Role of Clinical Methods, Chest Skiagram Sputum Microscopy and PCR in Diagnosis of Pneumocystis Jiroveci Pneumonia in HIV Patients with CD4 count less than 200 and the clinical outcome: A Comparative study in a Tertiary Care Hospital

BACKGROUND : Pneumocystis jiroveci Pneumonia (PCP) is one of the most predominant opportunistic infections occurring in HIV patients with CD4 count is less than 200.Even though Chest radiograph findings may be normal in 10-39% of PCP patients, it is commonly used for diagnosis in resource limited settings. The other diagnosis methods are Gomori Methanamine Silver(GMS) staining, PCR. Among them, GMS is considered as the gold standard test in diagnosing PCP. AIM AND OBJECTIVES : 1. Comparing role of clinical diagnosis, chest radiography, sputum microscopy and polymerase chain reaction for Pneumocystis jiroveci Pneumonia in HIV seropositive patients with CD4 less than 200. 2. To know the clinical outcome of PCP patients after treatment in our centre. STUDY DESIGN : Prospective cohort study. INCLUSION CRITERIA : 1) All HIV seropositive inpatients with CD4 count less than 200 cells/μL, 2) Age > 18 years. EXCLUSION CRITERIA : 1. HIV patients with CD 4 count > 200 cells/ Μl, 2. Age < 18 years, 3. Patients with sputum positive pulmonary tuberculosis. METHODS : 1. Recruitment of patients as per inclusion criteria, 2. Thorough clinical examination & pulse oximetry, 3. Taking Chest x ray PA view, 4. sputum collection after hypertonic saline nebulisation, 5. Subjecting one sample of sputum for Gomori Methanamine, Silver staining &another sample for Polymerase Chain Reaction, 6. Follow up the clinical course of patients after treatment, 7. Analysis of data using SPSS. RESULTS : Out of 151 HIV seropositive patients examined clinically ,81 individuals were diagnosed as PCP patients. But the sputum microscopy with Gomori methenamine silver staining which was taken as gold standard test diagnosed 41 cases of PCP only. PCR was positive in 2 more patients who were missed in GMS staining sputum PCR is having the highest sensitivity (100%), highest specificity (97%),highest positive predictive value (93%) and also highest negative predictive value(100%). Among 90 PCP patients diagnosed clinically ,74 of 90(82.2%) patients recovered from the illness after treatment&16 0f 90(17.8%) patients died due to illness. CONCLUSION : PCR or GMS staining should be used for diagnosing PCP whenever possible and to detect all cases of PCP in HIV patients without missing

kappa-Hefutoxin1, a novel toxin from the scorpion Heterometrus fulvipes with unique structure and function. Importance of the functional diad in potassium channel selectivity.

Journal of Biological Chemistry2773330040-3004

Reversible covalent direct thrombin inhibitors.

INTRODUCTION:In recent years, the traditional treatments for thrombotic diseases, heparin and warfarin, are increasingly being replaced by novel oral anticoagulants offering convenient dosing regimens, more predictable anticoagulant responses, and less frequent monitoring. However, these drugs can be contraindicated for some patients and, in particular, their bleeding liability remains high. METHODS:We have developed a new class of direct thrombin inhibitors (VE-DTIs) and have utilized kinetics, biochemical, and X-ray structural studies to characterize the mechanism of action and in vitro pharmacology of an exemplary compound from this class, Compound 1. RESULTS:We demonstrate that Compound 1, an exemplary VE-DTI, acts through reversible covalent inhibition. Compound 1 inhibits thrombin by transiently acylating the active site S195 with high potency and significant selectivity over other trypsin-like serine proteases. The compound inhibits the binding of a peptide substrate with both clot-bound and free thrombin with nanomolar potency. Compound 1 is a low micromolar inhibitor of thrombin activity against endogenous substrates such as fibrinogen and a nanomolar inhibitor of the activation of protein C and thrombin-activatable fibrinolysis inhibitor. In the thrombin generation assay, Compound 1 inhibits thrombin generation with low micromolar potency but does not increase the lag time for thrombin formation. In addition, Compound 1 showed weak inhibition of clotting in PT and aPTT assays consistent with its distinctive profile in the thrombin generation assay. CONCLUSION:Compound 1, while maintaining strong potency comparable to the current DTIs, has a distinct mechanism of action which produces a differentiating pharmacological profile. Acting through reversible covalent inhibition, these direct thrombin inhibitors could lead to new anticoagulants with better combined efficacy and bleeding profiles