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Biomedical subjects

J L Mehta

Publications and source records attributed to J L Mehta.

At least 19 recordsLinked to original sources
PubMed2006

Cardioprotective effects of rosiglitazone are associated with selective overexpression of type 2 angiotensin receptors and inhibition of p42/44 MAPK.

Current evidence points to renin-angiotensin system as a key mediator in ischemia-reperfusion injury. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand, has recently been shown to confer cardioprotection against ischemia-reperfusion in animal models. We sought to examine the expression of ANG II receptors during PPAR-gamma-mediated cardioprotection. Male Sprague-Dawley rats (nondiabetic) were fed either regular rat chow (control diet group, n = 9) or rosiglitazone-rich diet (rosiglitazone-rich diet group, n = 9) and were subjected to 1 h of myocardial ischemia followed by 1 h of reperfusion. A third group of rats had only thoracotomy and pericardiotomy and served as a sham control group (n = 9). Hemodynamics, infarct size, and expression of ANG II type 1 and type 2 receptors (AT1 and AT2) were measured in all groups. There was a 58% reduction of infarct size in the rosiglitazone-rich diet group (P < 0.01 vs. control diet group). Increased myocardial expression of AT(1) receptors in the ischemic-reperfused myocardium was attenuated in the rosiglitazone-rich diet group (P < 0.05 vs. control diet group). Importantly, myocardial AT2 mRNA and protein expression were significantly increased (by >100-fold) in the rosiglitazone-rich diet group (P < 0.05). These changes were accompanied by inhibition of p42/44 MAPK in the rosiglitazone-rich diet group, while the Akt1 expression, believed to mediate insulin sensitization, remained similar in all three groups. The cardioprotective effects of rosiglitazone against myocardial ischemia-reperfusion injury are independent of its insulin-sensitizing properties and are associated with significant overexpression of AT2 receptors along with inhibition of p42/44 MAPK.

Angiotensin I↗
PubMed2006

HBV genes induce cytotoxic T-lymphocyte response upon adeno-associated virus (AAV) vector delivery into dendritic cells.

Hepatitis B virus (HBV) has been an increasing problem throughout the world and remains difficult to treat. But immunotherapeutic approaches offer new, effective treatments. Three recombinant adeno-associated virus (AAV) type 2 vectors, carrying one of the HBV S, C or X gene, were used to load (transduce) professional antigen-presenting dendritic cells (DC) for the purpose of stimulating cytotoxic T lymphocytes (CTL) in vitro. It was found that all three recombinant AAV/HBV antigen virus loaded DC at approximately 90% transduction efficiency. Most importantly, all three AAV-loaded DC stimulated rapid, antigen-specific and major histocompatibility complex (MHC)-restricted CTL. In vitro, these CTL killed (30-50%) synthetic antigen-positive autologous targets as well as HepG2 liver cell targets. In comparing the three antigens, it was found that AAV/HBV-C-derived CTL consistently had the highest killing efficiency. CTL derived from AAV/HBV-C-loaded DC also showed significantly higher killing of targets than that from bacterially generated C-protein-loaded DC. Further studies showed that AAV/HBV-C-derived CTL had higher interferon (IFN)-gamma. These data suggest that AAV/HBV antigen gene-loading of DC may be useful for immunotherapeutic protocols against HBV infection and that the HBV C antigen may be the most useful for this purpose.

Antigens, CD↗
PubMed2005

Influence of statins on postoperative wound complications after inguinal or ventral herniorrhaphy.

The lipid-lowering agents, statins, are the most commonly prescribed class of drugs in the western world. Because of their widespread use, many patients undergo surgical procedures while on statins. Statins, in addition to cholesterol-lowering effects, also have anticoagulant, immunosuppressive, and antiproliferative properties that may affect the risk of local wound complications. This study investigated the relationship between statins and postoperative wound complications in a large cohort of patients undergoing inguinal or ventral hernia repair. Data mining was performed in the Veterans Integrated Service Network (VISN)16 Data Warehouse. This database contains clinical and demographic information about all veterans cared for at the ten VA Medical Centers that comprise the South Central VA Healthcare Network in the mid-south region of the US. Aggregate data (age, body mass index, smoking history, gender, race, history of diabetes, statin use, and postoperative wound complications) were obtained for all patients who underwent inguinal or ventral hernia repair during the period October 1, 1996-November 30, 2004. During the period of the query, 10,782 patients (10,676 male, 106 female), 1,242 (11.5%) of whom received statins, underwent herniorrhaphy. Statin use did not affect the risk of wound infection or delayed wound healing. Statin use was, however, associated with an increased rate of local postoperative bleeding complications (P=0.01). When the type of hernia, age, smoking, diabetes, and body mass index were included in a multivariate analysis, statins remained borderline significant as an independent predictor of wound hematoma/postoperative bleeding (P=0.04), odds ratio 1.6 (95% CI 1.03-2.44). Patients who undergo inguinal herniorrhaphy while on statins have an increased risk of postoperative wound hematoma/hemorrhage. Focus on additional factors that may affect the propensity to postoperative bleeding and on meticulous intraoperative hemostasis are particularly important in such patients.

Diabetes Mellitus↗
PubMed2005

Aortic stenosis: is it simply a degenerative process or an active atherosclerotic process?

Aortic stenosis remains the most common cause of cardiac valve replacement in developed countries. The prevalence of this condition increases with age, and many of the risk factors for coronary artery disease also appear related to the development and progression of aortic stenosis. Recent studies also suggest a relationship between calcium and lipid accumulation in both coronary artery disease and aortic stenosis. Most important, there is growing evidence that aggressive treatment of coronary artery disease risk factors, particularly hyperlipidemia, may influence the progression of aortic stenosis. In this article the current literature is reviewed as it relates to vascular biology, pathogenesis of aortic valve disease, and current and newly emerging management approaches in the care of the patient with aortic stenosis.

Aortic Valve Stenosis↗
PubMed2005

A trial of education, prompts, and opinion leaders to improve prescription of lipid modifying therapy by primary care physicians for patients with ischemic heart disease.

BACKGROUND: Recent clinical trials indicate that treatment with lipid modifying therapy improves outcomes in patients with ischemic heart disease (IHD) and low levels of high density lipoprotein (HDL) cholesterol. The results of these trials, however, have not been widely implemented in clinical practice. OBJECTIVES: To develop and test an intervention designed to increase the rate of prescription of lipid modifying therapy and to determine the relative effectiveness of three different prompts (progress notes, patient letters, or computer chart reminders). METHODS: The study was conducted in 11 US Department of Veterans Affairs Medical Centers. The effect of the intervention on the proportion of eligible patients receiving lipid modifying therapy was compared between five intervention sites and six matched control sites using a controlled before and after study design. Additionally, 92 providers within the intervention clinics were randomized to receive one of the three prompts. Data were analyzed using logistic regression modeling which incorporated terms to account for the clustered nature of the data. RESULTS: At the intervention sites the prescription rate increased from 8.3% during the pre-intervention period to 39.1% during the intervention (OR = 6.5, 95% CI 5.2 to 8.2, p<0.0001) but remained unchanged at the control sites. The interaction between group (control v intervention) and time period was highly significant (p<0.0001). The adjusted odds of receiving a prescription during the intervention period was 3.1 times higher at the intervention sites than at the control sites (95% CI 2.1 to 4.7). Overall, there was no significant difference in prescription rates among the three prompt groups. However, there was a significant interaction between prompt group and site, indicating that the efficacy of the prompts differed by site. CONCLUSION: An intervention for primary care providers consisting of an educational workshop, opinion leader influence, and prompts substantially increased the prescription rate of lipid modifying therapy.

Aged↗
PubMed2005

Plasma treatment of polyurethane coating for improving endothelial cell growth and adhesion.

The advantage of helium plasma treatment in enhancing endothelial cell growth and adhesion on polyurethane film coated on glass substrate is demonstrated with experimental data. Human coronary artery endothelial cell (HCAE) growth and attachment was studied on (1) bare glass substrate, used as control, (2) coated glass, with and without helium plasma treatment and (3) collagen-treated polyurethane-coated glass substrates. The untreated polyurethane film surface was rough (RMS = 690 nm) and highly hydrophobic (contact angle theta = 90 degrees). Cell growth on the untreated polyurethane surface was poor (cell concentration approximately 3750/cm2) compared to glass surface (cell concentration approximately 17 665/cm2). The atmospheric helium plasma treatment of the polyurethane film resulted in oxidation of the surface, a slight increase in roughness (RMS = 735 nm) and a significant drop in hydrophobicity (contact angle theta = 79 degrees). The critical surface tension (gamma c) of polyurethane film was also increased by 2 dynes/cm due to helium plasma treatment. These changes resulted in enhanced HCAE cell growth in polyurethane film (cell concentration approximately 16 230/cm2) compared to the untreated polyurethane film. The cell growth was also comparable to cell growth on a glass surface (17 665/cm2) and the collagen-treated polyurethane film surfaces (cell concentration approximately 21 645/cm2), respectively. Moreover, the strength of cell attachment on a plasma-treated surface (cell retention R = 89%) under laminar flow was significantly higher than that on a glass surface (R = 71%). While the collagen-treated polyurethane surface had the highest number of HCAE cells, the cell adhesion was found to be poor (R = 42%) compared to that of a plasma-treated surface. Thus, the overall performance of the plasma-treated polyurethane film surface on endothelial cell growth was better than other substrates studied here.

Cell Adhesion↗
PubMed2005

Trends in the care of patients with acute myocardial infarction at a university-affiliated Veterans Affairs Medical Center.

BACKGROUND: Acute cardiac care of the veterans at Veterans Administration (VA) hospitals has been thought of as poor in quality. We examined the use of life-saving, evidence-based medical therapy in patients admitted with acute myocardial infarction to the University of Arkansas for Medical Sciences-affiliated VA Medical Center in Little Rock and compared the use of this therapy with other hospitals in Arkansas and in the rest of the nation. METHODS: Use of life-saving medical therapy in 117 patients admitted with acute myocardial infarction from January 2002 to December 2002 was compared with the National Registry of Myocardial Infarction database for the identical period. RESULTS: Heparin/low-molecular-weight heparin and glycoprotein IIb/IIIa inhibitors were used in 88% and 66% of patients, respectively. Aspirin, beta adrenergic-blocking agents, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) were used in 92%, 93%, 62%, and 79% of the patients, respectively. The use of these therapies was better than in similar patients in Arkansas (P < .001) and the United States as a whole (P < .01). Calcium-channel blockers were used in 16% of the patients. At a mean follow-up period of 1.5 years, use of beta blockers and aspirin had decreased, whereas the use of statins and ACE inhibitors/ARBs was unchanged. CONCLUSION: This study shows that patients with acute myocardial infarction admitted to this university-affiliated VA Medical Center receive evidence-based life-saving medical therapy more often than in the rest Arkansas or in the entire United States. More important, patients at this federal institution continue to receive life-saving medical therapy during follow-up. Better use of evidence-based therapy may be related to affiliation of this VA Medical Center with a teaching institution where board certified cardiologists are involved in short- and long-term care of these patients.

Adrenergic beta-Antagonists↗
PubMed2005

Modulation of cardiovascular remodeling with statins: fact or fiction?

The concept of cardiac remodeling implies a complex mixture of myocardial ischemia, and increased wall stress that results in molecular, cellular and interstitial changes in the heart. Clinically, cardiac remodeling is manifested as a change in size, shape and function of the heart. Morphologically the key feature of remodeling is myocyte hypertrophy, myocyte loss from necrosis or apoptosis, as well as interstitial cell growth especially fibroblast proliferation leading to myocardial fibrosis. Cardiac remodeling is influenced by hemodynamic load, neurohumoral activation, and other factors that can further affect the remodeling process. Despite advances in the management of heart failure, morbidity and mortality still present major health care issues in these patients. Statins (HMG Coenzyme A reductase inhibitors) play a key role in the management of ischemic heart disease. Recent studies indicate that statins may modulate cardiac remodeling by affecting signals that cause fibroblast growth, and myocyte hypertrophy and loss. In this paper we review the mechanisms of cardiac remodeling and the mechanisms of potential beneficial effects of statins on cardiac remodeling.

Animals↗
PubMed2005

Pleuropericarditis and pericardial tamponade associated with inflammatory bowel disease.

Extraintestinal manifestations have been described with inflammatory bowel disease (IBD). Cardiac involvement in IBD is rare and may present as pericardial effusion, myopericarditis and conduction defects. Here we present a case of IBD with asymptomatic pericardial tamponade. A 37-year-old African-American man with ulcerative colitis with history of previous colectomy with ileorectal anastomosis was hospitalized for resection of the stricture of ileorectal anastomosis. The patient was afebrile with stable vitals and modest jugular venous distension, but no pulsus paradoxus. Cardiopulmonary examination was normal. A CT scan done to evaluate rise in liver function tests following removal of stricture showed a large 3.1 cm pericardial effusion. A transthoracic 2-D echocardiogram showed a moderate-sized posterior pericardial effusion limiting left ventricular filling. Central venous pressure was 18 mm Hg and the patient underwent drainage of 300 ml of old bloody pericardial effusion. Pericardial biopsy showed organizing fibrinohemorrhagic chronically inflamed pericardium without granuloma or neoplastic process. Serologies for EBV, Coxsackie virus and hepatitides were negative. Drug-related pericarditis seems less likely as the patient was not on sulfasalazine, and ANA, dsDNA and rheumatoid factor titers were negative. The patient was diagnosed to have pericardial tamponade associated with IBD.

Adult↗
PubMed2004

Evaluation of venous and arterial conduit patency by 16-slice spiral computed tomography.

BACKGROUND: Computed tomography has been shown to be useful in the evaluation of aortocoronary bypass grafts (CABG). This is the first prospective study to evaluate the accuracy of a new-generation scanner in the detection of patency and significant stenoses (>50% decrease in diameter) of venous and arterial grafts in patients with previous CABG. METHODS AND RESULTS: In 96 patients (80 males, mean age 62 years) with previous CABG, a multislice computed tomography (MSCT) scan was performed (collimation 16x0.625 mm). Patients with atrial fibrillation, renal failure, severe respiratory disease, severe heart failure, heart rate >70 bpm despite therapy, or unstable angina were excluded. A total of 285 conduits implanted on the native coronary arteries at the time of CABG were evaluated. MSCT data were analyzed by 2 independent radiologists and compared with the results of conventional angiography. Three patients were excluded from analysis. All conduits were judged evaluable in 84 patients. Among these patients, MSCT correctly diagnosed 54 occluded grafts and 4 significant stenoses on the body of the grafts. Of the 17 significant anastomotic lesions, MSCT correctly diagnosed 15. For these 84 patients, diagnostic accuracy was 99%, sensitivity was 97%, and specificity was 100%. When all 93 patients were considered, the sensitivity of MSCT in diagnosing significant stenoses was 96%. CONCLUSIONS: MSCT with the new-generation scanner allows for accurate assessment of venous and arterial conduits in patients with previous CABG with a high degree of sensitivity and specificity. Exclusion criteria and radiation exposure remain limitations of the method.

Aged↗
PubMed2004

Aspirin inhibits ox-LDL-mediated LOX-1 expression and metalloproteinase-1 in human coronary endothelial cells.

BACKGROUND: Aspirin is thought to exert salutary effects in vascular disease states by inhibiting platelet aggregation. Endothelial activation, accumulation of oxidized low-density lipoprotein (ox-LDL) and intense inflammation also characterize atherosclerotic plaque in acute myocardial ischemia. Ox-LDL induces expression of lectin-like receptors (LOX-1) on endothelial cells and leads to the expression of matrix metalloproteinases (MMPs), which destabilize the atherosclerotic plaque. We hypothesized that aspirin may interfere with LOX-1 expression and subsequent MMP activation. METHODS AND RESULTS: Cultured human coronary artery endothelial cells (HCAECs) were incubated with aspirin (1-5 mM), sodium salicylate (5 mM) or the cyclo-oxygenase inhibitor indomethacin (0.25 mM) before treatment with ox-LDL. Aspirin, in a dose- and time-dependent fashion, reduced ox-LDL-mediated LOX-1 expression (P<0.01). Ox-LDL also increased MMP-1 expression and activity, and treatment of HCAECs with aspirin decreased this effect (P<0.01). Ox-LDL also enhanced the activity of p38MAPK in HCAECs, and aspirin blocked this effect of ox-LDL (P<0.01). Treatment of HCAECs with salicylate, but not indomethacin, resulted in a suppression of LOX-1 expression, an effect similar to that of aspirin. Importantly, both aspirin and salicylate, but not indomethacin, decreased superoxide anion generation in ox-LDL-treated HCAECs (P<0.05). CONCLUSION: These observations suggest that aspirin inhibits ox-LDL-mediated LOX-1 expression and interferes with the effects of ox-LDL in intracellular signaling (p38MAPK activation) and subsequent MMP-1 activity. These novel effects of aspirin may complement its platelet inhibitory effect in acute myocardial ischemia.

Anions↗
PubMed2004

Mathematical estimation of the potential effect of vascular remodelling/dilatation on B-mode ultrasound intima-medial thickness.

BACKGROUND: Arterial diameter changes are known to impact wall thickness, but the clinical relevance of the changes is unclear. AIM: To use known mathematical relationships to estimate anticipated changes in arterial wall thicknesses occurring with enlargement of atherosclerotic regions. DESIGN: Mathematical relationships between a cylinder's diameter and its wall thickness were used to calculate the theoretical effect of diameter enlargement on the thickness of an atherosclerotic wall. METHODS: Equating the wall areas of two cylinders, one of smaller diameter than the other, allowed estimation of the degree of thickening that would be needed to maintain intima-medial thickness (IMT) after arterial remodelling. The difference in cylinder diameters was based on arterial diameter enlargement reported with atherosclerosis progression. Thus, the calculated wall changes estimate arterial changes which could go undetected if only IMT is measured by ultrasound. RESULTS: The expected IMT change for diameter enlargement is not a linear function of the diameter change, but varies depending upon initial size (diameter and IMT). Thus a 0.6 mm arterial diameter enlargement would be expected to cause a 0.039-0.235 mm change in IMT, depending on artery size. The estimated IMT change is similar to that associated with major atherosclerotic risk factors. DISCUSSION: The level of vascular remodelling reported with atherosclerosis could have a measurable impact on IMT, suggesting that indicators incorporating both diameter and IMT may be better disease indicators than IMT alone. Arterial diameters, as well as IMT, should be obtained in ultrasound studies of atherosclerosis.

Arteriosclerosis↗
PubMed2004

Exercise and myocardial tolerance to ischaemia-reperfusion.

UNLABELLED: It is well established that both short-term (1-5 days) and long-term (weeks to months) high intensity exercise (i.e. 70-75%VO2max) provides cardioprotection against ischaemia-reperfusion injury. However, it is unclear if moderate intensity exercise will also provide cardioprotection. AIM: Therefore, these experiments compared the protective effects of moderate vs. high intensity exercise in providing defense against ischaemia-reperfusion injury. METHODS: Male Sprague-Dawley rats were randomly assigned to one of three-experimental groups: (1) sedentary (control); (2) moderate intensity treadmill exercise (60 min day(-1) at approximately 55%VO2max); or (3) high intensity treadmill exercise (60 min day(-1) at approximately 75%VO2max). Hearts were exposed to 20 min of global ischaemia followed by 30 min reperfusion in an isolated working heart preparation. RESULTS: Compared with sedentary rats, both moderate and high intensity exercised rats maintained a higher (P < 0.05) percentage of pre-ischaemia cardiac output and cardiac work (cardiac output x systolic blood pressure) during reperfusion. No differences in the percent recovery of cardiac output and heart work existed (P > 0.05) between the two exercise groups. CONCLUSIONS: These data reveal that both moderate and high intensity exercise training provide equivalent protection against ischaemia-reperfusion injury.

Animals↗
PubMed2003

Role of genetics in prevention of coronary atherosclerosis.

Atherosclerosis is currently regarded as a complex disorder, triggered by gene-gene and gene-environment interactions. Despite the difficulties of multifactorial disease genetic analysis, significant progress has been achieved in the search for atherosclerosis susceptibility genes. Here, we review these advances with regard to genome scan results and candidate gene analysis.

Coronary Artery Disease↗