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Olivier Pradier

Publications and source records attributed to Olivier Pradier.

10 recordsLinked to original sources
PubMed2003

Conformal radiotherapy planning of cervix carcinoma: differences in the delineation of the clinical target volume. A comparison between gynaecologic and radiation oncologists.

PURPOSE: To assess uncertainties in the definition of the clinical target volume (CTV) for patients scheduled for primary radiotherapy of cervix carcinoma. METHODS AND MATERIALS: Seven physicians (five radiation oncologists and two gynaecologists) independently contoured the CTVs for three patients. All observers were provided with the same clinical information. CTVs were entered directly in the treatment planning system. Differences were analysed qualitatively and quantitatively. RESULTS: The qualitative analysis revealed a good agreement by all observers on anatomical structures identified to be at risk for tumour spread. Quantitatively, however, a large interobserver variability was found. The ratio between largest and smallest volumes ranged between 3.6 and 4.9 for all observers (3.6-4.9 for the radiation oncologists, 1.3-2.8 for the gynaecologists). The median three-dimensional difference in gravity centres ranged between 10.9 and 26.3mm for the respective patients. The ratio of common volumes to encompassing volumes ranged between 0.11 and 0.13 for the radiation oncologists, and between 0.30 and 0.57 for the gynaecologists. CONCLUSIONS: Although there was a good consistency in outlined anatomical structures, for the radiation therapy of carcinomas of the uterine cervix a large interobserver variability in CTV delineation concerning the magnitude and relative location of volumes was observed. Compared to other factors, e.g. set-up and organ motion, interobserver variability in CTV definition seems to have the highest impact on the geometrical accuracy in the radiotherapy of this tumour entity.

Adult↗
PubMed2003

Monocyte CD40 expression in severe sepsis.

D40 is a cell surface protein belonging to the tumor necrosis factor (TNF) receptor family. Ligation of monocyte CD40 by the T cell-derived CD40 ligand can trigger the production of various mediators, the transcription and activation of enzymes, and the upregulation of costimulatory molecules involved in the pathogenesis of sepsis. To test the hypothesis that CD40 is expressed on the surface of monocytes during sepsis, we measured CD40 expression by flow cytometry on freshly sampled monocytes from 40 patients with severe sepsis, including 15 patients with bacteremia, and from eight healthy volunteers. Plasma concentrations of interleukin (IL) 6, IL-10, and IL-13 were also measured. We detected CD40 only on monocytes from patients with sepsis (mean 6.5 +/- 0.4 median channel fluorescence). There was an inverse correlation between peak CD40 expression and survival (P = 0.05), particularly in the patients with bacteremia (P = 0.019). In the bacteremic group, there was an inverse correlation between CD40 expression and bilirubin levels (r2 = 0.52, P = 0.004) and plasma IL-6 concentrations (r2 = 0.30, P = 0.04). Our results showed that upregulation of CD40 expression on peripheral blood monocytes is a protective phenomenon during severe sepsis. Monocyte deactivation reflected by low CD40 expression may represent impairment of immune function associated with severity of illness and poor outcome. Further studies on monocyte phenotype and function may help to assess the immune status of patients with sepsis and perhaps be useful to guide immunomodulatory strategy in the future.

Adult↗
PubMed2002

Giant platelets in a case of deletion 11q24-qter confirmed by fluorescence in situ hybridization.

Here we report the association of giant platelets and an increase in platelet volume in a 19-month-old black female with de novo del 11q24-qter. The deletion, which was visible on karyotype, was further confirmed and more precisely localized by fluorescence in situ hybridization studies (FISH) that showed the deletion to lie distal to the MLL gene region (11q23). Clinically, the case presented less severe symptoms than Jacobsen syndrome-the well known partial deletion of the distal end of chromosome 11. Platelet glycoproteins CD 41, CD 42a, C 42b, CD 61, and PAC-1 were also assayed and found to be normally expressed. To our knowledge, giant platelets are described for the first time in the relevant deleted region.

Blood Platelet Disorders↗
PubMed2002

Does escalation of the apical dose change treatment outcome in beta-radiation of posterior choroidal melanomas with 106Ru plaques?

PURPOSE: To show the results of treating posterior uveal melanomas with 106Ru plaque beta-ray radiotherapy and to review and discuss the literature concerning the optimal apical dose prescription (100 vs. 160 Gy). METHODS AND MATERIALS: Forty-eight patients with uveal melanomas (median height 3.85 mm + 1 mm sclera) were treated with ruthenium plaques. The median apical dose was 120 Gy, the median scleral dose 546 Gy. RESULTS: After 5.8 years of follow-up, the overall 5-year survival rate was 90%, the disease specific 5-year survival rate was 92% (3 patients alive with metastasis). Six percent received a second ruthenium application, 10% of the eyes had to be enucleated. Local control was achieved in 90% of the patients with conservative therapy alone. Central or paracentral tumors showed 50% of the pretherapeutic vision after 4 years, and 80% of the vision was preserved in those with peripheral tumors. The main side effects were mostly an uncomplicated retinopathy (30%); macular degeneration or scarring led to poor central vision in 30% of cases. CONCLUSION: Brachytherapy with ruthenium applicators is an effective therapy for small- and medium-size posterior uveal melanomas. Our results are comparable to other series. The treatment outcome does not seem to be capable of improvement by increasing the apical dose. An internationally accepted model for defining the dosage in brachytherapy is needed.

Adult↗
PubMed2002

Bordetella pertussis toxin induces the release of inflammatory cytokines and dendritic cell activation in whole blood: impaired responses in human newborns.

Bordetella pertussis toxin (PTX), a key component of acellular pertussis vaccines, is known to be endowed with adjuvant properties. In experiments designed to get insights into the interactions between PTX and circulating immune cells, we first observed that addition of PTX to adult whole blood induced the release of IL-12 and TNF-alpha as well as maturation of myeloid dendritic cells (DC). These effects were still present with a toxin mutant devoid of ADP-ribosyltransferase activity but not with a formaldehyde-inactivated toxin. These findings indicate that cytokine production and DC maturation require the intact structure of PTX but not its enzymatic activity. Secondly, studies on DC generated in vitro by culturing monocytes with IL-4 and GM-CSF showed that PTX directly stimulates MHC class II and costimulatory molecules up-regulation, cytokine synthesis and NF-kappa B activation. Finally, comparison of data obtained in adult vs. cord blood revealed deficient responses of neonatal DC to PTX. These data suggest new applications of PTX and PTX mutants as vaccine adjuvants.

Adult↗
PubMed2002

Involved-field irradiation in combination with total-body irradiation (TBI) does not increase short-term toxicity compared to TBI alone in patients with advanced-stage low-grade non-Hodgkin lymphoma.

PURPOSE: High-dose therapy (HDT) is currently under investigation for patients with advanced low-grade non-Hodgkin lymphoma (NHL). We report on the toxicity of a modified HDT that combines total-body irradiation (TBI) with involved-field irradiation (IF-RT) for patients with bulky disease or residual lymphomas > 2 cm after induction chemotherapy. PATIENTS AND METHODS: 41 patients received HDT which consisted of high-dose cyclophosphamide and fractionated TBI (6 x 2 Gy) followed by autologous stem cell transplantation. Eleven patients received IF-RT prior to TBI, three patients had already received another radiotherapy treatment prior to HDT. RESULTS: After a medium follow-up of 19 months we observed an overall survival rate of 100%, and a relapse-free survival rate of 78%. Severe toxicity was observed only in one patient who developed a myelodysplastic syndrome, and another patient who showed signs of pneumonitis. About two thirds of the patients claimed minor toxicity of grade I-II according the LENT-SOMA scale, predominantly as a decrease in concentration, reduced sexual functioning, and musculo-skeletal pain. Correspondingly, laboratory tests showed grade I-II changes of blood counts, liver enzymes, hormone levels, and lung function. There was no excess toxicity in the patients who received IF-RT additional to TBI. CONCLUSIONS: HDT including TBI and prior IF-RT is feasible without excess morbidity. Careful follow-up is required to detect myelodysplastic syndrome or endocrine changes of ovarian or testicular function.

Adult↗
PubMed2002

Combined effect of topotecan and irradiation on the survival and the induction of chromosome aberrations in vitro.

BACKGROUND: Topotecan demonstrated radiosensitizing effects in vivo and in vitro, which are schedule- and cell line dependent. The underlying mechanisms are not fully understood. Topotecan interferes with DNA replication, transcription, and repair and may thus increase the frequency of radiation-induced lethal chromosome aberrations. MATERIAL AND METHODS: U-373 MG glioblastoma cells, WiDr colon adeno-carcinoma cells, as well as normal human fibroblasts and lymphocytes were irradiated (0-6 Gy) and exposed to varying topotecan doses (0.01-10 microM) always 15 minutes before and either 1 hour after (short-term) or 24 hours after (long-term) irradiation. Survival was measured by colony-forming assays, and chromosome aberrations were scored in Giemsa-stained metaphase spreads. Unirradiated cells served as specific controls. RESULTS: Topotecan alone reduced the clonogenic cell survival in a concentration- and time-dependent manner, and radiosensitization was observed for all cell lines tested. There was no correlation between clonogenic cell survival and the frequencies of treatment-induced chromosomal aberrations, neither in tumor cells nor in fibroblasts. In contrast, in lymphocytes increased frequencies of radiation-induced dicentric chromosomes were seen after the combined treatment. CONCLUSION: In certain cell types combined radiation/topotecan treatment may lead to increased frequencies of lethal chromosome aberrations. However, there is no evidence that the increased formation of lethal chromosome aberrations plays an important role in the topotecan-induced radiosensitization of human tumors.

Adenocarcinoma↗
PubMed2002

The impact of patient positioning on the adequate coverage of the uterus in the primary irradiation of cervical carcinoma: a prospective analysis using magnetic resonance imaging.

BACKGROUND AND PURPOSE: The intention of this prospective study is to assess the influence of different patient positionings and the use of belly boards on the coverage of the uterus by standard radiation fields. MATERIAL AND METHODS: In 21 women with carcinoma of the uterine cervix magnetic resonance imaging (MRI) scans in prone patient position with and without belly board and computed tomography (CT) scans in supine position were analysed after superimposing standard pelvic box fields. Further, all patients underwent a second MRI field control in prone position with belly board to detect intraindividual variations in the uterus position during treatment. RESULTS: Standard portals did not completely cover the uterus in supine position in 7/21 (33%), in prone position with belly board in 7/21 (33%) and without belly board in 5/21 (24%). Insufficient uterine coverage was found only in the anteroposterior direction. The mean distance (+/- standard deviation) between the field borders of the lateral portals and the uterus was in supine position anteriorly 3.4 cm (+/-2.2 cm) and posteriorly 1.8 cm (+/-1.3 cm), in prone position with belly board anteriorly 2.2 cm (+/-2.7 cm) and posteriorly 2.6 cm (+/-1.6 cm), prone without belly board anteriorly 3.3 cm (+/-2.4 cm) and posteriorly 1.9 cm (+/-1.1 cm). The difference was statistically significant between supine and prone position with belly board and between prone position with and without belly board. Repeated MRI controls during therapy showed no significant changes compared to the MRIs at the beginning of therapy. CONCLUSIONS: The use of standard radiation fields results in a high percentage of geographical misfits. Three-dimensional treatment planning is a prerequisite for adequate uterus coverage.

Adult↗
PubMed2002

Platelet function in sepsis.

OBJECTIVE: To evaluate platelet function in sepsis. DATA SOURCES: The MEDLINE database and bibliographies of selected articles. DATA SYNTHESIS: The common occurrence of thrombocytopenia in critically ill patients has been recognized for many years and is known to be associated with an increased mortality rate. Platelet function can be divided into four areas: activation, adhesion, aggregation, and secretion. Studies have found that activated platelets secrete key components of the coagulation and inflammatory cascades and are involved in the regulation of vascular tone. However, studies on platelet function in sepsis have been scarce, and their data are often conflicting. In sepsis, aggregation of circulating platelets seems to be reduced, yet platelet receptors are present in normal amounts. CONCLUSIONS: Platelets play a complex role in sepsis; they are able to modulate not only their own function but also that of cells around them. Further study is needed to better define the precise mechanisms and effects of platelet activation in sepsis and to determine the benefits and risks of inhibiting platelet function.

Animals↗