Manjunath H Hande

Influence of aerobic treadmill exercise on blood glucose homeostasis in noninsulin dependent diabetes mellitus patients.

The role of treadmill exercise on blood glucose homeostasis in noninsulin dependent diabetes mellitus (NIDDM) were studied using males between age of 45 and 60 years (X-52), who were clinically and biochemically-confirmed cases of NIDDM were taken into study group. Control group comprised of 10 males between age group of 45 to 60 (X-53) years. All the subjects were assessed by physician and were investigated to confirm diabetic status. The whole study period was extended for 6 weeks. The significant decrease in postprandial blood sugar (44.4 mg% for the study group and 32.2mg% for the control group) with a significant inter group difference (P<0.05) was observed. The mean decrease in fasting blood sugar (39.4mg% for the study group and 27.4mg% for the control group), with a marginal inter group difference (P<0.05) was observed. The treadmill exercise was found to be a definite tool in addition to drug and diet in glycemic control.

New molecular detection methods of malaria parasites with multiple genes from genomes.

For the effective control of malaria, development of sensitive, accurate and rapid tool to diagnose and manage the disease is essential. In humans subjects, the severe form of malaria is caused by Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) and there is need to identify these parasites in acute, chronic and latent (during and post-infection) stages of the disease. In this study, we report a species specific and sensitive diagnostic method for the detection of Pf and Pv in humans. First, we identified intra and intergenic multiloci short stretch of 152 (PfMLS152) and 110 (PvMLS110) nucleotides which is present up to 44 and 34 times in the genomes of Pf and Pv respectively. We developed the single-step amplification-based method using isolated DNA or from lysed red blood cells for the detection of the two malaria parasites. The limit of detection of real-time polymerase chain reaction based assays were 0.1copyof parasite/μl for PfMLS152 and PvMLS110 target sequences. Next, we have tested 250 clinically suspected cases of malaria to validate the method. Sensitivity and specificity for both targets were 100% compared to the quantitative buffy coat microscopy analysis and real-time PCR (Pf-chloroquine resistance transporter (PfCRT) and Pv-lactate dehydrogenase (PvLDH)) based assays. The sensitivity of microscopy and real-time PCR (PfCRT and PvLDH primers) assays were 80.63%; 95%CI 75.22%-85.31%; p<0.05 and 97.61%; 95%CI 94.50%-99.21%; p<0.05 in detecting malaria infection respectively when compared to PfMLS152 and PvMLS110 targets to identify malaria infection in patients. These improved assays may have potential applications in evaluating malaria in asymptomatic patients, treatment, blood donors and in vaccine studies.

Genetic and epigenetic changes in host ABCB1 influences malaria susceptibility to Plasmodium falciparum

Multiple mechanisms such as genetic and epigenetic variations within a key gene may play a role in malarial susceptibility and response to anti-malarial drugs in the population. ABCB1 is one of the well-studied membrane transporter genes that code for the P-glycoprotein (an efflux protein) and whose effect on malaria disease predisposition and susceptibility to drugs remains to be understood. We studied the association of single nucleotide variations in human ABCB1 that influences its function in subjects with uncomplicated and complicated malaria caused by Plasmodium falciparum (Pf). Global DNA methylation and ABCB1 DNA promoter methylation levels were performed along with transcriptional response and protein expression in subjects with malaria and healthy controls. The rs2032582 locus was significantly associated with complicated and combined malaria groups when compared to controls (p < 0.05). Significant DNA methylation difference was noticed between case and control (p < 0.05). In addition, global DNA methylation levels of the host DNA were inversely proportional to parasitemia in individuals with Pf infection. Our study also revealed the correlation between ABCB1 DNA promoter methylation with rs1128503 and rs2032582 polymorphisms in malaria and was related to increased expression of ABCB1 protein levels in complicated malaria group (p < 0.05) when compared to uncomplicated malaria and control groups. The study provides evidence for multiple mechanisms that may regulate the role of host ABCB1 function to mediate aetiology of malaria susceptibility, prognosis and drug response. These may have clinical implications and therapeutic application for various malarial conditions.

Categorical complexities of Plasmodium falciparum malaria in individuals is associated with genetic variations in ADORA2A and GRK5 genes

In the erythrocytes, malaria parasite entry and infection is mediated through complex membrane sorting and signaling processes. We investigated the effects of single-locus and multilocus interactions to test the hypothesis that the members of the GPCR family genes, adenosine A2a receptor (ADORA2A) and G-protein coupled receptor kinase5 (GRK5), may contribute to the pathogenesis of malaria caused by Plasmodium falciparum (Pf) independently or through complex interactions. In a case-control study of adults, individuals affected by Pf malaria (complicated n=168; uncomplicated n=282) and healthy controls (n=450) were tested for their association to four known SNPs in GRK5 (rs2230345, rs2275036, rs4752307 and rs11198918) and two in ADORA2A (rs9624472 and rs5751876) genes with malaria susceptibility, using techniques of polymerase chain reaction-restriction fragment length polymorphisms and direct DNA sequencing. Single-locus analysis showed significant association of 2 SNPs; rs5751876 (OR=3.2(2.0-5.2); p=0.0006) of ADORA2A and rs2230345 (OR=0.3(0.2-0.5); p=0.0006) of GRK5 with malaria. The mean of the serum creatinine levels were significantly higher in patients with variant GG (p=0.006) of rs9624472 in ADORA2A gene compared to AA and AG genotypes in complicated Pf malaria cases, with the G allele also showing increased risk for malaria (OR=1.3(1.1-1.6); p=0.017). Analyses of predicted haplotypes of the two ADORA2A and the four GRK5 SNPs have identified the haplotypes that conferred risk as well as resistance to malaria with statistical significance. Molecular docking analysis of evolutionary rs2230345 SNP indicated a stable activity of GRK5 for the mutant allele compared to the wild type. Further, generalized multifactor dimensionality reduction to test the contribution of individual effects of the six polymorphisms and higher-order interactions to risk of symptoms/clinical complications of malaria suggested a best six-locus model showing statistical significance. The study provides evidence for the role of ADORA2A and GRK5 that might influence the etiology of malaria infection.

A novel subtype of myeloproliferative disorder? JAK2V617F-associated hypereosinophilia with hepatic venous thrombosis

We report the case of a 27-year-old man, presenting with one episode of massive haematemesis and a history of persistent eosinophilia for the past 8 months. An evaluation revealed hepatic cirrhosis with portal hypertension, secondary to chronic Budd-Chiari syndrome. Further investigations confirmed a diagnosis of hypereosinophilic syndrome. Molecular genetic analysis was negative for FIP1L1-PDGFRA gene rearrangement, but positive for JAK2V617F mutation.

Atorvastatin-Induced Acute Pancreatitis

Atorvastatin-induced acute pancreatitis (AP) is one of the rare adverse effects available in the literature. We report a case of 53-year-old patient developed AP after treatment with atorvastatin monotherapy which resolved after drug withdrawal. Extensive workup on AP failed to reveal any other etiology for it. To our knowledge, this is one of the rare case reports of AP caused due to atorvastatin monotherapy and it further strengthens the fact that statins may cause AP. There is need of continued reporting of such a rare adverse effect of atorvastatin for increasing awareness and to manage and avoid the same.

Primary presentation with acute flaccid quadriparesis in Sjogren's syndrome sans sicca

We report the case of a 40-year-old housewife, who presented with vomiting since past 5 days and weakness of all four limbs since 1 day. Clinical examination confirmed the presence of flaccid quadriparesis with preserved tendon reflexes. Routine laboratory parameters showed severe hypokalaemia. On further evaluation she was diagnosed to have type 1 renal tubular acidosis secondary to Sjogrens syndrome. Sicca symptoms were conspicuous by their absence.

Community-acquired multidrug-resistant Gram-negative bacterial infective endocarditis

We describe two cases of bacterial endocarditis secondary to multidrug-resistant Gram-negative organisms. In both cases, the diagnosis was made in accordance with the modified Dukes criteria and confirmed by histopathological analysis. Furthermore, in both instances there were no identifiable sources of bacteraemia and no history of contact with hospital or other medical services prior to the onset of symptoms. The patients were managed in similar fashion with prolonged broad-spectrum antibiotic therapy and surgical intervention and made complete recoveries. These cases highlight Gram-negative organisms as potential agents for endocarditis, as well as expose the dissemination of such multidrug-resistant bacteria into the community. The application of an integrated medical and surgical approach and therapeutic dilemmas encountered in managing these cases are described.

Simultaneous occurrence of internal capsule infarct and cerebellar haemorrhage in a patient with hemiplegia.

A 68-year-old woman with hypertension with no history of cerebrovascular events presented with a left-sided hemiplegia which had developed acutely 2 days ago. She was not on maintenance therapy with antiplatelets or anticoagulants. A CT scan showed acute ischaemic infarction of the right internal capsule and cerebellar haemorrhage. Cardiac evaluation was normal. Doppler ultrasonography of the extracranial carotid and vertebral arteries showed diffuse arteriosclerotic changes, but did not reveal any haemodynamic occlusion. The simultaneous development of dual strokes was considered to be an extension of the same arteriosclerotic process to the intracranial carotid and basilar arteries.

Hot and cold: coexistent Graves’ disease and Hashimoto's thyroiditis in a patient with Schmidt's syndrome

A 37-year-old housewife presented with generalised fatigue, palpitations and weight loss over the past 3 months. Physical examination revealed signs of hyperthyroidism. Thyroid function tests confirmed the presence of thyrotoxicosis. Pertechnetate radionuclide imaging of the thyroid showed diffusely increased radiotracer uptake consistent with Graves’ disease and a cold nodule in the right lobe. Needle aspiration from the nodule yielded evidence of Hashimotos thyroiditis. The patient also tested strongly positive for antithyroid peroxidase antibodies. Simultaneous laboratory evaluation revealed primary adrenal failure and probable pernicious anaemia, thus producing a diagnosis of Schmidts syndrome. The patient was initiated on appropriate medical therapy for endocrinopathy. Graves’ disease was treated with radioablation.