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Biomedical subjects

A Chauhan

Publications and source records attributed to A Chauhan.

At least 73 records · Page 4Linked to original sources
PubMed1997

Reduced Anticoagulation with Antiplatelet Therapy Alone is Safe and Effective after "Bail-Out" Stenting for Failed Angioplasty.

The aim of this retrospective study was to compare the safety and efficacy of antiplatelet therapy alone with conventional anticoagulation with warfarin after Òbail-outÓ coronary stenting for failed balloon angioplasty at a tertiary referral centre. Eighty-two consecutive patients undergoing Òbail-outÓ stenting over a 22-month-period were studied. Forty patients received antiplatelet therapy alone with aspirin and ticlopidine and 42 patients received anticoagulation with warfarin for 30 days. The main outcome measures examined were death, myocardial infarction, coronary artery bypass surgery, repeat angioplasty, and significant vascular complications. The angiographic procedural success rate was 100% in both groups. At six weeks there were no deaths and no patient required emergency coronary artery bypass surgery in either group. There were three (7.1%, p = NS) stent thromboses and two (4.8%, p = NS) Q-wave myocardial infarctions in the warfarin group as compared to none in the antiplatelet group. There was a significantly higher incidence of vascular complications in the warfarin group (21.4% vs. 0%, p = 0.004). The length of hospital stay was significantly shorter in the antiplatelet group [3.4 (2.0) vs. 7.8 (2.6) days, p < 0.001]. This study suggests that reduced anticoagulation with antiplatelet therapy alone after Òbail-outÓ stenting is an effective and safe strategy which reduces vascular complications and hospital stay without increasing the rate of stent thrombosis.

Journal Article↗
PubMed1997

Antiplatelet therapy alone is safe and effective after coronary stenting: observations of a transition in practice.

OBJECTIVE: To evaluate the safety and efficacy of transition in practice after coronary stenting to antiplatelet therapy alone compared with anticoagulation with warfarin. DESIGN: Retrospective analysis of coronary stent management in a tertiary Canadian centre. PATIENTS: A total of 136 consecutive patients (146 lesions) were analyzed who underwent Palmaz-Schatz coronary stenting over a 15-month period and were treated with anticoagulation with warfarin (56 patients) or antiplatelet therapy alone with ticlopidine and acetylsalicylic acid (80 patients) during the transition in poststenting therapy in the authors' practice. Treatment was continued for 30 days in both groups. High pressure stent deployment was used in the majority of cases (greater than 90%), and use of intravascular ultrasound was infrequent (less than 12%). MAIN RESULTS: At 30 days, there were no clinical manifestations of stent thrombosis, coronary artery bypass surgery or repeat angioplasty in either group. One death occurred in the antiplatelet group. Periprocedural non-Q wave myocardial infarction occurred in two patients in the antiplatelet group and in one patient in the warfarin group. There was a significantly higher incidence of vascular complications in the warfarin group than in the antiplatelet group (14.3% versus 2.5%, respectively, P = 0.04). The length of hospital stay was significantly shorter in the antiplatelet group than in the warfarin group (3.0 +/- 1.8 versus 6.7 +/- 2.6 days, respectively, P < 0.001). CONCLUSIONS: Reduced anticoagulation with antiplatelet therapy alone after coronary stenting, despite infrequent use of intravascular ultrasound, is an effective and safe strategy with a low rate of vascular complications, a relatively short hospital stay and a low incidence of clinical manifestations of stent thrombosis.

Adult↗
PubMed1996

Profilin and gelsolin stimulate phosphatidylinositol 3-kinase activity.

Actin-binding proteins such as profilin and gelsolin bind to phosphatidylinositol (PI) 4,5-bisphosphate (PI 4,5-P2) and regulate the concentration of monomeric actin. We report here that profilin and gelsolin stimulate PI 3-kinase-mediated phosphorylation of PI 4,5-P2 (lipid kinase activity) in a concentration-dependent manner. This effect is specific to profilin and gelsolin because other cytoskeletal proteins such as tau or actin do not affect PI 3-kinase activity. In addition to lipid kinase activity, PI 3-kinase also has protein kinase activity: it phosphorylates proteins (p85 subunit of PI 3-kinase). However, the protein kinase activity of PI 3-kinase was not affected in the presence of profilin. Kinetic analysis, as a function of varying concentrations of ATP and PI 4,5-P2, showed that profilin affects the Vmax of PI 3-kinase without affecting k(m). Profilin may also affect PI 3-kinase activity by its direct association to the enzyme because dot-blot analysis using antibody to glutathione S-transferase (GST) suggested that GST-85 kDa, a fusion protein of PI 3-kinase, binds to profilin. However, PI 3-kinase did not affect the actin-sequestering ability of profilin (determined by pyrene-labeled actin), which indicates that actin and p85 do not share a common binding site on profilin. These studies suggest that profilin and gelsolin may control the generation of 3-OH phosphorylated phosphoinositides, which in turn may regulate the actin polymerization.

Actins↗
PubMed1996

Arrhythmogenic right ventricular dysplasia.

Right ventricular dysplasia is a primary disorder of the right ventricular myocardium characterised by a progressive replacement by adipose or fibrous tissue, proceeding from the epicardium towards the endocardium. Right ventricular dysplasia with the predominant clinical manifestation of an arrhythmia of right ventricular origin is defined as arrhythmogenic right ventricular dysplasia. There is, however, a wide spectrum of clinical presentation and physical findings owing to the polymorphism of the condition. The aetiology of right ventricular dysplasia remains unknown. Right ventricular angiography is currently regarded as the gold standard for the clinical diagnosis of right ventricular dysplasia Ventricular endomyocardial biopsy can be useful in confirming the diagnosis but a negative biopsy does not exclude the diagnosis of right ventricular dysplasia. There have been few electrophysiological studies and these, in general, have failed to help in risk stratification. Treatment is focused on the prevention of potentially lethal right ventricular electrical instability.

Adipose Tissue↗
PubMed1996

Effect of cerebrospinal fluid from normal and Alzheimer's patients with different apolipoprotein E phenotypes on in vitro aggregation of amyloid beta-protein.

We examined the effect of cerebrospinal fluid (CSF) from 23 Alzheimer's disease (AD) patients and 22 age-matched non-demented controls with apolipoprotein E4/4, 3/3, or 3/2 phenotypes on in vitro aggregation of amyloid beta-protein (A beta) 1-40 by Thioflavin T fluorescence spectroscopy. CSF from both AD and control groups inhibited A beta aggregation, as compared to that of phosphate buffered saline, in agreement with an earlier report (Wisniewski et al., 1993). However, there was significantly less aggregation of A beta in presence of CSF from AD than that from non-demented controls. The presence of CSF from controls with apoE3/3 phenotype resulted in higher A beta aggregation as compared to other phenotypes. There was a positive correlation between CSF apoE concentrations and A beta aggregation; whereas age, CSF soluble A beta levels or severity of dementia did not correlate with A beta aggregation. These results suggest that mechanism of sequestration of A beta in CSF may not be defective in AD. Amyloid formation in AD may be impact of altered balance of other factors such as amyloid-associated proteins/extracellular matrix components that can immobilize A beta in the brain, and promote its fibrillogenesis in AD.

Aged↗
PubMed1996

Apolipoprotein E polymorphism does not predict risk of restenosis after coronary angioplasty.

A recent report has suggested that the E4 allele of apolipoprotein (apo) E increases the risk of restenosis after percutaneous transluminal coronary angioplasty (PTCA) and also that it interacts synergistically with the deletion (D) allele of the angiotensin-converting enzyme (ACE) to increase the risk sixteen-fold. To investigate this further, we genotyped 231 subjects with successful PTCA who underwent planned repeat angiography at 4 months to assess the degree of restenosis. Subjects carrying the apo E4 allele (n = 71) were well matched with non-carriers (n = 160) for clinical and pre- and post-PTCA angiographic features. We found no increase in either apo E4 allele frequency (18.4% versus 15.6%, P = 0.42) or apo E4 homozygosity (2/106 versus 5/125, P = 0.30) in those with restenosis compared with those without. The relative risk of restenosis for apo E4 carriers was 1.11 (95% CI = 0.87-1.42). In apo E4 carriers, restenosis frequency was similar in those also carrying the ACE D allele and those without (28/55 (50.9%) versus 9/16 (56.2%), P = 0.71) and there was no significant increase in restenosis risk in carriers of both the apo E4 and ACE D alleles compared to the rest (odds ratio 1.30, 95% CI 0.68-2.50, P = 0.39). We conclude that in our cohort, the apo E4 allele does not either independently or acting synergistically with the ACE D allele increase the risk of restenosis after PTCA, and that apo E genotyping will not be a useful predictor of risk before the procedure.

Alleles↗
PubMed1996

Plasmid-encoded degradation of p-nitrophenol by Pseudomonas cepacia.

A Pseudomonas cepacia strain RKJ 200 capable of utilising p-nitrophenol (PNP+) as the sole source of carbon, nitrogen, and energy was isolated by selective enrichment. The degradation of PNP by this strain proceeds through an oxidative route as indicated by the accumulation of nitrite molecules in the culture medium. Initial studies indicate that the degradation of PNP occurs via hydroquinone as shown by thin layer chromatography and gas chromatography studies; hydroquinone is further degraded via the beta-ketoadipate pathway. A plasmid of approximately 50 kilobase pairs was found to be responsible for carrying genes for PNP degradation in this strain. This was based on the facts that the PNP- mutants lacked the plasmid and that the PNP+ phenotype could conjugally be transferred. In addition, the same plasmid also encoded resistance to inorganic zinc ions.

Biotransformation↗
PubMed1996

Promotion of synthetic amyloid beta-peptide fibrillization by cell culture media and cessation of fibrillization by serum.

Dulbecco's modified Eagle's medium promotes aggregation and fibrillization of the synthetic amyloid beta 1-40 and beta 1-42 peptides more than RPMI and OPTI media. Fibrillization in all of these media is faster than in phosphate-buffered saline and Tris buffer. Normal and heat-inactivated fetal bovine and human serum abolish amyloid fibril formation in buffers and cell culture media. Fibrillar amyloid formed during 2-day-long incubation in cell culture media and buffers is defibrillized by 1-day-long treatment with human and bovine serum. This study indicates that amyloid beta fibrillogenesis in cell culture should be studied in serum-free media or in media with a low concentration of serum.

Amyloid beta-Protein Precursor↗
PubMed1996

Cardioesophageal reflex: a mechanism for "linked angina" in patients with angiographically proven coronary artery disease.

OBJECTIVES: The purpose of this study was to investigate the presence of a cardioesophageal reflex in patients with coronary artery disease that may explain the mechanism of "linked angina." BACKGROUND: It has been previously shown that esophageal acid stimulation can reduce coronary blood flow in patients with syndrome X, suggesting the presence of a cardioesophageal reflex in humans. METHODS: We studied the effect of esophageal acid stimulation on coronary blood flow in 14 patients with angiographically documented significant coronary artery disease and in 18 heart transplant recipients. Hydrochloric acid (0.1 mol/liter) and 0.9% saline solution were infused in random, double-blind manner (60 ml over 5 min) through a fine-bore tube positioned in the patient's distal esophagus, and coronary blood flow measurements were obtained after each infusion by use of a 3.6F intracoronary Doppler catheter positioned in the proximal left anterior descending coronary artery. RESULTS: Coronary blood flow was reduced significantly by esophageal acid stimulation in the coronary artery disease group (before acid 70.4 +/- 14.3 ml/min, after acid stimulation 46.4 +/- 19.1 ml/min [mean +/- SD], p < 0.01). However, there was no significant difference in coronary blood flow during saline infusion (73.5 +/- 15.3 vs. 72.5 +/- 14 ml/min). Coronary blood flow in the heart transplant group was not affected by acid or saline infusion. CONCLUSIONS: Esophageal acid stimulation can cause animal attacks and significantly reduce coronary blood flow in patients with coronary artery disease. The lack of any significant effect in heart transplant recipients with heart denervation suggests a neural reflex.

Aged↗
PubMed1996

Aging-associated endothelial dysfunction in humans is reversed by L-arginine.

OBJECTIVES: This study investigated the hypothesis that aging selectively impairs endothelium-dependent function, which may be reversible by administration of L-arginine. BACKGROUND: An impaired response to acetylcholine with aging has been demonstrated in humans. However, the mechanisms underlying this impaired response of the coronary microvasculature remain to be determined. METHODS: We infused the endothelium-independent vasodilators papaverine and glyceryl trinitrate (GTN) and the endothelium-dependent vasodilator acetylcholine (1,3,10 and 30 micrograms/min) into the left coronary artery of 34 patients (27 to 73 years old) with atypical chest pain, negative exercise test results, completely normal findings on coronary angiography and no coronary risk factors. Coronary blood flow was measured with an intracoronary Doppler catheter. The papaverine and acetylcholine infusions were repeated in 14 patients (27 to 73 years old) after an intracoronary infusion of L-arginine (160 mumol/min for 20 min). RESULTS: There was a significant negative correlation between aging and the peak coronary blood flow response evoked by acetylcholine (r = -0.73, p < 0.0001). However, there was no correlation to papaverine (r = -0.04, p = 0.82) and GTN (r = -0.24, p = 0.17). The peak coronary blood flow response evoked by acetylcholine correlated significantly with aging before L-arginine infusion (r = -0.87, p < 0.0001), but this negative correlation was lost after L-arginine infusion (r = -0.37, p = 0.19). CONCLUSIONS: The results suggest that aging selectively impairs endothelium-dependent coronary microvascular function and that this impairment can be restored by administration of L-arginine, a precursor of nitric oxide.

Acetylcholine↗
PubMed1996

Cardio-oesophageal reflex in humans as a mechanism for "linked angina'.

The aim of this study was to investigate the hypothesis that oesophageal acid stimulation reduces coronary blood flow in humans as a result of the presence of a cardio-oesophageal reflex which may provide a mechanism for "linked angina'. We studied the effect of oesophageal acid stimulation on coronary blood flow in 35 syndrome X patients and 24 heart transplant patients. A fine tube was positioned into the patient's distal oesophagus. An intracoronary Doppler catheter was positioned in the proximal left anterior descending coronary artery for coronary blood flow measurements. Oesophageal instillation of 0.1 M hydrochloric acid was performed (60 ml over 5 min) and the measurements were repeated. The coronary blood flow was significantly reduced by acid oesophageal stimulation in the syndrome X group [pre-acid 78.9 +/- 36.4 ml. min-1, post-acid 50.8 +/- 32.9 ml.min-1 (P = 0.0001)]. However, coronary blood flow in the heart transplant group, in whom the heart is denervated, was unaffected by acid infusion. We conclude that oesophageal acid stimulation can produce angina and significantly reduce coronary blood flow in humans. The lack of any significant effect in the heart transplant group, in whom the heart is denervated, suggests a neural reflex.

Adult↗
PubMed1996

Anti-thrombotic therapy for non-rheumatic atrial fibrillation.

Recent randomized trials of antithrombotic therapy in non-rheumatic atrial fibrillation have helped to clarify the benefits of warfarin and aspirin. Low-risk patients (normotensives aged < 60 with normal left ventricular function) have a small risk of thromboembolic events and are unlikely to benefit significantly from anticoagulants, but may benefit from aspirin with little increase in risk of bleeding. High-risk patients (> 75 years, impaired left ventricular function, previous thromboembolism and/or associated conditions such as hypertension and diabetes mellitus) have an increased risk of thromboembolism, and benefit from long-term anticoagulant therapy to a greater degree than with aspirin, although at a risk of increased bleeding complications.

Aged↗
PubMed1996

Coronary flow reserve and oesophageal dysfunction in syndrome X.

The relative prevalence of abnormalities of coronary flow reserve and oesophageal function was ascertained in 32 syndrome X patients with typical angina chest pain, a positive exercise test, and normal coronary arteries. Coronary flow reserve in response to a hyperaemic dose of papaverine was measured using an intracoronary Doppler catheter positioned in the left anterior descending coronary artery. An abnormal coronary flow reserve was defined as being < 3.0. Patients were investigated for oesophageal dysfunction by manometry and 24-hour pH monitoring. Thirteen patients had an impaired coronary flow reserve (group 1) and 19 patients had a normal flow reserve (group 2). Eight of the 13 group 1 patients (62%) and 13 of the 19 group 2 patients (68%, p = NS) had evidence of oesophageal dysfunction on either manometry or pH studies. Therefore, a total of 26 (81%) syndrome X patients had either an abnormality of coronary flow reserve or oesophageal dysfunction suggesting that chest pain in these patients may be due to myocardial ischaemia or oesophageal dysfunction, thus confirming the heterogeneous nature of this syndrome. The prevalence of oesophageal abnormalities was independent of any abnormalities of coronary flow reserve.

Adult↗
PubMed1996

Pulmonary embolism--the role of thrombolytic therapy in its management.

In massive pulmonary embolism where there may be evidence of right ventricular dysfunction and acute pulmonary hypertension, anticoagulation therapy alone may prove inadequate. In such situations use of thrombolytic agents produces an improvement in haemodynamics compared to anticoagulants alone, although studies to date have been too small to address the issue of mortality benefit. It would appear that all age groups gain benefit from the use of thrombolytics. Studies that have compared thrombolytic agents and anticoagulants are discussed. In addition, the issues of the choice of thrombolytic agent and the different modes of delivery of therapy are addressed.

Anticoagulants↗
PubMed1996

Phosphoinositide-dependent in vitro phosphorylation of profilin by protein kinase C. Phospholipid specificity and localization of the phosphorylation site.

Phosphoinositides bind to profilin and regulate actin-based cytoskeletal protein assembly. We report here that profilin is phosphorylated in vitro by protein kinase C (PKC) in the presence of phosphoinositides and micromolar concentrations of calcium. PKC-mediated phosphorylation of profilin was observed only in the presence of phosphoinositides; phosphatidylserine and diacylglycerol (known activators of PKC) and other lipids, including phosphatidic acid and phosphatidylglycerol phosphate, did not activate the phosphorylation. The activation of PKC-mediated phosphorylation of profilin by phosphoinositides was as follows: phosphatidylinositol (PI) 4-phosphate (K(m) = 18 microM) > PI 4,5-bisphosphate (K(m) = 30 microM) > PI (no activation). About 0.5 mol phosphate was incorporated per mol of profilin. Phosphorylation of profilin by PKC was not affected by the presence of various concentrations of actin. Phospho-amino acid analysis showed serine to be the only amino acid phosphorylated. The amino acid sequence of a phosphopeptide from CNBr-digested profilin corresponded to the COOH-terminal peptide of profilin (Ala-Ser-His-Leu-Arg-Ser-Gln-Tyr). Further digestion of this phosphopeptide by trypsin generated two phosphopeptides (Arg-Ser-Gln-Tyr and Ser-Gln-Tyr), thereby confirming that the phosphorylation site was the antepenultimate Ser (Ala-Ser-His-Leu-Arg-Arg-Ser(P)-Gln-Tyr).

Actins↗
PubMed1995

Phosphatidylinositol 3-kinase: inhibition of intrinsic protein-serine kinase activity by phosphoinositides, and of lipid kinase activity by Mn2+.

Phosphatidylinositol (PI) 3-kinase is composed of 110 kDa catalytic and 85 kDa regulatory subunits. The 110 kDa subunit has two intrinsic kinase activities, i.e., Mn(2+)-dependent protein-serine kinase and Mg(2+)-dependent lipid kinase activities. These intrinsic kinases have been reported to be interdependent: protein-serine kinase phosphorylates the 85 kDa subunit of PI 3-kinase, which upon phosphorylation inhibits the lipid kinase activity of PI 3-kinase. We report here that phosphoinositides can selectively inhibit the protein-serine kinase activity of PI 3-kinase without affecting lipid kinase activity. This inhibition depends on the phosphorylation status of the phosphoinositides, i.e., PI 4,5-bisphosphate > PI 4-phosphate >> PI. Mn2+ (2 mM) protected protein kinase activity from phosphoinositides-mediated inhibition if added prior to interaction of PI 3-kinase with phosphoinositides. On the other hand, Mn2+ (2 mM) inhibited lipid kinase activity independent of its effect on the protein kinase activity of PI 3-kinase. The present study suggests that the protein-serine kinase and the lipid kinase activities of PI 3-kinase can be selectively inhibited by phosphoinositides and Mn2+ respectively.

Animals↗