Biomedical subjects

Rajneesh Malhotra

Publications and source records attributed to Rajneesh Malhotra.

14 recordsLinked to original sources

PubMed2006

Propensity case-matched analysis of off-pump versus on-pump coronary artery bypass grafting in patients with atheromatous aorta.

BACKGROUND: Patients with severe atheromatous disease of the aorta who underwent coronary artery bypass grafting have an increased risk of stroke and death. We hypothesize that in these high-risk patients off-pump coronary artery bypass grafting is associated with lower rates of stroke and mortality. METHODS: From January 1995 through June 2004, a total of 24,107 patients underwent coronary artery bypass grafting. Routine intraoperative transesophageal echocardiography was performed in 18,501, of which 6,991 (29.0%) were found to have severe atheromatous disease in the ascending aorta or aortic arch. Propensity matched-pairs analysis was used to match patients undergoing off-pump coronary artery bypass grafting (n = 3,000) with 3,000 patients undergoing conventional coronary artery bypass grafting by age, sex, ejection fraction, diabetes, preoperative intraaortic balloon pump, congestive heart failure, chronic obstructive pulmonary disease, acute myocardial infarction, peripheral vascular disease, history of stroke or cerebrovascular disease, renal disease, carotid artery disease, atrial fibrillation, emergency surgery, or previous cardiac surgery. RESULTS: Univariate analysis revealed decreased hospital mortality (1.4% versus 3.3%; p < 0.001) and stroke prevalence (0.50% versus 0.97%; p = 0.05) in off-pump coronary artery bypass grafting compared with conventional coronary artery bypass grafting. Multivariate analysis revealed that increased mortality was associated with conventional coronary artery bypass grafting (odds ratio, 2.6; p = 0.001), age (odds ratio, 2.1; p = 0.003), acute myocardial infarction (odds ratio, 1.8; p = 0.03), history of stroke or cerebrovascular disease (odds ratio, 1.6; p = 0.04), congestive heart failure (odds ratio, 2.1; p = 0.04), and diabetes mellitus (odds ratio, 1.9; p = 0.03). Multivariate analysis showed that off-pump coronary artery bypass grafting technique was the only independent predictor of decreased stroke rate (odds ratio, 1.4; p = 0.05). CONCLUSIONS: Off-pump coronary artery bypass grafting surgery in patients with atheromatous disease of the aorta is associated with lower risk of stroke and death. Routine intraoperative evaluation of the aorta is helpful in identifying the disease and directs the appropriate surgical technique.

Adult↗

PubMed2005

Functional role of lipid rafts in CD20 activity?

CD20 is a B-lymphocyte-specific integral membrane protein, implicated in the regulation of transmembrane calcium conductance, cell-cycle progression and B-lymphocyte proliferation. CD20 is proposed to function as a SOCC (store-operated calcium channel). SOCCs are activated by receptor-stimulated calcium depletion of intracellular stores. Sustained calcium conductivity across the plasma membrane mediated by SOCC activity is required for long-term calcium-dependent processes, such as transcriptional control and gene expression. Cross-linking of CD20 by antibodies (e.g. Rituxan) has been reported to induce a rapid redistribution of CD20 into specialized microdomains at the plasma membrane, known as lipid rafts. Recruitment of CD20 into lipid rafts and its homo-oligomerization are suggested to be crucial for CD20 activity and regulation. This review outlines recent biochemical studies characterizing the role of CD20 in calcium signalling in B-lymphocytes and evaluates an engagement of lipid rafts in the regulation of CD20-mediated calcium conductivity.

Antigens, CD20↗

PubMed2004

Concomitant carotid endarterectomy and coronary bypass surgery: outcome of on-pump and off-pump techniques.

BACKGROUND: There continues to be a dilemma regarding the best means of surgical management of significant carotid artery disease in patients requiring coronary artery bypass surgery. A combined approach of coronary artery bypass and carotid endarterectomy has shown good results in patients with concomitant carotid and coronary artery disease. We reviewed our results of coronary artery surgery using conventional cardiopulmonary bypass or off-pump techniques and carotid endarterectomy done as a combined procedure. METHODS: Between January 1996 and June 2002, 358 patients underwent concomitant coronary artery bypass and carotid endarterectomy. There were 140 males (84.3%) and 26 females (15.7%) in group I. Group II consisted of 158 males (82.3%) and 34 females (17.7%). One hundred sixty-six patients (group I) were done off pump whereas in 192 patients (group II), the procedure was done using conventional cardiopulmonary bypass. Carotid endarterectomy was performed before coronary artery bypass surgery in both groups. RESULTS: The average number of grafts were 3.4 +/- 0.8 with average operative time of 4.2 +/- 0.4 hours in group I, and 3.3 +/- 0.8 graft with operative time of 5.3 +/- 1.2 hours in group II (p = 0.239 and p < 0.001, respectively). There were 2 deaths (1.2%) in group I and 3 deaths (1.6%) in group II (p = 0.870). No patient from group I and 1 patient (0.5%) from group II had postoperative stroke (p = 0.941). Mean hospital stay was 9.0 +/- 1.2 days in group I and 11.2 +/- 1.7 days in group II (p < 0.001). At mean follow-up of 2.8 +/- 0.9 years in group I, 2 patients (1.2%) had late death due to cardiac failure and contralateral carotid endarterectomy was done in 2 patients (1.2%). Group II had mean follow-up of 2.4 +/- 0.6 years, during which 4 patients (2.1%) had late death and contralateral carotid endarterectomy was done in 3 patients (1.6%). Late stroke was seen in 1 patient (0.6%) from group I and 2 patients (1.0%) from group II. CONCLUSIONS: Concomitant carotid endarterectomy and coronary artery bypass is a safe and effective procedure in patients with significant coronary and carotid artery disease. Equally good results can be reproduced using cardiopulmonary bypass or off-pump techniques for coronary artery surgery, with low morbidity, mortality, and good long-term results.

Aged↗

PubMed2003

Regulation of B lymphocytes in health and disease. Meeting review.

Signal transduction by the B cell receptor (BCR) is an absolute requirement for the selection and development of B lymphocytes at multiple checkpoints. Binding to antigen via the BCR is complemented by a co-stimulus delivered through accessory and co-stimulatory cell surface molecules that regulate the signalling threshold. In addition, identification of genes associated with immunodeficiency syndromes has highlighted the importance of genetic regulation, particularly in immunoglobulin class-switching and somatic hypermutation. A 1-day symposium organised by the Biochemical Society considered some of the recent advances in our understanding of the molecules and regulatory pathways involved in B lymphocyte activation, differentiation and survival and the health consequences when threshold settings malfunction.

Animals↗

PubMed2003

Isolation and characterisation of potential respiratory syncytial virus receptor(s) on epithelial cells.

Respiratory syncytial virus (RSV) infection causes severe lower respiratory diseases in infancy, early childhood and the elderly. RSV infections respond poorly to current therapies. Therefore, we initiated a search for novel drug targets by investigating the characteristics and identity of RSV adhesion receptors on mammalian cells. Soluble human lectins, complex polysaccharides and a low molecular selectin antagonist, TBC1269, were used to characterise and isolate the RSV receptor on a human epithelial cell line (Hep2 cells). The binding characteristics of the RSV receptor on Hep2 cells were similar to those reported for L-selectin. The carbohydrate-based selectin antagonists, fucoidan and TBC 1269, inhibit RSV infection both in vitro and in a mouse model of infection. Furthermore, we have isolated annexin II as a potential RSV receptor on Hep2 cells. The expression of annexin II was increased after RSV infection. Recombinant annexin II binds to RSV G-protein, heparin and plasminogen and the binding is inhibited by a selectin antagonist, TBC1269. These findings indicate that inhibitors of annexin II could have potential in treating RSV infection.

Animals↗

PubMed2003

L-Selectin ligands in lymphoid tissues and models of inflammation.

Both lymphocyte recirculation through the lymphoid tissues and leukocyte recruitment to sites of inflammation are essential components of immune surveillance, and are necessary for sustained protection against pathogens. This process is mediated by the leukocyte-endothelial adhesion cascade of which the interaction of leukocyte L-Selectin with its endothelial ligand initiates the first critical tethering and rolling step. As well as discussing the constitutive L-Selectin ligands in lymphoid tissues, this review examines the literature regarding their induction in inflammation, and draws attention to recent findings regarding soluble L-Selectin ligands that suggest an emerging multifunctional role in leukocyte recirculation and inflammation.

Animals↗

PubMed2003

Mannose-binding lectin is a disease modifier in clinical malaria and may function as opsonin for Plasmodium falciparum-infected erythrocytes.

Variant alleles in the mannose-binding lectin (MBL) gene (mbl2) causing low levels of functional MBL are associated with susceptibility to different infections and are common in areas where malaria is endemic. Therefore, we investigated whether MBL variant alleles in 551 children from Ghana were associated with the occurrence and outcome parameters of Plasmodium falciparum malaria and asked whether MBL may function as an opsonin for P. falciparum. No difference in MBL genotype frequency was observed between infected and noninfected children or between children with cerebral malaria and/or severe malarial anemia and children with uncomplicated malaria. However, patients with complicated malaria who were homozygous for MBL variant alleles had significantly higher parasite counts and lower blood glucose levels than their MBL-competent counterparts. Distinct calcium-dependent binding of MBL to the membrane of P. falciparum-infected erythrocytes, which could be inhibited by mannose, was observed. Further characterization revealed that MBL reacted with a P. falciparum glycoprotein identical to the 78-kDa glucose-regulated stress protein of P. falciparum. MBL seems to be a disease modifier in clinical malaria and to function as an opsonin for erythrocytes invaded by P. falciparum and may thus be involved in sequestration of the parasite, which in turn may explain the association between homozygosity for MBL variant alleles and high parasite counts.

Adolescent↗

PubMed2003

Left ventricular fibroma causing atypical chest pain.

A 29-year-old man with atypical chest pain for 3 years and exertional angina for 3 months was found to have a large homogenous mass in the apicolateral area of the left ventricle. The mass, weighing 78 g, was excised successfully and identified as a fibroma.

Adult↗

PubMed2003

Off-pump surgery: a choice in unstable angina.

The benefit and safety of off-pump coronary artery bypass surgery in patients with unstable angina was assessed retrospectively. From February 1996 to October 2001, 5,306 patients underwent multivessel off-pump coronary artery bypass, of whom 920 (17%) had unstable angina. In these 920 patients, ejection fractions ranged from 15% to 70%, 203 (22%) had an ejection fraction of 20%-35%, and 11 (1%) had an ejection fraction < 20%. Triple-vessel disease was present in 625 patients. Preoperative intraaortic balloon pump support was used in 28 patients. Operative approaches included mid sternotomy (86%), lower partial sternotomy (9%), and left anterior thoracotomy (2%). The number of grafts ranged from 1 to 5 with a mean of 2.43 +/- 0.86, and 92.3% of patients received a left internal mammary artery graft. Twenty-two patients need intraoperative intraaortic balloon pumping. Ten patients (1%) suffered perioperative myocardial infarction. The mean hospital stay was 7.8 +/- 4.3 days. Hospital mortality was 2/920 (0.22%). Intraaortic balloon pumping was helpful in these cases of unstable angina refractory to medical therapy. Off-pump coronary artery surgery was found to be safe and beneficial in these patients.

Adult↗

PubMed2002

Identification and characterization of L-selectin ligands in porcine lymphoid tissues.

A human L-selectin-ZZ fusion protein was used to screen porcine inguinal lymph nodes for the presence of monoclonal antibody (mAb) MECA 79-negative ligands. Fractionation of lymph node-conditioned medium by anion-exchange chromatography revealed two distinct L-selectin-binding fractions, one containing a MECA 79 non-reactive species and the second containing two MECA 79 reactive species of approximately 84 000 and 210 000 molecular weight. The MECA 79 non-reactive species exhibited Ca2+- and lectin-dependent binding to L-selectin-ZZ in a solid-phase capture enzyme-linked immunosorbent assay (ELISA), and this was specifically disrupted by the addition of EDTA, mannose-6-phosphate and the blocking anti-L-selectin mAb, DREG-56. Enzymatic characterization of the ligand by trypsin, O-sialoglycoprotease endopeptidase, heparinases I and III, or chondroitinase ABC lyase digestion indicated that L-selectin binding was predominantly dependent upon a chondroitin sulphate-modified glycoprotein determinant. Although Coomassie Blue staining of sodium dodecyl sulphate (SDS) polyacrylamide gels did not reveal a detectable protein species, carbohydrate-specific staining using GlycoTrack revealed a single, heavily glycosylated protein of high molecular weight (> 220 000). These studies have revealed the existence of a MECA 79 non-reactive, chondroitin sulphate glycosaminoglycan-modified ligand, termed csgp>220, which is secreted by peripheral lymph nodes and may play a role in leucocyte trafficking to the lymph node.

Animals↗

PubMed2002

Hemodynamic changes during displacement of the beating heart using epicardial stabilization for off-pump coronary artery bypass graft surgery.

OBJECTIVE: To evaluate the hemodynamic alterations during off-pump coronary artery bypass graft surgery to determine the degree of impairment caused and the techniques to rectify them. DESIGN: Prospective, observational cohort study performed from January 2000 through September 2000. PARTICIPANTS: Patients (n = 500) with coronary artery disease undergoing multivessel off-pump coronary artery bypass graft surgery using the Octopus tissue stabilizer (Medtronic, Inc, Minneapolis, MN). Unstable patients with ongoing ischemia were excluded from the study. INTERVENTIONS: All patients were monitored with radial artery and pulmonary artery catheters and continuous transesophageal echocardiography monitoring with a multiplane transducer. The perioperative requirement of an intracoronary shunt, inotropes, or an intra-aortic balloon pump was noted. The effect of the Trendelenburg position and fluids on hemodynamics was observed. The need for defibrillation and institution of emergency cardiopulmonary bypass were major endpoints to determine the inability of the patient to tolerate displacement of the heart. MEASUREMENTS AND MAIN RESULTS: Mean patient age was 59.3 +/- 11.6 years. There were 204 (40%) patients in the high-risk category; 54 (10.8%) patients had left ventricular ejection fraction <25%. The mean number of grafts was 2.7 +/- 0.8. Vertical displacement of the heart to access the lateral and inferior walls decreased the mean arterial pressure by 18 +/- 4% (p < 0.01), with a concomitant increase in central venous pressure of 66 +/- 18% (p < 0.001). The stroke volume and the cardiac index were reduced by 35.7 +/- 11% (p < 0.001) and 45 +/- 13% (p < 0.001). On transesophageal echocardiography, there was development of new regional wall motion abnormalities in 59.2% and a decrease in global left ventricular functions in 61.2%. The use of inotropes was highest during anastomosis on the posterior wall-78.4% compared with 21.9% for the anterior wall. An intra-aortic balloon pump was used in 55 (11.2%) patients, and 7 (0.71 %) patients had to be put on emergency CPB. The in-hospital mortality was 1.2%. CONCLUSION: Most patients had hemodynamic changes easily correctable by fluids and inotropes. Monitoring of left ventricular and right ventricular function by transesophageal echocardiography enhances safety of the procedure and is recommended. The use of the Octopus II tissue stabilizer proved to be a safe and versatile means to stabilize the heart during off-pump coronary artery bypass procedures, especially in high-risk patients.

Cardiopulmonary Bypass↗

PubMed1999

Echocardiography in Minimally Invasive Direct Coronary Artery Bypass.

Minimally invasive direct coronary artery bypass (MIDCAB) is a recently developed, less-invasive alternative to standard bypass surgery. MIDCAB is performed through a small incision (2-3 inches) on the beating heart without the use of cardiopulmonary bypass or cardioplegia. It is associated with less trauma and a shorter hospital stay than conventional surgery. Transesophageal echocardiography helps in patient selection by detecting protruding aortic atheromas (PATHs), which are associated with a high risk of stroke during typical cardiopulmonary bypass. MIDCAB may be the technique of choice in patients with PATHs. Intraoperative echocardiography can detect wall motion abnormalities and helps in determining intraoperative myocardial ischemia and the postoperative prognosis. Duplex study of the internal mammary arteries is helpful in evaluating coronary anastomosis patency. Characteristically, a patent coronary anastomosis demonstrates a high diastolic flow fraction, with a ratio between peak diastolic and peak systolic flow velocity of > 1.

Journal Article↗

PubMed1998

Evaluation of Right Ventricular Function During CABG: Transesophageal Echocardiographic Assessment of Hepatic Venous Flow Versus Conventional Right Ventricular Performance Indices.

The vulnerability of right ventricle (RV) to ischemic insult during cardiac surgery is being increasingly recognized. This study aims to evaluate right ventricular function by measuring hepatic venous flow (HVF) patterns using intraoperative transesophageal echocardiography (TEE), and to compare HVF with other conventional two-dimensional echocardiographic and hemodynamic indices of RV performance. Patients undergoing coronary artery bypass grafting (CABG) were studied intraoperatively using a multiplane dual frequency 5/3.7-MHz phased array transducer, a pulmonary artery catheter, and an arterial catheter. Peak velocities and time velocity integrals of HVF pattern were studied. Peak systolic-diastolic ratio (S/D) of biphasic HVF and reverse flow ratio (% reverse flow/forward flow = % RF/FF) were also examined. Two-dimensional echocardiographic measurements included: (1) transverse plane long-axis (LA) and short-axis (SA) planimetered areas expressed as ratios; LA maximum major and minor-axis shortening fractions; (2) tricuspid annular plane systolic excursion (TAPSE) ratio. All data were obtained after induction of anesthesia (stage 1), after sternotomy (stage 2), aftercardiopulmonary bypass (CPB) (stage 3), and after sternal closure (stage 4). Pre-CPB all 35 patients had biphasic HVF by Doppler. In 31 patients peak S/D ratio was >1. After CPB, there was significant reduction in systolic forward flow (S wave), along with an increase in late systolic reverse flow (V wave) and an increase in % RF/FF. At this stage TAPSE ratio decreased (pre CPB 0.33 +/- 0.12 vs post CPB 0.30 +/- 0.11). There was simultaneous decrease in 2-D long-axis LA (pre CPB 0.52 +/- 0.11 vs post CPB 0.31 +/- 0.01) and max major axis LA (pre CPB 0.38 +/- 0.06 vs post CPB 0.31 +/- 0.11). Max major axis LA correlated significantly with changes in right atrial pressure (P < 0.05). Tricuspid annular motion diminished significantly at sternal closure. Hepatic systolic forward flow and TAPSE ratio can be an indirect measure of RV systolic functions in correlation with maximum major axis LA changes. Evaluation of HVF provides unique insight into right ventricular dynamics. It is an easy, safe, and sensitive method for assessing RV functions intraoperatively.

Journal Article↗

PubMedDate not supplied

Minimally invasive mitral valve surgery.

BACKGROUND: To reduce surgical trauma and the drawbacks associated with sternotomy, we performed robotically controlled, video-assisted mitral valve surgery, using either the port-access or the transthoracic clamp technique. METHODS AND RESULTS: Between September 1997 and September 2000, 221 patients (78 males, 143 females) underwent mitral valve surgery through a small right minithoracotomy using the port-access endovascular cardiopulmonary bypass system. Mitral valve exposure was facilitated with an endoscope attached to a voice-controlled robotic arm (AESOP 3000) allowing stabilization and voice-activated camera positioning. Twenty-six patients underwent mitral valve repair and 195 had valve replacement. In 197 patients, mitral valve surgery was the primary operation, while 24 were redo cases. Skin-to-skin mean operating time was 3.5 +/- 1.2 hours and aortic cross-clamp time was 58 +/- 16 min, mean intensive care unit stay was 22 +/- 7 hours and hospital stay 6.4 +/- 1.2 days. There was no re-exploration for bleeding. There was no late death or re-operation on mean follow-up of 16.4 +/- 12.2 months. Patients showed improvement in their NYHA functional class from 2.6 +/- 0.5 to 1.4 +/- 0.8 postoperatively. Outcomes were compared with those of our previous 220 patients who underwent mitral valve surgery with the median sternotomy approach. CONCLUSIONS: The use of video and robotic assistance in port-access mitral valve surgery not only minimizes the length of the incision, but also gives full visualization of the entire mitral valve apparatus. This approach provides comparable results with the sternotomy approach, as well as marked advantages of reduced intensive care unit stay. ,ower blood transfusion requirement, better cosmesis and earlier hospital discharge.

Adult↗