Contribution of insulin resistance to decreased baroreceptor sensitivity & cardiometabolic risks in pre-obesity & obesity.

BACKGROUND & OBJECTIVES: Although insulin resistance (IR) is a known complication in obesity, the physiological mechanisms linking IR with cardiometabolic risks in obesity have not been well studied. This study was conducted to assess the difference in cardiovascular (CV) risk profile in IR and non-IR (NIR) conditions, and contribution of IR to cardiometabolic risks in pre-obese and obese individuals. METHODS: Basal CV, blood pressure variability, autonomic function test and cardiometabolic parameters were recorded in pre-obese (n=86) and obese (n=77) individuals during 2012 and 2015. The association of altered cardiometabolic parameters with homeostatic model for IR (HOMA-IR) in pre-obese and obese groups and with baroreceptor sensitivity (BRS) in IR and NIR groups was calculated by appropriate statistical analysis. RESULTS: Decreased BRS, a known CV risk and cardiometabolic parameters were significant in IR (pre-obese and obese) group compared to the NIR group. Sympathovagal imbalance in the form of increased sympathetic and decreased parasympathetic activities was observed in individuals with IR. There was no significant difference in the level of independent contribution of HOMA-IR to cardiometabolic parameters in pre-obese and obese groups. Adiponectin and inflammatory markers had an independent contribution to BRS in IR group. INTERPRETATION & CONCLUSIONS: Findings of the present study demonstrated that the intensity of cardiometabolic derangements and CV risk were comparable between IR, pre-obese and obese individuals. Pro-inflammatory state, dyslipidaemia and hypoadiponectinaemia might contribute to CV risk in these individuals with IR. IR could possibly be the link between altered metabolic profile and increased CV risks in these individuals independent of the adiposity status.

Clinical profile & complications of neurotoxic snake bite & comparison of two regimens of polyvalent anti-snake venom in its treatment.

BACKGROUND & OBJECTIVES: The optimal anti-snake venom (ASV) dose required to treat neurotoxic snake envenomation is not known. Low-dose ASV (national protocol: maximum dose 200 ml) may be as efficacious as the conventional regimen (100 ml six hourly till all symptoms disappear), but a direct comparison of the regimens is not available. The aim of this study was to test the efficacy of low-dose ASV regimen against the conventional high-dose regimen. METHODS: The clinical profile of 51 patients with neurotoxic snake envenomation was studied. Patients were treated with either the national protocol or the conventional protocol for ASV administration. The time to complete recovery of symptoms, duration of mechanical ventilation and total dose of ASV were compared. RESULTS: More patients were females (28 vs. 23) bitten in the early morning hours (2400-0600 h). Thirty nine of 51 (76.4%) patients required mechanical ventilation. In terms of progression of neuroparalysis, time to complete resolution of ptosis and occurrence of VAP and ASV reactions, there was no difference. Duration of mechanical ventilation was less with the national protocol (24 vs. 43.5 h). Significantly less amount of ASV was used with the national protocol (224 vs. 982 ml) per patient. There were no mortality or permanent neurological sequelae with either regimen. INTERPRETATION & CONCLUSIONS: In this preliminary study, it was found that the national ASV protocol was as effective as the conventional regimen for neurotoxic snake bites. However, the findings need to be tested in a larger randomized controlled trial for definitive conclusions.

A Confounding Case of Inherited Factor V Deficiency Complicated by Inhibitors at First Presentation.

INTRODUCTION: Inherited factor V deficiency / Owren's disease has varied clinical manifestations ranging from asymptomatic laboratory abnormalities to massive hemorrhage. The acquired form due to inhibitors following antibiotic therapy, infection, or surgery is less common, and spontaneous development of inhibitors is not known. CASE REPORT: An 18-year-old boy presented with bleeding axillary and groin ulcers. At the age of 15, due to recurrent epistaxis and gum bleed, he was diagnosed with acquired factor V deficiency with positive inhibitor screen and treated with fresh frozen plasma (FFP) transfusion and temporary azathioprine. Coagulation workup at his current presentation also revealed acquired factor V deficiency with presence of inhibitors. The tests were repeated after 6 weeks of intermittent FFP transfusion, and the differences observed included negative inhibitor screen and complete correction on mixing studies, but factor V level was 2%. DISCUSSION: Evidence of inhibitors at presentation favored acquired disease. However, younger age of onset, detection of inhibitors 1 year after first episode of self-regressing bleed, lack of identifiable triggers, and persistent bleeding with reduced factor levels after disappearance of inhibitors favored inherited factor V deficiency. CONCLUSION: In this case report, we have described an interesting case of severe inherited factor V deficiency with spontaneous appearance and disappearance of inhibitors exhibiting nonspecific factor inhibitory activity.

A fatal case of thiacloprid poisoning.

Neonicotinoid insecticides are considered to be less toxic to humans compared to older insecticides such as organophosphates, carbamates, pyrethroids, and organochlorine compounds. However,reports of severe human toxicity with neonicotinoids are emerging. Acute human thiacloprid poisoning and death as a result have not been reported in the literature so far. Here we report a case of thiacloprid poisoning resulting from deliberate ingestion in a 23-year-old man, manifesting with status epilepticus, respiratory paralysis,rhabdomyolysis, metabolic acidosis, and acute kidney injury (AKI), and ultimately giving rise to refractory shock and death. Thiacloprid can cause fatal human toxicity when ingested heavily, and absence of an effective antidote raises concern in this regard.

Validation of the megakaryocyte fragmentation theory of finger clubbing in patients with cardiopulmonary diseases.

Dickinson and Martin had proposed that finger clubbing is caused by distal impaction of large-sized platelets that escape physiological fragmentation in lung vasculature. Empirical evidence to support this theory, however, is limited and conflicting. Moreover, this theory has not been verified in patients with lung diseases. We conducted a cross-sectional analytic study to validate the megakaryocyte fragmentation theory in patients with cardiopulmonary diseases. We studied four groups - patients with cyanotic heart diseases and clubbing (n = 20); patients with non-malignant lung diseases and clubbing (n = 25); patients with non-malignant lung diseases but no clubbing (n = 25); and healthy individuals (n = 25). We measured the distal phalangeal depth ratio, estimated the platelet volume indices, and examined the peripheral blood smear for the presence of large platelets. We found that patients with clubbing due to cyanotic heart diseases had a significantly lower platelet count (median [IQR] 201 [157-241] vs. 303 [258-334] × 10(3)/µl; p < 0.001), higher platelet volume (mean difference, Δ [95% CI] = 0.93 fl [0.37-1.49 fl]; p = 0.002) and platelet large cell ratio (Δ = 7.99% [3.71%-12.26%]; p < 0.001) as compared to healthy individuals. They were also significantly more likely to have large platelets on peripheral blood smear as compared to healthy individuals (9/25 vs. 0/25; p = 0.002). However, in patients with lung diseases, irrespective of the presence or absence of clubbing, platelet count and platelet volume indices were not different from healthy individuals. Our findings support the megakaryocyte fragmentation theory of finger clubbing in patients with cyanotic heart diseases. However, this theory does not explain the clubbing seen in non-malignant lung diseases.

Split-hand/feet malformation in three tamilian families and review of the reports from India.

Split-hand/foot malformation (SHFM) is a rare condition which can be either syndromic or nonsyndromic. We report three unrelated pedigrees, one with autosomal dominant (AD) inheritance and the other two with autosomal recessive (AR) pattern. We also briefly review the published reports from India.

Cerebral infarction leading to hemiplegia: A rare complication of acute pancreatitis.

Peripancreatic vascular thrombosis is a known complication of acute pancreatitis (AP) and chronic pancreatitis. However, hemiplegia resulting from cerebral infarction due to cerebral arterial thrombosis is a rare complication of AP. Here, we report a case of alcohol related severe AP with multi-organ dysfunction, which was complicated by large left sided middle cerebral artery territory infarct - leading to right sided hemiplegia in a 48-year-old male patient. The neurological and vascular thrombotic complications of pancreatitis, their pathogenesis and management are discussed in brief.

Body mass index contributes to sympathovagal imbalance in prehypertensives.

BACKGROUND: The present study was conducted to assess the nature of sympathovagal imbalance (SVI) in prehypertensives by short-term analysis of heart rate variability (HRV) to understand the alteration in autonomic modulation and the contribution of BMI to SVI in the genesis of prehypertension. METHODS: Body mass index (BMI), basal heart rate (BHR), blood pressure (BP), rate pressure product (RPP) and HRV indices such as total power (TP), low-frequency power (LF), normalized LF (LFnu), high-frequency power (HF), normalized HF (HFnu), LF-HF ratio, mean heart rate (mean RR), square root of the mean squared differences of successive normal to normal intervals (RMSSD), standard deviation of normal to normal RR interval (SDNN), the number of interval differences of successive NN intervals greater than 50 ms (NN50) and the proportion derived by dividing NN50 by the total number of NN intervals (pNN50) were assessed in three groups of subjects: normotensives having normal BMI (Group 1), prehypertensives having normal BMI (Group 2) and prehypertensives having higher BMI (Group 3). SVI was assessed from LF-HF ratio and correlated with BMI, BHR, BP and RPP in all the groups by Pearson correlation. The contribution of BMI to SVI was assessed by multiple regression analysis. RESULTS: LF and LFnu were significantly increased and HF and HFnu were significantly decreased in prehypertensive subjects in comparison to normotensive subjects and the magnitude of these changes was more prominent in subjects with higher BMI compared to that of normal BMI. LF-HF ratio, the sensitive indicator of sympathovagal balance had significant correlation with BMI (P=0.000) and diastolic blood pressure (DBP) (P=0.002) in prehypertensives. BMI was found to be an independent contributing factor to SVI (P=0.001) in prehypertensives. CONCLUSIONS: It was concluded that autonomic imbalance in prehypertensives manifested in the form of increased sympathetic activity and vagal inhibition. In prehypertensives with higher BMI, vagal withdrawal was predominant than sympathetic overactivity. Magnitude of SVI (alteration in LF-HF ratio) was linked to changes in BMI and DBP. BMI had an independent influence on LF-HF ratio. It was advised that life-style modifications such as yoga and exercise would enable achieve the sympathovagal balance and blood pressure homeostasis in prehypertensives.

Effect of gender on sympathovagal imbalance in prehypertensives.

Although recently the incidence of prehypertension has increased considerably, the pathophysiological mechanisms and the effects of gender in its causation have not yet been fully elucidated. Therefore, in this study body mass index (BMI), waist-hip ratio (WHR), basal heart rate (BHR), blood pressure (BP), rate pressure product (RPP), and spectral indices of heart rate variability (HRV) were reordered and analyzed in normotensive and prehypertensive males and females. It was observed that low frequency-high frequency (LF-HF) ratio, the sensitive indicator of sympathovagal imbalance (SVI), is significantly more (P < .001) in male prehypertensives compared with female prehypertensives. Although SVI in prehypertensives was found to be due to both sympathetic activation and vagal inhibition, contribution of vagal withdrawal was prominent in males. The LF-HF ratio was significantly correlated with BMI, WHR, BHR, BP, and RPP, which was more prominent in male prehypertensives and the degree of correlation was more for WHR and diastolic pressure. It was concluded that vagal inhibition plays an important role in critical alteration of SVI in the genesis of prehypertension, especially in males, and WHR could be a better indicator of SVI in prehypertensives. It was suggested that prehypertensives should improve their vagal tone to restore the sympathovagal homeostasis.

A simple mortality risk prediction score for viper envenoming in India (VENOMS): A model development and validation study.

BACKGROUND: Snakebite is a neglected problem with a high mortality in India. There are no simple clinical prognostic tools which can predict mortality in viper envenomings. We aimed to develop and validate a mortality-risk prediction score for patients of viper envenoming from Southern India. METHODS: We used clinical predictors from a prospective cohort of 248 patients with syndromic diagnosis of viper envenoming and had a positive 20-minute whole blood clotting test (WBCT 20) from a tertiary-care hospital in Puducherry, India. We applied multivariable logistic regression with backward elimination approach. External validation of this score was done among 140 patients from the same centre and its performance was assessed with concordance statistic and calibration plots. FINDINGS: The final model termed VENOMS from the term "Viper ENvenOming Mortality Score included 7 admission clinical parameters (recorded in the first 48 hours after bite): presence of overt bleeding manifestations, presence of capillary leak syndrome, haemoglobin <10 g/dL, bite to antivenom administration time > 6.5 h, systolic blood pressure < 100 mm Hg, urine output <20 mL/h in 24 h and female gender. The lowest possible VENOMS score of 0 predicted an in-hospital mortality risk of 0.06% while highest score of 12 predicted a mortality of 99.1%. The model had a concordance statistic of 0·86 (95% CI 0·79-0·94) in the validation cohort. Calibration plots indicated good agreement of predicted and observed outcomes. CONCLUSIONS: The VENOMS score is a good predictor of the mortality in viper envenoming in southern India where Russell's viper envenoming burden is high. The score may have potential applications in triaging patients and guiding management after further validation.

Prothrombotic Factors Have Significant Association with Arterial and Venous Strokes in Indian Tamilians.

BACKGROUND: Prothrombotic factors have been correlated with vascular events in young patients, with recurrent strokes, and with venous thromboembolisms. However, their prevalence in adult strokes, in healthy populations, and in specific ethnic groups is not well defined. We investigated the association of prothrombotic factors with strokes in a South Indian Tamil population. METHODS: In this hospital-based cross-sectional study, plasma homocysteine (Hcys), protein C and protein S activity levels, activated protein C resistance (APCR) as a surrogate for factor V Leiden (FVL), fibrinogen, and antithrombin III (ATIII) were determined from 75 consecutive patients with ischemic stroke (IS), 25 with cortical venous thrombosis (CVT), and 75 healthy control participants. The Student t test or Mann-Whitney U test was used for comparing prothrombotic factor levels between the stroke and control groups. The χ2 or Fisher exact test was used for comparisons of proportions of thrombophilia and estimation of odds ratios. Mid-P correction was done for multiple estimations. RESULTS: Hcys levels in patients with IS were significantly higher compared with those in healthy control participants (P = 0.02). Proportions of ATIII deficiency and hyperfibrinogenemia were significantly higher in the IS group, and no healthy control participants had hyperfibrinogenemia. Protein C deficiency was more frequent in those with IS (17%; P < 8 × 10-5) and CVT (P < 10-7) compared with healthy control participants, and protein C activity levels (P = 0.016) were also significantly lower in patients with CVT. Other parameters had no significant associations with IS and CVT. The frequency of protein S deficiency was high in healthy control participants (60%) and in both patients with IS (45%; P = 0.1) and patients with CVT (48%; P = 0.4). No patients or control participants had abnormal APCR. CONCLUSIONS: In Tamilian participants, several prothrombotic factors were associated with IS. Protein C deficiency alone was associated with CVT. Replication of the pattern in genetically linked populations around the world may affect management of stroke in those populations.

Chronic Kidney Disease after Snake Envenomation Induced Acute Kidney Injury.

Snake bite is an important cause for acute kidney injury (AKI) in the tropics and the victims are often otherwise healthy young adults without conventional risk factors for chronic kidney disease (CKD). Available literature on long-term outcomes of AKI -snake envenomation is limited, with only two small retrospective studies with follow-up periods of two years or less. In a hospital-based prospective and retrospective follow-up study, all consecutive adult patients who developed AKI and discharged alive were recruited in the prospective group and for retrospective analysis, we retrieved medical records of patients hospitalized with snake bite from the digitized medical records. Clinical and biochemical characteristics during hospitalization and on follow-up were collected. We recruited 193 patients with snake bite and AKI in a prospective (140) and a retrospective (53) group. Of the 193 AKI patients, 162 (84%) had estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at the time of discharge from hospital and at follow-up (n = 171) 29 (16.9%) had eGFR<60 mL/min/1.73 m2. Of the 116 patients with follow-up beyond one year, 30 (26%) had CKD. Overall 26 to 28% of patients went on to develop CKD depending on the duration of follow-up. Only very few (1.16%) patients progressed to ESRD. This is the largest follow-up study so far on snake bite-related AKI and provides further evidence that snake bite-associated AKI causes CKD on long-term follow-up. Older age, diabetes, severe AKI, and inadequate anti-snake venom administration were risk factors for the development of CKD on follow-up.

Cytologic aspects of T-cell acute lymphoblastic leukemia presenting as a massive pericardial effusion: a case report.

BACKGROUND: Acute lymphoblastic leukemia (ALL) with a clinical presentation of cardiac tamponade and the presence of blasts in the pericardial fluid is an uncommon event. A cytopathologist needs to adopt a cautious interpretive approach while dealing with a lymphoid-rich pericardial effusion in order to prevent a false negative diagnosis. CASE: A 27-year-old male presented with breathlessness, ascites, bilateral pedal edema and fever. He had mild hepatomegaly. On detailed clinical examination, a diagnosis of anemia with cardiac tamponade was made. Cytology of pericardial fluid revealed a large number of lymphoid cells in a hemorrhagic background that, under low magnification, closely resembled mature lymphocytes. However, a careful examination of May-Grünwald-Giemsa-stained cytologic smears, under an oil immersion objective (x 1,000), showed atypical lymphoid cells having blastoid morphology. Rare lymphoid cells displayed a "hand mirror" appearance. A hematologic workup was carried out to exclude leukemia/lymphoma. Complete blood count revealed pancytopenia with abnormal lymphoid cells. Bone marrow showed replacement by 90% lymphoblasts exhibiting periodic acid-Schiff stain, CD3 and terminal deoxynucleotidyl transferase positivity. A diagnosis of T-cell acute lymphoblastic leukemia (FAB L1) was offered, and the patient was started on a remission and induction regimen. However, he had a rapid downhill course and died of cardiorespiratory arrest. CONCLUSION: Both clinicians and cytopathologists need to be aware of rare instances in which ALL may present with a pericardial effusion as an initial manifestation. The abnormal lymphoid cells found in the pericardial fluid in such situations need to be interpreted cautiously, as their presence is of clinical significance.

Clinical Profile and Short Term Outcome of Adult Patients with Acute Myeloid Leukemia.

Acute myeloid leukemia has a poor outcome because of early deaths, high relapse rate and financial constraints. Our hospital provides care free of cost and this study assesses the short term outcome of acute myeloid leukemia in adults. The study was done from September 2013 to May 2015. All patients above 18 years of age were included. Cytarabine infusion 100 mg/m2 daily for 7 days and Daunorubicin 60 mg/m2 daily for 3 days was used for induction chemotherapy followed by three cycles of high dose cytarabine as post-remission therapy. One hundred and two patients were included in the study. 48% were males. The median age was 41 years. There was an intention to treat in 84 patients. 13 patients died before chemotherapy and 71 patients (57 non AML M3) received induction chemotherapy. 82% of them had a Eastern Cooperative Oncology Group performance score of ≤ 2. 28 (of 57 non AML M3) patients were alive after post-remission therapy (with 39% deaths during induction phase) and 15 of them were in remission after a median follow up of nine months. The overall event free survival at the end of the study was 22% (16 out of 71). Altogether, 63 out of 84 patients had died. Sepsis was considered as the cause of death in 46% of the patients, but the isolation of causative organism was limited (20%). The treatment outcomes of AML are poor at our centre and the current standard of care needs a significant improvement.

Gender specific association of endothelial nitric oxide synthase gene (Glu298Asp) polymorphism with essential hypertension in a south Indian population.

BACKGROUND: Endothelial derived nitric oxide (NO) plays a major role in blood pressure regulation. The role of missense variant eNOS-Glu298Asp has been demonstrated by many studies with conflicting results. Our objective was to investigate the association of eNOS gene polymorphism with essential hypertension in a south Indian population. METHODS: We carried out a case control study in 438 hypertensive patients and 444 healthy control subjects in a homogenous population. Genotyping was done by PCR-RFLP method. Multiple logistic regression analysis was used to detect the association between genotype and hypertension. RESULTS: The homozygous variant genotype Asp298Asp was significantly associated with hypertension (odds ratio 2.4; 95% CI, 1.23-5.0, p<0.01). Gender specific analysis showed both the heterozygous (odds ratio, 2.0; 95% CI, 1.3-2.9, p<0.01) and homozygous variants (odds ratio, 7.9; 95% CI, 2.0-4.1, p<0.001) were positively associated with hypertension in females. The variant allele Asp was higher in female hypertensives when compared to male hypertensive cases (22% vs. 16%). CONCLUSION: The eNOS gene polymorphism is a candidate gene for hypertension and the association to be gender specific with respect to females in a south Indian Tamilian population.

Lack of association between Glu(298) asp polymorphism of endothelial nitric oxide synthase (eNOS) gene and coronary artery disease in Tamilian population.

OBJECTIVE: Glu298 Asp polymorphism of endothelial nitric oxide synthase (eNOS) gene has been recently implicated as a genetic marker for coronary artery disease (CAD) in some studies. There is no information on the prevalence of this polymorphism and its relationship with CAD in south Indian population. METHODS: A case control study was performed for the determination of the influence of Glu298 Asp polymorphism of eNOS gene in Tamilian population of south India. The study subjects comprised of 100 angiographically proven CAD patients and 100 age- and sex-matched volunteers asymptomatic for CAD, with a low coronary risk score. Genotyping of the eNOS gene was done by the polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) method. RESULTS: The genotype distribution was not significantly different between CAD (GG; 72, GT; 26, TT; 2) and control subjects (GG; 79, GT; 18, TT; 3). The corresponding allele frequencies were G 0.85, T 0.15 and G 0.88, T 0.12, respectively. The odds ratio for the association of CAD with the Asp variant failed to achieve statistical significance (OR = 0.66; 95% CI: 0.11-4.04, P = 1.0). CONCLUSION: No significant association was observed between the Glu298 Asp polymorphism and CAD in this population group.

Prevalence and predictors of potential drug-drug interactions in patients of internal medicine wards of a tertiary care hospital in India.

BACKGROUND: Drug-drug interactions are a major source of adverse drug events (ADEs). Polypharmacy, age and the number of comorbid conditions are important predictors of adverse drug interactions. ADEs account for up to 5% of hospital admissions per year and an increase in the length of hospital stay. OBJECTIVE: To find the prevalence and predictors of potential drug-drug interactions (pDDIs) in patients admitted to the wards of an internal medicine department of a tertiary care hospital. METHOD: Patients admitted to internal medicine wards with prescriptions having more than one drug were selected. Demographic details including age, gender, number of comorbid conditions, number of drugs prescribed and the disease for which the patient was admitted were recorded in a case record form. Interactions were checked using Micromedex DrugReax software. RESULTS: A total of 939 patients were recruited for this study based on inclusion criteria. 433 prescriptions (46%) had one or more pDDIs, with a range of 1-13 drug interactions per prescription. A total of 1395 drug interactions were found, with 866 moderate drug interactions (62%), 435 major interactions (31.1%) and 89 minor interactions (6.3%). During the study period only three contraindicated drug combinations (0.2%) were recorded. A significant association (p<0.01) was found between the number of pDDIs and predictors, age and number of drugs. CONCLUSION: A total of 433 prescriptions (46%) had one or more pDDIs. Older patients and those prescribed >6 drugs are at major risk for occurrence of pDDIs. Moderate severity interactions were the highest number followed by major severity interactions.