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Biomedical subjects

H Singh

Publications and source records attributed to H Singh.

At least 307 records · Page 17Linked to original sources

Acute dystonia during fixed-dose neuroleptic treatment.

Eighty-six patients with acute psychotic exacerbations were treated with fixed dosage regimens of oral fluphenazine up to 10-30 mg/day in randomized, double-blind studies. Dystonic reactions occurred in 33.8% of the subjects at risk. Of these, 58% occurred by the third day, 88% by the fourth day, and 100% by the ninth day of treatment; most occurred later in the interdose interval. Significant predictors of dystonic reactions were higher fluphenazine mg/kg dosage and younger age. There was a trend toward a lower risk of dystonia in patients who received amobarbital sodium for agitation. Results are discussed in relation to possible mechanisms of neuroleptic-induced dystonia.

Adult↗

Defective oxidation of pristanic acid by fibroblasts from patients with disorders in propionic acid metabolism.

The alpha-methyl fatty acid, pristanic acid (2, 6, 10, 14 tetramethylpentadecanoic acid) is oxidised rapidly by normal skin fibroblasts in culture to CO2 and to water-soluble metabolites. The latter are secreted into the culture medium. Fibroblasts from patients with propionyl CoA carboxylase, and to a lesser extent from patients with methylmalonyl CoA mutase defects, show reductions in the amount of CO2 released, although the production of water-soluble metabolites is not affected. Our data indicate that propionic acid is produced from pristanic acid, and ultimately from its immediate precursor phytanic acid. As phytanic and pristanic acids are significant components of diets rich in ruminant fats, it is likely that they may contribute to the accumulation of propionate and its metabolites in disorders of propionate metabolism.

Amino Acid Metabolism, Inborn Errors↗

A large protein containing zinc finger domains binds to related sequence elements in the enhancers of the class I major histocompatibility complex and kappa immunoglobulin genes.

A cDNA from a B-cell library was previously isolated that encodes a sequence-specific DNA-binding protein with affinities for related sites in a class I major histocompatibility complex (MHC) and kappa immunoglobulin gene enhancers. We report here approximately 6.5 kilobases of sequence of the MBP-1 (MHC enhancer binding protein 1) cDNA. MBP-1 protein has a molecular weight predicted to be greater than 200,000. A DNA-binding domain with high affinity for the MHC enhancer sequence TGGGGATTCCCCA was localized to an 118-amino-acid protein fragment containing two zinc fingers of the class Cys2-X12-His2. Analysis of expression of MBP-1 mRNA revealed relatively high expression in HeLa cells and in a human retinal cell line, with lower levels in Jurkat T cells and in two B-cell lines. Interestingly, expression of MBP-1 mRNA was inducible by mitogen and phorbol ester treatment of Jurkat T cells and by serum treatment of confluent serum-deprived human fibroblasts.

Amino Acid Sequence↗

Cardiac hydatid cyst in a child.

Presentation of hydatid disease is uncommon in children, and cardiac hydatid cyst is rare at any age. The authors discuss a pediatric patient with cardiac hydatid cyst in the posterior wall of the left ventricle. The cyst was diagnosed by two-dimensional echocardiography and by serology. A 3 month course of mebendazole therapy was only partially effective. The patient remains asymptomatic 2 years after diagnosis. HYDATID DISEASE is endemic in the Middle East. In a study from a surgical hospital in eastern Libya, the disease accounted for 0.89 percent of all hospital admissions. The echinococcus cyst grows very slowly and unless located in a critical anatomic site, it takes many years to evolve. Consequently, presentation in pediatric patients is distinctly uncommon. In an epidemiologic study from Benghazi, only 11.7 percent of patients were under 10 years old. Cardiac hydatid disease is rare at any age, accounting for less than 2 percent of all hydatid disease. Since the introduction of two-dimensional echocardiography, more cases are being diagnosed. All the reports in the recent literature are in adult patients. We report here, however, a cardiac hydatid cyst in the left ventricular wall in a child.

Child↗

A comparative study of straight chain and branched chain fatty acid oxidation in skin fibroblasts from patients with peroxisomal disorders.

The beta-oxidation of stearic acid and of alpha- and gamma-methyl isoprenoid-derived fatty acids (pristanic and tetramethylheptadecanoic acids, respectively) was investigated in normal skin fibroblasts and in fibroblasts from patients with inherited defects in peroxisomal biogenesis. Stearic acid beta-oxidation by normal fibroblast homogenates was several-fold greater compared to the oxidation of the two branched chain fatty acids. The effect of phosphatidylcholine, alpha-cyclodextrin, and bovine serum albumin on the three activities suggests that different enzymes are involved in the beta-oxidation of straight chain and branched chain fatty acids. Homogenates of fibroblasts from patients with a deficiency in peroxisomes (Zellweger syndrome and infantile Refsum's disease) showed a normal ability to beta-oxidize stearic acid, but the oxidation of pristanic and tetramethylheptadecanoic acid was decreased. Concomitantly, 14CO2 production from the branched chain fatty acids by Zellweger fibroblasts in culture (but not from stearic acid) was greatly diminished. The Zellweger fibroblasts also showed a marked reduction in the amount of water-soluble metabolites from the radiolabeled branched chain fatty acids that are released into the culture medium. The data presented indicate that the oxidation of alpha- and gamma-methyl isoprenoid-derived fatty acids takes place largely in peroxisomes in human skin fibroblasts.

Adrenoleukodystrophy↗

Neuroleptic withdrawal in patients meeting criteria for supersensitivity psychosis.

In an attempt to prospectively validate the existence of supersensitivity psychosis (SSP), five schizophrenic patients meeting Chouinard's criteria for SSP and five non-SSP schizophrenic controls had neuroleptic treatment withdrawn for 2 weeks under double-blind conditions. The sudden worsening of psychotic symptoms and tardive dyskinesia postulated in the SSP group was not observed on the Brief Psychiatric Rating Scale, the Clinical Global Impressions scale, and the Abbreviated Dyskinesia Rating Scale. In conclusion, the authors' pilot data do not seem to support the existence of SSP.

Adult↗

Skinfolds in affluent Punjabi preschool children.

The skinfold thickness at three different sites (triceps, subscapular and suprailiac) were measured using Holtain Skin Fold Caliper in 941 children of 0-5 years of age. The sample consisted of children from affluent families of Ludhiana (Punjab) in order to include only the optimally growing children. The skinfold thickness at all the three sites showed a progressive rise in mean values upto the age of 1 year and thereafter the trend was downwards till the age of 5 years in both the sexes. The values were higher in girls in all age groups. The mean triceps skinfold thickness was the highest followed by subscapular and suprailiac thickness in both sexes in almost all age groups. There was no correlation between the body weight and skinfold thickness values (mean r value = 0.09). Triceps and suprailiac skinfold thickness were significantly lower than the corresponding British values in both the sexes in all age groups. However, the subscapular values were comparable with British values in the females of all age groups and also in males above three years of age. Larger multicentric studies are recommended to frame the norms for Indian children.

Anthropometry↗

The effect of insulin-like growth factor I on postburn hypermetabolism.

These studies were undertaken to examine the effects of insulin-like growth factor I (IGF-I) on the hypermetabolic state that follows major thermal injury. Male Sprague-Dawley rats weighing 275 to 325 gm were subjected to a 50% total body surface area, full-thickness scald burn. At the time of injury, osmotic pumps were surgically implanted and used to deliver IGF-I, 1000 micrograms/day, or an equivalent volume of placebo solution by constant infusion of 5 microliters/hr for 14 days. Metabolic rates were studied with oxygen-consumption measurements performed on days 3, 7, 10, and 14 after injury. Animal weight measurements were also performed at the above intervals, with serum total IFG-I levels measured at death. Total serum IGF-I levels were decreased significantly 14 days after injury compared with uninjured animals (p less than 0.05). Treatment with IGF-I resulted in a significant decrease in oxygen consumption and a significant increase in body weight compared with burned animals and those treated with placebo 10 and 14 days after injury (p less than 0.05). These data suggest that IGF-I causes a significant change in the metabolic response that follows severe thermal injury and point to a possible role for IGF-I in the treatment of patients after severe thermal injury.

Animals↗

Effect of decreased cerebrospinal fluid proteins on the spread of local anaesthetic drugs in pregnancy.

Cerebrospinal fluid (CSF) and plasma protein concentrations were determined in 60 ASA-I female patients, 30 non-pregnant women, who were to undergo lower abdominal or lower limb surgery (group I, controls) and 30 pregnant women at term, who were posted for lower segment caesarean section (group II). All patients received spinal analgesia. Time of onset of analgesia and level of analgesia achieved were compared in two groups. A significant fall (16.6%) was noted in the plasma proteins in pregnant (6.10 +/- 0.6 g/dl) women as compared to non-pregnant patients (7.30 +/- 0.44 g/dl; P less than 0.01). CSF proteins also showed a significant fall (43.2%) in pregnant (25.80 +/- 5.52 mg/dl), as compared to non-pregnant women (45.43 +/- 7.66 mg/dl; P less than 0.001). Dose of local anaesthetic drug required was significantly less (44%) in pregnant (3.21 +/- 0.29 mg/segment) as compared to non-pregnant women (5.73 +/- 0.74 mg/segment; P less than 0.01). Time of onset of block was significantly less in pregnant than in non-pregnant patients after the injection of drug (2.86 +/- 0.42 sec and 3.41 +/- 0.43 sec respectively; P less than 0.01). No correlation was found between plasma proteins and CSF proteins. CSF protein concentration also did not correlate with dose of local anaesthetic drug, or with time of onset of block. It is suggested that fall in CSF protein concentration may be another contributory factor in the reduced dose requirement of local anaesthetic drug for subarachnoid block during pregnancy.

Adult↗

Metabolism of saturated and polyunsaturated fatty acids by normal and Zellweger syndrome skin fibroblasts.

The metabolism of 1-11C-labelled derivatives of palmitic (C16:0), arachidonic (C20:4,n-6) lignoceric (C21:0) and tetracosatetraenoic (C24:4,n-6) acids was studied in normal skin fibroblast cultures and in cultures of fibroblasts from peroxisome-deficient (Zellweger's syndrome) patients. Radiolabelled products of the fatty acids included carbon dioxide. C14-24 saturated and mono-unsaturated fatty acids formed from released acetate either by synthesis de novo or by elongation of endogenous fatty acids, fatty acids formed by 2-6-carbon elongation of added substrates, and a number of water-soluble compounds, some of which were tentatively identified as the amino acids glutamine, glutamic acid and asparagine. The labelled amino acids were found predominantly in the culture medium. Zellweger's syndrome fibroblasts showed a marked decrease in radiolabelled carbon dioxide and water-soluble-product formation from (I-14C)-labelled arachidonic, tetracosatetraenoic and lignoceric acids but not from [I-14C]palmitic acid, and the production of radiolabelled C14-18 fatty acids was also diminished. However, the elongation of individual fatty acids was either normal or above normal. Our data support the view that the oxidation of 20:4, 24:4 and 24:0 fatty acids in cultured skin fibroblasts takes place largely in peroxisomes, and further that the acetyl-CoA released by the beta-oxidation process is available for the synthesis of fatty acids and amino acids. We speculate that the generation of C2 units used for synthesis is a major peroxisomal function and that this function is absent or greatly impaired in Zellweger's syndrome cells.

Carbon Dioxide↗