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Biomedical subjects

M Perol

Publications and source records attributed to M Perol.

At least 37 records · Page 2Linked to original sources

Humoral immune response within the lung in HIV-1 infection.

In order to study the humoral immune defences in the respiratory tract during HIV-1 infection, we measured the levels, local productions and anti-HIV and antibacterial activities of IgG and IgA in the bronchoalveolar lavage fluid (BALF) and serum of 61 adult patients with severe HIV infection and of 56 HIV- controls. Albumin was used as the serum transudation factor. The increase of immunoglobulin levels in the serum of HIV-infected patients was confirmed. The IgG level was also increased in epithelial lining fluid (ELF), whereas the total IgA level was unchanged and secretory IgA (SIgA) level was decreased. The ELF/serum immunoglobulin ratios suggested that the IgG present in ELF resulted mainly from transudation, in contrast to SIgA, which was synthesized locally in controls but greatly diminished in HIV-infected patients. IgG to HIV-1 could be detected in BALF of all the patients, but IgA to HIV-1 only in 30% of patients. BAL IgG reacted more consistently and with a broader array of HIV-1 antigens than did IgA. BAL IgA, when present in samples, reacted primarily with viral envelope antigens. Because IgA specificities to some HIV-1 antigens were detected more intensively by BAL than by serum immunoglobulins, we conclude that the mucosal immune response is distinct from that in serum. IgG antibody activity to Streptococcus pneumoniae was decreased in HIV-infected patients' sera, and IgA antibody activities to S. pneumoniae and to Pseudomonas aeruginosa were decreased in ELF in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗

Cost analysis of hospital treatment--two chemotherapic regimens for non-surgical non-small cell lung cancer. GFPC (Groupe Français Pneumo Cancérologie)

STUDY OBJECTIVES: compare the costs of two regimens of chemotherapy. Apply weighted costs to an economic model in a hospital perspective. DESIGN: prospective randomized study of two groups of patients receiving: branch B, mitomycin-navelbine-cisplatin (MNP); branch A, mitomycin-vindesine-cisplatin (MVP). SETTING: pneumologic units of University and non-University hospitals. METHODS: clinical evaluation during chemotherapy incorporated events enabling construction of an event tree. Direct hospital costs included those of: cytostatic agents, materials used and nursing time; costs of side-effects (medical and paramedical time, diagnostic and therapeutic examinations). Effectiveness was measured in terms of response rates. PATIENTS: 209 patients were included, 100 in arm B, 109 in arm A. RESULTS: the response rates were 25% in branch B, 17% in branch A. In the hypothesis of equivalence of the two strategies, we compared only overall mean cost per patient. Despite the fact arm B needed more hospital injections, the difference was low (+4.6%). For a difference in effectiveness, the opposite was observed for the average cost-effectiveness ratio: arm B was less costly (-12 339.40 FF for a responder). CONCLUSION: incorporation of economic parameters was found to have a bearing on the choice of chemotherapeutic regimen for the treatment of non-small cell lung cancer. Economic analyses of this kind can provide useful extra information for rational therapeutic decisions.

Adult↗

The limits of chemotherapy dose intensification using granulocyte colony stimulating factor alone in extensive small cell lung cancer.

Human Recombinant Granulocyte Colony Stimulating Factor (G-CSF) allows rapid neutrophil recovery after chemotherapy-induced leukopenia. In a prospective series of 54 patients with extensive small cell lung cancer, we evaluated the feasibility and efficacy of accelerated delivery of the AVI chemotherapy regimen. Treatment consisted of Doxorubicin 50 mg/m2 day 1, Etoposide 120 mg/m2 day 1-3 and Ifosfamide 2 g/m2 (+ Mesna 4 g) day 1 and 2 given every 2 weeks and followed by G-CSF (Neupogen, Amgen Roche 5 micrograms/kg/day s.c. day 4-14). Twenty-seven (50%) patients could not receive the total of six courses, seven because of severe septic complication, 10 because of Grade 4 thrombopenia, seven because of non-response and three because of patient refusal. Chemotherapy had to be delayed in 58 out of the 244 administered courses and this was due to thrombopenia in 48% of cases. The probability of optimal dose-on-time administration was 64% at three courses. The mean actually received dose intensity was 93% at six courses (27 patients treated). It was increased by 76% compared to our previously published conventional 3-week interval chemotherapy. The median neutrophil nadirs were stable during the successive treatment courses while haemoglobin and platelet values significantly worsened from cycle 1 to cycle 6. The overall response rate after three courses was 77% in the 48 evaluable patients. The median survival is 8 months overall and 5 months disease free. The actuarial survival is 22% at 2 years. We conclude that substantial dose intensification with accelerated chemotherapy and G-CSF support is feasible. However, the rate of severe infectious episodes is too high and thrombopenia is the main limiting factor. Either growth factors active on the megacaryocytic lineage or haematological rescue with peripheral blood stem cells might be useful in this setting.

Antineoplastic Combined Chemotherapy Protocols↗

[Isolated febrile intra-alveolar hemorrhage detected in leptospirosis].

We report observation of a patient of 25 years who presented with an isolated intra-alveolar haemorrhage occurring during the course of an illness suggestive of septicaemia. Considering the epidemiological context of inhalation of water from the River Saone, the diagnosis of acute leptospirosis ictero-haemorrhagica was considered and was confirmed by serological tests. Several publications draw attention to the pulmonary manifestations of acute leptospirosis which remains rare and poorly understood. Pulmonary disease is characterised not by an infectious alveolitis but by the occurrence of intra-alveolar haemorrhage whose pathogenetic mechanism remains under discussion.

Adult↗

[Rare etiology of multiple pulmonary lacunae].

Sarcoma of the common pulmonary artery are rare malignant tumors which can mimic pulmonary embolism. In the case presented here, the inaugural signs were particularly misleading: multiple pulmonary lacunae on computed tomography. The unusual aspect and asymmetric localizations at pulmonary angiography then suggested the doubtful nature of the embolism etiology. Magnetic resonance imaging findings suggested the diagnosis of sarcoma of the pulmonary artery. Certain diagnosis was obtained at pathology examination of the surgical specimen after thoracotomy. A malignant fibrous histiocytoma was identified. Curative resection was not possible and chemotherapy was performed. Unusual parenchymal lesions were then evidenced on the radiography. Better and better magnetic resonance imaging criteria are described in the literature and help distinguish between thromboembolism and sarcoma of the pulmonary artery. Follow-up of the clinical course is thus improved. It is nevertheless necessary to evaluate intravascular extension to determine whether curative surgery is possible.

Adult↗

[Diagnostic difficulties in angiosarcoma of the pulmonary artery with hemoptysis].

Intimal sarcomas growing from the pulmonary trunk or branches of the pulmonary artery, are rare tumours in which the diagnosis is most often made at autopsy or during a thoracotomy. Usually the clinical pictures is non specific resembling a severe pulmonary embolus which is resistant of all treatment. With the help of new imaging techniques, a pre-operative diagnosis is made in more than half the cases. When there is a tumour which is relatively localised and without endoluminal invasion, as in the observation reported here, the diagnosis rests on the histology from the operative specimen.

Angiography↗

Combination chemotherapy with gemcitabine and cisplatin in the treatment of advanced non-small cell lung cancer: preliminary results of an ongoing phase I/II study.

Collaborative phase I and II studies of the combination of gemcitabine and cisplatin in patients with advanced non-small cell lung cancer are ongoing at five centres in the UK and France. In the initial completed phase I study, 16 patients (15 evaluable) have been entered using a fixed dose of gemcitabine 1000 mg/m2 given as a 30 min intravenous infusion weekly for 3 weeks. On the third week the gemcitabine was immediately followed by cisplatin with pre- and post-hydration. This regimen required only 1 night of hospitalization every 4 weeks. The study design was for sequential groups of patients to receive 3 dose levels of cisplatin (60 mg/m2, 75 mg/m2 and 100 mg/m2) but these doses would be modified and the number of patients at any dose level could be increased if significant toxicity was observed. Three patients were to be entered at the first two dose levels and 10 patients were to confirm the maximum tolerated dose (if reached) or expand the database on toxicity at the final predetermined dose level. The major haematological toxicities were neutropenia (grade 4 in 3 patients) and thrombocytopenia (grade 3 or 4 in 5 patients) but both were of short duration and uncomplicated. Grade 3 nausea and vomiting occurred in 12 patients but was no worse than would be expected from cisplatin alone. Alopecia was not a problem (no hair loss in 10 patients and grade 1 or 2 in 6 patients) and no significant renal or neurotoxicity was seen. A phase II study using cisplatin 100 mg/m2 in combination with gemcitabine 1000 mg/m2 has been opened and to date 19 patients are evaluable for response. Eight (42%) have achieved partial remissions. The study is ongoing and will recruit 50 evaluable patients.

Antimetabolites, Antineoplastic↗

[Proximal bronchial cancer with hypoxemia due to right to left intrapulmonary shunt. Correction of hypoxemia after pneumonectomy].

The authors report a case of a patient who was in hospital for a bronchial cancer completely occluding the left superior and inferior lobar bronchi. Respiratory function tests showed: an FEV1 of 1.7 litres, FEV1 (vital capacity ratio of 60%), a TLC of 76% of the predicted value and a PaO2 of 52 mm of mercury with an elevated alveolar arterial oxygen gradient. The ventilation perfusion lung scan showed that the left lung was not ventilated but was perfused. A left pneumonectomy was judged to have removed the cancer and enabled a correction of the hypoxaemia. The authors recall the functional repercussions of absent ventilation of one lung by a proximal bronchial obstruction and the therapeutic implications in the realm of neoplastic pathophysiology.

Carcinoma, Bronchogenic↗

Limited disease small cell lung cancer: alternating combination of doxorubicin, etoposide, ifosfamide and hyperfractionated radiotherapy. Final results of a multicentric pilot study for the Groupe Lyonnias d'Oncologie Thoracique (GLOT).

In order to evaluate the effect on prolonging survival of alternating chemotherapy and radiotherapy schedules in patients with limited disease small cell lung cancer, 89 patients were included in a multi-institutional pilot study between January 1986 and May 1989. Treatment consisted of induction chemotherapy using the combination of doxorubicin, etoposide and ifosfamide (AVI) for four consecutive courses, followed by two cycles of the VI chemotherapy alternating with three hyperfractionated radiotherapy courses and then followed by two additional courses of AVI. Objective response to the four cycles of AVI combination was observed in 65 patients (75%). Thirteen out of 30 patients (44%) who were in partial response (PR) after induction chemotherapy were converted into complete response (CR) after the three alternating courses of chemotherapy and radiotherapy. The principal side effect related to combined modality treatment was acute radiation pneumonitis (21.5% cases) reversible except one which resulted in toxic death, and a second with chronic lung fibrosis with permanent WHO Grade 2 dyspnea (14%). Local relapse was observed in 47% of the patients who were considered in CR at the end of the treatment program and cerebral metastases were the first site of detectable relapse in 25% cases. The 3-year actuarial disease-free survival of the 89 patients is 5%, and the median actuarial survival is 14 months. This study shows that the promising survival rates seen in our previously published interim analysis were not maintained. Reasons for this might include the choice of a non cisplatinum containing induction chemotherapy, the late introduction of thoracic irradiation and/or to the use of non-restrictive criteria for selecting patients.

Adult↗

[Combination of cisplatin-mitomycin-vindesine for inoperable, non-small-cell bronchial cancers. French study group in pneumo-cancerology].

The efficacy of the association of cisplatinum-mitomycine and vindesine on inoperable non-small cell bronchial cancer has been assessed in a prospective study. Cisplatinum 120 mg/m2 and mitomycine 8 mg/m2 on day 1, day 28 and day 70, and vindesine 3 mg/m2 once per week for the first cycle, once every 15 days for the second and third cycles. 98 patients were included in the study between February 1989 and June 1990: there were 89 men and 9 women with a mean age of 60. There were 57 epidermoid cancers, 22 adenocarcinomas, 1 neuroendocrine carcinoma and 18 large cell cancers. There was an objective response (RO) in 25% (of whom 5% had a complete response) without any significant difference between the 56 cancers at stage III (32% RO) and 42 cancers in stage IV (17% RO). The median survival of the responders was 14 months again 5 months for the non-responders. The initial loss of weight seemed to be a prognostic factor because the number of objective responders was significantly greater in the patients with only a small weight loss: 37% of RO if the weight loss was less than 5%, against 11% for a weight loss of greater than 5%. The myelotoxicity of this association was important because 85% of those patients presented with a leucopenia at least grade II OMS. Peripheral neuropathies occurred in 27% of cases: 4 cases of cardiotoxicity were reported.

Actuarial Analysis↗

[Clinical and economic evaluation of the initial assessment of small cell cancer of the lung. Alternatives to classic evaluation. LGTO. The Lyon Group of Thoracic Oncology].

Alternatively to the usual evaluation summary, a characteristic of small cell lung cancer, is the probability of significant diffuse metastases; the prognosis is directly linked to the extent of these metastases. Moreover, the assessment of the initial extension becomes heavier and more costly as investigations continue and each new technology appears. In order to evaluate the contribution of each examination, a classification has been established as a function of the time-scale to obtain the results, of the technology involved, or whether the investigation is painful or not and any likelihood of iatrogenic side-effects. An assessment in three stages is proposed to achieve the most effective and cheapest diagnosis possible. In relation to the usual technique of assessment this sequential approach allows for a 27% reduction in the time-scale for the diagnosis of diffuse disease, 51.3% in terms of technical involvement, 46.3% in terms of pain and discomfort and 53.9% in terms of iatrogenic potential. At the same time a reduction in cost of 47.5% is observed.

Alkaline Phosphatase↗

[Isolated pleuropulmonary metastases of uterine sarcoma].

We report the case of a 52-year old post-menopausal woman in whom the finding of a right paravertebral mediastinal and pulmonary mass and a homolateral pleural effusion revealed the presence of a large uterine tumour. Pleural fluid cytology was in favour of an undifferentiated tumour, and biopsy of the endometrium pointed to a connective tissue tumour. Following immunohistochemical staining, hysterectomy combined with adnexectomy confirmed the diagnosis of uterine sarcoma. Later on, the patient underwent thoracoscopy which showed multiple pleural metastases. In view of concordant histological results and of the appearance of multiple spherical images at radiology, chemotherapy with adriamycin, ifosfamide and vincristine was instituted but proved to be ineffective: the patient died after two cycles of this therapeutic regimen.

Antineoplastic Combined Chemotherapy Protocols↗

[Comparison of 2 cisplatin and etoposide dosages in relapsing small cell lung cancer].

The synergistic combination of cisplatinum and etoposide appears as the best second line treatment in patients relapsing from small cell lung carcinoma (SCLC). In order to test the dose-effect relationship of cisplatinum and etoposide in this situation, we have performed a randomised phase II trial comparing 2 five-day regimens: cisplatinum 20 mg/m2/day+etoposide 60 mg/m2/day (arm A) versus cisplatinum 40 mg/m2/day+etoposide 100 mg/m2/day (arm B) every 4 weeks. Thirty-seven patients were included (arm A: 18, arm B: 19), and 32 were considered to be eligible (arm A: 15, arm B: 17). Eight patients were non evaluable, five of them because of toxic death occurring prior to the second course (arm A: one from neutropenia; arm B: three from neutropenia and one from thrombopenia). The two groups were well balanced with regard to the main prognostic factors (age, sex, performance status, LDH level, response to induction chemotherapy). An objective response was observed in 10/24 evaluable patients (arm A: 4, arm B: 6) and was considered as complete in one patient in arm A and in 2 pts in arm B; these two patients presented with cerebral metastases and their response lasted 9 and 15 weeks respectively. The mean duration of response was 11 weeks in arm A and 10.5 weeks in arm B. The median actuarial survival of the overall population of eligible patients was 15 weeks: 13 weeks in arm A and 16.5 weeks in arm B. The study was discontinued because of the 23.5% toxic deaths rate in the high doses arm in this heavily pre-treated population of patients. However, the high response rate (54% overall, 35% considering toxic death as a failure) is impressive and presents evidence for the dose/effect relationship in SCLC.

Aged↗

[Mediastinal-pulmonary sarcoidosis with unilateral pseudotumorous presentation. Apropos of a case].

We report a case of a patient of forty two years who was admitted with a chronic cough and had a left hilar "tumour". Scanning showed a hilar opacity with an air bronchogram. Fibreoptic bronchoscopy did not succeed in achieving a precise diagnosis, the biopsies showed no sign of malignancy. An open lung biopsy was necessary to establish the diagnosis of pulmonary mediastinal sarcoidosis with a pseudo-tumoral presentation and localised unilateral disease involving a segmental bronchus and the left upper lobe. There was a rapidly favourable outcome after treatment with steroids.

Adrenal Cortex Hormones↗

[Thromboembolic pulmonary arterial hypertension].

Thromboembolic pulmonary hypertension can occur in two different settings: either acute pulmonary embolism or chronic pulmonary thromboembolism. During acute pulmonary embolism, when the heart and lungs are normal, the mean pulmonary artery pressure never excesses 40 mmHg, this is the maximum pressure the right ventricle can stand. During chronic thromboembolism, the right ventricle can adapt to slowly increasing pulmonary artery pressure. The mean pulmonary artery pressure is usually very elevated and right heart failure is delayed. Diagnosis is difficult when an history of acute pulmonary embolism or phlebitis is lacking. At the beginning, the main differential is psychogenic dyspnea. A clue to the diagnosis is given by the pulmonary function test mainly arterial blood gases at rest and exercise and radionuclide perfusion scan. When the pulmonary hypertension is patent the main differential is primary pulmonary hypertension. No definitive clear cut can be made between multiple distal chronic thromboembolism and primary pulmonary hypertension.

Acute Disease↗