Studies on chick embryonic tibiae cultivated in a chemically defined medium.
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Biomedical subjects
Publications and source records attributed to C V Ramakrishnan.
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This report is the last of a series of nine publications from the Tuberculosis Chemotherapy Centre, Madras, concerning various aspects of an investigation of the role of ambulatory chemotherapy for pulmonary tuberculosis. It presents the attack rates of tuberculosis over a 5-year period of follow-up of close family contacts of patients, all of whom were treated for one year with isoniazid plus PAS, half (selected at random) in sanatorium and half at home. The incidence of active tuberculosis and of tuberculous infections was no greater in the contacts of patients treated at home than in the contacts of patients treated in sanatorium, either in the first year or over the subsequent four years. The major risk to the contacts resulted from exposure to the patient before diagnosis. These findings reaffirm that close family contacts of patients treated at home were at no additional risk of developing tuberculosis, provided the patients received effective chemotherapy. Finally, this study has shown that it is possible in South India to obtain extremely good co-operation from a group of families over a period of several years.
This report from the Tuberculosis Chemotherapy Centre, Madras, summarizes the progress over a 5-year period of 193 patients with newly diagnosed, sputum-positive pulmonary tuberculosis who were admitted to a concurrent comparison of home and sanatorium treatment for one year with isoniazid plus PAS. Previous reports have shown that, despite the traditional advantages of sanatorium treatment-rest, adequate diet, nursing and supervised drug-administration-the home patients responded nearly as well as the sanatorium patients in the first year; further, the relapse rates over a 2-year period of follow-up were similar. The findings in the present report are based on a 4-year period of follow-up and extend these conclusions, the relapse rates over the period being 7% for the home patients and 10% for the sanatorium patients.Patients who failed to respond to treatment in the first year and those who had a bacteriological relapse in the second or subsequent years were usually re-treated with reserve regimens, first with streptomycin plus pyrazinamide and, if this was ineffective, with cycloserine plus ethionamide. Considering the findings over the entire 5-year period, five home patients and three sanatorium patients died from non-tuberculous causes. Of the remainder, 5% of the home patients and 6% of the sanatorium patients died of tuberculosis, 4% in each series had bacteriologically active disease at five years and 90% and 89%, respectively, had bacteriologically quiescent disease at that time. These findings are very encouraging, particularly for developing countries such as India, where tuberculosis is a major problem and sanatorium beds are very few.
A previous report from the Tuberculosis Chemotherapy Centre, Madras, has shown that, if standard chemotherapy is given for one year, the response of patients treated at home in very poor environmental circumstances is nearly as good as that of those treated in sanatorium under much more favourable conditions. This paper reports on a four-year follow-up of all the patients whose disease was bacteriologically quiescent at the end of the year's treatment. During this period, all the patients were managed on a domiciliary basis; about a quarter of them received chemotherapy with isoniazid alone for two years, another quarter received the drug for one year and the rest received no specific chemotherapy. Despite adverse environmental factors (poor diet; long hours of work often involving strenuous physical activity; overcrowded living conditions; and, for the sanatorium patients, the stresses of returning suddenly to the unfavourable home environment), the great majority of patients in both series maintained quiescent disease throughout the follow-up period. Furthermore, the few patients whose disease relapsed bacteriologically were at no special dietary disadvantage in comparison with those who maintained quiescent disease throughout, nor did they show any appreciable differences in occupation, physical activity or living accommodation. These findings, together with the earlier ones, indicate that, despite adverse environmental circumstances, standard chemotherapy for an adequate period of time is sufficient in the great majority of patients for the attainment of bacteriological quiescence and its maintenance thereafter.
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Of 4,943 patients admitted to various chemotherapy studies over the past two decades at the Tuberculosis Research Centre, Madras, India, 21 were found to be repeatedly excreting mycobacteria other than Mycobacterium tuberculosis. The chest radiographic appearance of these patients was similar to that of those patients with tuberculosis. Thirteen patients yielded repeat isolates identified as photochromogens, especially those patients who had not previously had tuberculosis. Cultures from the remaining patients were positive for nonchromogens. Occupational exposure to dust was common. Follow-up studies indicated radiographic improvement in nine patients and a bacteriologic normal status in eleven. Ten patients had died. Results of antituberculosis drug regimens were variable, but response was considered unsatisfactory in nearly 50% of the patients.
Undernutrition during the suckling period imposed by maternal protein deficiency during lactation resulted in elevated inositol triphosphatase activity (units per gram of wet tissue) in the ileum and lower phytase activity in the duodenum and jejunum. Activities of inositol triphosphatase in the duodenum and jejunum and phytase in ileum were unaffected. Postweaning nutritional rehabilitation resulted in elevated specific activities of both enzymes in all segments; however, activities of whole segments were similar to the corresponding control values. Elevation of inositol triphosphatase (ileum) and decline of phytase (duodenum and jejunum) activities due to undernutrition were reversed by the administration of hydrocortisone or thyroxine during undernutrition. These results suggest that maturation of activities of inositol triphosphatase in ileum (by hydrocortisone) and phytase in all segments (by both hydrocortisone and thyroxine) is under hormonal regulation, and the effects of neonatal undernutrition may be partly due to hormonal imbalances.
OBJECTIVE: To assess the efficacy of a short course chemotherapy regimen for treating tuberculosis of the lymph nodes in children. DESIGN: Open, collaborative, outpatient clinical trial. SETTING: Outpatient department of the Tuberculosis Research Centre, paediatric surgery departments of the Institute of Child Health and Hospital for Children and the Government Stanley Hospital, Madras, South India. PATIENTS: Children aged 1-12 years with extensive, multiple site, superficial tuberculous lymphadenitis confirmed by biopsy (histopathology or culture). INTERVENTIONS: Patients were treated with a fully supervised intermittent chemotherapy regimen consisting of streptomycin, rifampicin, isoniazid, and pyrazinamide three times a week for two months followed by streptomycin and isoniazid twice a week for four months on an outpatient basis. Surgery was limited to biopsy of nodes for diagnosis and assessment. MAIN OUTCOME MEASURES: Response to chemotherapy was assessed by regression of lymph nodes and healing of sinuses and abscesses during treatment and follow up. Compliance with treatment and frequency of adverse reactions were also estimated. RESULTS: 197 Patients were admitted to the study and 168 into the analysis. The regimen was well tolerated and compliance was good with 101 (60%) patients receiving the prescribed chemotherapy within 15 days of the stipulated period of six months. Those whose chemotherapy extended beyond that period received the same total number of doses. Clinical response was favourable in most patients at the end of treatment. Sinuses and abscesses healed rapidly. Residual lymphadenopathy (exceeding 10 mm diameter) was present in 50 (30%) patients at the end of treatment; these nodes were biopsied. Fresh nodes, increase in size of nodes, and sinuses and abscesses occurred both during treatment and follow up. After 36 months of follow up after treatment only 5 (3%) patients required retreatment for tuberculosis. CONCLUSION: Tuberculous lymphadenitis in children can be successfully treated with a short course chemotherapy regimen of six months.