Browsing by Author "Thakur, C P"

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    ABO-blood groups in relation to ischaemic heart disease.
    (1966-04-01) Srivastava, D K; Thakur, C P; Das, M
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    Amphotericin B in resistant kala-azar in Bihar.
    (1993-03-01) Thakur, C P; Sinha, G P; Pandey, A K; Barat, D; Sinha, P K
    BACKGROUND. During the recent epidemic of kala-azar in Bihar, we identified a group of patients who were unresponsive to the two commonly used drugs--sodium stibogluconate and pentamidine. We evaluated the use of amphotericin B in these patients because it has been shown to be active in experimental animals against amastigotes and promastigotes, it has been found to be useful in South American patients and is now recommended by the World Health Organization as a second line drug. METHODS. We selected 300 patients who were unresponsive to sodium stibogluconate and pentamidine (out of 500 patients with kala-azar confirmed by demonstration of Leishmania donovani bodies in their splenic aspirates). Amphotericin B was given in a dose of 1 mg/kg body weight on alternate days starting with 0.05 mg/kg body weight with daily increments till a 1 mg dose was reached. A total dose of 20 mg/kg was given initially and repeated if the parasites persisted. The investigations done before and after treatment were splenic or bone marrow aspiration, measurement of the spleen and liver size, body weight, total and differential white cell counts, haemoglobin level, total serum protein, blood urea, serum creatinine, serum potassium, blood sugar, serum alanine and aspartate transaminase, electrocardiography and a chest X-ray. The efficacy of treatment was assessed at the end of treatment and after 6 months of follow up. RESULTS. After treatment with amphotericin B, 298 (99%) of the patients had been cured of their disease as evidenced by the disappearance of fever, reduction of hepatosplenomegaly, clearance of the parasites from the spleen and bone marrow and an absence of relapse on 6 months of follow up. Two hundred and sixty-eight (89%) patients required 1 g of the drug, 24 (8%) required 1.5 g and 6 (2%) required 2 g. All patients had shivering and fever during the infusion. Two had a cardiac arrest from which they could not be revived. Other complications included anorexia, stomatitis, jaundice, hypokalaemia and a rise in blood urea. However, these were only mild and improved after treatment was stopped. CONCLUSION. Amphotericin B is an effective drug for patients with kala-azar unresponsive to treatment with sodium stibogluconate and pentamidine, but it should be administered under close medical supervision.
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    Chemotherapy of leishmaniasis in India.
    (1987-01-01) Thakur, C P
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    Clinical and Laboratory Comparison of Different Brands of Amphotericin B Used for the Treatment of Kala-Azar: An Observational Study.
    (2008-12) Narayan, Shyam; Gupta, A K; Singh, Subhankar K; Lal, C S; Singh, V P; Sinha, P K; Das, P; Thakur, C P
    The communication presents clinical response of cases of visceral leishmaniasis to treatment by two different brands of Amphotericin B. FungizoneTM was found to be slightly better than Amphotericin BTM, however, the difference is not statistically significant.
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    Comparison of regimens of amphotericin B deoxycholate in kala-azar.
    (1996-05-01) Thakur, C P; Sinha, G P; Pandey, A K
    A total of 288 parasitologically proved patients of kala-azar were randomly allocated to three treatment groups. Patients in groups A, B and C received amphotericin B (AMB) in a dose of 1 mg/kg body weight (bw)/day, 0.75 mg/kg bw/day and 0.5 mg/kg bw/day for 20 days respectively. Apparent cure (afebrile at the end of therapy) occurred in all patients and parasitological cure in 96 (100%), 92 (96%) and 84 (88%) patients respectively in groups A, B and C. Ultimate cure (no relapse in six months of follow up) occurred in 95 (99%), 87 (91%) and 79 (82%) patients in groups A, B and C respectively. The difference between the ultimate cure in the three groups was significant (P < 0.05). The incidence of adverse events (rise in serum creatinine and fall in serum potassium, loss of appetite and shivering, rigor and fever during infusion indicative of renal, GIT and infusion related toxicities respectively) was similar in the three groups. This study showed that amphotericin B should be given at a dosage of 1 mg/kg bw/day for 20 days for Indian kala-azar patients to minimise relapses and prevent development of drug unresponsiveness.
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    Comparison of treatment regimens of kala-azar based on culture & sensitivity of amastigotes to sodium antimony gluconate.
    (2008-06-04) Thakur, C P; Thakur, Shabnam; Narayan, S; Sinha, Arun
    BACKGROUND & OBJECTIVE: Present treatment strategies for kala-azar (visceral leishmaniasis, VL) include use of first line drug sodium antimony gluconate (SAG) to all patients but a large number of patients do not get relief with this drug. If a patient does not respond to a full course of SAG, a second or third line drug is given. We undertook this study to test whether an improved outcome can be achieved by employing a strategy of treatment based on culture and sensitivity of amastigotes to SAG compared with conventional empirical treatment. METHODS: In a double-blind, randomized, controlled trial done in Balaji Utthan Sansthan, Patna, of the 181 patients screened,140 were finally randomly allocated to two groups A and B; group A patients were treated with SAG if their amastigotes were sensitive to SAG, and all patients in group B were treated with SAG to start with. Primary outcome measured was as no relapse within 6 months of follow up after cure and other outcomes measured were period of stay of patients in hospital, expenditure involved in the treatment, and infectivity periods of two groups, two-third of treatment period and whole of untreated period were taken as infectivity period. SAG was used at a dosage of 20 mg/kg given deep intramuscular injections in buttock for 28 days, amphotericin B (AMB) given at a dose of 1 mg/kg body wt daily for 20 days as a slow intravenous infusion in 5 per cent dextrose. RESULTS: Of the 70 patients in group A, 29 patients whose amastigotes were sensitive to SAG were treated with SAG, 2 patients were withdrawn due to drug toxicity; and 2 relapsed within 6 months of follow up and ultimate cure occurred in 25 (86.2%) patients only. Of the 70 patients in group B treated with SAG, 5 (7.1%) patients withdrew due to drug toxicity, 35 patients (50%) did not respond to treatment, 5 (7.1%) relapsed during 6 months of follow up and thus only 25 patients (35.7%) were ultimately cured. The difference between the two groups was significant (P<0.001). No patient died during treatment due to any toxicity because of early withdrawal of patients from treatment apprehending toxicity. Patients whose amastigotes were resistant to SAG, withdrawn from the study due to SAG toxicity, relapsed after cure with SAG, and who did not respond to SAG in both the groups were treated with AMB and all were cured. Groups B and A patients spent 3065 and 2340 days respectively in hospital, group B 1.3 times more than group A. The likely period of spread of parasites in society was 1965 days in group B and 1644 days in group A, group B 1.4 times more than group A. The total expenditure on treatment in groups B and A was dollars 65,575 and dollars 50,590 respectively; group B patient had to spend 1.3 times more than group A. INTERPRETATION & CONCLUSION: A new strategy for treatment of kala-azar based on culture and sensitivity of amastigotes improved the cure rate, saved expenditure on the patient's treatment, patients had to stay for shorter periods in hospital and reduced the chance of spread of SAG resistant disease in society. Till the government opts for better drugs, the treatment based on culture and sensitivity of the parasites to SAG may be a better method.
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    Correction of serum electrolyte imbalance prevents cardiac arrhythmia during amphotericin B administration.
    (1995-01-01) Thakur, C P
    Arrhythmias and cardiac arrest have been reported during amphotericin B administration but no effective technique has been described to prevent them. I saw two patients with kala-azar resistant to sodium stibogluconate who developed cardiac arrest after amphotericin infusion (in spite of tolerating a test dose). Both had low levels of serum sodium, potassium and calcium. After these were corrected the amphotericin B was restarted and the course of treatment completed successfully. I suggest that prior to giving amphotericin B to patients with resistant kala-azar their electrolyte imbalance should be corrected.
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    Dehydroemetine oral tablets in amoebiasis.
    (1969-02-01) Thakur, C P
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    Direct agglutination test for early diagnosis of Indian visceral leishmaniasis.
    (1996-09-01) Jha, T K; Thakur, C P; Singh, I J; Singh, T K; Jha, S
    In a prospective study, 80 cases of fever with hepatosplenomegaly, anemia and leucopaenia coming from the hyperendemic zones for visceral leishmaniasis of North-Bihar, India were screened and subjected to bone marrow or splenic puncture for demonstration of Leishman-donovan bodies (LDB) and DIRECT AGGLUTINATION TEST (DAT) with antigen prepared by Harith et al. 59 cases were confirmed for Visceral Leishmaniasis (VL) by demonstration of LDB in which DAT was also positive in different titres ranging from 1:1600 onwards. Out of 21 cases in which the bone marrow was negative for parasite, DAT was positive in 10 cases. 8 Out of 10 cases responded to WHO regimen of treatment with sodium stibogluconate (SSG). Remaining two cases who did not respond to this therapy became positive for parasites on subsequent splenic aspirate. They were treated with pentamidine isethionate and were cured. 11 out of 80 cases showing a titre of 1:400 or lower in DAT, 6 proved to be cases of enteric fever and 5 of malaria. Thus DAT using Harith's antigen was found to be 100% sensitive and specific in detection of early cases of Indian VL.
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    ECG changes in prolonged treatment of kala-azar with antimony compounds.
    (1988-06-01) Pandey, A K; Kumar, M; Thakur, C P
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    Effect of variation of temperature on the incidence of stroke.
    (1986-12-01) Thakur, C P; Anand, M P; Shahi, M P
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    Efficacy of amphotericin B in multi-drug resistant kala-azar in children in first decade of life.
    (1993-01-01) Thakur, C P; Sinha, G P; Sharma, V; Pandey, A K; Sinha, P K; Barat, D
    Fifty children in the first decade of life, and suffering from multiple drug resistant kala-azar, confirmed by demonstration of amastigotes in aspirates of bone marrow or spleen were treated with amphotericin B in gradually increasing dosage to a total dose of 20 mg/kg. All patients had classical features of severe kala-azar, and had taken more than one course of antimony and pentamidine, and three patients had taken one additional course of ketoconazole besides many courses of antimony and pentamidine. The clinical response started just after first infusion in 8 patients, and the patients became afebrile. By 5th infusion, all looked better and 18 patients became afebrile. By 15th infusion all patients were afebrile and cheerful. Their spleens became smaller and body weights and total white cell counts increased. Forty eight patients had parasitological cure at the end of treatment, and only 2 patients required an additional 5 infusions for parasitological cure. All patients were ultimately cured. No one relapsed within six months of follow up. All patients had shivering, rigor and rise of temperature on the day of infusion, which could be minimized with prior administration of low dose of hydrocortisone, but could not be eliminated. Eighteen patients had loose motions during treatment, while 14 patients had decrease in appetite which improved quickly when the treatment was over. Fourteen patients had transient rise of blood urea, in six patients serum creatinine also increased and 16 patients had a minor fall in serum potassium.(ABSTRACT TRUNCATED AT 250 WORDS)
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    Efficacy of prolonged therapy with stibogluconate in post kala-azar dermal leishmaniasis.
    (1990-03-01) Thakur, C P; Kumar, K
    Fifty three (30 male and 23 female), previously untreated, patients with post kala-azar dermal leishmaniasis (PKDL) were treated with sodium stibogluconate, at the dose of 20 mg/kg/bw/d/im/(with a maximum of 8.5 ml) for 120 days (or more, if necessary). All the patients were followed up for 12 months. The patients were assessed after 40 days and thereafter at an interval of 20 days. The mean age of onset was 24 yr, maximum number of patients developed the disease within 3 yr of apparent cure of kala-azar. Maximum number of patients sought treatment within 5 yr of the onset of PKDL. The disease affected the face (98%), trunk (83%), upper limb (72%), lower limb (40%), genetalia (6%), and mucus membrane of the tongue 40%. The lesions observed were nodules (19%), papules (30%), and hypopigmented (45%) and reddish macules (7%). The parasites could be demonstrated in the nodules (100%), papules (69%) and macules (59%). The response to treatment started in 72 per cent of patients in the first 20 days and in 40 days in all patients. All the nodules and papules disappeared in 120 days, and the macules within 200 days. The side effects of treatment noted were changes in S T and T in electrocardiogram (7%), arthralgia (11%), allergic rash (7%), swelling at the site of injection (5%), neuralgia (4%) and metalic taste (6%). The S T and T changes reverted to normal when the drug was discontinued for 20 days. Arthralgia improved with indomethacin. The higher dosages and longer course of treatment were well tolerated and resulted in a cure in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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    Electrolyte excretion pattern of normal and hypertensive.
    (1983-11-01) Thakur, C P; Kumar, A
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    Epidemiological, clinical & pharmacological study of antimony-resistant visceral leishmaniasis in Bihar, India.
    (2004-09-19) Thakur, C P; Narayan, S; Ranjan, A
    BACKGROUND & OBJECTIVES: Sodium antimony gluconate (SAG) is reported to be losing its efficacy in Bihar as a first line drug for treatment of visceral leishmaniasis (VL). Concerned with the increasing incidence of antimony-resistant VL patients in Bihar, we undertook an epidemiological, clinical and pharmacological study to formulate a scientific basis for choosing a suitable first line drug for VL. METHODS: Consecutive, fresh and parasitologically confirmed patients of VL from different geographical areas of Bihar were considered for inclusion in the study. Parasites isolated from patients were tested in vitro to assess their response to sodium antimony gluconate (SAG) to 20 microg/ml, response to 20 mg/kg of SAG for 5 days in experimentally induced VL in BALB/c mice from those isolates, and response to SAG in patients treated with SAG for 28 days. Similarly response in culture (1 microg/ml) to amphotericin B (AMB) of all 282 isolates, (1 mg/kg body wt for 20 days) in patients and infected BALB/c mice (1 mg/kg body wt for 5 days) was determined. Antimony levels of plasma were determined at 2, 8 and 24 h after intramuscular injection of SAG. Patients unwilling for SAG treatment or relapsed after SAG treatment and withdrawn from SAG group because of toxicity were treated with AMB. Plasma antimony levels were estimated by atomic absorption spectrometer. RESULTS: Though antimony sensitive and resistant patient were distributed in all 14 districts of Bihar studied, there was a significant variation from district to district. Of the 123 patients included in the SAG treatment group, 19 were withdrawn due to development of toxicity and 2 died; 178 patients were treated with AMB. No patient in AMB group developed any toxicity or died. Only 47 (46%) of 102 patients, 106 (37.6%) of 282 infected macrophages, 90 (52.9%) of 170 experimental infections were cured with SAG. Mc Nemar's test on paired comparisons showed statistical significance difference (P<0.01) between infected macrophage and experimental infection. AMB cured all patients, infected mice and cleared parasites from all isolates. INTERPRETATION & CONCLUSION: Antimony resistant strains of L. donovani were wide spread over different geographical areas in Bihar. SAG cured lesser percentage of VL cases clinically compared to AMB and should be replaced by AMB as a first line drug.
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    Evaluation of amphotericin B as a first line drug in comparison to sodium stibogluconate in the treatment of fresh cases of kala-azar.
    (1993-07-01) Thakur, C P; Sinha, G P; Sharma, V; Pandey, A K; Kumar, M; Verma, B B
    A total of 150 patients of kala-azar matched for age and sex and parasitologically proved were randomly allocated to two equal treatment groups. Patients in one group received amphotericin B(AMB) in a dose of 1 mg/kg body weight (BW) on alternate days starting with 0.05 mg/kg/bw on first day with daily increments, till a total dose of 20 mg/kg/bw was given; the patients in the second group received sodium stibogluconate (SAG) in the dose of 20 mg/kg/bw, im daily for 30 days. The efficacy, safety and cost-effectiveness of the two drugs were compared. Apparent cure (afebrile at the end of therapy) in 75 (100%) and 69 (92%) patients and ultimate cure (no relapse in six months of follow up) in 75 (100%) and 60 (80%) patients occurred in the AMB and SAG groups respectively. The difference between the ultimate cure in the two groups was significant (P < 0.001). Six (8%) and 9(12%) patients of SAG group showed primary (with no response to SAG during treatment) and secondary unresponsiveness (with no response to SAG after relapse) respectively and they were cured with amphotericin B.(ABSTRACT TRUNCATED AT 250 WORDS)
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    Evaluation of efficacy of longer durations of therapy of fresh cases of kala-azar with sodium stibogluconate.
    (1991-03-01) Thakur, C P; Kumar, M; Pandey, A K
    The efficacy and safety of three regimens of treatment for kala-azar (visceral leishmaniasis) with sodium stibogluconate were evaluated in a randomised clinical trial to ascertain the optimal duration of treatment for Indian patients. The study included a total of 312 (226 male, 86 female) patients with fresh kala-azar, confirmed by demonstration of parasites in aspirates from bone marrow or spleen, who were randomly allocated into three treatment groups of 104 patients in each to receive sodium stibogluconate intramuscularly. The dose of the drug was 20 mg/kg/body weight/daily with a maximum of 8.5 ml for 20, 30 and 40 days (groups A, B, C respectively). The response of treatment was assessed under blind conditions and patients were followed up each month for a period of six months. The number of patients who were apparently cured (i.e., those whose temperature had returned to normal at the end of their respective regimen and aspirates were free of parasites) was 91 (87%) in group A, 98 (94%) in group B, and 102 (98%) in group C. The difference between groups A and C was significant (P less than 0.01). The number of patients who were ultimately cured at six months was 74 (71%) in group A, 86 (83%) in group B and 98 (94%) in group C. These patients had not relapsed and were cured as confirmed by a bone marrow aspirate which was free of parasites. The difference between groups A and C (P less than 0.001) and groups B and C (P less than 0.05) were significant. However, the difference between groups A and B was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)