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.

Polymorphic variants of β1 adrenergic receptor gene (Ser49Gly & Arg389Gly) in healthy Tamilian volunteers.

Background & objectives: Several studies reported the polymorphisms of β1-adrenergic receptor gene in healthy volunteers and its influence on cardiovascular disorders. We investigated the genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism in healthy volunteers of South Indian Tamilian population vis-à-vis other major ethnic groups. Methods: The genetic variants were determined by using Taqman 5’ nuclease assay- real time PCR analysis in 533 normal healthy volunteers (18-60 yr; M=290; F=243). The allelic discrimination analysis was done by 7700 SDS software. Results: The estimated genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism were compared with other major populations. The frequencies of the variant alleles Gly49 and Gly389 were 15.1 and 25.8 per cent respectively. Interpretation & conclusions: Our study shows that interethnic variation exists in the polymorphisms of β1-adrenergic receptor gene and the results generated in this study might serve as a genetic marker for further studies in Tamilian (South India) population.

Gly460Trp polymorphism of the ADD1 gene and essential hypertension in an Indian population: A meta-analysis on hypertension risk.

BACKGROUND: Essential hypertension is a complex genetic trait. Genetic variant of alpha adducin (ADD1) gene have been implicated as a risk factor for hypertension. Given its clinical significance, we investigated the association between ADD1 Gly460Trp gene polymorphism and essential hypertension in an Indian population. Further, a meta-analysis was carried out to estimate the risk of hypertension. METHODS: In the current study, 432 hypertensive cases and 461 healthy controls were genotyped for the Gly460Trp ADD1 gene polymorphism. Genotyping was determined by real time PCR using Taqman assay. Multiple logistic regression analysis was used to detect the association between Gly460Trp polymorphism and hypertension. RESULTS: No significant association was found in the genotype and allele distribution of Gly460Trp polymorphism with hypertension in our study. A total of 15 case-control studies were included in the meta-analysis. There was no evidence of the association of Gly460Trp polymorphism with hypertension in general or in any of the sub group. CONCLUSIONS: We found that the Gly460Trp polymorphism is not a risk factor for essential hypertension in a south Indian Tamilian population. However, the role of ADD1 polymorphism may not be excluded by a negative association study. Further, large and rigorous case-control studies that investigate gene–gene–environment interactions may generate more conclusive claims about the molecular genetics of hypertension.

Electrocardiographic and echocardiographic changes in perinatal asphyxia.

OBJECTIVE: To study the usefulness of cardiac enzymes in evaluating myocardial damage in perinatal asphyxia. METHODS: Thirty term babies with perinatal asphyxia and without any congenital malformations were selected as cases. They were compared with thirty healthy term babies without asphyxia. Myocardial dysfunction was evaluated using clinical, electrocardiography, echocardiography and cardiac enzymes i.e, troponin-T and CK-MB levels. RESULTS: Among the 30 cases 23 had evidence of myocardial involvement while one baby in the control group had ECG evidence compatible with cardiac involvement. Cardiac enzymes were significantly increased in babies with perinatal asphyxia. The mean level of C-troponin-T among cases and controls were 0.22+/-0.28 and 0.003+/-0.018 while CK-MB levels were 121+/-77.4 IU/L and 28.8 +/- 20.2 IU/L respectively. C-troponin-T had higher sensitivity and specificity compared to CK-MB levels. Moreover, C troponin-T levels correlated well with severity and outcome in babies with perinatal asphyxia. CONCLUSION: C-Tropopnin assay is useful in evaluating the severity of myocardial damage and outcome in perinatal asphyxia.

Cardiac enzyme levels in myocardial dysfunction in newborns with perinatal asphyxia.

OBJECTIVE: To study the usefulness of cardiac enzymes in evaluating myocardial damage in perinatal asphyxia. METHODS: Thirty term babies with perinatal asphyxia and without any congenital malformations were selected as cases. They were compared with thirty healthy term babies without asphyxia. Myocardial dysfunction was evaluated using clinical, electrocardiography, echocardiography and cardiac enzymes i.e, troponin-T and CK-MB levels. RESULTS: Among the 30 cases 23 had evidence of myocardial involvement while one baby in the control group had ECG evidence compatible with cardiac involvement. Cardiac enzymes were significantly increased in babies with perinatal asphyxia. The mean level of C-troponin-T among cases and controls were 0.22+/-0.28 and 0.003+/-0.018 while CK-MB levels were 121+/-77.4 IU/L and 28.8 +/- 20.2 IU/L respectively. C-troponin-T had higher sensitivity and specificity compared to CK-MB levels. Moreover, C troponin-T levels correlated well with severity and outcome in babies with perinatal asphyxia. CONCLUSION: C-Tropopnin assay is useful in evaluating the severity of myocardial damage and outcome in perinatal asphyxia.

Rheumatic fever and rheumatic heart disease: primary prevention is the cost effective option.

OBJECTIVE: To measure the economic output/input ratios for the various options of prevention of rheumatic fever/rheumatic heart disease (RF/RHD) and check the viability of primary prevention vis-à-vis secondary and tertiary preventions. METHODS: Cost accounting of the various prevention options was calculated for each variable as available in literature. Actual data as obtainable for the financial year ending March 2006 were computed for the Pondicherry population. Both direct and indirect costs (including community/social costs) were worked out using mostly primary data and wherever necessary, secondary data. Certain scientific assumptions were used where exact data was not available. RESULTS: Primary prevention is the definite viable economic option (1:1.56) compared to secondary (1: 1.07) and tertiary (1: 0.12) preventions. In fact, the current stress on only secondary and tertiary preventions is found to be economically unviable. CONCLUSION: It is postulated that primary prevention as a practical policy in tackling RF and RHD can be recommended.

Outcome of scorpion sting envenomation after a protocol guided therapy.

OBJECTIVE: Scorpion sting (SS) envenomation is a life threatening emergency in children, though not so severe in adults. Attempt to develop protocol using prazosin and dobutamine and few other drugs to treat SS. METHODS: Children aged 0-13 years with a history of scorpion sting were studied. Clinical features, complications, drug therapy and outcome of the cases for the period 1992-97(N = 186) was collected by the authors and also from the medical records department (RETROSPECTIVE GROUP). Cases treated during 1997-2000 (N = 198) as per the protocol were recorded as PROSPECTIVE GROUP. All the cases were observed for at least for 24 hours. Cases coming within 4 hours of a sting were given a dose of Prazosin (30 mic.gm/Kg/dose) and were observed. Those who came after 4 hours & were asymptomatic received only symptomatic treatment. Cases with signs of envenomation received Prazosin every 6 hourly till recovery. Cases having acute pulmonary edema (APE) were treated with dobutamine and sodium nitroprusside drip. Complicated cases were monitored in PICU as per the protocol. RESULT: Complications associated with excessive parasympathetic and sympathetic stimulation were observed. Myocarditis was observed due to the toxin and excessive catecholamine, which complicated in left ventricular failure (LVF) and APE. Nearly half of the children with acute myocarditis developed APE. Death was mainly due to myocarditis and APE, with or without encephalopathy. Mortality was high in children who received steroid and antihistaminics outside and who came late (> 4 hours). CONCLUSION: Complication rate remained almost same in both the groups. There was a significant reduction in overall mortality (P = < 0.0155) and in deaths associated with APE (P = < 0.0001) after the protocol guided therapy. There was also a reduction in mortality in encephalopathy group though not statistically significant. This treatment protocol and aggressive management of APE reduced the mortality due to SS significantly.

Supravalvular aortic stenosis and coronary ostial stenosis in homozygous familial hypercholesterolemia.

Patients with homozygous familial hypercholesterolemia exhibit severe hypercholesterolemia, cutaneous and tendon xanthomata, and premature atherosclerosis from childhood. A rare presentation of this condition with supravalvular aortic stenosis and coronary ostial stenosis is described.

Prevalence of left atrial thrombus in rheumatic mitral stenosis with atrial fibrillation and its response to anticoagulation: a transesophageal echocardiographic study.

BACKGROUND: The frequency of occurrence of left atrial thrombi, and the effect of anticoagulation in patients with rheumatic mitral stenosis and atrial fibrillation is not well established. This study was conducted to evaluate the occurrence of left atrial body and left atrial appendage clots in patients with rheumatic mitral stenosis and atrial fibrillation, and to document the effect of long-term anticoagulation on clot dissolution. METHODS AND RESULTS: Consecutive patients with severe rheumatic mitral stenosis and atrial fibrillation were assessed by transesophageal echocardiography. Those with left atrial body or left atrial appendage clots were anticoagulated with oral nicoumalone. Transesophageal echocardiography was then repeated in patients on anticoagulation who were on regular follow-up, and in whom percutaneous transvenous mitral commissurotomy could be considered. Of the 490 patients studied, 163 had left atrial body or left atrial appendage clots. A repeat transesophageal echocardiographic examination was done in 50 patients who had optimal anticoagulation for a period of 6 months. Only 2 of the 17 patients who had left atrial body clots had successful clot dissolution after long-term anticoagulation, while the left atrial appendage clots disappeared in 31 of 33 patients (p<0.001). CONCLUSIONS: Left atrial clots are present in a third of patients with severe rheumatic mitral stenosis and atrial fibrillation. Isolated left atrial appendage clots in patients with rheumatic mitral stenosis and atrial fibrillation can disappear with long-term anticoagulation, while thrombi that extend into the left atrial body may persist despite optimal anticoagulation.

Pericardiectomy for constrictive pericarditis: is prolonged inotropic support a bad omen?

Sixty-seven patients who underwent pericardiectomy for constrictive pericarditis at JIPMER, Pondicherry between 1987 and 1998 were the subjects of the study. Pre-operatively 70% of cases were in the New York Heart Association classes III and IV categories with clinical signs suggestive of constriction ie, raised jugular venous pressure in 99%, pleural effusion in 77%, pedal oedema in 61% and ascites in 55% of the cases. Seventy-five per cent of the cases underwent pericardiectomy through a median sternotomy and the rest via left anterolateral thoracotomy. Low cardiac output was evidenced in 70% of cases postoperatively which was managed by early institution and prolonged use of inotropes. There was 9% mortality especially in the early part of the experience. Tuberculous pathology was confirmed histologically in 57% cases. Sixty-three per cent of cases are presenting in follow-up in New York Heart Association class I. Prolonged use of inotropes instituted early in postoperative period is recommended to prevent postoperative ventricular dysfunction with adrenaline being the preferred inotrope. It is concluded that postoperative New York Heart Association class and long term survival were not significantly influenced by pre-operative New York Heart Association class, operative approach or peri-operative low cardiac output syndrome requiring prolonged inotropic support.

Angioplasty of membranous obstruction of inferior vena cava.

Membranous obstruction of vena cava (MOVC) is a common cause of hepatic venous outflow obstruction. Surgical procedures utilized to relieve symptoms carry a high morbidity and mortality. A patient who presented with gradual onset ascites and dilated, tortuous veins over the anterior abdominal wall and the back was found to have MOVC by inferior vena cavogram. Balloon dilatation of the obstruction was done successfully through a transvenous approach. Following this, the patient improved remarkably. The procedure is safe, effective and easy to perform. This balloon angioplasty provides alternative method for treatment of membranous obstruction of vena cava.

A comparative evaluation of metoprolol and methyldopa in the management of pregnancy induced hypertension.

Thirty patients matched for age, parity, socioeconomic status and severity of pregnancy induced hypertension (PIH) were randomly allocated to treatment with metoprolol or methyldopa. The average fall in diastolic blood pressure was significant in the group treated with metoprolol as compared with the methyldopa group (p less than 0.01). There were 3 perinatal deaths in the methyldopa group and 1 in the metoprolol group; the mean birth weight of the babies was higher in cases treated with metoprolol. The results suggest metoprolol to be more efficacious with regard to control of hypertension and fetal outcome in cases of pregnancy induced hypertension.

Sensory nerve conduction in diabetes mellitus and diabetic neuropathy.

Electrophysiological evaluation of conduction in sensory fibres of right ulnar and median nerves were carried out in normal subjects and diabetics with and without neuropathy. The sensory conduction velocities of ulnar as well as median nerves are significantly depressed in both groups of diabetics, particularly in those with neuropathy. The diabetics with or without neuropathy require a higher strength of stimulus for conduction in both median and ulnar nerves as compared to the normal subjects. The amplitude of action potentials is also lowered in both ulnar and median nerves of the two groups of diabetics. Estimation of conduction velocities of sensory fibres can be considered as a more useful parameter than the measurement of amplitude of action potentials in the diagnosis and evaluation of neuropathy in diabetics. It is concluded that assessment of sensory nerve conduction in median nerve is a better indicator than that of ulnar nerve for this purpose.