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Biomedical subjects

F Rey

Publications and source records attributed to F Rey.

At least 55 records · Page 3Linked to original sources
PubMed1994

Environmental asbestotic pleural plaques in northeast Corsica: correlations with airborne and pleural mineralogic analysis.

We report a prevalence study of environmental pleural plaques in subjects over 50 years old from the northeastern Corsican village of Murato, built on asbestos surface deposits. The percentage of plaques was 41%, versus 7.5% in the control village of Vezzani. Although surface deposits contain both chrysotile and tremolite, airborne pollution and asbestos lung burden of exposed inhabitants consist essentially of tremolite as assessed by transmission electron microscopy (TEM). However, TEM analysis of the parietal pleura of three animals bred in exposed areas showed a predominance of short fibers of chrysotile. The respective roles of tremolite and chrysotile in inducing pleural plaques in Corsica should thus be considered.

Aged↗
PubMed1993

Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Part 1: Diagnosis.

BACKGROUND: To compare the diagnostic value of thoracoscopic biopsy, fluid cytology, and Abrams needle biopsy, the authors analyzed prospectively the records of 188 patients with malignant pleural mesothelioma examined between 1973 and 1990. Symptoms were pleural effusion in 173 patients, empyema in 1, spontaneous pneumothorax in 1, and radiologic tumor without effusion in 13. METHODS: Thoracoscopy was performed using a rigid thoracoscope under local anesthesia with neuroleptanalgesia. A total of 10-20 biopsies were taken from the parietal, diaphragmatic, and visceral pleura. Each diagnosis was confirmed by the French panel of mesothelioma pathologists. To prevent parietal seeding, radiation therapy at a dose of 21 Gy was administered during a period of 3 days to all points of entry. RESULTS: Tolerance to thoracoscopy was good. The only complications were subcutaneous emphysema (1 patient), local pleural infection (4 patients), hemorrhage of less than 100 ml (3 patients), and temperature of 38-38.5 degrees C (26 patients). In 137 patients, the cavity was free, and complete endoscopic inspection was achieved. In 51 patients, inspection was limited by adhesions that were severed to obtain biopsy. Nonspecific inflammation was observed in 12 patients (6.5%), nodules in 92 (49%), thickening in 21 (11%), and mixed lesions in 63 (33.5%). Diagnosis was achieved by thoracoscopy in 98% of patients, by fluid cytology in 26%, and by needle biopsy in 21%. CONCLUSION: In most patients, thoracoscopy allows complete visualization of the pleural cavity and provides high-quality biopsy samples. The diagnostic accuracy of thoracoscopy is similar to open thoracotomy, but the procedure is far less invasive, usually requiring that the patient remain in the hospital only 1 day.

Evaluation Studies as Topic↗
PubMed1993

Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Part 2: Prognosis and staging.

BACKGROUND: Thoracoscopy appears to be essential in identifying tumors at the beginning of pleural disease. METHODS: Between 1973 and 1990, diagnostic thoracoscopy was carried out in a prospective series of 188 patients with malignant pleural mesothelioma (MPM). Biopsy samples were obtained in all cases, and diagnosis was confirmed by the French panel of mesothelioma specialists. In all patients we noted the degree of involvement of the parietal, diaphragmatic, or visceral pleura, and classified patients according to the Butchart system: Stage I (66 patients), II (110 patients), III (4 patients), and IV (8 patients). To assess prognostic factors, a multivariate analysis of clinical and endoscopic findings was performed according to the Cox model. RESULTS: The most favorable factors were absence of weight loss at the time of diagnosis, absence of involvement of the visceral pleura, Butchart Stage I, and epithelial histopathologic type. When Stage I patients were subdivided into two groups according to whether or not they displayed involvement of the visceral pleura, a significant difference in survival was noted (32.7 months versus 7 months, respectively; P < 0.001). CONCLUSIONS: Based on these findings, we propose to divide Butchart or Mattson Stage I into two subgroups, i.e., Stage IA in which only the parietal or diaphragmatic pleura is involved and Stage IB in which the visceral pleura is invaded. In the International Union Against Cancer (UICC) classification, T1 should be used for tumors restricted to the parietal or diaphragmatic pleura and T2 for tumors with additional involvement of the visceral pleura.

Adult↗
PubMed1993

Intrapleural immunotherapy with escalating doses of interleukin-2 in metastatic pleural effusions.

BACKGROUND: The authors assessed the tolerance and efficacy of intrapleural interleukin-2 (IL-2) in patients with malignant effusion. METHODS: Twenty-three patients had a total of 25 metastatic pleural effusions; the patients were treated with recombinant IL-2 by means of a continuous intrapleural infusion for 5 days. The daily dosage used in this Phase I/II trial initially was 3 x 10(6) IU/m2/day; the dosage was increased with every third patient, culminating in a dosage of 24 x 10(6) IU/m2/day. RESULTS: One patient who had received the highest dosage died of renal failure on day 8. Ninety-six percent of patients had Grade 2-3 fever, which was easily controlled with paracetamol administration. Two (8%) patients had pleural empyema. All other side effects were mild and resolved spontaneously by the end of treatment. The objective response rate was 21.7%. The five patients who responded to IL-2 therapy were alive 7-24 months after treatment, and the survival rate of the whole group was 59% after 13 months. CONCLUSION: A daily dose of 10-24 x 10(6) IU/m2/day of IL-2 administered intrapleurally gave response rates similar to those reported in the literature using the intravenous route, but a much lower morbidity rate was recorded.

Adenocarcinoma↗
PubMed1993

Illegitimate transcription of the phenylalanine hydroxylase gene in lymphocytes for identification of mutations in phenylketonuria.

Taking advantage of the 'illegitimate' transcription of the phenylalanine hydroxylase (PAH) gene, we have been able to analyse the PAH cDNA sequence of hyperphenylalaninemic children in circulating lymphocytes. Using this approach, we have also identified 3 novel mutations in cDNA from liver and lymphocytes of two patients. One mutation, detected by the abnormal pattern of migration of an amplified fragment, is a C to T transition in the splice acceptor site of intron 10, which resulted in the skipping of exon 11 with the premature termination of RNA translation downstream from exon 12 (-3 IVS10). The other two mutations are missense mutations in exons 10 and 11 (respectively, L333F and E390G). The present study supports the view that circulating lymphocytes give easy access to PAH gene transcripts whose nucleotide sequence is identical to that reported in liver and therefore represent a useful tool for molecular genetic studies in phenylketonuria.

Amino Acid Sequence↗
PubMed1993

Genetic background of clinical homogeneity of phenylketonuria in Poland.

In order to elucidate the clinical homogeneity and severity of the hyperphenylalaninaemias in Poland, a total of 71 children with typical phenylketonuria (PKU) originating from western and northern Poland were screened for 13 mutations in the phenylalanine hydroxylase (PAH) gene. Eighty percent of all PKU alleles tested were found to carry an identified mutation. One mutation, namely the R408W mutation, accounted for more than 63% of mutant PAH alleles in Poland, the other 27% being accounted for by six mutations: IVS12nt1 (5%), IVSnt546 (5%), Y414C (4%), R252W (1.5%), R261Q (< 1%), and G272ter (< 1%). The predominance of the R408W mutation resulted in a high rate of homozygotes (35.2%) and compound heterozygotes for this mutation in children from western and northern Poland. The frequency and deleterious nature of this mutation probably accounts for the clinical homogeneity and severity of the hyperphenylalaninaemias in Poland. In addition, the high rate of the R408W mutation and its association with mutant haplotype 2 at the PAH locus in Poland give additional support to the Balto-Slavic origin of this mutant gene.

Base Sequence↗
PubMed1993

[Malignant mesothelioma: study of prognostic factors in a series of 188 cases].

From 1973 to 1990, 188 patients with pleural malignant mesothelioma entered a prospective study of this disease to assess the main prognostic factors. All had undergone thoracoscopy with endoscopic description of lesions, and multiple biopsies. The diagnostic yield of thoracoscopy was 98.4%. Multivariate analysis of main clinical, histopathological, endoscopic and radiological (including CT-scan) parameters was performed according to Cox's model. The most favorable factors were: absence of weight loss at the time of diagnosis, absence of involvement of the visceral pleural, Butchart stage I and epithelial histopathological type. Thoracoscopy allowed early diagnosis of the disease and a subdivision of Butchart stage I into stage IA (with normal visceral pleura) and stage IB (with invaded visceral pleural): median survivals are 32.7 and 7 months respectively. Like CT scan, thoracoscopy is therefore necessary in the staging of malignant mesothelioma.

Adult↗
PubMed1993

[Environmental mesotheliomas in northeast Corsica].

Since 1980, we have collected fourteen cases of mesothelioma induced by environmental exposure to asbestos, going back to childhood in patients from north-east Corsica, in a region which was remote from the asbestos mine of Canari. There were eight men and six women with a mean age of 69.5 +/- 4 years. Six patients presented with bilateral calcified pleural plaques as evidence of environmental exposure. The mineral analysis carried out on five patients (four had thoracoscopies and one an alveolar lavage), showed a moderate deposit of chrysotile (0.3 to 3.4 x 10(6) fibres per gram of dry tissue), and elevated level of tremolite (1.4 to 62 x 10(6) fibres/g). The ambient dosage of asbestos has confirmed the existence of environmental pollution by chrysotile fibres and above all by tremolite. In addition, the same type of fibres have been identified in the parietal pleural of animals subjected to the same risk. In this region, the risk is estimated, on the basis of our results, as 10 cases of mesothelioma per 100,000 inhabitants per year.

Adult↗
PubMed1993

Environmental pleural plaques in an asbestos exposed population of northeast Corsica.

The purpose of this study was to determine whether the inhabitants of villages environmentally exposed to asbestos, in northeast Corsica, had a higher incidence of pleural plaques. X-rays were obtained from subjects aged over 50 yrs, with no occupational exposure to asbestos or history of pleural disease, in one village exposed to asbestos, Murato, and a nonexposed, control village, Vezzani. In addition, the mineral content of the air and parietal pleura of animals in the exposed zone was studied, using transmission electron microscopy. The incidence of bilateral pleural plaques in the exposed population was 41%, as compared to 7.5% in the nonexposed population (p < 0.00001). The levels of airborne tremolite were higher in Murato (6-72 ng.m-3) than in Vezzani (< 1 ng.m-3), but chrysotile levels were similar. Significant numbers of chrysotile and tremolite fibres were identified in the parietal pleura of animals from the exposed village. This study confirms the well-known correlation between bilateral pleural plaques and environmental exposure to low levels of asbestos.

Aged↗
PubMed1992

Protein engineering of xylose (glucose) isomerase from Actinoplanes missouriensis. 1. Crystallography and site-directed mutagenesis of metal binding sites.

The structure and function of the xylose (glucose) isomerase from Actinoplanes missouriensis have been analyzed by X-ray crystallography and site-directed mutagenesis after cloning and overexpression in Escherichia coli. The crystal structure of wild-type enzyme has been refined to an R factor of 15.2% against diffraction data to 2.2-A resolution. The structures of a number of binary and ternary complexes involving wild-type and mutant enzymes, the divalent cations Mg2+, Co2+, or Mn2+, and either the substrate xylose or substrate analogs have also been determined and refined to comparable R factors. Two metal sites are identified. Metal site 1 is four-coordinated and tetrahedral in the absence of substrate and is six-coordinated and octahedral in its presence; the O2 and O4 atoms of linear inhibitors and substrate bind to metal 1. Metal site 2 is octahedral in all cases; its position changes by 0.7 A when it binds O1 of the substrate and by more than 1 A when it also binds O2; these bonds replace bonds to carboxylate ligands from the protein. Side chains involved in metal binding have been substituted by site-directed mutagenesis. The biochemical properties of the mutant enzymes are presented. Together with structural data, they demonstrate that the two metal ions play an essential part in binding substrates, in stabilizing their open form, and in catalyzing hydride transfer between the C1 and C2 positions.

Actinomycetales↗
PubMed1992

Linkage disequilibrium between phenylketonuria and RFLP haplotype 1 at the phenylalanine hydroxylase locus in Portugal.

RFLPs of 36 normal and 41 mutant alleles at the phenylalanine hydroxylase locus were determined in 31 Portuguese kindreds. A total of 14 haplotypes including 10 normal and 7 mutant alleles were observed. Almost 75% of all mutant alleles were confined within only two haplotypes, namely haplotype 9 (17.1%) and haplotype 1 (56.1%). This frequency of mutant haplotype 1 in Portugal is, to our knowledge, the highest for this mutant haplotype in all studies reported to date. Other mutant haplotypes were either rare (haplotype 2, 9.7%) or totally absent (haplotype 3, 0%). Only 24.5% of all mutant alleles were found to consistently carry identified mutations, particularly R261Q (9.8%), R252W (3.3%), R408W (1.6%) and delta I94 (3.3%). A new mutation, L249F, located in the seventh exon of the gene, accounted for 6.5% of all mutant alleles in our series. Interestingly, this mutant genotype was consistently associated with mutant haplotype 1 (P less than 0.01), as also observed for the R261Q mutation. It appears, therefore, that mutant haplotype 1 is genotypically heterogeneous in Portugal and that more than two mutations account for its prevalence in this country.

Alleles↗
PubMed1992

Follicle-stimulating hormone bioactivity in idiopathic normogonadotropic oligoasthenozoospermia: double-blind trial with gonadotropin-releasing hormone.

OBJECTIVE: To identify, among patients with idiopathic normogonadotropic oligoasthenozoospermia, those with low bioactive follicle-stimulating hormone (FSH), possibly because of inadequate gonadotropin-releasing hormone (GnRH) pulsatility, whose bioactive FSH and sperm could be improved by GnRH treatment. DESIGN: Randomized, double-blind, placebo-controlled trial with intranasal (IN) GnRH, followed by open GnRH treatment. SETTING: Outpatient endocrinology clinic. PATIENTS: Twenty-eight infertile men with idiopathic normogonadotropic oligoasthenozoospermia. INTERVENTIONS: Gonadotropin-releasing hormone or placebo was self-administered IN every 2 hours. MAIN OUTCOME MEASURES: Serum immunoreactive and bioactive FSH and semen analyses. RESULTS: Ten men showed a low basal FSH bioactive/immunoreactive ratio, which increased in 5 of them under GnRH without parallel sperm modification. Sperm improvements were observed in 10 patients with no parallel evolution of FSH bioactive/immunoreactive ratio. Unpredicted by sperm changes, three pregnancies developed on placebo and 5 on GnRH. CONCLUSIONS: Low bioactive FSH was not the cause of idiopathic normogonadotropic oligoasthenozoospermia in our patients and could not predict response to GnRH. Pulsatile GnRH did not improve sperm beyond random fluctuations.

Administration, Intranasal↗
PubMed1992

Pulsatile secretion of gonadotropins and prolactin during the follicular and luteal phases of the menstrual cycle: analysis of instantaneous secretion rate and secretory concomitance.

OBJECTIVE: To characterize the pulsatile secretions of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) during the menstrual cycle and to statistically evaluate their secretory concomitance. DESIGN: Pulsatility study performed during the midfollicular and midluteal phases of a same menstrual cycle, blood samples being collected every 10 minutes for 6 hours. SETTING: Participants investigated in the Division of Endocrinology, University Hospital. PARTICIPANTS: Nine healthy women (22 to 38 years) with regular menstrual cycles. MAIN OUTCOME MEASURES: Plasma LH, FSH, and PRL values were analyzed as raw and deconvoluted data, and the specific (nonrandom) secretory concomitance was evaluated statistically. RESULTS: The pulsatile secretion of LH was confirmed, and that of FSH and PRL was clearly established during both phases of the cycle by characterization of peak frequency, period, and amplitude. A specific secretory concomitance was assessed between LH and FSH in the follicular but not the luteal phase, and a tight concomitance between LH and PRL was demonstrated during both phases. CONCLUSIONS: These results are supportive of significant pulsatile secretions of the three hormones during the menstrual cycle, and they are demonstrative of a definite copulsatility of these hormones, suggestive of common regulatory factors in the complex temporal patterns of gonadotropin and PRL secretions along the cycle.

Adult↗
PubMed1992

[Phenotypic expression of 12 mutations of the phenylalanine hydroxylase gene].

BACKGROUND: Several mutations in the human phenylalanine hydroxylase (PAH) gene have been described and it may be interesting to tentatively correlate mutant genotypes and clinical phenotypes of phenylketonuria (PKU). METHODS: Twelve mutations were searched for using classical techniques of molecular biology in a total of 126 patients. 3 phenotypes were arbitrarily defined: typical PKU, atypical PKU or Mediterranean form, and persistent mild hyperphenylalaninemia. The patients were classified according to the residual in vivo PAH activity. RESULTS: Mutations were found in 64 patients. One mutation was found in each of the 2 alleles in 20 children. Only one mutation could be identified in the other 44. Only 45 children could be assigned to a phenotype. Mutations leading to total loss of PAH activity were associated with typical PKU (in homozygotes or compound heterozygotes). Mutations leading to residual PAH activity were associated in homozygotes with atypical PKU; they were also associated in compounded heterozygotes with atypical PKU, irrespective of the fact that the other allele suppressed enzyme activity or was unknown. A mutation which changed the affinity of PAH for phenylalanine was associated with mild hyperphenylalaninemia. CONCLUSION: The clinical heterogeneity of PKU can be correlated with identified mutations of the human PAH gene. Molecular studies do not help to predict either the phenotype or the long-term outcome. However, description of the biochemical changes combined with identification of the mutation should lead to a better understanding of consequences of mutation for PAH activity.

Child↗
PubMed1992

[Intellectual development after relaxing the diet at the age of 5 years in typical phenylketonuria].

BACKGROUND: No satisfactory controlled trial has yet been completed on typical phenylketonuria (PKU) patients whose treatment was relaxed at the age of 5 years. METHODS: 27 children having typical PKU were treated before the age of 3 months. The intake of phenylalanine and protein was carefully regulated during the first 5 years of life, after which the treatment was relaxed. All children were evaluated after at least 6 years on the relaxed diet. Their IQ scores and school performance were related to the degree of dietary control and plasma phenylalanine values. RESULTS: The IQ scores at 5 years of age were 100 +/- 10.8. Continued evaluation showed that IQ scores remained unchanged. Poor school performance was twice as frequent as in general population; the deficit in the IQ score of this group was 8 points below that of normal sibs. There was no correlation between plasma phenylalanine and the IQ score after the age of 5 years. The positive control decreased with aged. CONCLUSIONS: Children with typical PKU have an IQ deficit relative to their normal sibs just before relaxing treatment. Good dietary control until 5 years of age, maternal intelligence and continuing evaluation during relaxing diet are the best conditions for optimal intellectual progress. There is no evidence that continued treatment during adolescence is beneficial.

Child Development↗
PubMed1992

[Malignant mesothelioma: prognostic factors in a series of 125 patients studied from 1973 to 1987].

A continuous series of 125 patients hospitalized between 1973 and 1987 with pleural malignant mesothelioma were the subjects of this stepwise analysis. A diagnostic thoracoscopy was carried out in every patient and the histopathological diagnosis confirmed by the French Mesothelioma Panel of Pathologists. The main characteristics of the patients were: mean age 64 +/- 1 year, 104 male, 21 female; previous asbestos exposure was present in 98. The histopathological type was epithelial in 90, mixed in 22, fibrosarcomatous in 13. The endoscopic aspect was analysed in the same manner from the beginning as follows: involvement of the parietal, diaphragmatic or visceral pleura; extension of the tumor into the pleural cavity, macroscopic aspects of the lesions. According to the Butchart's classification 56 patients were at stage I, 61 at stage II, 3 at stage III, 5 at stage IV. A multivariate analysis (Cox model) showed that the best prognostic factor is the stage I which can be divided in 2 subtypes: exclusive involvement of the parietal and diaphragmatic pleura without invasion of the visceral pleura: stage IA (median survival 31.2 months). It is 6.75 months as soon as the visceral pleura is invaded (stade IB).

Aged↗