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F Duffaud

Publications and source records attributed to F Duffaud.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effect of smoking on micronucleated epithelial cells in smears from the uterine cervix.

A pilot study was conducted to determine whether any relationship exists between micronucleated cell rates of female uterine cervical epithelium and current smoking status. Cervical uterine cells obtained from 118 pre-menopausal females, seen between September 1994 and June 1995 at the Occupational Medecine Interprofessional Association (AIMT), were tested for micronucleated cells by the micronucleus assay. Of the 68 subjects taken from this population that provided a least a 1000 analysed cells, 36 were non-smokers and 32 were smokers. Age distributions were different between smokers and non-smokers but results showed that age had no effect on micronucleated cell levels. Micronucleated cervical cell rates reached 0.66% in non-smokers and 1.11% in smokers: these two levels were not statistically different. No association was noted between number of cigarettes smoked and micronucleated cell levels. Results suggested that consuming 5-20 cigarettes per day was not enough to show a smoking effect on cervical micronucleated cells. A test with a greater number of female subjects would be necessary to confirm this.

Adolescent↗
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

[Primary spinal osteosarcomas].

The rarity of primary osteosarcoma of the spine led us to index the 66 reported cases published in literature. From this analysis a difference was found between spinal osteosarcoma and osteosarcoma of the extremities. Tumors of the spine appear to be two times more frequent in the male population in their thirties. The average period between the beginning of the symptoms and the first consultation is seven months. Back pain is permanent and localized to the affected vertebra. In 80 percent of the cases, neurological symptoms already exist at the stage of the diagnosis. Magnetic resonance imaging (MRI), computed tomography and standard X-ray remain complementary in the morphological analysis of this tumor. All the aspects from the lytic to sclerotic forms are noted, although the lytic form is common. Among spinal osteosarcoma, the lumbar vertebrae are the most frequently affected. Diagnosis can only be established by pathology, even though this may also lead to some errors. In all the reported cases surgery is used, but carcinological methodology is not possible and a complete removal of affected tissue is difficult, with this being achieved in only a quarter of the cases. Radiation therapy, when used, requires doses of 70 Gy to 80 Gy without any certitude of controlling the tumour and with high risks of post-radiation complications. Chemotherapy on its own, despite the use of high-dose methotrexate, only has a temporary effect due to partial action on the primary center. Twenty years ago, only twenty percent of all patients suffering from osteosarcoma lived beyond two years, with worse prognosis for spinal osteogenic sarcoma. Today, the therapeutic approach for spinal tumors uses techniques developed in the treatment of osteosarcoma of the extremities, which can now expect more than seventy percent of all patients to live beyond five years. Present day methods recommend a rapid confirmation of the diagnosis, and then a neoadjuvant chemotherapy followed by surgery to remove all the affected area. This strategy allows an evaluation of the tumor chemosensitivity and to adapt the treatment in consequence. The latest results of this treatment on spinal osteosarcoma appear to be encouraging.

Humans↗
PubMed1997

[Primary spinal osteosarcoma. Apropos of a case].

We report a case of primary osteogenic sarcoma of the third lumbar vertebra, detailing the neuroradiologic and therapeutic aspects. The clinical presentation was limited to low back pain which radiated to the left thigh for 5 months. Lumbosacral spine roentgenograms revealed a sclerotic lesion of the left part of the body of the third lumbar vertebra. Treatment consisted of total vertebrectomy, chemotherapy completed with radiotherapy. Fourteen months after a complex combined treatment no recurrence was observed. A review of the literature highlighted the rarity of this tumor. Usually, patients with vertebral osteogenic sarcoma do poorly. Today, the therapeutic approach for these spinal tumors should use techniques developed in the treatment of osteosarcoma of the extremities because of their encouraging results.

Adult↗
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

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

[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↗
PubMed1994

Quantitative immunocytochemical assays of P-glycoprotein in breast carcinomas: correlation to messenger RNA expression and to immunohistochemical prognostic indicators.

BACKGROUND: Chemotherapy failure that is due to cellular drug resistance remains a major problem in most cancer patients. One type of drug resistance that has been characterized is the multidrug resistance phenomenon, which demonstrates a reduced ability of cancer cells to accumulate drugs as a result of the effects of an energy-dependent unidirectional drug efflux pump with a broad substrate specificity. This drug pump is composed of a 170-kd transmembrane glycoprotein referred to as the P-glycoprotein (P-gp) that uses energy in the form of adenosine triphosphate to transport drugs through a channel formed by transmembrane segments. PURPOSE: Our purpose was to detect the levels of P-gp expression in frozen untreated breast carcinomas by immunocytochemical assays and to correlate these levels to current prognostic indicators and, in a few cases, to MDR1 (also known as PGY1) mRNA expression by polymerase chain reaction (PCR). METHODS: The immunocytochemical expression of the multidrug resistance gene, P-gp, was investigated using a specific monoclonal antibody (JSB1) against P-gp in 5-microns frozen sequential sections of breast carcinomas obtained from 213 patients. Microscopic images of immunostained preparations were evaluated by image analysis and were compared with MDR1 transcription (mRNA) assessed by PCR in 16 patients. Quantitative P-gp immunocytochemical assays were correlated to histoprognostic factors and immunocytochemical indicators. RESULTS: Among the 213 breast carcinomas tested, 113 (53%) were P-gp positive, but in 28% of the tumors, the immunostained surface accounted for less than 5% of the total area stained. Quantitative immunocytochemistry reflecting the amount of intracellular P-gp antigen strongly correlated (r = 0.865; two-sided, P < .0001; Pearson's test) with the quantitative evaluation of the scanner analysis of mRNA transcripts. The P-gp expression was significantly (two-sided, P < .001) correlated with p53 expression in tumors, to cathepsin D and Ki67 (two-sided, P < .01) immunoreactivity, and to a lesser extent, the detection of estrogen receptor antigenic sites (two-sided, P = .019). P-gp expression was found to be independent of expression of progesterone receptor and pS2, pHER-2/neu, and CD31 in tumors and from patient age, tumor size, histologic types, grades and Nottingham prognostic index, and nodal status. CONCLUSIONS: The quantitative immunocytochemical assays of P-gp are correlated to PCR analysis of MDR1 expression, and such correlations can be useful in evaluating potential multidrug resistance in breast cancer. However, the clinical significance of P-gp immunodetections remains to be further determined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Pharmacokinetics of high-dose methotrexate in adult osteogenic sarcoma.

The pharmacokinetics of 222 infusions of high-dose methotrexate (MTX) with leucovorin rescue were studied in 22 adults with osteosarcoma. To reduce the variability of plasma concentration, we individualized dose regimens using a Bayesian method to reach a concentration of 10(-3) M MTX at the end of an 8-h infusion. The mean concentration observed at the end of the infusion was 1016 +/- 143 mumol/l. The mean dose delivered was 13.2 +/- 2 g/m2. The clearance was 49.1 +/- 11.7 ml min-1 m-2. The decay of the plasma concentration of MTX after completion of the infusion followed a two-compartment model with a t1/2 alpha of 2.66 +/- 0.82 h and a t1/2 beta of 15.69 +/- 8.63 h. The volume of distribution was 0.32 +/- 0.08 l/kg. As compared with previously published data, the interindividual and intraindividual variations in the concentration at the end of the infusion were reduced, with values of 14% and 5.9%-21%, respectively, being obtained. Severe toxicities were avoided, and there were only 3 hematologic and 8 digestive grade 3 side effects and no grade 4 complication. The t1/2 alpha and the MTX plasma concentrations at 23 and 47 h were correlated with renal toxicity (P < 0.001). However, no correlation was found between the pharmacokinetic parameters and other signs of toxicity. There was no significant difference in pharmacokinetics between the toxic and nontoxic groups. In the same manner, the parameters of the group of patients sensitive to MTX were not statistically significant different from those of the group of nonsensitive patients.

Adolescent↗
PubMed1992

The pleiotropic effects of interleukin 7 and their pathologic and therapeutic implications.

Interleukin-7 (IL-7) is a cytokine initially described as a growth factor for B cell progenitors. IL-7 also induces T cell proliferation and has pleiotropic effects. IL-7 enhances T-lymphocyte cytotoxicity, stimulates anti-tumoural properties of monocytes/macrophages, and induces tumour rejection in mice. It could thus be of interest in immunotherapy and may play a role in the generation of lymphoid neoplasia because leukaemic cells of B and T lineage express functional IL-7 receptors. Finally, IL-7 is, as IL-2, a cytokine of pivotal importance in the immune system, and so could be involved in abnormal immune response such as autoimmunity.

Animals↗
PubMedDate not supplied

[Studies on the genotoxic effects of crude liver oils from 3 species of Mediterranean sharks by means of in vitro micronucleus test using human lymphocytes].

Lymphoid system tumours have been identified in two subjects who used to handle for several years mediterranean shark liver oil and squalen extracted from this oil. Moreover, scientific data, reported in 1959 by Kröning, show the induction of lymphoid tumours in C57 B1 mice after exposure of their skin to squalen. These observations rose the question of a possible mutagenic power of shark liver oil. In order to determine the genotoxicity of these oils, in vitro assays have been performed on crude hepatic oil of three species of mediterranean sharks: two benthic sharks, Centrophorus granulosus and Galeus melastomus, and one pelagic specie, Prionace glauca. Genotoxicity of oils have been assayed using a micronucleus test which can detected simultaneously clastogen and aneugen effects. The incubation of human cells with the hepatic crude oils of Centrophorus granulosus increases the rate of the binucleated micronucleated cell in a dose dependent manner. The mean micronucleated cell rate was 9.0%. +/- 1.1 in controls and increased up to 27,1%. +/- 4,0 for the highest concentrations of oil extracts. Similar results have been obtained with crude hepatic oils of Galeus melastomus and Prionace glauca. The results of this experimental study show that the crude liver oils of three species of sharks are genotoxic and confirm a high carcinogenic risk.

Adult↗
PubMedDate not supplied

[Application of micronucleus test for the demonstration of antimutagenic properties of natural substances].

Authors have used a reliable and reproductible original model of controlled production of free radicals for the cytokinesis-block micronucleus assay. This mutagenicity test is of easy realization and quick interpretation. An experimental model is proposed to test mutagenic activity of free radical generators and antioxydant properties of many substances, such as ascorbic acid. Its addition to the culture medium showed a significant decrease in the rate of micronucleated cells exposed to the free radical generator. The study of other antioxydant compounds (beta-caroten and 5-hydroxyquinolin) have confirmed results previously obtained with ascorbic acid. Thus, the free radical generator coupled to the cytokinesis-block micronucleus assay represents a reliable test to study and evaluate the antioxydant power of natural substances.

Analysis of Variance↗
PubMedDate not supplied

[Doxorubicin and cisplatin genotoxicity: search for a real indication using the micronucleus test].

Doxorubicin and cisplatin are two major anticancer drugs, and are also known to be mutagen. Using short term mutagenesis tests, the cytokinesis-block micronucleus test and chromosome aberrations test, a study of the cytotoxicity and the mutagenicity of these two drugs has been aimed to determine a genotoxic of reference for these tests. Cisplatin and doxorubicin were genotoxic and gave positive results with the two tests. Since cisplatin was more cytotoxic than doxorubicin for a same genotoxicity, doxorubicin has been selected as a positive control for these two short-term mutagenesis tests. A study of the individual variability in the response to in vitro doxorubicin exposure was made using the cytokinesis-block micronucleus test, applied to cultured T lymphocytes form healthy subjects and cancer patients. Micronucleated cell rate before (T0) and after in vitro exposure to doxorubicin (T1) were determined in the two groups of subjects. Micronucleated cell rates T1 were significantly higher than T0 for healthy subjects and cancer patients. A calculated sensitivity index [(T1)-(T0)] is proposed to evaluate the individual sensitivity to the positive control doxorubicin.

Adult↗