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Biomedical subjects

D Roy

Publications and source records attributed to D Roy.

At least 127 records · Page 7Linked to original sources
PubMed1998

Is there a future for antiarrhythmic drug therapy?

Drug therapy has traditionally been the mainstay of treatment for both ventricular and supraventricular arrhythmias. However, increasing knowledge about the potentially significant adverse effects of these medications, together with the emergence of new, nonpharmacological approaches to the treatment of arrhythmias, has led some to question the future of antiarrhythmic drug therapy. Antiarrhythmic drugs are quite effective in terminating a variety of arrhythmias, including atrioventricular (AV) node re-entrant and AV tachycardias (particularly calcium antagonists and adenosine), atrial flutter (class III agents) and atrial fibrillation (class IA and IC drugs. The chronic use of antiarrhythmic drugs has been increasingly limited by a fear of adverse effects (especially proarrhythmia) and the availability of highly effective nonpharmacological alternatives (particularly ablation for re-entrant tachycardias involving the AV node and bypass tracts and cardiovertor/defibrillators for malignant ventricular arrhythmias. Atrial fibrillation (AF) continues to be a therapeutic challenge for which there is no safe and curative nonpharmacological therapy. Antiarrhythmic drugs of classes IA, IC and III show efficacy in preventing recurrence of AF but there are concerns about possible pro-arrhythmic complications. In the future, antiarrhythmic agents will continue to be used acutely to terminate a broad range of sustained arrhythmias. Chronic use is likely to depend on the development of safer and/or more effective compounds, as well as on improved ways of predicting which patients are likely to develop pro-arrhythmic reactions. The development of molecular electrophysiology will allow for the identification of agents with selected ion channel blocking profiles which may prove efficacious with a lower risk of complications. Finally, an improved understanding of arrhythmia substrates may permit the identification of therapy that prevents arrhythmias by acting on the underlying substrate, rather than simply trying to modify the electrical end product.

Anti-Arrhythmia Agents↗
PubMed1998

Selective impairment in GLUT4 translocation to transverse tubules in skeletal muscle of streptozotocin-induced diabetic rats.

We previously reported that insulin induces the translocation of GLUT4 to both the plasma membrane and the transverse tubules (T-tubules) in rat skeletal muscle (Am J Physiol 270:E667-E676, 1996). The aim of the present study was to investigate whether the insulin-resistant glucose utilization of skeletal muscle from streptozotocin (STZ)-induced diabetic rats is linked to an impaired translocation of GLUT4 to the plasma membrane, the T-tubules, or both surface compartments. Whole-body insulin-mediated glucose disposal, assessed during a hyperinsulinemic-euglycemic clamp, was reduced by 48% (P < 0.01) in diabetic rats as compared with controls. Subcellular membrane fractions enriched with plasma membranes, T-tubules, or GLUT4-enriched intracellular membranes were isolated from hindlimb muscles of control and insulin-stimulated rats, and GLUT4 content was measured by Western blot analysis. In the absence of insulin (unstimulated), GLUT4 content in muscle of diabetic rats was markedly lower (by approximately 40%) in both the T-tubules and the intracellular membrane fraction as compared with controls. In contrast, the transporter protein levels were similar in the plasma membrane fraction. In skeletal muscle of control animals, the hyperinsulinemic clamp induced GLUT4 translocation from the intracellular membrane pool to both the plasma membrane and the T-tubule-enriched fractions (approximately 2.2-fold to approximately 2.5-fold). Surprisingly, insulin increased plasma membrane GLUT4 content to comparable levels in control and diabetic rat skeletal muscle. However, insulin-mediated GLUT4 translocation to the T-tubules was significantly reduced in the same muscle. Whole-body insulin action was significantly correlated with GLUT4 protein levels in the T-tubules, but not with the transporter content in either plasma membranes or intracellular membranes. These results strongly suggest that peripheral resistance to insulin action on glucose disposal in STZ-induced diabetic rats is caused by a selective impairment of GLUT4 translocation to skeletal muscle T-tubules.

Animals↗
PubMed1998

Benign superior vena cava syndrome due to suppurative mediastinal lymphadenitis: anterior mediastinoscopic management.

The benign superior vena cava syndrome is an uncommon medical emergency. We describe a case of the superior vena cava syndrome caused by suppurative mediastinal lymphadenitis. The organisms isolated from various cultures were group C beta-hemolytic Streptococcus, Fusobacterium species, Corynebacterium species, Eikenella corrodens, and Streptococcus milleri. These anaerobic bacteria are part of the normal flora of the upper respiratory tract and the oral cavity. Anterior mediastinoscopy through the right parasternal approach was used to drain the anterior mediastinal abscess and to establish the etiologic factor.

Adult↗
PubMed1998

Adhesion of Aeromonas hydrophila to water distribution system pipes after different contact times.

Scanning electron microscopy observation was used to investigate the ability of Aeromonas hydrophila to attach to various water distribution pipe surfaces, such as stainless steel, copper, and polybutylene, after different contact times at ambient and storage temperatures. Surface energy value of each surface was estimated by contact angle measurements using water, alpha-bromonaphthalene, and dimethyl sulfoxide. Our results indicated that Aeromonas cells could easily attach to all surface types after exposures as short as 1 or 4 h at both temperatures (4 and 20 degrees C). Polybutylene, a low-energy surface (41.2 mJ.m-2), followed by stainless steel (65.7 mJ.m-2), was most colonized by Aeromonas cells, whereas few cells were observed on copper, which has a surface energy of 45.8 mJ.m-2. Extracellular materials could also be observed on polybutylene surfaces, especially after 1 and 4 h of exposure at the refrigeration temperature.

Aeromonas hydrophila↗
PubMed1998

Craniocervical dural fistula associated with cervical myelopathy: angiographic demonstration of normal venous drainage of the thoracolumbar cord does not rule out diagnosis.

We report a case of craniocervical dural arteriovenous fistula with perimedullary venous drainage associated with cervical myelopathy in which spinal angiography showed a normal venous phase after injection of the artery of Adamkiewicz. We conclude that because of the complex venous drainage of the spinal cord, a dural arteriovenous fistula with spinal drainage cannot be ruled out solely because a normal venous phase is seen in the lower part of the cord, as has previously been suggested.

Aged↗
PubMed1998

Secondhand smoke, hypofibrinolysis, and Legg-Perthes disease.

In 39 children with Legg-Perthes disease who were nonsmokers, the specific aim was to assess relationships among parental cigarette smoking during pregnancy, household smoking before diagnosis of Legg-Perthes disease, hypofibrinolysis, and thrombophilia. Fifteen (38%) children had no secondhand smoke exposure; 24 (62%) had secondhand smoke exposure before their diagnosis. Seventeen (71%) of these 24 children were exposed while in utero to smoking by a parent or live in relative and also had exposure to household smoke during childhood; seven (29%) had only household smoke exposure in childhood. In the full cohort of 39 children, secondhand smoke exposure correlated inversely with the major stimulator of fibrinolysis, stimulated tissue plasminogen activator activity. Of the children exposed to smoking, 48% had low stimulated tissue plasminogen activator activity (< 2.19 IU/ml) compared with 7% of the children without secondhand smoke exposure and 14% of 22 healthy control children. Secondhand smoke exposure had no significant effects on other measures of coagulation. Secondhand smoke exposure while in utero and during childhood appears to lower stimulated tissue plasminogen activator activity and additionally may depress heritable low stimulated tissue plasminogen activator activity, leading to hypofibrinolysis. Hypofibrinolysis may facilitate thrombotic venous occlusion in the head of the femur, leading to venous hypertension and hypoxic bone death, Legg-Perthes disease.

Adult↗
PubMed1997

Pilot study and protocol of the Canadian Trial of Atrial Fibrillation (CTAF).

Antiarrhythmic drug prophylaxis in patients with atrial fibrillation (AF) is associated with a high incidence of arrhythmic recurrence. Uncontrolled studies have suggested that low-dose amiodarone may be superior in terms of efficacy to other antiarrhythmic drugs while having an acceptable side effect profile. The Canadian Trial of Atrial Fibrillation (CTAF) is a 25-center study sponsored by the Medical Research Council of Canada to determine the best treatment strategy to maintain sinus rhythm in patients with persistent or paroxysmal AF. Recruitment began in November 1996 and will continue for 1.5 years. Patients are randomized to receive either low-dose amiodarone or conventional antiarrhythmic drug therapy. Patients assigned to the amiodarone group will receive an oral loading regimen of 10 mg/kg/day during a minimum 14-day period. Patients assigned to conventional antiarrhythmic therapy will receive 1 of 2 agents commonly used in AF prophylaxis: sotalol or propafenone. Drug selection and loading, and electrical cardioversion, if necessary, will be performed within 21 days of randomization. The long-term maintenance dose of amiodarone is 200 mg/day. We have planned a minimum follow-up period of 1 year. The primary end point is the time to the first relapse of AF. Data will be analyzed on an intention-to-treat basis. Secondary outcomes are medication toxicity, mortality, major clinical events, costs of each approach, and quality of life. For the purpose of sample size calculations, it is anticipated that recurrence of AF at 1 year will occur in 50% of patients on conventional treatment compared with 35% in those receiving amiodarone. In order to have an 80% power and a 2-tailed type I error of 0.05, assuming a 15% loss to follow-up rate, a total sample size of 400 patients will be required. A pilot study done at the Montreal Heart Institute has shown that the research protocol is feasible.

Amiodarone↗
PubMed1997

Characterization of Streptomyces sp. strain DRS-1 and its ampicillin transformation product.

Incubation of ampicillin with whole cells of Streptomyces sp. DRS-1 resulted in accumulation of four compounds different from ampicillin. One of them was isolated, purified and partially characterized. On the basis of spectroscopic characteristics, RF value and antibacterial activity the compound was identified as cephalexin. It could also be obtained from ampicillin by using crude protein extract of the strain.

Ampicillin↗
PubMed1997

Continuous veno-venous hemodiafiltration using bicarbonate dialysate.

We report our experience with 11 children treated by continuous veno-venous hemodiafiltration. The median age was 5.0 years (range 3 days to 14 years). Access was via dual-lumen subclavian or femoral vein catheters. Hemofilters were chosen on the basis of patient size and dialysis requirements. Bicarbonate-buffered dialysis solution was prepared shortly before use by supplementation of a specially prepared base solution with commercially available electrolyte solutions. The mean ultrafiltration rate was 37.4 +/- 27 ml/kg body weight per hour. Urea and creatinine clearances were 15.1 +/- 6.4 ml/kg body weight per min and 16.4 +/- 8.4 ml/kg body weight per min, respectively. Metabolic acidosis was readily controlled in all patients. Of the 11 patients, 7 ultimately recovered normal renal function.

Acidosis↗
PubMed1997

Profound effects of the weak environmental estrogen-like chemical bisphenol A on the growth of the mammary gland of Noble rats.

In the present study we have examined the effects of the environmental estrogenic chemical bisphenol A on proliferative activity, cell cycle kinetics and differentiation of the mammary gland of female Noble rats. Differentiation measured by the degree of lobular maturation revealed that the conversion of immature structures to mature structures was significantly increased in response to exposure to both low (0.1 mg/kg/day) and high (54 mg/kg/day) doses of bisphenol A compared to controls. The proliferative activity of epithelial cells was increased by 143% over controls by the exposure of animals to the low dose of bisphenol A, whereas a 220% increase over controls was observed for the high dose of bisphenol A. The labelling index and growth fraction were 19% and 27%, respectively, for a low dose of bisphenol A; and 27% and 45%, respectively, for a high dose of bisphenol A, compared to 18% and 31%, respectively, in controls. A significant increase in the conversion of mammary epithelial cells from G0, to G1, and S-phase cells by 1.8 and 4.5-fold, respectively, was observed in animals exposed to the high dose of bisphenol A compared to that of controls. Based on the previously reported estrogenic activity of an equivalent dose of bisphenol A to that of diethylstilbestrol (DES) (0.1 mg/kg/day), a calculated theoretical dose of the order of 10(6)-fold higher of bisphenol A will be required to produce the same biological effects as DES. A comparison of the proliferative activity of DES and that of an equivalent dose of bisphenol A observed in this study, however, revealed that its influence on proliferative activity in the epithelial cells of the mammary gland was profound. The weak estrogenic activity of bisphenol A does not explain its profound effect on cell proliferation observed in this study. Perturbation of the cell cycle is considered a risk factor for the development of cancer. Bisphenol-mediated perturbation of the cell cycle in epithelial cells may produce adverse effects in the mammary glands of Noble rats.

Air Pollutants, Occupational↗
PubMed1997

Biochemical and molecular changes at the cellular level in response to exposure to environmental estrogen-like chemicals.

Estrogen-like chemicals are unique compared to nonestrogenic xenobiotics, because in addition to their chemical properties, the estrogenic property of these compounds allows them to act like sex hormones. Whether weak or strong, the estrogenic response of a chemical, if not overcome, will add extra estrogenic burden to the system. At elevated doses, natural estrogens and environmental estrogen-like chemicals are known to produce adverse effects. The source of extra or elevated concentration of estrogen could be either endogenous or exogenous. The potential of exposure for humans and animals to environmental estrogen-like chemicals is high. Only a limited number of estrogen-like compounds, such as diethylstilbestrol (DES), bisphenol A, nonylphenol, polychlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (DDT), have been used to assess the biochemical and molecular changes at the cellular level. Among them, DES is the most extensively studied estrogen-like chemical, and therefore this article is focused mainly on DES-related observations. In addition to estrogenic effects, environmental estrogen-like chemicals produce multiple and multitype genetic and/or nongenetic hits. Exposure of Syrian hamsters to stilbene estrogen (DES) produces several changes in the nuclei of target organ for carcinogenesis (kidney): (1) Products of nuclear redox reactions of DES modify transcription regulating proteins and DNA; (2) transcription is inhibited; (3) tyrosine phosphorylation of nuclear proteins, including RNA polymerase II, p53, and nuclear insulin-like growth factor-1 receptor, is altered; and (4) DNA repair gene DNA polymerase beta transcripts are decreased and mutated. Exposure of Noble rats to DES also produces several changes in the mammary gland: proliferative activity is drastically altered; the cell cycle of mammary epithelial cells is perturbed; telomeric length is attenuated; etc. It appears that some other estrogenic compounds, such as bisphenol A and nonylphenol, may also follow a similar pattern of effects to DES, because we have recently shown that these compounds alter cell cycle kinetics, produce telomeric associations, and produce chromosomal aberrations. Like DES, bisphenol A after metabolic activation is capable of binding to DNA. However, it should be noted that a particular or multitype hit(s) will depend upon the nature of the environmental estrogen-like chemical. The role of individual attack leading to a particular change is not clear at this stage. Consequences of these multitypes of attack on the nuclei of cells could be (1) nuclear toxicity/cell death; (2) repair of all the hits and then acting as normal cells; or (3) sustaining most of the hits and acting as unstable cells. Proliferation of the last type of cell is expected to result in transformed cells.

Animals↗
PubMed1997

Estrogen-nucleic acid adducts: guanine is major site for interaction between 3,4-estrone quinone and COIII gene.

The carcinogenicity of estrogens in rodents and man has been attributed to either alkylation of cellular macromolecules and/or redox-cycling, generation of active radicals and DNA damage. Metabolic activation of estradiol leading to the formation of catechol estrogens is believed to be a prerequisite for its genotoxic effects. 4-Hydroxyestradiol is a potent inducer of tumors in hamsters. Previous studies have shown that 3,4-estrone quinone (3,4-EQ) can redox-cycle and is capable of inducing exclusively single strand DNA breaks in MCF-7 breast cancer cells, as well as react with various nucleophiles including amino acids and nucleic acids to give Michael addition products. In this paper we examined the nature of the interaction of 3,4-EQ with COIII gene and analysed the estrogen-DNA adducts by 32P-post-labeling. The reaction of 3,4-EQ with the COIII gene followed by polymerase arrest assay showed several stop sites in which guanine was preferentially attacked by 3,4-EQ and, to a lesser extent, with Ade, Cyt and Thy. 32P-Post-labeling analysis of the reaction of 3,4-EQ with COIII gene gave one major adduct which was found to be identical to that obtained from reaction of dGMP with 3,4-EQ. The observation that obstruction of in vitro replication of COIII template bound to 3,4-EQ suggests that estrogen quinone adducted lesions can arrest DNA polymerase. These results indicate that 3,4-EQ may be genotoxic and may provide one possible explanation for the carcinogenic effects of estrogens.

Binding Sites↗
PubMed1997

Resistance to activated protein C and Legg-Perthes disease.

Thrombophilia may cause thrombotic venous occlusion in the femoral head, with venous hypertension and hypoxic bone death, leading to Legg-Perthes disease. Resistance to activated protein C, the most common thrombophilic trait, was measured in 64 children with Legg-Perthes disease. Genomic deoxyribonucleic acid was studied to delineate the CGA-->CAA substitution at position 1691 of the Factor V Leiden gene responsible for resistance to activated protein C. The activated protein C ratio was calculated by dividing clotting time obtained with activated protein C-calcium chloride by clotting time obtained with calcium chloride alone. Resistance to activated protein C, with a low activated protein C ratio (less than 2.19, the 5th percentile for 160 normal pediatric controls) was the most common coagulation defect, found in 23 of 64 children with Legg-Perthes disease versus 7 of 160 pediatric controls. Eight of 64 children with Legg-Perthes disease had a low activated protein C ratio and the mutant Factor V gene (7 heterozygotes, 1 homozygote) versus 1 of 101 normal pediatric controls. Two or 3 generation vertical and horizontal transmission of heterozygosity for the mutant Factor V gene was found in 4 of the 8 kindreds. Of 64 children with Legg-Perthes disease, only 14 (22%) had entirely normal coagulation measures. Resistance to activated protein C appears to be a pathogenetic cause of Legg-Perthes disease.

Blood Coagulation Disorders↗
PubMed1997

Nonexocytotic noradrenaline release from rat cardiac synaptosomal-mitochondrial fractions.

Nonexocytotic noradrenaline (NA) release was examined in rat cardiac synaptosomal-mitochondrial fractions prelabeled with [3H]NA (300 nM; 1 h at 37 degrees C). Ischemic conditions (1 mM iodoacetate + 2 mM NaCN; 15 min at 37 degrees C) evoked a Ca(2+)-independent release of [3H]NA from isolated synaptosomes, which represented 33.4% of total content, whereas the release evoked by 56 mM K+ was Ca2+ dependent and represented 5.8% of total content. Tyramine, phencyclidine (PCP), and rimcazole also caused important Ca(2+)-independent releases of [3H]NA (from 12 to 45% of total content) with median effective concentrations (EC50s) of 6.8, 182, and 41.8 microM, respectively. The release responses evoked by ischemic conditions, tyramine, PCP, and rimcazole were mimicked by the delta-receptor ligand, 1,3-ditolyl guanidine (DTG), and blocked by the uptake 1 inhibitor, desipramine (100 microM). The delta 1-receptors ligands, (+)-3-hydroxyphenyl-N-(1-propyl)piperidine ((+)-3-PPP) and (+)N-allylnormetazocine [(+)SKF-10047], were potent blockers of the release of [3H]NA evoked by ischemic conditions but not by PCP or rimcazole. These data indicate that ischemic conditions and PCP/delta 2-receptor ligands induce carrier-mediated NA efflux from cardiac sympathetic nerve terminals, whereas delta 1-receptor ligands produce marked inhibition of the ischemic response.

Animals↗
PubMed1997

The role of transvenous embolization in the treatment of intracranial dural arteriovenous fistulas.

OBJECTIVE: To evaluate the role of transvenous embolization in the treatment of intracranial dural arteriovenous fistulas (DAVFs), including its efficacy and safety. METHODS: We retrospectively studied the charts of 24 patients (21 women and 3 men) treated for an intracranial DAVF since 1990 in whom a transvenous approach was attempted either alone (16 patients) or in combination with arterial embolization (8 patients). There were 12 cavernous sinus, 9 transverse-sigmoid sinus, 2 inferior petrosal sinus, and 1 intradiploic fistulas. Three fistulas were Type I, 12 were Type IIa, and 9 were Type IIa+b, according to the revised Djindjian's classification. Transvenous embolic agents included coils (17 patients), detachable balloons (6 patients), bucrylate (2 patients), and silk sutures (1 patient). RESULTS: Anatomic cure was proven in 21 patients (87.5%). Clinical cure was obtained in 23 cases (96%), as follows: 15 patients with a single transvenous approach, 6 with a combined arteriovenous approach, and 2 with an arterial approach after failure of venous access. There was one persistent cavernous fistula despite coil packing of the cavernous sinus. Complications were as follows: five transient and one permanent sixth nerve palsies in cavernous DAVFs, two transient labyrinthic dysfunctions in transverse sinus DAVFs, and one subarachnoid hemorrhage without sequelae. CONCLUSION: Transvenous embolization is a useful and safe approach in the management of intracranial DAVFs.

Adult↗
PubMed1997

Safety and efficacy of endovascular treatment of acutely ruptured aneurysms.

OBJECTIVE: To study the safety and efficacy of endovascular treatment of acutely ruptured aneurysms with Guglielmi detachable coils. METHODS: From August 1992 until December 1995, 75 patients were referred for endovascular treatment of acutely ruptured aneurysms. There were 49 women and 26 men, with a mean age of 55 years. Patients were classified according to the Hunt and Hess grading system. There were 18 Grade I patients (24%), 13 Grade II patients (17%), 30 Grade III patients (40%), 11 Grade IV patients (15%), and 3 Grade V patients (4%). Fifty patients (66%) were treated within 48 hours, and 64 (85%) were treated within 1 week of hemorrhage. The most frequently treated aneurysms were located at the basilar bifurcation (32%), anterior communicating artery (16%), posterior communicating artery (15%), and ophthalmic segment of the carotid artery (11%). Most of the aneurysms were smaller than 15 mm (77%). Fifty-six percent of the aneurysms had small (4 mm) necks, and 44% had wide (> 4 mm) necks. Clinical follow-up was performed at 6 months, and results were classified according to the Glasgow Outcome Scale (GOS). Control angiograms were performed immediately, at 6 months, and yearly thereafter. RESULTS: Immediate angiographic results were considered to be satisfactory in 58 patients (77%) (complete obliteration, 40%; residual neck and dog ear, 37%). Technical failures occurred in 5 patients (7%), and 12 patients experienced some residual opacification of their aneurysms (16%). The procedure-related mortality and morbidity rate was 8%. At 6 months, the outcomes were as follows: GOS score of 1, 50 patients (66.7%); GOS score of 2, 4 patients (5.3%); GOS score of 3, 4 patients (5.3%); and GOS score of 5, 17 patients (22.7%). The main causes of death and disability at 6 months were the direct effect of the initial hemorrhage (9%), delayed ischemia (6.7%), subsequent bleeding (4%), intraprocedural rupture (4%), open surgical complications (3%), and unrelated deaths (4%). Six-month angiographic follow-up data were available for 50 patients (67%). The morphological results were considered to be satisfactory in 44 of these 50 patients (88%) (complete occlusion, 46%; residual neck or dog ear, 42%). CONCLUSION: Endovascular treatment of acutely ruptured aneurysms was attempted without clinically significant complication in 92% of the patients. The morphological results were unsatisfactory in 23% of the patients. Complete obliteration of the sac, with or without residual neck, is essential to prevent subsequent bleeding, which occurred in 5% of the patients. The overall outcome at 6 months was similar to that of surgical series, despite a selected group of patients with negative prognostic factors.

Acute Disease↗