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Biomedical subjects

F Richard

Publications and source records attributed to F Richard.

At least 37 records · Page 2Linked to original sources
PubMed2001

Impaired G protein coupling of the neurotensin receptor 1 by mutations in extracellular loop 3.

The neurotensin receptor 1, NTS1, is a G protein-coupled receptor. We have shown previously that the NTS1 receptor-binding site of the peptide agonist involved residues in extracellular loop 3 and at the extracellular junction of transmembrane domains 4 and 6. Here, we investigated by site-directed mutagenesis residues in extracellular loop 3 that might be involved in agonist-induced activation of the rat NTS1 (rNTS1) receptor. Wild type and mutated receptors were expressed in COS (African green monkey kidney fibroblasts) cells. Labeled agonist and antagonist binding as well as inositol phosphate and cAMP productions were studied. Compared to the wild type NTS1 receptor, the W339A, F344A, H348A and Y349A mutant receptors exhibited (i) decreased proportion of high over low affinity agonist binding sites, (ii) increased sensitivity of high affinity agonist binding to GTP gamma S, and (iii) impaired G protein coupling of high affinity agonist-receptor complexes. The data are consistent with the C-terminal part of extracellular loop 3 being essential for allowing high affinity agonist-NTS1 receptor complexes to couple to G proteins.

Animals↗
PubMed2001

Blood lipid concentrations and risk of myocardial infarction.

In western countries, individuals with plasma lipid concentrations above a set threshold value are judged to be at risk of coronary heart disease. However, in Algeria, people tend to have lower lipid concentrations than those in the developed world, and might, therefore, be excluded from preventive strategies and denied treatment. We did a study in Algeria in which we investigated the plasma lipid profiles of 67 individuals who had had a myocardial infarction, and 70 controls. We compared our results with those of two other similar studies done in France and Ireland. An increase in concentration of total cholesterol and LDL cholesterol, and a decrease in HDL cholesterol, was associated with raised risk of myocardial infarction in our study, but lipid concentrations rarely reached the recommended threshold values. However, cholesterol ratios (total/HDL, LDL/HDL) provided consistent and comparable estimates of cardiovascular risk across the three populations. Our results raise the question of whether threshold recommendations for cardiovascular risk prevention, in populations with low concentration of plasma lipids, should be made.

Adult↗
PubMed2001

Fate of a renal tubulopapillary adenoma transmitted by an organ donor.

Organ transplantation from cadaveric donors has a risk of cancer transmission. However, some reports indicate that kidneys bearing small carcinomas can be safely transplanted, as can other organs harvested from the same donor. We report herein the case of two allograft recipients (left kidney and heart with no evidence of tumor) who developed a renal carcinoma soon after transplantation. The initial tumor of the donor was a 17-mm tubulopapillary adenoma found on the right kidney, which was not transplanted. The left kidney recipient rejected all residual tumoral cells after graft removal and immunosuppression discontinuation. The heart recipient died 7 months after transplantation from metastasis of a renal carcinoma. This strongly suggests that circulating carcinoma cells were present at the time of organ retrieval and that they were not cleared by in situ perfusion. In contrast with the literature data, this report indicates that patients with small renal tubulopapillary tumors should not be considered for organ donation.

Adenoma, Villous↗
PubMed2001

The angiotensin I converting enzyme gene as a susceptibility factor for dementia.

The frequency of a genetic susceptibility vascular factor, the deletion (D) allele of the angiotensin I converting enzyme gene (ACE), coding for a key enzyme of the renin angiotensin system, was characterized in two independent case--control studies. The results of the current study suggest that bearing at least one ACE D allele is a risk factor to develop dementia for subjects older than 74 years. This observation reinforces the hypothesis of a major implication of vascular risk factors in the occurrence of all types of dementia.

Aged↗
PubMed2001

Patency of percutaneous transluminal coronary angioplasty sites at 6-month angiographic follow-up: A key determinant of survival in diabetics after coronary balloon angioplasty.

BACKGROUND: Several reports have demonstrated a high mortality rate in diabetic patients treated by standard coronary balloon angioplasty. No clear explanation has been provided for this finding. METHODS AND RESULTS: Consecutive diabetic patients successfully treated by standard coronary balloon angioplasty (n=604) were enrolled in a follow-up program including repeated angiography at 6 months and long-term clinical follow-up. Clinical follow-up was available in 603 patients (99.8%). Twelve patients died, 2 underwent bypass surgery before scheduled repeated angiography, and 76 declined angiography. Determinants of long-term mortality were analyzed in the 513 patients with angiography at 6 months and long-term clinical follow-up (mean follow-up, 6.5+/-2.4 years). On the basis of the results of repeated angiography, 3 groups of patients were defined: group 1, 162 patients without restenosis (32%); group 2, 257 patients with nonocclusive restenosis (50%); and group 3, 94 patients with coronary occlusion (18%). Overall actuarial 10-year mortality rate was 36%. Actuarial 10-year mortality was 24% in group 1, 35% in group 2, and 59% in group 3 (P:<0.0001). Multivariate analysis demonstrated that coronary occlusion was a strong and independent correlate of long-term total mortality (hazard ratio, 2.16; 95% CI, 1.43 to 3.26; P:=0.0003) and cardiac mortality (hazard ratio, 2.38; 95% CI, 1.48 to 3.85; P:=0.0004). CONCLUSIONS: This study demonstrates that restenosis, especially in its occlusive form, is a major determinant of long-term mortality in diabetic patients after coronary balloon angioplasty.

Aged↗
PubMed2001

Genetic susceptibility factors for Alzheimer's disease.

Alzheimer's disease is the most frequent cause of dementia. Family and twin studies have suggested that genetic factors play a role in Alzheimer's disease development. Some Alzheimer's disease cases show an autosomal dominant inheritance pattern and thus allow the discovery of major disease genes. However, most Alzheimer's disease cases are sporadic. These cases are mainly due to the effects of several different genes and of interactions between genetic susceptibility factors and environmental factors. Such interactions are illustrated by the apolipoprotein E epsilon4 allele, associated with a higher risk of Alzheimer's disease. Other genetic susceptibility factors have been reported but variously confirmed in Alzheimer's disease: apolipoprotein E receptors, alpha2-macroglobulin or angiotensin I converting enzyme genes. Thus, except for a small percentage of Alzheimer's disease cases with a dominant inheritance pattern, the genetic component of the vast majority of cases is underlain by complex interactions of genetic susceptibility factors and environmental conditions.

Alzheimer Disease↗
PubMed2001

Urodynamic monitoring during percutaneous sacral nerve neurostimulation in patients with neurogenic detrusor hyperreflexia.

The purpose of this study was to assess urodynamics parameter changes induced by acute sacral neurostimulation (SNS) in spinal cord injury (SCI) patients with neurogenic detrusor hyperreflexia. Fourteen SCI patients with urge incontinence owing to a hyperreflexive bladder were prospectively evaluated. Neurostimulation was performed on the root that obtained the best motor response (10 Hz, 210 microseconds) and amplitude ranges of >0 to 10 V. The urodynamics study was done in the prone position. Four cystometries were recorded before (two), during (one), and 10 minutes after stimulation (one). Maximal bladder capacity (MBC) (volume to first leakage), bladder volume at first uninhibited contraction (BV(1stC)), and maximal detrusor pressure during uninhibited contractions (P(det)max) were compared. Left S3 foramen was the most commonly used (9/14). Mean amplitude of stimulation was 4.5 V (range, 0.5-8.5 V). Statistically significant differences (Mann-Whitney U-test) were found for MBC, BV(1stC), and P(det)max with mean variations of +206.8 mL (+107%, P < 0.001), +151.5 mL (+98%, P < 0.01), and -23.4 cm H2O (-27%, P < 0.05), respectively. Patient gender and SCI level did not reveal any difference. Patients who reached a MBC of up to 400 mL (+278.2 mL, +129%, n = 10) with SNS had statistically significant improvement of BV(1stC) (+210.2 mL, +125%, P < 0.01) and P(det)max (-33.3 cm H2O, -38%, P < 0.01). Acute temporary SNS in SCI patients has a profound effect on key urodynamics parameters. These neurologically impaired patients with detrusor hyperreflexia may be appropriate candidates for implantable SNS.

Adult↗
PubMed2001

Genetic analysis of synphilin-1 in familial Parkinson's disease.

alpha-Synuclein is present in Lewy bodies of patients with both sporadic and familial Parkinson's disease. However, pathogenic mutations Ala30Pro and Ala53Thr in alpha-synuclein are rare causes of disease. Synphilin-1 has been demonstrated to associate with alpha-synuclein and promote the formation of cytosolic inclusions in vitro. Two-point genetic linkage analysis of a dinucleotide repeat within the synphilin-1 gene initially implicated this locus as a cause of Parkinson's disease in three of nine families. However, subsequent haplotype, sequencing, and association analyses in these three families and an independent case-control series suggest that variability within the locus does not confer susceptibility to Parkinson's disease.

Aged↗
PubMed2001

Paraneoplastic limbic encephalitis, a complication of the testicular cancer.

We report a case of paraneoplastic limbic encephalitis related to a testicular neoplasm. The syndrome is characterized by progressive amnesia and psychiatric disturbances resulting from an inflammatory reaction probably related to an immune response to the neuronal proteins expressed by tumors. It is usually associated with small cell lung cancer. In other cases, testicular cancer occurs more frequently than expected. Cranial magnetic resonance imaging may show increased signal intensity in the limbic cortex. Genitourinary examinations are sometimes inadequate. Testicular ultrasonography is recommended if no tumor is detected on the chest and abdominal computed tomography scan. The outcome of the treatment of the testicular cancer on the paraneoplastic syndrome is variable.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Anatomic and functional results of transperitoneal-transvesical vesicovaginal fistula repair.

OBJECTIVES: To evaluate the anatomic and functional results of transperitoneal-transvesical repair of simple and complex vesicovaginal fistulas (VVFs). METHODS: Between 1978 and 1995, 30 VVFs in 28 patients (mean age 44.6 years, range 21 to 80) were treated by way of a transperitoneal-transvesical approach. VVFs were secondary to hysterectomy in 67.8% of cases; 46.7% of VVFs were considered complex fistulas. Fifty percent of the VVFs were retrotrigonal and 40% were trigonal. A flap was interposed in 70% of cases. The vaginal fistula orifice was left open in 66% of cases, and 33% of VVFs required ureteral reimplantation. The mean duration of bladder drainage was 15.8 days (range 6 to 42), and the mean follow-up was 30 months (range 23 days to 14.6 years). The anatomic and functional results were evaluated by physical examination, cystoscopy, and a self-assessment questionnaire. Success was defined as the disappearance of the fistula. RESULTS: The overall success rate was 85% (24 of 28). The success rate was 87.5% for simple VVFs, 71% for complex VVFs, 93% for retrotrigonal VVFs, 66% for cervicotrigonal VVFs, and 80% for fistulas requiring ureteral reimplantation. Postoperative voiding disorders were reported in 38% of patients. CONCLUSIONS: Transperitoneal-transvesical repair of simple and complex VVFs remains the reference treatment for a disease that has become rare in countries with a well-developed healthcare system, but that is disabling and poorly tolerated by patients after the treatment of another disease.

Adult↗
PubMed2001

A retrospective analysis of the results of p(65) + Be neutrontherapy for the treatment of prostate adenocarcinoma at the cyclotron of Louvain-la-Neuve. Part I: Survival and progression-free survival.

PURPOSE: To retrospectively evaluate survival, progression-free survival (PFS) and biological response in a series of patients irradiated with mixed neutron/photon beams for locally advanced prostate cancer in our institution. PATIENTS AND METHODS: Three hundred and eight patients were treated between January 1990 and December 1996. Fifty-five of these were recruited for pT3 or pN1 tumors after radical prostatectomy. Neoadjuvant androgen deprivation was given in 106 patients. The treatment protocol consisted of a mixed photon/neutron irradiation in a two-to-three proportion, up to a total equivalent dose of 66 Gy (assuming a clinical RBE value of 2.8). Pre- and post-treatment PSA determinations were available in practically all cases. Study endpoints were overall survival (OAS) and progression-free survival (PFS). The Cox proportional hazard regression model was used to investigate the prognostic value of baseline characteristics on survival and progression-free survival were a progression was defined as local, regional, metastatic or biological progression. Mean age was 69 years (49-86); mean pretreatment PSA was 15 (0.5-330) in all patients and 14 (0.5-160) in those receiving neoadjuvant hormonotherapy; seven patients only had an initial PSA < or = 4 ng/mL; 15% were T1, 46% were T2, 28% were T3 or pT3 and 4% were T4 (7% unspecified); WHO grade of differentiation was I in 38%, II in 38% and III in 14% (5% unspecified). RESULTS: The median follow-up was 2.8 years (0-7.8). Five-year overall survival (OAS) was 79% (95% CI: 71-87%) and 5-year progression-free survival (PFS) was 64% (95% CI: 54-74%) for the entire series. PFS in patients with an initial PSA > or = 20 ng/mL was the same. PFS could be predicted by two optimal Cox regression models, one including histological grade (p = 0.003) and initial PSA (p = 0.0009) as cofactors, the other including histological grade (p = 0.003) and T stage (p = 0.02). The main prognostic factors for overall survival were PSA and age. Biological responses with PSA < 1.5 ng/mL, < 1 ng/mL and < 0.5 ng/mL at any time after treatment were documented in 70%, 61% and 47% of the patients, respectively. CONCLUSION: Five-year OAS was 79%, PFS was 64%, and biological response was 70% for prostate cancer patients treated with mixed photon/neutron beams as applied at Louvain-la-Neuve, which are good results as compared with the literature. The usual prognostic factors were confirmed.

Adenocarcinoma↗
PubMed2001

Agonism, inverse agonism, and neutral antagonism at the constitutively active human neurotensin receptor 2.

Two G protein-coupled neurotensin (NT) receptors, termed NTR1 and NTR2, have been identified so far. In contrast to the NTR1, which has been extensively studied, little is known about the pharmacological and biological properties of the NTR2. In the course of characterizing NT analogs that exhibited binding selectivity for the NTR2, we discovered that this receptor constitutively activated inositol phosphate (IP) production. Here, we report on the constitutive activity of the human NTR2 (hNTR2) transfected in COS cells and on compounds that exhibit agonism, inverse agonism, and neutral antagonism at this receptor. IP levels increased linearly with time, whereas they remained constant in mock-transfected cells. Furthermore, IP production was proportional to the amount of hNTR2 present at the cell membrane. SR 48692, a nonpeptide antagonist of the NTR1, stimulated IP production, whereas levocabastine, a nonpeptide histamine H1 antagonist that binds the NTR2 but not the NTR1, behaved as a weak partial inverse agonist. NT analogs modified at position 11 of the NT molecule, in particular by the introduction of bulky aromatic D amino acids, exhibited binding selectivity at the hNTR2 and also behaved as partial inverse agonists, reversing constitutive IP production up to 50%. Finally, NT barely affected constitutive IP production but antagonized the effects of both agonist and inverse agonist compounds, thus behaving as a neutral antagonist. The unique pharmacological profile of the hNTR2 is discussed in the light of its sequence similarity with the NTR1 and the known binding site topology of NT and SR 48692 in the NTR1.

Amino Acid Sequence↗
PubMed2001

Feasibility of a temporary urethral stent through the striated sphincter in patients in the early phase (6 months) of spinal cord injury.

OBJECTIVE: To assess the feasibility of a temporary urethral stent through the striated sphincter in patients in the early phase (before 6 months) of spinal cord injury (SCI) in a department of neurological rehabilitation. METHODS: Fourteen consecutive men with SCI with urinary retention within 6 months after SCI were prospectively treated. Thirteen patients were tetraplegic (C2 to C7) and 1 was paraplegic. All patients were managed with indwelling catheters (10) or intermittent catheterization (4). The Nissenkorn polyurethane urethral stent was inserted across the external sphincter under local anesthesia for an anticipated 4-month duration. RESULTS: No perioperative complications were encountered. Hospital mean stay at the urological department was 1.9 days (range 1-4 days). All patients had good emptying of the bladder (residual urine less than 100 ml) and were free of all types of catheterization. Five stents had to be repositioned in the first 2 weeks, 1 was removed for obstruction at 2.5 months. There was no lithiasis, no upper urinary tract alteration, no symptomatic infection nor local discomfort during follow-up. At a mean of 3.7 months after implantation, 10/14 (71.5%) patients chose sphincterotomy by permanent urethral stent and 4 had stent removal for learning of self-intermittent catheterization (3) and indwelling catheter (1). CONCLUSIONS: The temporary sphincter stent is a new, feasible and reversible technique to manage neuropathic bladder dysfunction in the early phase after SCI. A randomized study on intermittent catheterization should be conducted. It should consider patients' and nursing caregivers' evaluations.

Adult↗
PubMed2001

Chromosome homologies between man and mountain zebra (Equus zebra hartmannae) and description of a new ancestral synteny involving sequences homologous to human chromosomes 4 and 8.

Using human chromosome painting probes, we looked for homologies between human and mountain zebra (Equus zebra hartmannae, Equidae, Perissodactyla) karyotypes. Except for two very short segments, all euchromatic regions were found to have a human homologous chromosome segment. Conserved syntenies previously described in various mammalian orders were detected. Each synteny corresponded to a chromosomal region homologous to two parts of human chromosomes: HSA3 and HSA21, HSA7 and HSA16, HSA12 and HSA22, and HSA16 and HSA19. Chromosomal segments homologous to a part of HSA11 and HSA19p are found syntenic in zebra, horse and donkey, suggesting that this group of synteny has been inherited from an Equidae or Perissodactyla common ancestor. A synteny of segments homologous to parts of HSA4 and HSA8 was observed in zebra and horse. It also exists in the rabbit (Lagomorpha) and several Carnivora species. A second group of taxa which does not have this region of synteny is composed of primates, Chiroptera and Insectivora, and possibly also Cetacea and Scandantia. Thus, the presence or absence of this region of synteny may separate two groups of eutherian mammals.

Animals↗
PubMed2001

[Results of an epidemiologic surgery carried out with men 50-80 years of age to study urinary disorders, quality of life and sexual function].

OBJECTIVE: The prevalence of urinary symptoms, their impact on quality of life and sexuality and the man's attitude in relation to these problem were studied by a self-administered questionnaire (including I-PSS, 6 questions of DAN-PSS-1, BPHQL9 and IIEF). MATERIAL AND METHODS: This questionnaire was sent by mail to a national representative sample of 3,500 French men aged 50 to 80 years. Of the 2,372 men who returned an interpretable questionnaire, 21%, 33% and 42% belonged to the severe or moderate category for symptoms, tolerance of symptoms, and alteration of quality of life, respectively. RESULTS: 81% of men reported sexual activity during the last 4 weeks. 8.3% of men were treated with "antiprostate" medical treatments, and 8% had been operated (16% of them were treated medically after the operation). Only 29% and 17% of men had talked about their sexual and urinary problems, respectively. CONCLUSION: Alteration of functional and perceived sexuality was correlated with age and the severity of symptoms in non-operated patients, but the poor correlations between scales evaluating sexuality and symptoms indicate that sexuality is a difficult aspect to investigate.

Aged↗
PubMed2001

[Clinical evaluation of urinary incontinence in the woman].

Clinical assessment of stress and urge incontinence in women is always necessary before making therapeutic decisions. During the full bladder examination stress incontinence triggered by cough may suggest cervicourethral hypermobility. Leakage during the Vasalva manoeuvre may reveal incontinence due to intrinsic sphincter deficiency. The pad test provides an objective quantitative measurement of the degree of incontinence. Symptom scores enable intra- and inter-individual comparisons. Psychosocial implications are studied with specific quality-of-life scales. Together, these tests improved therapeutic strategies for managing stress and urge incontinence, providing an objective evaluation of the different treatments and thus a better medico-economic approach to the problem.

Female↗
PubMed2000

Patterns of chromosomal imbalances in invasive breast cancer.

Invasive breast carcinomas are characterized by a complex pattern of chromosomal alterations. We applied comparative genomic hybridization (CGH) to analyze 105 primary breast carcinomas using histograms to indicate the incidence of DNA imbalances of tumor subgroups and difference histograms to compare invasive ductal carcinomas (IDC) with lobular carcinomas (ILC), well and poorly differentiated carcinomas (G1/G3) and estrogen receptor-positive and -negative tumors (ER(+)/ER(-)). Only single imbalances showed a higher incidence in ILC compared with IDC, i.e., gains on chromosomes 4 and 5q13-q23 as well as deletions on chromosomes 6q, 11q14-qter, 12p12-pter, 16q, 17p, 18q, 19, and 22q. Of these, particularly gains of 4 and losses at 16q21-q23, and 18q12-q21 were statistically significant. For most loci, IDC showed more alterations providing a genetic correlate to the fact that ductal carcinoma overall is associated with a worse prognosis than ILC. Of these, many imbalances showing statistical significance were also observed in G3 and ER(-) tumors, i.e., deletions at 2q35-q37, 3p12-p14, 4p15-p16, 5q, 7p15, 8p22-p23, 10q, 11p, 14q21-q31, 15q, and gains at 2p, 3q21-qter, 6p, 8q21-qter, 10p, 18p11-q11, and 20q, suggesting that they contribute to a more aggressive tumor phenotype. By contrast, gains on chromosome 5q13-q23 as well as deletions at 6q, 16q and 22q were more prevalent in G1 and ER(+) tumors. The ratio profiles of all cases as well as histograms are accessible at our CGH online tumor database at http://amba.charite.de/cgh. Our results highlight distinct chromosomal subregions for cancer-associated genes. In addition, these imbalances may serve as markers for a genetic classification of invasive breast cancer.

Adult↗