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J J Lafitte

Publications and source records attributed to J J Lafitte.

At least 55 records · Page 3Linked to original sources
PubMed1997

Long-term survivors of small-cell lung cancer (SCLC): a French multicenter study. Groupe d'Oncologie de Langue Française.

BACKGROUND: The aim of this study was to analyze SCLC patients beyond 30 months, particularly their outcome, their way of life, and factors which could influence relapses, second-primary cancers and death. PATIENTS AND METHODS: Between January 1986 and May 1995, 263 SCLC patients who survived longer than 30 months were included from 52 French institutions. The analysis was performed on the 155 cases confirmed by a pathologic review. RESULTS: Physical, mental and psychological states were considered as normal at 30 months in respectively 70.3%, 87.7% and 67.7% of patients, not influenced by prophylactic cranial irradiation, number of chemotherapy cycles, CCNU or cisplatin. Therapeutic sequelae were neurological impairment (13%), pulmonary fibrosis (18%) and cardiac disorders (11%) at 30 months. Return to work was possible for 40% of patients in the first two years following diagnosis. Among 43 relapsing patients, 33 benefited from a second-line treatment. Their median survival was 12 months since retreatment, and seven patients have survived again longer than 30 months. Age > 60 at the time of diagnosis was found as an independent factor increasing the risk of relapse beyond 30 months (OR = 2.46, IC 95% (1.16-5.26), P = 0.01). The risk of relapse became less than 10% beyond five years. Twenty patients (13%) developed a second primary cancer in a mean time of 58.6 months. The risk of second primary cancer was increased by a number of chemotherapy cycles > 6 (OR = 3.25, IC 95% (1.08-9.8) P = 0.02) and by an age > 60 (OR = 2.92, IC 95% (1.07-7.97), P = 0.03). Five- and 10-year survival rates were respectively 68% and 44%. In these patients having reached a 30-month survival, three independent factors were predictive of a survival longer than five years: age < or = 60 at the time of diagnosis (OR = 2.85, IC 95% (1.23-6.6), P = 0.01), chest radiotherapy (OR = 3.1, IC 95% (1.28-7.69), P = 0.006) and absence of relapse (OR = 4.5, IC 95% (1.75-12.5), P = 0.002). This study suggests that: 1) therapeutic sequelae are rather mild, allowing return to work in 40% of patients; 2) relapsing 30-month survivors can benefit from second-line treatment; 3) SCLC cure can be achieved with a 10-year follow-up.

Adult↗
PubMed1997

The fucosylation and secretion of mucins synthesized in human bronchial cells vary according to growth conditions.

In order to evaluate the importance of an extracellular matrix on mucin secretion, human bronchial epithelial cells were cultured for 3 weeks on either plastic or type I collagen. By metabolically labeling cells with tritiated glucosamine, we found that cells grown on collagen secreted more radiolabeled mucins than cells grown on plastic, and their amount increased from week 1 to week 3 in both conditions. Secreted mucins were also assayed by ELISA using an anti-Lewis b monoclonal antibody. The amount of immunoreactive mucins secreted by cells grown on plastic during the first 2 weeks of culture was much lower than that of cells grown on collagen. This indicated that the expression of the Lewis b antigen on mucins secreted by cells grown on plastic was very low during the first 2 weeks of radiolabeling and increased during the third week to reach levels that were comparable to the levels of expression by cells grown on collagen. The expression of the Lewis b epitope and the mRNA level of fucosyltransferases FUT2 and FUT3, which are involved in Lewis b synthesis, varied in a similar way. The two fucosyltransferases were expressed later in cells cultured on plastic than in cells grown on collagen. These results suggest that growth conditions influence both the biosynthesis and secretion of respiratory mucins.

Bronchi↗
PubMed1997

Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution.

The polymorphic cytochrome P450 CYP2D6 is involved in the metabolism of various drugs of wide therapeutic use and is a presumed susceptibility factor for certain environmentally-induced diseases. Our aim was to define the mutations and alleles of the CYP2D6 gene and to evaluate their frequencies in the European population. Using polymerase chain reaction-single strand conformation polymorphism analysis, 672 unrelated subjects were screened for mutations in the 9 exons of the gene and their exon-intron boundaries. A total of 48 point mutations were identified, of which 29 were novel. Mutations 1749 G-->C, 2938 C-->T and 4268 G-->C represented 52.6%, 34.3% and 52.9% of the mutations in the total population, respectively. Of the eight detrimental mutations detected, the 1934 G-->A, the 1795 Tdel and the 2637 Adel accounted for 65.8%, 6.2% and 4.8% respectively, within the poor metabolizer subgroup. Fifty-three different alleles were characterized from the mutation pattern and by allele-specific sequencing. They are derived from three major alleles, namely the wild-type CYP2D6*1A, the functional CYP2D6*2 and the null CYP2D6*4A. Five allelic variants (CYP2D6*1A, *2, *2B, *4A and *5) account for about 87% of all alleles, while the remaining alleles occur with a frequency of 0.1%-2.7%. These data provide a solid basis for future epidemiological, clinical as well as interethnic studies of the CYP2D6 polymorphism and highlight that the described single strand conformation polymorphism method can be successfully used in designing such studies.

Alleles↗
PubMed1997

["Primary" diffuse interstitial fibrosis in coal miners: a new entity? Study Group on Interstitial Pathology of the Society of Thoracic Pathology of the North].

It is well known that silica exposure leads in an experimental model to the development of an acute fibrotic process. In human beings two main observations have already been done: (1) silica exposure is frequently associated with the development of connective tissue disease (CTD), especially progressive systemic sclerosis; (2) 10 to 20% patients with CTD developed pulmonary fibrosis. In this context we report 26 cases of coal miners who presented with clinical, radiological, biological and functional characteristics mimicking idiopathic pulmonary fibrosis (IPF), with or without associated coal worker's pneumoconiosis (CWP). All were men; mean age was 68 +/- 9.2 years. Twenty-three were smokers. Duration of exposure was 28.8 +/- 9.1 years. All the patients had dyspnea (stage III, IV in the NHYA classification) and diffuse crackles. Eleven out of 26 had finger clubbing. Computed tomography showed honeycombing (23 cases), and/or ground glass opacities (6 cases) with bronchiectasis (3 cases) predominant in the lower lobes; 19 had radiological signs of CWP, micronodules (n = 16) and nodules (n = 3) predominant in the upper lobes. BAL exhibited an increased % of neutrophils (11.9 +/- 16.1%). Lung function demonstrated a restrictive pattern (TLC = 73 +/- 15.6% and VC = 80 +/- 18% of predicted values) associated with a decreased DLCO (51.8 +/- 23.6% of predicted values) and hypoxemia (at rest = 66.5 +/- 11.2 mmHg, upon effort = 56 +/- 12 mmHg). Lung biopsies were performed in four cases and demonstrated interstitial fibrosis of intraalveolar septum with an accumulation of immune and inflammatory cells similar to the one described in IPF. The association between IPF and silica exposure with or without associated CWP points out the problem of legal recognition of idiopathic-like pulmonary fibrosis as a complication of the occupational exposure of coal workers.

Adult↗
PubMed1996

Congenital bilateral absence of the vas deferens (CBAVD) and cystic fibrosis transmembrane regulator (CFTR): correlation between genotype and phenotype.

To assess better the link between congenital bilateral absence of the vas deferens (CBAVD) and cystic fibrosis (CF), we compared sweat chloride values, analysis of the CFTR intron 8 poly(T) tract length and analysis of 10 exons in a population of 38 patients with CBAVD. The data indicate that this population can be divided into three groups of patients. In the first group of 15 patients with abnormal sweat chloride (> 60 mmol/l), the frequency of CF mutations is high. In the second group of 18 patients with equivocal sweat chloride (between 40 and 60 mmol/l), the frequency of the 5T variant is high; 6 patients have a delta F508 mutation and a 5T variant and 1 patient is homozygous for the 5T variant; a 5T variant has been detected in 3 other patients, and a delta F508 mutation in another patient. A third group of 5 patients is probably not related to CF: these patients have other congenital abnormalities of the urogenital tract, low chloride values (< 40 mmol/l) and apparently no abnormality of the CF gene.

Adult↗
PubMed1996

Postresection irradiation for T2 N0 M0 non-small cell carcinoma: a prospective, randomized study.

BACKGROUND: Stage I nonirradiated T2 N0 non-small cell lung carcinoma has a postoperative prognosis not very different from stage II irradiated T1 N1 carcinoma. The hypothesis was that more locoregional malignant sites are overlooked in T2 N0 M0 than in T1 N0 M0 tumors, considering the better prognosis of this last group, and that T2 N0 cancer might benefit from postresection irradiation. METHODS: From 1985 to 1991, 163 non-small cell lung carcinomas were classified T2 N0 M0 and randomized for irradiation or nonirradiation after operation. After revision of all the cases, 132 were included in this study: 60 were irradiated and 72 were not irradiated. All were followed up. The study was closed in October 1995. Statistical analysis was then performed considering volume, location, cell type, survival, and recurrence in the two groups. RESULTS: One hundred thirteen patients were followed up during a minimum of 5 years: the survival was 44.2%. There was no significant difference considering cell type or irradiation. There was no recurrence-free survivor beyond 5 years with a tumor invading the visceral pleura. At the close of the study (follow up, 4 years 3 months to 10 years 1 month), 49 of 132 patients were alive. The median survival was 3 years 11 months. Fifty-nine patients had died of local (21) or distant (40) recurrences (2 patients had both local and distant recurrence). There was again no significant difference considering cell type or irradiation, either in the survival or in the mode of recurrence. CONCLUSIONS: Stage I T2 N0 M0 non-small cell lung carcinoma tends to manifest distant metastasis. Prospective studies of stratified systemic adjuvant therapy should improve the present moderate result of radical resection in this group of tumors.

Adult↗
PubMed1996

Lack of relation between genetic polymorphism of cytochrome P-450IID6 and sporadic idiopathic Parkinson's disease.

We investigated genetic polymorphism of the cytochrome P-450 CYP2D6 gene from white patients with idiopathic Parkinson's disease (IPD). The mutations of the CYP2D6 gene associated with the poor metabolizer (PM) phenotype of the debrisoquine/sparteine polymorphism were analyzed in DNA of 130 IPD patients by a polymerase chain reaction (PCR)-based DNA amplification combined with Xba I restriction fragment length polymorphism (RFLP) analysis in 105 patients. Another mutation located in exon 6 was analyzed by Hha I RFLP in 94 IPD patients. The frequencies of the different CYP2D6 gene mutations were compared to the frequencies in sex- and age-matched white control population with chronic bronchitis. The rate of genotypically defined PM and the frequencies of the different mutations were not significantly different in IPD patients and controls. These results fail to confirm the previously reported results concerning CYP2D6 gene mutations in IPD. These equivocal results might be related to methodologic problems. However, other hypotheses have been suggested: impairment of neuronal CYP 2D6 expression, transient modification of CYP 2D6 phenotype, or linkage of CYP2D6 gene to the candidate gene locus directly involved in IPD.

Aged↗
PubMed1996

[Inhaled nitric oxide test for patients with stable chronic obstructive pulmonary disease: value and feasibility].

Patients suffering from chronic lung disease (CLDP) often develop secondary pulmonary hypertension (HP), which contributes to right ventricular dysfunction and worsens their prognosis. In order to evaluate the severity of this HP, pharmacodynamics tests are periodically proposed to these patients. Therefore, the administration of vasodilators is limited by systemic and pulmonary side-effects. Inhaling nitric oxide gas (NO) has been reported to induce a selective pulmonary vasodilation. The purpose of this study was to evaluate the safety and efficacy of an inhaled NO test perfected in our service. Sixteen CLDP were investigated in the absence of acute pulmonary failure. All had severe pre-capillary HP, confirmed after placement of a thermodilution pulmonary-artery catheter (mean pulmonary artery pressure >20 mmHg, pulmonary capillary wedge pressure >12 mmHg). Each subject breathed spontaneously NO in a concentration of 10 ppm for 15 minutes. They were connected through a facial mask and a one-way valve put on the inspiratory connection of a ventilator (Drager-Evita), to a tank of nitrogen with a NO concentration of 900 ppm. Hemodynamic variables and gas exchange were measured before, during and after gas inhalation. The inspired fractions of NO and NO2 were determined using a Polytron analyser (Drager). The methemoglobin levels were measured with spectrophotometry (OSM3). Inhaled NO acts as a selective pulmonary arterial vasodilator, without systemic effect. The action on the shunt is variable. Methemoglobin levels are remained <0.01%. All the patients were satisfied with the way of NO administration. In view of the lack of systemic effects, its seems that the NO inhaled test proposed in this study may be used accurately to evaluate the HP of chronic lung disease patients.

Adult↗
PubMed1996

Pneumocystis carinii pneumonia in rheumatoid arthritis patients treated with methotrexate. A report of two cases.

Use of methotrexate to treat rheumatoid arthritis is associated with pulmonary adverse effects in 3% to 5% of cases. In addition to immunoallergic lung disease, bronchitis and pneumonia due to pyogenic organisms, opportunistic lower respiratory tract infections have been reported, including, to our knowledge, 18 cases of Pneumocystis carinii pneumonia. We report two new cases of P. carinii pneumonia in methotrexate-treated rheumatoid arthritis patients. One case occurred in a 62-year-old woman with a nine-year history of seropositive rheumatoid arthritis treated for the last seven months with methotrexate, 15 mg per week, and prednisone, 10 mg/d. The other patient was a 58-year-old woman who had been diagnosed with rheumatoid arthritis 18 months earlier and had been receiving 15 mg per week of methotrexate for eight months in combination with 12.5 mg of prednisone per day. Both patients had negative tests for the human immunodeficiency virus. Symptoms consisted of fever, cough and dyspnea, with interstitial infiltrates on chest films, hypoxia, and lymphopenia (700 and 600/mm3, respectively). The diagnosis was confirmed by bronchoalveolar lavage. Both patients recovered under treatment with trimethoprim-sulfamethoxazole. An analysis of the 20 cases of P. carinii pneumonia reported to date in methotrexate-treated rheumatoid arthritis patients demonstrated a number of characteristics: the rheumatoid arthritis was of recent onset in some cases (a few months in one patient); lymphopenia was present in two thirds of cases; one-third of patients were not receiving corticosteroid therapy; the dosage and duration of methotrexate therapy varied widely, from 5 to 30 mg per week and two to 48 months; and four patients died.

Anti-Infective Agents↗
PubMed1996

[Diabetes insipidus revealing pituitary metastasis of bronchial carcinoma].

Pituitary metastasis are rare but represent an important differential diagnosis of intrasellar tumorous syndromes. We report one case of intrasellar metastasis of a bronchial adenocarcinoma in a 50 year old woman. Clinical syndrome associated a tumorous syndrome (cephalalgia, bitemporal hemianopsia) and an anterior and posterior hypopituitarism biologically proven. A large intra and suprasellar mass which compressed the optic chiasma and highly enhanced after gadolinium injection was found by nuclear magnetic resonance imaging. The surgical biopsy displayed a pituitary metastasis of a right inferior lobar bronchial adenocarcinoma with bone secondary localizations. Cerebral radiotherapy and corticotherapy allowed recovery of visual loss but did not prevent rapid death. The clinical and radiological features which may evoke an intrasellar metastasis were: the tumorous syndrome associated with or revealed by diabetes insipidus, loss of spontaneous hypersignal of the neurohypophysis in nuclear magnetic resonance imaging, bulking pituitary stalk, bilobar character of the mass which is in favour of rapid cell proliferation, postero-superior extension, lowering of the V3 floor and very strong and homogeneous signal after gadolinium injection.

Carcinoma, Bronchogenic↗
PubMed1995

Characterization of a sulfotransferase from human airways responsible for the 3-O-sulfation of terminal galactose in N-acetyllactosamine-containing mucin carbohydrate chains.

A galactose 3-O-sulfotransferase activity able to transfer a sulfate group from adenosine 3'-phosphate 5'-phosphosulfate to methyl galactosides or terminal N-acetyllactosamine-containing carbohydrate chains from human respiratory mucins was characterized in microsomal fractions prepared from human respiratory mucosa. The reaction products, methyl alpha- or beta-galactose 3-sulfate and three oligosaccharide alditols containing the sequence HSO3-3Gal beta 1-4GlcNAc beta 1-6GalNAc-itol were identified by high performance anion-exchange chromatography. Using methyl beta-galactoside as a substrate, the optimum activity was obtained with 0.1% Triton X-100, 30 mM NaF, 20 mM Mn2+, and 10 mM AMP in a 30 mM 2-(N-morpholino)ethanesulfonic acid buffer at pH 6.1. The apparent Km for methyl beta-galactoside and for adenosine 3'-phosphate 5'-phosphosulfate were observed at 0.69 x 10(-3) M and at 4 x 10(-6) M respectively. This sulfotransferase is different from that responsible for sulfatide synthesis.

Adenosine Monophosphate↗
PubMed1995

Secretion and mRNA expression of TNF alpha and IL-6 in the lungs of pneumoconiosis patients.

Exposure to coal-mine dust leads to coal workers' pneumoconiosis (CWP), characterized by the development of a perifocal and progressive fibrotic reaction. In order to confirm their in vivo participation in the pathogenesis of CWP, the expression of tumor necrosis factor (TNF) and interleukin-6 (IL-6) was evaluated in bronchoalveolar lavage (BAL) specimens collected from 12 patients with simple pneumoconiosis (SP) and six with progressive massive fibrosis (PMF), and in pulmonary tissue from one patient with SP and three with PMF. Expression of TNF and IL-6 was assessed using both in situ hybridization and immunohistochemistry. The number of positive cells found in BALF was significantly higher for patients with PMF (TNF = 55 +/- 6%; IL-6 = 46 +/- 12.8%) than for those with SP (TNF = 34 +/- 11.6%; IL-6 = 26 +/- 10.2%) or normal controls (TNF = 15 +/- 5.5%; IL-6 = 13.3 +/- 6%), and was correlated with cytokine concentrations in supernatants from alveolar macrophages (AM). In lung biopsies, the expression of messenger ribonucleic acid (mRNA) for TNF was associated with the presence of coal dust and was limited to lung macrophages; mRNA for IL-6 was detected in mononuclear phagocytes but also in other types of cells such as endothelial cells. Monokine synthesis was confirmed by immunohistochemistry. These data confirm that TNF and IL-6 production is increased in the lungs of pneumoconiotic patients. Moreover TNF and IL-6 expression was associated with the presence of coalmine dust particles, suggesting a direct role of mineral particles in the cytokine production and development of pneumoconiotic lesions in CWP.

Adult↗
PubMed1995

Relationship between a mild alpha 1 proteinase inhibitor deficiency and respiratory symptoms in a family.

A 34-year-old man with pulmonary emphysema was found to have a mild alpha 1 proteinase inhibitor (alpha 1 PI) deficiency. alpha 1 PI status was investigated in this patient and in 35 members of his family. The alpha 1 PI investigations included alpha 1 PI concentration and phenotype and serum inhibitory capacity for trypsin and pancreatic elastase. Fifteen members of the family had alpha 1 PI concentration and inhibitory capacities below the lower normal limit. Five of these members were characterized by the heterozygous MP phenotype and the 10 others by an apparently homozygous M phenotype, in which the M allele may be associated with another unidentified deficiency allele. Two members of the family had alpha 1 PI concentration and elastase inhibitory capacity below the lower normal limits and trypsin inhibitory capacity within the normal range. They were both characterized by the MP phenotype. Six of these 17 members (three of PI type M and three of PI type MP) showed chronic pulmonary symptoms, whereas among the 19 alpha 1 PI non deficient members, no member had a history of significant pulmonary symptoms.

Adult↗
PubMed1995

Expression of human mucous proteinase inhibitor in respiratory tract: a study by in situ hybridization.

Human mucous proteinase inhibitor (MPI) is present in bronchial secretions, where it participates in the protection of lung structures against degradation by leukocyte elastase. The protein has been localized by immunohistochemical studies and immunogold labeling essentially in the serous cells of the submucosal glands and also in the surface epithelial cells of central and peripheral airways. However, until now no gene expression study has been performed at the tissue level. In this study, in situ hybridization was used to precisely study MPI mRNA expression in bronchial tissue sections with a specific radiolabeled oligonucleotide probe. By light microscopy, MPI gene expression was localized exclusively in the serous and seromucinous acini of the submucosal glands of large airways. The MPI gene was expressed in submucosal glands of normal and carcinomatous tissue sections, whereas it was not expressed in bronchial and bronchiolar surface epithelia.

Base Sequence↗
PubMed1995

High-dose and low-dose systemic corticosteroids are equally efficient in acute severe asthma.

The optimal amount of systemic corticosteroids to be used in acute severe asthma remains an unresolved issue. In this double-blind, randomized study we compared two doses of methylprednisolone (1 vs 6 mg.kg-1 q.d.) in asthmatics presenting with an acute severe asthma attack, unresponsive to an intensive beta 2-agonist regimen administered during a run-in period. Concurrent therapy, including oxygen, inhaled and intravenous salbutamol, and aminophylline was strictly standardized. The response was assessed by serial bedside spirometry. The primary outcome measurement was forced expiratory volume in one second (FEV1) (expressed as percentage of predicted values) at 24 and 44 h. The trial was designed in order to achieve a statistical power of 90%. Twenty three patients were included in the low-dose group and 24 in the high-dose group. Both groups were comparable in terms of demographic profiles, history of asthma, and severity of the current attack. Improvement in pulmonary function was similar in both groups. At 44 h, the mean (+/- SD) FEV1 values were 53 +/- 22 and 45 +/- 14% in the low and in the high-dose group respectively (NS). We conclude that high dose systemic corticosteroids offer no further benefit over low-doses in the treatment of severe acute asthma.

Acute Disease↗