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Biomedical subjects

P Dufour

Publications and source records attributed to P Dufour.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial.

Oral capecitabine (Xeloda) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings pound3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings pound1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK.

Administration, Oral↗
PubMed2006

Comparison of four diagnostic tests for the identification of serum antibodies in small ruminants infected with Mycoplasma agalactiae.

AIM: To determine the diagnostic capability of a newly developed Western blot (WB) assay for the detection of serum antibodies against Mycoplasma agalactiae compared with conventional serological tests, and to identify the best test for routine diagnostic use. METHODS: The serological test methods used were: two commercial indirect enzyme-linked immunosorbent assays (ELISA), viz ELISA-1, using a bacterial antigen preparation, and ELISA-2, using a recombinant protein (lipoprotein p48) antigen; the complement fixation test (CFT); and a newly developed WB assay, the latter both using a bacterial antigen preparation. Thirty sera from goats infected with M. agalactiae and 97 sera from non-infected sheep were tested using all four methods. RESULTS: Staining patterns in the WB were quite variable. An immuno-dominant band of 41 kDa was detected in 63% of sera from infected animals. The same band also appeared, although mostly very weakly, in 10% of sera from non-infected animals. When suspicious or very weak reactors were omitted, the diagnostic sensitivity (DSE) and diagnostic specificity (DSP), respectively, for the four assays were: WB=56.7%, 97.9%; ELISA-1=76.7%, 99.0%; ELISA-2=56.7%, 100%; and CFT=40.0%, 94.8%. CONCLUSIONS: ELISA-1 performed best in this comparison. While the WB can be used, it did not have a technical advantage over the ELISA. The CFT should be discouraged as the primary screening method for contagious agalactia and should be replaced by ELISA-1. Results from this study confirm that serological test methods for contagious agalactia are useful for the detection of infected flocks but will not detect every individual infected animal.

Animals↗
PubMed2005

Latent acute promyelocytic leukemia t(15;17)(q22;q12-21) and sarcoidosis: long-term cohabitation.

The association of sarcoidosis with hematological malignancies is a well-known phenomenon. To our knowledge, we report the first case involving sarcoidosis and acute promyelocytic leukemia (APL) t(15;17)(q22;q12-21). The major interest lies in the chronology of the two diseases: the APL demonstrated an unusual smoldering evolution, suggesting that pre-existing sarcoidosis may have a non-fortuitous immunological impact on leukemic clone proliferation.

Journal Article↗
PubMed2005

[Spontaneous intrauterine depression skull: myth or reality?].

In spite of the fact that there are many articles considering that intrauterine depressed skull fractures are caused essentially by instrumental extraction, literature is scarce about spontaneous foetal head injuries. Here, we report the case of two depressed skull fractures and one of linear fracture not associated with any known trauma during the pregnancy or delivery. The etiological process leading to the idiopathic character of such lesions, the aetiology, the treatment and the prognostic will be discussed. The forensic problem raised by such cases is very important.

Forensic Medicine↗
PubMed2004

Identification of candidate genes for in vitro androgenesis induction in maize.

Extensive studies have been conducted to understand the genetic control of in vitro androgenesis, but little is know about the genes and the mechanisms involved in the switch that allows an immature pollen grain to develop as an embryo. We have developed two maize isogenic lines with high androgenetic aptitude, named AH5-44 and AH5-49, through backcross and selection from a high-responsive DH229 line on the non-responding A188 line genetic background. The genomic structure of these two lines was precisely described with microsatellite markers. Five regions retained from the parent DH229 highly responsive to androgenesis were localised in both AH5-44 and AH5-49. Sequences expressed on microspores extracted from the four lines were amplified using a cDNA-AFLP protocol. For each line, eight culture conditions were compared: microspores extracted after tassel recovery, after 7 or 14 days in cold room and after 1-4 days of in vitro culture. This genetic and developmental screening allowed us to identify four sequences, including a new HSP70-like candidate gene. Possible implication of the identified sequences in androgenesis response is discussed.

Base Sequence↗
PubMed2004

Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials.

This study evaluates the efficacy of capecitabine using data from a large, well-characterised population of patients with metastatic colorectal cancer (mCRC) treated in two identically designed phase III studies. A total of 1207 patients with previously untreated mCRC were randomised to either oral capecitabine (1250 mg m(-2) twice daily, days 1-14 every 21 days; n=603) or intravenous (i.v.) bolus 5-fluorouracil/leucovorin (5-FU/LV; Mayo Clinic regimen; n=604). Capecitabine demonstrated a statistically significant superior response rate compared with 5-FU/LV (26 vs 17%; P<0.0002). Subgroup analysis demonstrated that capecitabine consistently resulted in superior response rates (P<0.05), even in patient subgroups with poor prognostic indicators. The median time to response and duration of response were similar and time to progression (TTP) was equivalent in the two arms (hazard ratio (HR) 0.997, 95% confidence interval (CI) 0.885-1.123, P=0.95; median 4.6 vs 4.7 months with capecitabine and 5-FU/LV, respectively). Multivariate Cox regression analysis identified younger age, liver metastases, multiple metastases and poor Karnofsky Performance Status as independent prognostic indicators for poor TTP. Overall survival was equivalent in the two arms (HR 0.95, 95% CI 0.84-1.06, P=0.48; median 12.9 vs 12.8 months, respectively). Capecitabine results in superior response rate, equivalent TTP and overall survival, an improved safety profile and improved convenience compared with i.v. 5-FU/LV as first-line treatment for MCRC. For patients in whom fluoropyrimidine monotherapy is indicated, capecitabine should be strongly considered. Following encouraging results from phase I and II trials, randomised trials are evaluating capecitabine in combination with irinotecan, oxaliplatin and radiotherapy. Capecitabine is a suitable replacement for i.v. 5-FU as the backbone of colorectal cancer therapy.

Administration, Oral↗
PubMed2004

Conflicting effects of caffeine on apoptosis and clonogenic survival of human K1 thyroid carcinoma cell lines with different p53 status after exposure to cisplatin or UVc irradiation.

Caffeine has been widely described as a chemo/radiosensitizing agent, presumably by inhibiting DNA repair, and affecting preferentially cells with an altered p53 status. We evaluated the effects of caffeine using isogenic and isophenotypic K1 cells derived from a papillary thyroid carcinoma and displaying either a wild type or a mutated p53 status. Apoptosis and clonogenic survival were examined after exposure of the cells to cisplatin or UVc irradiation. We find that at the most currently used concentration, 2mM, caffeine hinders cisplatin or UVc induced apoptosis in K1 cells. In addition, at this already barely achievable concentration in vivo, caffeine does not decrease their clonogenic survival. Hence in our cellular model, caffeine does not behave as a chemo- or a radiosensitizer. Although surprising, these results (1) are in agreement with the delayed G2/M block caused by caffeine that we previously observed in normal human fibroblasts and K1 cells and (2) allow us to elucidate some discrepancies concerning this molecule throughout the literature such as increase or decrease of apoptosis and clonogenic survival, activation or deactivation of molecules involved in DNA damage repair and proliferation inhibition but accelerated G2/M traverse.

Antineoplastic Agents↗
PubMed2004

Cisplatin enhances the cytotoxicity of fast neutrons in a murine lymphoma cell line.

The utilization of high linear energy transfer (LET) radiations, such as fast neutrons or carbon ions (hadrontherapy), offers promising perspectives in radiotherapy. While it is well known that by combining radiotherapy and chemotherapy, important therapeutic advantages can be obtained to cure cancer, there have been, so far, very few investigations on the effects of treatments combining an irradiation with high-LET particles and cancer drugs. The present study was therefore undertaken to examine the effects of exposure to 65 MeV fast neutrons combined with cisplatin in a murine T cell lymphoma (RDM4) in vitro. The cells were irradiated at doses ranging from 2 to 8 Gy without or with addition of cisplatin shortly before the irradiation, at concentrations between 0.3 and 12.5 micro M. These treatments were applied concomitantly. Proliferation and apoptosis were assessed at different time intervals thereafter. The combination of irradiation with cisplatin was found to be more cytotoxic than either treatment alone. Furthermore, the cytotoxicity induced by this cotreatment resulted not only from apoptosis but also from other forms of cell death.

Animals↗
PubMed2003

[Antiphospholipid antibodies in HELLP syndrome: clinical and biological study in 68 women].

PURPOSE: Pregnancy complicated by the HELLP syndrome and antiphospholipid syndrome have rarely been reported. We report a study on anticardiolipin antibodies in HELLP syndrome. METHODS: Between March 1996 and September 1999, anticardiolipin antibodies were checked in all women with HELLP syndrome hospitalised in a maternity of the North of France. The women with positive anticardiolipin antibodies were seen month later in a internal medicine department. RESULTS: In the period 68 women with HELLP syndrome were checked for anticardiolipin antibodies. Apl were present in 9 patients (Incidence 42.8/1000 HELLP Year). They persisted after the accident only in 3 patients. Antiphospholipid syndrome was diagnosed in 2 patients, prevalence between the HELLP syndrome for the 42 month period was 0.03. CONCLUSIONS: HELLP syndrome may be a manifestation linked to the antiphospholipid syndrome and may revealed it.

Adult↗
PubMed2002

[Interest in intestinal resection for treatment of advanced ovarian cancer].

AIM OF THE STUDY: Digestive surgery is often necessary for surgical management of advanced ovarian carcinoma. PATIENTS AND METHODS: In a series of 62 patients with stage III ovarian carcinoma, postoperative morbidity and mortality, overall survival after 5 years and disease-free survival after 2 years were studied and corelated with several patients criteria (age, stage of the disease, residual disease, type of surgery, CA125 normalisation delay, postoperative complications and hospital stay). Patients were divided into two groups according to the surgical treatment. The first group (n = 17) included patients treated by gynecologic and digestive surgery, the second group (n = 45) included patients treated by gynecologic surgery only. All patients were proposed for chemotherapy included platyn salt. Mean age was 60 years (range: 20-83). The stage of the cancer was stage IIIa in 7 cases, stage IIIb in ten and stage IIIc in 45. RESULTS: Postoperative mortality was 3.5% (2/62). Postoperative morbidity was 26% (13/62). No statistical differences were noted for hospital stay, general morbidity, surgical morbidity when a gastric resection or a colon resections or a splenectomy were performed. Overall survival at 5 years was 56%. Residual disease less than 2 cm3 is the only prognostic factor for overall survival (56% vs 23% [P = 0.03]) and disease-free survival (86% vs 46% [P = 0.02]). CONCLUSION: This study including 62 patients confirmed the prognostic significance of extensive cytoreductive surgery for treatment in advanced ovarian epithelial cancer without increasing the postoperative morbidy and mortality.

Adult↗
PubMed2002

[Hyperemesis in the first trimester of pregnancy: role of biological hyperthyroidism and fetal sex].

OBJECTIVES: Our objectives were to link hyperemesis gravidarum with biochemical hyperthyroidism and hormonal modification (HCG and estradiol) and to test the hypothesis that biological abnormalities (ionogram and liver enzyme) are more often reported in hyperemesis gravidarum with biochemical hyperthyroidism. STUDY DESIGN: Thirty three patients admitted in "Hôpital Jeanne de Flandre" with hyperemesis gravidarum were studied prospectively. RESULTS: Twenty-two patients (66.7%) had biochemical hyperthyroïdsm (suppressed thyroid stimulating hormone or increased triiodothyronine index or tetraiodothyronine index). Hyperthyroid patients were more likely than euthyroid patients to have abnormal electrolyte levels (16/22 [72.7%] vs 3/1 [27.3%], P < 0.02) or increased liver enzyme levels (8/22 [36.4%] vs 3/11 [27.3%]). The severity of hyperemesis was found to vary directly with the degree of hyperthyroidism. We report a female predominance among the offspring of mothers with hyperemesis gravidarum. CONCLUSION: Our results are suggestive of the involvement of hyperthyroidism and fetal sex in the pathogenesis of hyperemesis gravidarum. Also these hypothesis are not clearly understood, human chorionic gonadotrophin occurred in the two mechanisms.

Adult↗
PubMed2002

Induction of apoptosis by high linear energy transfer radiation: role of p531.

The involvement of the tumor suppressor p53 gene in the sensitivity of many cell types towards low linear energy transfer (LET) radiation is now well established. However, little information is available on the relationship between p53 status of tumor cells and their ability to undergo apoptosis following exposure to high-LET radiation. Here we present the results of experiments carried out with the human lymphoblastoid cell line TK6 and its p53 knock-out counterpart NH32. Cells were irradiated at doses ranging from 0.25 to 8 Gy with fast neutrons (65 MeV), carbon ions (95 MeV/nucleon), and X rays (15 MV). For both cell lines, the occurrence of apoptosis, determined by the quantification of hypodiploid particles as well as the activation of several caspases, was compared with their sensitivity towards high-LET radiation. Results indicate that p53 is involved in the response of TK6 cells to fast neutrons and carbon ions, as measured by cell proliferation and occurrence of apoptosis. However, p53-deficient cells are still able to undergo apoptosis following irradiation. This suggests that heavy ions and fast neutrons induce cellular damage that is not under the control of p53. The involvement of executioner caspases in high-LET radiation induced apoptosis was also evaluated by use of specific inhibitors.

Apoptosis↗
PubMed2002

Involvement of TP53 in apoptosis induced in human lymphoblastoid cells by fast neutrons.

We investigated the involvement of TP53 in apoptosis induced by fast neutrons in cells of three human B-lymphoblast cell lines derived from the same donor and differing in TP53 status: TK6 (wild-type TP53), WTK1 (mutant TP53) and NH32 (knockout TP53). Cells were exposed to X rays or to fast neutrons at doses ranging from 0.5 to 8 Gy. Apoptosis was determined by measurements of the sub-G0 /G1-phase DNA content and by the externalization of phosphatidylserine. Fast neutrons induced extensive apoptosis in TK6 cells, as shown by the formation of hypodiploid particles, the externalization of phosphatidylserine, and the activation of caspases. In contrast, cell death was triggered at a significantly lower rate in cells lacking functional TP53. However, TP53-independent cell death also expressed the morphological and biochemical hallmarks of apoptosis. Proliferation tests and clonogenic assays showed that fast neutrons can nevertheless kill WTK1 and NH32 cells efficiently. The absence of functional TP53 only delays radiation-induced cell death, which is also mediated by caspases. These results indicate that fast-neutron irradiation activates two pathways to apoptosis and that the greater relative biological effectiveness of fast neutrons reflects mainly an increase in clonogenic cell death.

Apoptosis↗
PubMed2002

[Pathophysiology of gestational diabetes].

During pregnancy, a number of maternal metabolic changes occur early and continue throughout pregnancy which help optimize the transfer of nutrients to the fetus. During normal pregnancy, there are a decrease in insulin sensibility which is physiological, progressive and reverse. For glucose tolerance to be maintained in pregnancy it is necessary for maternal insulin secretion to increase sufficiently to counteract the fall in insulin sensitivity. The metabolic characteristic of women with gestational diabetes is insufficient insulin secretion to counteract the pregnancy related fall in insulin sensitivity. There are a lot of factors that could explain the mechanism of insulin secretion and insulin sensitivity during normal pregnancy and gestational diabetes mellitus. Although glucose tolerance normalizes shortly after pregnancy with gestational diabetes in the majority of women, the risk of developing overt diabetes, especially type 2 diabetes is markedly increased. The mechanisms which could explain gestational diabetes are the same as type 2 diabetes mellitus. We could speculate that these two diseases are identical for alterations in carbohydrate metabolism, but at different stages.

Diabetes, Gestational↗
PubMed2002

[Maternal and fetal outcome].

Gestational diabetes, a glucose tolerance disorder of variable severity which occurs or is diagnosed for the first time during pregnancy, constitutes a public health problem because of its frequency (1 to 6% of all pregnancies) and its short-or long term consequences for the foetus and/or the mother. There is as yet still no consensus concerning screening and diagnosis criteria, therapeutic management and the reality of the disease. This population is a high risk population of diabetes mellitus, especially of type 2 diabetes. We could think that the introduction of specific prevention programs in this group could delay or avoid diabetes mellitus and its complications. The mechanisms which could explain gestational diabetes are the same as type 2 diabetes mellitus. We could speculate that these two diseases are identical for alterations in carbohydrate metabolism, but at different stages. It has been reported that the offspring of gestational diabetics mothers are at risk of obesity and glucose intolerance. Therapeutic management of the mother and/or the offspring should be better defined. The screening for gestational diabetes provides an opportunity of identify a large population of women and children at risk of diabetes. It should be possible to avoid diabetes mellitus by specific therapeutic programs in these populations.

Diabetes Mellitus, Type 2↗
PubMed2001

Alpha-interferon does not increase the efficacy of 5-fluorouracil in advanced colorectal cancer.

Two meta-analyses were conducted to quantify the benefit of combining alpha-IFN to 5FU in advanced colorectal cancer in terms of tumour response and survival. Analyses were based on a total of 3254 individual patient data provided by principal investigators of each trial. The meta-analysis of 5FU +/- LV vs. 5FU +/- LV + alpha-IFN combined 12 trials and 1766 patients. The meta-analysis failed to show any statistically significant difference between the two treatment groups in terms of tumour response or survival. Overall tumour response rates were 25% for patients receiving no alpha-IFN vs. 24% for patients receiving alpha-IFN (relative risk, RR = 1.02), and median survivals were 11.4 months for patients receiving no alpha-IFN vs. 11.5 months for patients receiving alpha-IFN (hazard ratio, HR = 0.95). The meta-analysis of 5FU + LV vs. 5FU + alpha-IFN combined 7 trials, and 1488 patients. This meta-analysis showed an advantage for 5FU + LV over 5FU + alpha-IFN which was statistically significant in terms of tumour response (23% vs. 18%; RR = 1.26;P = 0.042), and of a borderline significance for overall survival (HR = 1.11;P = 0.066). Metastases confined to the liver and primary rectal tumours were independent favourable prognostic factors for tumour response, whereas good performance status, metastases confined to the liver or confined to the lung, and primary tumour in the rectum were independent favourable prognostic factors for survival. We conclude that alpha-IFN does not increase the efficacy of 5FU or of 5FU + LV, and that 5FU + alpha-IFN is significantly inferior to 5FU + LV, for patients with advanced colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗