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Biomedical subjects

R Singh

Publications and source records attributed to R Singh.

At least 19 recordsLinked to original sources

Potential anti-AIDS naphthalenesulfonic acid derivatives. Synthesis and inhibition of HIV-1 induced cytopathogenesis and HIV-1 and HIV-2 reverse transcriptase activities.

Several naphthalenedi- and trisulfonic acids have been synthesized and evaluated for inhibitory potential against cytopathogenesis and purified recombinant human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) reverse transcriptase (RT). The most potent derivative that emerged from the anti-RT study was a small molecule 6 (MW = 840), a dipalmitoylated derivative of 2,7-naphthalenedisulfonic acid. Analog 6 demonstrated 50% inhibitory concentration (IC50) values of 2.42 and 0.86 microM for HIV-1 and HIV-2 RT, respectively. The second most active compound was also a derivative of the same naphthalenedisulfonic acid but contained only one palmitoyl moiety. This compound 9 displayed IC50 values of 4.8 and 3.7 microM for HIV-1 and HIV-2 RT, respectively. Both analogs 6 and 9 are active at noncytotoxic doses, exhibit slightly higher potencies for the RT of HIV-2 over HIV-1, and demonstrate activities superior to the hexasulfonic acid derivative suramin (IC50 values of 9.4 and 15.5 microM for HIV-1 and HIV-2 RT, respectively). In the cytopathogenesis assay, the most active compound is a bis naphthalenedisulfonic acid derivative 17, containing a flexible octamethylene spacer and exhibiting an in vitro therapeutic index of 29.7. Most striking, however, is the influence of the palmitoyl functionality in the naphthalenedisulfonic acid series to confer activity against both HIV-1 and HIV-2 RT.

Enzyme Inhibitors

Effects of guava intake on serum total and high-density lipoprotein cholesterol levels and on systemic blood pressure.

There is evidence that inclusion of high fiber foods such as oats, fruits and vegetables in the diet can decrease fat intake and modulate blood lipids. To test this hypothesis, 61 group A and 59 group B patients with essential hypertension were administered guava fruit preferably before meals in a foods-to-eat approach rather than foods-to-restrict, in a randomized and single-blind fashion for 12 weeks. At entry into the study, mean age, male sex, mean body mass index, percentages of risk factors and mean levels of blood lipids were comparable between groups A and B. Adherence to guava consumption was assessed by questionnaires and weighing of guava intake by 24-hour recall after 12 weeks of follow-up. Nutrient intakes including saturated and total fat were significantly decreased; carbohydrates, total and soluble fiber and vitamins and mineral intakes were significantly higher in group A than in group B at 12 weeks. There was a significant net decrease in serum total cholesterol (9.9%), triglycerides (7.7%) and blood pressures (9.0/8.0 mm Hg) with a significant net increase in high-density lipoprotein cholesterol (8.0%) after 12 weeks of guava fruit substitution in group A than in group B. By adding moderate amounts of guava fruit in the usual diet, changes in dietary fatty acids and carbohydrates may occur, providing significant amounts of soluble dietary fiber and antioxidant vitamins and minerals without any adverse effects. There is a greater decrease in lipoprotein metabolism and blood pressures.

Blood Pressure

Effect of fat-modified and fruit- and vegetable-enriched diets on blood lipids in the Indian Diet Heart Study.

This study was designed to test the efficacy of the administration of fruits and vegetables for 12 weeks as an adjunct to a prudent diet in decreasing blood lipids in 310 (intervention; group A) and 311 (control; group B) patients with risk factors of coronary artery disease (CAD) in a parallel, single-blind fashion. At entry to the study, sex, mean age, body weight, body mass index, systolic and diastolic blood pressures, and blood lipoproteins were comparable between both groups. Tasty fruits and vegetables were given to patients to eat before major meals for better nutrient adherence and adequacy. Dietary intakes were determined by questionnaires and by weighing of fruit and vegetable intake. Fruits and vegetables decreased total cholesterol level by 6.5% and low-density lipoprotein cholesterol level by 7.3% in group A, whereas the levels were unchanged in group B. The high-density lipoprotein cholesterol levels that decreased during the diet stabilization period in both groups, increased by 5.6% in group A after 12 weeks. Serum triglycerides also decreased (7%) more in group A than B. Fasting blood glucose decreased by 6.9% in group A and by 2.6% in group B. The combined effect of a fat-modified diet plus fruits and vegetables was greater than these changes. Because tasty fruits were taken by the patients before meals (when they are hungry) and are easily available at reasonable cost in our marketing and buying capacity, the compliance was excellent.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose

Randomised controlled trial of cardioprotective diet in patients with recent acute myocardial infarction: results of one year follow up.

OBJECTIVE: To test whether a fat reduced diet rich in soluble dietary fibre, antioxidant vitamins, and minerals reduces complications and mortality after acute myocardial infarction. DESIGN: Randomised, single blind, controlled trial. SETTING: Primary and secondary care research centre for patients with myocardial infarction. SUBJECTS: 505 patients with suspected acute myocardial infarction. Those with definite or possible acute myocardial infarction and unstable angina based on World Health Organisation criteria were assigned to diet A (n = 204) or diet B (n = 202) within 24-48 hours of infarction. INTERVENTIONS: Both groups were advised to follow a fat reduced diet. Group A was also advised to eat more fruit, vegetables, nuts, and grain products. MAIN OUTCOME MEASURES: Mortality from cardiac disease and other causes. Serum lipid concentrations and compliance with diet. RESULTS: Blood lipoprotein concentrations and body weight fell significantly in patients in group A compared with those in group B (cholesterol fell by 0.74 mmol/l in group A v 0.32 mmol/l in group B, 95% confidence interval of difference 0.14 to 0.70, and weight by 7.1 v 3.0 kg, 0.52 to 7.68). The incidence of cardiac events was significantly lower in group A than group B (50 v 82 patients, p less than 0.001). Group A also had lower total mortality (21 v 38 died, p less than 0.01) than group B. CONCLUSIONS: Comprehensive dietary changes in conjunction with weight loss immediately after acute myocardial infarction may modulate blood lipoproteins and significantly reduce complications and mortality after one year.

Adult

An Indian experiment with nutritional modulation in acute myocardial infarction.

In a randomized, single-blind intervention trial, 406 patients 24 to 48 hours after acute myocardial infarction (AMI) were assigned to either diet A (204 patients, group A) or B (202 patients, group B) for 6 weeks. At entry to the study, mean age, male sex, risk factors, complications, possible and definite AMI, and drug therapy were comparable between the 2 groups. Dietary adherence to intervention and control diets was checked by questionnaire, and drug therapy by tablet count. Group A received significantly lower calories, a higher percentage of calories from complex carbohydrates, vegetable/fish proteins, polyunsaturated fatty acids, and a higher polyunsaturated/saturated fat ratio diet than did group B (higher total calories and saturated fatty acids). Group A also received less dietary cholesterol, salt and caffeine, and higher soluble dietary fiber, vitamins and minerals than did group B. After 6 weeks, group A had a significant decrease in mean serum total (-20.5 vs -8.6 mg/dl) and low-density lipoprotein (-16.6 vs -6.4 mg/dl) cholesterols, and triglycerides (-15.5 vs -7.6 mg/dl), with no decrease in high-density lipoprotein cholesterol (-1.5 vs -1.3 mg/dl) compared with the initial levels and changes in group B. Group A also had a greater decrease in mean body weight (3.4 vs 1.3 kg) than that of group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Increased CSF HVA response to arecoline challenge in Alzheimer's disease.

The effects of the muscarinic agonist, arecoline, on the concentration of homovanillic acid (HVA) in the cerebrospinal fluid of patients with Alzheimer's disease (AD) and controls were examined. Patients and controls received intravenous infusions of arecoline and a lumbar puncture was performed four hours after the infusion began. Arecoline induced a significant increase in the concentration of HVA in cerebrospinal fluid of Alzheimer's disease patients (p < .01) but not in controls. The differential HVA response to a muscarinic agonist in Alzheimer's disease is suggestive of an alteration in muscarinic receptor response. This finding may have potential implications for the pathophysiology and treatment of Alzheimer's disease.

Aged

Serum phospholipase A2 enzyme activity and immunoreactivity in a prospective analysis of patients with septic shock.

Massive elevations of serum phospholipase A2 activity have been documented in patients with septic shock. Serum PLA2 activity correlated to the degree and duration of circulatory collapse, while purified native PLA2 reproduced hypotension in experimental animals. In a prospective study of patients with septic shock, we have determined the relationship of PLA2 enzyme activity to PLA2 immunoreactivity using radiolabelled E. coli phospholipid substrate and an ELISA specific for group II human nonpancreatic PLA2. In all patients, there was a clear concordance of the two assays. Maximal PLA2 concentration was increased a mean of 554-fold over normal levels. We found no evidence to support the presence of activating or inhibitory proteins. These data confirm that the observed increase in serum PLA2 activity in septic shock is due to intravascular release of group II nonpancreatic PLA2.

Antibodies, Monoclonal

Long-term results of transplantations to repair median, ulnar, and radial nerve lesions by a microsurgical interfascicular autogenous cable graft technique.

A comprehensive analysis of 187 patients (78 median, 86 ulnar, and 23 radial nerve lesions) treated by an interfascicular autogenous nerve grafting technique is presented. After a follow-up of at least 18 months good motor recovery was achieved in 72% of median nerve lesions, 77% of ulnar nerve lesions, and 57% of radial nerve lesions. Good functional sensory recovery was found in 36% of median, 45% of ulnar, and 48% of radial nerve lesions. It appears by multivariate analysis that the results obtained generally were better in younger patients, in patients with a shorter preoperative delay, and in cases with a shorter transplant.

Adolescent

Methylated cap structures in eukaryotic RNAs: structure, synthesis and functions.

There are more than twenty capped small nuclear RNAs characterized in eukaryotic cells. All the capped RNAs appear to be involved in the processing of other nuclear premessenger or preribosomal RNAs. These RNAs contain either trimethylguanosine (TMG) cap structure or methylated gamma phosphate (Mppp) cap structure. The TMG capped RNAs are capped with M7G during transcription by RNA polymerase II and trimethylated further post-transcriptionally. The Mppp-capped RNAs are transcribed by RNA polymerase III and also capped post-transcriptionally. The cap structures improve the stability of the RNAs and in some cases TMG cap is required for transport of the ribonucleoproteins from cytoplasm to the nucleus. Where tested, the cap structures were not essential for their function in processing other RNAs.

Animals

Nutritional modulators of lipoprotein metabolism in patients with risk factors for coronary heart disease: diet and moderate exercise trial.

To study the role of diet as a risk factor for coronary heart disease (CHD), 463 adults (25-65 years, 419 males) at risk of or with CHD were assigned to group A (n = 231) receiving a cardiovasoprotective diet or group B (n = 232) receiving a normal diet in a randomized, single-blind fashion. Age, sex, risk factors and incidence of CHD were comparable between the two groups. Group A received a significantly higher percentage of calories in relation to complex carbohydrates, vegetable proteins, polyunsaturated fatty acids, and had a higher polyunsaturated:saturated fatty acid (P:S) ratio compared to control group B, which received more saturated fat and cholesterol. Group A also received more soluble dietary fiber and magnesium (Mg) and was physically more active than group B. Exercise and dietary adherence were tested by a questionnaire. After 12 weeks, results indicated a significant decrease in mean serum total cholesterol (9.0 vs 3.1%), low-density-lipoprotein cholesterol (LDL-C) (9.8 vs 3.8%) and triglyceride (11.1 vs 5.4%), and an increase in serum Mg (8.5%) in the intervention group compared to initial levels. No significant changes in mean levels were noted in the control group. Body weight significantly decreased and physical activity was significantly higher in the intervention group compared to the control group during the 12-week followup on similar intakes of energy. There were insignificant changes in high-density-lipoprotein cholesterol (HDL-C) in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Is a full team required for emergency management of pediatric trauma?

Pediatric trauma centers often do not meet the guidelines requiring a trauma team as recommended by the American Academy of Pediatrics (AAP). We reviewed our experience with a team consisting of a pediatric emergency physician, resident, nurse, and respiratory therapist. The surgical and pediatric critical care residents and staff were available within 5 minutes. We conducted a retrospective chart review of 146 patients (aged 8.1 +/- 4.8 years) between 1987 and 1989, with Injury Severity Scores (ISS) greater than or equal to 16 or admitted to the pediatric critical care unit. The time of presentation, surgical services consulted, and the nature of the injury were obtained from chart review. The Pediatric Trauma Score (PTS), the Revised Trauma Score (RTS), the Injury Severity Score (ISS), Glasgow Coma Scale (GCS) score, and Pediatric Risk of Mortality (PRISM) were used to determine the severity of insult and physiologic derangement on admission. The Modified Injury Severity Score (MISS) was determined and the Delta score for Disability Assessment was assigned at discharge. The Delta score was also determined at 3-month intervals up to one year. The probability of survival (Ps) was calculated, using the ISS and RTS. The Z statistic for this group of patients was then determined, using the Major Trauma Outcome Study (MTOS) methodology. The percentages of patients who were normal, disabled, and dead were 61%, 31.5%, and 7.5%, respectively, at 6 months follow-up. Eleven deaths were expected based on PRISM and TRISS analysis. Our mortality and morbidity figures were comparable with those of centers with teams based on AAP guidelines.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Effects of maturation and aging on the skeletal muscle glucose transport system.

Insulin resistance in old, compared with young, humans and animals has been well documented. The resistance is due primarily to defects in skeletal muscle. In the present study, skeletal muscle sarcolemmal membranes were purified from five age groups of female Fischer rats ranging from 2 to 24 mo. Basal specific D-glucose transport was not significantly different among any of the groups. Maximum insulin-stimulated transport was progressively decreased from 96.4 +/- 5.0 pmol.mg-1.15 s-1 in the 2-mo-old animals to 70.8 +/- 8.9 pmol.mg-1.15 s-1 in the 24-mo-old animals. Most of the decrease occurred during maturation, and in fact there was no significant difference in maximum transport among the 8-, 16-, and 24-mo-old rats. The decrease in insulin-stimulated transport in the 24-mo-old animals was due to a reduction in the number of glucose transporters translocated into the sarcolemma membrane (9.8 +/- 0.6 vs. 7.8 +/- 0.6 pmol/mg protein). The intracellular or microsomal pool of glucose transporters was not significantly different between the 2- and 24-mo-old animals (8.8 +/- 0.6 vs. 8.5 +/- 0.9/mg protein). Western blotting revealed no differences in the cellular GLUT-4 contents between the 2- and 24-mo-old rats. The number of insulin receptors (2.3 +/- 0.4 vs. 2.1 +/- 0.5 pmol/mg protein) was not significantly different. Tyrosine kinase activity of the insulin receptor was, however, significantly reduced in the 24-mo-old compared with the 2-mo-old animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Effects on serum lipids of adding fruits and vegetables to prudent diet in the Indian Experiment of Infarct Survival (IEIS).

In a randomized, single-blind and controlled trial, the effects of the administration of fruits and vegetables (mean 582 vs. 188 g/day) for 12 weeks were compared as adjuncts to a prudent diet in the management of 202 group A and 204 group B patients with acute myocardial infarction (AMI). Fruits and vegetables decreased total serum cholesterol level (26.4 vs. 13.8 mg/dl, p less than 0.01) low-density lipoprotein cholesterol (20.0 vs. 9.8 mg/dl, p less than 0.01), triglycerides (20.6 vs. 10.6 mg/dl, p less than 0.01) and fasting blood glucose (22.4 vs. 12.6 mg/dl, p less than 0.01) levels more significant in the intervention group than changes in the control group. Adherence to dietary advice was assessed by questionnaires. Total adherence score in group A was significantly higher than in group B. Group A patients also had a significantly smaller rise in lactate dehydrogenase cardiac enzyme which indicates that the protective effects of such a diet may be observed within 1 week. There was a significantly greater decrease in mean blood pressure in group A than changes in group B. These data suggest that fruits and vegetables, because of their high soluble dietary fibre and possibly high antioxidant contents, may be a useful and safe adjunct to a prudent diet in the treatment of patients with AMI. The use of fruits and vegetables may be preferred over oat bran, psyllium and guar gum because of their high content of vitamins and minerals.

Cholesterol

Influence of milk factors on riboflavin uptake by rat intestinal everted sac.

The uptake of riboflavin was measured in Krebs' medium and a system consisting of riboflavin-free dialyzed milk (providing milk factors) equalized to Krebs' medium with respect to different salt concentration and pH. The final riboflavin concentration in the medium ranged between 0.1 and 0.5 microM. Total riboflavin incorporation was greater in the milk system and the increase ranged between 120 and 134% in comparison with Krebs' medium (100%). The Michaelis-Menten constant (Km) and Vmax for labelled riboflavin uptake were calculated by Lineweaver-Burk plotting of data. Km value decreased from 1.23 microM for Krebs' medium to 0.75 microM in the presence of milk factor(s). Vmax values were 62 and 60 pmol/100 mg tissue/min for Krebs' and milk systems, respectively. It was concluded that milk factor(s) enhanced intestinal uptake of riboflavin.

Animals

Glutamate and other CSF amino acids in Alzheimer's disease.

The authors compared CSF amino acid levels of 10 patients with mild to moderate dementia and probable Alzheimer's disease who had never received antidepressant or neuroleptic medication with those of 10 normal subjects of similar age. The Alzheimer's patients had significantly higher levels of CSF glutamate. This finding was not related to age, sex, or severity of dementia. Elevated CSF glutamate may reflect greater glutamatergic activity early in the course of Alzheimer's disease. The authors speculate that the excitotoxic effects of glutamate may contribute to progressive neuronal loss in Alzheimer's disease.

Age Factors

Nasopharyngeal presentation of pituitary tumors. Differential diagnosis and treatment.

The intranasal presentation of pituitary tumors is rare. We describe six patients with supposedly intranasal carcinomas, treated by surgery, local chemotherapy, and/or radiotherapy. Because of the favorable clinical course, immunohistochemical reexamination of tumor tissue was done, which showed a macroprolactinoma in four and a nonfunctioning pituitary adenoma in two patients. Interestingly, anterior pituitary function was normal in four and only slightly disturbed in two of them. The radiological appearance of the sellar region was completely normal in two patients. Routine immuno-histochemistry would have prevented inappropriately aggressive therapy. Dopamine agonist therapy was effective in the four macroprolactinoma patients, but the nasopharyngeal localization of the tumor seems to increase the risk of rhinorrhea and/or meningitis.

Adenoma

Forced vital capacity in Malaysian females.

Spirometry was performed on 614 female subjects ranging in age from 13 to 69 years and comprising all the main races in Malaysia. They were divided into six age categories. Mean forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were 2.51 +/- 0.02 and 2.31 +/- 0.02l, respectively. Both FVC and FEV1 correlated negatively with age. Regression analysis revealed an age-related decline in FVC of 220 ml per decade of life. Multiple stepwise regression of the data for the prediction of an individual's FVC above the age of 20 years gave an equation: FVC(l) = 0.0312 (height)-0.022 (age)-1.64. Predicted FVC values derived from equations based on other populations were considerably higher than the observed mean in this study. Our study, therefore, reemphasizes the need to be cautious when applying formulae derived from one population to another. Grossly erroneous conclusions may be reached unless predicted equations for lung-function tests for a given population group are derived from studies based on the same population group.

Adolescent

A comparative study of bronchodilator actions of ipratropium bromide (atrovent) & salbutamol (ventolin) on exercise induced bronchial asthma.

The bronchodilator actions of salbutamol and ipratropium bromide were compared in 30 established cases of bronchial asthma, before and after exercise. It was noticed that after exercise (brisk walk for 3 min.) the PFT values of FVC, PEFR and FEV-1, decreased remarkably from the basal values, the mean fall of 17.91%, 10.68% & 14.8% respectively was noticed. Salbutamol showed improvement in FVC, PEFR, FEV-1, of 20.86%, 15.96% & 17.98% respectively from basal values, while Ipratropium bromide showed improvement by 18.31%, 13.01% & 20.90% respectively. It was also noted that salbutamol is a better drug amongst smokers, patients with family history of bronchial asthma, and in younger age groups. Ipratropium bromide was better in elderly patients (> 40 yrs.) and in those with eosinophillia.

Adult