Response rates of standard interferon therapy in chronic HCV patients of Khyber Pakhtunkhwa (KPK)

<p>Abstract</p> <p>Background</p> <p>Interferon based therapy is used to eradicate the Hepatitis C Virus from the bodies of the infected individuals. HCV is highly prevalent in Khyber Pakhtunkhwa (KPK) that is why it is important to determine the response of standard interferon based therapy in Chronic HCV patients of the region.</p> <p>Study design</p> <p>A total of 174 patients were selected for interferon based therapy. The patients were selected from four different regions of KPK. After confirmation of active HCV infection by Real Time PCR, standard interferon with ribavirn was given to patients for 6 months. After completion of therapy, end of treatment virologic response (ETR) was calculated.</p> <p>Results</p> <p>Out of total 174 patients, 130 (74.71%) showed ETR and 44 (25.28%) did not show ETR. In district Bunir, out of 52 patients, 36 (69.23%) showed ETR and 16 (30.79%) did not show ETR. In district Mardan, out of the total 74 patients, 66 (89.18%) were negative for HCV RNA and 8 (10.81%) were resistant to therapy. In Peshawar, out of 22, 16 (60%) were negative and 6 (40%) were positive for HCV RNA at the end of 6 months therapy. In the Federally Administered Tribal Area (FATA), out of 18 only 10 (55.5%) were negative and 8 (44.45%) were positive for active HCV infection.</p> <p>Conclusion</p> <p>It is concluded that the response of antiviral therapy against HCV infection in chronic HCV patients of KPK province is 74.71%. The high response rate may be due to the prevalence of IFN-responsive HCV genotypes (2 and 3) in KPK.</p

Synpolydactyly and HOXD13 polyalanine repeat: addition of 2 alanine residues is without clinical consequences

<p>Abstract</p> <p>Background</p> <p>Type II syndactyly or synpolydactyly (SPD) is clinically very heterogeneous, and genetically three distinct SPD conditions are known and have been designated as SPD1, SPD2 and SPD3, respectively. SPD1 type is associated with expansion mutations in <it>HOXD13</it>, resulting in an addition of ≥ 7 alanine residues to the polyalanine repeat. It has been suggested that expansions ≤ 6 alanine residues go without medical attention, as no such expansion has ever been reported with the SPD1 phenotype.</p> <p>Methods</p> <p>We describe a large Pakistani and an Indian family with SPD. We perform detailed clinical and molecular analyses to identify the genetic basis of this malformation.</p> <p>Results</p> <p>We have identified four distinct clinical categories for the SPD1 phenotype observed in the affected subjects in both families. Next, we show that a milder foot phenotype, previously described as a separate entity, is in fact a part of the SPD1 phenotypic spectrum. Then, we demonstrate that the phenotype in both families segregates with an identical expansion mutation of 21 bp in <it>HOXD13</it>. Finally, we show that the HOXD13 polyalanine repeat is polymorphic, and the expansion of 2 alanine residues, evident in unaffected subjects of both families, is without clinical consequences.</p> <p>Conclusion</p> <p>It is the first molecular evidence supporting the hypothesis that expansion of ≤ 6 alanine residues in the HOXD13 polyalanine repeat is not associated with the SPD1 phenotype.</p

Adherence to the European Society of Cardiology (ESC) guidelines for chronic heart failure - A national survey of the cardiologists in Pakistan

<p>Abstract</p> <p>Background</p> <p>The aims of this study were to evaluate the awareness of and attitudes towards the 2005 European Society of Cardiology (ESC) guidelines for Heart Failure (HF) of the cardiologists in Pakistan and assess barriers to adherence to guidelines.</p> <p>Methods</p> <p>A cross-sectional survey was conducted in person from March to July 2009 to all cardiologists practicing in 4 major cities in Pakistan (Karachi, Lahore, Quetta and Peshawar). A validated, semi-structured questionnaire assessing ESC 2005 Guidelines for HF was used to obtain information from cardiologists. It included questions about awareness and relevance of HF guidelines (See Additional File <supplr sid="S1">1</supplr>). Respondents' management choices were compared with those of an expert panel based on the guidelines for three fictitious patient cases. Cardiologists were also asked about major barriers to adherence to guidelines.</p> <suppl id="S1"> <title> <p>Additional file 1</p> </title> <text> <p><b>Questionnaire</b>. Description: Questionnaire that was administered to participants.</p> </text> <file name="1471-2261-11-68-S1.DOC"> <p>Click here for file</p> </file> </suppl> <p>Results</p> <p>A total of 372 cardiologists were approached; 305 consented to participate (overall response rate, 82.0%). The survey showed a very high awareness of CHF guidelines; 97.4% aware of any guideline. About 13.8% considered ESC guidelines as relevant or very relevant for guiding treatment decisions while 92.8% chose AHA guidelines in relevance. 87.2% of respondents perceived that they adhered to the HF guidelines. For the patient cases, the proportions of respondents who made recommendations that completely matched those of the guidelines were 7% (Scenario 1), 0% (Scenario 2) and 20% (Scenario 3). Respondents considered patient compliance (59%) and cost/health economics (50%) as major barriers to guideline implementation.</p> <p>Conclusion</p> <p>We found important self reported departures from recommended HF management guidelines among cardiologists of Pakistan.</p

Evolution of apoptosis-like programmed cell death in unicellular protozoan parasites

Apoptosis-like programmed cell death (PCD) has recently been described in multiple taxa of unicellular protists, including the protozoan parasites Plasmodium, Trypanosoma and Leishmania. Apoptosis-like PCD in protozoan parasites shares a number of morphological features with programmed cell death in multicellular organisms. However, both the evolutionary explanations and mechanisms involved in parasite PCD are poorly understood. Explaining why unicellular organisms appear to undergo 'suicide' is a challenge for evolutionary biology and uncovering death executors and pathways is a challenge for molecular and cell biology. Bioinformatics has the potential to integrate these approaches by revealing homologies in the PCD machinery of diverse taxa and evaluating their evolutionary trajectories. As the molecular mechanisms of apoptosis in model organisms are well characterised, and recent data suggest similar mechanisms operate in protozoan parasites, key questions can now be addressed. These questions include: which elements of apoptosis machinery appear to be shared between protozoan parasites and multicellular taxa and, have these mechanisms arisen through convergent or divergent evolution? We use bioinformatics to address these questions and our analyses suggest that apoptosis mechanisms in protozoan parasites and other taxa have diverged during their evolution, that some apoptosis factors are shared across taxa whilst others have been replaced by proteins with similar biochemical activities

Secondary prevention of heart disease – knowledge among cardiologists and Ω-3 (Omega-3) fatty acid prescribing behaviors in Karachi, Pakistan

<p>Abstract</p> <p>Background</p> <p>The use of omega-3 fatty acids is a currently proven strategy for secondary prevention of heart disease. The prescription practices for this important nutraceutical is not currently known. It is imperative to assess the knowledge of cardiologists regarding the benefits of omega-3 fatty acids and to determine the frequency of its prescription. The aim of the study was to determine the practices and associations of dietary fish prescribing among cardiologists of Karachi and to assess their knowledge of fish oil supplementation and attitudes toward dietary practices.</p> <p>Methods</p> <p>A cross sectional survey was conducted during the period of January to March, 2008. A self report questionnaire was employed. All practicing cardiologists of Karachi were included in the study. Multiple logistic regression analysis was performed to determine the independent factors associated with high fish prescribers.</p> <p>Results</p> <p>The sample comprised of a total of 163 cardiologists practicing in Karachi, Pakistan. Most (73.6%) of the cardiologists fell in the age range of 28 – 45 years and were male (90.8%). High fish prescribers only comprised 36.2% of the respondents. After adjusting for age and gender, multivariate analysis revealed that only the variable of knowledge about fish oil's role in reducing sudden cardiac death was independently associated with high fish prescribers OR = 6.38 [95% CI 2.58–15.78].</p> <p>Conclusion</p> <p>The level of knowledge about the benefits of omega-3 fatty acids is high and the cardiologists harbor a favorable attitude towards dispensing dietary fish advice. However, the prescription practices are less than optimal and not concordant with recommendations of organisations such as the American Heart Association and National Heart Foundation of Australia. The knowledge of prevention of sudden cardiac death in CVD patients has been identified as an important predictor of high fish prescription. This particular life-saving property of omega-3 fatty acids should be the focus of any implemented educational strategy targeted to improve secondary CVD prevention via omega-3 fatty acid supplementation.</p

Biochemical Properties of a Novel Cysteine Protease of Plasmodium vivax, Vivapain-4

Plasmodium vivax affects hundreds of millions each year and results in severe morbidity and mortality. Plasmodial cysteine proteases (CPs) play crucial roles during the progression of malaria since inhibition of these molecules impairs parasite growth. These CPs might be targeted for new antimalarial drugs. We characterized a novel P. vivax CP, vivapain-4 (VX-4), which appeared to evolve differentially among primate Plasmodium species. VX-4 showed highly unique substrate preference depending on surrounding micro-environmental pH. It effectively hydrolyzed benzyloxycarbonyl-Leu-Arg-4-methyl-coumaryl-7-amide (Z-Leu-Arg-MCA) and Z-Phe-Arg-MCA at acidic pH and Z-Arg-Arg-MCA at neutral pH. Three amino acids (Ala90, Gly157 and Glu180) that delineate the S2 pocket were found to be substituted in VX-4. Alteration of Glu180 abolished hydrolytic activity against Z-Arg-Arg-MCA at neutral pH, indicating Glu180 is intimately involved in the pH-dependent substrate preference. VX-4 hydrolyzed actin at neutral pH and hemoglobin at acidic pH, and participated in plasmepsin 4 activation at neutral/acidic pH. VX-4 was localized in the food vacuoles and cytoplasm of the erythrocytic stage of P. vivax. The differential substrate preferences depending on pH suggested a highly efficient mechanism to enlarge biological implications of VX-4, including hemoglobin degradation, maturation of plasmepsin, and remodeling of the parasite architecture during growth and development of P. vivax