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Biomedical subjects

A Grover

Publications and source records attributed to A Grover.

At least 19 recordsLinked to original sources

A randomized controlled clinical trial to evaluate the efficacy, safety, cost-effectiveness and effect on PAI-1 levels of the three low-molecular-weight heparins--enoxaparin, nadroparin and dalteparin. The ESCAPe-END study.

BACKGROUND: Comparative data for efficacy and safety between various low-molecular-weight heparins (LMWHs) in patients with unstable angina is not available. The present study was conducted to compare the efficacy, safety, cost-effectiveness and effects on plasminogen activator inhibitor-1 (PAI-1) levels of three LMWHs--enoxaparin, nadroparin and dalteparin. METHODS: The study was a prospective, randomized, comparative, open with blinded endpoints (PROBE design) assessment with a 30-day follow-up. The primary endpoint of efficacy was a composite of cardiovascular death, myocardial infarction, recurrent angina and need for intervention. Cost-effectiveness was calculated by calculating the incremental cost-effectiveness ratio. Plasma PAI-1 levels were estimated by ELISA. RESULTS: A total of 150 patients were available for intention-to-treat analysis. There was no significant difference at 30 days in the primary endpoint or in any of the individual components in the three groups. The secondary endpoint of silent ischemia was also not significantly different. Adverse events were similar in the three groups. The PAI-1 levels were not significantly different in the three groups. The total cost of treatment in the three groups was similar. CONCLUSION: Any of the three LMWHs evaluated in this study were similar with respect to efficacy, safety, PAI-1 levels and cost-effectiveness.

Adult↗

A meta-analysis of trials comparing Cypher and Taxus stents in patients with obstructive coronary artery disease.

AIMS: Drug-eluting stents have been shown to be superior to bare metal stents in reducing restenosis rates. Recently head-to-head trials comparing sirolimus-eluting stents and paclitaxel-eluting stents have been reported. An early combined analysis of these comparative trials is needed. The present meta-analysis was carried out to compare the effects of sirolimus-eluting stents with paclitaxel-eluting stents on the restenosis rate, major adverse cardiac events and late loss of arterial lumen diameter in patients with obstructive coronary artery disease. METHODS: Electronic (Medline, Cochrane and Embase) and manual search (Index Medicus and cross references of retrieved articles) were carried out for all the relevant articles up till March 2005. Only randomized trials with adequate data for calculation of odds ratio for restenosis rates and major adverse cardiac events using the method of DerSimonian & Laird and standardized mean difference for late loss of arterial lumen diameter were included. RESULTS: Four studies were found to be eligible for inclusion in the meta-analysis. Restenosis rate and late loss of arterial lumen diameter were significantly reduced by sirolimus-eluting stents as compared with paclitaxel-eluting stents (OR 0.598, 95% CI 0.400, 0.893, pooled mean difference -0.414, 95% CI -0.492, 0.336, respectively). The incidence of major adverse cardiac events was less with sirolimus-eluting stents as compared with paclitaxel-eluting stents (OR 0.727, 95% CI 0.518-1.018) but the results were not statistically significant. CONCLUSIONS: Sirolimus-eluting stents are superior to paclitaxel-eluting stents in decreasing restenosis rate and late loss of arterial lumen diameter. However, no statistically significant difference in major adverse cardiac events was noted between the two stents.

Coronary Stenosis↗

Genotypic diversity in a localized population of Ralstonia solanacearum as revealed by random amplified polymorphic DNA markers.

AIMS: To assess genotypic diversity within Ralstonia solanacearum isolates of a single field. METHODS AND RESULTS: A total of 44 field isolates and 22 in vitro generated clones of R. solanacearum were studied for genotypic diversity by random amplified polymorphic DNA (RAPD) technique. Genomic DNA of these isolates and clones was extracted by proteinase-K-SDS lysis mini-prep method. RAPD analysis was done with 30 decamer primers. The data were analysed using NTSYSpc 2.02h software. Forty-two out of 44 field isolates and all the clonal isolates were identified as distinct genotypes at 70% similarity level. CONCLUSION: Very high level of genome variability was observed within the field and clonal isolates of R. solanacearum. This might be a reason for the wide host range of this bacterium and for quick breakdown of wilt resistance in host plants. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that it would be difficult to design specific diagnostic protocol for R. solanacearum even for a localized population and to breed cultivars with broad-spectrum resistance.

DNA, Bacterial↗

Study design and rationale of a mock phase I trial as an educational tool for clinical pharmacology residents.

OBJECTIVE: To invite comments and suggestions from the phase I trialists, the world over, on the design and rationale provided by us for conducting a mock phase I trial for training clinical pharmacology residents. METHODS: The trial will be conducted by clinical pharmacology residents of the Post Graduate Institute of Medical Education and Research. After a thorough evaluation of Preclinical toxicity data of a pharmaceutical product provided by a dummy pharmaceutical firm, a randomized, double-blind, placebo controlled, parallel group design with dose escalation of the product will be carried out. A single dose administration will be followed by monitoring the participants for 24 h and again at one week. After obtaining results of the previous group, the next higher dose will be administered. Evaluation of the learners will be done by two independent teachers who will mark them for actual conduct of the study and writing a report of the study. Subsequently, we will try to publish the results of the mock trial and invite further comments. CONCLUSIONS: This trial designed primarily for training purposes will be instrumental in equipping the residents with the expertise for conducting phase I trials.

Adolescent↗

A meta-analysis of clinical trials of paclitaxel- and sirolimus-eluting stents in patients with obstructive coronary artery disease.

AIM: This meta-analysis was conducted to compare the effects of drug (paclitaxel and sirolimus)-eluting stents with bare metal stents on major adverse cardiac events, restenosis rates and late loss of arterial lumen diameter in patients with obstructive coronary artery disease. METHODS: Randomized, controlled clinical trials comparing sirolimus- and paclitaxel-eluting stents with bare metal stents were identified through electronic and manual search. Fixed effects method of Mantel-Haenszel and random effects method of DerSimonian and Laird were used for computing the pooled odds ratio (OR) and 95% confidence intervals (CI) for major adverse cardiac events and restenosis rates. Standardized mean difference with 95% CI was calculated for late-loss of arterial lumen diameter. RESULTS: A total of 13 studies were included in the meta-analysis. As compared with bare metal stents, the use of sirolimus- and paclitaxel-eluting stents significantly reduced the major adverse cardiac events (pooled OR 0.35; 95% CI 0.24-0.50), restenosis rates (pooled OR 0.27; 95% CI 0.15-0.47), and late loss of arterial lumen diameter (mean difference 0.57 mm, 95% CI 0.49-0.68). CONCLUSION: Paclitaxel- and sirolimus-eluting stents significantly reduced the incidence of major adverse cardiac events, restenosis rates, and late loss of arterial lumen diameter as compared with bare metal stents.

Cell Proliferation↗

Azygos continuation of interrupted inferior vena cava in association with sick sinus syndrome.

Various diagnostic and therapeutic procedures of the right side of the heart and the systemic venous system have increased the need for ready access to the inferior vena cava (IVC) through the transfemoral route. Anatomical variations or obstruction of the IVC can make these procedures difficult. The case of 47 year old woman with an interrupted infrahepatic IVC with azygos continuation accompanied by sick sinus syndrome and a structurally normal heart is reported. Negotiating a temporary pacing lead from the IVC to the right atrium was difficult. Ultimately, the lead took the course from the IVC to azygos vein to superior vena cava to right atrium to right ventricular apex. Permanent VVI pacing through the right subclavian route was uneventful, as the superior vena cava and its tributaries had a normal course. An awareness of the existence of these anomalies before pacing can lead to the use of an alternative route for pacing, which may avoid undue delay of an otherwise urgently needed procedure.

Azygos Vein↗

Hyperphosphorylation-induced self assembly of murine tau: a comparison with human tau.

Alzheimer's disease-like neurofibrillary pathology is neither seen in rodents nor in transgenic animals expressing the disease causing mutant human APP or mutant human presenilins. Whether the absence of this pathology is due to inability of the murine tau to self assemble into filaments or due to some other factors is not understood. In this study, we compared recombinant murine and human taus in their ability to form filaments by AD-like hyperphosphorylation in vitro. Human and murine taus, 0N4R, were generated as recombinant proteins and phosphorylated with rat brain extract as a source of protein kinases. We found that murine tau could be hyperphosphorylated to similar stoichiometry and manner as human tau. Upon hyperphosphorylation, murine tau was able to self polymerize into bundles of paired helical filament- and straight filament-like morphology. The filaments obtained from self assembly of murine tau closely resembled those formed from identically treated human tau. Moreover, like human tau, 60-70% of murine tau aggregated on hyperphosphorylation.

Animals↗

Re-use of explanted DDD pacemakers as VDD- clinical utility and cost effectiveness.

Re-use of DDD pulse generators explanted from patients died of unrelated causes is associated with an additional cost of two transvenous leads if implanted as DDD itself, and high rate of infection according to some studies. We studied the clinical and economical aspects of reutilization of explanted DDD pacemakers programmed to VDD mode. Out of 28 patients who received VDD pacemaker during the period, October 2000- September 2001 in the Department of Cardiology, PGIMER, Chandigarh, 5 poor patients were implanted with explanted DDD pulse generators programmed to VDD mode. Each implantation was planned and carried out according to a standard protocol. The age ranged from 45 to 75 (mean-61) years. The indications for pacing were complete heart block (4) and second degree AV block (1). The clinical profile, costs and complications, if any were noted and followed up at regular intervals. The results were compared with patients who received new DDD pulse generators during this period. The additional cost for the atrial lead was not required in these patients. None of these patients had any local site infection. Compared to the two-lead system, the single lead system provided more rapid implantation and minimized complications associated with placement of an atrial lead. The explanted DDD pacemaker can be safely reused as VDD mode with same efficacy in selected patient population. This is associated with lower cost and complications compared to reimplantation as DDD itself.

Journal Article↗

Changing trends in the hospital management of unstable angina: a drug utilization analysis.

OBJECTIVE: The current study was designed to investigate drug utilization in the management of unstable angina in India and to examine the changing trends in the management of unstable angina over the past 4 years. METHODS: We conducted a prescription survey to examine the use of antianginal drugs in patients with unstable angina in a tertiary care Indian hospital. The use of concurrent medications such as antidiabetic, antihypertensive and lipid-lowering agents was also examined. This study results were compared with a similar study done in this institute 4 years earlier. RESULTS: A total of 159 consecutive prescriptions were evaluated. Aspirin (86%), nitroglycerin infusion (77%) and low-molecular weight heparins (93%) were the most frequently prescribed drugs. Enoxaparin accounted for 76% of the total LMWH use. One of the heparins was used by 92% of all patients, angiotensin-converting enzyme inhibitors (ACEIs) and beta-blockers by 70% and 67%, respectively. Lipid-lowering agents (57%), antidiabetic agents (16%) and antianxiety agents (33%), in addition to antianginals, were also frequently co-administered. Time trend analysis showed that the use of unfractionated heparin fell from 35% to 10% and the use of ACEIs and enoxaparin increased from 17% to 70% and from 51% to 71%, respectively. CONCLUSIONS: The study showed that unfractionated heparin is less frequently used in the treatment of unstable angina than in the past and that ACEIs are preferred to calcium channel blockers. Enoxaparin remains the most commonly used low-molecular weight heparin for this indication. A variety of low-molecular weight heparins are available for therapy but comparative clinical trials of efficacy and pharmacoeconomic studies comparing the various LMWHs still need to be carried out.

Angina, Unstable↗

Estrogen potentiates the combined effects of transforming growth factor-beta and tumor necrosis factor-alpha on adult human osteoblast-like cell prostaglandin E2 biosynthesis.

Reports that estrogen treatment modulates arachidonic acid metabolism by bone and bone cells are found in the literature. However, conflicting indications of the relationship that exists between estrogen and arachidonic acid metabolism emerge from the analysis of those reports. The present studies were undertaken to determine if estrogen effected the production of prostaglandins (PG) in human osteoblast-like (hOB) cell cultures derived from adults, under basal or cytokine-stimulated conditions. A 48-hour estrogen pretreatment did not modify hOB cell PG biosynthesis on a qualitative basis, and PGE2 formation predominated under all tested conditions. Estrogen pretreatment did lead to increased PGE2 production in specimens stimulated conjointly with transforming growth factor-beta1 and tumor necrosis factor-alpha ( p < 0.001). No changes in PGE2 production were observed in estrogen pretreated specimens stimulated singly with either tested cytokine, nor in samples in which either TGFbeta or TNF was replaced by interleukin-1beta. Anti-estrogen (ICI 164,384) inclusion prevented the estrogen-dependent increase in PGE2 production in the TGFbeta plus TNF-stimulated samples. These results suggest that an estrogen effect on bone cell prostaglandin biosynthesis may be most evident and significant under conditions in which the cells are exposed to multiple osteotropic cytokines, a condition that applies during the bone remodeling process.

Adult↗

Maternal and perinatal outcome in rheumatic heart disease.

OBJECTIVES: To study the maternal and perinatal outcome of pregnancies complicated by rheumatic heart disease. METHODS: A retrospective study was carried out in the cardio-obstetric clinic of the Postgraduate Institute of Medical Education and Research, Chandigarh (India) over a period of 13 years (1987-1999) involving 486 pregnant patients with rheumatic heart disease. Maternal and perinatal outcome was reviewed. RESULTS: Three hundred and four patients (63.3%) had single valve involvement and mitral stenosis was the most predominant lesion (89.2%). One hundred and seventy one (38.6%) patients had undergone surgical correction prior to the onset of pregnancy. One hundred and thirteen patients (22.6%) were identified as NYHA class III-IV. Mitral valvotomy was performed during pregnancy in 48 patients. The incidence of preterm birth and small for gestational age newborns was 12% and 18.2%, respectively. There were 10 maternal deaths, of which eight patients were NYHA III and IV. CONCLUSIONS: Rheumatic heart disease in pregnancy is associated with significant maternal and perinatal morbidity in NYHA class III-IV patients.

Adult↗

Effect of different aspirin doses on platelet aggregation in patients with stable coronary artery disease.

BACKGROUND: Aspirin is widely used as an antiplatelet agent in the primary and secondary prevention of cardiovascular disease. In order to spare prostacyclin formation and reduce gastrointestinal side-effects, very low doses of aspirin have been introduced. However, it remains unclear whether these low doses are equally effective with respect to inhibition of platelet aggregation. AIMS: In a randomized, controlled study in 60 patients with stable coronary artery disease, the effects on platelet aggregation of five doses (50, 80, 100, 162.5 and 325 mg) of aspirin, which are widely used in clinical practice, given for 70 days, were investigated. Two reagents, adenosine diphosphate (ADP) and epinephrine, were used to induce platelet aggregation in platelet-rich plasma. An age- and sex-matched group of people without coronary artery disease served as the control. RESULTS: ADP- and epinephrine-induced platelet aggregation was 78.2 +/- 12.8% and 76.7 +/- 15.5% of maximum aggregation in the control group. Aspirin inhibited platelet aggregation in a dose-dependent manner. Minimum platelet aggregation was observed at a dose of 325 mg aspirin (27.5 +/- 17.4% with ADP). Doses of 50 and 80 mg aspirin were much less effective in inhibiting platelet aggregation (59.1 +/- 11.4% and 50.3 +/- 12.1% with ADP, respectively). Doses of 100 and 162.5 mg aspirin produced significantly greater inhibition of platelet aggregation than lower doses (36.2 +/- 11.7% and 38.5 +/- 19.8% platelet aggregation with ADP, respectively). CONCLUSION: Our results demonstrate that doses of aspirin less than 100 mg are not as effective at inhibiting platelet aggregation as doses greater than 100 mg.

Adenosine Diphosphate↗

Isolation and expression analysis of salt stress-associated ESTs from contrasting rice cultivars using a PCR-based subtraction method.

Salt stress adversely affects the growth of rice plants. To understand the molecular basis of salt-stress response, four subtracted cDNA libraries were constructed employing specific NaCl-stressed tissues from salt-tolerant (CSR 27 and Pokkali) and salt-sensitive (Pusa basmati 1) rice cultivars. An efficient PCR-based cDNA subtraction method was employed for the isolation of the salt-stress responsive cDNA clones. In all, 1,266 cDNA clones were isolated in the course of this study, out of which 85 clones were end-sequenced. Database search of the sequenced clones showed that 22 clones were homologous to genes that have earlier been implicated in stress response, 34 clones were novel with respect to their function and six clones showed no homology to sequences in any of the public database. Northern analysis showed that the transcript expression pattern of selected clones was variable amongst the cultivars tested with respect to stress-regulation.

Blotting, Northern↗

Distribution of cells bearing B-cell alloantigen(s) in North Indian rheumatic fever/rheumatic heart disease patients.

Numerous investigators have developed monoclonal antibodies against B-cell alloantigen(s) of rheumatic fever. However, the developed monoclonals do not have the same significance in all the populations. We have developed a battery of monoclonals against B-cell alloantigens of North Indian rheumatic fever patients. In the present study, we have used these monoclonals to examine the frequency of rheumatic antigens in 30 patients with recurrence of rheumatic activity (RRA), 30 of rheumatic heart disease (RHD) patients and 50 controls using alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. These patients were examined at the time of registry and after three months follow up. RRA patients showed higher percentage of lymphocyte positive as compare to RHD and controls. Interestingly, on follow-up RRA patients showed significant decline in positive lymphocyte as compare to first visit whereas no such change was observed in RHD patients. There were 90-93% of RRA and RHD patients positive with these monoclonals. A significant age variation of rheumatic cells was also noticed in all groups of rheumatic patients. We conclude that monoclonals raised from the same ethnic population are highly specific and cost effective to use them to develop an easy field test system such as APAAP, to identify the individual at risk, to develop rheumatic fever. It is also suggested that the alloantigen marker may persist through out life and gets activated after recurrence of the disease.

Adolescent↗

Involvement of nitric oxide in the antiaggregatory effect of enalapril.

This study was conducted to examine the effects of single dose enalapril (1.6 mg/kg) on platelet aggregation alone and after an intravenous bolus dose of the nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine (L-NNA; 40 mg/kg). Blood samples were collected before and 1, 2 and 6 h after the administration of drugs in rhesus monkeys. Enalapril was administered via a nasogastric tube while L-NNA was administered by the intravenous route. Platelet aggregation was stimulated with adenosine diphosphate (ADP) in platelet rich plasma (PRP). Enalapril significantly inhibited platelet aggregation with a peak effect at 6 h. Upon administration of L-NNA, there was a significant increase in the percentage of platelet aggregation. This effect was partially antagonized by enalapril. The present study demonstrates that enalapril may possess antiaggregatory effects, which may be mediated via nitric oxide mechanisms.

Adenosine Diphosphate↗