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Biomedical subjects

R Balasubramanian

Publications and source records attributed to R Balasubramanian.

At least 37 records · Page 2Linked to original sources

Management of non-pulmonary forms of tuberculosis: review of TRC studies over two decades.

Tuberculosis Research Centre, Chennai has been conducting randomized controlled clinical trials in both adults and children (n = 1015) in various non-pulmonary forms of tuberculosis, for the last two decades. This communication discusses the salient findings of these studies. The important finding is that short course chemotherapeutic regimens have been proven to be highly effective in tuberculosis of spine, superficial tuberculous lymphadenitis, abdominal tuberculosis, brain tuberculoma and Pott's paraplegia. However, in tuberculous meningitis, the outcome appears to be directly related to the stage of the disease on admission. The intermittent regimens have been found to be as effective as daily regimens. The other important aspects highlighted are the need to obtain bacteriological/histo-pathological confirmation by resorting to relevant diagnostic procedures, value of Mantoux as a diagnostic tool and role of surgery.

Adult↗

Oral progestogen combined with testosterone as a potential male contraceptive: additive effects between desogestrel and testosterone enanthate in suppression of spermatogenesis, pituitary-testicular axis, and lipid metabolism.

The effects of a synthetic oral progestogen, desogestrel (DSG), administered with low dose testosterone (T) were investigated to determine the optimal combination for suppression of gonadotropins and spermatogenesis to targets compatible with effective male contraception. Twenty-four healthy male volunteers (33.2 +/- 0.9 yr) were randomly assigned to 3 groups (n = 8) to receive: 1) 300 microg DSG orally daily and 100 mg T enanthate, i.m., weekly; 2) 300 microg DSG and 50 mg T enanthate; or 3) 150 microg DSG and 100 mg T enanthate for 24 weeks. To investigate the individual contribution to the combined action, DSG was administered alone for the first 3 weeks, and T enanthate was added on day 22. After 24-week treatment, sperm density in 78% (18 of 23) of the subjects became azoospermic, whereas 91.7% (22 of 24) and 95.8% (23 of 24) suppressed to less than 1 million/mL and less than 3 million/mL, respectively. The 300 microg DSG with 50 mg T enanthate combination induced azoospermia in 8 of 8 subjects, and the suppression of sperm density was significantly greater than that in the 300 microg DSG/100 mg T enanthate group, but was not different from that in the 150 microg DSG/100 mg T enanthate group. DSG (300 or 150 microg daily) alone in the first 3 weeks suppressed LH, FSH, and T to 60.6%, 48.0%, and 35.4%, respectively, of the baseline. Addition of T enanthate (50 and 100 mg weekly) raised plasma T to the physiological range and induced a further fall in LH and FSH to the limits of assay detection. There was no consistent difference in mean LH and FSH levels among the three groups during treatment or recovery, except that FSH remained detectable in a higher proportion of samples from the group receiving 300 microg DSG with 50 mg T enanthate. Total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol decreased by 9.3 +/- 1.7%, 10.3 +/- 2.6%, and 7.7 +/- 2.8%, respectively, during treatment with DSG alone with no difference between 300 and 150 microg. Addition of T enanthate (both 50 and 100 mg weekly) induced a further fall only in high density lipoprotein cholesterol to 22.6 +/- 3.7% from the baseline. In summary, the combined actions of oral DSG with low doses of T enanthate were highly effective in suppressing pituitary-testicular functions in adult men. The optimal regimen for inducing azoospermia was 300 microg DSG daily with 50 mg T enanthate weekly. Oral DSG exerted discernible effects on lipid metabolism. We conclude that the combination of oral progestogens with low dose T is a promising approach to achieve effective reversible male contraception.

Administration, Oral↗

Socio-economic impact of tuberculosis on patients and family in India.

OBJECTIVE: To quantify the socio-economic impact of tuberculosis on patients and their families from the costs incurred by patients in rural and urban areas. DESIGN: An interview schedule prepared from 17 focus group discussions was used to collect socio-economic demographic characteristics, employment, income particulars, expenditure on illness and effects on children from newly detected sputum-positive pulmonary tuberculosis patients. The direct and indirect costs included money spent on diagnosis, drugs, investigations, travel and loss of wages. Total costs were projected for the entire 6 months of treatment. RESULTS: The study population consisted of 304 patients (government health care 202, non governmental organisation 77, private practitioner 25), 120 of whom were females. Mean direct cost was Rs.2052/-, indirect Rs.3934/-, and total cost was Rs.5986/- ($171 US). The mean number of work days lost was 83 and mean debts totalled Rs.2079/-. Both rural and urban female patients faced rejection by their families (15%). Eleven per cent of schoolchildren discontinued their studies; an additional 8% took up employment to support their family. CONCLUSIONS: The total costs, and particularly indirect costs due to TB, were relatively high. The average period of loss of wages was 3 months. Care giving activities of female patients decreased significantly, and a fifth of schoolchildren discontinued their studies.

Absenteeism↗

Hydrolysis of surfactant-associated phosphatidylcholine by mammalian secretory phospholipases A2.

Hydrolysis of surfactant-associated phospholipids by secretory phospholipases A2 is an important potential mechanism for surfactant dysfunction in inflammatory lung diseases. In these conditions, airway secretory phospholipase A2 (sPLA2) activity is increased, but the type of sPLA2 and its impact on surfactant function are not well understood. We examined in vitro the effect of multiple secretory phospholipases A2 on surfactant, including their ability to 1) release free fatty acids, 2) release lysophospholipids, and 3) increase the minimum surface tension (gammamin) on a pulsating bubble surfactometer. Natural porcine surfactant and Survanta were exposed to mammalian group I (recombinant porcine pancreatic) and group II (recombinant human) secretory phospholipases A2. Our results demonstrate that mammalian group I sPLA2 hydrolyzes phosphatidylcholine (PC), producing free fatty acids and lysophosphatidylcholine, and increases gammamin. In contrast, mammalian group II sPLA2 demonstrates limited hydrolysis of PC and does not increase gammamin. Group I and group II secretory phospholipases A2 from snake venom hydrolyze PC and inhibit surfactant function. In summary, mammalian secretory phospholipases A2 from groups I and II differ significantly from each other and from snake venom in their ability to hydrolyze surfactant-associated PC.

Animals↗

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↗