Ramakrishnan Lakshmy

AIIMS Bhopal All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India

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Publications (89)397.82 Total impact

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    ABSTRACT: This study aimed to investigate the biochemical profile of blood plasma of patients with coronary artery disease (CAD) and angiographically normal subjects (controls) to determine biomarkers for their differentiation. In this double blind study, 5 mL venous blood was drawn before angiography from CAD patients (n=60) and controls (n=13) comprising angiography normal individuals. In vitro high-resolution NMR spectroscopy of these blood plasma samples was carried out at 400 MHz, and intensity data were analysed with partial least square discriminant analysis. Categorization of subjects as controls or CAD patients and the patients further as single vessel disease (SVD), double vessel disease (DVD) and triple vessel disease (TVD) was done at the end of the study based on their angiography reports. Raised levels of lipids, alanine (Ala) and isoleucine/leucine/valine (Ile/Leu/Val) were observed in CAD patients compared with controls. Partial least square discriminant analysis showed separation between controls vs CAD patients. TVD patients showed increased levels of Ile/Leu/Val and Ala compared with controls and SVD. Alanine, Ile/Leu/Val, and LDL/VLDL appear as possible biomarkers for distinguishing between controls and patients with SVD and TVD. A metabolic adaptation of myocardium may play a role in raising the Ala level.
    Journal of Biosciences 03/2015; 40(1). DOI:10.1007/s12038-014-9493-1 · 1.94 Impact Factor
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    ABSTRACT: BACKGROUND: Association of vitamin D deficiency with coronary heart disease (CHD) has been widely reported. Emerging data has shown high prevalence of vitamin D deficiency among Indians. However, this association has not been studied in Indians. METHODS: A case-control study with 120 consecutive cases of first incident acute myocardial infarction (MI) and 120 age and gender matched healthy controls was conducted at All India Institute of Medical Sciences, New Delhi. The standard clinical and biochemical risk factors for MI were assessed for both cases and controls. Serum 25 (OH) vitamin D assay was performed from stored samples for cases and controls using radioimmunoassay. RESULTS: Vitamin D deficiency [25(OH) D < 30 ng/ml] was highly prevalent in cases and controls (98.3% and 95.8% respectively) with median levels lower in cases (6 ng/ml and 11.1 ng/ml respectively; p < 0.001). The cases were more likely to have diabetes, hypertension and consume tobacco and alcohol. They had higher waist hip ratio, total and LDL cholesterol. Multivariate logistic regression analysis revealed severe vitamin D deficiency [25(OH) vitamin D < 10 ng/ml] was associated with a risk of MI with an odds ratio of 4.5 (95% CI 2.2-9.2). CONCLUSIONS: This study reveals high prevalence of vitamin D deficiency among cases of acute MI and controls from India, with levels of 25 (OH)D being significantly lower among cases. Despite rampant hypovitaminosis, severe vitamin D deficiency was associated with acute MI after adjusting for conventional risk factors. This association needs to be tested in larger studies in different regions of the country.
    Indian Heart Journal 02/2015; 67(1):27–32. · 0.17 Impact Factor
  • Ramakrishnan Lakshmy, Mohamad Tarik, Ransi Ann Abraham
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    ABSTRACT: Older adults represent a substantial number of the world population, which is set to grow considerably in the coming years. The health challenges faced by the older adults are unique. Several age-related changes in them make phlebotomy difficult. Application of dried blood has been demonstrated to be useful in the other similarly vulnerable population, the neonates. Similar approach of standardization and demonstration of use of dried blood spots (DBS) for analytes of interest in older adult population would be highly appreciated. There are very few reports of use of DBS in older adults. There are several potential areas of interest for older adults in which DBS assays are available but have not been applied for screening in them. This review describes a brief general overview of DBS, its advantages and disadvantages and potential use in disease diagnosis in older adults.
    Bioanalysis 12/2014; 6(23):3121-31. DOI:10.4155/bio.14.242 · 3.03 Impact Factor
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    ABSTRACT: Abstract Aims: This study estimated the levels of glycemic control among subjects with self-reported diabetes in urban and rural areas of four regions in India. Research Design and Methods: Phase I of the Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) Study was conducted in a representative population of three states of India (Tamil Nadu, Maharashtra, and Jharkhand) and one Union Territory (Chandigarh) and covering a population of 213 million people. Using a stratified multistage sampling design, individuals ≥20 years of age were recruited. Glycemic control among subjects with self-reported diabetes was assessed by measurement of glycated hemoglobin (HbA1c), estimated by the Variant™ II Turbo method (Bio-Rad, Hercules, CA). Results: Among the 14,277 participants in Phase I of INDIAB, there were 480 subjects with self-reported diabetes (254 urban and 226 rural). The mean HbA1c levels were highest in Chandigarh (9.1±2.3%), followed by Tamil Nadu (8.2±2.0%), Jharkhand (8.2±2.4%), and Maharashtra (8.0±2.1%). Good glycemic control (HbA1c <7%) was observed only in 31.1% of urban and 30.8% of rural subjects. Only 22.4% of urban and 15.4% of rural subjects had reported having checked their HbA1c in the past year. Multiple logistic regression analysis revealed younger age, duration of diabetes, insulin use, and high triglyceride levels to be significantly associated with poor glycemic control. Conclusions: The level of glycemic control among subjects with self-reported diabetes in India is poor. Urgent action is needed to remedy the situation.
    Diabetes Technology &amp Therapeutics 08/2014; DOI:10.1089/dia.2014.0018 · 2.29 Impact Factor
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    ABSTRACT: This study was undertaken in view of the paucity of data regarding the profile of prothrombotic factors in children with ischemic stroke. Sixty-four children with ischemic stroke were prospectively evaluated for presence of prothrombotic factors over a 2 year period. The blood samples were analyzed for protein C (PC), protein S (PS), activated protein C resistance (APCR), factor V Leiden (FVL), anti-thrombin-III (AT-III), lipoprotein (a) [Lp(a)], lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL) immunoglobulin (Ig) M and IgG, homocysteine, and methylenetetrahydrofolate reductase (MTHFR) at least 3 months after the onset of stroke. At least one prothrombotic factor was identified in 45.3% children (29/64). These included hyperhomocysteinemia (11/64), PC deficiency (9/64), aCL (8/64), PS deficiency (5/64), APCR (3/64), AT-III deficiency (2/64) and LA (1/64). Multiple factors were coexistent in 17.2% (11/64). The prevalence of PC deficiency, PS deficiency and co-existence of multiple abnormalities observed were similar to the published literature. Elevated Lp(a) and APCR were less prevalent. FVL and MTHFR were not seen in any of the study children. Forty-five percent of children had at least one prothrombotic abnormality. Hyperhomocysteinemia, PC deficiency, aCL and PS deficiency were the most frequent prothrombotic abnormalities.
    Journal of Clinical Neuroscience 08/2014; 21(8). DOI:10.1016/j.jocn.2013.10.030 · 1.32 Impact Factor
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    ABSTRACT: Genetic polymorphism and epistasis play a role in etiopathogenesis of Alzheimer's disease (AD) and vascular dementia (VaD). In this case-control study, a total of 241 patients were included in the study to see the effect of paraoxonase 1 (PON1; rs662 and rs85460) and apolipoprotein E (ApoE) genes in altering the odds of having AD and VaD along with serum PON and lipid profile. The presence of at least 1 variant allele of rs662, but not rs85460, increased the risk of having AD by 1.8-fold (95% confidence interval [CI]: 0.97-3.40) and VaD by 3.09-fold (95% CI: 1.4-6.9). The interaction between PON1 genes (rs662 and rs85460) and ApoE genes showed synergistic epistasis in altering the odds of significantly having both AD and VaD. On the other hand, low serum level of high-density lipoprotein and low level of serum PON activity were found associated significantly (P ≤ .001 in both cases) only in patients with VaD as compared to healthy control.
    American Journal of Alzheimer s Disease and Other Dementias 06/2014; DOI:10.1177/1533317514539541 · 1.43 Impact Factor
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    ABSTRACT: Cardiovascular Disease (CVD) has emerged as the leading cause of death in the world. This burden is disproportionately higher in low and middle income countries like India. Obesity is associated not only with increased risk for CVD but is also an independent risk factor for other risk factors of CVD like diabetes and hypertension. Indices like BMI, Waist Circumference (WC), waist hip ratio (WHR), Waist circumference to height ratio (WHtR) and Body Adiposity Index (BAI) are used to estimate central obesity.
    03/2014; 9(1-1):e297. DOI:10.1016/j.gheart.2014.03.2299
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    ABSTRACT: Association of vitamin D deficiency with coronary heart disease (CHD) has been widely reported. Emerging data has shown high prevalence of vitamin D deficiency among Indians. However, this association has not been studied in Indians. A case-control study with 120 consecutive cases of first incident acute myocardial infarction (MI) and 120 age and gender matched healthy controls was conducted at All India Institute of Medical Sciences, New Delhi. The standard clinical and biochemical risk factors for MI were assessed for both cases and controls. Serum 25 (OH) vitamin D assay was performed from stored samples for cases and controls using radioimmunoassay. Vitamin D deficiency [25(OH) D < 30 ng/ml] was highly prevalent in cases and controls (98.3% and 95.8% respectively) with median levels lower in cases (6 ng/ml and 11.1 ng/ml respectively; p < 0.001). The cases were more likely to have diabetes, hypertension and consume tobacco and alcohol. They had higher waist hip ratio, total and LDL cholesterol. Multivariate logistic regression analysis revealed severe vitamin D deficiency [25(OH) vitamin D < 10 ng/ml] was associated with a risk of MI with an odds ratio of 4.5 (95% CI 2.2-9.2). This study reveals high prevalence of vitamin D deficiency among cases of acute MI and controls from India, with levels of 25 (OH)D being significantly lower among cases. Despite rampant hypovitaminosis, severe vitamin D deficiency was associated with acute MI after adjusting for conventional risk factors. This association needs to be tested in larger studies in different regions of the country. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.
    03/2014; 9(1-1):e214. DOI:10.1016/j.gheart.2014.03.2001
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    ABSTRACT: Low level of vitamin B12 and folic acid has been reported to play an important role in the pathogenesis of Alzheimer's disease (AD) and vascular dementia (VaD). Serum folic acid and vitamin B12 were assayed in 80 AD and 50 VaD cases and in 120 healthy controls. The reduced folate carrier (RFC1) gene, rs1051266, which encodes the RFC 1, protein was analyzed for polymorphism by polymerase chain reaction-restriction fragment length polymorphism. It was observed that the patients having folic acid <8.45 ng/mL had 2.4 (95% confidence interval [CI]: 1.4-4.5) times higher odds of having AD and 2.1 (95% CI: 1.1-4.2) times higher odds of having VaD than patients having folic acid ≥8.45 ng/mL. Serum vitamin B12 level did not show any such statistically significant effect in altering the odds. No direct association was found between variant (G) allele or genotype of rs1051266 with AD and VaD cases. On serum folate level no association was observed with gene polymorphism.
    American Journal of Alzheimer s Disease and Other Dementias 02/2014; 29(1):38-44. DOI:10.1177/1533317513505131 · 1.43 Impact Factor
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    ABSTRACT: The decreased number and senescence of circulating endothelial progenitor cells (EPCs) are considered markers of vascular senescence associated with aging, atherosclerosis, and coronary artery disease (CAD) in elderly. In this study, we explore the role of vascular senescence in premature CAD (PCAD) in a developing country by comparing the numerical status and senescence of circulating EPCs in PCAD patients to controls. EPCs were measured by flow cytometry in 57 patients with angiographically documented CAD, and 57 controls without evidence of CAD, recruited from random patients <= 50 years of age at All India Institute of Medical Sciences. EPC senescence as determined by telomere length (EPC-TL) and telomerase activity (EPC-TA) was studied by real time polymerase chain reaction (q PCR) and PCR-- ELISA respectively.Result: The number of EPCs (0.18% Vs. 0.039% of total WBCs, p < 0.0001), and EPC-TL (3.83 Vs. 5.10 kb/genome, p = 0.009) were markedly lower in PCAD patients compared to controls. These differences persisted after adjustment for age, sex, BMI, smoking and medications. EPC-TA was reduced in PCAD patients, but was statistically significant only after adjustment for confounding factors (1.81 Vs. 2.20 IU/cell, unadjusted p = 0.057, adjusted p = 0.044). We observed an association between increased vascular cell senescence with PCAD in a sample of young patients from India. This suggests that early accelerated vascular cell senescence may play an important mechanistic role in CAD epidemic in developing countries like India where PCAD burden is markedly higher compared to developed countries.
    BMC Cardiovascular Disorders 11/2013; 13(1):104. DOI:10.1186/1471-2261-13-104 · 1.50 Impact Factor
  • New England Journal of Medicine 10/2013; 369(18):1770. DOI:10.1056/NEJMc1313105 · 54.42 Impact Factor
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    ABSTRACT: To evaluate the efficacy and safety of tranexamic acid (TXA) versus epsilon aminocaproic acid (EACA) in patients undergoing thoracic aortic surgery. A prospective randomized study. A tertiary care center. The study was conducted on 64 consecutive adult patients undergoing thoracic aortic surgery with cardiopulmonary bypass (CPB). Group EACA received a bolus of 50 mg/kg of EACA after induction of anesthesia over 20 minutes followed by maintenance infusion of 25 mg/kg/h until chest closure. Group TXA received a bolus of 10 mg/kg of TXA after induction of anesthesia over 20 minutes followed by maintenance infusion of 1 mg/kg/h until chest closure. Cumulated mean blood loss, total packed red blood cells, and blood product requirement up to 24 h postoperatively were comparable between groups. A significant renal injury (EACA 40% v TXA 16%; p = 0.04) and increased tendency for renal failure (EACA 10% v TXA 0%, p = 0.11; relative risk 2.15) were observed with EACA compared to TXA. There was increased tendency of seizure with TXA (EACA v TXA: 3.3% v 10%; p>0.05, relative risk 1.53). There was significant increase in the D-dimer from preoperative to postoperative values in Group EACA. (p< 0.01). Both EACA and TXA were equally effective in reducing the perioperative blood loss and transfusion requirement in patients undergoing thoracic aortic surgery. While significant renal injury was observed with EACA, there was a tendency for higher incidence of seizure with TXA. Prospective placebo-controlled trials recruiting larger sample size using sensitive biomarkers are required before any recommendations.
    Journal of cardiothoracic and vascular anesthesia 09/2013; DOI:10.1053/j.jvca.2013.04.003 · 1.48 Impact Factor
  • Ramakrishnan Lakshmy
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    ABSTRACT: Development of metabolic syndrome is attributed to genes, dietary intake, physical activity and environmental factors. Fetal programming due to maternal nutrition is also an important factor especially in developing countries where intrauterine growth retardation followed by excess nutrition postnatally is causing mismatch predisposing individuals to development of metabolic syndrome and its components. Several epidemiological and animal studies have provided evidence for the link between intrauterine growth retardation and adult metabolic diseases. Deficiency of macronutrients, protein and carbohydrates, during pregnancy and gestation results in lower infant birth weight, a surrogate marker of fetal growth and subsequently insulin resistance, glucose intolerance, hypertension and adiposity in adulthood. The role of micronutrients is less extensively studied but however gaining attention with several recent studies focusing on this aspect. Several mechanisms have been proposed to explain the developmental origin of adult diseases important among them being alteration of hypothalamic pituitary axis, epigenetic regulation of gene expression and oxidative stress. All of these mechanisms may be acting at different time during gestation and contributing to development of metabolic syndrome in adulthood.
    Reviews in Endocrine and Metabolic Disorders 09/2013; 14(3). DOI:10.1007/s11154-013-9266-4 · 3.81 Impact Factor
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    ABSTRACT: To compare: (i) prevalences of thinness in school-children by four body mass index references in common use [Centre for Disease Control (CDC); Cole; Indian Academy of Pediatrics (IAP); World Health Organization (WHO)]; and (ii) relationship of thinness with absence of cardio-metabolic risk factors in these BMI references. Cross-sectional. Schools in Delhi. Anthropometry and blood pressure were measured in 16,245 school children aged 5 to 18 years. Fasting lipids and blood sugar were estimated in 2796 subjects. Age and sex-specific prevalences of thinness and predictive ability of reference cut-off for detecting any cardio-metabolic risk factor were compared. Prevalences of thinness varied with reference employed more so for boys. Overall prevalence of thinness was least with IAP reference and highest with CDC cutoffs (6.6% to 16.9% in boys, 6.5% to 10.3% in girls). Children identified as thin by any reference had comparable, significantly lower risks (ORs 0.59 to 0.73) of associated cardiometabolic aberrations. In subjects with any cardiometabolic or blood pressure aberration, the prevalence of thinness was highest with CDC and least with IAP definition. Prevalences of thinness vary considerably with the reference employed. Thin children, identified by any reference, have a lower risk of associated cardio-metabolic aberrations; however, thinness is a poor diagnostic test for this purpose. In populations undergoing nutrition transition, there is a need to link cardio-metabolic risk factors with recommended anthropometric criteria to define undernutrition.
    Indian pediatrics 06/2013; 50(11). DOI:10.1007/s13312-013-0283-x · 1.01 Impact Factor
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    ABSTRACT: The ability to use dry blood spots (DBSs) on filter paper for the analysis of urea levels could be an important diagnostic tool for areas that have limited access to laboratory facilities. We developed a method for the extraction and quantification of urea from DBSs that were stored on 3M Whatman filter paper and investigated the effect of long-term storage on the level of urea in DBSs. DBSs of 4.5 mm in diameter were used for our assay, and we determined the urea levels in blood using a commercially available enzymatic kit (UV GLDH-method; Randox laboratories Ltd., UK). The DBSs on filter discs were stored at 4℃ or at 37℃ for 120 days. The mean intra- and inter-assay coefficient of variance for our method of urea extraction from dried blood was 4.2% and 6.3%, respectively. We collected 75 fresh blood samples and compared the urea content of each fresh sample with the urea content of DBSs taken from corresponding fresh blood samples. Regression analysis reported a regression coefficient (r) value of 0.97 and a recovery of urea from dried spots was 102.2%. Urea concentrations in DBSs were stable for up to 120 and 90 days when stored at 4℃ and 37℃, respectively. Our results show that urea can be stored and quantitatively recovered from small volumes of blood that was collected on filter paper.
    Annals of Laboratory Medicine 05/2013; 33(3):190-2. DOI:10.3343/alm.2013.33.3.190 · 1.48 Impact Factor
  • Journal of the American College of Cardiology 03/2013; DOI:10.1016/S0735-1097(13)61351-0 · 15.34 Impact Factor
  • Food and Nutrition Sciences 01/2013; 04(09):94-97. DOI:10.4236/fns.2013.49A1015
  • Anju Sarupria, Neeti Makhija, Ramakrishnan Lakshmy, Usha Kiran
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    ABSTRACT: OBJECTIVE: The purpose of this study was to compare 2 different doses of ε-aminocaproic acid (EACA) and assess their relative efficacy and safety in children undergoing corrective surgery for tetralogy of Fallot (TOF). DESIGN: A prospective, randomized, controlled study. SETTING: A tertiary care center. PARTICIPANTS: One hundred twenty children undergoing corrective surgery for TOF using cardiopulmonary bypass (CPB). INTERVENTIONS: Group 1 received 100 mg/kg of EACA after induction, upon initiation of CPB, and after protamine. Group 2 received 75 mg/kg of EACA after induction, followed by a maintenance infusion of 75 mg/kg/h until chest closure, and an additional 75 mg/kg upon initiation of CPB. Group 3 did not receive any antifibrinolytic agent or placebo. MEASUREMENT AND MAIN RESULTS: Cumulative mean blood loss, total packed red blood cells, and fresh frozen plasma requirements were significantly less in group 2 (p ≤ 0.01). There were no significant differences in the total platelet concentrate transfused, re-exploration rate, incidence of renal failure, arrhythmias, neurologic complications, mortality, or length of intensive care unit stay among the 3 groups. The incidences of perioperative ST/T changes and chest closure time were significantly less in group 1 and group 2 (p ≤ 0.01). The duration of mechanical ventilation was significantly less in group 2 (p ≤ 0.01). CONCLUSIONS: EACA was effective in reducing the postoperative blood loss and transfusion requirements in children undergoing corrective cardiac surgery on CPB for TOF. The dose regimen of 75 mg/kg after induction, followed by a maintenance infusion of 75 mg/kg/h until chest closure, and an additional 75 mg/kg upon initiation of CPB were more effective.
    Journal of cardiothoracic and vascular anesthesia 09/2012; 27(1). DOI:10.1053/j.jvca.2012.07.001 · 1.48 Impact Factor
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    ABSTRACT: Context:Randomized control trials (RCT) of the effect of vitamin D/calcium supplementation on skeletal muscle strength have not shown promising effect in the elderly.Objective:Our objective was to assess the effect of vitamin D and/or calcium on muscle strength in young adults with vitamin D deficiency.Design and Setting:We conducted a RCT using a factorial design at a tertiary-care center from September 2010 to April 2011.Subjects:A total of 173 healthy females with mean age, body mass index, and 25-hydroxyvitamin D [25(OH)D] of 21.7 ± 4.4 yr, 20.8 ± 2.96 kg/m(2), and 9.3 ± 3.37 ng/ml, respectively, were block randomized to 1) double placebo, 2) calcium/placebo, 3) cholecalciferol/placebo, and 4) cholecalciferol/calcium for 6 months. Cholecalciferol was given at 60,000 IU/wk for 8 wk followed by 60,000 IU/fortnight. Elemental calcium was given in doses of 500 mg twice per day for 6 months.Methods:Assessment included hand grip (primary outcome) and pinch grip strength, distance walked in 6 min, dyspnea score, quality of life by Short Form (36) Health Survey (SP-36), serum 25(OH)D, 1,25-dihydroxyvitamin D, and intact PTH.Results:The serum 25(OH)D increased significantly to 29.9 ± 8.35 and 27.0 ± 9.54 ng/ml in two groups on cholecalciferol. The mean hand grip strength (19.4 ± 3.92, 21.1 ± 3.31, 20.6 ± 3.92, and 20.1 ± 4.00 kg) and its increase from baseline (0.3 ± 2.25, 0.3 ± 2.64, -0.3 ± 2.41, and 0.6 ± 2.30 kg) were comparable in four groups at 6 months. Quality of life, urinary calcium/creatinine ratio, and adverse effects were also comparable in groups.Conclusion:Oral cholecalciferol/calcium supplementation in the dose/schedule used is effective and safe in increasing and maintaining serum 25(OH)D. However, this does not lead to improved skeletal muscle strength in young females.
    The Journal of Clinical Endocrinology and Metabolism 08/2012; 97(12). DOI:10.1210/jc.2012-2340 · 6.31 Impact Factor

Publication Stats

1k Citations
397.82 Total Impact Points

Institutions

  • 2009–2014
    • AIIMS Bhopal All India Institute of Medical Sciences
      Bhopal, Madhya Pradesh, India
  • 1999–2014
    • All India Institute of Medical Sciences
      • • Department of Cardiac Biochemistry
      • • Department of Cardiology
      New Dilli, NCT, India
  • 2005
    • Sunder Lal Jain Hospital
      Old Delhi, NCT, India
  • 1997
    • National Institute of Animal Nutrition and Physiology
      Bengalūru, Karnātaka, India