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Biomedical subjects

F Richard

Publications and source records attributed to F Richard.

At least 19 recordsLinked to original sources

Effects of the molecular weight of peg molecules (8, 20 and 35 KDA) on cell function and allograft survival prolongation in pancreatic islets transplantation.

The normopotassic solution SCOT (Macopharma, France) used for the isolation of the islets of Langerhans may improve both graft function and survival. We believe that this is due to the immunoprotective properties of polyethyleneglycol (PEG) (20 kDa; 1.5 mM/L), which is contained in this solution. However, the optimal PEG chain length remains to be determined. Three extracellular type solutions (SCOT without PEG) containing various PEG-8 kDa, 20 kDa, or 35 kDa- at 1.5 mM/L were compared in vitro for viscosity and osmolarity as well as in vivo using a murine model of pancreatic islet allotransplantation. We compared the effects of the various solutions on functional cell recovery (primary nonfunction rate, PNF) and immunoprotection (allograft survival time). We showed that the viscosity of PEG 35 kDa solutions was too high for physiological use. PEG 20 kDa solution provided the best graft function (0% PNF, P < .05). PEG 8 kda and 20 kDa solutions significantly increased allograft survival time compared to the PEG 35 kDa solution (P < .05). Graft survival was similar with PEG 20 kDa and PEG 8 kDa solutions: 27.50 +/- 3.70 days versus 23.13 +/- 4.39 days (NS). However, the number of PNF with PEG 8 kDa solution (50%) was significantly higher (P < .01) than that with the PEG 20 kDa solution (0%). These preliminary results indicated that the optimal chain length at 1.5 mM/L of PEG is 20 kDa.

Animals↗

Use of the SCOT solution in kidney transplantation: preliminary report.

SUBJECT: This article reports preliminary findings relating to the use of a new preservation solution, the Solution de Conservation des Organes et des Tissus (SCOT), in renal transplantation. This fourth-generation solution combines an extracellular-like composition with 20 kDa polyethylene-glycol, known for its cell-protection capacity and immunocamouflage properties. METHODS: We have reported preliminary data obtained in 29 transplantations (25 cadaveric donors and 4 living related donors) between December 2004 and November 2005. The SCOT solution was used for both in situ flush and static preservation. We compared primary organ nonfunction and delayed graft function rates as well as blood creatinine levels in recipients of grafts processed with SCOT solution, versus University of Wisconsin solution (paired for age with the previous group) and with EuroCollins solution (historic data). RESULTS: We observed delayed graft-function in 10% of the SCOT-processed group, 14% in the University of Wisconsin solution group, and 23% of the EuroCollins group. No case of primary organ nonfunction was reported. Creatinine levels in both SCOT and University of Wisconsin solution groups were similar. We did not observe any humoral or cellular graft rejection in the first 3 months after transplantation. In light of these preliminary results, the use of SCOT is safe for kidney preservation in the human setting. Further experience is warranted to assess the clinical consequences of its immunocamouflage properties as described in animal models.

Adenosine↗

Different patterns of Mini Mental Status Examination responses in primary progressive aphasia and Alzheimer's disease.

Primary progressive aphasia (PPA) syndrome is frequently misdiagnosed--particularly in favour of Alzheimer's disease (AD). Misdiagnosis is related to the heterogeneity of language disorders at onset, variability in the rate of clinical progression and the low prevalence of PPA syndrome, compared with AD. The aim of this study was to determine whether a patient's first Mini Mental Status Examination (MMSE) might provide insight into differentiating between PPA and AD. We compared item scores for the first, complete MMSE in consecutive patients with PPA versus matched patients with AD. Word recall and constructional praxis were significantly better in patients subsequently diagnosed as suffering from PPA. Patients with AD performed significantly better in terms of word registration, object naming, repetition and verbal direction. Our findings indicate that the various MMSE item scores may be helpful in differentiating PPA and AD in the first few years of the disease.

Aged↗

APOE genotype, cholesterol level, lipid-lowering treatment, and dementia: the Three-City Study.

OBJECTIVE: To examine the association of plasma cholesterol levels, lipid-lowering agent (LLA) intake, and APOE genotype with dementia prevalence. METHODS: The Three-City Study is a population-based cohort of 9,294 subjects selected from the electoral rolls of three French cities (Bordeaux, Dijon, Montpellier). Baseline examination included extensive assessment of exposure to vascular risk factors (including cholesterol levels and LLA use [statin or fibrate]) and clinical diagnosis of dementia. RESULTS: Two percent of participants were demented at baseline. Overall 32.4% of participants had hyperlipidemia, and 15.6% were prescribed statins and 13.7% fibrates. After adjusting for age, gender, education level, and study center, the odds ratio (OR) for dementia was observed to be lower among LLA users (OR = 0.61, 95% CI = 0.41 to 0.91) compared with subjects taking no LLAs. There was no differential effect between statin and fibrate users. The odds for dementia were increased in subjects with hyperlipidemia (OR = 1.43, 95% CI = 1.03 to 1.99). Further adjustment for potential confounders did not modify these associations. In addition, the association between LLA intake and dementia was not modified by APOE genotype, whereas hyperlipidemia was significantly associated with increased dementia prevalence only in non-epsilon4 carriers and non-Alzheimer disease cases. Finally, in participants taking LLAs, the odds for dementia were decreased only in those having normal lipid levels. CONCLUSIONS: This observational study provides further evidence that lipid-lowering agents are associated with decreased risk of dementia, whereas hyperlipidemia is associated with increased odds for non-Alzheimer-disease-type dementia. These effects appear to be independent of all major potential confounders.

Aged↗

Diversity and specificity of ectomycorrhizal fungi retrieved from an old-growth Mediterranean forest dominated by Quercus ilex.

We analysed the ectomycorrhizal (ECM) fungal diversity in a Mediterranean old-growth Quercus ilex forest stand from Corsica (France), where Arbutus unedo was the only other ECM host. On a 6400 m2 stand, we investigated whether oak age and host species shaped below-ground ECM diversity. Ectomycorrhizas were collected under Q. ilex individuals of various ages (1 yr seedlings; 3-10 yr saplings; old trees) and A. unedo. They were typed by ITS-RFLP analysis and identified by match to RFLP patterns of fruitbodies, or by sequencing. A diversity of 140 taxa was found among 558 ectomycorrhizas, with many rare taxa. Cenococcum geophilum dominated (35% of ECMs), as well as Russulaceae, Cortinariaceae and Thelephoraceae. Fungal species richness was comparable above and below ground, but the two levels exhibited < 20% overlap in fungal species composition. Quercus ilex age did not strongly shape ECM diversity. The two ECM hosts, A. unedo and Q. ilex, tended to share few ECM species (< 15% of the ECM diversity). Implications for oak forest dynamics are discussed.

Mediterranean Region↗

Is there a relation between APOE expression and brain amyloid load in Alzheimer's disease?

BACKGROUND: It has been proposed that, independent of the epsilon4 allele, APOE promoter polymorphisms (-491 A/T and -219 G/T) may be risks factor for Alzheimer's disease by modulating APOE expression. OBJECTIVE: To measure the level of APOE expression in Alzheimer's disease. METHODS: Brains were obtained at necropsy from 114 patients with early and late onset sporadic Alzheimer's disease in Greater Manchester (UK) during years 1986 to 2001. Total RNA was extracted from 84 brains. Purified lymphocytes were obtained from fresh blood from 16 probable Alzheimer cases from Lille (France). APOE and beta-actin gene expression was determined by reverse transcriptase polymerase chain reaction in brain and lymphocytes. RESULTS: An inverse correlation between APOE expression level and A beta loads was observed. As previously described and extended to 114 cases here, an association between the -219 TT genotype and a higher level of parenchymal A beta deposition was found, irrespective of APOE epsilon4 allele status. This effect was more pronounced in older individuals, whereas higher A beta load appeared more closely related to epsilon4 in the younger age group (cut off point at the median age at death (72.5 years)). The -219 TT genotype was associated with a decrease in APOE expression. There was a 60% decrease in APOE expression in lymphocytes from probable Alzheimer cases v controls (p = 0.01). CONCLUSIONS: In the oldest individuals, reduced APOE expression, modulated in part by -219 G/T polymorphism, may influence risk and constitute a determinant A beta load in Alzheimer's disease.

Actins↗

Lipid lowering agents are associated with a slower cognitive decline in Alzheimer's disease.

BACKGROUND: Data from epidemiological studies and animal models imply that disturbances in cholesterol metabolism are linked to Alzheimer's disease susceptibility. Lipid lowering agents (LLAs) may have implications for the prevention of Alzheimer's disease. OBJECTIVE: To investigate whether LLAs are associated with a slower cognitive decline in Alzheimer's disease. METHODS: An observational study in 342 Alzheimer patients followed in a memory clinic for 34.8 months (mean age 73.5 years, mini-mental state examination score (MMSE) 21.3 at entry); 129 were dyslipaemic treated with LLAs (47% with statins), 105 were untreated dyslipaemic, and 108 were normolipaemic. The rate of cognitive decline was calculated as the difference between the first and last MMSE score, divided by the time between the measurements, expressed by year. Patients were divided into slow and fast decliners according to their annual rate of decline (lower or higher than the median annual rate of decline in the total population). RESULTS: Patients treated with LLAs had a slower decline on the MMSE (1.5 point/year, p = 0.0102) than patients with untreated dyslipaemia (2.4 points/year), or normolipaemic patients (2.6 points/year). Patients with a slower decline were more likely to be treated with LLAs. Logistic regression analysis, with low annual cognitive decline as the dependent variable, showed that the independent variable LLA (treated with or not) was positively associated with the probability of lower cognitive decline (odds ratio = 0.45, p = 0.002). CONCLUSIONS: LLAs may slow cognitive decline in Alzheimer's disease and have a neuroprotective effect. This should be confirmed by placebo controlled randomised trials in patients with Alzheimer's disease and no dyslipaemia.

Aged↗

Synthesis of novel types of copper-bipyridyl porphyrins and characterization of their interactions and reactivity with DNA.

The inherent ability to interact with DNA makes cationic metallo-porphyrins attractive targets as antitumor drugs. Many studies describe their interaction with DNA and the mechanism by which they induce DNA cleavage. Since porphyrins can be used as anchors for chemically reactive groups, it is possible to modify them to generate a family of compounds with specific functions. In the present work, we used chemical groups such as copper-bipyridinium (Cu-bpy), which hydrolyze phosphodiester bonds, and a porphyrin core to synthesize two novel Cu(2)-bpy-porphyrins. Their interactions with DNA have been characterized using classic spectroscopic methods, and their oxidative and hydrolytic reactivity toward supercoiled plasmid DNA has been studied in vitro. Our results show that Cu(2)-bpy-porphyrins interact with DNA via external association and intercalation and that their ability to cleave DNA and the mechanisms depends on the experimental conditions.

2,2'-Dipyridyl↗

Chromosome painting comparison of Leontopithecus chrysomelas (Callitrichine, Platyrrhini) with man and its phylogenetic position.

Using human probes of whole chromosomes, the homoeologies between human and Leontopithecus chrysomelas (Platyrrhini) karyotypes were established. Thirty-three conserved segments were observed between the two species. Intrachromosomal rearrangements between the two species were identified using hybridization of chromosome arm probes of human chromosomes 1 and 3. We also used chromosomal data to investigate phylogenetic relationships of Callitrichines. These data were encoded using Cebus capucinus , a species which kept fairly ancestral chromosomes, as reference. Two equi-parsimonious trees, including reversion or convergence events, were obtained. The monophyly of Callitrichines is confirmed. They share nine chromosomal rearrangements at least. The Cebuella-Callithrix group forms a clade sharing five rearrangements at least. According to the tree considered, the Tamarins, Leontopithecus and Saguinus share two chromosomal rearrangements restricted to these two taxa or none. Callimico accumulated seven chromosomal rearrangements unshared with other taxa, at least. To avoid convergence and reversion events, we propose the hypothesis of a network (or populational) evolution. Six chromosomal rearrangements would have occurred during the period of this network evolution. Finally, the karyotype of the last common ancestor to all Callitrichines has been reconstructed. It possessed 48 chromosomes.

Animals↗

Highly conserved chromosomes in an Asian squirrel (Menetes berdmorei, Rodentia: Sciuridae) as demonstrated by ZOO-FISH with human probes.

The chromosomes of Menetes berdmorei (Rodentia, Sciuridae, Sciurinae) were studied by ZOO-FISH using whole human chromosome probes. All homoeologies between M. berdmorei and human chromosomes were determined, except for two small chromosome segments. Twelve human chromosomes are conserved in a unique block of synteny; ten are split into two and one into three blocks. Thus, a small number of interchromosomal rearrangements, about twenty, separates human from this squirrel karyotype. Homoeologies between human and the presumed ancestral chromosomes of Sciurinae could also be deduced, as well as those with the presumed ancestral chromosomes of eutherian mammals. Sciurinae chromosomes appear to be much closer to those of non-rodent mammals than those of Muridae and Cricetidae species studied so far. Thus, they provide an interesting tool to link the rodent genome to those of other mammals.

Animals↗

Reconstruction of the ancestral karyotype of eutherian mammals.

Applying the parsimony principle, i.e. that chromosomes identical in species belonging to different taxa were likely to be present in their common ancestor, the ancestral karyotype of eutherian mammals (about 100 million years old) was tentatively reconstructed. Comparing chromosome banding with all ZOO-FISH data from literature or studied by us, this reconstruction can be proposed with only limited uncertainties. This karyotype comprised 50 chromosomes of which 40-42 were acrocentrics. Ten ancestral pairs of chromosomes were homologous to a single human chromosome: 5, 6, 9, 11, 13, 17, 18, 20, X and Y (human nomenclature). Nine others were homologous to a part of a human chromosome: 1p + q (proximal), 1q, 2p + q (proximal), 2q, part of 7, 8q, 10p, 10q and 19p (human nomenclature). Finally, seven pairs of chromosomes, homologs to human chromosomes 3 + 21, 4 + 8p, part of 7 + 16p, part of 12 + part of 22 (twice), 14 + 15, 16q + 19q, formed syntenies disrupted in man.

Animals↗

[Hospital deliveries in Morocco or how to reconcile different logics].

BACKGROUND: In Morocco, the majority of maternal deaths and severe obstetrical complications occurs outside a health structure. If accessibility to a referral hospital is clearly a problem, this problem can be exacerbated by the perception that women and their family have of the quality of care received in these maternity services. The objective of this article is to explore how women who went through a severe obstetrical complication experienced their hospitalisation and to confront this experience with the caregivers'perception. METHODS: This study was carried out in Tetouan and Sidi Kacem between July 1999 and January 2001. Semi-structured individual interviews were held with 94 women who underwent an episode of severe morbidity, 91 family members, as well as 4 focus groups and 53 interviews with health staff members. RESULTS: Though all show gratitude towards the hospital staff for having saved their life, half of the women and their relatives reported problems of behaviour and attitude of the staff: verbal violence, baksheesh, patronage, lack of empathy and discrimination against certain categories of the population. These result from a complex interplay of factors: the stress-load within the profession, the institutional context which by its failures leads to or allows these behaviours and the representations peculiar to each of the players, the providers and the users. CONCLUSION: In order to be professionally more effective, it would be in the caregivers'interest to set up a system of communication that would place the patient back in the centre of hospital care.

Adolescent↗

Development and validation of a high-performance liquid chromatography-mass spectrometry assay for the determination of artemether and its metabolite dihydroartemisinin in human plasma.

A sensitive and selective method is described for the determination of artemether and its active dihydroartemisinin metabolite in human plasma using artemisinin as internal standard. The method consists of a liquid-liquid extraction with subsequent evaporation of the supernatant to dryness followed by the analysis of the reconstituted sample by liquid chromatography-mass spectrometry (LC-MS) in single ion monitoring mode using atmospheric pressure chemical ionization (APCI) as an interface. Chromatography was performed on a C(18) reversed-phase column using acetonitrile-glacial acetic acid 0.1% (66:34) as a mobile phase. The method was fully validated over a concentration range of 5-200 ng/ml using 0.5 ml of human plasma per assay. Stability assessment was also included. The method was applied to the quantification of artemether and its metabolite in human plasma of healthy volunteers participating in pharmacokinetic drug-drug interaction studies.

Antimalarials↗

Neurogenic bladder management and cutaneous non-continent ileal conduit.

STUDY DESIGN: Prospective monocentric follow-up study. OBJECTIVES: To assess the results of cutaneous non-continent diversion for neurogenic bladder management. SETTINGS: Department of Urology (Pitié-Salpétrière Hospital), Department of Neurological Rehabilitation (Raymond Poincaré Hospital), Assistance Publique-Hopitaux de Paris, University Paris VI and V. METHODS: We reviewed the charts of 33 consecutive patients (19 women, 14 men), operated between 1979 and 1999. Twenty-one patients had spinal cord injury (SCI), four had multiple sclerosis, three had various forms of myelitis and five had central neurological diseases. Diversion was indicated for upper urinary tract protection (17), perineal dryness (14) and/or functional or social reasons (20). Before the operation, 20 of the 33 patients (60.6%) presented urologic complications related to bladder management, including triggered micturition, indwelling catheter or intermittent catheterization: urethrocutaneous fistula (4), complicated enterocystoplasty (2), watering pot perineum and severe decubitus ulcerations (14). Ileal conduit (also named ileoureterostomy) was performed alone for 19 patients (57.6%), and in combination with simultaneous cystectomy in 14 patients. We reviewed patient outcome and early and late complications. RESULTS: Mean follow-up was 48 months (1 to 20 years). All problems related to catheters or incontinence had resolved. There were no deaths or early re-operations. Twelve patients (12 out of 33, 36%) had one or more peri-operative complication, including ileus (1), uretero-ileal anastomosis leak (1) and sepsis (1). During follow-up, four of the 19 patients who did not undergo cystectomy developed pyocystitis (3 secondary cystectomies performed between 6 and 56 months). All patients achieved perineal dryness. CONCLUSIONS: The ileal conduit procedure is a safe and well-tolerated procedure in neurologically impaired patients. This procedure is suitable for most neurogenic patients with refractory lower urinary tract dysfunctions.

Adult↗