A Series of Case Reports of Autochthonous Visceral Leishmaniasis,Mostly in Non-Endemic Hilly Areas of Nepal

The government of Nepal has committed to eliminate visceral leishmaniasis (VL) by 2015. The expansion of VL into new areas would constitute a major obstacle to achieving this goal. We report a series of autochthonous VL cases from areas currently considered non-endemic, mostly in hilly regions of Nepal.     

First Isolation of Dengue Virus from the 2010 Epidemic in Nepal

Dengue is an emerging disease in Nepal and was first observed as an outbreak in nine lowland districts in 2006. In 2010, however, a large epidemic of dengue occurred with 4,529 suspected and 917 serologically-confirmed cases and five deaths reported in government hospitals in Nepal. The collection of demographic information was performed along with an entomological survey and clinical evaluation of the patients. A total of 280 serum samples were collected from suspected dengue patients. These samples were subjected to routine laboratory investigations and IgM-capture ELISA for dengue serological identification, and 160 acute serum samples were used for virus isolation, RT-PCR, sequencing and phylogenetic analysis. The results showed that affected patients were predominately adults, and that 10% of the cases were classified as dengue haemorrhagic fever/ dengue shock syndrome. The genetic characterization of dengue viruses isolated from patients in four major outbreak areas of Nepal suggests that the DENV-1 strain was responsible for the 2010 epidemic. Entomological studies identified Aedes aegypti in all epidemic areas. All viruses belonged to a monophyletic single clade which is phylogenetically close to Indian viruses. The dengue epidemic started in the lowlands and expanded to the highland areas. To our knowledge, this is the first dengue isolation and genetic characterization reported from Nepal.     

Contrasting co-inheritance of alpha and beta mutations in delta beta thalassemia and hereditary persistence of fetal hemoglobin: a study from India

ABSTRACT

Background and objectives: Coinheritance of δβ thalassemia and HPFH with inherited factors is sparsely documented and may affect treatment modalities. So, we screened the presence of α deletion and β mutations in δβ thalassemia and HPFH disorders in 52 cases with high Hb F concentration.

Material and methods: Fifty-two individuals with raised HbF levels were study subjects. CZE was done for quantitative assessment of hemoglobin variants. Asian Indian inversion deletion break point type A, B and HPFH-3 were done by GAP-PCR.

Results: 18/52 cases of δβ Gγ (Aγδβ)0 thalassemia and 28/52 cases of HPFH-3 deletion were characterized. 6/52 patients with raised HbF levels were negative for δβ Gγ (Aγδβ)0 and HPFH-3 deletion. 9/18 (50%) were heterozygous for Gγ(Aγδβ)0 break point type A, 6/18 (33%) were heterozygous for break point type B and 3/18 (17%) were homozygous. Of the nine patients heterozygous for Gγ(Aγδβ)0 break point type A, three (33%) patients were double heterozygous with alpha 3.7?kb deletion and two (22%) patients showed compound heterozygosity with IVS 1–5(G–C) mutation. 4/9 (45%) patients were Gγ(Aγδβ)0 heterozygous.

Discussion and conclusion: We found 5/18(27.β) δβ-thalassemia cases with co-inherited alpha 3.7 deletion and 3/18 (16β) cases with IVS 1–5(G–C) mutation. Patients showed features of thalassemia intermedia phenotype among which those with co-inherited IVS 1–5(G–C) mutation showed severe phenotype as compared to those with co-inherited alpha 3.7 deletion. So, we highlight importance of genotyping of patients with δβ thalassemia or HPFH and coinheritance with inherited factors which plays crucial role in clinicopathological profile and setting up prenatal diagnostic protocol.     

Impact of interleukin 6 promoter polymorphisms (−174 G > C, −572 G > C and −597 G > A) on plasma IL-6 levels and their influence on the development of DVT: a study from India

ABSTRACT

Objectives: To evaluate the association of interleukin 6 (IL-6) levels with deep vein thrombosis (DVT) and to assess the impact of IL-6 promoter polymorphisms (?174G?>?C, ?572G?>?C and ?597G?>?A) on its plasma levels and their influence in the development of DVT in India.

Methods: One hundred DVT patients and 100 age and sex-matched healthy controls were study subjects. IL-6 polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism. IL-6 levels were detected by enzyme-linked immunosorbent assay.

Results: Significantly raised IL-6 levels were observed in patients as compared to controls. (Patients: 13.73?±?6.30?pg/ml, Controls: 11.83?±?4.47?pg/ml, p?=?0.014). The prevalence of C allele of ?572G?>?C polymorphism was significantly higher in patients than controls (Patients: 39.5%, Controls: 27.5%, p?=?0.011, χ²=6.463). Subjects with GC and CC genotype had significantly higher IL-6 levels than GG genotype (p=<0.001). Patients with GC and CC genotype increased the DVT risk by 1.39 fold (OR^a: 1.39, CI: 0.74–2.62) and 2.69 fold (OR^a: 2.42, CI: 1.08–6.70), respectively. IL-6 ?174G?>?C and ?597G?>?A polymorphisms were not associated with raised IL-6 levels and nor with thrombotic risk (?174G?>?C: p?=?0.823 χ²=0.369; ?597G?>?A: p?=?0.678 χ²=1.08).

Conclusion: Our study emphasizes the importance of ?572G?>?C polymorphism in increasing IL-6 levels, thereby showing its significant role in DVT in India. IL-6 ?174G?>?C and ?597G?>?A were neither associated with raised plasma IL-6 levels nor with thrombotic risk. Thus ?572G?>?C polymorphism detection may be one of the connecting links between IL-6 and thrombotic risk in Indian DVT patients.     

Heart failure in people with type 2 diabetes vs. those without diabetes: A retrospective observational study from South India

Background and aimDespite diabetes being an independent risk for HF, only some DM patients develop HF and hence our aim was to compare the clinical features of DM with and without HF and non-DM with and without HF.MethodsA retrospective observational study was conducted among 397 individuals who visited two tertiary care centres. They were classified into 4 groups – DM with HF(DM-HF), DM without HF, non-DM with HF(non-DM-HF) and non-DM without HF. We assessed and compared the clinical profile of DM with HF vs. DM without HF and non-DM with HF groups respectively.ResultsThe parameters such as age, BMI, BP, eGFR showed significant difference between the groups. People with DM-HF were older compared to DM without HF group(58.9 ± 9.2vs.49.5 ± 9.3; p < 0.001). An increasing trend was observed in HF prevalence with increasing duration of DM among the DM-HF group. DM-HF showed a higher prevalence of hypertension and coronary artery disease(CAD) by history than DM without HF group. DM-HF group(91.2%) had HF with preserved left ventricular ejection fraction(HFpEF) whereas a high proportion(43.5%) of non-DM-HF group had HF with reduced LV ejection fraction(HFrEF).ConclusionsThe DM-HF group differed from other groups significantly in age, diabetes duration, HbA1c level, prevalence of hypertension, CAD and HFpEF.     

Influence of tissue factor polymorphisms (603A>G and 5466A>G) on plasma tissue factor levels and their impact on deep vein thrombosis risk in young Indian population

Deep vein thrombosis (DVT) is multifactorial disorder and well known to cause substantial morbidity and mortality. There is sparse data in the Asian population, particularly India regarding association of tissue factor (TF) gene single nucleotide polymorphisms (SNPs) with plasma TF levels in DVT. So, we analyzed the distribution of SNPs (603A>G and 5466A>G) in India, to evaluate their effect on TF levels in DVT patients. Plasma level and SNPs (603A>G and 5466A>G) of TF gene were screened in subjects (100 DVT patients and 100 controls). Patients had significantly higher TF levels than controls (patients: 84.95?±?17.16 pg/ml, controls: 70.55?±?15.87 pg/ml, p?G polymorphism was significantly higher in patients than controls (patients: 40.5% controls: 27.5%, p?=?0.004). Subjects with AG and GG genotype had significantly higher TF levels than AA genotype (p?=?0.001). After multiple logistic regression analysis, risk of DVT was increased 1.398 fold (95% CI 0.738–2.651) and 4.41 fold (95% CI 1.404–13.884) with AG and GG genotype respectively. Allelic and genotypic frequencies of 5466A>G polymorphism was neither associated with TF levels nor with DVT. We found high TF level in patients with TF 603A>G polymorphism, which is an important predisposing factor in increasing risk of DVT in young Indians. Furthermore, GG genotype of 603A>G polymorphism augments the risk of thrombosis by 4.4 fold, thus highlighting the significance of this polymorphism in the development of DVT. So, we suggest that inclusion of 603A>G polymorphism in prothrombotic work-up may be helpful in making the treatment strategy in DVT patients.     

Cryoablation versus radiofrequency ablation for treatment of pediatric atrioventricular nodal reentrant tachycardia: Initial experience with 4-mm cryocatheter

BACKGROUND: Initial reports have shown cryoablation to be safe and efficacious for treatment of atrioventricular nodal reentrant tachycardia (AVNRT). No direct comparisons of cryoablation vs radiofrequency (RF) catheter ablation in pediatric patients have been made. OBJECTIVES: The purpose of this study was to compare the outcomes of cryothermal vs RF catheter ablation for treatment of AVNRT in pediatric patients. METHODS: We retrospectively reviewed consecutive ablation procedures for treatment of AVNRT at a single arrhythmia center. The RF group consisted of patients who underwent RF ablation from 2002 until cryothermy became available. The cryoablation group consisted of patients who underwent cryothermal ablation from 2004 to 2005. The groups were compared for procedural and electrophysiologic outcomes. RESULTS: RF (n = 60, age 14 +/- 4 years) and cryoablation (n = 57, age 14 +/- 4 years) groups had similar demographic and baseline parameters. Procedural times were shorter in the RF group (RF ablation 112 +/- 31 minutes vs cryoablation 148 +/- 46 minutes, P < .001). Fluoroscopy times were comparable (RF ablation 21 +/- 15 minutes vs cryoablation 20 +/- 13 minutes, P = .77). In an intention-to-treat analysis, success of the procedure was 100% for RF ablation and 95% for cryoablation (P = .11). No permanent AV block occurred in either group. Recurrence rates were higher for the cryoablation group, but this did not reach statistical significance (RF ablation 2% vs cryoablation 8%, P = .19). CONCLUSION: Cryoablation appears to be similar to RF for ablation of AVNRT with respect to short-term efficacy and safety of the procedure in a pediatric population. Recurrence rates are higher with cryoablation.     

Perceived psychosocial stress and cardiovascular risk factors in obese and non-obese patients

Background Patients after their first myocardial infarction are characterized by increased levels of perceived stress and abdominal obesity compared to a matched control group. In the setting of primary prevention, the association of stress and cardiovascular risk factors in obese and non-obese individuals is not known. Methods and results: For this prospective cross-sectional study, primary care physicians recruited consecutive patients with BMI >30 and the next two individuals presenting with a BMI <30 as controls (n=414). The 10-year risk of death from cardiovascular disease determined by the European Society of Cardiology Heart- Score Germany was associated with BMI (p<0.0001). However, waist circumference and waist-tohip ratio predicted the calculated cardiovascular risk better than BMI. Psychosocial risk factors were determined using the INTERHEART questionnaire. Obesity was positively associated with depression (p=0.005) but not with perceived stress. In contrast to obesity or depression, the extent of perceived general stress inversely correlated with cardiovascular risk (never stress: 4.4±2.8%, some period: 2.4±2.7%, several periods: 1.4±2.3% and permanent: 0.65±0.5%; p=0.0001). Similarly, additional parameters of stress (stress at home, stress at work, financial stress, stressful life events) as well as locus of control were inversely associated with cardiovascular risk factors. A medical history of general stress was correlated with younger age and increased smoking. Conclusions Waist to hip ratio powerfully predicts the cardiovascular risk estimated by HeartScore in primary prevention. Perceived stress assessed by a standardized questionnaire does not positively correlate with traditional cardiovascular risk factors and warrants further evaluation as a routine tool for primary care physicians.     

Blood and Plasma Lipoprotein Distribution and Gender Differences in the Plasma Pharmacokinetics of Lipid-Associated Annamycin

Abstract: The objectives of this study were to determine the lipoprotein distribution of unbound annamycin and liposomal annamycin within human and rabbit blood and plasma and to evaluate the plasma pharmacokinetics of liposomal annamycin in male and female rabbits following a single intravenous bolus of the compound. Annamycin and liposomal annamycin were incubated in human and rabbit blood and plasma for 60 min. at 37°C. Following incubation blood and plasma samples were assayed by HPLC for drug in each of the lipoprotein and lipoprotein-deficient plasma fractions. To evaluate the plasma pharmacokinetics of liposomal annamycin in male versus female rabbits, a single intravenous bolus dose (5 mg/kg) of liposomal annamycin was administered to male and female rabbits. Sequential blood samples were obtained from the animals following the dose, analyzed for drug, and the pharmacokinetics determined using multicompartmental methods. The incorporation of annamycin into liposomes composed of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol resulted in no significant differences in blood versus plasma lipoprotein drug distribution. Furthermore, no differences in the plasma distribution of liposomal annamycin were observed when the drug was either incubated in vitro for 1 hr or 1 hr following intravenous administration into New Zealand male white rabbits. The plasma clearance and volume of distribution of liposomal annamycin were decreased and a increase in plasma AUC in female as compared to male rabbits following a single intravenous bolus of liposomal annamycin was observed. These findings suggest that the lipoprotein distribution of liposomal annamycin is not different when incubated in blood or plasma and that in vitro liposomal annamycin plasma distribution is similar to in vivo. Furthermore, it appears that the pharmacokinetics of liposomal annamycin are different following administration to male versus female rabbits.