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1.
Egypt Heart J ; 73(1): 7, 2021 Jan 11.
Article in English | MEDLINE | ID: mdl-33428005

ABSTRACT

BACKGROUND: Dual antiplatelet therapy is the current standard of care after acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). We intended to study the pattern of use of ticagrelor in patients with acute coronary syndrome undergoing PCI and the effect of switching over to other P2Y12 receptor inhibition on clinical outcomes. RESULTS: All patients aged > 18 years who had been admitted with acute coronary syndrome and had been provided ticagrelor as the second antiplatelet agent were included as study participants. The primary outcome of the study was the composite outcome of death, recurrent myocardial infarctions, re-intervention, and major bleeding. We studied 321 patients (54 female patients, 16.82%). The mean age of the patients was 56.65 ± 11.01 years. Ticagrelor was stopped in 76.7% on follow-up. It was stopped in 6.3%, 13.5%, 13.1%, 21.9%, and 45.1% of patients during the first month but after discharge, between first and third months, between 3 and 6 months, between 6 and 12 months, and after 12 months, respectively. In the majority of patients, ticagrelor was replaced by clopidogrel (97.9%). It was stopped according to the physician's discretion in 79.3% of patients, whereas it was the cost of the drug that made the patient to get swapped to another agent in 18.6%. No difference in the primary composite outcome was observed between the groups where ticagrelor was continued post 12 months and ticagrelor was continued and ticagrelor was switched-over to another agent. Similarly, no difference in death, recurrent myocardial infarctions, re-interventions, or major bleeding manifestations was observed between the two groups. CONCLUSION: In patients with acute coronary syndrome who undergo PCI, we observed that early discontinuation of ticagrelor and switching over to other P2Y12 inhibitors after discharge did not affect clinical outcomes.

2.
Mol Biol (Mosk) ; 46(4): 598-604, 2012.
Article in English | MEDLINE | ID: mdl-23113348

ABSTRACT

Abelmoschus esculentus (okra) is one of the polysaccharide rich crop plants. The polysaccharides interfere with nucleic acids and protein isolation thereby affecting the downstream molecular analysis. So, to understand the molecular systematics of okra, high quality DNA, RNA and proteins are essential. In this study we present a method for extracting genomic DNA, RNA and proteins from polysaccharide rich okra tissues. The conventional extraction procedures were integrated with purification treatments with pectinase, RNase and proteinase K, which improved the quality and quantity of DNA as well. Using SDS, additional washes with CIA and NaCl precipitation improved the RNA isolation both quantitatively and qualitatively. Finally, ammonium acetate mediated protein precipitation and re-solubilization increased the quality of total protein extracts from the okra leaves. All of the methods above not only eliminated the impurities but also improved the quality and quantity of nucleic acids and proteins. Further, we subjected these samples to versatile downstream molecular analyses such as restriction endonuclease digestion, RAPD, Southern, reverse transcription-PCR and Western analysis and were proved to be successful.


Subject(s)
Abelmoschus/metabolism , DNA, Plant/isolation & purification , Molecular Biology/methods , Plant Proteins/isolation & purification , Polysaccharides/isolation & purification , Abelmoschus/chemistry , Acetates/chemistry , Chemical Precipitation , DNA, Plant/chemistry , Endopeptidase K/metabolism , Nucleic Acids/chemistry , Plant Proteins/chemistry , Polygalacturonase/metabolism , Polysaccharides/chemistry , RNA, Plant/isolation & purification , Ribonucleases/metabolism
3.
Ayu ; 31(2): 251-4, 2010 Apr.
Article in English | MEDLINE | ID: mdl-22131720

ABSTRACT

Caesalpinia bonduc (L.) Roxb. (Kuberaksha) is an Ayurvedic herb used in the management of malaria, liver disorders, worms, edematous conditions, etc. Based on classical Ayurvedic textual indications and recent pharmacological studies, its leaf powder was selected for studying its effect clinically on filaria. Before conducting the clinical trails, this leaf powder was subjected to certain chemical studies to find the pH, ash value, extractive values, High Performance Thin Layer Chromatography (HPTLC), etc. for standardization of the drug.

4.
Article in English | MEDLINE | ID: mdl-17600761

ABSTRACT

Pelecypod shell originated from Kolleru lake of Andhra Pradesh is used in the present work. It contains Mn(II) and Fe(III) in traces. The EPR spectrum of the compound is due to Mn(II) which is in three independent sites. The three g values are evaluated with slight differences. The hyperfine component varies from 9.33 to 9.49mT. The zero field splitting parameter is also ranges from 43.8(1) to 44.1(1)mT. Using the covalence parameter the number of ligands around metal is estimated as 20. In EPR spectrum Fe(III) is identified. The optical absorption spectrum is attributed to Mn(II) in octahedral geometry. Further 10 Dq band is attributed to Fe(II) in the optical absorption spectrum. NIR spectral results are due to water fundamentals, whereas IR and Raman spectrum is due to carbonate ion fundamentals.


Subject(s)
Bivalvia/anatomy & histology , Bivalvia/chemistry , Electron Spin Resonance Spectroscopy/methods , Spectrophotometry/methods , Spectrum Analysis, Raman/methods , Animals , Vibration
5.
Food Addit Contam ; 24(12): 1367-73, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17917911

ABSTRACT

The effects of cotton-corn rotation and glyphosate use on levels of soil-borne Aspergillus flavus, aflatoxin and fumonisin contamination in corn and cotton seed were determined during 2002-2005 in Stoneville, Mississippi (USA). There were four rotation systems (continuous cotton, continuous corn, cotton-corn and corn-cotton) for both glyphosate-resistant (GR) and non-GR cultivars-herbicide system arranged in a randomized complete block design with four replications. Aspergillus flavus populations in surface (5-cm depth) soil, sampled before planting (March/April), mid-season June) and after harvest (September), ranged from 1.47 to 2.99 log (10) cfu g(-1) soil in the four rotation systems. Propagules of A. flavus were higher in the continuous corn system compared to the continuous cotton system on three sample dates, and cotton rotated with corn decreased A. flavus propagules in three of nine sample dates. Propagules of A. flavus were significantly greater in plots with GR cultivars compared to non-GR cultivars in three samples. In cotton seed, aflatoxin and fumonisin levels were similar (< or = 4 microg kg(-1) and non-detectable, respectively) regardless of rotation and glyphosate. In corn grain, aflatoxin was above the regulatory level (> or = 20 microg kg(-1)) only in GR cultivar in 2004 and 2005. Fumonisin was higher in non-GR cultivar (4 mg kg(-1)) regardless of rotation in 2004; however, in 2002, 2003 and 2005, aflatoxin and fumonisin levels were similar regardless of rotation and glyphosate. These results indicate the potential for increased aflatoxin and fumonisin levels (1 of 4 years) in corn; however, climatic conditions encountered during this study did not allow for mycotoxin production. In laboratory incubation studies, fairly high concentrations of glyphosate were required to inhibit A. flavus growth; however no short-term effect of soil treatment with glyphosate on A. flavus populations were observed. These data suggest that altered populations of A. flavus or higher aflatoxin concentrations in corn grain were due to indirect effects of the GR cropping system.


Subject(s)
Aspergillus flavus/growth & development , Glycine/analogs & derivatives , Gossypium/microbiology , Mycotoxins/analysis , Plants, Genetically Modified/microbiology , Zea mays/microbiology , Agriculture/methods , Analysis of Variance , Aspergillus flavus/isolation & purification , Glycine/analysis , Mississippi , Soil/analysis , Glyphosate
6.
J Indian Med Assoc ; 105(1): 25-8, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17802973

ABSTRACT

Prediabetes occurs due to two basic defects--insulin resistance and/or beta-cell failure. An observation suggested that insulin resistance may be associated with essential hypertension. There are some thoughts to favour the argument that insulin resistant Individuals are at a higher risk to develop hypertension as compared to insulin sensitive individuals. Some pathophysiological causes which have been commonly observed and hypothesised are narrated in this article. Management of hypertension in prediabetes should include antihypertensives and therapeutic lifestyle modification. To manage hypertension in prediabetes one should think for dietary modification, reduced salt intake, physical activity, smoking cessation, use of statins and antihypertensives.


Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension/complications , Insulin Resistance/physiology , Prediabetic State/complications , Antihypertensive Agents/classification , Blood Glucose/analysis , Humans , Hypertension/blood , Hypertension/drug therapy , Life Style , Prediabetic State/blood , Risk Factors
7.
EuroIntervention ; 02: 310-317, 2007. ilus
Article in English | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1062670

ABSTRACT

Background: SIMPLE II was a multi-centre, prospective registry study aimed at investigating the safety andefficacy of the Infinnium™ (Sahajanand Medical Technologies Pvt. Ltd, India) paclitaxel-eluting stent forthe treatment of single de novo lesions in the native coronary arteries.Methods: One hundred and three patients with symptomatic coronary artery disease were treated for singlede novo native coronary artery lesions using the Infinnium™ stent (paclitaxel concentration1.4 mcg/mm2 released over 48 days) in a multi-centre, prospective study performed on 3 continents (Asia,Europe and South America). The primary safety endpoint was major adverse cardiac events at 30 days(MACE 30d) and efficacy was assessed by in-stent binary restenosis as measured by quantitative coronaryangiography (QCA) at six-month follow-up. A clinical follow-up was scheduled at nine months.Results: The mean patient age was 58.5 years; 70.9% were males; 43.7% had unstable angina and 38.8%previous myocardial infarction. Risk factors included hypertension in 62.1%, hypercholesterolemia in52.4%, current smoking in 32.0% and diabetes in 28.2%. Stent implantation was successful in all patients,with more than one stent being implanted in 9 patients (8.7%). Hierarchical MACE 30d was 2.9%. At ninemonths, 101 patients had clinical follow-up (1 patient had died and 1 refused). There was one death(1.0%), one Q-wave myocardial infarction (Q MI) (1.0%), three non-Q MIs (2.9%), one clinically-driven targetlesion Coronary Artery Bypass Grafting (CABG) (1.0%), and one clinically-driven target lesion repeatpercutaneous coronary intervention (re-PCI) (1.0%). The overall event-free rate at nine months was 93.2%.QCA revealed in-stent and in-segment late loss of 0.38±0.49 mm and 0.18±0.46 mm, resulting in binaryrestenosis rates of 7.3% and 8.3%, respectively. There was one case of late stent thrombosis in the patientexperiencing the Q MI and subsequent re-PCI...


Subject(s)
Angioplasty , Coronary Restenosis , Myocardial Revascularization
8.
EuroIntervention ; 2(3): 310-7, 2006 Nov.
Article in English | MEDLINE | ID: mdl-19755306

ABSTRACT

BACKGROUND: SIMPLE II was a multi-centre, prospective registry study aimed at investigating the safety and efficacy of the Infinnium (Sahajanand Medical Technologies Pvt. Ltd, India) paclitaxel-eluting stent for the treatment of single de novo lesions in the native coronary arteries. METHODS: One hundred and three patients with symptomatic coronary artery disease were treated for single de novo native coronary artery lesions using the Infinnium stent (paclitaxel concentration 1.4 mcg/mm2 released over 48 days) in a multi-centre, prospective study performed on 3 continents (Asia, Europe and South America). The primary safety endpoint was major adverse cardiac events at 30 days (MACE 30d) and efficacy was assessed by in-stent binary restenosis as measured by quantitative coronary angiography (QCA) at six-month follow-up. A clinical follow-up was scheduled at nine months. RESULTS: The mean patient age was 58.5 years; 70.9% were males; 43.7% had unstable angina and 38.8% previous myocardial infarction. Risk factors included hypertension in 62.1%, hypercholesterolemia in 52.4%, current smoking in 32.0% and diabetes in 28.2%. Stent implantation was successful in all patients, with more than one stent being implanted in 9 patients (8.7%). Hierarchical MACE 30d was 2.9%. At nine months, 101 patients had clinical follow-up (1 patient had died and 1 refused). There was one death (1.0%), one Q-wave myocardial infarction (Q MI) (1.0%), three non-Q MIs (2.9%), one clinically-driven target lesion Coronary Artery Bypass Grafting (CABG) (1.0%), and one clinically-driven target lesion repeat percutaneous coronary intervention (re-PCI) (1.0%). The overall event-free rate at nine months was 93.2%. QCA revealed in-stent and in-segment late loss of 0.38+/-0.49 mm and 0.18+/-0.46 mm, resulting in binary restenosis rates of 7.3% and 8.3%, respectively. There was one case of late stent thrombosis in the patient experiencing the Q MI and subsequent re-PCI. CONCLUSIONS: The Infinnium paclitaxel-eluting stent appears to be safe and efficacious for the treatment of single de novo lesions in coronary arteries in a patient population with symptomatic coronary artery disease (CAD).

9.
J Assoc Physicians India ; 51: 175-7, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12725262

ABSTRACT

OBJECTIVE: To determine the prevalence of renal artery disease and to correlate the underlying risk factors like age, sex, diabetes, hypertension, urea and creatinine in patients who have undergone angiogram for cardiovascular diseases. METHODS: Retrospective analysis of the reports of angiogram of patients who have undergone cardiac catheterization in Vijaya Heart Foundation for cardiovascular diseases. RESULTS: The prevalence of renovascular stenosis is 12.4%. Prevalence of hypertension and diabetes in the group of patients with renovascular stenosis compared with group having coronary artery disease is not statistically significant (p > 0.8). Univariate and multivariate logistic identified age, diabetes, hypertension and urea as independent predicators of renal artery stenosis; while variables like sex and serum creatinine were not associated. CONCLUSION: High prevalence of unsuspected renovascular abnormalities is found in patients who undergo angiography for cardiovascular disease. Factors like age, diabetes, hypertension and urea could be clinical predicators of renal artery stenosis. Hence renal arteries should be visualized routinely in patients undergoing coronary angiogram for cardiovascular disease.


Subject(s)
Cardiac Catheterization , Cardiovascular Diseases/epidemiology , Kidney Diseases/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/complications , Cardiovascular Diseases/diagnosis , Female , Humans , India/epidemiology , Kidney Diseases/diagnosis , Kidney Diseases/etiology , Male , Middle Aged , Prevalence , Retrospective Studies , Risk Factors
10.
Metabolism ; 49(11): 1417-23, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11092504

ABSTRACT

The euglycemic and hypolipidemic activities of PAT5A, a novel pyridine analog of thiazolidinedione, have been evaluated in different animal models. Administration of PAT5A to db/db mice resulted in dose-dependent decreases in plasma glucose, triglyceride, and insulin levels, and an improved glucose tolerance. The glucose-lowering activity of PAT5A was better than that of troglitazone and comparable to that of rosiglitazone. In addition, PAT5A showed better lipid-lowering activity than troglitazone or rosiglitazone. A similar profile was seen in ob/ob mice. In high-fat-fed Sprague Dawley rats, PAT5A treatment reduced plasma triglyceride and total cholesterol levels. An in vitro peroxisome proliferator activated receptor gamma (PPARgamma) transactivation assay in HEK-293 cells showed poor transactivation for PAT5A compared with rosiglitazone. PAT5A did not show any PPARalpha- or PPARdelta-activating properties. Ex vivo study in db/db mice treated with PAT5A showed decreased activity of liver glucose 6-phosphatase, a key enzyme in gluconeogenesis. A 28-day probe toxicity study in Wistar rats did not show any treatment-related alterations in hematologic and biochemical parameters, nor any macroscopic and microscopic changes in the vital organs, whereas rosiglitazone treatment increased liver and heart weights. Our results indicate that PAT5A is a potent insulin sensitizer and hypolipidemic compound with a weak PPARgamma activation potential. Both in vivo and in vitro results suggest that PAT5A improves glucose kinetics and lipid levels through mechanisms not related to PPAR activation.


Subject(s)
Hypoglycemic Agents/pharmacology , Hypolipidemic Agents/pharmacology , Pyrrolidines/pharmacology , Receptors, Cytoplasmic and Nuclear/agonists , Thiazoles/pharmacology , Thiazolidinediones , Transcription Factors/agonists , Animals , Cholesterol, Dietary/administration & dosage , Glucose-6-Phosphatase/metabolism , Hypoglycemic Agents/toxicity , Hypolipidemic Agents/toxicity , Liver/drug effects , Liver/enzymology , Male , Mice , Mice, Inbred C57BL , Pyrrolidines/toxicity , Rats , Rats, Sprague-Dawley , Receptors, Cytoplasmic and Nuclear/genetics , Thiazoles/toxicity , Transcription Factors/genetics , Transcriptional Activation/drug effects
11.
Cathet Cardiovasc Diagn ; 38(4): 377-8, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8853147

ABSTRACT

We describe a patient who developed the unusual haemodynamic phenomenon of periodic intermittent electromechanical dissociation during regular sinus tachycardia about 20 hours after mitral valve replacement with a tilting disc mechanical prosthesis. Echocardiographic confirmation allowed prompt and life saving corrective surgery for a stuck prosthetic valve disc.


Subject(s)
Heart Arrest/physiopathology , Heart Valve Prosthesis , Hemodynamics/physiology , Mitral Valve , Adult , Cardiopulmonary Bypass , Heart Arrest/surgery , Humans , Male , Prosthesis Failure
13.
Indian J Med Sci ; 48(11): 256-60, 1994 Nov.
Article in English | MEDLINE | ID: mdl-7868162

ABSTRACT

Epidemiological studies have indicated a lower incidence of cardiovascular disease in populations with a high habitual intake of marine fish and fish oils, and this apparent protection may be due to the presence of n-3 fatty acids in the dietary fish. Two populations, a rish consuming one from coastal area and an inland one with non fish consuming from Nellore district or South India were selected for the present study. A total of one thousand healthy subjects were randomly chosen (500 in each population) from both sexes, aged from 20 to 70 years. The concentration of serum cholesterol, triacylglycerol and LDL-cholesterol were significantly lower in fish consumers, whereas HDL-cholesterol was higher in fish consumers than in non fish consumers. The difference between the percent quantities of the three n-3 fatty acids (eicosapentaenoic, docosapentaenoic and docosahexaenoic acids) was highly significant (p < 0.001) with a greater value in fish consumers.


Subject(s)
Cardiovascular Diseases/epidemiology , Diet, Atherogenic , Fatty Acids/blood , Feeding Behavior , Fish Products , Adult , Aged , Aging/blood , Animals , Cholesterol/blood , Female , Fishes , Humans , India , Male , Middle Aged , Risk Factors , Triglycerides/blood
17.
Int J Cardiol ; 31(1): 33-7, 1991 Apr.
Article in English | MEDLINE | ID: mdl-2071248

ABSTRACT

Pseudoaneurysms of the ascending aorta is a rare postoperative complication which, once identified, needs urgent attention. This report describes 5 consecutive patients with this complication who presented 2-15 months following open heart surgery. The role of cross-sectional echocardiography in diagnosis of this condition is highlighted.


Subject(s)
Aorta/diagnostic imaging , Aortic Aneurysm/etiology , Cardiac Surgical Procedures/adverse effects , Echocardiography , Adult , Aortic Aneurysm/diagnostic imaging , Female , Humans , Male , Middle Aged , Postoperative Complications
18.
Indian Heart J ; 42(2): 113-6, 1990.
Article in English | MEDLINE | ID: mdl-2081607

ABSTRACT

The records of 362 patients of Ventricular Septal Defect (VSD) were analysed to find out the incidence of aortic regurgitation (AR) and their hemodynamic and angiographic features. Thirty-seven patients (10.2%) were found to have AR, whose mean age was 13.4 years (range: 2-45) and male to female ratio was 5:1. Of the 37 cases 31 (84%) had infracristal and 6 (16%) had supracristal VSD. In 31 patients with infracristal VSD the prolapsing cusp was Right Coronary Cusp (RCC) in 14 (48%), Noncoronary Cusp (NCC) in 12 (41%) and both RCC and NCC in 3 (11%). Of the 6 patients with supracristal VSD the prolapsing cusp was RCC in 5 (83%) and NCC in 1 (17%). In two patients the AR was due to bicuspid aortic valve. The pulmonary artery pressure was normal in 26 of 37 (70.2%) patients and the left to right shunt was 1.5:1 or less in 23 of 37 (62%) patients. Nineteen of the 37 patients (51.3%) had grade I or II AR and the remaining 18 (48.7%) had grade III or IV AR. There was no relationship between the severity of AR and the location of the VSD. In conclusion, in this series, the incidence of VSD+AR is relatively higher and that of supracristal VSD is lower. In majority of patients the left to right shunt is small and pulmonary artery pressure within normal limits. The prolapse of RCC is more common in supracristal VSD and there is no relation between the severity of AR and the location of the VSD.


Subject(s)
Aortic Valve Insufficiency/complications , Heart Septal Defects, Ventricular/complications , Adolescent , Adult , Angiography , Aortic Valve Insufficiency/epidemiology , Aortic Valve Prolapse/complications , Child , Child, Preschool , Female , Heart Septal Defects, Ventricular/epidemiology , Hemodynamics , Humans , Male , Middle Aged
19.
Indian Heart J ; 42(1): 62-5, 1990.
Article in English | MEDLINE | ID: mdl-2351402

ABSTRACT

The hemodynamic data and electrocardiograms of thirty-three patients of moderate to severe aortic stenosis were analysed retrospectively to find out if there was any correlation between 12 lead ECG-QRS score and left ventricular peak systolic pressure (LVPSP) and/or peak systolic gradient (PSG) across the aortic valve. The mean age of the study population was 33.33 (+/- 15.02SD) years, with the male to female ratio being 9:2. The mean 12 lead ECG-QRS score in these 33 patients was 281 mm (+/- 46.02SD), the mean LVPSP 203.52 mmHg (+/- 46.62SD) and the mean PSG across the aortic valve was 81.0 mmHg (+/- 41.62SD). There was good correlation of 12 lead ECG-QRS score with LVPSP (r = 0.47, P less than 0.001) and with PSG across the aortic valve (r = 0.58, P less than 0.001), latter being more significant. The best correlation was however found between 12 lead ECG-QRS score and PSG across the aortic valve in patients over 35 years of age (r = 0.88). In conclusion there is a direct relationship between 12 lead ECG-QRS score and peak systolic gradient across the aortic valve and the latter can be approximately calculated non-invasively with the help of regression equation- Peak systolic gradient (in mmHg) = 12 lead ECG-QRS score/3 - 10.6


Subject(s)
Aortic Valve Stenosis/diagnosis , Electrocardiography , Adolescent , Adult , Cardiac Catheterization , Child , Child, Preschool , Female , Humans , Male , Middle Aged
20.
Indian Heart J ; 41(5): 296-300, 1989.
Article in English | MEDLINE | ID: mdl-2599538

ABSTRACT

The coronary angiograms of 1,500 cases performed between 1981 and 1989 were analysed to find out the incidence of Myocardial Bridge (MB) and its significance as regards myocardial ischemia. Sixteen of these (1.06%) were found to have MB. Their ages ranged from 27-70 years (m = 49.2) and male:female ratio was 13:3. Out of 16 patients, 7 (group A) had associated coronary artery disease (CAD) (7 of 1421; 0.49%) and remaining 9 (group B) had no associated CAD (9 of 79; 11.39%). All the MB were found on left anterior descending artery (LAD) (3 on proximal LAD and 13 on mid LAD). No MB was found on right coronary artery (RCA) or circumflex arteries. The location of the MB did not affect the pattern of CAD. Chronic stable angina was the commonest presenting symptom in group A patients (5 out of 7) and atypical angina in group B patients (5 out of 9). Majority of group B patients had either normal or nonspecific ST-T changes in ECG (7 out of 9). However, the presence of previous myocardial infarction or ECG evidence of 'Q' wave infarction (2 out of 2) was always associated with significant CAD. Similarly, regional wall motion abnormalities on echocardiogram were always found in patients with significant CAD and old myocardial infarction. All 9 patients with MB and normal coronary arteries were managed conservatively with good relief of symptoms, whereas other seven patients were managed on the merits of the underlying CAD. In conclusion, the MB is a normal variant found incidentally on coronary angiography, and does not have any definite clinical correlations or pathological significance.


Subject(s)
Coronary Angiography , Coronary Vessel Anomalies/epidemiology , Adult , Aged , Angina Pectoris/etiology , Chronic Disease , Female , Humans , India/epidemiology , Male , Middle Aged
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