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Biomedical subjects

A Gervais

Publications and source records attributed to A Gervais.

At least 19 recordsLinked to original sources

Regulation of microglial development: a novel role for thyroid hormone.

The postnatal development of rat microglia is marked by an important increase in the number of microglial cells and the growth of their ramified processes. We studied the role of thyroid hormone in microglial development. The distribution and morphology of microglial cells stained with isolectin B4 or monoclonal antibody ED1 were analyzed in cortical and subcortical forebrain regions of developing rats rendered hypothyroid by prenatal and postnatal treatment with methyl-thiouracil. Microglial processes were markedly less abundant in hypothyroid pups than in age-matched normal animals, from postnatal day 4 up to the end of the third postnatal week of life. A delay in process extension and a decrease in the density of microglial cell bodies, as shown by cell counts in the developing cingulate cortex of normal and hypothyroid animals, were responsible for these differences. Conversely, neonatal rat hyperthyroidism, induced by daily injections of 3,5,3'-triiodothyronine (T3), accelerated the extension of microglial processes and increased the density of cortical microglial cell bodies above physiological levels during the first postnatal week of life. Reverse transcription-PCR and immunological analyses indicated that cultured cortical ameboid microglial cells expressed the alpha1 and beta1 isoforms of nuclear thyroid hormone receptors. Consistent with the trophic and morphogenetic effects of thyroid hormone observed in situ, T3 favored the survival of cultured purified microglial cells and the growth of their processes. These results demonstrate that thyroid hormone promotes the growth and morphological differentiation of microglia during development.

Animals↗

Hepatitis after intravenous buprenorphine misuse in heroin addicts.

BACKGROUND: Sublingual buprenorphine is used as a substitution drug in heroin addicts. Although buprenorphine inhibits mitochondrial function at high concentrations in experimental animals, these effects should not occur after therapeutic sublingual doses, which give very low plasma concentrations. CASE REPORTS: We report four cases of former heroin addicts infected with hepatitis C virus and placed on substitution therapy with buprenorphine. These patients exhibited a marked increase in serum alanine amino transferase (30-, 37-, 13- and 50-times the upper limit of normal, respectively) after injecting buprenorphine intravenously and three of them also became jaundiced. Interruption of buprenorphine injections was associated with prompt recovery, even though two of these patients continued buprenorphine by the sublingual route. A fifth patient carrying the hepatitis C and human immunodeficiency viruses, developed jaundice and asterixis with panlobular liver necrosis and microvesicular steatosis after using sublingual buprenorphine and small doses of paracetamol and aspirin. CONCLUSIONS: Although buprenorphine hepatitis is most uncommon even after intravenous misuse, addicts placed on buprenorphine substitution should be repeatedly warned not to use it intravenously. Higher drug concentrations could trigger hepatitis in a few intravenous users, possibly those whose mitochondrial function is already impaired by viral infections and other factors.

Administration, Sublingual↗

Decrease in serum ALT and increase in serum HCV RNA during pregnancy in women with chronic hepatitis C.

BACKGROUND/AIMS: The natural history of chronic hepatitis C infection during pregnancy has not been clearly established, and thus our aim was to assess serum alanine aminotransferase levels and serum HCV RNA levels during pregnancy. METHODS: Twenty-six pregnant women with chronic hepatitis C were studied. Serum alanine aminotransferase was assessed within the 3 months before, monthly during and within the 3 months after pregnancy. In 12 women, serum HCV RNA levels were quantified by the branched DNA assay. Twenty-six age-matched non-pregnant women with chronic hepatitis C were followed up for 1 year, and used as a comparison group. RESULTS: During pregnancy, serum alanine aminotransferase levels decreased in the second and third trimesters. The third trimester levels were significantly lower than serum alanine aminotransferase levels before pregnancy (p=0.0001). Seventy-seven percent of the pregnant women with increased pre-pregnancy levels had normalization of serum alanine aminotransferase levels. In the second or third trimesters, serum HCV RNA levels increased. The third trimester serum HCV RNA levels were significantly higher than levels before pregnancy (p=0.01). No significant change in serum alanine aminotransferase or HCV RNA levels was observed in the control group. CONCLUSION: In pregnant women with chronic hepatitis C, serum alanine aminotransferase levels decrease, and serum HCV RNA levels increase during the second and third trimesters.

Adult↗

Activation of ionotropic glutamate receptors reduces the production of transforming growth factor-beta2 by developing neurons.

Neuronal cultures derived from developing rat cerebral cortex were used to investigate the influence of glutamate receptors on the neuronal production of transforming growth factor-beta2 (TGFbeta2), a multifunctional cytokine that modulates neuronal and glial growth. Long-term exposure (48 h) of cortical neurons to selective antagonists of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors markedly increased TGFbeta2 levels in the culture medium. Conversely, treatment with NMDA or kainate reduced TGFbeta2 to levels below those in untreated cultures. The effect of kainate did not require NMDA receptor activity. Neuronal depolarization with K+ also reduced TGFbeta2 levels by opening voltage-gated L-type Ca2+ channels. Semi-quantitative RT-PCR measurements of neuronal TGFbeta2 mRNA showed that NMDA or AMPA/kainate receptor stimulation reduced TGFbeta2 mRNA levels. These results demonstrate that tonic activation of glutamate-gated cation channels downregulates neuronal expression of the TGFbeta2 gene and provide evidence for a novel mechanism whereby excitatory amino acids could influence the development of glial and neuronal lineages.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Lifestyle health risk assessment. Do recently trained family physicians do it better?

OBJECTIVE: To determine whether recently trained family physicians were more likely to routinely assess lifestyle health risks during general medical evaluations. To document physicians' perceptions of the difficulties of lifestyle risk assessment, of medical training in that area, and of how often they saw patients with lifestyle health risks. DESIGN: Anonymous mailed survey conducted in 1995. SETTING: Family practices in the province of Quebec. PARTICIPANTS: Stratified random sample of 805 active family physicians of 1111 surveyed; 25 were ineligible or could not be located, and 281 did not respond (74.1% response rate). MAIN OUTCOME MEASURES: Proportion of physicians graduating before and after 1989 who reported routinely (with 90% or more of their patients) assessing their adult and adolescent patients during general medical evaluations for substance use, sexual risk behaviours, and history of family violence and sexual abuse. RESULTS: Except for asking about drug use, recently trained family physicians did not report better assessment of lifestyle health risks during general medical examinations than family physicians who graduated more than 10 years ago did. In both groups, routine assessment averaged 82% for tobacco use, 68% for alcohol consumption, and 20% to 40% for sexual risk behaviours. Screening for family violence and sexual abuse was rare, but more frequently reported by older women physicians. Only 20% to 40% of recent graduates rated their medical training adequate for evaluating illicit drug use, family violence, and sexual abuse. CONCLUSION: Recently trained family physicians do not assess most lifestyle risk factors any better than their more experienced colleagues.

Adolescent↗

Do physicians assess lifestyle health risks during general medical examinations? A survey of general practitioners and obstetrician-gynecologists in Quebec.

BACKGROUND: In Canada several guidelines have been published for the screening of lifestyle health risks during general medical examinations. The authors sought to examine the extent to which such screening practices have been integrated into medical practice, to measure physicians' perceived level of difficulty in assessing these risks and to document physicians' evaluation of their formal medical training in lifestyle risk assessment. METHODS: An anonymous mail survey was conducted in 1995 in Quebec with a stratified random sample of 1086 general practitioners (GPs) and with all 241 obstetrician-gynecologists (Ob-Gyns). The authors evaluated the proportion of physicians who reported routine assessment (with 90% or more of their patients) of substance use, family violence and sexual history during general medical examinations of adult and adolescent patients; the proportion of those who find inquiring about these issues difficult; and the proportion of those who evaluated their medical training in lifestyle risk assessment as adequate or excellent. RESULTS: The overall response rate was 72.6%. Among adult patients, 82.2% of the GPs reported routinely assessing tobacco use, 67.2% alcohol consumption, 34.2% illicit drug use and 3.2% family violence; the corresponding proportions for assessment among adolescent patients were 77.1%, 61.8%, 52.9% and 5.6%. Comparatively fewer Ob-Gyns reported routinely assessing these issues (56.1%, 28.6%, 20.4% and 1.3% respectively among adults and 62.7%, 35.2%, 26.8% and 2.8% respectively among adolescents). In the area of sexual history, condom use was routinely assessed by more Ob-Gyns than GPs (47.0% v. 28.2%); however, the proportion of Ob-Gyns and GPs was equally low for assessing number of partners (24.8% and 23.1%), sexual orientation (18.8% and 16.9%) and STD risk (26.2% and 21.2%). The vast majority of GPs and Ob-Gyns reported finding it difficult to assess family violence (86.5% and 93.0%) and sexual abuse (92.7% and 92.4% respectively). Over 80% of the physicians felt that they had had adequate or excellent medical training in assessing risk behaviours for heart disease and STD risk. The proportion who felt this way about their training in screening for illicit drug use, family violence and sexual abuse ranged between 12.7% and 31.6%. INTERPRETATION: Although morbidity and mortality associated with smoking, alcohol consumption, illicit drug use, unsafe sexual practices, family violence and sexual abuse have been well documented, routine screening for these risk factors during general medical examinations has yet to be integrated into medical practice.

Adolescent↗

Sexual health risk assessment and counseling in primary care: how involved are general practitioners and obstetrician-gynecologists?

OBJECTIVES: This study examined physicians' evaluation of sexual health risks during a general medical examination and sexually transmitted disease (STD) counseling during consultations for adolescent contraception and treatment of an STD. METHODS: An anonymous mail survey was conducted in 1995 with a stratified random sample of 1086 general practitioners and all 241 obstetrician-gynecologists practicing in Quebec, Canada. RESULTS: Fewer than half of the respondents reported routinely inquiring about condom use and number of sexual partners during a general medical examination. Female general practitioners engaged in more sexual health risk assessment and counseling than male general practitioners. CONCLUSIONS: This study suggests a low level of involvement in STD prevention by generalists and obstetrician-gynecologists.

Adolescent↗

Structure-specific binding recognition of a methanogen chromosomal protein.

The archaeon Methanosarcina thermophila expresses large amounts of a small basic protein, called MC1 (methanogen chromosomal protein), which was previously identified as a DNA-binding protein possibly involved in DNA compaction in some methanogenic species. We have investigated the binding of MC1 to various kinds of branched DNA molecules whose double helix axis is severely kinked. We show that MC1 is able to distinguish and to bind preferentially to four-way junctions. This preferential binding is observed in the absence and presence of divalent cations. However, we find that MC1 has a low affinity for bulged DNA structures. These results show how MC1 is able to discriminate between different deformations of the DNA double helix.

Archaeal Proteins↗

Apolipoprotein E and multiple sclerosis: a biochemical and genetic investigation.

Apolipoprotein E (apo E) is postulated to be a major lipid carrier protein in the brain involved in brain development and repair. Multiple sclerosis (MS) is a major demyelinating disease characterized by destruction of myelin and marked alteration of myelin cholesterol and lipid metabolism. We have determined serum and cerebrospinal fluid (CSF) apo E concentrations using an original time-resolved immunofluorometric assay and calculated intrathecal apo E concentration. Apo E concentrations were determined in 13 control subjects and 129 neurological patients: 34 definite MS patients, 25 with Guillain-Barré syndrome (GBS), 32 with amyotrophic lateral sclerosis (ALS) and 38 with other neurological diseases. Seven clinical parameters (sex, age, age at MS onset, duration of the disease, course, clinical status and disability score) were considered in MS patients. Significant (P < 0.01) decrease in CSF apo E was observed in MS, linked to a decrease in intrathecal apo E. The decreased CSF apo E concentration in MS patients occur independent of the apo E genotype. Apo E is considered as a neurotrophic factor in the brain. Any decrease in intrathecal apo E synthesis would thus contribute to progression of neurological diseases, such as MS.

Adult↗

Six French sheathless coronary angioplasty using a novel technique to introduce the guiding catheter: the INTRUC, a preliminary retrospective study.

This registry describes our preliminary experience with a novel introducing-catheter allowing direct percutaneous introduction of the 6F guiding catheter (G-C), minimizing the puncture size, preventing vessel scraping, and improving the pushability and torque response of the G-C. In 1995, 203 patients had sheathless PTCA, using this device. Eighty-five percent were male. Mean age was 65+/-10 years. Thirty-nine percent had stable angina, 35% unstable angina, 7% evolving infarction, and 19% recent infarction. Two hundred fifty-six lesions were treated (1.26/patient). One hundred eight patients (52%) received one (85%) or more than one (15%) stent. The procedural success rate was 98%. Mean coronary stenosis was 82+/-10% and decreased to 20+/-15% after PTCA. No major complication occurred. The guiding catheter was immediately removed in 95% of patients, despite heparinization. No patient required surgery or blood transfusion for vascular complications, and only 7 had minor local complications (3.5%). Sheathless angioplasty provides no technical difficulties and has the same safety and quality as conventional angioplasty using a sheath. Immediate removal of the guiding catheter, without keeping vascular access, has no deleterious effect, allows early mobilization, and may limit the risk of vascular complications.

Adult↗

Novel muscle chloride channel (CLCN1) mutations in myotonia congenita with various modes of inheritance including incomplete dominance and penetrance.

Autosomal-dominant and -recessive myotonia congenita are caused by mutations in the skeletal muscle voltage-gated chloride channel gene (CLCN1). We searched for mutations in this gene in 20 unrelated families with myotonia congenita. We identified 11 different mutations in 10 families. Two of five new mutations (Ala313Thr and Ile556Asn) were both autosomal recessive and dominant with either reduced penetrance or incomplete dominance. Mutations in the CLCN1 gene do not therefore necessarily behave in a classic Mendelian manner.

Adult↗

Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-alpha therapy.

BACKGROUND: Less than 20% of patients with chronic hepatitis C have a sustained response to interferon-alpha therapy. The long-term benefit of interferon-alpha with regard to hepatic viral clearance and histologic improvement remains unknown. OBJECTIVE: To determine the long-term biochemical, virologic, and histologic outcomes in patients with chronic hepatitis C who have a sustained response to interferon-alpha therapy. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS: 80 patients who had chronic hepatitis C, had a sustained biochemical and virologic response to interferon-alpha therapy, and were followed for at least 12-months. MEASUREMENTS: Serum hepatitis C virus (HCV) RNA detected by polymerase chain reaction (PCR); HCV genotyping determined by line probe assay; liver histologic studies; liver HCV RNA detected by PCR on frozen liver tissue samples (in 27 patients); and repeated measurements of serum alanine aminotransferase (ALT) levels. Liver biopsy was done before treatment in all 80 patients, and at least one biopsy was done in 69 patients 1 to 6 years after treatment. RESULTS: The 80 patients had follow-up 1 to 7.6 years (mean +/- SD, 4.0 +/- 2.0 years) after interferon-alpha treatment. The follow-up period was 1, 2, 3, 4, 5, 6, and more than 6 years in 11, 13, 14, 18, 10, 12, and 2 patients, respectively, after the end of therapy. During the entire follow-up period, 93% (95% CI, 84% to 97%) of patients had persistently normal serum ALT levels. Serum HCV RNA remained undetectable in 96% (CI, 89% to 99%) of patients. A comparison of liver histologic findings before and 1 to 6.2 years after interferon-alpha treatment showed a clear improvement in 94% (CI, 83% to 99%) of patients. In 62% of patients, the last biopsy done showed normal or nearly normal histologic findings. Liver HCV RNA was detectable before treatment in all 13 patients tested and was undetectable 1 to 5 years after treatment in all 27 patients tested. CONCLUSIONS: In patients with chronic hepatitis C who have persistently normal serum ALT levels and no detectable serum HCV RNA 6 months after interferon-alpha therapy, a long-term sustained biochemical and virologic response is generally seen. This response is associated with an absence of detectable intrahepatic HCV RNA and marked histologic improvement.

Alanine Transaminase↗

[Systematic use of 4 French catheters for left heart catheterization and coronary angiographies].

The feasibility of left heart catheterisation and coronary angiography using small calibre 4 French catheters was assessed in a prospective register of 355 consecutive patients. The average age was 64 +/- 10 years: 21% were women. The indications were: evaluation of coronary artery disease (279 patients), control of bypass graft patency (38 patients including 34 internal mammary artery grafts), 26 valvular lesions (including 15 aortic stenoses) and 12 cardiomyopathies. In 20.5% of cases, the catheterisation was performed on an out-patient basis. The catheters used for coronary opacification were Cordis Pigtail and Amplatz; mammary, multipurpose and right Judkins were used occasionally. The operators used on average 2.14 catheters, without difficulty in 13% of cases. A larger catheter was not required in any of the cases. There were no complications. The angiograms were estimated to be of good quality in 96% of cases. With the exception of patients undergoing immediate angioplasty and 9 patients with severe hypertension or anticoagulant therapy, the patients did not require compressive dressings on the puncture site and could be mobilised early. There were no local complications at the puncture site. The results of this study suggest that 4 F catheters can be used systematically for left heart catheterisation with safety. A short period of training is required after which good quality angiograms can be obtained without technical problems. Compressive dressings are not necessary after this type of investigation.

Adult↗

Do women physicians do more STD prevention than men? Quebec study of recently trained family physicians.

OBJECTIVES: To examine differences attributable to sex of family physicians in their practices and in their perceptions of sexual history taking and safer sex counseling, and to ascertain whether sex of physicians influences counseling about condoms. DESIGN: Cross-sectional survey. SETTING: Quebec family practices. PARTICIPANTS: Recently graduated (1991) Quebec family physicians: 54 men and 92 women. MAIN OUTCOME MEASURES: Frequency and content of sexual history, frequency of safer sex counseling, perceived level of comfort in taking a sexual history, perceived adequacy of medical training to take sexual histories, perceived difficulty with sexual history taking according to patients' characteristics, and perceived effectiveness of safer sex counseling. RESULTS: Response rate was 80% of 183 physicians contacted. There were few differences attributable to sex of physician in family physicians' practices and perceptions regarding sexual history taking. Men's perceptions regarding the difficulty of sexual history taking did not vary according to patient's sex, but most women reported more difficulty with male patients. Male physicians reported more difficulty with teenagers; female physicians experienced more difficulty questioning adults. More than 85% of male and female physicians reported recommending condom use to a patient in their practice at least weekly. Women physicians seemed to do more condom-related counseling than their male colleagues, even after controlling for other variables. Salaried practice in a local community health centre did not influence condom-related counseling. CONCLUSIONS: Women family physicians are more inclined than men to counsel patients about condom use. Increasing numbers of women in family practice could have a beneficial effect on prevention of STDs and undesired pregnancies.

Adolescent↗

Preferential binding of the archaebacterial histone-like MC1 protein to negatively supercoiled DNA minicircles.

The interaction of the archaebacterial MC1 protein with 207 bp negatively supercoiled DNA minicircles has been examined by gel retardation assays and compared to that observed with the relaxed DNA minicircle. MC1 binding induces a drastic DNA conformational change of each minicircle, leading to an increase of the electrophoretic mobility of the DNA. A slight increase in salt concentration enhances the amount of bound MC1, and high NaCl concentrations are required to dissociate the complexes. Furthermore, the salt effect on binding depends on the supercoiling state of the DNA. The dissociation rates decrease with increasing linking difference of the minicircles relative to their relaxed configuration to reach a maximum at -2 turns. In addition, differences between the topoisomers are also observed in terms of stoichiometry of the strongest complexes. So with the -2 topoisomer the complex with two MC1 molecules is the most stable, while with the -1 and -3 topoisomers, the strongest ones are those with one MC1 molecule per DNA ring.

Archaeal Proteins↗