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Biomedical subjects

R Malhotra

Publications and source records attributed to R Malhotra.

At least 109 records · Page 6Linked to original sources

Cardioprotective effects of diltiazem infusion in the perioperative period.

OBJECTIVE: To evaluate the perioperative effects of intravenous diltiazem infusion on left ventricular functions, hemodynamics and as an anti-ischemic and antiarrhythmic agent in patients undergoing coronary artery bypass grafting (CABG). METHODS: A double blind, randomised study was performed on 71 patients undergoing elective CABG. Infusion of diltiazem (0.1 mg/kg per h, n = 34) or nitroglycerin (1 microgram/kg per min, n = 37) was given for 24 h starting from onset of cardiopulmonary bypass. Holter monitoring, electrocardiogram and serum cardiac enzymes levels were used to diagnose myocardial ischemia. Myocardial function was assessed by perioperative transesophageal echocardiography. RESULTS: The two groups did not differ with respect to preoperative and operative data. Diltiazem had no influence on hemodynamic parameters except for significant reduction in post operative heart rate and pulse pressure rate. Transient ischemic events (dilitiazem 10.2% versus nitroglycerin 33.3%, P = 0.15) and transient coronary spasm (diltiazem-6.8% versus nitroglycerin 25.9%, P = 0.15) were reduced in the diltiazem group as compared with the nitroglycerin group. The postoperative incidence of atrial fibrillation (diltiazem 3% versus nitroglycerin 22%, P = 0.03), supra ventricular tachycardia (diltiazem-3% versus nitroglycerin-22%, P = 0.03) and average ventricular premature contraction per h (diltiazem-40.2 +/- 10.2 versus nitroglycerin 53.8 +/- 12.3, P < 0.01) were significantly lower in the diltiazem group. Transesophageal echocardiography showed no significant difference in left ventricular functions and better preservation of left ventricular diastolic functions in post cardiopulmonary bypass period in diltiazem group. In addition mean deceleration time for the E wave on a 12 h post cardiopulmonary bypass period was significantly lower in the diltiazem group as compared with nitroglycerin (diltiazem 131 +/- 6 versus nitroglycerin 171 +/- 6, P < 0.01). CONCLUSION: The present study demonstrates that diltiazem infusion provides superior anti-ischemic protection and control of supraventricular arrhythmias as compared to nitroglycerin and does not produce any negative inotropic effect, as demonstrated by transesophageal echocardiography.

Aged↗

L-Selectin--a signalling receptor for lipopolysaccharide.

The activation of leukocytes by bacterial cell-wall lipopolysaccharide contributes to the pathogenesis of septic shock. We propose that in neutrophils, and possibly other leukocytes, L-selectin can act as a low-affinity lipopolysaccharide receptor. Inhibitors of L-selectin may therefore be of therapeutic value in treating this life-threatening condition.

Animals↗

The role of Tc-99m bone imaging in the management of pain after complicated total hip replacement.

A case of reflex sympathetic dystrophy (RSD) after total hip replacement (THR) is reported. It is a very unusual cause of pain after any arthroplasty procedure. Three-phase bone imaging diagnosed the condition and sympathetic blockade was used for confirming and treating the condition. The role of the bone scan in differentiating RSD from other causes of pain after THR is highlighted.

Ankle Joint↗

Role for L-selectin in lipopolysaccharide-induced activation of neutrophils.

The activation of leucocytes by bacterial cell wall lipopolysaccharide (LPS) contributes to the pathogenesis of septic shock. LPS is known to interact with several cell-surface proteins, including CD14, when presented as a complex with serum LPS-binding protein. However, the identity of the receptor responsible for LPS signalling and leucocyte activation is unknown. Interestingly, mice deficient in cell-surface L-selectin were dramatically resistant to the lethal effects of high doses of LPS in a model of septic shock. Recently we reported that L-selectin binds to cardiolipin and other charged phospholipids at a site distinct from the carbohydrate-binding site. Structural similarities between charged phospholipids and the lipid A moiety of LPS prompted us to investigate interactions between L-selectin and LPS. Herein we show that L-selectin is a neutrophil surface receptor for LPS and lipotechoic acid. The binding of LPS to L-selectin is independent of serum and Ca2+, and is blocked by antibodies to L-selectin and fucoidan. Furthermore, the interaction of LPS with cell-surface L-selectin results in superoxide production, indicating that L-selectin can mediate both binding and activation of human neutrophils. These findings suggest novel therapeutic approaches for the treatment of septic shock.

Animals↗

Anionic phospholipids bind to L-selectin (but not E-selectin) at a site distinct from the carbohydrate-binding site.

It is known that L-selectin binds to glycoconjugates containing the tetrasaccharide sialyl Lewis X in a Ca2+-dependent manner. In addition, a number of other acidic oligosaccharides (for example heparin or chondroitin sulphate) or glycolipids (for example sulphatides) bind to L-selectin independent of cations. In this paper we have established that L-selectin binds to charged phospholipids, such as cardiolipin and phosphatidylserine, but not to neutral phospholipids such as phosphatidylcholine. No interaction between E-selectin and any phospholipid was observed. The interaction between L-selectin cardiolipin was inhibited by dextran sulphate, fucoidan, mannose 6-phosphate and monoclonal antibodies previously reported to block the interaction between L-selectin and its natural ligands. Analysis of the amino acid sequence of the selectins indicated that L-selectin, but no E-selectin, contains a sequence homologous to the putative cardiolipin-binding epitope found in plasma glycoprotein beta2I. Glycoprotein beta2I and a peptide corresponding to the putative cardiolipin-binding epitope in beta2I inhibited the binding of L-selectin to cardiolipin or fucoidin. Based on the binding characteristics, sequence analysis and structural modelling of L-selectin, we suggest that the amino acid sequence KKNKED (residues 84-89) is a novel site for the binding of acidic species to L-selectin. This motif is localized close to the putative carbohydrate-binding domain of L-selectin and may be a second site within the lectin domain for the interaction of leucocyte L-selectin with its natural endothelial ligands.

Amino Acid Sequence↗

Bipolar hip arthroplasty in ankylosing spondylitis.

Nineteen severely affected hips in 12 young patients with ankylosing spondylitis were treated with bipolar hip arthroplasty followed by a comprehensive postoperative rehabilitation programme. Additional operative procedures of adductor tenotomy, knee flexion release, supracondylar femoral osteotomy for genu valgum and tendo Achillis lengthening for equinus contracture were required in 13 limbs. After a mean follow-up of 45.8 months, results were good in all cases with respect to relief from pain, and there was significant improvement in posture and function. All the patients resumed employment. The average gain in sum total range of hip movements was 194 deg, and the mean preoperative Harris hip score of 27.8 improved to 82.6 after bipolar arthroplasty. Ectopic ossification did not develop in any case. Bipolar hip arthroplasty appears to be ideally suited for young patients with ankylosing spondylitis.

Adult↗

Morphometric analysis of the right gastroepiploic artery and the internal mammary artery.

BACKGROUND: The internal mammary artery (IMA) and the right gastroepiploic artery (RGEA) are frequently used as conduits for coronary artery bypass grafting. METHODS: Morphometric measurements and histologic characteristics of the RGEA and the IMA were studied in 25 patients undergoing coronary artery bypass grafting. RESULTS: External radius was found to be more in the IMA (range, 18 to 56 microns; mean, 39.56 microns) in comparison with the RGEA (range, 24 to 51 microns; mean, 32.52 microns; p < 0.01). There was no significant difference between the vessels in intimal thickness (IMA: 0.0 to 0.25 micron; mean, 0.05 micron; RGEA: 0.0 to 0.28 micron; mean, 0.09 micron), internal radius (IMA: 5 to 47 microns; mean, 28.40 microns; RGEA: 16 to 42 microns; mean, 23.56 microns), area of media (IMA: 1,690 to 3,476 microns2; mean, 2,777.52 microns2; RGEA: 1,659 to 3,600; mean, 3,012.44 microns2), intimal thickening index (IMA: 0.0 to 0.02; mean, 0.01; RGEA: 0.0 to 0.13; mean, 0.01), and medial index (IMA: 0.14 to 0.60; mean, 0.36; RGEA: 0.18 to 0.63; mean, 0.39). Histologic examination of the RGEA showed more defects in continuity of internal elastic lamina and rich smooth muscle cells in the media. CONCLUSIONS: There was no difference in the morphometric measurements of the IMA and the RGEA except external radius, which was greater for the IMA. The histologic differences found in the RGEA may indicate an increased propensity for atherosclerosis of the RGEA as compared with the IMA. Some concern regarding the long-term patency of the RGEA in myocardial revascularization is warranted.

Adult↗

Methaemoglobinaemia presenting with status epilepticus.

A case is reported of methaemoglobinaemia presenting with recurrent fits in the absence of cyanosis. A low oxygen saturation measured on pulse oximetry that fails to improve with oxygen treatment, the presence of "chocolate brown" blood that does not change on exposure to air, and a high PaO2 arterial blood gas with oxygen therapy should support such a diagnosis. A diagnostic blood methaemoglobin level should be obtained.

Adult↗

Comparative study of the structural and functional properties of a bovine plasma C-type lectin, collectin-43, with other collectins.

Collectin-43 (CL-43) is a recently described bovine plasma protein containing both collagenous regions and C-type-lectin domains [Holmskov, Teisner, Willis, Reid and Jensenius (1993) J. Biol. Chem. 268, 10120-10125; Lim, Willis, Reid, Lu, Laursen, Jensenius and Holmskov (1994) J. Biol. Chem. 269, 11820-11824]. CL-43 was purified by affinity chromatography on mannan-Sepharose. On SDS/PAGE under reducing conditions the purified lectin showed a double band at about 43 kDa, with the upper band representing the intact molecule and the lower band a truncated form that lacked the N-terminal nine amino acid residues. Under non-reducing conditions, only one band was seen at 120 kDa. Analytical gel chromatography and sucrose-density-gradient centrifugation of the purified molecule, showed a Stokes radius of 9.1 +/- 0.3 nm (91 +/- 3 A) and a sedimentation coefficient (s20,w) of 3.6 +/- 0.1 S. These values correspond to a molecular mass of 119-138 kDa under non-denaturing condition in solution. The frictional coefficient (f/f0) was 2.7, indicating extreme elongation due to the collagenous segment. Only monomer subunits, with 37.4 +/- 1.7-nm-long rods, were seen by electron microscopy. These findings indicate that CL-43, in contrast with the other circulating collectins, is found only as a single subunit composed of three polypeptide chains. Two-dimensional gel electrophoresis showed that CL-43 has two isoforms, with pI values of 4.9 and 5.3, corresponding to the native form and the truncated form of the molecule respectively. CL-43, like conglutinin, lung surfactant protein A and mannan-binding protein (MBP), was shown to bind to the collectin receptor. Bovine MBP caused the activation of the complement system as revealed by the deposition of complement component C4 upon incubation of diluted serum in wells containing MBP bound to solid-phase mannan. CL-43, lung surfactant protein D (SP-D) and conglutinin showed no complement-activating properties under the same conditions. Conglutinin binds fluid- and solid-phase iC3b, while CL-43 and MBP do not show such reactivity.

Animals↗

Bipolar hemiarthroplasty in femoral neck fractures.

Thirty-two elderly patients with a femoral neck fracture treated by bipolar hemiarthroplasty and 36 patients (matched for age) with an Austin-Moore hemiarthroplasty were followed-up and compared. Bipolar replacement resulted in a higher percentage of satisfactory results, less postoperative pain, greater range of movement, more rapid return to unassisted activity, fewer unsatisfactory results and no acetabular erosion. The device functioned as bipolar in all the cases studied for inner-bearing motion.

Aged↗

Collectins and viral infection.

Members of the collectin protein family are beta-inhibitors of influenza virus infectivity. They bind to carbohydrate on the surface of influenza virus and sterically inhibit virus interaction with host cells, and may also act as opsonins. We propose that collectins, by interacting with glycosylated viruses, act as innate inhibitors of viral infection.

Animals↗

Glycosylation changes of IgG associated with rheumatoid arthritis can activate complement via the mannose-binding protein.

The glycosylation of the circulating immunoglobulin-gamma (IgG) antibody molecules changes in rheumatoid arthritis. The extent of the changes correlates with the disease severity and reverses in remission. We demonstrate here that the alteration in glycosylation associated with rheumatoid arthritis can create a new mode for the interaction of IgG with complement through binding to the collagenous lectin mannose-binding protein (MBP). Rheumatoid arthritis is associated with a marked increases in IgG glycoforms that lack galactose (referred to as G0 glycoforms) in the Fc region of the molecule and that terminate in N-acetyl glucosamine (GlcNAc). We show, using nuclear magnetic resonance (NMR) and X-ray data, that these terminal GlcNAc residues become accessible for MBP binding. We further demonstrate that multiple presentation of IgG-G0 glycoforms to MBP results in activation of the complement. This suggests that a contribution to the chronic inflammation of the synovial membrane could arise from the localization of the IgG-G0 glycoforms in the affected joint and from resulting activation of complement.

Arthritis, Rheumatoid↗