[Action of neodymium 3-sulfo-isonicotinate on the mechanism of coagulation in guinea pigs and rabbits].
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Biomedical subjects
Publications and source records attributed to J Tremblay.
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In addition to other known markers of the human prostate, it was shown that the prostatic fraction of the split ejaculate was rich in a 16-kDa protein with properties not described previously. This protein was purified from human seminal plasma using ammonium sulfate precipitation, DEAE-Sepharose CL-6B ion exchange chromatography, and gel filtration on Sephadex G-100. The purified protein showed a single prominent spot on two-dimensional gel electrophoresis. The sequence of the first 40 amino acids that could be positively identified was identical to that of a prostatic secretory protein of 94 amino acids (PSP94) previously designated as beta-inhibin. Antibodies produced in rabbits against the purified protein were used to develop a radioimmunoassay. These antibodies appeared to recognize only the NH2-terminal portion of the native molecule since they did not react with a synthetic peptide composed of the 28 C-terminal residues. The radioimmunoassay showed that the concentration of the protein was 1320 +/- 183 micrograms/ml in the seminal plasma of adult fertile men and 1134 +/- 136 micrograms/ml in vasectomized patients. In hypertrophic and adenocarcinomatous prostates, the concentrations were 326 +/- 156 and 104 +/- 23 micrograms/ml, respectively, while values were lower than 0.060 micrograms/ml in the testis, epididymis, vas deferens and liver. The blood plasma concentration was 0.019 +/- microgram/ml in 23 asymptomatic men 45 to 65 years old and 0.115 +/- 0.036 microgram/ml in eight patients with prostate cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
Environmental factors such as stress, diet, and physical activity have long been recognized as playing an important role in the pathogenesis of essential hypertension. Individuals may vary in their response to these factors depending on differences in genes determining physiologic systems that mediate the response. In this article we discuss gene-environment interactions that contribute to the development of essential hypertension (environmental susceptibility to hypertension) and those that are involved in control of the disease (pharmacogenetics).
Although individuals who exhibit both alcohol and cocaine dependency are seen increasingly in traditional alcoholism rehabilitation settings, their comparability with "pure" alcoholics is unclear. Sociodemographic, psychological, cognitive, and substance abuse status were, therefore, monitored in a group of alcoholics (n = 64) versus a group of cocaine dependent alcoholics (n = 82) on admission and just prior to discharge from 28-day multimodal treatment settings. At admission, cocaine-dependent alcoholics were younger, more likely to be unmarried, have more extensive substance use histories as well as more frequent prior treatments than "pure" alcoholics. Additionally, members of both groups exhibited abnormalities on psychological indices. Both psychological and cognitive indices revealed significant between-group differences which subsequent analyses found to be a confound of the marked age discrepancy between groups. From admission to discharge, scores on both psychological and cognitive indices declined significantly in both groups. Urine assay data revealed a greater tendency for cocaine-dependent alcoholics to relapse during treatment. While the psychological and cognitive data largely argue for the comparability of groups of patients classified as "pure" alcoholics with those who are dependent on both alcohol and cocaine, the latter group may have more difficulty in achieving abstinence during treatment. The interpretability of behavioral indices gathered only at treatment admission is questioned.
Problem drinkers (N = 49) and individuals presenting with both alcohol and cocaine problems (N = 51) admitted to a traditional 28-day alcoholism treatment milieu were compared on their psychosocial, psychological, neuropsychological functioning and substance abuse at admission as well as at six months posttreatment follow-up. On admission, alcohol and cocaine patients were younger, more likely to live alone or with their family of origin, to report having started using alcohol at an earlier age, to have fewer alcohol-related problems and to have fewer years of but more diversity in their substance abuse than the alcohol-only patients. Otherwise both groups were more similar than different on psychosocial, psychological and neuropsychological dimensions. At six-months posttreatment, both groups showed similar improvement on most dimensions of functioning measured. However, a significantly greater proportion of the alcohol and cocaine abusers admitted to having relapsed in the previous six months, reported significantly fewer average days of abstinence than the alcohol group since terminating treatment, and were more likely to present urine specimens indicative of recent substance abuse at the six-month follow-up interview. Thus, traditional approaches to alcoholism treatment may be less effective in establishing abstinence for individuals with both alcohol and cocaine problems. Adaptations to treatment to reduce the risk for relapse faced by alcohol and cocaine abusers in such milieu are discussed.
Cortisol secretion in ACTH-independent primary adrenal Cushing's syndromes was previously believed to be autonomous. In most cases, the pathophysiology of the disease was largely unknown. However, recent work by our group and others have shown that these cortisol-producing adrenocortical tumors may be under the control of inappropriate, illicit or ectopic hormone receptors. This review provides a rapid overview of the physiology of the normal adrenal cortex and outlines recent findings supporting the hypothesis that cortisol production may be regulated by a diversity of abnormal or ectopic hormone receptors in primary adrenal Cushing's syndrome.
BACKGROUND: Approximately 10% of patients hospitalized with community-acquired pneumonia (CAP) are bacteremic. Bacteremic Streptococcus pneumoniae pneumonia (BSPP) is the number one cause of mortality, representing up to 70% of all CAP deaths. In fact, all CAP guidelines have identified this issue as one of the most important issues when establishing their recommendations. OBJECTIVE: To assess the impact of dual antibiotic therapy in patients with BSPP. PATIENTS AND METHODS: All cases of BSPP in patients 18 years of age and older who were hospitalized from 1995 to 2000 were retrospectively analyzed. The standard initial therapeutic regimen used was cefuroxime with or without a macrolide from 1995 to 1997, and ceftriaxone and azithromycin or clarithromycin from 1998 to 2000. During the 1995 to 1997 period, only 16% of the patients initially received a macrolide, whereas all patients in the 1998 to 2000 period received a macrolide at admission. RESULTS: Ninety-five patients (49 men, 46 women) with a mean age of 63 years (range 20 to 98 years) were included in the present study. The mean pneumonia severity index at admission was 113 for the monotherapy cohort and 114 for the dual therapy group. At admission, 30.5% of patients had a leukocyte count greater than 20 109/L, 11.5% had a systolic blood pressure less than 90 mmHg, 44.2% had a respiratory rate greater than 30 breaths/min and 33.6% had nausea/vomiting, necessitating some form of therapy or preventing the patient from eating. In addition, 16.8% had no fever at admission. Overall, 72.5% became afebrile within 48 h. Fifteen (15.8%) patients died (four within the first 72 h). The mortality rate was significantly higher in the monotherapy group (11 of 42 patients; 25.6%) than in the dual therapy cohort (four of 53 patients; 7.5%) (OR 0.23; 95% CI 0.07 to 0.74). Antibiotic resistance was not associated with increased mortality. CONCLUSION: The combination of ceftriaxone plus a macrolide significantly reduced the mortality rate compared with monotherapy (cefuroxime) in patients with CAP that have the highest mortality rate.
This study examined the contribution of cAMP signaling to the modulation of vascular smooth muscle cell (VSMC) proliferation by adenosine. At a concentration of 1 mM, adenosine inhibited [(3)H]-thymidine uptake, measured as the initial rate of isotope influx, by 10-fold. Diminution of [(3)H]-thymidine uptake by adenosine was independent of the presence of A(1)- and A(2)-receptor antagonists, indicating that adenosine competes with thymidine for plasma membrane transporter-binding sites. Considering these results, in order to estimate [(3)H]-thymidine DNA labeling, VSMCs were preincubated with adenosine for 48 h, and adenosine was then omitted during the subsequent 2 h of incubation in [(3)H]-thymidine-containing medium. In serum-depleted VSMCs, preincubation with 100 microM or 1,000 microM adenosine augmented DNA synthesis by approximately 6- and 3-fold, respectively, whereas the increment of DNA synthesis triggered by serum was decreased in the presence of adenosine by 20-30%. Both cAMP production and inhibition of DNA synthesis by adenosine in serum-supplied cells were independent of the presence of the A(1)-antagonist 1,2-dipropyl-8-cyclopentylxanthine (DPCPX), but were abolished by the A(2)-antagonist 1,3-dimethyl-7-propylxanthine (DMPX). In contrast, the activation of DNA synthesis in serum-depleted cells by adenosine was decreased in the presence of DPCPX and DMPX by approximately 30 and 40%, respectively. Both in serum-supplied and -depleted VSMCs, dose-dependent elevation of cAMP production with an adenylate cyclase activator, forskolin, reduced DNA synthesis by up to 40-60%. Thus, our results show that in addition to suppressing thymidine uptake, adenosine depresses the DNA synthesis triggered by serum-derived growth factors and stimulates DNA synthesis in serum-depleted cells. These data also suggest that the inhibition of DNA synthesis is mediated by cAMP production where the activation of DNA synthesis is independent of cAMP signaling.
The increased frequency of hypertension in diabetes and of abnormalities of carbohydrate metabolism in hypertension are now well established. It is conceivable that the high coincidence of the two diseases is based on a common metabolic defect. Studies of platelets permit the evaluation of the stimulatory, phosphoinositol-linked and the inhibitory, cyclic adenosine 3',5'-monophosphate-dependent pathways of cell activation. Furthermore, platelets may be relevant for the development of angiopathy through their contents of growth factors. Abnormalities of platelet aggregation have been demonstrated in hypertension and diabetes. They are accompanied by exaggerated stimulation of adenylate cyclase in hypertension and abnormal activity of cyclic guanosine 3',5'-monophosphate phosphodiesterase in diabetes. Defective function of platelets is also observed in patients and animals when the two diseases are present at the same time. Both increased and decreased aggregation have been described in these two diseases in the literature. The apparent discrepancies may be due to different types of platelet preparation, evaluation of aggregation, evolution of defect with age, and form of the disease. Integrated studies of biochemical mechanisms responsible for cell activation are needed to characterize the exact defect present in diabetes and hypertension in platelets.
The initial description of GIP-dependent Cushing's syndrome suggested that abnormal or ectopic expression of adrenal receptors for various ligands may underlie other cases of ACTH-independent hypercortisolism. GIP-dependent Cushing's syndrome has been described in patients with unilateral adenomas or bilateral ACTH-independent macronodular adrenal hyperplasia (AIMAH) and results from the adrenal overexpression of non-mutated GIP receptor. In AIMAH, other patients were identified in whom regulation of cortisol production resulted from an abnormal adrenocortical response either to vasopressin, beta-adrenergic receptor agonists, hCG/LH, or serotonin 5-HT-4 receptor agonists. The identification of the presence of an abnormal adrenal receptor offers the possibility of a new pharmacological approach to control hypercortisolism by suppressing the endogenous ligands or by using specific antagonists of the abnormal receptor.
The hypothesis that experimental pulmonary air embolism would lead to bronchoconstriction in the upper lungs and a shift in ventilation toward the lower lung regions was tested in anaesthetized and paralyzed dogs. During constant rate air infusion (0.15 ml X kg-1 X min-1), regional distribution indices were obtained using radioactive xenon boli injected at the mouth at residual volume. The results show that there was a shift of inspired xenon toward the dependent lungs after 30 min of air infusion and that this shift was accompanied by a rise in pulmonary artery pressure, a slight decrease in vital capacity, a significant increase in closing volume and an increase in airway resistance. Inspiring 5% CO2 after the shift did not reverse the distribution of xenon boli. Intravenous injection of isoproterenol after the changes had occurred, on the other hand, invariably returned the distribution toward control values. These findings indicate that hypoventilation and bronchoconstriction occurred in the non-dependent lungs during pulmonary air embolism.
Thermosensitivity has been demonstrated in hypertensive rats and mice, and hypertension is frequent in hyperthermia-susceptible pigs. We have demonstrated that thermosensitivity segregates with hypertension in mice as a recessive trait in a single locus termed Tms. Since thermosensitivity can be demonstrated in cells obtained from neonatal hypertensive animals and persists after several passages in culture, it was of interest to study its cellular determinants. We undertook studies of candidate genes of cellular thermosensitivity, hsp70 being the major heat stress gene. First, we have observed an enhanced hsp70 mRNA accumulation in the hypertensive rat, mouse and human after heat shock of the whole animal, of its isolated organs or cultured cells. This increased accumulation of hsp70 mRNA in hypertension is due to its increased transcriptional rate. A restriction fragment length polymorphism (RFLP) of hsp70 was documented in hypertensive rats, which allowed the study of the segregation of this locus with hypertension in recombinant inbred strains of rats. At least one copy of hsp70 has been localized in RT1, the major histocompatibility complex of the rat, with polymorphism demonstrated with BamHI outside of the coding region of hsp70. This polymorphism segregates with 15 mmHg of systolic blood pressure. More recently, our studies led us to identify a polymorphism in another heat stress gene, hsp27. This polymorphism has been identified by PCR SSCP and is located in the 3' region, close to the termination translation codon.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine attitudes and beliefs related to AIDS among the population of metropolitan Montreal of Haitian origin, we conducted serial cross-sectional surveys between 1987 and 1990 among a random sample of 777 men and women aged 15 to 39. Data on perceived risk of AIDS and attitudes towards HIV testing were collected in home settings using a combination of face-to-face structured interviews and a self-administered questionnaire. Multivariate analysis was conducted to determine predictors of attitudes towards people with HIV. The fear of being infected with HIV is great in this population. The social representation of illness in this community is very much influenced by religious beliefs. Scores for the five-item scale suggest only moderately favourable attitudes towards persons with HIV compared to Montrealers in general. Attitudes towards persons with AIDS were positively associated with years of schooling and a higher perceived risk of getting infected (p < or = 0.01).
STUDY OBJECTIVE: To evaluate the influence of a high-fat meal on the pharmacokinetics and pharmacodynamics of the novel atypical antipsychotic drug ziprasidone. DESIGN: Open, randomized, three-way crossover study. SETTING: University-based research facility. SUBJECTS: Eight healthy male volunteers. INTERVENTIONS: Ziprasidone 20 mg was administered under fasting conditions (treatment A), and directly after (treatment B) and 2 hours after (treatment C) a standard high-fat breakfast. MEASUREMENTS AND MAIN RESULTS: Serial blood samples were obtained over 36 hours. Three objective psychometric tests were employed to evaluate daytime vigilance at baseline and 2 hours after each dose. Ziprasidone had a significant effect on area under the curve (AUC0-infinity), maximum serum concentration, and half-life (analysis of variance all p<0.05), with the mean AUC0-infinity being significantly greater (627.2 +/- 206.4 vs 371.0 +/- 126.5 ng x hr/ml, ANOVA with Bonferroni's criteria p<0.016) and half-life significantly shorter (4.7 +/- 0.8 vs 6.6 +/- 1.3 hrs, ANOVA with Bonferroni's criteria p<0.016) after treatment B compared with treatment A. Although similar trends were observed after treatment C compared with treatment A, the differences did not reach statistical significance when Bonferroni's correction criteria were applied (p>0.016). CONCLUSION: These data suggest an increase in systemic exposure to the highly lipophilic compound ziprasidone when taken after fatty foods, possibly due to improved drug dissolution and solubilization. The drug's longer half-life under fasting conditions may reflect dissolution-limited absorption, although this could not be directly assessed. Despite postprandial increases in ziprasidone AUC0-infinity and maximum concentration, daytime vigilance was not affected.