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Biomedical subjects

B Milleron

Publications and source records attributed to B Milleron.

At least 19 recordsLinked to original sources
PubMed1998

Neutrophil alveolitis in bronchioloalveolar carcinoma: induction by tumor-derived interleukin-8 and relation to clinical outcome.

Tumor infiltrate, predominantly constituted by lymphocytes, may represent an important prognostic factor in bronchioloalveolar carcinoma (BAC), in addition to tumor extension and histological type. In the present study, we determined the presence, the origin, and the prognostic importance of neutrophils that also participate in leukocyte infiltrates of BAC. Neutrophil alveolitis was determined immunohistochemically in both lung biopsies and bronchoalveolar lavage (BAL) fluid samples from 29 patients with histologically proved BAC. The local expression of interleukin (IL)-8 was determined by immunohistochemical and immunoenzymatic techniques. Neutrophil counts were analyzed in relation to the clinical outcome of patients by the Kaplan-Meier method and Cox's univariate and stepwise multivariate models. Lymphocytes and neutrophils dominated the inflammatory cell population in the lower respiratory tract of patients with BAC. Neutrophils were located mainly in the alveolar lumen and seldom in alveolar wall whereas lymphocytes were exclusively present in alveolar wall. A relationship was observed between the number of neutrophils and the level of IL-8 in BAL fluid suggesting the involvement of that chemokine in neutrophil recruitment. The tumor cells were the predominant cells that appeared to express IL-8 by immunolocalization. The presence of increased numbers of neutrophils was significantly associated with a poorer outcome in patients with BAC (P = 0.02). In a multivariate analysis, the neutrophil percentage in BAL fluid was an independent predictor of clinical outcome. The risk of death was increased substantially (rate ratio, 5.2; 95% confidence interval, 1.1 to 24.7) among patients with BAL neutrophil percentage of > or = 39% (median of the distribution) as compared with the others. In BAC, neutrophils accumulate in the alveolar lumen. Elaboration of IL-8 by tumor cells may be responsible for this event, which is associated with a significantly higher risk of death.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1998

Monitoring of p53 autoantibodies in lung cancer during therapy: relationship to response to treatment.

Alteration of the p53 gene is the most frequent genetic alteration in human cancer, and it leads to the accumulation of mutant p53 in the nucleus of tumor cells. In addition, it has been shown that patients with various types of neoplasias have p53 antibodies in their sera. ELISA was used to detect anti-p53 antibodies in their sera of 167 patients with lung cancer. Among these, 32 individuals (16 positive for p53 antibodies and 16 negative) were monitored over a period of 30 months for p53 antibodies. Twelve of 16 antibody positive patients had reduced titers during chemotherapy that led to partial or complete remissions of disease. The specificity of these antibodies was confirmed by two different ELISA procedures and by immunoprecipitation. The very rapid, specific decrease in these antibodies during therapy suggests that a constant level of tumoral cells with nuclear accumulating p53 protein is necessary for a detectable humoral anti-p53 response. The good correlation found between the specific evolution of the p53 antibody titer and the response to therapy suggests that p53 antibodies could represent a useful tool for checking the response to therapy and for monitoring some relapses before they are clinically detectable.

Antibody Formation↗
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

Diagnosis of smear-negative pulmonary tuberculosis using sequence capture polymerase chain reaction.

Techniques based on the polymerase chain reaction (PCR) can be used to rapidly identify DNA from Mycobacterium tuberculosis in clinical samples from patients with tuberculosis, but prior studies evaluating this approach in the diagnosis of paucibacillary forms of pulmonary tuberculosis have reported poor sensitivity and/or specificity. We have developed a procedure in which mycobacterial DNA in crude samples is specifically captured prior to amplification, thereby concentrating the target sequences and removing irrelevant DNA and other inhibitors of the amplification reaction (sequence capture PCR). To evaluate the usefulness of this approach in the diagnosis of paucibacillary forms of pulmonary tuberculosis, sequence capture PCR was performed prospectively on samples of bronchoalveolar lavage fluid from consecutive patients suspected of having pulmonary tuberculosis but for whom three consecutive samples of respiratory secretions were smear negative. Of the 27 patients evaluated, active tuberculosis was diagnosed in nine; sequence capture PCR was positive for all of these patients, including the three for whom all specimens submitted for culture were negative. No positive results were obtained for lavage fluid from the 18 patients for whom the diagnosis of active tuberculosis was subsequently excluded or 25 additional patients undergoing bronchoalveolar lavage for evaluation of other pulmonary problems, even though many of these patients had a history of prior tuberculosis or radiographic evidence of prior tuberculous infection. Paucibacillary forms of pulmonary tuberculosis can be rapidly identified with high sensitivity and specificity using sequence capture PCR performed on samples obtained by bronchoalveolar lavage.

Adult↗
PubMed1997

MDR1-Pgp 170 expression in human bronchus.

MDR1 P-glycoprotein (Pgp 170), a member of the adenosine triphosphate (ATP) binding cassette transporters, acts as an efflux pump for various hydrophobic agents, particularly for xenobiotics such as benzo(a)pyrene. It has also been shown to regulate cell-volume activated chloride channels. Pgp 170 could, therefore, be of particular importance in cellular mechanisms of defence in the airways and in the control of mucus layer composition. For these reasons, we evaluated the precise localization of Pgp 170 in human adult airways. Fresh non-neoplastic bronchial specimens were collected from 33 patients (26 smokers, four exsmokers and three nonsmokers) who underwent surgery for lung carcinoma. The presence of MDR1 messenger ribonucleic acid (mRNA) was demonstrated by reverse transcriptase chain reaction (RT-PCR) in bronchial epithelial cells collected by gentle scraping from either smokers, exsmokers or nonsmokers. Immunodetection of Pgp 170 using a panel of monoclonal antibodies (MRK16, JSB1, C219, C494) was performed either on cryostat or paraffin-embedded sections of histologically normal bronchial tissue. Pgp 170 was constantly detected with intense labelling at the apical surface of ciliated epithelial cells from the surface epithelium or ciliated collecting ducts, and on apical and lateral surfaces of serous cells from bronchial glands. No staining of mucus-secreting cells was observed. Pgp 170 was also demonstrated at the luminal surface of endothelial cells of bronchial capillaries. In conclusion, the expression of MDR1 P-glycoprotein in bronchial structures, particularly at the epithelial apical surface, suggests important roles for this transmembrane protein in human airways.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Dose-intensity of a four-drug chemotherapy regimen with or without recombinant human granulocyte-macrophage colony-stimulating factor in extensive-stage small-cell lung cancer: a multicenter randomized phase III study.

PURPOSE AND METHODS: We investigated whether a high-dose chemotherapy regimen of cyclophosphamide 1,800 mg/m2, 4'-epidoxorubicin 60 mg/m2, etoposide 330 mg/m2, and cisplatin 120 mg/m2 given monthly for four cycles with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) support (5 micrograms/kg daily for 10 days) could improve the survival of patients with extensive-stage small-cell lung cancer (SCLC) compared with a standard-dose regimen (cyclophosphamide 1,200 mg/m2, 4'-epidoxorubicin 40 mg/m2, etoposide 225 mg/m2, and cisplatin 100 mg/m2) given monthly for six cycles. Planned cumulative doses of the drugs were the same in both treatment arms except for cisplatin (which was 80% in the higher-dose plus rhGM-CSF group). RESULTS: At the time of the preplanned interim analysis, 125 patients, 60 in the standard-dose group and 65 in the higher-dose plus rhGM-CSF group, had entered the study; 116 were eligible, 55 in the standard-dose group and 61 in the higher-dose group. All patients were included in the analyses. The cumulative doses of each drug actually delivered were significantly higher in the standard-dose group. No difference in response rates was observed between the two groups. There were significantly greater hematologic toxicities, documented infections, and transfusions of RBCs and platelets in the higher-dose plus rhGM-CSF group. Patients in this group proved to have a shorter survival duration and a shorter time to relapse than patients in the standard-dose group (median overall survival: standard-dose, 10.8 months; higher-dose, 8.9 months; log-rank test with adjustment for prognostic variables, P = .0005; respective probabilities of relapse at 1 year, 77 +/- 0.6 and 96 +/- 2.2; log-rank test, P = .013). CONCLUSION: A 50% increase in dose-intensity for this four-drug regimen could not be achieved with GM-CSF due to excessive toxicity in patients with extensive-stage SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Primary pulmonary lymphoma].

There are three distinct clinico-anatomical entities today covered by the definition of a primary clonal pulmonary lymphoid proliferation. These are pulmonary lymphomas of B cell phenotype, of low grade malignancy, B cell lymphomas of high grade malignancy and finally lymphomatoid granulomatosis whose clonal characteristic is sometimes difficult to confirm. This general review aims to specify the pathophysiological, diagnostic, prognostic and therapeutic aspects of these different types. Low grade B cell lymphoma is the most common pulmonary lymphoma. Their development depends on mucosa associated lymphoid tissue. They are most often indolent and present as a chronic alveolar opacity. Their prognosis is excellent and the modalities of treatment are discussed (no therapy, surgery or monochemotherapy). High grade B cell pulmonary lymphomas are much rarer and may result from the transformation of a low grade lymphoma or arise in a particular situation such as imunodepression. Their prognosis is poor and the therapeutic possibilities depend most often on the underlying disease. The presence of lymphomatoid granulomatosis in this group of pulmonary lymphomas is debatable. The demonstration of a clonal character of this proliferation is practically never obtained and there is often extra pulmonary disease. The prognosis of this type of illness is extremely variable because certain studies have shown a cure using corticosteroids and cyclophosphamide whilst others have found that the disease is always fatal in spite of using strong polychemotherapy.

Humans↗
PubMed1997

[Radiation- and chemically-induced respiratory manifestations].

There are frequently respiratory complications with cancer particularly in primary lung carcinoma. Among these are bronchopulmonary infections with or without endobronchial obstruction, carcinomatous lymphangitis, thromboembolic disease and haemorrhagic disease as well. Radiotherapy and chemotherapy may induce various respiratory complications which diagnosis can be of varying shades of difficulty. The classical post radiation pneumonitis occurring exclusively in the field of radiation hardly poses any problem unless it could be masking a recurrence. Certain clinical manifestations address very difficult problems of differential diagnosis by their lack of specificity and by their often unforeseeable character (except for bleomycin fibrosis which is perfectly dose dependent). Moreover patients often have multiple treatments and the identification of the single responsible agent becomes very difficult. We will not discuss here the infectious or secondary haemorrhagic complications of radiotherapy or chemotherapy but rather the anaphylactic manifestations, diffuse interstitial pneumonia with lymphocytic alveolitis or fibrosis, eosinophilic pneumonia, non-cardiogenic pulmonary oedema, bronchiolitis obliterans with organising pneumonia and the rare pulmonary vascular disorders such as pulmonary veno-occlusive disease.

Alveolitis, Extrinsic Allergic↗
PubMed1996

Diffuse panbronchiolitis in an Asian immigrant.

Diffuse panbronchiolitis (DPB) is a disease with chronic inflammation exclusively located in the region of the respiratory bronchiole. It is largely restricted geographically to the Far East, and cases in Western countries are exceptional, even among Asian immigrants. A patient of Asian origin with DPB who had been living in France for 10 years is described. Only re-examination of the initial open lung biopsy specimen after an eight year period allowed this rare disease to be diagnosed correctly. The known efficacy of low dose erythromycin in DPB was again confirmed after failure of long term high dose corticosteroid therapy administered before an accurate diagnosis had been made.

Adult↗
PubMed1996

[Current aspects of spinal tuberculosis. Apropos of 10 cases].

Between 1990 and 1993 we observed 10 cases of spinal tuberculosis. Magnetic resonance imaging largely contributed to diagnosis and detection of early neurological complications. Medical treatment is essential and must be given for a sufficient duration. Indications for surgery are exceptional and are usually reserved for severe neurological complications.

Adult↗
PubMed1996

[Drug-induced pneumopathies accompanied by acute respiratory insufficiency].

Drug induced pneumonias accompanying acute respiratory failure are defined by a delay in presentation of less two months and severe hypoxaemia (PaO2 < 60 mmHg in ambient air). They are poorly indexed, often poorly understood by the clinician and pose difficult problems both of diagnosis and treatment. This general review touches successively on hypoxaemic drug induced pneumonia observed in oncology and haematology then those observed outside this very specific context. In each of the two groups five questions are posed: 1) Which patients? 2) Which clinical patterns? 3) What initial diagnostic discussion? 4) Which successful elements support the drug induced hypothesis? 5) What outcome? The replies obtained were compared to case reports from the literature (188 references) or from recent general reviews concerned more specifically with the hypoxaemic forms.

Acute Disease↗
PubMed1995

CYP2D6 genotype and lung cancer risk according to histologic type and tobacco exposure.

Polymorphism for CYP2D6 was determined genetically as part of a hospital-based case-control study. The cases were males with a histologically confirmed lung cancer diagnosis, < 75 years old, and no previous cancer diagnosis. Male controls were matched for age, hospital and residence area. This study includes 301 cases and 310 controls. A DNA bank was established for 547 patients (89.5%), and genotypes for CYP2D6 were differentiated by the Heim and Meyer method for the DNA samples of 249 cases and 271 controls. Among the cases, the frequencies of homozygous for the wild-type (EM), heterozygous (HEM) and homozygous for the mutant alleles (PM) were 62%, 32% and 7%; among the controls: 57%, 37% and 6%. Using EM as the reference, and adjusting for age, hospital and residence, we estimated the odds ratios for the HEM group and the PM group at 0.8 (95% CI [0.5-1.2]) and 1.1 (95% CI [0.5-2.4]) respectively. The PM frequency among the cases of adenocarcinoma was twice as high as among the controls (OR = 1.8, 95% CI [0.7-4.9]). This result was not observed among squamous and small cell carcinoma (OR = 0.7, 95% CI [0.3-1.8]). Twelve different case-control studies on CYP2D6 and lung cancer have so far been performed; the ORs they estimate range from 0.1 to 2.0, with a median value of approximately 0.6. This result lends some support to the hypothesis that belonging to the PM group is associated with a slight protective effect against lung cancer, but does not take into account the possibility that results may vary according to histologic type. In this context, the suggestion of a positive relationship between CYP2D6 and adenocarcinoma seems to us to merit investigation.

Adult↗
PubMed1995

Silica-associated connective tissue disease. A study of 24 cases.

We prospectively studied all patients hospitalized for connective tissue disease (CTD) in our French rheumatology clinic from January 1979 to December 1989. Our aims were 1) to determine if CTDs associated with occupational exposure to silica (Si) are currently observed in a rheumatology clinic, and, if so, 2) to describe the major features of Si-associated CTD, and 3) to specify which individuals are affected by Si-associated CTD. Patients were divided into 2 groups based on their responses to a questionnaire: those who had been exposed to Si, and those who had no occupational exposure to Si. Among the 764 patients with CTD studied, 24 (3%) were patients with Si-associated CTD and 740 (97%) were patients with non-Si-associated CTD. The sex ratio between the 2 groups was significantly different with a high frequency of men and of immigrants in the Si-associated CTD group. Two thirds of the patients exposed to Si were male miners or sandblasters, but the other third had more unusual exposures to Si, which may involve members of all socio-economics sectors and both sexes, such as sculpture or exposure to abrasive powders. Progressive systemic sclerosis (PSS) was significantly more prevalent in the Si-associated CTD group. This group also consisted of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), dermatomyositis (DM), and other autoimmune diseases. Si-associated CTD was characterized by the frequency of radiologic lung fibrosis, impaired pulmonary function tests, secondary Sjögren syndrome, and antinuclear antibodies. The number of mineral particles and crystalline Si content were raised in all the bronchoalveolar lavage specimens of Si-exposed patients but in none of those of nonexposed patients. In some cases of Si-associated CTD, the disease was reversible after early cessation of Si exposure. Epidemiologic studies are required to confirm our hypothesis that not only PSS and RA but also SLE and DM are associated with occupational exposure to Si. Pending such results, exposure to Si should be sought in the history of any patient with CTD, especially in a male patient with pulmonary signs, and if present, exposure should be stopped. In the meantime, steps should be taken to ensure that workers exposed to Si in all environments have adequate protection.

Adult↗