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Biomedical subjects

I Monnet

Publications and source records attributed to I Monnet.

At least 37 records · Page 2Linked to original sources
PubMed1998

Routine use of granulocyte colony-stimulating factor is not cost-effective and does not increase patient comfort in the treatment of small-cell lung cancer: an analysis using a Markov model.

PURPOSE: The clinical indications and economic consequences of human granulocyte colony-stimulating factor (G-CSF) prescription during small-cell lung cancer (SCLC) chemotherapy remain controversial. The aim of this study, based on a Markov model, was to assess the impact of routine G-CSF use in the treatment of SCLC on costs and patient comfort. Markov models allow the modeling SCLC chemotherapy, in which the risk of febrile neutropenia (FN) is continuous over time and may occur more than once. PATIENTS AND METHODS: We used a Markov model to compare three strategies: a chemotherapy dose reduction after FN and nonuse of G-CSF ("never" strategy), secondary use of G-CSF ("CSF if FN" strategy) and primary use of G-CSF ("systematic CSF" strategy). Model baseline probabilities were based on a review of medical records for all patients (n = 39) treated for SCLC in our unit during 1993 (when G-CSF was not used) and on published reductions in the incidence of FN obtained by using G-CSF. Two different types of rewards were used: a cost-utility scale that took into account the costs of FN (CFN) episodes and G-CSF (CCSF) courses; and a comfort-utility scale that took into account the discomfort of FN and G-CSF therapy. Costs were analyzed from the health care payer's perspective and utilities were assessed prospectively in standardized interviews with treated SCLC patients. RESULTS: The never strategy was the least costly ($4,875 [United States] versus $5,816 and $7,690 for CSF if FN and systematic CSF) and gave the highest comfort value (378 U v 365 and 327 for CSF if FN and systematic CSF). Sensitivity analyses showed that the never strategy remains the less costly when the probability of a first FN episode was less than 49%, the probability of FN recurrence was less than 60%, or the CFN was less than $6,077, or the CCSF was greater than $863. In terms of patient comfort, the never strategy was the best choice, except for patients who considered that a course of G-CSF caused little or no discomfort, whether or not it prevented FN. CONCLUSION: Routine use of G-CSF during SCLC chemotherapy is not justified by clinical benefits, improved patient comfort, or economic considerations.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

[Thiamine deficiency. A cause of cardiac insufficiency not to be ignored].

Thiamine deficiency is one of the classical causes of high out put for heart failure. Deficiency of this vitamin may be nutritional or secondary to alcoholic intoxication. We felt it would be interesting to describe a typical case of cardiac beriberi in order to recall the clinical presentation and the pathophysiology.

Acidosis↗
PubMed1997

Higher doses of alpha-interferon do not increase the activity of the weekly cisplatin-interferon combination in advanced malignant mesothelioma.

Management of advanced malignant mesothelioma (MM) still requires innovative systemic therapy as its prognosis is poorly affected by currently available chemotherapy. The combination cisplatin and alpha-interferon (alpha-INF) has synergistic antitumoral activity in preclinical models and interesting activity in phase I-II clinical trials. Weekly CDDP (60 mg/m2) and alpha-IFN (3 MUI/d: d1-d4) in combination was tested in a previous phase I-II study in 23 MM patients, with a 36% objective response rate (ORR). A trial with higher doses of alpha-IFN in the same combination schedule was conducted to explore an incrementalist hypothesis. Thirty patients with MM received the same CDDP dose (60 mg/m2/w) and doubled doses of alpha-IFN (6 MUI/d: d1-d4). The treatment protocol consisted of two cycles of 4 weeks on/4 weeks off followed by two shorter cycles of 3 weeks on/3 weeks off, in the absence of life-threatening toxicity or progressive disease. All patients were evaluable for toxicity. The main treatment-limiting side-effects were digestive intolerance (nausea, vomiting) and severe asthenia. Antitumoral efficacy was not increased (ORR = 27%). Haematological and neurological toxicities were moderate and manageable. The antitumoral activity of the CDDP-alpha-IFN combination with higher doses of the latter is similar to our previous experience, but tolerance issues make it a poorer choice for eventual comparative trials, or as a standard therapeutic indication.

Adult↗
PubMed1997

Differential responsiveness of human and rat mesothelioma cell lines to recombinant interferon-gamma.

Recombinant human interferon-gamma (r-hu-IFN-gamma) has been found to exert an antitumor action in vivo in early stages of human malignant mesothelioma, and an antiproliferative effect in vitro. In order to study the mechanisms of cytostasis in mesothelioma cells, we examined two IFN-gamma-controlled metabolic pathways known to mediate growth arrest in various cell types, measuring production of the antiproliferative compound nitric oxide (NO) and degradation of tryptophan in nine human mesothelioma cell lines (HMCLs) displaying different sensitivities to the antiproliferative effect of r-hu-IFN-gamma. Two rat mesothelioma cell lines were also studied. IFN-gamma receptor was present and functional in HMCLs, regardless of their sensitivity to the growth-inhibitory effect of r-hu-IFN-gamma. However, no NO synthase activity or the resulting antiproliferative molecule NO were induced in HMCLs treated either with r-hu-IFN-gamma alone or with a combination of r-hu-IFN-gamma and other cytokines, and/or with lipopolysaccharide (LPS). In responsive HMCLs, r-hu-IFN-gamma induced strong indoleamine-2,3-dioxygenase (IDO) activity, which causes rapid degradation of tryptophan; however, the correlation between r-hu-IFN-gamma-mediated growth arrest and IDO induction was not absolute. In rat mesothelioma cells, NO synthase was induced in response to murine IFN-gamma + interleukin-1beta (IL-1beta) treatment, and played a role in the cytokine-mediated antiproliferative activity. However, NO production did not seem to be the unique antiproliferative mechanism induced by cytokines in these cells. Our results indicate that two classical pathways accounting for some of the cytostatic effects of IFN-gamma in rodent cells are not efficient in human mesothelioma cells, and suggest that cytokine-induced growth inhibition is mediated by a different pathway in HMCLs.

Animals↗
PubMed1996

Combined systemic chemoimmunotherapy in advanced diffuse malignant mesothelioma. Report of a phase I-II study of weekly cisplatin/interferon alfa-2a.

PURPOSE: To assess the tolerance, toxicity, and antitumoral activity of the weekly combination of cisplatin (CDDP) and interferon alfa-2a (IFNalpha2a) in advanced diffuse malignant mesothelioma (DMM). PATIENTS AND METHODS: Twenty-six patients with DMM (23 pleural and three peritoneal), previously untreated, were enrolled onto this study between August 1991 and December 1992. All patients had measurable disease defined by computed tomographic (CT) scan and diagnostic confirmation by histopathology review panel. IFNalpha2a (3 x 10(6) IU subcutaneously on days 1 to 4) and CDDP (60 mg/m2/wk on day 2) were given weekly. Initially planned as a 5-weeks-on/3-weeks-off treatment cycle, poor patient tolerance observed in the first 12 patients treated (group A) led to schedule adaptation with a shorter treatment sequence and prolongation of the rest period (4 weeks on/4 weeks off) in the following 14 patients (group B). At least two cycles were administered to each patient in the absence of tumor progression. RESULTS: Twenty-six patients were assessable for toxicity and 25 for efficacy (World Health Organization [WHO] criteria). Sixty-eight cycles of IFN/CDDP were given, with a median of three cycles per patient (range, one to five). Toxicity was mainly clinical, with progressive anorexia, asthenia, and prolonged nausea/emesis; these side effects have limited treatment acceptance in many patients. Thrombocytopenia and leukopenia were rarely noted as treatment-limiting toxicities. Objective responses (all partial) were obtained in 10 patients (95% confidence interval [CI], 20% to 60%). The median response duration was 11 months (range, 6 to 18). The median time to progression (TTP) for the whole cohort was 6 months and the median survival time was 12 months (range, 5 to 32). Objective responders had a significantly longer median TTP (21 months) and survival time (25 months) than nonresponders (3 and 8 months, respectively). CONCLUSION: The results of this pilot phase I-II study show encouraging antitumor activity in this traditionally resistant tumor, even if the specific contribution of IFN remains speculative and needs further clinical research. Our ongoing program is exploring the dose-intensity impact of IFN dose within the same combination.

Adult↗
PubMed1995

Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission.

BACKGROUND: Prophylactic cranial irradiation in patients with small-cell lung cancer decreases the overall rate of brain metastases without an effect on overall survival. It has been suggested that this treatment may increase neuropsychological syndromes and brain abnormalities indicated by computed tomography scans. However, other retrospective data suggested a beneficial effect on overall survival for patients in complete remission. PURPOSE: Our purpose was to evaluate the effects of prophylactic cranial irradiation on brain metastasis, overall survival, and late-occurring toxic effects in patients with small-cell lung cancer in complete remission. METHODS: We conducted a prospective study of 300 patients who had small-cell lung cancer that was in complete remission. The patients were randomly assigned to receive either prophylactic cranial irradiation delivering 24 Gy in eight fractions during 12 days (treatment group) or no prophylactic cranial irradiation (control group). A neuropsychological examination and a computed tomography scan of the brain were performed at the time of random assignment and repeatedly assessed at 6, 18, 30, and 48 months. Patterns of failure were analyzed according to total event rates and also according to an isolated first site of relapse, using a competing-risk approach. RESULTS: Two hundred ninety-four patients who did not have brain metastases at the time of random assignment were analyzed. The 2-year cumulative rate of brain metastasis as an isolated first site of relapse was 45% in the control group and 19% in the treatment group (P < 10(-6)). The total 2-year rate of brain metastasis was 67% and 40%, respectively (relative risk = 0.35; P < 10(-13)). The 2-year overall survival rate was 21.5% in the control group and 29% in the treatment group (relative risk = 0.83; P = .14). There were no significant differences between the two groups in terms of neuropsychological function or abnormalities indicated by computed tomography brain scans. CONCLUSIONS: Prophylactic cranial irradiation given to patients with small-cell lung cancer in complete remission decreases the risk of brain metastasis threefold without a significant increase in complications. A possible beneficial effect on overall survival should be tested with a higher statistical power. IMPLICATIONS: The results of the trial favor, at present, the indication of prophylactic cranial irradiation for patients who are in complete remission. A longer follow-up and confirmatory trials are needed to fully assess late-occurring toxic effects. The possible effect on overall survival needs to be evaluated with a larger number of patients in complete remission, and a meta-analysis of similar trials is recommended.

Aged↗
PubMed1995

Human malignant mesothelial cells: variability of ultrastructural features in established and nude mice transplanted cell lines.

The aim of this study was to determine, by transmission electron microscopy, the differentiation features of 21 human malignant mesothelioma cell lines (HMCLs) established from 13 specimens of 12 confirmed human malignant mesotheliomas, and of tumours induced in nude mice injected with 16 HMCLs. Fifty per cent of HMCLs showed typical mesothelial differentiation (long and slender microvilli, desmosomes, perinuclear intermediate filaments); 29 per cent did not show differentiation; and the remainder were poorly differentiated. Three human tumour specimens gave several different HMCLs; the cell lines obtained from a given tumour exhibited variable mesothelial differentiation. Eleven HMCLs were compared with the native tumour. Four were similar to the tumour and seven were less well differentiated, in most cases in relation to their microvilli. With six HMCLs, tumours induced in nude mice were less well differentiated than the corresponding cell lines, whereas with four HMCLs, tumours were equally or better differentiated. However, in most nude mice tumours, typical mesothelial microvilli were present. These results show that cell lines established from malignant mesothelioma may exhibit dedifferentiated features. However, while the variability in ultrastructural differentiation may result from the culture microenvironment, it could also be related to the state of differentiation, of the native tumour sample and to tumour cell heterogeneity.

Animals↗
PubMed1994

Intrapleural treatment with recombinant gamma-interferon in early stage malignant pleural mesothelioma.

BACKGROUND: This report presents the results of a prospective multi-institutional study of intrapleural treatment with gamma-interferon in patients with Butchart's Stages I and II epithelial or mixed malignant pleural mesothelioma. METHODS: Interferon was administered at a dose of 40 million units twice a week for 8 weeks intrapleurally via a catheter or an implantable port. Thoracoscopic or surgical biopsy was performed if computed tomography scan 2 weeks after the end of treatment demonstrated a reduction in tumor size. Survival was calculated after a follow-up of at least 18 months. Prognostic factors were identified by univariate and multivariate analyses (Cox model). RESULTS: Eighty-nine patients were included over 46 months. Eight histologically confirmed complete responses and nine partial responses with at least a 50% reduction in tumor size were obtained. The overall response rate was 20%. Most responses were achieved in patients with early stage disease. The response rate for patients with Stage I disease was 45%. Tolerance of interferon was good. Treatment was performed on an outpatient basis. The main side effects were hyperthermia, liver toxicity, neutropenia, and catheter-related infection. CONCLUSIONS: Gamma-interferon is effective mainly in Stage I mesothelioma, especially if the tumor is confined to the parietal or diaphragmatic pleura (Stage IA).

Aged↗
PubMed1994

Intrapleural production of interleukin 6 during mesothelioma and its modulation by gamma-interferon treatment.

In vivo production of monokines was analyzed in 17 human malignant pleural mesotheliomas. High concentrations of interleukin 6 (IL-6) were detected in pleural effusions, contrasting with low levels of IL-1 beta and tumor necrosis factor alpha. This production arose from malignant cells, as shown by immunochemical analysis of pleural cells and by production of IL-6 by mesothelial cell lines. Intrapleural administration of recombinant human gamma-interferon to six patients led to a marked decrease in intrapleural IL-6 concentrations in all cases. This treatment was associated with in situ activation of macrophages and cytotoxic T-lymphocytes, as indicated by increased intrapleural neopterin and soluble CD8 concentrations. In vitro gamma-interferon had no effect on the production of IL-6 by mesothelial cell lines but decreased the growth of 3 of 6 mesothelioma cell lines. These results indicate that systemic manifestations of malignant mesothelioma, including fever, cachexia, and thrombocytosis may be related to the production of IL-6 by malignant cells, and that local gamma-interferon infusion may reduce this production by stimulating antitumoral immunity and/or by directly decreasing the proliferation of malignant cells.

Biopterins↗
PubMed1994

Determination of the blood lactate:pyruvate ratio as a noninvasive test for the diagnosis of zidovudine myopathy.

OBJECTIVE: To evaluate the use of the lactate: pyruvate ratio as a test for the detection of zidovudine myopathy. METHODS: Twenty consecutive human immunodeficiency virus-infected patients with muscle involvement and 20 without muscle involvement were studied prospectively. Blood lactate and pyruvate levels and serum creatine kinase levels were tested, muscle involvement was assessed both clinically and electrophysiologically, and muscle biopsy was performed in patients with myopathy. RESULTS: Nine patients had biopsy-proven zidovudine myopathy. All 9 had a high lactate:pyruvate ratio, with elevations on 2 of 2 determinations in 6 patients and on 1 of 2 in 3 patients. Two of 11 patients with other myopathies and 2 of 20 patients without myopathy had a high lactate:pyruvate ratio on 1 of 2 determinations. CONCLUSION: The lactate:pyruvate ratio, when determined repeatedly, is a sensitive test for detecting mitochondrial muscular toxicity of zidovudine.

Adult↗
PubMed1994

Extended operations after induction therapy for stage IIIb (T4) non-small cell lung cancer.

Twenty-three patients with stage IIIb (T4) non-small cell lung cancer received induction chemotherapy (median, 2 cycles) with (n = 12) or without (n = 11) radiation (median, 45 Gy) before operation. Nine tumors involved the carina (n = 8) or lateral tracheal wall (n = 1), 11 were located centrally and invaded the proximal pulmonary artery (n = 6), veins (n = 3), or both (n = 2), three were apical tumors involving T4 structures, and six were associated with histologically diseased mediastinal nodes. Five complete and 18 partial responses were observed after induction treatment. Resection of all residual tumor at the primary site and involved vestiges was possible in 21 patients (91%); in two apical tumors, tumor was left behind. Nine right tracheal sleeve and 11 intrapericardial pneumonectomies and three resections of apical tumors were performed; 11 patients (48%) had radical mediastinal lymph node dissection. Complete sterilization of the primary tumor was observed in 3 patients (13%). Mean operating time was 209.3 +/- 86.8 minutes, and mean blood loss was 896.9 +/- 1031 mL. Major postoperative complications occurred in 6 patients (26%), including hemothorax requiring drainage (n = 1) or reoperation (n = 1), acute distress syndrome (n = 2), and bronchopleural fistula (n = 2), and their incidence was significantly higher (p = 0.0003) among patients receiving induction chemoradiation than among those receiving chemotherapy alone (42 versus 9%). Early (< 1 month) postoperative mortality was 8.6% (n = 2). With a median follow-up of 25 months (range, 12 to more than 39 months), the projected 3-year overall survival was 54%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Immunocytochemical characterization of cell lines from human malignant mesothelioma: characterization of human mesothelioma cell lines by immunocytochemistry with a panel of monoclonal antibodies.

A panel of nine monoclonal antibodies was used to characterize human mesothelioma cell lines that we established from human malignant mesothelioma. The antigens detected were cytokeratin, vimentin, epithelial membrane antigen, carcinoembryonic antigen, Leu-M1 (CD15), desmin, factor VIII-related antigen (von Willebrand factor antigen), OV632, and ME1, a specific monoclonal antibody directed against human malignant mesothelioma. The technique used was the alkaline phosphatase anti-alkaline phosphatase method. All 30 cell lines, either epithelial, sarcomatous, or mixed, showed strong reactivity with cytokeratin and vimentin antibodies. None of the cell lines demonstrated any reactivity with carcinoembryonic antigen, Leu-M1, or factor VIII antibodies; moreover, all of 22 cell lines studied were positive for ME1 antibody and 10 of 12 cell lines studied were positive for OV632. Some interesting features were noted: only two of the 30 cell lines presented a weak positive staining with epithelial membrane antigen, and nine of 19 cell lines tested demonstrated a cytoplasmic staining pattern with desmin antibody. These results show that established human mesothelioma cell lines still possess the immunocytochemical characteristics that are basically consistent with the immunohistochemical features described in tumor tissues of malignant mesothelioma. These characteristics can be used to identify the mesothelioma cells grown from human malignant mesothelioma. Hence, the mesothelioma cell lines will provide a useful tool for the investigation of the cell biology of the tumor and the mechanisms of mesothelial cell transformation, as well as the in vitro evaluation of the effects of some drugs in order to develop new therapies for malignant mesothelioma.

Actins↗
PubMed1993

Initial chemotherapeutic doses and survival in patients with limited small-cell lung cancer.

BACKGROUND: Moderate increases in the initial doses of certain chemotherapeutic drugs, such as cisplatin and cyclophosphamide, may prolong overall survival in patients with limited small-cell lung cancer. METHODS: We conducted a prospective study of 105 patients with limited small-cell lung cancer. The patients were randomly assigned to receive higher or lower initial doses of cisplatin (100 or 80 mg per square meter of body-surface area) and cyclophosphamide (300 or 225 mg per square meter daily for four days); all patients received the same doses of doxorubicin and etoposide. The first course of chemotherapy was followed by five additional courses and by three courses of radiotherapy. All patients received the lower doses of cisplatin and cyclophosphamide and the same doses of doxorubicin and etoposide from the second through the sixth cycle of chemotherapy. RESULTS: The median follow-up was 33 months. The two-year survival rate for the 55 patients who received the higher doses of chemotherapy was 43 percent, as compared with 26 percent for the 50 patients who received the lower doses (P = 0.02). The rates of complete response at six months were 67 percent in the higher-dose group and 54 percent in the lower-dose group (P = 0.16). Disease-free survival at two years was 28 percent in the higher-dose group, as compared with 8 percent in the lower-dose group (P = 0.02). Side effects from treatment were not increased in the higher-dose group. CONCLUSIONS: Higher initial doses of cyclophosphamide and cisplatin improve disease-free and overall survival in patients with limited small-cell lung cancer.

Aged↗
PubMed1993

In vitro effects of recombinant human interferon gamma on human mesothelioma cell lines.

Malignant mesothelioma is a tumor arising from serous surfaces and often related to asbestos exposure. Malignant mesothelioma is resistant to various forms of therapy. Radiotherapy, surgery or chemotherapy only slightly improve prognosis. IFN-gamma produces complete or partial responses in stage-I patients with malignant mesothelioma. The in vitro biological effect of IFN-gamma on malignant mesothelioma cells remains poorly elucidated. In the present study, 32 well-characterized human mesothelioma cell lines (HMCL) were treated with r-hu IFN-gamma at 4 doses and cell growth was determined by a colorimetric method (MTT assay). Among the 32 HMCLs tested, II exhibited significant cell-growth inhibition; 16 were insensitive to r-hu IFN-gamma, and 5 were slightly inhibited. The sensitive cell lines were strongly inhibited by r-hu IFN-gamma. Our results show that HMCL exhibit a large range of responses to r-hu IFN-gamma, some of which can be compared with those obtained in vivo in humans.

Aged↗
PubMed1993

Cytochrome c oxidase reaction improves histopathological assessment of zidovudine myopathy.

Zidovudine can induce a mitochondrial myopathy with ragged-red fibers and partial cytochrome c oxidase deficiency. In an attempt to improve histological assessment of zidovudine myopathy, we evaluated cytochrome c oxidase histochemical reaction in the muscle of 10 patients with biopsy-proven zidovudine myopathy (Group 1), 10 myopathic zidovudine receivers without typical histopathological features of zidovudine myopathy (Group 2), and 10 human immunodeficiency virus (HIV)-infected patients not treated by zidovudine who had an immunohistological profile of HIV-associated myopathy or other neuromuscular disorders (Group 3). Among zidovudine receivers, cytochrome c oxidase deficiency was found in 10 of 10 patients from Group 1 and 7 of 10 from Group 2. No cytochrome c oxidase deficiency was observed in patients not treated by zidovudine. When present, cytochrome c oxidase-negative fibers accounted for 2 to 28% of fibers, and there was no difference for the number of cytochrome c oxidase-negative fibers between Group 1 and Group 2. Most patients with cytochrome c oxidase deficiency that could be evaluated clinically after muscle biopsy improved after withdrawal of zidovudine (5 of 7 in Group 1, 5 of 5 in Group 2). Patients who did not improve had an HIV-associated myopathy concurrently with zidovudine myopathy. We conclude that cytochrome c oxidase reaction may be used as a reliable marker of zidovudine mitochondrial toxicity in HIV-infected patients with muscular symptoms.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Systemic mastocytosis following mediastinal germ cell tumor: an association confirmed.

A 24-year-old man had a mediastinal embryonal carcinoma containing yolk sac foci. Combination chemotherapy with cisplatin, bleomycin, etoposide, and vinblastine was given, and the residual mass was then resected. Histology showed only necrotic cells. No other treatment was given. Two years later the patient presented with episodes of flushing and syncopes related to a systemicmastocytosis. Bone marrow examination showed a diffuse infiltration with large, atypical mast cells often with multilobulated nuclei. The patient suffered several episodes of cardiovascular collapse and died during one of these episodes, 8 months after the diagnosis of systemic mastocytosis and 40 months after the diagnosis of mediastinal tumor. Autopsy findings included the absence of mediastinal tumor and a diffuse liver and spleen mast cell infiltration. This was the second case with the similar clinicopathologic picture of two rare diseases being associated. This fact supports the hypothesis of a distinct entity, part of the mediastinal germ cell tumor/hematologic malignancy syndrome. The hypothesis of a cytokine secretion induced by mediastinal germ cell tumor supporting mast cell proliferation may be considered.

Adult↗