FLV used as monotherapy in vivo showed suppressive effects of HCV clinically that are modest, variable, and often short-lived. These findings support "proof-of-concept" for pilot trials combining fluvastatin with standard therapy. Statins and fluvastatin, in particular, appear to be safe for use in hepatitis C.

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Different parameters of fibrinolytic systems like t-PA, PAI, D-dimer, and inhibitors of blood coagulation, i.e., protein C (PC), protein S(PS), and antithrombin III (AT-III), have been studied in cases of acute malaria due to Plasmodium falciparum and plasmodium vivax infection, and these patients were followed up. It was observed that the plasma PAI-1 was very high in cases of P. falciparum malaria infection as compared to normal controls and P. vivax infection. The changes in complicated cases of P. falciparum were remarkable as compared to uncomplicated ones. The PC, PS, and AT-III levels were also low in P. falciparum, particularly so in complicated cases, and were normal in P. vivax infection. The factor VIII R:Ag levels were invariably high in acute malaria. On follow-up of some of these cases the values came back to normal after the antiparasite treatment. The monocyte procoagulant activity was found to be significantly higher in P. falciparum infection as compared to that of P. vivax infection. All these findings therefore contribute towards the production of a hypercoagulable state in P. falciparum infection and partly explain the complications of P. falciparum infection like cerebral malaria.

The estimated incidence of end-stage renal disease (ESRD) in Pakistan is 100 per million population. Paucity and high costs of renal replacement therapy allows only 10% to get dialysis and 4-5% transplants. Our center, a government organization, started a dialysis and transplant program in 1980s where all services were provided free of charge to all patients. It was based on the concept of community government partnership funded by both partners. The guiding principles were equity, transparency, accountability and development of all facilities under one roof. This partnership has sustained itself for 30 years with an annual budget of $25 million in 2009. Daily 600 patients are dialyzed and weekly 10-12 receive transplants. Oneand 5-year graft survival of 3000 transplants is 92% and 85%, respectively. The institute became a focus of transplantation in Pakistan and played a vital role in the campaign against transplant tourism and in promulgation of transplant law of 2007, and also helped to increase altruistic transplants in the country. This model emphasizes that in developing countries specialized centers in government sector are necessary for transplantation to progress and community support can make it available to the common man.

BackgroundHepatitis B virus (HBV) genotypes have distinct geographic distribution. Moreover, much genetic variability has been described in the precore (PC) and basal core promoter (BCP) regions of the HBV genome. The local prevalence of HBV genotypes and mutations has not been well studied. The aim of the present study is to determine the prevalence of HBV genotypes and mutations in the PC and BCP region in HBV strains in Karachi.MethodsA total of 109 chronic hepatitis B patients with detectable HBV DNA by a PCR assay were enrolled in the study. Sera were tested for HBeAg, anti-HBe antibody and liver profile. HBV genotypes and mutations in the PC and BCP regions were detected by INNO-LiPA line-probe assays.ResultsOf the 109 patients investigated, 38 (35%) were HBeAg positive while 71 (65%) were HBeAg negative. Genotype D was present in 100% of the patients. Two patients had co-infection with genotype A. There was no significant difference in the baseline characteristics, mean ALT levels, and presence of clinical cirrhosis in patients with HBeAg positive or negative strains with or without PC and BCP mutations. Of the 38 HBeAg positive patients, 9 (24%) had PC and BCP mutations. In the HBeAg negative patient group, mutations were detected in 44 (62%) of the strains investigated. More than one mutation was common, seen in 26 (37%) patients with HBeAg negative disease and 6 (16%) patients with HBeAg positive disease. Twelve (17%) HBeAg negative patients had dual T1762 and A1764 mutations. None of the HBeAg positive patients had T1762 mutation. Mutations were undetectable in 27 (38%) of patients with HBeAg negative disease.ConclusionOur study shows that type D is the main HBV genotype in Karachi, Pakistan. Significant numbers of patients infected with this genotype have PC and BCP variants. Mutations at more than one site are common. Patients harboring these mutants do not differ significantly in their clinical presentation from patients having wild type infection.

Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology. In this study we compared a recently published tagging single nucleotide polymorphism (SNP) (rs1495741) to the conventional 7-SNP genotype (G191A, C282T, T341C, C481T, G590A, A803G and G857A haplotype pairs) and systematically analysed if novel SNP combinations outperform the latter. For this purpose, we studied 3177 individuals by PCR and phenotyped 344 individuals by the caffeine test. Although the tagSNP and the 7-SNP genotype showed a high degree of correlation (R=0.933, P<0.0001) the 7-SNP genotype nevertheless outperformed the tagging SNP with respect to specificity (1.0 vs. 0.9444, P=0.0065). Considering all possible SNP combinations in a receiver operating characteristic analysis we identified a 2-SNP genotype (C282T, T341C) that outperformed the tagging SNP and was equivalent to the 7-SNP genotype. The 2-SNP genotype predicted the correct phenotype with a sensitivity of 0.8643 and a specificity of 1.0. In addition, it predicted the 7-SNP genotype with sensitivity and specificity of 0.9993 and 0.9880, respectively. The prediction of the NAT2 genotype by the 2-SNP genotype performed similar in populations of Caucasian, Venezuelan and Pakistani background. A 2-SNP genotype predicts NAT2 phenotypes with similar sensitivity and specificity as the conventional 7-SNP genotype. This procedure represents a facilitation in individualized dosing of NAT2 substrates without losing sensitivity or specificity.

The prevalence of pediatric RRT and transplantation are low in developing countries, 6-12 and <1 to 5 per million child population (pmcp), respectively. This is due to low GDP/capita of <$10 000, government expenditure on health of <2.6-9% of GDP and paucity of facilities. The reported incidence of pediatric CKD and ESRD is <1.0-8 and 3.4-35 pmcp, respectively. RRT and transplantation are offered mostly in private centers in cities where HD costs $20-100/session and transplants $10 000-20 000. High costs and long distance to centers results in treatment refusal in up to 35% of the cases. In this backdrop 75-85% of children with ESRD are disfranchised from RRT and transplantation. Our center initiated an integrated dialysis-transplant program funded by a community-government partnership where RRT and transplantation was provided ''free of cost'' with life long follow-up and medication. Access to free RRT at doorsteps and transplantation lead to societal acceptance of transplantation as the therapy of choice for ESRD. This enabled us to perform 475 pediatric transplants in 25 years with 1-and 5-year graft survival of 96% and 81%, respectively. Our model shows that pediatric transplantation is possible in developing countries when freely available and accessible to all who need it in the public sector.

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