Serum creatinine levels in infants.
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Biomedical subjects
Publications and source records attributed to S Awasthi.
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Based upon kinetic, structural, and immunologic properties, we have demonstrated that human tissues have three major forms of aldo-keto reductases: aldose reductase (AR), and aldehyde reductases I (AR I) and II (AR II). The proposed subunit compositions are AR, alpha; AR I, alpha-beta; and AR II, delta. Only AR can effectively reduce glucose to sorbitol. The beta subunits in AR I alter the substrate specificity of AR and prevent conformational changes required for the activation of alpha subunits. Partially purified AR (by DE-52) from human erythrocytes expresses biphasic kinetics with glucose and glyceraldehyde. The enzyme can be activated with glucose + glucose-6-P + NADPH and is strongly inhibited by sorbinil, alrestatin, and quercetrin, and by ADP, 2,3DPG, 1,3DPG, and 3PGA. The activated enzyme expresses monophasic kinetics with substrates (Km glucose less than 1 mmol/L) and is less susceptible to inhibition by synthetic AR inhibitors and phosphorylated intermediates. The enzyme from human brain, aorta, muscle, and ocular tissues was also activated under similar conditions. Erythrocyte enzyme was activated by incubation of blood with 30 to 50 mmol/L glucose. In diabetic subjects with blood sugar levels higher than 250 mg%, almost all the erythrocyte enzyme exists in the activated form. As demonstrated by enzyme-linked immunosorbent assay (ELISA), the increase in AR activity (in vivo and in vitro) was due to the activation of the enzyme and not to the de novo synthesis. In each case, the activation of the enzyme was confirmed by NADPH oxidation and the formation of proportionate amounts of sorbitol.
We have proposed earlier a three gene loci model to explain the expression of the aldo-keto reductases in human tissues. According to this model, aldose reductase is a monomer of alpha subunits, aldehyde reductase I is a dimer of alpha, beta subunits, and aldehyde reductase II is a monomer of delta subunits. Using immunoaffinity methods, we have isolated the subunits of aldehyde reductase I (alpha and beta) and characterized them by immunocompetition studies. It is observed that the two subunits of aldehyde reductase I are weakly held together in the holoenzyme and can be dissociated under high ionic conditions. Aldose reductase (alpha subunits) was generated from human placenta and liver aldehyde reductase I by ammonium sulfate (80% saturation). The kinetic, structural and immunological properties of the generated aldose reductase are similar to the aldose reductase obtained from the human erythrocytes and bovine lens. The main characteristic of the generated enzyme is the requirement of Li2SO4 (0.4 M) for the expression of maximum enzyme activity, and its Km for glucose is less than 50 mM, whereas the parent enzyme, aldehyde reductase I, is completely inhibited by 0.4 M Li2SO4 and its Km for glucose is more than 200 mM. The beta subunits of aldehyde reductase I did not have enzyme activity but cross-reacted with anti-aldehyde reductase I antiserum. The beta subunits hybridized with the alpha subunits of placenta aldehyde reductase I, and aldose reductase purified from human brain and bovine lens. The hybridized enzyme had the characteristic properties of placenta aldehyde reductase I.
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The main objective of this study was to elicit proportional cause specific mortality in the underfives in the urban slums of Lucknow in North India. The families with under five mortality in the 28 randomly selected slums in 1993 were located from the records of the slum health workers and verbal autopsy was conducted to assign a cause of death. There were 71 deaths among 2796 children. The annual under five mortality was 25.4 and the under five mortality rate was 126.7. After the neonatal period, "high fever" that could not be classified into any other disease incorporated in the verbal autopsy instrument, was the most common symptom associated with death, seen in 21.1% cases (95% C.I.: 15.5-34.4%) followed by these diseases: pneumonia in 19.7%, diarrhea in 18.3% and measles in 11.4%. "High fever" as the leading symptom associated with death is being reported for the first time from the urban slums of India. There is an urgent need to identify the underlying etiologies of death due to "high fever" and the policy implications are that children with fever must receive immediate and continued medical attention till the symptom persists.
The study aim was to predict, using serum bilirubin level measured 18 to 24 hours (SB, 18-24) after birth, the occurrence of peak serum bilirubin level > 15 mg/dL (hyperbilirubinemia) or the requirement of phototherapy, any time from the second to fifth postnatal day. The study was conducted on a prospective cohort of 274 neonates born in north India. The main outcome measures were (a) hyperbilirubinemia and (b) phototherapy. Serum bilirubin level was estimated at 18-24 hours of age and then daily from second to fifth postnatal day. Exclusion criteria were Rh incompatibility, asphyxia and life threatening congenital malformations; and neonates of women with gestational diabetes or history intake of drugs affecting the fetal liver. Hyperbilirubinemia was found in 12.8%; and 19.3% neonates received phototherapy. Dichotomous SB 18-24, using a cut-off of > 3.99 mg/dL, as the "prediction test" had the following sensitivity and specificity for predicting (a) hyperbilirubinemia: 67% and 67%, respectively, and (b) the treatment with phototherapy: 64% and 68%, respectively. We concluded that by using SB 18-24 as the "prediction test", approximately two-thirds of neonates were test negative and had about one in ten chances of re-admission for treatment of hyperbilirubinemia, if discharged. After further validation, our results will be of benefit to neonates delivered in developing countries.
Allylamine is an aliphatic amine that causes vascular lesions in aorta and medium-sized arteries. This primary amine has been shown to be metabolized to acrolein both in vivo and in vitro. Acrolein may cause allylamine's toxic effects, since it acts as a strong peroxidizing agent itself; in addition, deamination of allylamine is accompanied by production of hydrogen peroxide. To investigate the relative roles of oxidative stress and lipid peroxidation in allylamine intoxication, we conducted an acute in vivo time-course study following administration of allylamine (150 mg/kg) to rats by gavage. Animals were sacrificed at 1, 3 and 5 h after allylamine treatment, and subcellular fractions of aorta, epicardium and endocardium were assayed for enzymes of the oxidant defense system and thiol (-SH) status, capacity for lipid peroxidation, and .OH radical generation. Results suggest that in vivo treatment with allylamine causes preferential damage to aortic mitochondria. A marked depletion of total and free -SH content was found in aorta, epicardium and endocardium, with a striking increase in the formation of thiobarbiturate-reactive substance by aortic mitochondria at all time points. A significant increase in the capacity to generate .OH was found in aorta (with lesser increases in epicardium and endocardium) after allylamine treatment. Levels of defense system enzymes were not consistently altered, however. In a totally in vitro experiment, liposomes incubated with acrolein (0.2-2 mM) showed a proportional increase in lipid peroxidation of liposomal membrane. A likely basis of allylamine's cardiovascular toxicity is acrolein-induced lipid peroxidation, especially in mitochondria.
Spermidine was found to inhibit the in vitro formation of thiobarbituric acid-reactive material from sonicated vesicles of rat brain and individual phospholipids, especially in the presence of externally added iron. With arachidonic acid incorporated liposomes spermidine inhibited lipid peroxidation in the presence or the absence of Fe2+, to similar extent. Thus spermidine inhibition of lipid peroxidation may not be entirely iron-dependent.
Diverticular disease of colon is a rare entity in our country; true incidence of which is not known. We present three cases of diverticular disease, two with lower gastro-intestinal (GI) hemorrhage and one with sigmoid colon perforation and peritonitis. All three patients underwent emergency surgical treatment. Two patients survived and one died. No further complications were noted on follow up.
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In a 69-year-old man with hepatomegaly, a diagnosis of primary non-Hodgkin's lymphoma (NHL) of the liver was made by fine needle aspiration (FNA). At the time of presentation there was no evidence of involvement of the lymph nodes, bone marrow or any other organ. Although hepatic involvement is common in advanced stages of Hodgkin's disease and NHL, primary lymphoma of the liver is rare. The purpose of this paper is to report a rare occurrence of primary lymphoma of the liver and to demonstrate the possibility of making this diagnosis by FNA.
Patients with carcinoma of the gall bladder (CaGB) may have atypical presentations and unusual associations. Out of 324 patients with CaGB seen at a tertiary referral center in northern India, 26 (8%) had atypical clinical presentations and 34 (10%) had unusual associations. The atypical presentations were empyema (5), acute cholecystitis (3), post-cholecystectomy benign biliary stricture (3), carcinoma of the head of pancreas (3), gastric outlet obstructions (2) and liver abscess (1). Unusual associations were common bile duct stones (18), left supraclavicular lymph node metastasis (11), Mirizzi's syndrome (3), inguinal lymph node metastasis (1) and umbilical metastasis (1). Majority of these patients had advanced disease and curative resection was not possible; a worthwhile palliation was however possible in the majority.
BACKGROUND: This study aimed to identify the predictors of hospital mortality in children with acute infective disorders of the central nervous system using an aggregate Modified Glasgow Coma Scale (MGCS) score and other clinical variables assessed within 24 hours of hospitalization. METHODS: We did a prospective cohort study in a teaching and referral hospital in Lucknow, North India. Consecutive children aged 1 month to 12 years of age admitted with acute infective disorders of the central nervous system were included in the study. The diagnosis was based on the presence of symptoms of fever, headache or irritability with or without vomiting, and either altered sensorium or first episode of seizures or both. The main outcome measure was hospital-based mortality. RESULTS: Of the 230 patients included in the study, 42.2% had pyogenic meningitis, 36.9% had tuberculous basal meningitis and 20.9% had meningo-encephalitis. There were 43 (18.7%) deaths of which 44.2% were within 3 days of admission. Death was associated with the day 1 aggregate MGCS score only. The area under the curve of four strata of aggregate MGCS was 0.63 (SE 0.05). The likelihood ratio for discharge with an aggregate MGCS score of < 5 was 0.52 (95% CI:0.29-0.95) and > 10 was 5.52 (9% CI:1.02-31.96). CONCLUSION: The MGCS can be used to predict discharge in patients with acute infective disorders of the central nervous system within 24 hours of hospitalization. The scale is simple, can be applied at the bedside and does not depend on any investigations. In developing countries with limited investigative facilities it can be used for identification and selective referral of patients with a higher risk of death to specialized centres. This study validates the predictive value of the MGCS.