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Articles by G Karthikeyan
Total Records ( 3 ) for G Karthikeyan
  G Karthikeyan and B. M. Mayosi

Rheumatic fever and rheumatic heart disease continue to be major public health problems in the developing world, particularly in the countries of sub-Saharan Africa. Because of its cost effectiveness, secondary prophylaxis is advocated as the principal means of disease prevention and control. However, in developing countries, valvular damage, due to earlier, unrecognized episodes of rheumatic fever, has already occurred by the time secondary prophylaxis is instituted. Secondary prophylaxis cannot reduce the incidence of new cases of rheumatic fever and has not been shown to alter the natural history of rheumatic valvular disease. Experience from several regions of the world suggests that incorporation of a strategy of primary antibiotic prophylaxis into a comprehensive program for disease control can reduce the incidence of rheumatic fever and rheumatic heart disease. In this article, we argue that a strategy of primary antibiotic prophylaxis, with appropriate modifications, can be successfully implemented in resource-poor settings across the world and should be a key component of any rheumatic heart disease control program. This, we believe, is essential for reducing the global burden of rheumatic heart disease.

  G Karthikeyan , R. S Math , N Mathew , B Shankar , M Kalaivani , S Singh , V. K Bahl , J Hirsh and J. W. Eikelboom

Background— No large prospective studies have evaluated the efficacy of fibrinolytic therapy for left-sided prosthetic valve thrombosis, yet it remains the first line of treatment in developing countries.

Methods and Results— We performed a randomized controlled trial comparing an accelerated infusion with the conventional infusion of streptokinase in 120 patients with a first episode of left-sided prosthetic valve thrombosis. The primary outcome measure was the occurrence of a complete clinical response, defined as objectively documented complete restoration of valve function in the absence of major complications. The secondary outcome was a composite of death, major bleeding, embolic stroke, or non–central nervous system systemic embolism. Patients were recruited over a 2.5-year period at a single center in India. Complete clinical response occurred in 38 (64.4%) of 59 patients with the accelerated infusion compared with 32 (53.3%) of 60 with the conventional infusion (hazard ratio 1.6, 95% confidence interval 0.9 to 2.5, P=0.055). There was no significant difference in the occurrence of the composite secondary outcome (hazard ratio 1.4, 95% confidence interval 0.5 to 3.5, P=0.50) or major bleeding (hazard ratio 2.2, 95% confidence interval 0.6 to 7.7, P=0.24) with the accelerated infusion. The success rate with fibrinolytic therapy was low overall (59%) and very low in patients in New York Heart Association functional class III/IV (24%).

Conclusions— The large number of patients recruited from a single center underscores the massive burden of prosthetic valve thrombosis in developing countries. Fibrinolytic therapy with streptokinase is less efficacious than previously believed. The accelerated streptokinase infusion is not better than the standard infusion for left-sided prosthetic valve thrombosis. Developing countries urgently need more effective strategies to prevent and treat prosthetic valve thrombosis.

  J Kumar , G Garg , A Kumar , E Sundaramoorthy , K. R Sanapala , S Ghosh , G Karthikeyan , L Ramakrishnan and Sengupta Indian Genome Variation Consortium

Background— An elevated level of homocysteine (hyperhomocysteinemia) has been implicated as an independent risk factor for cardiovascular diseases. Deficiency of dietary factors like vitamin B12, folate, and genetic variations can cause hyperhomocysteinemia. The prevalence of hyperhomocysteinemia in the Indian population is likely to be high because most Indians adhere to a vegetarian diet, deficient in vitamin B12. In the background of vitamin B12 deficiency, variations in genes involved in homocysteine metabolism might have a greater impact on homocysteine levels.

Methods and Results— We genotyped 44 nonsynonymous single-nucleotide polymorphisms (nsSNPs) from 11 genes involved in homocysteine metabolism and found only 14 to be polymorphic. These 14 nsSNPs were genotyped in 546 individuals recruited from a tertiary care center in New Delhi, India, and it was found that choline dehydrogenase (CHDH A119C) and methylenetetrahydrofolate reductase (MTHFR C677T) were significantly associated with plasma total homocysteine levels (P=0.009 and P=0.001, respectively). These 2 SNPs were further genotyped in 330 individuals recruited from the same center, and the association remained significant even after increasing the sample size. Furthermore, we found the possibility of a significant interaction between vegetarian diet and the 2 polymorphisms that could explain the variation of homocysteine levels. We also genotyped all the polymorphic nsSNPs in apparently healthy individuals recruited from 24 different subpopulations (based on their linguistic lineage) spread across the country to determine their basal frequencies. The frequencies of these SNPs varied significantly between linguistic groups.

Conclusion— Vegetarian diet along with CHDH A119C and MTHFR C677T play an important role in modulating the homocysteine levels in Indian population.

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