Biomedical subjects
Publications and source records attributed to S RADHAKRISHNA.
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A controlled comparison by the Tuberculosis Chemotherapy Centre, Madras, of the merits of home as compared with sanatorium treatment for pulmonary tuberculosis showed that, at the end of a year of chemotherapy with isoniazid plus p-aminosalicylic acid (PAS), the response of the home patients closely approached that of the sanatorium patients. The present report reviews the progress of those patients in the controlled comparison whose disease had attained bacteriological quiescence by the end of the year of combined chemotherapy. During the second year, half of the patients received further chemotherapy, with isoniazid alone, and half received a placebo, calcium gluconate. During the third year, half of those who were treated with isoniazid in the second year and whose disease remained quiescent continued to receive that drug and all the remaining patients with quiescent disease received the placebo. In the second and third years all the patients were treated at home and administered the medicaments to themselves.It has been concluded from this follow-up study that in the second and third years there was relatively little difference between the progress of the patients whose disease attained quiescence following a year of domiciliary treatment with isoniazid plus PAS and that of those whose disease attained quiescence following a year's treatment with the same drugs in sanatorium; that a second or third year of further treatment with isoniazid alone gave no better results than a year of combined chemotherapy, followed by careful observation of the patient and further chemotherapy if relapse occurred; and that the relapse rate among the patients with residual cavitation at the end of the year of combined chemotherapy was slightly higher than that among the patients with no residual cavitation at the end of the first year.
The authors present a second report from the Tuberculosis Chemotherapy Centre, Madras, on the incidence of tuberculosis in close family contacts of tuberculous patients. The patients initially received a year's chemotherapy either at home or in sanatorium in a controlled comparison of the merits of domiciliary as opposed to institutional treatment. The first report presented data relating to the prevalence and the attack rate of tuberculosis among the contacts during the first year of treatment of the index cases; this second report presents the attack rate for the 2-year period since the start of treatment for the index cases. During the second year all the index cases were managed at home, those with active disease, and half of those with quiescent disease, at the end of the first year receiving further chemotherapy. The findings of the 2-year study confirm those of the earlier study-namely, that the incidence of tuberculosis in the contacts of patients originally treated at home was no greater than that in the contacts of patients originally treated in sanatorium and that the major risk to the contacts resulted from exposure to the patient before diagnosis. As in the earlier report, the question of instituting chemoprophylaxis for the young contacts of tuberculous patients is discussed. The authors consider that close family contacts living in over-crowded, urban conditions in the developing countries are valuable groups for chemoprophylactic investigations.
This study from the Tuberculosis Chemotherapy Centre, Madras, compares patients infected with isoniazid-resistant tubercle bacilli ("R" patients) with those infected with isoniazid-sensitive tubercle bacilli ("S" patients) as regards, first, their pretreatment status and, secondly, their response to a year's chemotherapy, either with isoniazid plus p-aminosalicylic acid (PAS) or with isoniazid alone. With regard to the first comparison, there was, on admission to treatment, little difference between the R and S patients in terms of the extent of the radiographic lesion, the extent of cavitation or the bacterial content of the sputum, but there were major differences in the age and sex distributions, the R patients showing a greater preponderance of young males than the S patients. As to the second comparison, statistically significant differences in the bacteriological response to treatment of the S and the R patients were observed in both the isoniazid-plus-PAS and the isoniazid-alone series, the response of the S patients being much better than that of the R patients. When the response to treatment was assessed in terms of radiographic progress and weight changes, however, hardly any difference was observed between the progress of the S and the R patients. The reasons for the response in the R patients are discussed.
Since isoniazid is metabolized in man to several derivatives with little or no specific activity against the tubercle bacillus, its rate of inactivation in the body may have an important bearing on its efficacy as an antituberculosis drug. The inactivation rate, though constant in any one person, is known to vary from individual to individual and from race to race. A series of studies on the rate of inactivation of isoniazid in Indian patients with pulmonary tuberculosis has recently been undertaken at the Tuberculosis Chemotherapy Centre, Madras. The present paper describes the first of these studies, in which the concentration of isoniazid in the serum of patients admitted to a controlled comparison of four domiciliary chemotherapeutic regimens was determined by microbiological assay four-and-a-half hours after administration of a standard dose of isoniazid (3 mg/kg body-weight). Patients with serum levels of 0.58 mug/ml or more were classified as slow inactivators of isoniazid and those with levels below 0.58 mug/ml as rapid inactivators. By this definition, 195 (61%) of the 321 patients studied were found to be slow inactivators and 126 (39%) rapid inactivators. A relationship was shown between sex and the rate of inactivation, there being a significantly higher proportion of rapid inactivators among the females than among the males. The observed estimates of the error of the microbiological assay procedure are discussed and possible ways of reducing the error suggested.
In order to find out whether chemotherapy with isoniazid affects the virulence in the guinea-pig of tubercle bacilli that do not develop resistance to the drug, virulence tests were carried out on isoniazid-sensitive cultures obtained from 20 South Indian tuberculous patients before treatment and after three months of chemotherapy with isoniazid. No significant difference in virulence was observed between the cultures obtained on admission to treatment and those obtained after three months of chemotherapy. This is a finding with important implications for large-scale surveys of the distribution of attenuated strains of tubercle bacilli from untreated patients in India and other countries. Detailed and repeated inquiries as to previous chemotherapy are not important in such surveys, provided that sensitivity tests are done on all the cultures.
The authors present a report from the Tuberculosis Chemotherapy Centre, Madras, on the prevalence and attack rate of tuberculosis among close family contacts of tuberculous patients in South India undergoing domiciliary chemotherapy either with isoniazid plus PAS or with one of three regimens of isoniazid alone. The report gives (a) the prevalence of tuberculosis among the contacts at the time of diagnosis of the disease in the patients and (b) the incidence of tuberculosis in the contacts during the first year of treatment of the patients. The contacts were divided into four series, corresponding to the four chemotherapeutic regimens of the patients.The prevalence of active tuberculosis was found to be particularly high among children under five years of age, being 12.0% as compared with 7.6% for all age-groups combined. The incidence of active tuberculosis during the year of treatment of the patients was also found to be highest in the under five years' age-group-a further indication that child contacts are especially vulnerable to infection. The incidence was considerably higher in the first quarter of the year than in the other quarters, and it was lowest in the last quarter. This finding, together with the fact that the attack rates in the four contact series were not related either to the duration of bacteriological positivity in the patients or to the period of excretion of isoniazid-resistant organisms by the patients, suggests that the major risk to contacts in the first year results from exposure to the patient before treatment rather than from exposure during treatment. These results thus confirm the findings in an earlier study by the Centre of the contacts of patients in a controlled comparison of chemotherapy with isoniazid plus PAS at home and in sanatorium.
A series of studies on the virulence in the guinea-pig of tubercle bacilli isolated before treatment from Indian tuberculous patients admitted to a controlled comparison of different regimens of domiciliary chemotherapy has recently been undertaken by the Tuberculosis Chemotherapy Centre, Madras. The main object of these studies was to determine whether the differences in virulence of the tubercle bacilli obtained from Indian patients before the start of chemotherapy were related to the severity or type of the patients' disease at that time and to the subsequent response to treatment. Before these relationships could be investigated, however, it was necessary to find out whether the results of the virulence tests, which were carried out over a period of two-and-a-half years at the Centre and at the Microbiological Research Establishment, Porton, England, could be considered as a unified whole-that is, as if they had all been done on the same day in the same laboratory.A proportion of the cultures was stored at - 20 degrees C for 44-78 weeks, but this did not affect their virulence. Inter-experimental variation was found to be small in the Porton series of tests and undetectable in the Madras series, and the results in the latter series could be successfully adjusted to those in the former by allowing for differences in the means and standard deviations of the distributions for the two series. The measure of virulence used was found to be reasonably acceptable for the analysis of variance technique. Suggestions are made as to ways of improving the efficiency of the experimental design in future studies.
This is the last of a series of three reports from the Tuberculosis Chemotherapy Centre Madras, on a study undertaken with the object of finding out whether differences in the virulence in the guinea-pig of tubercle bacilli isolated from South Indian tuberculous patients before the start of chemotherapy are related to the severity of the patients' disease on admission to treatment and to the subsequent response to chemotherapy. The 281 patients in this study were drawn from the patients admitted to a 1-year comparison of four domiciliary chemotherapeutic regimens: (a) 3.9-5.5 mg/kg isoniazid plus 0.2-0.3 g/kg sodium PAS daily, divided into two doses (PH series); (b) 7.8-9.6 mg/kg isoniazid alone daily in one dose (HI-1 series); (c) 7.8-9.6 mg/kg isoniazid alone daily, divided into two doses (HI-2 series); (d) 3.9-5.5 mg/kg isoniazid alone daily, divided into two doses (H series).No evidence was found of an association between the virulence of the organisms and any pretreatment condition of known prognostic importance. There was no association between pretreatment virulence and progress during treatment in the PH series (the most effective regimen). In the other series, however, the progress was more satisfactory in patients infected with organisms of low virulence than in those infected with organisms of high virulence, the association between virulence and progress attaining statistical significance in the combined HI-2 and H series (the least effective regimens) and only just failing to do so in the smaller HI-1 series.Possible explanations are put forward both for the absence of an association between virulence and severity of disease on admission and for the presence of an association between virulence and response in the patients treated with isoniazid alone.
Before the advent of antituberculosis chemotherapy, a diet rich in calories, proteins, fats, minerals and vitamins was generally considered to be an important, if not essential, factor in the treatment of tuberculosis. The introduction of specific antituberculosis drugs, however, has so radically altered the management of the disease that the role of diet has to be reconsidered in the light of the recent advances in treatment. An evaluation of the influence of diet in the treatment of pulmonary tuberculosis with isoniazid plus p-aminosalicylic acid was recently undertaken by the Tuberculosis Chemotherapy Centre, Madras, in the course of a controlled comparison of home and sanatorium chemotherapy for tuberculous patients from a poverty-stricken community in Madras City. Despite the fact that during the year of treatment the home patients subsisted on a markedly poorer diet, were physically more active and, on the average, gained less weight than the sanatorium patients, the overall response to treatment in the home series closely approached that in the sanatorium series, although there was a tendency for tubercle bacilli to disappear earlier in the latter. Direct evidence has been presented that none of the dietary factors studied (calories, carbohydrates, total and animal proteins, fats, minerals and vitamins) appears to influence the attainment of quiescent disease among tuberculous patients treated for one year with an effective combination of antimicrobial drugs, and that initial chemotherapy of patients at home can be successful even if the dietary intake is low throughout the period of treatment.
The results of a study by the Tuberculosis Chemotherapy Centre, Madras, of the merits of home as compared with sanatorium treatment for pulmonary tuberculosis have indicated that treatment at home is satisfactory in the majority of cases. Before domiciliary chemotherapy can be introduced on a large scale, however, it must be established that it does not expose the patient's contacts to a special risk of infection, avoided by his isolation in a sanatorium. Accordingly, a further study was undertaken by the Centre to determine (a) the prevalence of tuberculosis among the family contacts of patients, and (b) the incidence of clinical tuberculosis and of tuberculous infections in the family contacts of the home and sanatorium groups of patients during the first year of treatment. The findings of this study indicate that the major risk for contacts lies in exposure to the infectious case before diagnosis, whether the patient subsequently remains at home or is isolated in a sanatorium appearing to have little importance, if the patients at home are treated with effective chemotherapy. Children under seven years of age proved to be particularly vulnerable to infection. The management of young contacts by chemoprophylaxis or by BCG vaccination, or by both measures, has been discussed.
In a comparison of home and sanatorium treatment for tuberculous patients in India, pretreatment cultures of tubercle bacilli showed a higher average level of resistance to p-aminosalicyclic acid (PAS) than pretreatment cultures from a representative sample of patients in Great Britain. The investigation described in the present paper was therefore undertaken to find out the nature of the difference in the PAS sensitivity of cultures from Indian and British patients. In this investigation, carried out jointly at the Tuberculosis Chemotherapy Centre, Madras, and the Postgraduate Medical School of London, sputum specimens from 147 Indian and 93 British patients were cultured and subjected to sensitivity tests. The tests were set up on slopes containing various concentrations of PAS and inoculated with 10(5) viable units of the cultures, and the minimal concentrations of PAS inhibiting the growth of 20, 50 and 100 colonies were determined. According to the 20-colony end-point-the one commonly used in routine sensitivity tests-the Indian strains were significantly more resistant than the British strains. This difference in sensitivity was not apparent, however, in either the 50-colony or the 100-colony results. The presence of a small proportion of resistant organisms was found to be a general characteristic of the Indian strains, but did not appear to be related to any special tendency for the patient to fail to respond to treatment with PAS. Since a chance increase in the inoculum size might well affect the 20-colony results, the authors recommend a tenfold decrease in the size of the inoculum used in routine PAS-sensitivity tests on Indian patients.
A recent report by the Tuberculosis Chemotherapy Centre, Madras, showed that the response of patients to a year's domiciliary treatment for pulmonary tuberculosis with isoniazid plus p-aminosalicylic acid closely approached that of patients to a year's sanatorium treatment with the same combination of drugs. The present report summarizes the findings of a second year's study, carried out on those patients in the first-year study whose disease had attained bacteriological quiescence by the end of the year of combined chemotherapy. The main objects of this follow-up study were to determine (a) whether relapse in the second year was more frequent among the patients originally treated at home than among those originally treated in sanatorium, (b) whether a second year of antituberculosis chemotherapy, with isoniazid alone, would reduce the relapse rate and (c) the influence of residual cavitation at one year, the so-called "open negative" syndrome, on the results in the second year. During the second year all the patients were treated at home, either with isoniazid or with a placebo, calcium gluconate; in each case the medicine was administered by the patients themselves. It was found that there was very little difference in the relapse rates of the "home" and "sanatorium" groups, that a second year of treatment with isoniazid alone did not influence the likelihood of relapse, and that patients with the open negative syndrome fared slightly less well in the second year than patients without residual cavitation.
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