hepatic histology demonstrated scattered foci of necrosis in eight of the eight +L animals and in only one of eight -L animals. These data demonstrate that protection of TPN solutions from light minimizes TPN-associated alterations in hepatobiliary function and histology. These histologic changes observed in the +L animals are in contrast to previous reports of TPN-induced histologic changes, suggesting a different mechanism. Our observations suggest that consideration be given to the implications of exposing TPN solutions to light.

Animals↗
PubMed1992

Glutathione and tissue amino acid responses to light-exposed parenteral nutrients.

Effects of infusion of light-exposed (+L) or light-protected (-L) total parenteral nutrition solutions were investigated in rats. The parenteral infusions were carried out for 7 days through jugular cannulas in freely moving rats in metabolic cages. Plasma tyrosine and citrulline, hepatic methionine, valine, isoleucine, leucine and tyrosine, and biliary cystathionine were significantly greater in the -L than +L rats, whereas biliary arginine was significantly lower in the -L compared to +L rats. Bile flow, biliary inorganic phosphate and glucose were significantly lower, whereas biliary total glutathione (GSH+GSSG) was significantly greater in the -L compared to +L animals. These data suggest adverse effects on hepatobiliary function due to light exposure of parenteral nutrients. The endogenous markers used suggest that tight junction permeability, bile acid-independent flow, glutathione and amino acid homeostasis are altered by light exposure and that these changes can be minimized by light protection. The mechanisms involved in the induction of these changes need to be elucidated. The role of light exposure of parenteral nutrients during routine clinical use in the induction of hepatic dysfunction, a common metabolic complication of parenteral nutrition, needs to be considered.

Amino Acids↗
PubMed1992

Biliary endogenous inorganic phosphate, D-glucose, IgA and transferrin are differentially altered by hydrostatic pressure.

Our objective was to determine the effects of hydrostatic biliary pressure on excretion patterns of endogenous solutes which reflect various pathways of bile formation. A stable in vivo model was developed using anesthetized rats intraduodenally infused with taurocholate to maintain bile flow. Bile was collected during a 2-h basal period, a 4-h pressure period where elevation of the bile duct cannula decreased bile flow to 1/3 the basal rate, and a 2-h period after release of hydrostatic biliary pressure. During pressure treatment, bile salt concentration gradually increased approximately 3-fold, biliary inorganic phosphate concentrations rapidly rose approximately 5-fold, and biliary glucose concentration progressively rose approximately 17-fold. Concentrations of proteins in bile were affected differently with extreme decreases in IgA, moderate decreases in total protein and leucine aminopeptidase, and minimal change in transferrin. By 2 h after pressure release, only the alterations in biliary glucose and IgA persisted. The observed striking and persisting increases in biliary glucose are tentatively explained as an impaired reabsorption of glucose by the biliary tract.

Animals↗
PubMed1992

Hepatic function during short-term total parenteral nutrition: effect of exposure of parenteral nutrients to light.

Total parenteral nutrition (TPN) solutions either exposed to light (+L) or protected from light (-L) were infused for 5 days through jugular cannulas in freely moving rats placed in metabolic cages. At the end of the 5 day period, bile flow, biliary inorganic phosphate and biliary gamma-glutamyl transferase activity, as well as biliary concentrations of several essential and branch chain amino acids were significantly lower in the -L animals compared to +L animals. In addition, biliary glutathione was significantly lower in the +L animals. In both groups of animals, plasma tyrosine decreased significantly from pre-TPN values despite a doubling of plasma phenylalanine concentrations suggesting that tyrosine may become a conditionally essential amino acid in rats provided TPN. Our findings indicate that short-term parenteral infusion of light exposed TPN solutions alters hepatobiliary function as well as amino acid homeostasis and that the changes are minimized by light protection of the infusates. The exact mechanisms of the contribution of light exposure in the induction of hepatic dysfunction remain to elucidated.

Amino Acids↗
PubMed1991

Effect of protein/energy ratio on growth and behavior of premature infants: preliminary findings.

Premature infants weighing less than 1550 gm at birth were randomly assigned to receive one of three formulas identical in composition except for protein content (2.2, 2.7, and 3.2 gm.100 kcal-1) to determine the effects on growth, protein nutritional status, and behavior. Data collected for 2 weeks from the time of achieving an enteral energy intake of 100 kcal.kg-1.day-1 included measurements of weight, length, head circumference, and skin-fold thickness, and concentrations of plasma amino acids, serum total protein, prealbumin, retinol-binding protein, and urea nitrogen. In a subset of infants, behavior was assessed at the end of the feeding study with the Neonatal Behavior Assessment Scale. Except for the concentrations of plasma amino acids, there were no significant differences in growth or in other biochemical measurements among the three groups, but there were significant differences in the orientation, habituation, and stability clusters of the behavior assessment. Further, there were significant correlations between the plasma amino acid values and the behavioral clusters. These preliminary data suggest a relationship between protein intake in the neonatal period and behavioral outcome at the end of the feeding period in the absence of differences in growth and gross markers of protein nutritional status. The behavioral items noted to differ among the groups may indicate later cognitive outcome; detailed studies about behavioral responses to neonatal dietary intakes and later outcome seem indicated.

Amino Acids↗
PubMed1991

Feeding the premature infant after hospital discharge: growth and biochemical responses.

We conducted a double-blinded, randomized trial in premature infants after hospital discharge to test the hypotheses that growth and biochemical responses in those fed a formula with a reduced protein content (1.3 gm/dl) would be similar to those in infants fed a standard infant formula (protein 1.5 gm/dl). Twenty low birth weight infants were followed for 16 weeks from the time of hospital discharge. Growth (weight, length, and head circumference) and biochemical responses (total protein, prealbumin, retinol-binding protein, and blood urea nitrogen values) were similar in the two groups of infants. Plasma amino acids reflected the differences in protein intakes and were similar to previously reported values for premature infants fed human milk or formula. These results demonstrate similar growth and biochemical responses in preterm infants fed a standard infant formula and a formula with a protein content closer to that of human milk.

Amino Acids↗