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Biomedical subjects

D Roy

Publications and source records attributed to D Roy.

At least 199 records · Page 11Linked to original sources
PubMed1994

Dissection of intracranial vertebral arteries revealed by subarachnoidal haemorrhage. Report of seven cases.

Between April 1986 and April 1991, seven cases of meningeal haemorrhage consecutive to dissection of the 4th segment of a vertebral artery were observed at the Neuroradiology Department of the Nancy University Hospital. Four of the 7 patients were men, and 3 were women; mean age varied from 45 to 61 years. The clinical presentation was not suggestive, except in one case where the haemorrhagic episode was associated with Wallenberg's syndrome, pointing to the aetiological diagnosis. The outcome was variable. Two patients died of early complications of the haemorrhage which occurred before treatment could be given. In 2 others patients treated with antiplatelet agents the outcome was favourable; however, at angiography the lesions regressed in one of these two patients, but they progressed in the other with formation of a false aneurysm. The remaining 3 patients were treated by endovascular occlusion of the lesion-bearing vessel: one died of complications of a haemorrhage-induced vasospasm; the other two are symptomless after a 2 to 6 months follow-up.

Aortic Dissection↗
PubMed1994

[Breast cancer screening: is family medicine intervention effective?].

A non-randomized controlled trial was conducted in two family medicine centers. The objectives were to evaluate whether or not a systematic prescription by family physicians of a screening mammography to women aged 50 to 69 belonging in majority to a disadvantaged socio-economic group, would permit to reach at least 60% of them and to explore which factors were associated with compliance to the prescription. The experimental intervention consisted in the prescription by the family physician of a mammogram to those patients found eligible for the screening procedure irrespective of the reason for encounter. A total of 468 of the 870 women who consulted a physician during the study period were eligible for a screening mammography. In the experimental group, the mammography prescription rate was 89% for eligible women. At the end of the study, 58.8% (95% Conf. Int.:51.9%-65.7%) of the women in the experimental group and 13.4% (95% Conf. Int.:9.4%-17.4%) of those in the control group had passed a mammography (p < 0.0001). The adjusted odds ratio for the family physician's intervention was 14.98 (95% Conf. Int.:7.86-28.58). Women over 60 years of age and those who perceived themself more vulnerable to breast cancer were more likely to respond positively to their physician's recommendation. This study confirms that family physicians can effectively reach, in the area of clinical prevention, individuals who might not be reached otherwise.

Aged↗
PubMed1993

Canadian Implantable Defibrillator Study (CIDS): study design and organization. CIDS Co-Investigators.

The Canadian Implantable Defibrillator Study (CIDS) is an on-going randomized multicenter clinical trial that compares implantable cardioverter-defibrillator (ICD) therapy against amiodarone in patients with prior cardiac arrest or hemodynamically unstable ventricular tachycardia. Eligible patients are equally randomized to receive or not receive an ICD as initial management. Those not receiving an ICD receive amiodarone. All patients are seen in follow-up every 6 months. The primary outcome event cluster is arrhythmic death or any other death occurring within 30 days of therapy initiation. Secondary outcomes are all-cause mortality and nonfatal occurrences of ventricular tachycardia or fibrillation. The goal of the study is to recruit 400 patients over 4 years. All patients will be followed to the end of the year. This will result in an 80% chance of detecting a reduction in arrhythmic death of 58% by ICD if such a difference in truth exists. Recruitment began in October 1990 and 184 patients have been enrolled to date.

Amiodarone↗
PubMed1993

Insulin-like growth factor 1 receptors are increased in estrogen-induced kidney tumors.

We have previously demonstrated that membrane receptor protein tyrosine kinase(s) activities are higher in estrogen-induced kidney tumors in comparison with such activities in the normal kidney. In the present work we have investigated the growth factor binding sites in estrogen-induced kidney tumor and in normal kidney membranes in an attempt to understand the mechanism of activation of membrane protein tyrosine kinase(s) and their possible relationship to the induction of estrogen-induced tumors. The characteristics of the normal hamster kidney membrane insulin-like growth factor 1 (IGF-1) receptor are similar to those reported for kidney and extrarenal tissues of other rodents. The binding of 125I-IGF-1 to the normal kidney or tumor membranes was saturable and dependent on time, protein, pH, and temperature. The binding of 125I-IGF-1 to the tumor membranes was significantly higher when compared to the binding activity of the membranes obtained from age-matched normal kidney. The Scatchard analysis of the binding data of both tumor and normal kidney revealed a single class binding site for IGF-1 with Kd of 1.7 and 1.8 nM and maximum binding capacities of 4150 and 2050 fmol/mg protein, respectively. Therefore, the difference observed in 125I-IGF-1 binding between tumor and normal kidney membranes was due to an increase in the number of IGF-1 binding sites with no change in the affinity of receptors for IGF-1. An enhanced level of IGF-1 receptors in tumor membranes also was visualized by autoradiography following affinity labeling of membrane proteins subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Under reducing conditions of electrophoresis, two molecular bands of M(r) 240,000 and M(r) 130,000 were evident. The M(r) 130,000 band represents the alpha subunit of IGF-1 receptors, and the M(r) 240,000 band may represent the aggregates of the receptor subunits which were not reduced completely. IGF-1 stimulated normal kidney or tumor membrane protein tyrosine kinase(s) (wheat germ lectin agarose-purified membrane proteins) in a dose-dependent fashion. Therefore, the alteration of IGF-1 binding activity of the tumor membrane receptors and stimulation of IGF-1-mediated membrane protein tyrosine kinase activity in tumor tissues suggest that events coupled to this membrane receptor may play a role in estrogen stimulation of renal carcinoma.

Animals↗
PubMed1993

Comparison between patient-controlled analgesia and intramuscular meperidine after thoracotomy.

A prospective randomized controlled study was performed to assess the efficacy and safety of patient-controlled analgesia (PCA) in patients undergoing thoracotomy. This method was compared with a conventional pain management technique consisting of regularly scheduled im injections of analgesics. Forty adult patients were randomly assigned to receive intravenous PCA or im meperidine treatment over a 48-hr period after surgery. Care was taken to optimize analgesia in patients of both groups. The McGill Pain Questionnaire, visual analogue and verbal-numeric scales were administered at regular intervals to measure various components of the patients' pain experience, degree of pain relief, adverse side effects and overall treatment efficacy. Functional recovery after surgery was also examined. The results showed good and comparable analgesia with both pain-control methods. However, a greater number of patients receiving im injections required dosage adjustments than in the PCA group. Patients' and nurses' evaluations of overall treatment efficacy also favoured PCA treatment. There were no major group differences in the side effect profile. Recovery pattern was also comparable in the two groups except for the length of hospitalisation. There were fewer long-stay patients in the PCA than in the im group. Meperidine intake was similar in both groups but considerable interpatient variation was seen. In conclusion, PCA is a safe, effective and individualized treatment method for controlling pain after thoracotomy. There appears to be some clinical advantages of PCA over im dosing regimens for analgesia after thoracotomy.

Adult↗
PubMed1993

In vivo genotoxicity of sodium ortho-phenylphenol: phenylbenzoquinone is one of the DNA-binding metabolite(s) of sodium ortho-phenylphenol.

We have previously demonstrated microsomal cytochromes P450-dependent redox cycling of o-phenylphenol and in vitro genotoxicity of o-phenylphenol. In the present work, we have investigated in vivo covalent modification in skin DNA by Na-o-phenylphenol using the 32P-postlabeling method in an attempt to understand the biochemical mechanism of promotion of chemical-induced skin carcinogenesis by Na-o-phenylphenol. Topical application of Na-o-phenylphenol or phenylhydroquinone, a hydroxylated metabolite of o-phenylphenol, to female CD-1 mice skin produced 4 distinct major and several minor adducts in skin DNA. The total covalent bindings in skin DNA produced by treatment of mice with 10 mg and 20 mg Na-o-phenylphenol (doses shown to be effective for tumor promotion) were 0.31 fmoles/microgram DNA and 0.62 fmoles/microgram DNA, respectively. The adducts were not observed in untreated animal skin DNA. Pretreatment of mice with alpha-naphthylisothiocyanate, an inhibitor of cytochromes P450, or indomethacin, an inhibitor of prostaglandin synthase, resulted in lower levels of DNA adducts produced by Na-OPP. The in vitro incubation of DNA with o-phenylphenol or phenylhydroquinone in the presence of cytochromes P450 activation or prostaglandin synthase activation system produced 4 major adducts. The adduct pattern observed in the presence of in vitro enzymatic activation systems appears to be similar in chromatographic mobility to the in vivo adduct pattern. The chemical reaction of DNA or deoxyguanosine monophosphate with pure phenylbenzoquinone, an electrophilic metabolite of o-phenylphenol, also produced 4 major and several minor adducts. The 4 major adducts obtained in chemical reaction of phenylbenzoquinone with deoxyguanosine monophosphate are identical in chromatographic mobility to those of in vivo or in vitro DNA adducts. The results of this study demonstrated that o-phenylphenol or phenylhydroquinone, a hydroxylated metabolite of o-phenylphenol, is able to covalently bind to DNA. DNA binding can be inhibited by the inhibitor of cytochromes, P450 alpha-naphthylisothiocyanate or prostaglandin synthase, indomethacin. One of the DNA-binding metabolite(s) of o-phenylphenol both in vivo and in vitro may be phenylbenzoquinone. We conclude that Na-OPP is genotoxic. Genotoxicity caused by Na-o-phenylphenol treatment in CD-1 mice may play a role in the promotion of dimethylbenz[a]anthracene-induced skin neoplasm.

Animals↗
PubMed1993

Results of a comparative study of low energy direct current with radiofrequency ablation in patients with the Wolff-Parkinson-White syndrome.

OBJECTIVE: To compare two new power sources for catheter ablation in patients with the Wolff-Parkinson-White syndrome. DESIGN: 120 consecutive patients with accessory pathways had catheter ablation. Low energy direct current (DC) was used in the first 60 patients and radio-frequency current in the next 60 patients. SETTING: Electrophysiological laboratory of a large heart institute. PATIENTS: 72 men and 48 women (mean (SD) age 35 (14) years (range 9-75)). The accessory pathways were in the left free wall in 73 patients. They were posteroseptal in 35 patients, in the right free wall in five, and anteroseptal in seven. There was no significant difference in the clinical or electrophysiological variables between the two ablation groups. RESULTS: Catheter ablation with low energy direct current was successful in 55/60 patients (92%) and radiofrequency energy was successful in 52/60 patients (87%). Low energy direct current was also successful in four of the eight patients in whom radiofrequency ablation had failed. Radiofrequency ablation was successful in two of the five patients in whom low energy direct current ablation had failed. The mean (SD) procedure and fluoroscopy times for successful ablation were 3.2 (1.5) h and 61 (40) min respectively. These times were similar for both power sources. Accessory pathway conduction recurred in 17 patients (28%) who had low energy direct current and four patients (7%) who received radiofrequency energy (p < 0.004). All patients with recurrence of an accessory pathway had successful re-ablation. CONCLUSIONS: Both new power sources successfully ablated accessory pathways, (overall success rate 94% (113/120 patients)). Radiofrequency ablation, however, did not require general anaesthesia and was associated with a significantly lower rate of recurrence of accessory pathway conduction. Therefore radiofrequency should be used initially for ablation. Low energy direct current may be most useful as a back-up in patients in whom radiofrequency ablation fails.

Adolescent↗
PubMed1993

The carcinogenic activity of ethinyl estrogens is determined by both their hormonal characteristics and their conversion to catechol metabolites.

Estrogens induce kidney tumors in Syrian hamsters. The mechanism of carcinogenesis is unknown and has been investigated in this study using a weak carcinogen, 17 alpha-ethinyl estradiol (EE), and a strongly carcinogenic estrogen, 17 alpha-ethinyl-11 beta-methoxyestradiol [moxestrol (MOX)]. We investigated rates of conversion of estrogens to catechol metabolites and rates of their methylation to methyl ethers in order to examine the hypothesis that catechol metabolites mediate estrogen-induced carcinogenesis. Rates of conversion of MOX to catechol metabolites by hamster liver or kidney cortex microsomes were 40-50% of those with estradiol as substrate. However, the rate of catechol-O-methyltransferase-catalyzed methylation of 2-hydroxy-MOX was the least of the catechol metabolites examined when incubated with cytosol of hamster kidney. In contrast, EE was converted to catechol metabolites by hamster liver and kidney microsomes at rates 25-35% of those obtained with estradiol. These catechol metabolites of EE were methylated by catechol-O-methyltransferase of hamster kidney cytosol at rates slightly lower than those observed with catechols of estradiol. The progesterone receptor binding of EE and MOX was investigated, because progesterone is known to inhibit estrogen-induced carcinogenesis in the hamster kidney. Neither estradiol nor MOX inhibited the binding of progesterone to its receptor in hamster kidney cytosol. However, in the presence of 20 nM EE, the binding affinity of radiolabeled progesterone to receptor was inhibited (increase in Kd from 0.98 nM in controls to 3.02 nM in the presence of EE). Maximum binding values (5.0 fmol/mg protein in controls and 6.0 fmol/mg protein in the presence of EE) were not significantly altered. These results support the hypothesis that estrogen-induced carcinogenesis is mediated by catechol estrogen metabolites. The carcinogenic estrogen MOX is converted to catechol metabolites at lower rates than estradiol, but their methylation may be sterically hindered by the 11 beta-methoxy substituent. In contrast, the rates of conversion of the weakly carcinogenic EE to catechol metabolites are low, whereas their methylation rates are only marginally lower than those of 2- and 4-hydroxyestradiol. The decreased capacity of EE to form catechol metabolites in conjunction with its partial progestin agonist activity in the target organ of hamsters may contribute to the low tumor incidence.

Animals↗
PubMed1993

Modifications in the low mobility group nuclear proteins by reactive metabolites of diethylstilbestrol.

In this study we have investigated the potential of nuclear activation system to convert diethylstilbestrol (DES) to reactive metabolites, which bind to low mobility nonhistone nuclear proteins. Reaction of DES with nuclei in the presence of cumene hydroperoxide or NADPH revealed binding of DES in low mobility group (LMG) nonhistone nuclear proteins analyzed by both organic solvent extraction and gel electrophoresis methods. Gel electrophoresis experiments revealed that five LMG proteins of MW 130, 108, 72, 51, and 45 KDa were irreversibly bound to 3H-DES. The kinetic constants, Km and Vmax, of this binding reaction in the presence of cumene hydroperoxide were 39 uM and 1225 pmol/mg protein/30 min, respectively. This binding was significantly inhibited by cytochromes P450 inhibitors. Low molecular weight thiols, i.e., glutathione and cysteine, or thiol modifiers such as n-ethylmaleimide, dithionitrobenzoic acid, and hydroxymercuric benzoate, drastically inhibited binding. The binding of DES metabolites to both transcriptionally active and inactive chromatins LMG proteins was observed. In summary, DES is metabolized to transcriptionally active chromatin LMG protein binding metabolites presumably by nuclear cytochromes P450. These data suggest that an analogous in vivo modification in the transcriptionally active chromatin LMG nonhistone proteins by DES metabolites may influence gene transcription.

Animals↗
PubMed1993

Pulsatile tinnitus and dural arteriovenous fistula of the transverse sinus.

A case of dural arteriovenous fistula of the transverse and sigmoid sinus presenting with a pulsatile tinnitus is described. On the basis of this demonstrative case, we review the clinical presentation, pathogenesis, diagnostic imaging and principles of treatment of this disease. Emphasis is put on the importance of careful diagnostic evaluation because of potential cerebrovascular complications associated with dural fistulas.

Arteriovenous Fistula↗
PubMed1993

Increased oxidative stress in the liver of mice treated with trichloroethylene.

In this study the trichloroethylene treatment-associated production of oxidative stress in mouse liver by measurements of changes in oxygen consumption, the disappearance of beta-nicotinamide adenine dinucleotide reduced form (NADPH), and the rate of malondialdehyde formation have been investigated. The treatment of mice with trichloroethylene (TCE), trichloroacetic acid (TCA), a metabolite of TCE, or clofibrate, a peroxisome proliferator, resulted in an increase in the oxygen consumption of liver microsomes compared to the values of the untreated controls. A maximum increase in the level of oxygen consumption in liver microsomes was observed in the mice treated with TCE, followed by clofibrate and TCA treatments. All three agents also increased the rate of NADPH oxidation in mice liver microsomes compared with untreated controls. NADPH oxidation was increased four fold by TCE or clofibrate (38 or 37 nmol/min) and two fold by TCA treatment (17 nmol/min) over that of the control animals (9 nmol/min). The concentration of malondialdehyde was higher in all three treated groups in comparison with control values. Malondialdehyde levels were elevated by 227%, 191%, and 118% by treatment with TCE, clofibrate, and TCA, respectively. Increases in the levels of oxygen consumption, NADPH disappearance, and malondialdehyde production in microsomes from liver of mice treated chronically with TCE or TCA are all indicative of elevated levels of oxidative stress. Increased oxidative stress may be involved in the induction of TCE-associated hepatotoxicity.

Animals↗
PubMed1993

Informed consent.

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Contrast Media↗
PubMed1992

Catalysis of the oxidation of steroid and stilbene estrogens to estrogen quinone metabolites by the beta-naphthoflavone-inducible cytochrome P450 IA family.

Diethylstilbestrol (DES) or catecholestrogens are metabolized by microsomal enzymes to quinones, DES Q or catecholestrogen quinones, respectively, which have been shown to bind covalently to DNA and to undergo redox cycling. The isoforms of cytochrome P450 catalyzing this oxidation of estrogens to genotoxic intermediates were not known and have been identified in this study by (a) using microsomes of rats treated with various inducers of cytochrome P450; (b) using purified cytochrome P450 isoforms; and (c) examining the peroxide cofactor concentrations necessary for this oxidation by microsomes or pure isoenzymes. The highest rate of oxidation of DES to DES Q was obtained using beta-naphthoflavone-induced microsomes (14.0 nmol DES Q/mg protein/min) or cytochrome P450 IA1 (6.4 pmol DES Q/min/pmol P450). Isosafrole-induced microsomes or cytochrome P450 IA2 oxidized DES to quinone at one-third or one-fifth of that rate, respectively. Low or negligible rates of oxidation were measured when oxidations were catalyzed by microsomal rat liver enzymes induced by phenobarbital, ethanol, or pregnenolone-16 alpha-carbonitrile or by pure cytochromes P450 IIB1, IIB4, IIC3, IIC6, IIE1, IIE2, IIG1, or IIIA6. Cytochrome P450 IA1 also catalyzed the oxidation of 2- or 4-hydroxyestradiol to their corresponding quinones. The beta-naphthoflavone-induced microsomes and cytochrome P450 IA1 had the highest "affinity" for cumene hydroperoxide cofactor (Km = 77 microM). Cofactor concentrations above 250 microM resulted in decreased rates of oxidation. The other cytochrome P450 isoforms required much higher cofactor concentrations and were not inactivated at high cofactor concentrations. The data demonstrate that beta-naphthoflavone-inducible cytochrome P450 IA family enzymes catalyze most efficiently the oxidation of estrogenic hydroquinones to corresponding quinones. This oxidation may represent a detoxification pathway to keep organic hydroperoxides at minimal concentrations. The resulting quinone metabolites may be detoxified by other pathways. However, in cells with decreased detoxifying enzyme activities, quinones metabolites may accumulate and initiate carcinogenesis or cell death by covalent arylation of DNA or proteins.

Animals↗
PubMed1992

Enhanced expression of membrane phosphoproteins tyrosine phosphorylation in estrogen-induced kidney tumors.

We demonstrate for the first time that the expression of tyrosine containing membrane phosphoproteins is elevated in estrogen-induced kidney tumors, which is evident from both the types of experiments, i.e., alkali-resistant phosphorylation of membrane proteins and immunoprecipitation of tyrosine containing phosphoproteins. Tyrosine phosphorylation of proteins or peptides was modulated by the growth factors (EGF, IGF-I) and by the inhibitors of tyrosine protein kinase(s). The kinetic analyses revealed that tumor membranes have high affinity and catalytically more efficient tyrosine phosphorylating kinase enzyme(s) compared to that of normal membranes which have low affinity and catalytically less efficient kinase enzyme(s). It is proposed that overexpression of tyrosine containing membranal phosphoproteins may be involved in the induction and growth of estrogen-induced renal neoplasm.

Animals↗
PubMed1992

Lack of effectiveness of antiestrogens RU 39,411 or keoxifene in the prevention of estrogen-induced tumors in Syrian hamsters.

As part of a search for an effective and safe antiestrogen to be used as adjunct therapy in the treatment of breast cancer, we examined the potential of RU 39,411 and keoxifene to inhibit the incidence of estradiol-induced kidney tumors in Syrian hamsters. Groups of 10 hamsters were chronically treated with implants of either keoxifene, RU 39,411, estradiol plus keoxifene, or estradiol plus RU 39,411 for 8 months. Five hamsters received only estradiol and 5 control animals remained untreated. There was a 100% kidney tumor incidence in estradiol-treated hamsters, which was not statistically different from that in animals co-treated with estradiol plus keoxifene (3 of 4 hamsters with tumors) or estradiol plus RU 39,411 (7 of 8 hamsters with tumors). Rodents treated only with antiestrogen remained tumor free. In addition to kidney tumors, testicular cancer was also found in animals cotreated with either estradiol plus keoxifene (2 of 4 hamsters with tumors) or estradiol plus RU 39,411 (3 of 8 hamsters with tumors). Two animals of this latter group also developed liver tumors. Testicular or liver neoplasms were not observed in hamsters implanted only with estradiol or only with antiestrogen. The lack of inhibition of estrogen-induced carcinogenesis in hamsters by RU 39,411 or keoxifene suggests that these two antiestrogens are not as effective as previously tested substances in inhibiting the appearance of this cancer. However, their concentrations were sufficient to induce, in combination with estradiol, the development of testicular tumors in these hamsters.

Animals↗
PubMed1992

Target organ-specific inactivation of drug metabolizing enzymes in kidney of hamsters treated with estradiol.

Chronic treatment of hamsters with estradiol for several months has previously been shown to decrease the specific content of cytochrome P450 in the kidney, a target of hormonal carcinogenesis, but not in liver. The reason for this decrease in metabolic enzyme activity is unknown and has been examined in this investigation. We now report that the decrease in specific content of renal cytochrome P450 by 73% in response to estradiol was not affected by co-treatment with tamoxifen for 1 month. The subcutaneous infusion of 250 micrograms/day estradiol for 7 days lowered renal cytochrome P450 by 71% from control values and was therefore used for further mechanistic studies. This treatment decreased renal activities of estradiol 2- or 4-hydroxylase by 77 to 80%, of 7-ethoxycoumarin-O-deethylase by 66% of control values, respectively, and completely eliminated aryl hydrocarbon hydroxylase activities, whereas liver enzymes remained unaffected. After 7 days of infusion of estradiol, fluorescent products of lipid peroxidation were more than doubled in hamster kidney but remained unchanged in liver. The possibility of enzyme destruction by binding of estradiol 2,3-quinone to metabolizing enzymes was investigated in vitro. In the presence of 2-hydroxyestradiol, cumene hydroperoxide, and microsomes, conditions known to favor the oxidation of the steroid to quinone, the binding of catechol estrogen metabolite to microsomal protein increased 60 fold over control values in the absence of cofactor. Purified rat liver cytochrome P450c also oxidized 2-hydroxyestradiol to 2,3-estradiol quinone. The rate of oxidation was linear for the first 2-3 min, but thereafter decreased with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗