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.
Ion pairs contribute to several functions including the activity of catalytic triads, fusion of viral membranes, stability in thermophilic proteins and solvent-protein interactions. Furthermore, they have the ability to affect the stability of protein structures and are also a part of the forces that act to hold monomers together. This paper deals with the possible ion pair combinations and networks in 25% and 90% non-redundant protein chains. Different types of ion pairs present in various secondary structural elements are analysed. The ion pairs existing between different subunits of multisubunit protein structures are also computed and the results of various analyses are presented in detail. The protein structures used in the analysis are solved using X-ray crystallography, whose resolution is better than or equal to 1.5 A and R-factor better than or equal to 20%. This study can, therefore, be useful for analyses of many protein functions. It also provides insights into the better understanding of the architecture of protein structure.
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