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Biomedical subjects

M Parent

Publications and source records attributed to M Parent.

At least 19 recordsLinked to original sources

Moclobemide versus fluoxetine for a major depressive episode.

The efficacy and tolerability of moclobemide (300-600 mg daily) and fluoxetine (20-40 mg daily) were compared in a 6-week, double-blind study of 65 inpatients and 34 outpatients suffering from major depressive episodes (DSM III-R). No statistically significant differences between the two treatment groups were noted regarding efficacy (HDRS, CGI) or safety (adverse events, laboratory examination, vital signs). Moclobemide (300-600 mg daily) and fluoxetine (20-40 mg daily) would thus appear to be comparable both in antidepressant efficacy and tolerability. Doubling the low dosage in non-responders after 3 weeks resulted in a statistically significant improvement of CGI in the moclobemide group by comparison with the fluoxetine group at study end, suggesting that 600 mg moclobemide/day can still improve the patient's condition, while 40 mg fluoxetine/day does not. Sexual dysfunction was reported in two patients taking fluoxetine.

Adolescent

Point mutation of the mitochondrial tRNA(Leu) gene (A 3243 G) in maternally inherited hypertrophic cardiomyopathy, diabetes mellitus, renal failure, and sensorineural deafness.

The A 3243 G mutation of the mitochondrial tRNA(Leu) gene was found to segregate with maternally inherited diabetes mellitus, sensorineural deafness, hypertrophic cardiomyopathy, or renal failure in a large pedigree of 35 affected members in four generations. Presenting symptoms almost consistently involved deafness and recurrent attacks of migraine-like headaches, but the clinical course of the disease varied within and across generations. The A 3243 G mutation has been previously reported in association with the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome (MELAS) and with diabetes mellitus and deafness. To our knowledge, however, hypertrophic cardiomyopathy is not a common feature in people with the A 3243 G mutation and renal failure has not been hitherto reported in association with this mutation. The present observation gives additional support to the variable clinical expression of mtDNA mutations in humans.

Adenine

[Potentially inappropriate benzodiazepine prescriptions in elderly nursing home patients].

OBJECTIVE: To evaluate the incidence of benzodiazepine overprescription as a cause of benzodiazepine overuse in nursing homes. DESIGN AND SETTING: Physicians were asked to complete a multiple-choice questionnaire for patients receiving at least one benzodiazepine and to indicate the reason for the prescription. To control for social desirability bias, two fictitious cases were submitted to each physician. Overprescription was defined as a prescription for benzodiazepine that differed from the indications given in the product monograph. PARTICIPANTS: Family physicians of patients living in three nursing homes in the Quebec City area were solicited by mail to take part in the survey. RESULTS: Fifteen physicians treating 152 patients, whose average age was 82.1 years (range 50 to 100 years), agreed to take part in the study. It was found that 77.1% of the patients had been taking a benzodiazepine for more than a year. For 14.5% of the prescriptions, there was no official indication. The reasons most frequently cited for these prescriptions were that the physician was renewing a prescription given before he took charge of the patient, the patient's refusal to discontinue use of the medication, pressure from the nursing staff, and the fact that the patient was causing a disturbance. In 4% of the cases (6 answers), the physician acknowledged that there was no indication for prescribing a benzodiazepine. CONCLUSION: This study shows that, in 14.5% of cases, overprescription could be a cause of benzodiazepine overuse in nursing homes.

Aged

Tumor-forming ability in athymic nude mice of human cell lines devoid of mitochondrial DNA.

We have examined the contribution of the mitochondrial genome to the tumorigenic phenotype expressed by human cell lines derived from an ovarian and a cervical carcinoma and from an osteogenic sarcoma. All these continuous cell lines are anchorage-independent in soft agar and form tumors in athymic nude mice. Long-term exposure of the cells to ethidium bromide, an intercalating agent which inhibits mitochondrial DNA replication, gave rise to subclones depleted of mitochondrial DNA and RNA molecules and displaying either anchorage independence or dependence. These respiratory-deficient subclones contain disorganized and enlarged mitochondria, are auxotrophic for uridine and pyruvate, and grow in vitro at a rate nearly identical or moderately slower than their respective parent. The tumor-forming ability of both anchorage-independent and -dependent cell lines was tested by s.c. and intramuscular implantation of the cells in nude mice. We found that the tumorigenic capacity was influenced by the route of inoculation. Subcutaneously, mitochondrial DNA-less cell lines are either poorly or nontumorigenic, while all but one cell line form tumors when implanted into the hind leg muscle. The relative in vivo growth rate of the parent and the mitochondrial DNA-less subclones reflects their respective in vitro rate of growth. All intramuscular tumors introduced into culture mimic the molecular and phenotypic traits of the injected cells, with the exception of the anchorage-dependent cell lines which give rise to anchorage-independent tumor cell lines. The present observations indicate that human cells without mitochondrial DNA have the capacity to proliferate and form tumors in vivo.

Animals

Cloning and characterization of a cDNA encoding elongation factor 1 alpha from chicken cells devoid of mitochondrial DNA.

Using a subtractive hybridization procedure, we isolated a cDNA clone encoding elongation factor 1 alpha (EF-1 alpha) from chicken cells devoid of mitochondrial (mt) DNA (rho0). The sequence encodes 1691 nucleotide (nt) residues and contains an open reading frame of 463 codons. Compared with the sequences from human, mouse and Xenopus laevis, the highest degree of sequence identity is detected in the 3' untranslated (> 90%) and coding (> 85%) regions. The gene evolved mainly by transitions occurring at the third codon position. Most transitions are silent and amino acid (aa) sequence identities are greater than 95%. Comparison of the protein domains interacting with cellular components (GTP/GDP, tRNAs and beta-actin) reveals that they are highly conserved in species belonging to the four traditional eukaryotic kingdoms. The expression of the EF-1 alpha transcript is elevated in chicken rho0 cells. A single RNA band at 1800 nt is observed in both parental and rho0 cells. Southern blot analysis of restricted DNA from chick embryo fibroblasts (CEF) suggests that only one gene encoding EF-1 alpha exists in the chicken genome.

Amino Acid Sequence

Use of 191Pt radiotracer for the development of enrichment procedures to detect natural levels of platinum in biological and environmental materials.

The 191Pt-radiotracer is a powerful tool to develop separation and preconcentration methods for Pt. The radiotracer was produced either through 190Pt (n, gamma) 191Pt reaction on Pt enriched in 190Pt, or through 191Ir (p,n) 191Pt reaction on natural Ir, followed by Pt/Ir separation. The solvent extraction behavior of 191Pt(IV) from HCl with tributylphosphate, rubeanic acid in tributylphosphate and thenoyltrifluoroacetone in n-butylalcohol/acetophenone, followed by back-extraction with 2 mol/L NH4OH was studied. The overall recovery from a biological matrix is up to 80%. Trace amounts of 191Pt were also preconcentrated as bis-(carboxymethyl) dithiocarbamate chelates on an XAD-4 microcolumn and eluted with EtOH/1 mol/L HNO3. More than 80% is recovered in 2 mL or about 70% in 300 microL.

Chromatography, Ion Exchange

Platelet-induced vasomotion of isolated canine coronary artery in the presence of halothane or isoflurane.

To determine the effect of 1.5 MAC of two volatile anesthetics (halothane and isoflurane) on platelet-induced contraction of canine coronary artery, isolated, denuded coronary rings were suspended between two stirrups, placed into organ chambers filled with an oxygenated Krebs-Ringer solution, and connected to an isometric force transducer. Human platelets were obtained from healthy donors and introduced into the organ chambers in increasing amounts to reach 20,50 and, 70 x 10(9) platelets/L. The tension generated in both the control and anesthetic-treated rings was recorded; only halothane reduced the tension induced by platelet activation in the organ chambers. In some experiments, aliquots of Krebs-Ringer solution were taken to determine the amount of 5-HT and TB2 released by 70 x 10(9) human platelets in the presence and absence of the anesthetics. Only halothane reduced TA2 production by the activated platelets. Finally, the contractile response of isolated denuded canine coronary artery rings to U46619, a thromboxane analog, was measured in the presence and absence of the anesthetics. Neither halothane nor isoflurane attenuated the response. In another series of experiments, in vitro platelet aggregation was induced by epinephrine, collagen, ADP, or arachidonic acid in the presence or absence of 1.5 MAC isoflurane or halothane. Both anesthetics significantly reduced the aggregation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5

Endemic nosocomial transmission of Staphylococcus epidermidis bacteremia isolates in a neonatal intensive care unit over 10 years.

To assess long-term nosocomial transmission, trends in antibiotic resistance, and expression of potential virulence factors, 86 randomly selected Staphylococcus epidermidis bloodstream isolates obtained from 80 patients in a neonatal intensive care unit (NICU) over a 10-year period were studied. Pulsed-field gel electrophoresis (PFGE) analysis of SmaI-digested whole chromosomal DNA revealed distinctive banding patterns that persisted in the NICU over long periods. Pattern A included 22 isolates (26%) obtained during 1983-1990, and pattern B included 24 isolates (28%) from 1983 to 1991. All 10 isolates examined in 1984 fell into one of these two patterns. Isolates with either pattern expressed polysaccharide/adhesin (PSA) and slime; 90% and 87% were resistant to oxacillin and gentamicin, respectively, with no trends over time. These findings suggest that distinct clones of S. epidermidis can become endemic in NICUs over periods as long as a decade and that nosocomial transmission plays an important role in neonatal S. epidermidis bacteremia.

Bacteremia

Does halothane interfere with the release, action, or stability of endothelium-derived relaxing factor/nitric oxide?

BACKGROUND: Halothane attenuates endothelium-dependent relaxation. To differentiate halothane's effect on endothelium-derived relaxing factor/nitric oxide (EDRF/NO) production from its effect on nitric oxide action on vascular smooth muscle, halothane's effect on endothelium-dependent relaxation was studied in a bioassay system. METHODS: Indomethacin-treated, bovine aortic endothelial cells (BAEC) grown on microcarrier beads, continuously perfused by oxygenated and carbonated (95% O2, 5% CO2) Krebs-Ringer solution served as nitric oxide donors while an isolated denuded rabbit aortic ring directly superfused by the effluent of the BAEC and precontracted with phenylephrine was used to detect EDRF/NO release. The effect of basal and bradykinin-stimulated EDRF release on the tension of the vascular ring was measured. In the bioassay, it was possible to treat either the vascular denuded ring alone or the vascular ring plus the BAEC with halothane by adding it to the perfusate either upstream or downstream from the BAEC. Halothane (final concentration 2.2%) was added to the perfusate at these two positions, and its effect on the relaxation induced by EDRF/NO was determined. In some experiments, the preparations were treated with hemoglobin or L-monomethyl-L-arginine to attenuate the relaxation induced by the EDRF/NO pathway. Finally, halothane's effect on vascular relaxation induced by an increasing concentration of sodium nitroprusside was measured. Halothane's concentration in the perfusate was determined by gas chromatography using electron capture for anesthetic measurement. RESULTS: EDRF/NO released by the BAEC was responsible for the relaxation of the vascular ring. Halothane added to the perfusate potentiated the tension induced by phenylephrine (7.1 +/- 1.89%) and attenuated the relaxation induced by the release of EDRF/NO. This effect was reversible after discontinuation of halothane. Halothane's effect was present even when the anesthetic was added to the perfusate downstream to the perfusion of the endothelial cells. Halothane had no effect on the vascular relaxation induced by sodium nitroprusside. CONCLUSIONS: The authors' data demonstrate that halothane does not interfere with endothelial cell release of EDRF/NO and its smooth muscle cell relaxation but seems to modify either EDRF/NO half-life or its activated redox form.

Animals

Effect of rapamycin on rat aortic ring vasomotion.

Rapamycin (RAPA) is an antifungal antibiotic with interesting new immunosuppressive properties. We evaluated RAPA's effects in vitro on basal and stimulated tension of isolated intact or denuded rat aortic rings. Rings were prepared in an organ chamber and contracted with 40 mM KCl (reference 100%). Some rings were treated with either RAPA's polysorbate/polyethylene glycol-based (PEG) vehicle (0.8% vol/vol) or with different concentrations of RAPA (10, 100, and 1,000 ng/ml) diluted in PEG; untreated rings were used as controls. Variation in tension with time (2 h) and the dose-response to thromboxane A2 analogue (U46619) and phenylephrine (PE) were measured in controls and treated rings. PEG potentiated the increase in basal tension in rings with endothelium after 2-h treatment (44.66 +/- 3.59 vs. 14.82 +/- 2.43% for controls, p < 0.05, n = 10). RAPA antagonized the contraction induced by its own vehicle dose dependently. At 1,000 ng/ml, RAPA caused relaxation of intact rings below the control level (4.29 +/- 2.20 vs. 14.82 +/- 2.43%, p < 0.05, n = 10), but not in rings without endothelium. RAPA did not modify the response to PE or U46619 in rings with endothelium. RAPA relaxed the vessels by an endothelium-dependent mechanism, and this effect can be modulated by its vasoconstrictive PEG vehicle.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5

[Subcortical dementia of the Neumann type. Contribution of diagnostic imaging].

A 36 year-old patient presented with a dementia of frontal type, gait disturbances, incontinence and a pseudo-bulbar palsy, which caused death at age 40. Brain biopsy of the frontal lobe showed an extensive deep subcortical gliosis. A high level of GFAP was detected by immunoblotting in the biopsy. Clinical and neuropathological observations are similar to cases described as Neumann Progressive Subcortical Gliosis. Single Photon Emission Computer Tomography showed a bilateral frontotemporal hypoperfusion, and Magnetic Resonance Imaging large periventricular and subcortical hyperintensities in both hemispheres, the brainstem and the cerebellum. The hyperintensities on T2-weighted MR images might be related to the intense gliosis. The contribution of such imaging data to diagnosis must be confirmed by other clinico-pathological cases.

Adult

Myasthenia gravis and steroid-induced myopathy of the respiratory muscles.

OBJECTIVE: We report a case of corticosteroid-induced myopathy with involvement of respiratory muscles observed in a myasthenic patient. PATIENT: A 37-years-old woman, under corticosteroid treatment for two years for typical myasthenia gravis was admitted to ICU for acute myasthenic respiratory failure. Weaning from mechanical ventilation remained impossible despite 4 plasma exchanges and azathioprine. The patient exhibited a progressive 12 kg weight loss with muscular weakness and atrophy. MEASUREMENTS AND RESULTS: Peripheral and diaphragmatic electromyography as well as histological study were consistent with a steroid-induced myopathy. Discontinuation of corticosteroid treatment was followed by a rapid weight gain with general improvement and allowed weaning from mechanical ventilation with a complete recovery. CONCLUSION: This case provides evidence that corticosteroid-induced myopathy may be observed in myasthenia gravis and may involve the respiratory muscles as well as the peripheral musculature.

Adrenal Cortex Hormones

Fluid intake patterns in schizophrenia and normal controls.

1. Patterns of fluid intake and urine output was examined in schizophrenia and normal controls. 2. Fluid intake and urine output were significantly higher in schizophrenic patients. 3. Bouts of drinking correlated significantly with fluid intake but did not differ significantly between schizophrenic patients and normal controls. 4. Schizophrenic patients drink more per bout compared to normal controls.

Adult

Central neurocytomas. Critical evaluation of a small-cell neuronal tumor.

We report herein the clinical and pathological features of 20 patients with central neurocytomas. Investigations for various differentiation antigens and cell type-specific markers were performed by immunohistochemistry using paraffin-embedded tissue. In addition, the expression of L1 adhesion molecule and of the various N.CAM (neural cell adhesion molecule) isoforms were investigated by immunoblotting studies in two frozen specimens. Central neurocytomas are clinically characterized by their intraventricular localization, occurrence in young adults, and good prognosis. It rarely occurs in patients over 50, but such cases have a poor prognosis. Total surgical excision is the best treatment. Radiotherapy is appropriate if surgery is incomplete or contraindicated. Histologically, central neurocytomas display the following features: an oligo-like pattern, usually associated with large fibrillary rosettes or perivascular arrangement, and a rich endocrine-type vasculature. Central neurocytomas have a remarkably homogeneous antigenic profile. GFAP expression is only found in scattered reactive astrocytes, S100 protein in reactive astrocytes and rare tumor cells. Among the pan-neuroendocrine markers, central neurocytomas always express neuron-specific enolase; they frequently express synaptophysin but never chromogranin A. Synaptophysin is the most reliable immunohistological marker for central neurocytomas; however, immunoreactivity could be lost with long formalin fixation. In these cases, electron microscopy is used to support the neuronal nature of the tumor cells. The expression of L1 adhesion molecule and the isoform 180 of N.CAM, indicates that central neurocytomas are formed by cells committed to neuronal phenotype. Nevertheless, advanced neuronal differentiation may be absent, as suggested by the persistence of embryonic N.CAM, the nonexpression of neurofilament proteins, and the absence of mature synapses in numerous cases. Central neurocytomas and neuroblastomas share some biochemical properties, but their respective clinicopathological features and biological behavior are dramatically different.

Adolescent

[Primary malignant teratoma of the thyroid. Two cases involving immunohistochemical and ultrastructural studies].

Two cases of primary malignant teratoma of the thyroid are reported. The first case, which occurred in a 21-year-old female, was mostly composed of tumoral neural tissue and foci of foetal cartilage. The patient died with lung metastases within 5 months after the first symptoms. The second case, which occurred is a 8-year-old infant female, had epithelial and mesenchymal components without neural tissue. This case had a better prognosis with survival of four years after initial diagnosis. The different tumoral components were identified by a thorough histopathological examination of the thyroidectomy with immunological and ultrastructural studies. As for other teratomas, presence of immature neural tissue bore a poor prognosis. The clinical, histopathological features and the histogenesis of this rare tumour are described and literature is reviewed.

Adult