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Biomedical subjects

F Richard

Publications and source records attributed to F Richard.

At least 19 recordsLinked to original sources

D allele of the angiotensin I-converting enzyme is a major risk factor for restenosis after coronary stenting.

BACKGROUND: Although intracoronary stent implantation significantly reduces restenosis compared with balloon angioplasty, a minority of patients still develop restenosis predominantly due to neointimal hyperplasia. Experimental studies suggest that the renin-angiotensin system is involved in neointimal hyperplasia after arterial injury. In humans, the plasma and cellular levels of ACE are associated with an I/D genetic polymorphism in the ACE gene, DD patients having higher levels. METHODS AND RESULTS: We investigated a possible relation between the ACE I/D polymorphism and restenosis in 146 patients who underwent successful implantation of a Palmaz-Schatz stent and had 6-month follow-up angiography. The minimal lumen diameter (MLD) before and after the procedure did not differ significantly among the three groups of genotypes (DD, ID, and II). At follow-up, MLD had a significant inverse relationship to the number of D alleles present (DD, 1.65 +/- 0.71 mm; ID, 1.84 +/- 0.60 mm; II, 2.05 +/- 0.61 mm; P < .007). Late luminal loss during the follow-up period was significantly related to the number of D alleles (DD, 0.89 +/- 0.61 mm; ID, 0.60 +/- 0.52 mm; II, 0.40 +/- 0.53 mm; P < .0001). The relative risk of restenosis (defined as a > 50% diameter stenosis at follow-up) approximated by the adjusted odds ratio was 2.00 per number of D alleles (95% confidence interval, 1.03 to 3.88, P < .04). CONCLUSIONS: The ACE I/D polymorphism influences the level of late luminal loss after coronary stent implantation. These results suggest that the renin-angiotensin system may be implicated in the pathogenesis of restenosis after coronary stenting.

Aged

The angiotensin II type 1 receptor gene polymorphism is associated with coronary artery vasoconstriction.

OBJECTIVES: This study sought to assess the potential association of the angiotensin-converting enzyme (ACE) and angiotensin II type 1 (AT1) receptor gene polymorphisms on coronary vasomotion in humans. BACKGROUND: Abnormal coronary vasomotion plays a role in the clinical expression of coronary atherosclerosis. The components of the renin-angiotensin system are important determinants of vasomotor tone. Furthermore, epidemiologic evidence suggests that these components are involved in the pathogenesis of coronary artery disease. Indeed, two genetic polymorphisms of the ACE and AT1 receptor genes were synergistically associated with the occurrence of myocardial infarction. The influence of these genetic polymorphisms on the risk of myocardial infarction may be related, at least in part, to a deleterious effect on coronary vasomotion. METHODS: We studied the response of angiographically normal human coronary arteries after intravenous injection of methylergonovine maleate, a potent vasoconstrictor whose effects have been previously explored in various aspects of coronary artery disease. We characterized the ACE and AT1 receptor genotypes in a consecutive series of 140 patients with normal coronary arteries. Coronary vasomotion was assessed with quantitative coronary angiography. RESULTS: No effect of the ACE gene polymorphism was detected. Conversely, the patients carrying the AT1 receptor CC genotype (n = 13) had significantly greater vasoconstriction in distal coronary vessels (p < 0.009). CONCLUSIONS: The AT1 receptor gene polymorphism is associated with coronary vasomotion in humans.

Adult

Effect of smoking cessation on lipoprotein A-I and lipoprotein A-I:A-II levels.

Cigarette smoking is associated with low plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo) A-I levels, which may explain, in part, its deleterious effects on coronary heart disease (CHD). In a group of ex-smokers, we assessed the influence of smoking cessation on apo A-I particle levels. Plasma lipid, apolipoprotein, and lipoparticle concentrations of 58 subjects who had completely stopped smoking (ex-smokers) were compared with those of 37 subjects who had continued smoking (smokers) before and after a smoking cessation counseling program. Nutritional intake was recorded before and after the program to adjust for potential interaction with plasma lipid variables. Smokers and ex-smokers were similar in gender distribution, age, body mass index (BMI), social status, and nutrient intake. There were significantly greater increases in total cholesterol (P < .04), HDL-C (P < .005), HDL2-C (P < .008), and lipoprotein (Lp) A-I:A-II (P < .04) in ex-smokers than in smokers. After smoking cessation, ex-smokers consumed more vegetable protein (P < .02) and polysaccharides (P < .04) and had higher plasma levels of HDL-C (P < .0004), apo A-I (P < .001), Lp A-I (P < .007), and Lp A-I:A-II (P < .01) than smokers. Adjustments on nutritional variables did not show any additional difference between ex-smokers and smokers, suggesting that smoking per se effects Lp A-I and Lp A-I:A-II levels. In conclusion, HDL particles including Lp A-I and Lp A-I:A-II are higher in ex-smokers than in smokers.

Adult

Long-term effects of localized spinal radiation therapy on vertebral fractures and focal lesions appearance in patients with multiple myeloma.

The occurrence of new vertebral fractures and focal marrow lesions was determined and compared in irradiated and nonirradiated vertebrae of 12 patients with multiple myeloma (MM), prospectively followed using magnetic resonance imaging (MRI) of the thoraco-lumbar spine after localized spinal radiation therapy. During follow-up (mean 35 months), fractures appeared in 5% of irradiated vertebrae and in 20% of nonirradiated vertebrae: new focal lesions appeared in 4% of irradiated vertebrae and in 27% of nonirradiated vertebrae. This study demonstrates a beneficial long-term effect of localized radiation therapy, consisting of a reduced incidence of vertebral fractures and focal marrow lesions in irradiated vertebrae.

Aged

Emergence and scattering of multiple neurofibromatosis (NF1)-related sequences during hominoid evolution suggest a process of pericentromeric interchromosomal transposition.

Type 1 neurofibromatosis (NF1) gene encodes for a member of the GTPase activating protein family and is considered to be a tumor suppressor gene. Its very high rate of de novo mutation in humans led us to study a specific feature of this gene: the presence of numerous NF1-related sequences. According to our results, the human genome contains at least 11 NF1-related sequences, nine of which are scattered near centromeric sequences of seven different chromosomes. These NF1-related sequences, whose extent is quite varied according to loci, are unprocessed copies of the NF1 gene, and bear numerous mutations. A phylogenetic analysis of the six largest sequences indicates that they are all derived from a common ancestor, which would have appeared 22-33 million years ago, and was subsequently duplicated several times during hominoid evolution. The most recent duplication and interchromosomal transposition occurred in the last million years suggesting that the process could still be ongoing. Intriguing similarities between the evolution of alpha-satellite DNA and NF1-related sequences suggest the involvement of a common genetic mechanism for the generation and pericentric spreading of these NF1 partial copies.

Animals

Association of angiotensin converting enzyme and angiotensin II type 1 receptor genotypes with left ventricular function and mass in patients with angiographically normal coronary arteries.

OBJECTIVE: To analyse the potential association of the angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) gene polymorphisms on left ventricular function and mass in patients with normal coronary arteries. DESIGN: Consecutive sample. SETTING: University hospital. SUBJECTS: 141 consecutive white patients referred for coronary angiography and with angiographically normal coronary arteries. Patients with valvar diseases, cardiomyopathies, or a history of myocardial infarction were excluded. MAIN OUTCOME MEASURES: Left ventricular variables were measured for all patients. The ACE and AT1R genotypes were determined with a polymerase chain reaction based protocol using DNA prepared from white blood cells. A general linear model was used to compare data according to the ACE and to the AT1R genotypes. RESULTS: A strong association was observed between left ventricular mass and systemic hypertension (mean (SD) hypertension: 114 (31) g/m2; no hypertension 98 (23) g/m2; P < 0.003). However, no influence of ACE and AT1R polymorphisms on left ventricular mass was found, regardless of systemic hypertension. The subjects homozygous for the AT1R CC mutation had a significantly lower ejection fraction than those with allele A (AC+AA) (mean (SD) 62(12)% and 68(10)%, respectively, P < 0.05). No synergistic interaction of ACE and AT1R gene polymorphisms on left ventricular function and mass was found. CONCLUSIONS: These data do not support an association of the ACE and AT1R genotypes on left ventricular hypertrophy in white patients with normal coronary arteries.

Angiotensin II

Cloning, sequencing and in vitro functional expression of recombinant donkey follicle-stimulating hormone receptor: a new insight into the binding specificity of gonadotrophin receptors.

Among all mammalian FSH receptors (FSH-R; including donkey (dk) FSH-R), only horse (hs) FSH-R does not bind hsLH/chorionic gonadotrophin (CG). In order to delineate the structural origin of hsFSH-R specificity precisely, we have cloned dkFSH-R cDNA from donkey testis mRNA by RT-PCR. Transiently expressed dkFSH-R endowed COS-7 cells with both hsLH/CG- and FSH-binding activity, as well as FSH-induced cAMP production. The deduced dkFSH-R amino acid sequence shares 96% identity with the hsFSH-R: notably, in the hormone-binding domain, the specificity of hsFSH-R may be ascribed to only four divergent amino acids: Thr 173, Asp 202, Asn 268 and Pro 322. Interestingly, hsAsn 268 could bear an additional N-glycosylation. According to receptor negative specificity, these amino acids could be implicated in preventing LH/CG binding to FSH-R.

Amino Acid Sequence

[Elaboration and validation of a specific quality of life questionnaire for urination urgency in women].

Urgent micturition interferes with the quality of life (QoL) of women suffering from this symptom. In order to evaluate this disturbance of quality of life and the benefits of treatment, a self-administered questionnaire, specific to the disorders of urgent micturition in women, was developed from a pre-existing scale (Measurement of Urinary Handicap, MUH). The following developmental methodology was adopted: Generation of a first instrument from the patient's descriptions collected by a multidisciplinary group of clinicians: formulation of questions, regrouping of questions into dimensions, choice of reference period and modalities of response. Content validation and test of comprehension in 20 patients. Transverse pilot study (98 patients) designed to reduce the number of questions and analyse the internal reliability and clinical validity. Reproducibility study. The final questionnaire comprises 24 items grouped into 5 dimensions: activities (8 items), emotional repercussions (5), self-image (5), sleep (3), well-being (3). The relevance of regrouping of the questions in their dimension and of calculation of a global score was confirmed by a principal component analysis and multifactorial analysis. The internal reliability and reproducibility of the scores were satisfactory, with a Cronbach alpha of > 0.70 and an intraclass correlation coefficient > 0.80, respectively. The clinical validity of the questionnaire was verified: the QoL scores of patients became significantly lower as the symptoms became more severe. A specific, reliable and clinically valid questionnaire, expressed in the form of a global score and a profile, was able to be developed. The profile of patients suffering from urgent micturition reflects the repercussions of the disease on the major and specific domains of their QoL. This questionnaire presents the required properties to be used in clinical trials designed to evaluate the effects of treatments on the patients' QoL, as a complement to classical clinical evaluations.

Activities of Daily Living

[Isolated Burch type indirect colposuspension of the bladder neck in the treatment of stress urinary incontinence in women. Long-term results].

OBJECTIVES: Burch indirect colposuspension remains the reference surgical operation in the treatment of female urinary stress incontinence. The stability of the results is highly controversial and the causes of failure remain hypothetical. The objective of this study was to analyse the long-term results of this technique. METHODS: 100 women suffering from pure urinary stress incontinence, in whom a Burch indirect colposuspension was performed, were included in this study. These patients were reviewed with a mean follow-up of 5.2 years and a questionnaire designed to assess the results was sent to their homes. RESULTS: 64% of patients no longer suffered from incontinence. Deterioration of the results was observed up to 5 years after the operation, but subsequently remained stable. The results were operator-independent. Low sphincter pressure (< 30 cm H2O), preoperative detrusor instability, insufficient hormonal impregnation and a history of pelvic surgery were the main factors predictive of failure of this technique. CONCLUSION: This study confirms the benefit provided by this technique in almost two-thirds of patients and indicates the risk factors of failure which must be taken into account before proposing Burch indirect colposuspension to a woman suffering from urinary stress incontinence.

Adult

[Imaging of small renal tumors].

The increased incidence of detection of small renal tumours, less than or equal to 3 cm in diameter, is related to the generalization and improvement of radiological techniques. Many asymptomatic renal tumours are discovered by ultrasonography and computed tomography. Medical imaging is now able to identify simple cysts (morphological characters, absence of blood supply), angiomyolipomas (demonstration of the fatty contingent) and other solid renal tumours (tumour enhancement on computed tomography). Plain, followed by postcontrast CT looking for contrast enhancement of the lesions is the examination of choice in this context. MRI with Gadolinium injection looking for neoplastic enhancement can be useful in doubtful cases. Medical imaging is able to reliably demonstrate the vascular nature of solid lesions, but cannot distinguish between renal cancer, oncocytoma or another benign solid tumour. Medical imaging allows precise preoperative mapping when partial nephrectomy is envisaged.

Adenoma, Oxyphilic

[Diagnosis of cancer of the prostate (I): Advancements in knowledge and practice since the consensus conference of 1989. The "Cancer of the Prostate" subcommittee of the Committee of Oncology of the French Association of Urology].

The prostatic cancer screening policy in France is defined by recommendations established at the 1989 consensus conference. Mass or individual screening by serum specific prostatic antigen (PSA) assay is not recommended. The Oncology Committee of the Association Française d'Urologie has up-dated the knowledge concerning prostatic cancer screening since 1989. The results are published in the form of a series of articles referring to the criteria used as prerequisites for cancer screening programmes. This article describes: 1) Current screening and treatment recommendations in France and in other countries. 2) The progress in our understanding of the prognosis, diagnosis and treatment of prostatic cancer, justifying revision of the screening policy. 3) The methodology and results of prospective screening studies and the projections of these results on the basis of the French population. Despite the 1989 recommendations, individual screening by serum PSA assay is widely performed both due to the characteristics of the test (simple blood test, low cost, high positive predictive value) and information of the public by the media concerning the morbidity and mortality related to prostatic cancer. The current data of the literature are unable to define the impact of PSA screening on the morbidity and mortality of prostatic cancer. Randomized prospective studies are currently underway. The absence of proof of a favourable impact of PSA screening is only one of the causes of the controversy concerning this screening technique, as another source of controversy is the magnitude of iatrogenic disorders induced by screening. In patients with raised PSA, the diagnostic examinations (biopsy) and curative treatments (surgery or radiotherapy) proposed are invasive, responsible for considerable morbidity and non-negligible mortality. Finally, the cost of screening remains unknown. Future recommendations must adapt their conclusions to changes in the current situation, in which prostatic cancer is simultaneously considered to be a non-serious disease which does not justify screening and a serious disease, as soon as the diagnosis is made, justifying, for 95% of urologists, an invasive and mutilating treatment in men with a life expectancy of more than 10 years.

Attitude to Health

Early effect of ApoE-epsilon 4 allele on cognitive results in a group of highly performing subjects: the EVA study. Etude sur le Vieillissement Artériel.

We examined the association between apolipoprotein E (ApoE) epsilon 4 allele and cognitive performances in a population sample of 1174 high functioning volunteers aged 59-71 years. The neuropsychological battery included the Mini Mental State Examination (MMSE) and nine tests assessing visual attention, verbal memory, visual processing, logical reasoning, psychomotor rapidity, visual memory, auditory attention and verbal fluency. The ratio of genotypes with zero, one or two epsilon 4 alleles was 70.6%, 21.4% and 1.9%, respectively. The epsilon 4 allele was significantly associated with lower scores for visual attention, psychomotor rapidity and MMSE. In the best performer subgroup (MMSE score above 25, n = 1028), all relationships persisted. Our findings demonstrate that the ApoE-epsilon 4 allele is early associated with low normal cognitive performances in areas which are not specifically affected at the subclinical onset of dementia.

Aged

The deletion allele of the angiotensin I converting enzyme gene as a genetic susceptibility factor for cognitive impairment.

Experimental evidences suggest an implication of the renin angiotensin system (RAS) as a potential determinant of cognitive functions. To explore this hypothesis, we compared the distribution of an insertion (I)/deletion (D) polymorphism of the gene coding for the angiotensin I converting enzyme (ACE), a key enzyme of the RAS, in 228 elderly with cognitive impairment to that of 255 controls. The ACE D allele frequency was higher in the group with cognitive impairment (0.594) than in controls (0.514) (P < 0.02). The ACE DD genotype carriers had an increased risk of cognitive impairment (OR = 1.60, 95% CI (1.04-2.36), P < 0.03), independent of other risk factors of cognitive impairment: age, gender and presence of the apolipoprotein E epsilon 4 allele. This association was stronger in men (OR = 3.25, 95% CI (1.40-7.58), P < 0.006). This result suggests a possible implication of the RAS in human brain and cognitive functions.

Aged

Evidence for earlier stabilization of cyclosporine pharmacokinetics in de novo renal transplant patients receiving a microemulsion formulation.

Sequential cyclosporine pharmacokinetic assessments were performed at four centres within the context of a double-blind, multicenter clinical trial comparing the safety and tolerability of the conventional formulation with cyclosporine for microemulsion in de novo renal transplant patients. The initial average daily oral dose was 9.3 mg/kg given in two divided doses every 12 hr with subsequent dose reductions individually titrated to maintain trough concentrations within the target therapeutic range. Pharmacokinetic profiles were assessed at week 2, once between weeks 4-6, and at week 12 in 12 patients on the conventional formulation and 9 patients on the microemulsion. Over the study duration, cyclosporine daily doses were comparable in both study arms and were reduced in parallel from 9.2 to 6.9 to 4.7 mg/kg/day at the three successive pharmacokinetic visits. Dose-normalized peak and area-under-the-curve (AUC) increased between the week 2 and week 4-6 assessments for both formulations. Thereafter, these parameters continued to increase for the conventional formulation but exhibited a high degree of within-in patient stability for the microemulsion between week 4-6 and week 12. Between-formulation comparisons indicated that the rate and extent of cyclosporine absorption from the microemulsion were significantly higher over the study duration. Specifically, at week 2, 4-6 and 12, dose-normalized AUC was 49%, 63%, and 32% higher for the microemulsion. Intrasubject coefficients of variability for pharmacokinetic parameters of the conventional formulation ranged from 26.3% to 68.2%. Corresponding values for the microemulsion were reduced by approximately half, ranging from 13.1% to 38.7%. The correlation between predose trough concentration and AUC was stronger for the microemulsion (r(2)0.819 vs. 0.635) over the full range of systemic exposures attained throughout the study. These results provide initial evidence that, as doses are reduced with time posttransplant, the cyclosporine dose-exposure relationship from the microemulsion may stabilize earlier than that from the conventional formulation, allowing increased pharmacokinetic control over cyclosporine use in this critical posttransplant period.

Administration, Oral

ZOO-FISH suggests a complete homology between human and capuchin monkey (Platyrrhini) euchromatin.

Chromosome comparisons using in situ hybridization of all human chromosome-specific libraries on Capuchin monkey (Cebus capucinus, Cebidae, Platyrrhini) metaphases were performed with a new technique simultaneously revealing a G-banding and chromosome "painting." A complete homology between human (HSA) and C. capucinus (CCA) chromosomes was demonstrated, except for constitutive heterochromatin. Eleven C. capucinus chromosomes are homologous to 11 human chromosomes: CCA 2 = HSA 4; CCA 3 = HSA 6; CCA 12 = HSA 9; CCA 16 = HSA 11; CCA 10 = HSA 12; CCA 11 = HSA 13; CCA 20 = HSA 17; CCA 8 = HSA 19; CCA 23 = HSA 20; CCA 24 = HSA 22; and CCA X = HSA X. Ten C. capucinus chromosomes are homologous to parts of human chromosomes: CCA 13 = HSA 8q; CCA 14 = HSA 2q; CCA 15 = HSA 1p + 1q proximal; CCA 17 = HSA 7 part; CCA 18 and 19 = HSA 3 part; CCA 21 and 22 = HSA 1q distal; CCA 25 = HSA 10p; and CCA 26 = HSA 15q part. Six C. capucinus chromosomes are homologous to parts of two human chromosomes: CCA 1 = HSA 5 + 7 part; CCA 4 = HSA 2p + q proximal + 16q; CCA 5 = HSA 10q + 16p; CCA 6 = HSA 14 + 15 part; CCA 7 = HSA 8p + 18; and CCA 9 = HSA 3 part + 21. Many previous banding comparisons were confirmed but several cryptic or complex rearrangements could be identified. With the C. capucinus karyotype having been shown to be fairly ancestral, this comparison opens the possibility to compare human chromosomes to most Cebidae species.

Animals

The relationship between sexual life and urinary condition in the French community.

As part of a large, nationwide community-based study in France on health and urinary condition, involving 2011 men aged between 50 and 80 years, information was collected on sexual life factors (e.g., frequency of sexual desires and sexual relations, and the frequency of having difficulties with erection and ejaculation) in addition to an assessment of overall sexual life satisfaction. Data on sexual life were obtained by means of a self-administered questionnaire, while information on the frequency of urinary symptoms was obtained by a professional interviewer. The median number of sexual relations decreased with age from "once per week" in those aged 50-59 years to "less than once per week" in those aged 60-69 years to "never" in those aged over 70 years, while the percentage reporting difficulty with erection at least some of the time increased from 20 to 38% between 50-59 and 70-79 years, respectively. The number of sexual relations during the past month was by far the most important factor having an influence on overall sexual life satisfaction, with those men reporting relations less than once per week almost 10 times more likely to be dissatisfied. Severity of overall urinary symptoms (as well as many individual symptoms) was also inversely related to sexual life satisfaction, and the association persisted after taking account of the strong influence of age and the frequency of sexual relations. All other factors being equal (age, number of relations, comorbidities, and previous prostate surgery), the likelihood of men being dissatisfied with sexual life increased twofold in men with moderate symptoms and fourfold in those with severe symptoms. The results obtained in the current study should be considered preliminary, given the complexity of the relationship between these two factors and the lack of previously published evidence. They certainly call for further studies, which should include a detailed assessment of sexual function and a clinical assessment of the urinary condition.

Aged