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Summary Purpose The purpose of the study was to assess the possible benefit of the combination vinorelbine (NVB)-cisplatin (DDP) in comparison with NVB alone in advanced non- small cell lung cancer (NSCLC), not treated previously. It also involved confirmation of the efficacy of vinorelbine as monotherapy. Patients and methods In this phase 111 trial, 231 eligible patients were stratified by centre and randomized to receive either NVB alone, 30 mg/m2/week or the combination of NVB 30 mg/m2/week and DDP 80 mg/m2/3 weeks. Patients were to be treated for a minimum of 6 weeks, with the first response assessment performed 9 weeks after the beginning of treatment. Results The two groups differed in terms of objective response rates (16% and 43%, respectively, p = 0.0001) and median time to progression (10 weeks and 20 weeks, p = 0.0001). However, the difference was not significant for median survival time (32 weeks, 33 weeks, p = 0.48). The addition of DDP resulted in an increase in toxicity, in particular renal, hematologic, neurologic and emetic. This toxicity led to treatment discontinuation in 8% and 21% of patients, respectively. Respectively 3% and 13% of patients stopped treatment early during objective response (toxicity or refusal). Conclusions The NVB-DDP combination increased objective response rates and time to progression in comparison with NVB alone, but did not influence the survival of patients. The activity of NVB in the treatment of advanced NSCLC was confirmed.

Optimal dosage for chemotherapy administered to patients on chronic hemodialysis remains a difficult question. We report the case of a patient with chronic renal failure on hemodialysis for 9 years who was treated for small-cell lung cancer. The chemotherapy protocol combined carboplatin and etoposide at doses adapted to creatinine clearance. Tumor regression was observed after 6 cycles without major intolerance.

Since a high tissue penetration of dirithromycin (D) has been assessed in early studies, the aims of this study were to determine D concentrations in bronchial mucosa and secretions in patients suffering from an acute exacerbation of chronic bronchitis (AECB), to compare intra-individual bronchial mucosa and secretion concentrations and to relate bronchial concentrations of D and clinical efficacy. The main inclusion criteria were comprised of (1) AECB, defined by the presence of an increase in dyspnea, sputum production and change in sputum purulence, and (2) clinical indication of fiberoptic bronchoscopy allowing performance of bronchial biopsies. All patients were treated with a 500-mg once-daily D dose for 5 days. Patients were randomly divided into three groups, according to sampling times (24, 48 and 72 h after the last dose). Tissue concentration analyses were performed by one blinded microbiologist (microbiological agar diffusion assay). The results showed: (1) 37 out of the 46 patients (80.4%) had a favorable response to treatment at the time of fiberoptic bronchoscopy (14 cured, 23 improved); (2) bronchial mucosa concentrations were high in all groups, and (3) mean values at 24, 48 and 72 h after the last dose were respectively 6.51 ± 1.44, 6.61 ± 2.7, 5.67 ± 1.02 mg·kg–1; no statistical difference was observed between the groups. In bronchial secretions collected simultaneously, concentrations were lower, i.e. 1.26 ± 0.3, 0.61 ± 0.12, 0.84 ± 0.12. Significant associations were observed between bronchial mucosa and secretion concentrations (r = 0.71, p = 0.0001), and between clinical response and bronchial concentrations (p = 0.03, Kruskall-Wallis test). In conclusion, these results may confirm the clinical significance of tissue concentrations measured in bronchial tissues of patients with AECB.

We describe a 28-year-old subject employed as a roofer in a construction company since the age of 19, who developed work-related symptoms of a cough, shortness of breath, wheezing, rhinitis and headaches. A description of a usual day at work suggested that the symptoms worsened while he was sawing corrugated fiber cement. Baseline spirometry was normal, and there was a mild bronchial hyperresponsiveness to carbachol. A skin patch test to chromium was negative. A specific inhalation challenge showed a boderline fall in forced expiratory volume in 1 s (FEV1) after exposure to fiber cement dust. Exposure to nebulization of potassium dichromate (K2Cr2O7), at 0.1 mg·ml–1 for 30 min, was followed by an immediate fall by 20% FEV1. Simultaneously, a significant increase in bronchial hyperresponsiveness was demonstrated.

International audience; Previous studies have suggested the utility of D-Dimer ELISA assays in eliminating a diagnosis of pulmonary embolism (PE). Our objectives were to evaluate the performance of a new, rapid, quantitative, and automated Liatest D-Dimer Assay in patients with suspected PE. Three hundred eighty-six consecutive patients referred to our institution between March 1992 and December 1996 for clinically suspected PE, with recent clinical signs not exceeding 1 wk, were included in this study. Diagnosis of PE was based on clinical evaluation, radionuclide lung imaging, lower limb examination, and, when required, pulmonary angiography. D-Dimer performances, for both Liatest D-Dimer and standard D-Dimer ELISA (Asserachrom DDi), assays, were assessed at the end of the study. Among the 386 patients tested, 146 (37.8%) were classified as PE-positive. Liatest D-Dimer assay had a 100% sensitivity (95% confidence interval, 97 to 100%) and a negative predictive value of 100% (95% confidence interval, 94 to 100%). A normal result, below the cutoff of 500 ng/ml, occurred in 83 of the 386 (21%) patients. There was a strong agreement between Liatest D-Dimer and Asserachrom DDi analyses. These findings suggest that this rapid, quantitative, and automated D-Dimer assay provides a useful diagnostic tool for the clinician with regard to exclusion of PE.

International audience; In previous studies, enzyme-linked immunosorbent assays (ELISA) for plasma D-dimer analysis have demonstrated high sensitivity, suggesting their potential usefulness in excluding deep venous thrombosis (DVT). We evaluated the usefulness of a new D-dimer test (Liatest D-dimer) for suspected DVT in a prospective study of patients admitted to the hospital because of recent (not exceeding 1 week before admission) clinical signs. Contrast venography or compression ultrasonography or both were performed within 24 hours of admission. A new quantitative determination of D-dimer concentration using a suspension of microlatex particles coated with specific antibodies was tested. A standard plasma D-dimer ELISA measurement was also performed. Of 464 patients, 276 had a proven DVT (distal, 74; proximal, 202). For a cutoff level of 400 ng/mL, sensitivity of the Liatest method in the diagnosis of overall DVT was 94.6% (95% confidence interval, 92.0%-97.0%), and the specificity was 35% (95% confidence interval, 28%-42%). The sensitivity and negative predictive value were 98.5% and 95.6%, respectively, in the diagnosis of proximal DVT, but only 83.8% and 84.6%, respectively, in the diagnosis of distal DVT. This new rapid Liatest D-dimer assay seems to be highly sensitive and could replace the ELISA method in excluding patients with proximal DVT. Both methods provide lower sensitivity for distal DVT.

The Asthma Quality of Life Questionnaire (AQLQ) is a well-validated instrument. Our objectives were to explore the cross-sectional validity of the French version, using usual outcomes of asthma, as well as assessment of knowledge of asthma, self-management and compliance. A self-administered version of the AQLQ was given to 124 consecutive patients recruited from two out-patient clinics and an emergency room in order to reflect a wide range of asthma severity. The other outcomes of asthma measured were the FEV1, patient-perceived asthma severity using a visual analogue scale, compliance, knowledge of asthma condition and self-management autonomy. Correlations were predicted before analysis ( r0.5, strong correlation, ++ r = 0.35-0.5, moderate correlation and + r = 0.20-0.35, fair correlation). The AQLQ scores correlated moderately to strongly with asthma severity and fairly with the pulmonary function results. Of the behavioural outcomes assessed, only knowledge of asthma correlated fairly with the AQLQ scores, as expected. This study of the French version of the AQLQ, while showing similar cross-sectional correlations with functional assessment and asthma severity to those observed with the original English version, suggested in addition a positive association between quality of life and knowledge of asthma.

A Phase I trial of carboplatin therapy was performed on patients with locally advanced non-small cell lung cancer who had been previously treated with cisplatin, mitomycin and a vinca aklaloïd. This was administered as a daily bolus infusion or as a continuous infusion for 6 weeks with concurrent daily thoracic radiation. All patients had to be objective responders or to show no change after chemotherapy. The carboplatin was started at 10 mg/m2 per day, and increased to 15 mg/m2 per day and 20 mg/m2 per day, if treatment was feasible in successive cohorts of at least six patients. The radiation therapy consisted of 62-66 Gray on the tumor and the ipsilateral mediastinal nodes, 50 Gray on the mediastinum and 40-45 Gray on the supraclavicular lymph nodes. Twenty-nine patients took part in this study. Thrombocytopenia was the principal dose-limiting toxicity, with 15 mg/m2 per day of bolus or continuous infusion. Other toxicities included a fall in haemoglobin level, a fall in white-blood cell count, nausea and vomiting. The median survival time was 12 months, but the response rate cannot be determined among patients selected on the basis of response to chemotherapy. The recommended Phase II dose for patients previously treated with cisplatin containing chemotherapy, is 10 mg/m2 per day of either a bolus or continuous infusion.

International audience; BACKGROUND: The value of a risk factor analysis in the presence of a clinically suspected deep venous thrombosis (DVT) has been assessed mainly in inpatient populations. The aim of this prospective study was to evaluate the potential association between DVT and acquired circumstances suspected as risk factors, in a cohort of outpatients with a clinically suspected DVT. METHODS: Consecutive outpatients referred for a clinically suspected DVT, with recent clinical signs, not exceeding 1 week, were included. Before venography, all patients were interviewed by a trained physician to detect the presence of risk factors. RESULTS: From March 1992 to February 1994, 277 patients were included; venography was positive in 162 (58.4%). Five independent variables were significantly associated with the occurrence of DVT; in a multivariate analysis, 64.7% of patients were correctly classified; odds ratios for having DVT in the presence of these underlying conditions were respectively: 1.75 for age over 65 years, 1.68 for prior history of venous thromboembolism, 1.69 for high risk circumstances (any type of surgery or leg trauma within the past 3 months), 5.59 for malignancy, and 2.56 for varicose veins. CONCLUSIONS: In outpatients referred for a clinically suspected DVT, recognition of associated conditions might increase the certainty of the diagnosis.

Rhabdomyosarcoma is a malignant tumour generally observed in children or adolescents; thoracic localization is rare. The authors report a case of embryonary rhabdomyosarcoma of the thoracic wall in a 36-year-old subject. Pathology examination of surgical specimens confirmed the diagnosis. Treatment included surgical exeresis together with pre- and post-operative chemotherapy combining doxorubicine (40 mg/m2/cycle), ifosfamide (6 g/m2/cycle) and dacarbazine (900 mg/m2/cycle). Local recurrence, requiring radiotherapy, was observed a few months later and led to the patient's death after a 9-month clinical course.

We report the case of an asymptomatic 51-year-old man, presenting with chest X-ray abnormalities consisting in multiple pulmonary nodules; the diagnosis of mesenchymal cystic hamartoma of the lung was made by an open lung biopsy, revealing both nodules of mesenchymal cells and cysts with a lining of normal or metaplastic epithelium. Clinical and pathological characteristics of this rare entity are reviewed.

Formoterol aerosol, a long-acting new beta 2-mimetic was administered over a year at a dose of 12 micrograms twice daily, to 62 chronic obstructive bronchitics of mean age 66 +/- 6 years and of whom the basal VEMS was at 12,801 +/- 0.59. Clinical tolerance of the product was good with undesirable effects in 13 patients, the most frequent being shaking. No untoward effect was seen on systolic or diastolic arterial pressure, or the heart rate over successive visits at 1, 3, 6, 9 months and one year. Electrocardiographic surveillance found in only four patients electrical abnormalities that may be due to Formoterol, these were patients without previous cardiac problems but of advanced mean age. Functionally, a significant improvement of basal VEMS was noticed from the 6th month. The VEMS improved significantly after administration of 12 micrograms on successive visits, without tachyphylactic signs. Well tolerated, with functional benefits, Formoterol is a promising product amongst the long-acting beta 2-mimetics. Its usefulness and limitations in the basic treatment of these chronic bronchopathies remains to be defined.

We report the results of a combined of chemotherapy with CDDP and 5 FU repeated every 3 weeks in sixteen men (age range 31-73 years) with brain metastases. CT was performed after 2, 4 and 6 cycles to assess efficiency. Response was considered complete when no lesion was found on the CT scan and partial when the lesion shrunk to least half its the total volume. After two cycles, the response rate was 8/16 (50%). Treatment toxicity was mild with only one case of severe but reversible myelotoxicity (grade III). CDDP and 5 FU combined chemotherapy can be a useful treatment for brain metastasis of lung carcinoma.

Chemotherapy is not a common treatment for cerebral metastases. The authors report results of combination chemotherapy with cisplatin (CDDP) and fluorouracil (5-FU). Sixteen men (age range 31-73 years) with brain metastases were treated with CDDP 20 mg/m2/day in continuous infusion for 5 days (d 1-5) and 5-FU 1 g/m2/day in continuous infusion for 4 days (d 1-4), and the treatment schedule repeated every 3 weeks. A brain computerized tomography after 2, 4 and 6 cycles was performed to assess efficacy. It was considered that complete response was achieved if no lesion was found on the CT scan, and partial response if at least half of the total volume had decreased. After 2 cycles, the response rate was therefore 8/16 (50%). Treatment toxicity was very mild with only 1 case of severe but reversible myelotoxicity (grade III). It is concluded that chemotherapy combination with CDDP and 5-FU is a useful treatment for brain metastasis of lung carcinoma.

Age and circumstances of menopause (natural or artificial) are detailed in 104 cases of recent myocardial infarction (MI). The results of this study with statistical analysis show no correlation between the age at menopause and the age at onset of MI; so, for this study, an early menopause, cannot be considered, whatever circumstances, as a risk factor for coronary heart disease.

Among non-chromaffin paragangliomas, the so-called aorticopulmonary or branchiomeric mediastinal chemodectomas are very rare tumors. A case is reported, and 57 similar cases described in the literature are reviewed. As recommended by Olson, a separate group was instituted of 21 cases of the so-called posterior mediastinal or aorticosympathetic group of the costovertebral groove. In principle, aorticopulmonary chemodectomas are non-functional, and in 9 out of 10 cases follow a slow and benign course extending over many, or even tens of years. In contrast to carotid and jugular paragangliomas they are rarely multifocal: when this is the case it is difficult to confirm the presence of metastases, this being however the most reliable criterion of their malignancy. The fortuitous discovery on a radiography of a tumor of the anterior and middle compartments of the upper mediastinum should invoke the presence of an aorticopulmonary chemodectoma, and lead to arteriography of the aortic arch region. Diagnosis is made essentially by pathological examination. Treatment is exclusively by surgical excision, and this was complete in nearly half of the cases treated. Prognosis is not hopeless after partial removal, however, and a relatively comfortable survival can be obtained extending over many years.

Two cases of systemic lupus erythematosus (SLE) complicated by pneumonia which resulted in death are reported. The first patient, a 21-year old woman, died of acute diffuse lupus pneumonia; the initial and unusual radiological image of "multiple balloons" progressed within 2 months to terminal interstitial fibrosis. The second patient, a 60-year old woman, died of infection on an interstitial pneumonia which turned into severe fibrosis within 16 months. Acute or chronic lupus pneumonia is uncommon, but it may follow a very serious course. Clinically, true lupus pneumonia must be distinguished from all other types of lung involvement in SLE, such as infection, pulmonary haemorrhage or oedema, iatrogenic pathology, thromboembolic disease, etc. The pathogenetic mechanism of pulmonary lesions directly related to SLE is obscure, although some lung biopsy specimens have shown positive immunofluorescence. Concerning treatment, the initial response to corticosteroid therapy is usually very good, especially in the acute forms of the disease. However, in severe cases immunosuppressive drugs or even plasma exchanges must be added to steroids. For treatment to be rapidly initiated the diagnostic procedures must be completed in the early stages of the disease, involving, when necessary, surgical lung biopsy.

In a 59-year old sand-blaster, histologically proven silicosis was complicated by systemic lupus erythematosus (SLE) and focal glomerulonephritis with IgG, IgA and ClQ deposits. Nothing likely to facilitate SLE was detected by investigating the familial background, the HLA phenotype and the complement system. This type of SLE differs from drug-induced lupus-like syndromes by a high level of anti-double helix DNA antibodies and by the renal lesions observed. The connection between silicosis and SLE lies in changes in humoral immunity, i.e. polyclonal activation and production of antinuclear antibodies. A decrease in the number of suppressor T-cells may also be held responsible.

Lymphocytes forming E rosettes, active E, autologous and EA antibodies were studied in 66 subjects (56 men, 10 women, mean age 59, range: 40-85 years) who presented with lung cancer classified on the TMN scale in stages I and II: 19; stage III: 20; stage IV: 27. In comparison to the controls, there was a significant reduction (p less than 0.01) in E, autologous and EA rosettes in the patients. A reduction in E active rosettes (compared to controls) was noted for stage IV cases (p less than 0.01) and rose with the stage. The formation of rosettes was reduced in 50 squamous carcinomas compared to 12 anaplastic carcinomas for E rosettes (p less than 0.01) and E active (p less than 0.02). If one compares the actuarial survival curves of 37 patients with E act rosettes greater than or equal to 23% and of 29 with a level of less than 23%, the mean survival for all stages combined was 14.1 months in the first group and 8.2 months in the second group. Associated with an extension of the tumour, the immunological system has a role in determining outcome and lymphocytes forming active E rosettes appear to be the subpopulation most closely correlated with survival.

T lymphocyte subpopulations by monoclonal antibodies have been studied in 17 atopic asthmatics and 17 normal subjects age and sex matched, we found a significant decrease of total T lymphocytes with significant decrease of CD4 antigen bearing cells in the patients, the pollenogenic asthmatics being responsible for this difference with the controls. We did not find any study of the literature evaluating T lymphocyte subpopulations in atopic patients with regard to allergen type. The pathogenic hypothesis are discussed.

We found a significant decrease of OKT8 + ve cells in silicosis patients (18.1%), but also in unaffected exposed workers (19.0%), when compared with sex- and age-matched controls (22.8%). The proportion of OKT8 + ve cells was significantly lower in subjects with antinuclear antibodies (15.7%) and in those with IgG-rheumatoid factors (16.3%).

E, E-active and autologous-rosette-forming-lymphocytes (E, Eact-, auto-RFC) were studied in 66 patients with lung cancer (2 stage I, 17 stage II, 20 stage III, 27 stage IV), 42 patients with head and neck cancer (14 stage III, 28 stage IV) and 22 patients with esophagus cancer (11 stage II, 6 stage III, 5 stage IV). Compared to controls, E-RFC were found to be depressed in each of the three different localizations (p less than 0.001), Eact-RFC were found to be depressed in head and neck as well as esophagus cancer (p less than 0,05 and p less than 0,01 respectively) and auto-RFC were found to be depressed in lung and esophagus cancer (p less than 0,01). Mean survival times of patients with RFC over and under 1 SD below the average value were compared. Significant differences were demonstrated in E-RFC and auto-RFC for head and neck cancer and in Eact-RFC for lung cancer.

Five new cases of solitary fibrous mesothelioma of the visceral pleura support this review of the literature. Well encapsulated, mostly pedunculated, the implantation on the visceral pleura remains asymptomatic for a very long time and is more likely to be an incidental finding on a chest radiograph. Two extrathoracic signs are associated with certain huge tumors : hypoglycemia and osteoarthropathy. Histologic examination discloses whorls of collagen with scattered spindle-shaped cells. Electron microscope reveals characteristic features of both fibroblasts and mesothelial cells. Complete surgical removal is the best treatment for localized fibrous mesotheliomas of the visceral pleura. Recurrences after resection are rare and late recurrence, as long as 16 years after initial excision, usually behaves in a benign fashion.

Five new cases of solitary fibrous mesothelioma of the visceral pleura support this review of the literature. Well encapsulated and usually pediculated, these tumours remain asymptomatic for a long time and are in most cases an incidental finding on radiographs of the chest. The precise site of the tumour can be identified by artificial pneumothorax. Some large tumours are accompanied by extrathoracic signs, i.e. hypoglycemia and hypertrophic pulmonary osteoarthropathy. Histological examination discloses whorls of collagen fibres with scattered spindle-shaped cells. Electron microscopy reveals characteristic features of both fibroblasts and mesothelial cells. Complete surgical removal is the best treatment of localized fibrous mesotheliomas of the visceral pleura. Post-surgical recurrences are rare, and late recurrences (up to 16 years after excision) are usually benign and of good prognosis.

Two cases of inappropriate antidiuresis are reported, one associated with small cell anaplastic bronchial carcinoma, the other secondary to acute hydrocephalus. ttreatment with demethylchlortetracycline proved effective in both cases. Treatment of the inappropriate antidiuretic syndrome is discussed and the advantages of demethylchlortetracycline emphasised. This antibiotic seems to represent the treatment of choice of the chronic syndrome of inappropriate antidiuresis.

Acquired ichtyosis appears to be a rather rare paraneoplasic syndrome, mainly observed during the course of Hodgkin's disease, but also accompanying visceral cancers. Two cases of generalised ichtyosis in patients with bronchial carcinoma are reported, emphasis being placed on the need for systematic investigations to determine this possible aetiology. Diagnostic problems are discussed, as well as hypotheses concerning the pathogenicity of these affections, which is still obscure, emphasis being placed on the secretory potential of these tumours and the role of immunological phenomena.

The visual evoked potentials (VEPs), somatosensory evoked potentials (SEPs) and the electroencephalogram (EEG) have been studied in 16 subjects presenting chronic respiratory insufficiency (CRI) with normal consciousness. The SEPs latencies were increased but the VEPs latencies were not. The EEG was little disturbed and did not seem to provide useful information in CRI without encephalopathy.

Eleven patients with bronchial epidermoid carcinoma and undergoing treatment with cis-D.D.P. (II) were kept under electrophysiological and clinical surveillance. No other neurotoxic medication was added. The total dose of cis-D.D.P. was 300 mg/m2 over a period of three months: namely, three courses of 100 mg/m2 distributed over 5 days. Following the pretreatment check-up, the patients were divided into two groups: those without any electrophysiological abnormality (group A), and those without clinical abnormality but with a delayed latency H of the Hoffmann Reflex (group B). Patients in group A showed a slowing down of the motor nerve conduction velocity of the Median and Peroneal Nerves after a course of 100 mg, without accompanying worsening of the conduction velocity after 300 mg/m2, and prolongation of the distal latency of the sensory Median Nerve after 300 mg/m2; in group B, no significant change of electrophysiological clinical features were noted. In the two groups a non-significant reduction in amplitude of evoked responses were noted. These findings are more consistent with an axonal injury than with functional myelin injury. The authors review the existing literature and discuss the physiopathologic mechanisms of cis-D.D.P. peripheral neuropathies.

We report a case of pseudo-tumoral pulmonary amyloidosis in which the diagnosis was achieved by a transbronchial biopsy and ultimately confirmed by a necropsy examination of the lung. The lung disorder was isolated without any co-existing disturbance of the immunological system.

The authors report their experience of the evolution and treatment of spontaneous pneumothorax in the adult, in a series of 124 cases, starting from January 1965 to May 1975. Recurrences occur in 27% of cases whatever therapeutics are used. They discuss frequency and modality in relation to the etiology and the proposed treatment of pneumothorax.

Immunity-linked cells include the lymphocytes and phagocytes. The former can be counted by the rosette techniques or by monoclonal antibodies, while for the latter their function is determined mainly. Good correction has been demonstrated, for example, between the number of so-called E active rosettes and both tumor extension and patient survival. The surgical act itself exaggerates the satellite anomalies of the cancer, but in any case it is followed by immunotherapy which justifies a second application of immunologic techniques.

Antiperinuclear factor (APF) might be a specific serum rheumatoid factor directed towards keratohyaline granules. It was found to be present in 40 of 79 (50.6%) patients with primary and in 21 of 36 (58.3%) patients with metastatic lung cancer, compared with 12 of 95 (12.6%) sex- and age-matched normal controls. Additionally, APF frequency and titer correlated well with tumor dissemination, even though no relationship could be shown with histopathological type.

The gene of cystic fibrosis is localised on the long arm of chromosome 7. DNA probes placed close to the gene enable a study of restriction polymorphism to follow the transmission of the gene in index families. It is now possible to counsel those families, who already have an affected child, with an early antenatal diagnosis at ten weeks after the last period. In our personal experience, based on a study of the genotype of 48 families, 70% were informative when they were studied by two probes corresponding to the local pJ3.11 and met. When the latter probes Km19-XV2c were studied concurrently useful information was achieved in 96%. DNA analysis non enables the detection of the chromosome carrying the deleterious gene in practically every family where there is a child suffering from the disease.