Biomedical subjects

R Favre

Publications and source records attributed to R Favre.

At least 55 records · Page 3Linked to original sources

PubMed1998

Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) proteolysis in patients with colorectal cancer: possible association with the metastatic potential of the tumor.

The limited proteolysis of insulin-like growth factor (IGF)-binding protein (IGFBP)-3 is a key event in the regulation of endocrine bioavailability of IGFs. Here, we investigated IGFBP-3 and IGFBP-3 proteolysis in serum from patients with colorectal cancer both before and at different times following surgery. In vivo IGFBP-3 proteolysis, estimated by immunoblot analysis of IGFBP-3 fragments in serum, and in vitro IGFBP-3 protease activity of serum, estimated by a 125I-IGFBP-3 degradation assay, allowed us to identify 2 groups of patients (IGF-M vs. IGF-NM) with respect to their status for mobilizing the IGF system. In IGF-M patients, in vivo and in vitro IGFBP-3 proteolysis were significantly elevated (156% and 181% of the age-matched control pool, respectively) and accompanied by a decrease in intact IGFBP-3 (38% of the control pool). The IGFBP-3 proteolytic processing was further increased in response to surgical ablation of the tumor (mean increase 45-55%), then gradually returned to levels comparable with controls. In contrast, IGF-NM patients exhibited a minimal alteration of in vitro IGFBP-3 protease activity and even an inhibition of in vivo IGFBP-3 proteolysis, whereas intact IGFBP-3 was unaltered when compared with controls. Moreover, this pattern was not further significantly altered in response to the surgical stress. None (0/6) of the IGF-M patients vs. 70% (5/7) of the IGF-NM patients developed a metastatic disease (median duration of follow-up 26 months). Neither elevated amounts of pro-IGF-II nor presence of detectable IGFBP-3 protease inhibitors in the circulation could explain the observed suppression of IGFBP-3 proteolytic processing in IGF-NM patients. These results indicate that inhibition of IGFBP-3 proteolysis and invasive properties of cancer cells are related in colorectal cancer patients.

Adenocarcinoma↗

PubMed1998

Immuno-cross-reactivity of CUT-1 and cuticlin epitopes between ascaris lumbricoides, Caenorhabditis elegans, and Heterorhabditis.

Cuticlin is the insoluble residue of nematode cuticle. It has been proved that cuticlin and CUT-1-like epitopes are conserved between the free-living Caenorhabditis elegans and the entomopathogenic nematode Heterorhabditis sp. The cloning of a cut-1 homologous gene from the animal intestinal parasite Ascaris lumbricoides has allowed us to extend the study of immuno-cross-reactivity at the ultrastructural level to this important species. Antibodies against recombinant CUT-1 protein and against cuticlin from Ascaris as well as from C. elegans were used for immuno-labeling ultrathin sections of high-pressure cryoprocessed worms. All the antisera used showed the same specific pattern of localization on sections of C. elegans of Heterorhabditis dauer larvae, and of Ascaris larvae in mature eggs. It was also shown that sera raised against the cuticlin residue contain anti-CUT-1 antibodies. CUT-1-like proteins are thus possibly important components in the immune response of hosts to invading nematodes. The results presented support the use of C. elegans as a model for the study of vertebrate parasitic nematodes.

Animals↗

PubMed1998

[Chondrosarcoma in nasal fossae and Maffucci's syndrome].

INTRODUCTION: Maffucci's syndrome is a congenital non-hereditary disease very similar to Ollier's disease and associates multiple cutaneous hemangiomas, dyschondroplasia and often enchondromas. EXEGESIS: We report a unique case involving synchronous localization of chondrosarcoma in nasal fossae and anterior chest wall, disclosing Maffucci's syndrome. CONCLUSION: Atypical chondrosarcoma localization must lead to further investigation of potential multiple enchondromatosis.

Adult↗

PubMed1998

[Importance of micronucleus tests in cultured binuclear T lymphocytes for the detection of genotoxic events in cancer patients].

The cytokinesis-blocked micronucleus assay (CBMN) is a short-term mutagenesis test which offers an easier and less tedious alternative to metaphase chromosome analysis, with the advantage that exposure to both clastogens and aneugens may be detected. The CBMN assay has been used in evaluating the genotoxic consequences of exposures to environmental and occupational mutagens and carcinogens. Micronucleated cell rates (MN cell rates) were assessed in cytokinesis-blocked lymphocytes of 70 male and female cancer patients prior to any anticancer treatment. The study of interindividual variation factors showed that only age significantly affect MN cell rate, whereas sex, tobacco, alcohol, imaging techniques and tumour stage had no significant effect. The comparison of micronucleated cell rates in 198 healthy subjects and 70 cancer patients matched for age and sex showed a statistically significant difference. Spontaneous elevated MN cell rates of cancer patients refer to previous exposition of genotoxic or mutagenic environmental agents. Moreover, the MN cell rates in cancer patients most probably refers to various cellular lesions and genetic damages.

Adult↗

PubMed1997

Bimonthly high dose leucovorin and 5-fluorouracil 48-hour continuous infusion in patients with advanced colorectal carcinoma. Groupe d'Etude et de Recherche sur les Cancers de l'Ovaire et Digestifs (GERCOD).

BACKGROUND: It has been suggested that there is a relationship between 5-fluorouracil (5-FU) dose levels and response rates. A bimonthly 2-day regimen of leucovorin (LV) and 5-FU bolus plus infusion has been found to be superior to a monthly 5-FU bolus with low dose LV. Based on these reports, a first-line Phase II study was performed in 101 patients with advanced colorectal carcinoma who were given a bimonthly combination of high dose LV and a high dose 48-hour infusion of 5-FU. METHODS: The selected regimen included a 2-hour infusion of LV, 500 mg/m2, on each of 2 consecutive days and a 48-hour infusion of 5-FU, 1.5 to 2 g/m2/24 hours starting after Day 1 of LV treatment every 2 weeks until there was evidence of disease progression. Evaluation was performed every six cycles. This study reports the treatment of 101 patients with measurable disease. RESULTS: World Health Organization toxicity Grade 3-4 occurred in 15% of patients, nausea in 2%, diarrhea in 5.1%, mucositis in 4%, neutropenia in 4% (Grade 4: 2%), hand-foot syndrome in 2%, alopecia in 4%, and encephalopathy in 1%. The overall response rate was 33.7%. Five patients had a complete response (5%), and 29 had a partial response (28.7%). In 45 patients disease was stable (44.6%), and in 19 patients there was disease progression (18.8%). Three patients (3%) could not be evaluated. The median progression free survival was 8 months and median survival was 18 months. CONCLUSIONS: In the current study, bimonthly high dose LV and a high dose 48-hour infusion of 5-FU had activity in patients with advanced colorectal carcinoma. Toxicity is notably low, and the regimen is suitable for use in combination with other drugs.

Adenocarcinoma↗

PubMed1997

A Bayesian dosing method for carboplatin given by continuous infusion for 120 h.

Carboplatin (CBDCA), an analogue of cisplatin, exhibits reduced toxicity but wide interpatient variability of its pharmacokinetic parameters. Individualization of the CBDCA dose is therefore necessary. Although various formulas have been developed for this purpose, major side effects have been reported on CBDCA administration by short-term infusion (0.5 or 1 h). We therefore propose a new schedule of CBDCA administration. Instead of a dosing method based on the estimation of renal function when a classic administration schedule is used, we propose a pharmacokinetic dosing method (Bayesian method), whereby CBDCA is given by continuous infusion for 120 h. First, CBDCA was given to 21 patients to determine the population pharmacokinetic parameters of carboplatin. Then, on the basis of total platinum plasma concentration measurements and Bayesian estimation of pharmacokinetic parameters, it was possible to individualize the CBDCA dose within the first 24 h of the infusion. This new protocol for CBDCA administration was evaluated in 36 new patients (60 courses). Three theoretical end points at the end of the infusion were considered. For a given theoretical end point, 20 courses were taken into account. The theoretical end points (i.e., 1, 1.5, and 1.8 mg/l) were compared with the concentrations measured at the end of the infusion, which were 0.99 +/- 0.10, 1.41 +/- 0.13, and 1.72 +/- 0.20 mg/l, respectively. This Bayesian dosing method can easily be used in clinical practice, and the determination of predictive performances has shown that the method is precise and unbiased. With no more toxicity or practical difficulties than those produced by other methods, and with acceptable tolerance, it was possible to reach a median dose that was 20% higher than the usual dose (484 +/- 190 mg/m2 as compared with 400 mg/m2). In conclusion, this new schedule of CBDCA administration appears to be interesting in terms of tolerance. However, new studies are required to confirm that this new scheme leads to equal or better efficacy than the classic protocol.

Adult↗

PubMed1997

Comparison between micronucleated lymphocyte rates observed in healthy subjects and cancer patients.

Micronucleated cell rates were assessed in cytokinesis-blocked lymphocytes of 198 male and female healthy subjects (HS) not occupationally exposed to genotoxic risks and of 70 male and female cancer patients (CP) prior to any anticancer treatment. In the HS group, spontaneous micronucleated cell rates (MN cell rates) were 9.7 +/- 2.8 per 1000 binucleated lymphocytes and 9.8 +/- 3.1 for males and females respectively. In the CP group, spontaneous MN cell rates were 21.1 +/- 15.3 per 1000 binucleated lymphocytes and 19.1 +/- 11.2 for males and females respectively. Moreover, they were shown to have a large inter-individual variability in the two groups. The study of inter-individual variation factors showed that only tobacco could affect MN cell rate in HS whereas age and sex apparently had no significant effect. In the CP group, only age significantly affected MN cell rate, whereas sex, tobacco, alcohol, imaging techniques and tumour stage had no significant effect. There was no significant difference in the distribution of gender between HS and CP, whereas there was a significant difference in the distribution of age and tobacco between the two groups. The comparison of MN cell rates in 54 HS and 54 CP matched for age and sex showed a statistically significant difference. Spontaneous MN cell rates of these two populations reflect environmental exposure. Moreover, for CP it most probably refers to various cellular lesions and genetic damage.

Adolescent↗

PubMed1997

[Clinical pilot study on repeated use of heparin, vancomycin, colimycine locked flush solution for central intravenous implanted catheter in oncology].

With an anti-infectious and an antithrombotic prophylaxis aims, a locked flush solution including heparin and vancomycin, was used systematically for implantable venous access system for each patient, from january to april 1995. Since the 6th of april 1995, in order to widen the antibiotic spectrum on Gram negative bacteriae, we added colimycin at the flush solution. In 1995, 342 hospitalised patients held this type of venous access and received chemotherapy and/or radiochemotherapy for cancer. Two thousand six hundred thirty three manipulations were done, 575 with the first flush solution, 2058 with the second. During the year, 15 implantable access system (4.4%) were considered as infected, only 3 (0.9%) were removed, in the first period. THe infectious rate seemed to be stable, but the bacterial assessment to be modified between the two periods. The Gram negative bacterial infections seemed to decrease with colimycin addition (33% versus 50%). These results must be confirmed by a long term and/or randomized study.

Anti-Bacterial Agents↗

PubMed1996

[Dose expression of antineoplastic drugs].

Anticancer drugs dosage are currently adjusted to body surface area. This measure is supposed to be the best morphometric parameter to adjust anticancer drug doses. However, dose adjustment to body surface area has not historically been rigorously demonstrated. We propose a method to objectively test this parameter utility. The statistical justification of drug adjustment to body surface area can use mathematical equations to be expressed. We can demonstrate that body surface area and plasmatic total clearance of a drug should be correlated to adjust dose anticancer drug to body surface area. When we test the hypothesis of body surface area and plasmatic clearance correlation for cytarabine and adriamycin we did not find any significant correlation. For these anticancer drugs, dose adjustment to body surface area increase their pharmacokinetic and efficiency variabilities. The concept of dose-intensity is probably the best justification of individual dose adjustment from plasmatic drug samples, and from pharmacokinetic and pharmacodynamic studies. The determination of the "maximal tolerable exposition" and of the "minimal effective exposition" should reduce the overexpression of toxic risks and avoid the ineffective underexpositions. However, it is difficult to precisely define these two expositions and to research the most relevant pharmacokinetic parameters to their measure. Area under curve appears to be their most appropriate expression.

Antineoplastic Agents↗

PubMed1996

[Individual dose adjustment of high-dose methotrexate in clinical practice].

Since its discovery in 1948 the clinical applications of methotrexate have widened; and in order to overcome resistances to methotrexate, the concept of high-dose methotrexate has been proposed. The use of rescue by folinic acid, as well as rapid dosage of MTX coupled with pharmacokinetic studies, have permitted us to administer an optimum dose of drug, with maximum therapeutic effects, but with reduced toxicity. Individual adaptation of posology, calculated using the test dose or according to population pharmacokinetic with a Bayesian method of parameter estimation (which allows us to adjust the dose of high-dose methotrexate during its infusion) permits control of inter and intra-individual variations of this drug. After analysis of the different methods proposed, we now present the results of 778 courses of treatment by high-dose methotrexate (while separating 238 courses for osteosarcoma as these formed a homogeneous group of patients). Theoretical maximum concentration and length of infusion were decided by physicians, followed by individual adaptation of posology by pharmacologists at the sixth hour of infusion of methotrexate. This treatment unites maximum security for the patient with no serious side effects (no grade 4 toxicity according to WHO classification), while receiving an optimum dose of methotrexate. In courses of MTX for osteosarcoma, the dose of MTX can be further intensified without risk, by administering on average 65% more than the usual dose in adults (8 g/m2) and 10% more than the usual dose in children (12 g/m2).

Antimetabolites, Antineoplastic↗

PubMed1995

Prenatal diagnosis of a congenital astrocytoma: a case report and literature review.

Congenital intracranial tumors are very rare. We report an endovaginal ultrasonographic diagnosis of an anaplastic astrocytoma at 31 weeks' gestation. Other means, such as antenatal magnetic resonance imaging and fetal blood sampling were not shown to have any diagnostic advantage. A detailed literature review of the topic is provided.

Adult↗

PubMed1995

Spontaneous regression of fetal pulmonary sequestration.

The prenatal diagnosis of pulmonary sequestration can usually be made by the third trimester of pregnancy, from the combination of an intrathoracic mass and indirect signs such as cardiac deviation, fetal hydrops, pleural effusion and polyhydramnios. We describe four cases in which pulmonary hyperechogenicity was detected before 26 weeks' gestation. In three cases the hyperechogenic mass was isolated. In all cases it had mostly regressed during the pregnancy. A review of the cases of isolated pulmonary sequestration that have been diagnosed during the antenatal period is presented. Antenatal evolution was found to be unpredictable regardless of the type or severity of the case at the first diagnosis. We propose a classification to define more clearly the optimal management of pulmonary sequestration.

Adult↗

PubMed1995

Prospective study on fetal weight estimation using limb circumferences obtained by three-dimensional ultrasound.

The aim of this prospective study was to evaluate the usefulness of fetal weight estimation in a prospective study, based on formulae derived from a previous retrospective study, using forward stepwise multiple regression analysis. Three-dimensional ultrasound was used to make reproducible measurement of limb circumferences, which formed the basis of our models. A total of 213 women with singleton pregnancies were scanned in the week prior to delivery and the following variables were measured: biparietal diameter, head circumference, transverse abdominal diameter, abdominal circumference, femur length, thigh circumference and arm circumference. The whole population was divided into three subgroups according to the abdominal circumference (< 10th centile, 10-90th centile, and > 90th centile). We demonstrated the need for only two models for accurate fetal weight estimation, one for the small-for-dates fetuses and a second for the others. The most accurate results were obtained for the macrosomic fetuses with a standard deviation of 8.8%. Our data confirm the usefulness of measurement of fetal thigh circumference for the the small-for-dates-fetuses and arm circumference for the other groups. We concluded that the use of three-dimensional ultrasound could facilitate the accurate prediction of fetal weight.

Adolescent↗

PubMed1995

Dosage adjustment of high-dose methotrexate using Bayesian estimation: a comparative study of two different concentrations at the end of 8-h infusions.

Bayesian estimation (BE) of pharmacokinetic parameters enables the clinician to adjust the dosage of high-dose methotrexate (HDMTX) to correct the inter- and intraindividual variation of concentrations that are responsible for severe toxicity. In this study of 672 HDMTX infusions, we validated an approach that consisted of reaching as nearly as possible a theoretical concentration of 5.10(-4) M or 10(-3) M at the end of an 8-h infusion by adjusting, when necessary, the dosage at the 6th h. The BE of the clearance was compared with that obtained by maximum likelihood estimation (MLE), which was used as reference. BE performance was evaluated by calculating the bias and precision that indicated an overestimation of clearances obtained by BE compared with the higher clearance of the MLE in the group of patients receiving the higher dose (15 and 37.9%). Linear regression analysis of clearance obtained by BE and MLE showed a correlation (p < 0.0001) in both groups of patients with a closer link in those with the lower dose. However, in current clinical practice the important point is to obtain MTX concentration that is as close as possible to the desired concentration. Adjustments were evaluated by comparing the obtained concentrations with the desired theoretical concentration. There was no bias and precision was satisfactory in both groups of patients (15 and 12%, respectively, for 5.10(-4) M and 10(-3) M). This method makes it possible to limit the inter- and intraindividual variations of concentrations. As a result, severe complications were essentially nonexistent and were never life threatening.

Adolescent↗

PubMed1995

[Gastroschisis. Management. 50 cases].

OBJECTIVE: Demonstrate the need for a multidisciplinary antenatal approach to laparoschisis. MATERIAL AND METHODS: A retrospective series of 50 children who underwent surgery for laparoschisis between 1975 and 1994 in the Infant Surgery Department of the Strasbourg University Hospitals. Postoperative outcomes were evaluated as a function of the stage of laparoschisis and surgical technique. Follow-up was also examined. RESULTS: Depending on the periods evaluated, ultrasound diagnosis varied from 16 to 92% and was made at 21 weeks gestation on the average. Lesions observed were atresia of the bowel (10%), complete intestinal involution (2%), and perivisceritis (88%). Complete parietal closure was achieved after bowel emptying in 58% of the newborns. Postoperative mortality, usually in vere severe forms, fell from 46% to 15% over the 20-years study period. CONCLUSION: Antenatal echography can confirm the diagnosis of laparoschisis. It can be used to define risk factors (size, bowel dilatation(s), mesenteric blood flow) allowing planned extraction in an Infantile Surgery Unit. This multidisciplinary attitude should help to improve overall outcome.

Abdominal Muscles↗

PubMed1995

Immuno-gold-labelling of CUT-1, CUT-2 and cuticlin epitopes in Caenorhabditis elegans and Heterorhabditis sp. processed by high pressure freezing and freeze-substitution.

CUT-1 and CUT-2 are two distinct protein components of cuticlin, the insoluble residue of the cuticles of nematodes. In previous experiments of gold-immuno-labelling on sections of chemically fixed Caenorhabditis elegans, CUT-1 and CUT-2 epitopes were specifically lost. Cryo-immobilization of C. elegans under high pressure followed by freeze-substitution, however, resulted in a good preservation of these antigenic sites and of the ultrastructure of the worms. The entomopathogenic nematode Heterorhabditis sp. processed by the same cryopreparation protocol has shown a strong reactivity with anti-sera raised against CUT-1, CUT-2 and against the whole cuticlin residue of C. elegans. The localization of these epitopes was conserved across the two species.

Animals↗

PubMed1995

[Tests of micronucleus count in lymphocytes: a validation study].

In spite of the development of new automated methods proposed for scoring of micronuclei, manual analysis of micronucleated cells by light microscopy is still largely employed. The purpose of this study was to define the minimal number of mononucleated and binucleated cells representative of the total number of cells of the side, to determine the division rate. The second aim was to define the minimal number of binucleated cells representative of the total number of the binucleated cells on the same slide, to determine the rate of binucleated micronucleated cells. Total mononucleated, binucleated and polynucleated cells were scored in each slide for determining the 'theoretical division rate'. Among total binucleated lymphocytes observed in each slide, micronucleated cells containing one, two or more micronuclei were scored to determine the 'theoretical micronuclei rate'. Then, 'experimental division rates' were calculated by dividing microscope slides into random areas of 500 lymphocytes, and recording mononucleated, binucleated cells. 'Experimental micronuclei rates' were determined by dividing microscope slides into random areas of 500 binucleated cells, and recording micronucleated cells containing one or more micronuclei. 'Experimental division rates' obtained by examining sets of 4000 cells were shown to be not representative of the corresponding 'theoretical rate' (statistical difference by the chi-squared test, p < 0.05)). 'Experimental micronuclei rates' obtained by examining sets of 500 binucleated cells were shown to be representative of the corresponding 'theoretical micronuclei rate' (no statistical difference by the chi-squared test, p > 0.05).

Adult↗

PubMed1995

[Comparative value of transverse abdominal diameter and fetal abdominal perimeter. 3844 biometric examinations].

OBJECTIVE: Assess charts of abdominal size as they are used in a routine ultrasound screening, on a non selected population with 5 operators, to compare the interest of transverse abdominal diameter (TAD) with abdominal circumference (AC). METHOD: Retrospective study, in the department of Antenatal Diagnosis of the Centre Médico-Chirurgical et Obstétrical between September 1991 and August 1994. MAIN OUTCOME MEASURES: Abdominal biometry and gestational age to characterize the prenatal trophicity. Neonatal weight and gestational age at birth to characterize neonatal trophicity. RESULTS: Between 32 and 36 weeks, the TAD charts detected only one SGA (small for gestational age) out of 10. However, the AC sensitivity was 54.5% with a specificity of 94%. In the same period, the TAD charts suspect LGA (large for gestational age) for one exam out of two. The charts of AC have about the same performance to detect LGA and SGA. CONCLUSION: For a routine ultrasound screening between 32 and 36 weeks gestational age, the AC charts have to be preferred to TAD charts.

Abdomen↗