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R Combes

Publications and source records attributed to R Combes.

At least 19 recordsLinked to original sources
PubMed2004

[Estimating the specificity of a University Hospital Centre. Example of the colonoscopy (EPAGE survey)].

OBJECTIVE: The specificity of a University Hospital Centre is usually assessed from its teaching and research capacity. The EPAGE survey, an instrument used to help decision making available on the Internet, permitted us to compare the prescription of a routine exploration, gastrointestinal endoscopy, between the University Hospital Center in Clermont-Ferrand and the Hospital Centre in Moulins. The aim was to demonstrate the differences in daily practice between these two geographically close hospital centres and hence to underline the specificity of a University Hospital Centre that is not taken into account in the financing systems of such hospitals. Method The data collected were taken from the EPAGE trial, a prospective mutlicentre study that included 21 European and Canadian centres. Data was collected from the University Hospital centre in Clermont-Ferrand over two periods: from December 2000 to March 2001, then from December 2001 to February 2002, and from the Hospital Centre in Moulins, from December 2000 to the end of November 2001. For this Article, only the patients' characteristics, indications for gastrointestinal endoscopy and opportunity rate were analysed. Comparison of patients' categories from the 2 centres was conducted according to their DRG (diagnostic related group) (homogeneous patient group) classification, thus allowing calculation of the mean of the SIA (synthetic index of activity) points in the two centres. RESULTS: 221 cases of gastrointestinal endoscopy performed in the University Hospital centre and 292 in the Hospital Centre were included in the survey. No statistically significant difference was found in the reasons motivating a gastrointestinal endoscopy, with regard to the indications listed on the EPAGE website. There were 18% of unlisted indications in the University Hospital Centre versus 4.8% in the Hospital Centre (p<1.10-6). Using the DRG nomenclature, calculation of the mean SIA points at the University Hospital Centre per patient was of 1161 versus 1147: non significant deviation of 1.2% in favour of the University Hospital Centre. DISCUSSION: - Conclusion The difference in reasons motivating a gastrointestinal endoscopy found between the two centres concerned rare, complex or innovating situations. This illustrates the role of a Regional Reference University Hospital Centre, an aspect clearly underestimated when measuring mixed cases according to the HPG. Study of the financing and/or information systems is warranted and might resolve the apparent underestimation of the current financing system.

Adult↗
PubMed2000

Prospects for reducing and refining the use of dogs in the regulatory toxicity testing of pharmaceuticals.

A workshop was held to critically discuss the need for a nonrodent species and the role of the dog in regulatory toxicity testing of pharmaceuticals; to discuss opportunities to reduce and refine the use of dogs in preclinical toxicology; and to identify a number of specific recommendations which could be feasibly achieved to move the process forward. To facilitate a preliminary evaluation of the contribution of dog studies to the risk assessment process, anonymised, unpublished data were provided from fully evaluated, repeat-dose toxicity studies in the rat and dog. Results of the International Life Sciences Institute (ILSI) Human Toxicity Project were also presented and discussed. Analysis of the data demonstrated that the dog can provide additional toxicity information, which, in some cases, was shown to be predictive for humans. Discussions indicated that there is potential for achieving a reduction in dog use and several possible approaches were identified. To further the progress of this initiative, there is a need to collate the results of pharmacology, toxicology, and clinical studies to address some of the proposed approaches. One of the outcomes of the workshop will be the establishment of a steering group to co-ordinate data collation for further analysis.

Animal Testing Alternatives↗
PubMed1998

The effectiveness of Salmonella strains TA100, TA102 and TA104 for detecting mutagenicity of some aldehydes and peroxides.

Several aldehydes and peroxides were tested for mutagenicity using Salmonella typhimurium tester strains TA97a, TA100, TA102 and TA104, in the presence and absence of Aroclor-induced liver S9 mix from F344 rats and B6C3F1 mice, in either preincubation or vapour phase protocols. Some chemicals were tested in additional Salmonella strains. Benzaldehyde, butyraldehyde, benzoyl peroxide, 4-chlorobenzaldehyde, isobutyraldehyde, propionaldehyde and veratraldehyde were non-mutagenic. Acetaldehyde and dicumyl peroxide gave inconsistent results and furfural gave equivocal responses in TA100 and TA104. Cumene hydroperoxide, formaldehyde and glutaraldehyde were mutagenic in TA100, TA102 and TA104. trans-Cinnamaldehyde exhibited a weak mutagenic response in TA100 with mouse liver S9 only. 2,4,5-Trimethoxybenzaldehyde was mutagenic only in strain TA1538 with rat liver S9. With the exception of butanone peroxide, which was mutagenic only in TA104, all chemicals mutagenic in strains TA102 and/or TA104 were also mutagenic in TA100. The data do not, therefore, support the preferential use of strains TA102 and TA104 for screening aldehydes and peroxides for mutagenicity. For a number of these chemicals the advantages of using TA102 or TA104 was in the increased responses compared with those obtained with TA100. Two of the four peroxides were mutagenic and one of these was mutagenic only with TA104. This suggests that strains TA102 and TA104 be used if peroxides are not mutagenic in TA100 or TA97.

Aldehydes↗
PubMed1995

[Diagnosis of colitis caused by cytomegalovirus infection in AIDS. Comparative value of total colonoscopy and rectosigmoidoscopy (apropos of 24 cases). AIDS GIT].

OBJECTIVES: To evaluate the respective diagnostic value of flexible rectosigmoidoscopy and colonoscopy in the cytomegalovirus colitis. METHODS: Twenty-four patients with AIDS were studied retrospectively. The entry criteria were: flexible rectosigmoidoscopy or colonoscopy, with 2 rectal and 2 caecal biopsies, presenting cytomegalovirus inclusions bodies linked to an inflammation at least on one colonic biopsy. RESULTS: Twenty-four patients had 29 colonoscopies. In 16 cases colonoscopy was performed to the caecum. The endoscopic findings of the 16 full colonoscopies were: 7 right colitis, 5 diffuse colitis, 2 bisegmentary colitis, 1 proctitis and 1 non endoscopic lesion. The histologic findings of the 16 full colonoscopies were: 5 cytomegalovirus inclusions on rectal biopsies and 16 on caecal biopsies. For the 13 incomplete colonoscopies, 11 had inclusions on rectal biopsies. So the flexible rectosigmoidoscopy was not sufficient to find inclusions 13 times out of 29. CONCLUSION: Our study indicates that in the cytomegalovirus colitis, inclusions predominate in the caecum, isolated right colitis exists and extra-colonic cytomegalovirus disease is not always found. For these reasons full colonoscopy is necessary for diagnosis in patients with normal flexible rectosigmoidoscopy.

AIDS-Related Opportunistic Infections↗
PubMed1994

Activation by caecal reduction of the azo dye D & C red no. 9 to a bacterial mutagen.

D & C Red No. 9 is a monoazo dye used for manufacturing printing inks, rubber and plastics, and as an additive in cosmetics and drugs. In an NTP carcinogenicity study in rats and mice it induced splenic sarcomas and liver nodules in male rats; no chemical-related tumours were induced in mice. On the basis of its contradictory responses in a range of in vitro tests and its inactivity in several in vivo genotoxicity assays, it has been suggested that the dye may act as a non-genotoxic carcinogen. We tested the dye in the Salmonella mutagenicity assay using several different protocols. The dye was not mutagenic when tested using the standard (aerobic) preincubation protocol. Variable responses were seen when the flavin mononucleotide (FMN) reduction protocol was used. A third protocol was provided by incubating the test compound overnight with a rat caecal preparation under anoxic conditions to reduce the azo bond. Ethyl acetate extracts of this incubation mixture, when tested in the standard preincubation protocol using induced rat liver S9, yielded dose-related mutagenic responses in TA100, and a weak response in TA98. The presuemed major reduction product, 1-amino-2-naphthol (1-A-2-N) was mutagenic to TA100, but not TA98, in standard protocols with S9. The results show that it is necessary to use a protocol in which D & C Red No. 9 is reduced in order to demonstrate the mutagenicity of this dye. The non-genotoxicity previously reported for D & C Red No. 9, may have been due to insufficient reductive cleavage.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerobiosis↗
PubMed1992

Ozone is mutagenic in Salmonella.

Ozone is a highly reactive gas that has been tested for genotoxicity in a number of systems. Induced genetic damage resulting from ozone treatment may not be readily observed because of the high toxicity of the chemical and difficulties in generating and administering controlled concentrations. The mutagenicity of ozone was investigated in Salmonella typhimurium using a plate test protocol designed for reactive vapours and gases. Ozone, at two to three consecutive doses, induced weak, albeit statistically significant, mutagenic responses in tester strain TA102 with and without Aroclor-induced rat liver S9 (lowest effective mean concentration of 0.019 ppm; 35 min total exposure). However, dose-related responses were not always obtained. No mutagenicity was detected in strains TA98, TA100, or TA1535, with or without S9. In strain TA104, ozone induced a weak response only at a single dose with S9; this response was not reproducible. Mutagenicity was dependent on the ozone flow rate and total exposure time, with variations in the optimum dose-time regimen leading to toxicity or complete inactivity. The data show that ozone is a very weak bacterial mutagen and only when tested under narrowly prescribed, subtoxic dosing conditions.

Animals↗
PubMed1992

The role of glutathione in the bacterial mutagenicity of vapour phase dichloromethane.

Dichloromethane (DCM) vapour by inhalation is carcinogenic to rodents and is an in vivo rodent cell clastogen and a bacterial mutagen. It has been suggested that the bacterial mutagenicity of DCM is mediated by glutathione (GSH) conjugation. The involvement of endogenous and exogenous GSH in the conversion of DCM to a bacterial mutagen has been studied in a vapour phase protocol using wild-type and GSH-deficient (NG54; gsh) Salmonella typhimurium TA100 strains in the presence and absence of various rat liver fractions. The effect of the duration of exposure was also investigated in these Salmonella strains and in E. coli WP2 uvrA pKM101. Dose- and time-related increases in revertants occurred with all metabolic activation systems used (without exogenous metabolic activation; with Aroclor-induced rat liver S9, microsomes, or cytosol fractions), with minor quantitative differences among the 3 strains. Mutagenicity was marginally highest in the presence of cytosol at the highest DCM concentrations. Strain NG54 gsh, which contains approximately 25% of the TA100 level of GSH/microgram protein, was slightly less responsive to DCM-induced mutagenicity than TA100. Addition of 0.33 mumoles/plate of GSH had little effect on the mutagenic responses of TA100 or NG54 in the presence or absence of S9. In these 2 strains, exogenous S9 produced small increases in mutagenicity at the highest concentrations of DCM (2 and 4% v/v). These results suggest that if an interaction between DCM and GSH is required for the activation of DCM to a bacterial mutagen, it occurs at low levels of endogenous GSH and is not significantly affected by GSH supplementation.

Animals↗
PubMed1979

[Pituitary microadenoma of Cushing's disease. Course following transsphenoidal excision. Four cases (author's transl)].

Transsphenoidal microsurgery was performed in four patients with a pituitary microadenoma who presented Cushing's disease. Preoperative features were the following: 1) Clinical and laboratory signs of hypercortisolism 2) No radiological evidence of an adrenal tumor 3) Normal or increased ACTH plasma levels 4) Sellar tomograms suggesting the presence of a pituitary microadenoma in only one case. Postoperative outcome after 3 to 30 months follow-up showed persistence or even improved reactivity of the various pituitary functions and especially the early occurence of corticotropin deficiency in all 4 patients. This isolated deficiency regressed spontaneously after 6 and 12 months (2/4 cases). Twenty-four hour studies of ACTH and cortisol profiles and dexamethasone suppression as well as response to metyrapone confirmed the resumption of physiological corticotropin regulation.

Adenoma↗