Search PubMed⌕ Search

Biomedical subjects

C Gimenez

Publications and source records attributed to C Gimenez.

At least 19 recordsLinked to original sources
PubMed2006

Phase II trial of temozolomide and cisplatin followed by whole brain radiotherapy in non-small-cell lung cancer patients with brain metastases: a GLOT-GFPC study.

BACKGROUND: Brain metastases (BM) considerably worsen the prognosis of non-small-cell lung cancer (NSCLC) patients. The usefulness and choice of chemotherapy remain uncertain in this indication since these patients are excluded from most clinical trials. We conducted a phase II study to determine the efficacy and tolerability of up-front chemotherapy with association of temozolomide and cisplatin in NSCLC patients with BM. PATIENTS AND METHODS: Fifty NSCLC patients with BM received temozolomide (200 mg/m(2)/day for 5 days every 28 days) and cisplatin (75 mg/m(2) at day 1 of each cycle), up to six cycles, followed by whole brain radiotherapy (WBRT). An evaluation was carried out every two cycles and after WBRT. WBRT was performed earlier in case of progressive disease at any time or stable disease after cycle 4. RESULTS: Eight objective responses were achieved (16%). Overall median survival was 5 months. Median time to progression was 2.3 months. Ten patients (20%) presented a grade 3/4 neutropenia and 11 patients (22%) presented a grade 3/4 thrombopenia. CONCLUSION: This study demonstrates a lack of efficacy of up-front chemotherapy with association of temozolomide and cisplatin in these patients. Nevertheless, it supports the feasibility of chemotherapy before brain radiotherapy in NSCLC patients with BM.

Adult↗
PubMed2006

Cost-minimization analysis of a phase III trial comparing concurrent versus sequential radiochemotherapy for locally advanced non-small-cell lung cancer (GFPC-GLOT 95-01).

BACKGROUND: We conducted an economic analysis of a phase III clinical trial comparing sequential radiochemotherapy (RT-CT) with concurrent RT-CT in patients with locally advanced non-small-cell lung cancer. PATIENTS AND METHODS: The trial was a randomized multicenter study comparing three cycles of chemotherapy (arm A) followed by radiotherapy against an RT-CT combination (two cycles of platinum etoposide) followed by two cycles of platinum-vinorelbine (arm B). The economic analysis adopted the payer's perspective and only included direct costs. Costs (euro, 1996-2003) were recorded until the cut-off date. A cost minimization analysis and a sensitivity analysis were carried out. RESULTS: Data from 173 patients were used in the economic study. Protocol costs tended to be higher in arm B, while relapse costs were significantly higher in arm A. The total number of hospital days was higher in arm B. The average total cost per patient was euro16,074 in arm A and euro15,245 in arm B (P=0.15). The cost minimization analysis favored arm B. This advantage persisted in the sensitivity analysis. CONCLUSIONS: Concurrent RT-CT was not the more costly strategy in this phase III trial, despite lengthier hospitalization for toxicity. Other studies of similar design are needed to confirm these results in future randomized trials.

Adolescent↗
PubMed2005

[Use of 153Sm-EDTMP to relieve pain from bone metastasis in lung cancer].

INTRODUCTION: The treatment of bone metastasis from lung cancer is palliative in nature with elimination of pain being the primary goal. Management is based on pharmacologicalmethods (steroids, morphine, and pamidronate) and radiotherapy. However, other treatments have been developed including the systemic radiopharmaceutical 153Sm-EDTMP. CASE REPORTS: We report data from 6 lung cancer patients with bone metastases treated with 153Sm-EDTMP. Demographic and therapeutic data, pain evaluation by visual analogue scale (VAS) and change in opioid analgesia requirements (expressed as intravenous morphine equivalent) as well as survival were studied. Pain associated with bone metastasis (median VAS = 8 [7-9], median morphine dose = 167 mg [100-800 mg]) did not significantly improve (median VAS after 153Sm-EDTMP = 8.5 [5-10], median morphine dose after 153Sm-EDTMP = 185 mg [30-2 200 mg]) in this group of patients. CONCLUSION: Our results combined with current data in the literature concerning the use of this treatment in the treatment of bone pain associated with metastatic lung cancer suggest that at present its use cannot be recommended outside the context of clinical of clinical trials.

Aged↗
PubMed2004

[Disordered higher functions in a smoker].

INTRODUCTION: Paraneoplastic syndromes sometimes lead to the discovery of an intrathoracic tumour, notably small cell lung cancer (SCLC). MATERIALS AND METHODS: We report the case of a patient presenting with a paraneoplastic syndrome characterised by disordered higher functions and convulsions, representing a paraneoplastic encephalo-myelitis (PEM). This PEM led to the diagnosis of SCLC. The diagnostic features and progress of the PEM are discussed. CONCLUSION: Recognition of PEM allows the diagnosis and early treatment of the underlying cancer, strongly influencing the prognosis, particularly in SCLC.

Carcinoma, Small Cell↗
PubMed2003

[Acute pulmonary toxicity due to gemcitabine: a role for asbestos exposure?].

INTRODUCTION: Gemcitabine is an important drug in the treatment of non-small cell lung cancer. Myelosuppression is the most common toxic effect but its use sometimes leads to severe pulmonary toxicity by means of diffuse alveolar damage or sub-acute interstitial pneumonitis. METHODS: A retrospective study was made of all the patients treated in our department with this drug, alone or in combination. Episodes of acute dyspnoea during the course of chemotherapy were identified, and data were collected concerning the past history, the illness and the treatment in patients who had developed a respiratory failure attributable to gemcitabine. RESULTS: 312 patients had been treated with gemcitabine over a 5 year period and 18 had developed episodes of acute dyspnoea, of which 6 (1.9%) were attributed to the drug itself. Of these patients 4 had notifiable industrial disease (no. 30bis) secondary to asbestos exposure (odds ratio=85, 95% confidence interval 13-546) and 5 were active smokers. The possible role of intracellular ATP pool depletion secondary to asbestos exposure or smoking as a predisposing factor in the development of gemcitabine pulmonary toxicity is discussed. CONCLUSION: Smoking and asbestos exposure should be taken into account in future studies of gemcitabine pulmonary toxicity.

Acute Disease↗
PubMed2003

[Tolerance of fiberoptic bronchoscopy by self-administered questionnaire: in the words of the patients].

INTRODUCTION: Fibreoptic bronchoscopy is currently undertaken by the majority of respiratory physicians, but under varying conditions. Though complications are rare the tolerance of this examination is sometimes poor, particularly when it is performed under local anaesthesia. The undesirable effects may reduce the value of the examination as well as causing discomfort for the patient. METHODS: A prospective study of the tolerance of the endoscopic examination was made on 100 consecutive patients by self-administered questionnaire. RESULTS: There were no major and 7 minor complications (7%). 45% of the patients were anxious but the experience of the operator tended to reassure them (p=0.07). 30% of the patients reported some pain, which tended to be exacerbated by anxiety (44% vs 18%, p=0.008) and the supine position (57% vs 43%, p=0.047). 37% of patients reported nausea, and 50% dyspnoea, without any significant predictive factor. 79% would agree to a repeat examination under the same conditions and 92% said that they had received information appropriate to the examination undergone. CONCLUSION: The tolerance of fibreoptic bronchoscopy under local anaesthesia is poor and perhaps overestimated by respiratory physicians. Patient information is essential. A national enquiry could lead to the standardisation of techniques.

Anesthesia, Local↗
PubMed2003

[An experimental study on the systemic distribution of calibrated talc after intra-pleural injection].

INTRODUCTION: Among the agents used to produce pleural symphysis talc is the most effective and least expensive. However, its use is controversial on account of the description of respiratory complications associated with subsequent systemic spread of the talc particles. This hypothesis rests on clinical and experimental observations of talc particles in the viscera. However, all talc preparations are not identical and this extra-pleural spread could be dependent on particle size. This experimental study was undertaken to determine whether there was systemic spread of a calibrated talc preparation used routinely in clinical practice following intra-pleural administration in rats. METHODS: 48 rats received 20 mg (11 rats) and 40 mg (33 rats) of calibrated talc suspended in 1 ml of physiological saline by intra-pleural injection. The animals were randomised for sacrifice at 24 hours (22 rats) and 72 hours (22 rats) after the injection. The lungs, parietal pleura, diaphragm, liver, spleen, pericardium, brain and blood were examined by light microscopy and polarised light to search for bi-refringent particles. RESULTS: No deaths occurred during the procedure. At the time of sacrifice no pleural symphysis was seen. In 5 animals some talc particles were seen in the extra-thoracic organs: in the liver in 3 in the spleen in 1 and one particle in the brain of one animal examined by electron microscopy. No talc particles were found in the blood. CONCLUSIONS: Intra-pleural injection of calibrated talc, (Steritalc-Novatech-Plan de Grasse-France) has a weak systemic spread in > small animals. These results may be related to the diameter of the talc particles used (mean 33.6 microns; median 31.3 microns). The hypothesis that systemic spread is influenced by the diameter of the talc particles needs to be supported by experimental studies using talc particles of smaller diameter in order to compare the systemic distribution of the different preparations.

Animals↗
PubMed2000

Familial osteoarthritis and Milwaukee shoulder associated with calcium pyrophosphate and apatite crystal deposition.

OBJECTIVE: To characterize and define the phenotypes observed in a large Italo-Argentinean kindred with osteoarthritis, chondrocalcinosis, and Milwaukee shoulder (MS). METHODS: Seventy-five members were evaluated with a history, examination, and radiographs of shoulders, spine, hands, and knees. Superior subluxation of the glenohumeral joint was graded using shoulder radiographs and tomography and nuclear magnetic resonance imaging and 3 dimensional computed tomography was performed on selected members. In 31 family members peripheral blood DNA was utilized for genetic linkage analysis of several candidate gene loci previously linked to chondrocalcinosis phenotypes, as well as those implicated in the proper patterning of skeletal elements and cartilage differentiation. In addition, direct sequence analysis of type II collagen gene (COL2A1), the gene that codes for the major structural protein of cartilage, was undertaken in 3 affected and 3 unaffected members of the family. RESULTS: MS was seen in one member of the first generation and 6 members of the 2nd generation, while 8 members of the 3rd generation showed an incomplete form of MS. Isolated superior subluxation of the shoulder was seen in 16 other family members of the 3rd and 4th generations. Osteoarthritis of the spine and peripheral joints was seen in 31 affected members, while chondrocalcinosis was observed in 6 members of the first generation. Shoulder synovial fluid from 2 patients showed the presence of both apatite and calcium pyrophosphate dihydrate crystals. Direct analysis of the COL2A1 gene indicated no known disease determining mutations in affected members, thus excluding this gene as a candidate gene in this family. Genetic linkage to several candidate loci, including the chondrocalcinosis loci on chromosomes 5p and 8q, as well as loci for HOX A and C were also excluded. Linkage analyses of other loci for the HOX B and D genes and the PAX 1 and 9 genes were uninformative in this kindred. CONCLUSION: This kindred illustrates an unusual type of osteoarthritis with secondary intraarticular and periarticular calcification and MS in the most severely affected elderly members. A search for linkage to some potential candidate genes was either excluded or uninformative. Further linkage analysis to identify potential candidate genes is in progress.

Adult↗
PubMed1999

Recanalization of thrombosed superficial femoral arteries with a hydraulic thrombectomy catheter in a canine model.

OBJECTIVE: This experiment was conducted to evaluate efficacy and safety of the Oasis thrombectomy catheter on arterial thrombosis in dogs. MATERIALS AND METHODS: Thrombosis was induced in 18 femoral arteries of nine mongrel dogs. Recanalization of the thrombosed femoral artery was performed using a thrombectomy catheter 7-10 days after thrombus induction. Pre- and postprocedural arterial status was documented by angiography. After mechanical thrombectomy, the animals were sacrificed and the femoral arteries were harvested and examined macro- and microscopically. Additionally, in vitro fragmentation was carried out to determine particle size and distribution from the recovered effluent. RESULTS: Subacute thrombosis was successfully created in 15 femoral arteries. Full recanalization was achieved in 80% (12/15) of the thrombosed femoral arteries without any residual thrombus. No significant downstream embolization was documented angiographically. Endothelial denudation was observed in all the treated arteries along with occasional disruption of the internal elastic lamina. No medial injury was seen. Ninety-eight percent of thrombus was liquefied, defined as particles smaller than 15 microm, by the catheter. Particles larger than 400 microm represented 0.27% of the original clot weight. CONCLUSION: Occluded femoral arteries with 7- to 10-day-old thrombus can be efficiently recanalized with the Oasis catheter in dogs without any significant complication. This thrombectomy catheter appears to be highly effective and safe and requires no sophisticated equipment. Blood loss was our major concern regarding use of this catheter but can be minimized by strictly controlling activation time and restricting the inflow into the vascular segment being treated.

Animals↗
PubMed1998

Enhanced MHC class II-restricted presentation of measles virus (MV) hemagglutinin in transgenic mice expressing human MV receptor CD46.

This study analyzes the role of the measles virus (MV) receptor, i.e. the human CD46 molecule, in the MHC class II-restricted presentation of MV hemagglutinin (H). We generated transgenic mice ubiquitously expressing CD46, with a similar level of transgene expression on the surface of antigen-presenting cells (APC), i.e. B cells, dendritic cells (DC) and macrophages. APC isolated from transgenic mice and nontransgenic controls were tested for their ability to present MV H to H-specific CD4+ I-Ed-restricted T cell hybridomas. All three populations of APC were capable of presenting MV to T cell hybridomas, DC being the most efficient. Expression of CD46 on B lymphocytes increased MHC class II-dependent presentation of MV H up to 100-fold, while CD46-transgenic DC stimulated H-specific T cell hybridomas up to 10-fold better than nontransgenic DC. Interestingly, expression of CD46 did not change the presentation efficiency of transgenic macrophages, indicating that CD46-dependent enhancement of antigen presentation depends on the nature of the APC. Furthermore, a single injection of UV-inactivated MV particles into CD46-transgenic mice, but not nontransgenic controls, induced generation of MV-specific T lymphocytes and production of anti-H antibodies, suggesting a role for CD46 in the efficient capture of MV in vivo. These results show for the first time that one ubiquitously expressed cell surface receptor, like CD46, could function in receptor-mediated antigen presentation both in vitro and in vivo and its performance depends on the type of APC which expresses it.

Animals↗
PubMed1998

Increased chromosome abnormalities in human preimplantation embryos after in-vitro fertilization in patients with recurrent miscarriage.

Recurrent miscarriage is a pathological condition induced by maternal and embryonic causes. This paper describes a prospective study to determine the real incidence of aneuploidy for autosomes 13, 16, 18, 21, 22, and gonosomes in preimplantation human embryos obtained from patients with recurrent pregnancy loss after ovarian stimulation in an IVF-ET programme. Our results indicate that aneuploidy for the chromosomes analysed are abnormally higher in embryos obtained after IVF from recurrent abortion patients (58%) compared to non-recurrent abortion patients undergoing IVF. Furthermore, monosomies are six times more frequent than trisomies (47:8) in preimplantation embryos from recurrent abortion patients. Based on the present study, preimplantation genetic diagnosis (PGD) of embryos obtained from patients with recurrent miscarriage could prove advantageous in diagnosing abnormal embryos and selecting normal embryos for transfer.

Abortion, Habitual↗
PubMed1997

Neuronal dependency of the glycine transporter GLYT1 expression in glial cells.

Two membrane-localized transporter proteins (GLYT1 and GLYT2) are responsible for removal of extracellular glycine in the mammalian CNS. Whereas GLYT1 seems to be expressed mainly in glial cells, GLYT2 is neuronal. The highest concentrations of both transporters are found in glycinergic areas of the nervous system. The expression of these proteins may be under regulatory control. We demonstrate here that GLYT1 is not expressed in pure glial cultures, but it is expressed by diverse types of glial cells in mixed neuronal/glial cultures. In these mixed cultures, the glial expression of GLYT1 is down-regulated after selective elimination of the neurons. The absence of expression in pure glial cultures and the observed reduction in the GLYT1 expression after neuronal loss support the existence of a regulatory cross-talk between neurons and glia to initiate and sustain the glial expression of GLYT1.

Amino Acid Transport Systems, Neutral↗
PubMed1996

Congenital and acquired lung hernias.

Lung hernia is defined as a protrusion of lung parenchyma beyond the confines of the musculoskeletal thorax. Lung hernias can be classified according to location (i.e., cervical, thoracic, or diaphragmatic) and etiology. Approximately 80% of reported cases of lung hernia are acquired, usually related to trauma or surgery. Symptoms are few, infrequent, and vague. A painless, local, and inconstant bulging is evident on physical examination. The diagnosis of a lung herniation is accomplished using chest radiographs in the most cases. Surgery is usually reserved for large hernias or incarcerated hernias.

Hernia↗
PubMed1996

Type III bare lymphocyte syndrome: lack of HLA class II gene expression and reduction in HLA class I gene expression.

The bare lymphocyte syndrome (BLS) consists of an association between a combined immunodeficiency disease and a significantly reduced expression of either human histocompatibility leukocyte antigens (HLA) class I (HLA-A, -B, -C) or HLA class II (HLA-DP, -DQ, -DR) at the cell surface. BLS type III, the more frequent form of this syndrome, is characterized by impaired expression of both class I and class II antigens on patients' cells, in particular on leukocytes. We describe herein the demonstration that expression of HLA class I molecules was reduced by approximately half on Epstein-Barr virus-transformed B cells (LCL) derived from type III BLS patients. HLA class I mRNA level was also decreased to the same extent. Expression of HLA class I molecules was also very significantly reduced at the surface of these fibroblasts as was mRNA specific for HLA class I. Simultaneously, the expression of HLA-DR molecules on LCL was even more greatly decreased, and the expression of HLA-DQ antigens was virtually abolished. Molecular analysis demonstrated an absence of mRNA for the alpha- and beta-chains of HLA-DQ and HLA-DR in the patients' lymphocytes. In general, such patients present with an association of an absence of expression of HLA class II antigens and a significantly reduced expression of HLA class I antigens. The mechanism of this association is still uncertain.

Child↗
PubMed1995

Chronic and acute respiratory effects among grain mill workers.

Exposure to flour dust may induce chronic respiratory manifestations as well as acute ventilatory effects. We compared the prevalence of respiratory symptoms, ventilatory impairment, and variations in pulmonary function over the workshift in a group of mill workers exposed to wheat flour and in referent workers. One hundred and forty-two men exposed to flour in a mill and 37 referent workers were included in this study. Each subject completed a standardized questionnaire. Pulmonary function tests were performed before and after the workshift. The assessment of environmental exposure to flour showed high concentrations during some jobs with a high percentage of inhalable particles and a low concentration of respirable particles. The exposed workers had a significantly higher prevalence of usual cough and usual phlegm than the referents. The prevalence of asthma, based on the questionnaire, was similar. Before the workshift, the exposed workers had significantly lower mean lung function values for peak flow rate and forced expiratory flow rate at 75% of the vital capacity than the referents. After the workshift, all the lung function values showed a slight decrease, significant for forced vital capacity and forced expiratory volume during 1 s in both groups. Among the exposed workers, the asthmatic subjects had a significantly higher decrease across the shift than the nonasthmatic workers. This result is probably linked to bronchial hyperreactivity. Among nonasthmatic subjects, the decrease was larger in nonexposed workers than in exposed workers. A higher prevalence of respiratory symptoms and lower pulmonary function values were observed among mill workers by comparison with referents. Moreover, the data suggest that asthmatic status and the time of spirometric measurements need to be taken into account in epidemiological studies on exposure to airborne allergens. In addition, the study does not exclude a healthy worker effect with selection of dust-resistant subjects or better identification of asthmatic subjects among the workers exposed to an allergenic substance than among the nonexposed workers.

Adult↗
PubMed1995

Cell-to-cell contact via measles virus haemagglutinin-CD46 interaction triggers CD46 downregulation.

CD46 downregulation by measles virus (MV) occurs after expression of virus haemagglutinin (H) protein on the surface of the infected cell and is a consequence of CD46-H interaction on the cell membrane. To assess whether CD46 downregulation also occurs after CD46-H interaction when these two molecules are expressed on distinct cells, we used human T cell line Jurkat (expressing CD46) and transfected murine fibroblast line L stably expressing MV-H protein (L.H). FACS analysis shows that cell-to-cell contact of 1 h at 37 degrees C triggers a reduction of CD46 cell surface labelling as detected by MCI20.6, GB24 and J4-48 monoclonal antibodies. This reduction is similar to that observed after MV infection or after infection with recombinant vaccinia virus encoding MV-H protein. By contrast, MV-H protein was downregulated only when CD46-H interaction occurred on the same cell membrane. CD46 downregulation is specific for CD46-H interaction because it was not observed after coincubation of Jurkat cells with either L cells expressing MV nucleoprotein (L.NP) or L cells. Moreover, this downregulation could be blocked by either anti-CD46 or anti-H antibodies. The H-mediated CD46 downregulation is reversible and restricted to CD46 since expression of other surface markers (CD3, CD14, CD47 and CD63) is unaffected. It is apparently not mediated in a protein kinase (PK) A- or PKC-dependent manner. Altogether, our results provide an unequivocal demonstration that interaction between the extracellular domains of CD46 and MV-H is sufficient to trigger CD46 downregulation.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Invariant chain expression similarly controls presentation of endogenously synthesized and exogenous antigens by MHC class II molecules.

I-Ak- and I-Ed-transfected L fibroblasts were supertransfected with cDNA coding for hen egg lysozyme (HEL) or measles virus hemagglutinin (HA). Well-defined cell culture conditions allowed us to obtain L cells with either no detectable endogenous Ii mRNA or a high level of endogenous Ii mRNA induced by serum starvation. Cells supertransfected with mouse Ii chain gene stably expressing a high level of Ii chain were also used as APC in parallel experiments. Class II presentation of endogenously secreted HEL or an ER-retained form of HEL to the HEL-specific I-Ak-restricted 3A9 T cell hybridoma was found to be strongly enhanced in cell transfectants expressing Ii chain. Similar results were obtained with the presentation of transmembrane HA to the HA-specific I-Ed-restricted TH5.143 T cell hybridoma. These findings correlate with those obtained with the presentation of exogenous HEL and HA. In addition, as reported to be the case for exogenous antigen, expression of a large amount of endogenous HA by the APC supplants the requirement for Ii chain expression in the enhancement of antigen presentation. These data demonstrate that presentation by MHC class II molecules of a given antigen, either exogenously provided or endogenously synthesized, is controlled in a similar manner by the Ii chain.

Animals↗