[Monosynaptic reflex and voluntary command in man].
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Biomedical subjects
Publications and source records attributed to C Morin.
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The effects of hydrocortisone, triamcinolone, prednisolone and dexamethasone have been investigated in vitro using mitochondria isolated from rat brain. Respiratory control ratio (RCR), oxygen consumption, ATP synthesis, enzymatic activities of involved complexes and superoxide anion generation have been measured to assess the effects of these drugs. Our data showed that the decrease of RCR induced by glucocorticoids was due to a common inhibition of oxidative phosphorylation (State 3) and of complex V activity and a modification of the proton-fluxes through the mitochondrial inner membrane. These effects were quantitatively limited, since they occurred at concentrations lower than 2 nM. Dexamethasone was the only one able to induce a specific inhibition of complex I activity and to decrease the superoxide anion radical generation. Inhibition of complex V and partial reversion of uncoupling seem to be common properties of glucocorticoids. The theoretical consequence of these inhibitions could be the modulation of the mitochondrial function, oxygen consumption rate, ATP synthase activity and superoxide anion radical production, involved in many patho-physiological phenomena.
OBJECTIVE: To identify cytologic parameters on Pap smears of women with an atypical squamous cells of undetermined significance (ASCUS) diagnosis that could help cytologists to indicate whether a particular ASCUS case is most likely related to cervical intraepithelial neoplasia (CIN) grade 1 or 2/3. STUDY DESIGN: A total of 360 eligible women diagnosed with ASCUS and referred to the colposcopy clinic of Saint-Sacrement Hospital participated in the study. Eligible women were those aged 18-50 years, newly diagnosed with ASCUS, with no history of cervical biopsies or treatment, and not pregnant at the time of the visit. Colposcopically directed biopsies of lesions were obtained. All Pap smears were reviewed according to 36 different cytomorphologic criteria. The regression logistic model was used to estimate the odds ratios (ORs) for the associations between cytologic criteria observed in smears and the diagnosis of CIN made on biopsies. All cytologic criteria significantly (P < .05) associated with CIN were entered in the models, and a backward selection was done to determine independent cytologic predictors of CIN 1 and 2/3. RESULTS: Biopsies revealed that 22.2% of the study population had concurrent CIN. CIN I and 2/3 were identified in 61 (16.9%) and 19 women (5.3%), respectively. Clear perinuclear spaces (OR = 2.5, P = .002) and moderate nuclear atypia (OR = 4.4, P = .02) were two cytologic criteria independently associated with CIN 1. Four independent predictors of CIN 2/3 were identified: the presence of clear perinuclear spaces (OR = 5.9, P = .004), hyperchromasia (OR = 3.9, P = .04), moderate anisokaryosis (OR = 13.1, P = .01 and increased nuclear volume of metaplastic cells (OR = 5.1, P = .007). CONCLUSION: These observations may help cytologists to better categorize ASCUS lesions as intraepithelial ones and will also contribute to improving the Bethesda definition of ASCUS. Further studies are planned to validate these observations.
Glucocorticoids play an important role in circulatory homeostasis. They modulate peripheral resistance by their direct action on blood vessels. We have previously shown that glucocorticoids increase preproendothelin-1 gene transcription rate in vascular smooth muscle cells (Morin C et al. 1998, BBRC 244:583). Endothelin-1 is a potent vasoactive peptide involved in the maintenance of vascular tone as well as in pathophysiological states. In this report we show that glucocorticoids increase preproendothelin-1 expression in rat aorta. The rise in preproendothelin-1 steady state mRNA level is dose-dependent with a maximal 2.3-fold stimulation 8 hours following a 0.35 and a 2.5 mg/kg dexamethasone injection. A lower dose of dexamethasone (0.13 mg/kg) also increased preproendothelin-1 expression in rat aorta. Since endothelin-1 levels are regulated at the transcriptional step, the increase in mRNA is likely to be paralleled by increased protein synthesis and vasoconstrictor action. Moreover, systolic blood pressure was significantly elevated in rats who received the 0.35 and 2.5 mg/kg doses of dexamethasone. Together, our results strongly suggest that the increase in preproendothelin-1 expression by glucocorticoids contributes to the regulatory action of these corticosteroids on blood pressure in health and disease.
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Nonhormonal contraceptives that act by blocking energy metabolism within sperm have the advantage over spermatogenic inhibitors by their fast onset of infertility and their almost immediate restoration of fertility after withdrawal of the contraceptive agent. This study was done to test new chlorinated compounds for their contraceptive potency on rodent and human sperm in vitro. Cells were incubated in a medium containing glucose as the sole energy source with 1-chloro-3-hydroxypropanone (CHOP) and 1,6-dichloro-1,6-dideoxy-D-fructose (DCDF), chlorinated analogues of glycolytic substrates, as well as racemic (R,S)-alpha-chlorohydrin (ACH). After incubation, enzymatic activity and kinematic parameters were estimated. A dose-dependent inhibition of the glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), of rat and mouse distal cauda epididymidal and human ejaculated sperm by ACH, CHOP, and DCDF was demonstrated. Triosephosphate isomerase (TPI) was inhibited by ACH, but not by CHOP and DCDF, irrespective of species. All compounds inhibited sperm motility and kinematic parameters with increasing concentration. The results confirm that inhibition of glycolytic enzymes of sperm, including those of human, can be effectively brought about by a variety of chloro-compounds that can be converted to (S)-3-chlorolactaldehyde, the stereospecific chloro-derivative of the enzyme's natural substrate, (R)-glyceraldehyde 3-phosphate, and could be developed into contraceptive agents for men.
A mitochondrial dysfunction has been suggested to explain chronic renal toxicity observed in ciclosporine A therapy. Our study has investigated whether trimetazidine allows inhibition of mitochondrial alteration induced by ciclosporine A. Oxidative phosphorylation was measured by polarography, calcium fluxes by a specific calcium electrode and the mitochondrial swelling by determination of the optical density at 520 nm, using a spectrophotometer. The ciclosporine A effect on the respiratory control was fully inhibited by trimetazidine (EC50 5.10 x 10(-7) M; Emax 11 per cent). Trimetazidine also inhibited the ciclosporine effects on calcium fluxes, i.e. calcium accumulation into the matrix and delay of efflux. Trimetazidine allows a decrease of mitochondrial dysfunction induced by ciclosporine A.
Mammography is the most important method for the diagnosis and the screening of breast diseases. Sensitivity and accuracy of mammography are very high in the detection of breast cancer. The use of the stereotaxic localization and fine-needle aspiration of nonpalpable breast lesions improve its effectiveness. The American Breast Cancer Detection Demonstration Project (BCDDP) has demonstrated the benefits of breast screening for women over 40 years of age. Many American medical associations and societies have adopted the guidelines based on the BCDDP results, promoting breast cancer screening for these women. However, recently released results of some randomized breast screening studies demonstrated only a 5% reduction in mortality from breast cancer in women 40-49 years of age, and a 40% reduction for women aged over 50 years. There is no explanation for this dilemma at the present time. However, screening mammography should stay available for women over 40 years of age.
Troponin (I or T) has become the gold-standard marker in acute coronary syndromes during the last few years, as confirmed by a national survey realized within french clinical chemists, cardiologists and emergency practitioners. The importance of this marker and the heterogeneousness of circulating forms of troponin after myocardial necrosis fully justify international studies about standardization of this assay, which is a central bulk to reach a global market coherence. Checking analytical problems, although necessary, must be absolutely associated with an informed clinical interpretation. The knowledge of the crucial thresholds of each assay, the kinetic curves and the specificity limits of troponin assays allow the best use of their potential in diagnosis and prognosis together with an optimal patient care in very different clinical settings, in addition to others clinical and technical arguments. The quality improvement through successive generations of assay kits must nowadays persuade the physicians never to ignore a significant and valid troponin increase, which mainly reveals a cardiac injury, whatever its origin.
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We report on 162 cases of human papillomavirus (HPV) infection of the cervix seen in a two-year period in which the cell sample showed such marked atypia that errors of interpretation could easily have been made. These atypical condylomata are difficult to diagnose cytologically as well as histologically because they mimic dysplasia or carcinoma in situ and, on smears, even invasive squamous carcinoma. HPV particles associated with fibrillar material were found within nuclei of these lesions; their nature was further proved by the immunoperoxidase test. This new form of HPV infection of the cervix showed a 9.1% rate of progression to more advanced cervical lesions. The cytologic finding of atypical condylomata is an indication for colposcopy, confirmative biopsy and appropriate treatment.
Twelve biopsies from condylomatous lesions of the human cervix were examined by transmission electron microscopy in order to study koilocytotic cells. The ultrastructure of koilocytes, revealed mainly cytoplasmic changes in the perinuclear area. These changes first appeared in cells of the intermediate layers and extended to the surface of the epithelium. The cells involved showed small perinuclear areas, with a fine granular material, which appeared as a lysis of the cytoplasmic matrix, forming microvacuolelike structures that gradually enlarged and fused together, ending with the formation of a large clear zone (koliocytosis). Binucleation and polylobulation were constant features. Intranuclear virus particles were often associated with koilocytes. Tubules and large bundles or single filamentous structures were also observed in koilocytes detected in smears and biopsies. This study provides further evidence that the koilocytes is the result of a process characterized by cellular changes due to cytopathogenic effect of the human papillomavirus.
Few studies have documented how schizophrenic patients perceived their needs and which coping skills they have spontaneously developed. All 48 patients of the Louis-H. Lafontaine Young Adults Clinic, a specialised schizophrenia clinic in Montreal, were invited to complete the Task Motivation and Problem Appraisal in Long Term Psychiatric Patients questionnaire. Our study utilised a descriptive approach and a classification of patient's reported problems and their coping skills. A panel of researchers and clinical staff then regrouped patient's perceived problems into four categories: symptoms, coping strategies, organisation of daily activities and interpersonal contacts. The main coping strategies utilised by these young patients are confrontation (52%) emotion-centered coping (57%). Clinical applications can be drawn from paying attention to the reports of schizophrenic patients. For example, rehabilitation activities can be developed which cater to their perceived needs. Because of frontal lobe hypoactivity, which make cognitive appreciation more difficult, their coping strategies should be diversified. Patients suffering from negative symptoms of schizophrenia mainly attempt to modify emotional impact, until they have discovered a way of confronting deficit symptoms. Better motivation to therapeutic programmes would result from paying attention to their perspectives.
This study reviewed at skeletal maturity 180 congenitally dislocated, subluxed, and dysplastic hips in 122 patients treated by the same surgeon by using Salter's innominate osteotomy (IO). The mean follow-up was 12 years. The sex of the patient, the laterality and height of the dislocation, the preoperative acetabular angle, the amount of femoral antetorsion, or the development of postoperative complications (except avascular necrosis of the femoral head), or a combination of these were not found to have a significant influence on the result. However, those patients who had a previous unsuccessful treatment of the hip, who developed pre- or postoperative avascular necrosis, who were unable to be restored by the osteotomy to a normal acetabular angle, or who required an open reduction of the hip joint (or who had a combination of these) were more likely to have an abnormal result. An important finding was that patients who underwent IO before age 4 years were the most likely candidates to receive a very satisfactory result.