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Biomedical subjects

R Balasubramanian

Publications and source records attributed to R Balasubramanian.

At least 19 recordsLinked to original sources

Randomised controlled clinical trial of short course chemotherapy in abdominal tuberculosis: a five-year report.

OBJECTIVES: To assess and compare the efficacy of a 6-month short-course chemotherapy regimen (SCC) with that of a 12-month standard regimen in the treatment of abdominal tuberculosis. DESIGN AND SUBJECTS: A total of 193 adult patients with evidence of abdominal tuberculosis were randomly allocated to one of two daily regimens: 1) a 6-month SCC regimen with rifampicin, isoniazid and pyrazinamide for 2 months followed by rifampicin with isoniazid for another 4 months (6R series) and 2) and 12-month standard regimen of ethambutol and isoniazid with streptomycin supplemented for 2 weeks (12E series). Surgery was undertaken only for patients suspected to have obstruction or perforation of the intestine. RESULTS: A total of 163 (85 6R, 78 12E) patients were available for efficacy analysis after exclusion of 30 patients for various reasons. At the end of treatment clinical status was normal in 84 (99%) in 6R patients and in 73 (94%) in 12E patients. Of these, 147 patients completed follow-up for 5 years; none had relapsed requiring treatment for abdominal tuberculosis. CONCLUSION: A 6-month SCC regimen has been found to be as effective as the standard 12-month regimen in the treatment of all forms of abdominal tuberculosis.

Adolescent

Short-course chemotherapy in the treatment of Pott's paraplegia: report on five year follow-up.

OBJECTIVE: To assess the efficacy of 9-month short-course chemotherapy (SCC) and to study the pattern of neurological recovery in patients with Pott's paraplegia. DESIGN: Patients with recent onset of spastic paraplegia due to clinically and radiologically active spinal tuberculosis involving vertebral bodies of level D4-L1 were treated with streptomycin, rifampicin, isoniazid and ethambutol daily for the first 2 months, followed by rifampicin plus isoniazid twice weekly for the next 7 months. The study was conducted in 2 phases. In the first phase 10 patients were admitted to the open trial where all patients had undergone modified Hong Kong surgery in addition to chemotherapy. In the next phase 23 patients enrolled in the study were randomly allocated to receive either chemotherapy alone or surgery plus chemotherapy. All the patients were followed for 5 years from the start of treatment. A scoring system was devised to predict neurological recovery. RESULTS: In all, 33 patients were admitted and treated with SCC. Thirteen patients were allocated to the chemotherapy (CHEM) regimen; of these 3 patients had to be operated upon for clinical deterioration; the remaining 20 had surgery plus chemotherapy; 4 were excluded for various reasons, leaving 29 patients in the analysis. None relapsed requiring treatment. CONCLUSION: A combination of surgery (when indicated) and SCC of 9 months' duration is effective in the treatment of Pott's paraplegia. All patients had neurological recovery by the end of 9 months; 8 recovered with chemotherapy alone. Complete motor recovery was seen in 62% by the 3rd month and 90% by the 6th month.

Adolescent

Studies on psychopharmacological effects of Nelumbo nucifera Gaertn. rhizome extract.

Methanolic extract of rhizomes of Nelumbo nucifera (NNRE) was investigated for different psychopharmacological actions in rats and mice. The extract was found to cause reduction in spontaneous activity, decrease in exploratory behavioural pattern by the head dip and Y-maze test, reduction in muscle relaxant activity by rotarod, 30 degrees inclined screen and traction test and potentiated the pentobarbitone induced sleeping time in mice significantly.

Animals

Feasibility of involving literate tribal youths in tuberculosis case-finding in a tribal area in Tamil Nadu.

SETTING: Tribal area in South India with a population of 96,000, where the tuberculosis case-finding activity was very poor. OBJECTIVES: To investigate the feasibility of (1) involving literate (who can read and write) tribal youth volunteers for detecting cases of pulmonary tuberculosis (PT) in their respective hamlets; and (2) antituberculosis drug delivery to sputum-positive patients at their homes by village health nurses (VHNs). DESIGN: One volunteer from each of 61 hamlets was selected and trained in the detection of subjects with chest symptoms, sputum collection and transportation to the Primary Health Centre for smear examination. All smear-positive patients were treated with 2RHZ/6TH and the drugs were supplied by VHNs fortnightly at their homes. RESULTS: During a period of 1 year (1992-93), the total population screened was 9383 persons; of these 5755 were aged 15 years and above. A total of 338 symptomatic subjects were identified; 12 sputum-positive cases were detected and started on treatment. Antituberculosis drugs were supplied by VHNs to patients for the first 9 months of the study and by literate youths for the next 3 months. Spot drug checks revealed that 11 of the 12 patients were regular in drug consumption. CONCLUSION: It is feasible to train literate tribal youth volunteers within a short time to detect subjects with chest symptoms in the community and thereby cases of pulmonary tuberculosis. They can serve as an excellent model for community participation in difficult areas.

Antitubercular Agents

Cytosolic and membrane-bound chitinases of two mucoraceous fungi: a comparative study.

Chitinases isolated from membrane and cytosolic fractions of two mucoraceous fungi, Choanephora cucurbitarum and Phascolomyces articulosus, were investigated. The membrane-bound chitinase was isolated by Bio-Gel P-100 and DEAE Bio-Gel A chromatographic techniques. On SDS-PAGE the chitinase from both fungi migrated as a single band of M(r) 66 kDa. The cytosolic chitinase from the mycelial extracts of these fungi was separated by heat treatment, ammonium sulphate precipitation, and by affinity chromatography with regenerated chitin. SDS-PAGE showed two bands for each fungus with M(r) of 69.5 and 55 kDa in C. cucurbitarum and M(r) 69.5 and 53 kDa in Ph. articulosus. Chitinases, membrane bound or cytosolic, hydrolyzed regenerated chitin, colloidal chitin, glycol chitin, N,N'-diacetylchitobiose, and N,N',N"-triacetylchitotriose. Heavy metals, inhibitors, and N-acetylglucosamine inhibited chitinase activity, whereas trypsin and an acid protease enhanced its activity. Chitinase preparations showed lysozyme activity that was inhibited by histamine but not by N-acetylglucosamine. There was no N-acetylglucosamanidase activity, but beta-1,3 glucanase activity was found in cytosolic preparations only. Despite slight differences in their molecular mass, both the membrane-bound and cytosolic chitinases showed similarities in substrate utilization, response to inhibitors, and activation by trypsin and acid protease; pH and temperature optima also were similar.

Chitinases

Pharmacokinetics of oral and transdermal triprolidine.

In this open, nonrandomized, three-way crossover study, six healthy male volunteers received single doses of triprolidine (TPL) hydrochloride syrup orally (2.5 mg) and wore transdermal TPL patches (5 mg and 10 mg doses) to compare the pharmacokinetic profiles and dose tolerance of the two formulations. A washout period of at least 1 week was scheduled between the three dosing periods. Blood samples were collected at defined times, and plasma concentrations were determined using a radioimmunoassay. Maximum plasma drug concentration (Cmax) decreased from 5.6 +/- 2.9 ng/mL (mean +/- SD) with oral dosing to 2.0 +/- 1.0 ng/mL and 4.2 +/- 2.0 ng/mL following 5 mg and 10 mg transdermal doses, respectively. Time to reach peak concentration (tmax) increased from 2.0 +/- 1.2 hours with oral dosing to 12.0 +/- 5.9 and 14.3 +/- 9.9 hours following 5 mg and 10 mg transdermal doses, respectively. The differences between AUC0-alpha values with the oral syrup and the 5 mg and 10 mg transdermal doses were not significant when normalized to 2.09 mg (TPL base). The bioavailabilities of the 5 mg and 10 mg transdermal doses relative to the oral 2.09 mg doses were 0.89 +/- 0.32 and 1.04 +/- 0.33, respectively. Mild erythema and pruritus were the most common adverse effects secondary to TPL transdermal application. Drowsiness observed following oral TPL, was not evident following either transdermal dose. The results of this study, therefore, indicate that TPL can be absorbed transdermally, providing consistent plasma concentrations.

Administration, Cutaneous

Five year results of a 3-month and two 5-month regimens for the treatment of sputum-positive pulmonary tuberculosis in south India.

A controlled study of three short-course regimens was undertaken in South Indian patients with newly diagnosed, sputum-positive pulmonary tuberculosis. The patients were allocated at random to one of three regimens: a) Rifampicin, streptomycin, isoniazid and pyrazinamide daily for 3 months (R3); b) the same regimen as above but followed by streptomycin, isoniazid and pyrazinamide twice-weekly for a further period of 2 months (R5); c) the same as R5 but without rifampicin (Z5). A bacteriological relapse requiring treatment occurred by 5 years in 16.8% of 113 R3, 5.2% of 97 R5, and 20.0% of 115 Z5 patients with organisms sensitive to streptomycin and isoniazid initially. The differences in the relapse rates between the R3 and R5 regimens and the R5 and Z5 regimens were statistically significant (p less than 0.01 for both). Considering patients with organisms initially resistant to streptomycin or isoniazid or both, 7 of 52 patients (4 R3, 2 R5, 1 Z5) had a bacteriological relapse requiring retreatment.

Adolescent

Pharmacokinetics of acrivastine after oral and colonic administration.

Six healthy male volunteers participated in this randomized, crossover open-label pharmacokinetic study consisting of two dosing segments separated by a washout period of at least 5 days. During each dosing segment, each volunteer received 12 mg of acrivastine, an investigational histamine H1-receptor antagonist, in a syrup form either orally or by colonic administration in random order. After oral and colonic administration, respectively, the following mean +/- SD pharmacokinetic parameters were obtained: Cmax 179 +/- 11 and 13.8 +/- 5.2 ng/ml; tmax, 0.85 +/- 0.13 and 3.60 +/- 0.56 hr; AUC0-12 hr, 576 +/- 57 and 104 +/- 46 hr.ng/ml. Differences between the oral and colonic administration for all three parameters were statistically significant (P less than 0.001). The mean +/- SD relative bioavailability of acrivastine from colonic compared to oral dosing was 0.18 +/- 0.09. It may be concluded, therefore, that appreciable absorption of acrivastine from the colon does not take place. These results suggest that comparison of pharmacokinetic profiles of some drugs after oral and colonic administration may be a useful technique for predicting bioavailability from a sustained release oral formulation.

Administration, Oral

Treatment of pulmonary tuberculosis with short course chemotherapy in south India--5-year follow up.

A controlled clinical trial of three short-course chemotherapy regimens was undertaken in patients with newly diagnosed bacteriologically positive pulmonary tuberculosis. The patients were randomly allocated to receive one of three regimens: rifampicin, streptomycin, isoniazid and pyrazinamide daily for 2 months, followed by streptomycin, isoniazid and pyrazinamide twice weekly for 3 months (R/5) or for 5 months (R/7), or the same regimen as R/7 but without rifampicin (Z/7). A bacteriological relapse requiring retreatment occurred by 5 years in 7.1% of 126 R/5, 4.0% of 124 R/7 and 6.7% of 253 Z/7 patients with organisms initially sensitive to streptomycin and isoniazid; none of these differences is statistically significant. Of the 31 relapses, 16 occurred within 2 years of the completion of chemotherapy and the remaining 15 between 2 and 5 years. Among 65 patients with initial drug resistance to streptomycin or isoniazid or both, there were six bacteriological relapses requiring retreatment.

Adolescent

A new technique in computer modeling of molecules with transparency effect, due to partially stripped surfaces.

Conventional space filling molecular modeling in computers, using the scan method, takes considerable computer time and effort. In depicting the CPK-image on a computer screen, the hidden-point removal is the main task and on such an image, the front-line atoms hide the back-benchers and their whereabouts become completely unknown, in a given view of the picture. While in search of a simple and faster algorithm for producing surface graphics of molecules, we have developed a novel method, which is considerably faster than the conventional one and it has an interesting transparency-effect which would be useful in the various fields of molecular designs.

Algorithms

Effect of wheat bran on bowel function and fecal calcium in older adults.

Seven healthy older volunteers participated in a 33-day study consisting of three sample collection periods, a 10-day control, and two 10-day experimental periods. Subjects consumed their usual self-selected diets throughout and a daily wheat bran supplement (30 g) during the two experimental periods. Food intake was recorded daily by subjects and accuracy and completeness checked daily by personal interview. Apparent calcium absorption decreased significantly from 22.1 +/- 5.6% (mean +/- SD) during the control to 8.6 +/- 5.2% during the second bran period. The wheat bran supplement significantly increased wet and dry stool weights but had no effect on stool moisture or defecation frequency. Gastrointestinal transit time of a dose of chromium decreased significantly, from 75 +/- 33 to 54 +/- 19 hr; of a dose of polyethylene glycol insignificantly, from 98 +/- 59 to 69 +/- 46 hr. Mean recovery of 21 doses of chromium of 98.7 +/- 5.0% verified that stool collection was complete. The results suggest that the ability of wheat bran to regulate bowel function in the apparently healthy older adult may be accompanied by increased fecal calcium losses similar to what has been reported for younger adults.

Aged

Name that beat.

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Electrocardiography

Mutagenicity of benzylic acetates, sulfates and bromides of polycyclic aromatic hydrocarbons.

Studies were performed to determine the direct mutagenicity of the acetates and some bromides and sulfates of hydroxymethyl polycyclic aromatic hydrocarbons in S. typhimurium strains TA98 and TA100. Benzylic acetates, bromides and sulfates were synthesized and characterized. The compounds tested were benzyl alcohol, 5-hydroxymethylchrysene, 1-hydroxymethylpyrene, 6-hydroxymethylbenzo[a]pyrene, 6-(2-hydroxyethyl)benzo[a]pyrene, 6-hydroxymethylanthanthrene, 9-hydroxymethylanthracene, 9-hydroxymethyl-10-methylanthracene, 7-hydroxymethylbenz[a]anthracene, 7-(2-hydroxyethyl)benz[a]anthracene, 12-hydroxymethylbenz[a]anthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene, 12-hydroxymethyl-7-methylbenz[a]anthracene, 1-hydroxy-3-methylcholanthrene, 2-hydroxy-3-methylcholanthrene, 3-hydroxy-3, 4-dihydrocyclopental[cd]pyrene and 4-hydroxy-3, 4-dihydrocyclopental[cd]pyrene. The benzylic sulfate esters of 6-hydroxymethylbenzo[a]pyrene and 7-hydroxymethylbenz[a]anthracene were the most mutagenic compounds, whereas the aliphatic sulfate ester of 7-hydroxyethylbenz[a]anthracene did not cause an increase in mutations above background. All meso-anthracenic benzylic acetate esters were mutagenic in both strains with various degrees of activity, whereas the corresponding non-benzylic esters were inactive, as expected. Of the non-meso-benzylic acetate esters, only the 3-acetoxy-3, 4-dihydrocyclopenta[cd]pyrene was mutagenic. In the benzylic bromide series, only the eight mesoanthracenic were mutagenic, whereas benzyl bromide and 5-bromomethylchrysene were inactive. The aliphatic bromides, 6-(2-bromoethyl)benzo[a]pyrene and 7-(2-bromoethyl)benz[a]anthracene did not display significant activity. The potencies of the acetate esters more accurately reflect the mutagenicity because the rate of solvolysis did not compete with the reactivity of the esters with bacterial DNA. In the case of benzylic sulfates and bromides, the rate of solvolysis was very rapid and could have diminished the level of mutagenicity, depending on the assay conditions. These results demonstrate that meso-anthracenic benzylic acetates, sulfates and bromides are mutagenic, whereas benzylic acetate esters attached to other carbon atoms are inactive.

Acetates

Determining compliance with a dietary fiber supplement.

The purpose of this pilot study was to evaluate possible ways to determine compliance with a dietary fiber supplement. A wheat bran supplement (30 g daily) significantly increased mean daily wet and dry stool weights (SW) in 7 adults, when compared to SW during an ad libitum low-fiber diet (paired t-test, P less than .01). Because unpaired data would be used during a clinical trial, distribution of the 7 ad libitum low-fiber mean SW observations was used to establish a reference distribution and an upper confidence limit against which the bran supplement SW could be compared. Only one of the seven bran supplement mean SW was above the confidence limit of the low-fiber period, independent of the number of days of collection (2-10) used to calculate the individual mean daily SW. Total fecal output over varying periods of time (2-10 days) suffered the same intersubject and intrasubject variability. Most (5-6) of the bran mean daily SW were above the group mean SW of the low-fiber period. However, this dose of bran was large enough to significantly decrease calcium absorption, and differences in SW produced by lower doses of wheat bran would probably not be as great. The bulk (greater than or equal to 80%) of a single dose of a fecal marker, chromium sesquioxide, which could be incorporated into a specific day's fiber supplement, was recovered in 5 days of excretion during the control period and in 4 days during the bran period. However, the blue color of the chromium before ingestion is clearly a negative feature. Another marker, polyethylene glycol, could not be recovered in excreta when transient time was 4 days or more. In a separate study, demonstration of very little overlap in the concentration of fecal neutral detergent fiber between the control and bran periods suggests that fecal fiber may be a marker of compliance with a fiber supplement.

Aged

Origins of life: conformational energy calculations on primitive tRNA nestling an amino acid.

We report conformational energy calculations on our proposal of a molecular interaction theory for the origin of the nucleic acid-directed, adaptor-mediated synthesis of proteins that links the phenomena of chemical and biological evolution. A particular conformation of a pentanucleotide turns out to be a double-sided template for a primitive decoding system. It is able to neatly nestle an amino acid via hydrogen bonds, and this complex is found to be an energetically favourable conformation. The total potential energy of the complex is calculated using semi-empirical potential energy functions. A local-minimum conformation is obtained and its features are reported. The template conformation of the pentanucleotide is found to have an energy value far lower than a regular helical conformation. When the amino acid is nestled in the cleft of the template-conformation through specific hydrogen bonds, the energy is further lowered. A D-amino acid nestled into the PIT (Primitive tRNA) is found to be less stable than its L counterpart, as revealed by energy calculations.

Amino Acids

Suppressed proliferation of lymphatic tissue in diabetic and adrenalectomized-diabetic rats.

One week following induction of diabetes in rats by alloxan administration, the thymus and spleen showed marked involution and a highly significant depression of in vivo incorporation of [3H]deoxycytidine into the DNA of these tissues. Adrenalectomy of diabetic rats reduced the decline of lymphatic tissue weight, but uptake of [3H]deoxycytidine into thymic and spleen DNA remained suppressed. These results indicate that in alloxan-induced diabetes, the observed depressed lymphatic tissue weight and cellular proliferation are not simply due to the elevated plasma level of corticosteroids, but are either a result of the insulin deficiency per se or due to other metabolic alterations associated with the diabetic condition.

Adrenal Glands