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J L Pujol

Publications and source records attributed to J L Pujol.

At least 91 records · Page 5Linked to original sources
PubMed1992

Chest tumor response measurement during lung cancer chemotherapy. Comparison between computed tomography and standard roentgenography.

Chemotherapy of lung cancer has, until now, been an experimental approach that requires careful evaluation of tumor response. The growing number of lung cancer patients now undergoing chemotherapy has led to a rapid increase in the number of computed tomography (CT) scans performed. Eighty consecutive lung cancer patients (55 non-small cell and 25 small cell lung cancers) were included in a prospective study to analyze whether the standard chest roentgenography is as effective as computed tomography in evaluating tumor response. Both standard chest roentgenography and CT scanning were performed before the chemotherapy began and were repeated after 10 to 12 wk of treatment. Response evaluations were performed according to the World Health Organization recommendations. When two-dimensional measurements were possible, the indicator lesions were defined as measurable tumors. Both roentgenography methods were used, independently, to classify the response into the following categories: complete response, partial response, minor response, stable disease, and progressive disease. A comparison of CT scans versus standard chest roentgenography as a measurement of indicator lesion showed a concordance of borderline significance (kappa = 0.146, p less than 0.05); a significant asymmetry was demonstrated (McNemar = 35.6, p less than 0.001), indicating that CT scanning may be a more appropriate method for measuring tumors than standard chest roentgenography. Moreover, no concordance was observed comparing CT scan and standard chest roentgenography measurability in the subgroups of patients with T3 or T4 tumor, hilar tumor, and patients with pleural effusion or atelectasis in which the McNemar test of symmetry constantly showed a better measurability using CT scan.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Airway macrophages releasability in bronchial asthma.

Asthma is a multifactorial disease on genetic basis. Its development is influenced by maternal and environmental factors, i.e. allergens and adjuvants. Early identification of candidates at high risk for development of asthma will enable giving recommendations on preventive measures focussing on exposure to tobacco smoke and other pollutants, indoor and outdoor allergens and possibly viral infections during infancy.

Asthma↗
PubMed1992

[Evolution of bronchial hyperreactivity during post-exercise asthma].

The occurrence of a late reaction following exercise induced asthma is questionable and its relationship with the non specific bronchial hyperreactivity is poorly known. In this study, nine patients (age 15-21 years) underwent an exercise challenge in order to (a) determine the incidence of immediate and late phase reaction and (b) analyse the modifications of non specific bronchial hyperreactivity. Study design was a follow; day-3: determination of bronchial responsiveness to metacholine; day 0: control day with FEV1 measurements every hour for 11 hours; day 1: exercise challenge followed by a careful observation of change in FEV1; day 2: new determination of bronchial responsiveness to metacholine. An immediate exercise induced bronchial obstruction was observed in 5 patients. A late phase reaction (6th hour) with a fall of FEV1 equal to or more than 20% has been demonstrated in two patients. For the former, the change in FEV1 did not differ from the value of the control day. For the second, the FEV1 changed spontaneously during the control day so that decreases of FEV1 during control and challenge days were parallel. Thus, no late phase reaction were observed (F = 0.46; ns). There was no modification of bronchial responsiveness to metacholine (pre-exercise: 1,784 +/- 1,970 [SD]; post-exercise 1,827 +/- 2,231 micrograms [SD]). The lack of true late phase reaction when the post-exercise change in FEV1 is compared to the one of a control day and the absence of modification of non specific bronchial hyperreactivity weaken the hypothesis of an inflammatory mechanism of exercise induced asthma.

Adolescent↗
PubMed1992

[Local immune response in allergic asthma].

The key issue in asthma research is allergen capture and presentation. An increase in understanding in this area may result in the development of new types of therapeutic drugs, although at present there remain a number of points to be elucidated. In this paper, we review recent research in this field. Allergens are small air-conducted soluble antigens which are capable of inducing a specific immune response characterized by a significant synthesis of IgE. The allergen passes through the bronchial epithelium and specialized antigen presenting cells (APC) capture and present the antigen to T-cells, causing their activation via an interaction with class II MHC molecules on the APC. Allergens are also capable of activating other cell types and the subsequent release of inflammatory mediators, chemoattractants and cytokines may result in bronchial inflammation which is one of the cardinal signs of asthma.

Allergens↗
PubMed1991

[Informed consent and the physician-patient relations in thoracic oncology].

Medical ethics have always required patient consent as a prerequisit to therapy. The law concerning the "protection of persons accepting to be subjects in biomedical research" requires specific oral and written information to be given to all patients entering a clinic research project. New effects of the principal of "informed consent", on the physician-patient relationship, are analysed. Fifty patients with bronchial cancer were included in controlled studies from June 1989 to June 1990. These patients were asked to give their informed consent involving 5 different studies (2 Phase II studies investigating tolerance to a new treatment and 3 Phase III studies comparing a new treatment with a reference treatment). The patients were informed beforehand of the possibility of a research treatment and the legal requirement for their signature as well as to the possibilities of replacement solutions in case they refused. Detailed and adapted information concerning the different therapeutic solutions and their predictable side effects were presented before reading the informed consent statement. Of the 50 informed consent statements proposed, 49 were accepted. The principal of informed consent was favourably apprehended by the patients (active participation, notion of protection, information source, possibility of dialogue) and induced conditions of better acceptation by the patient. Nevertheless, it was more difficult to obtain statements of consent for studies comparing a new treatment with a reference treatment than for studies simply proposing a new treatment alone.

Adult↗
PubMed1991

[Neoadjuvant chemotherapy of non-small cell bronchial cancers].

Lung cancer is frequent and serious. Squamous cell carcinomas, adenocarcinomas and undifferentiated non-small cell carcinomas account for 80 percent of all lung cancers. Patients with one or the other of these carcinomas and potentially curative surgical resection, but they represent only one quarter of all carcinomas. In patients with regionally more advanced carcinomas, notably when the mediastinal lymph nodes are invaded, surgical resection only results in a 5 to 15 percent survival rate at 5 years. At this stage of lung cancer, an effective cytostatic treatment may improve the survival rate, inasmuch as most therapeutic failures are due to metastatic progression. Neoadjuvant (preoperative) chemotherapy is now undergoing evaluation by controlled trials. This therapeutic strategy rests on two arguments: 1) patients treated with chemotherapy for locally advanced lung carcinomas may subsequently benefit from complete resection in over 50 percent of the cases; 2) neoadjuvant chemotherapy might sterilize the subclinical metastatic disease at the time of diagnosis. Studies are in progress to evaluate the effectiveness of neoadjuvant chemotherapy in terms of survival. Until the final results are available, this treatment cannot be proposed as a consensual therapeutic solution, but feasibility studies are encouraging.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Skin test reactivity in patients suffering from lung and breast cancer.

Mast cells and histamine-mediated reactions may be altered in patients with cancer. In an attempt to characterize the possible skin defects in patients with cancer, we tested 22 patients suffering from lung cancers, 30 from breast cancers, and 30 age-matched normal individuals, using several compounds, in investigating the pathophysiology of the skin response. Histamine hydrochloride (10 and 100 mg/ml) and codeine phosphate (9%) were tested by prick test. Substance P (50 and 500 ng per injection site), phentolamine (20 micrograms per injection site), and carbachol (1 microgram per injection site) were tested by intradermal skin tests. Skin mast cells were also microscopically examined in 10 patients with lung cancer, five with breast cancer, and 10 normal subjects. The mean wheal sizes induced by all the tested substances were similar in patients with cancer and chronic bronchitis and in normal individuals. The flare to histamine, codeine phosphate, and substance P was completely abolished in 7/22 patients with lung cancer, but the lack of flare was not related to the age of the patients, nor to the staging of cancer, nor to metastasis. The mean numbers of alcian blue-stained or toluidine blue-stained positive mast cells were similar in normal subjects and in subjects with cancer. This study does not confirm the skin hyporeactivity of patients with cancer.

Adult↗
PubMed1991

Bacterial ribosomal immunostimulants prime alveolar macrophages in vivo to produce interleukin 1 in vitro.

Alveolar macrophages (AMs) may play a key role in human respiratory immune defenses, partially by synthesizing and releasing interleukin 1 (IL = 1). D53 (Ribomunyl), a composite bacterial ribosomal immunostimulant, has been recognized as an efficient prevention of respiratory tract infections. In vitro, D53 enhances the IL-1 production by mouse spleen adherent cells. A thymocyte proliferative response assay was used to evaluate the in vitro IL-1 production by AMs in healthy subjects who received D53 immunostimulant. Twelve nonsmoking healthy subjects took part in a prospective double-blind placebo control study. On day 1, a first bronchoalveolar lavage (BAL) was performed to assess IL-1 production by unstimulated and lipopolysaccharide (LPS) stimulated AM. Then, subjects were randomized to receive D53 (n = 6) or its placebo (n = 6) by both oral and subcutaneous injection routes from day 1 to day 15. On day 15, a second BAL was done and AM IL-1 production was again tested. IL-1 production on day 15 did not significantly differ from day 1 in both D53-treated and placebo groups either when AMs were unstimulated or were stimulated with concentrations of LPS resulting in maximal IL-1 production. However, in the D53-treated group, but not in the placebo group, IL-1 production induced by low LPS concentration (5 mg/L) was significantly higher (mean +/- SEM: 1,238 +/- 287 U/10(6) AM) on day 15 in comparison with day 1 (577 +/- 113 U/10(6) AM; p less than 0.05, Wilcoxon W test) and in comparison with the control group (day 15 IL-1 production induced by 5 mg/L LPS, 758 +/- 175 U/10(6) AM; p less than 0.05, Mann-Whitney U test). Moreover, in the D53-treated group, the optimal LPS concentration (ie, LPS concentration that induced maximal IL-1 production) was significantly lower on day 15 (mean +/- SD: 11 +/- 7 mg/L) than on day 1 (16 +/- 7 mg/L; p less than 0.05 Wilcoxon W test). We conclude that D53 immunostimulant in vivo primes AM to produce IL-1 following low LPS concentration stimulation. This may partially explain the protective effect of D53 immunostimulant against respiratory tract infection.

Adjuvants, Immunologic↗
PubMed1990

In situ evaluation of growth fraction determined by monoclonal antibody Ki-67 and ploidy in surgically resected non-small cell lung cancers.

Ploidy and growth fraction were analyzed by means of a computer-assisted image processor in surgically resected non-small cell lung cancer (NSCLC). This study was done in order (a) to evaluate the distribution of anti-Ki-67 immunostaining and (b) to correlate this distribution to ploidy status and pTNM stage of NSCLC. Thirty-two patients underwent a surgical resection for primary NSCLC following complete staging. Indirect immunoperoxidase reactions of monoclonal antibody Ki-67 were done on frozen tissue sections. Integrated optical density and index of stained nuclear surface were calculated by means of a computer-assisted image processor in 120 fields of each preparation in order to quantify the Ki-67 immunostaining. DNA content was determined by means of cytometry of Feulgen-stained cytological prints. The ploidy status was defined for each tumor by DNA index, percentage of hypodiploid cells, and type of DNA content histogram (near diploid, hyperdiploid, hypodiploid, and multiploid). Reproducibility of immunostaining quantitative analysis was demonstrated by iterative measurements of the same slide. Intratumoral heterogeneity of Ki-67 immunostaining induced integrated optical density variation assessed on six nonconsecutive tissue sections from at least two regions of the same tumor. This intratumoral variability was 15 times lower than integrated optical density variability between tumors. The Ki-67 immunostaining varied significantly according to the DNA content histogram type (P less than 0.05, Kruskal-Wallis test); most of the specimens with high Ki-67 immunostaining were multiploid or hypodiploid. Moreover, Ki-67 immunostaining correlated to the percentage of hypodiploid cells. Ki-67 immunostaining and ploidy status did not vary significantly according to the tumor-nodes-metastasis stage. We conclude that (a) quantitative analysis of Ki-67 immunostaining is a reliable evaluation of growth fraction in NSCLC if a large number of fields are analyzed to take into account intratumoral variability, (b) hypodiploidy and multiploidy are frequent abnormalities of DNA content, (c) Ki-67 immunostaining is significantly higher in hypodiploid and multiploid tumors. Thus, determination of growth fraction and ploidy in surgically resected NSCLC specimens may be considered as complementary prognostic parameters independent of the stage of the disease.

Adenocarcinoma↗
PubMed1990

Tumor-tissue and plasma concentrations of platinum during chemotherapy of non-small-cell lung cancer patients.

Tumor-tissue and plasma concentrations of platinum were studied prospectively in two groups of eight patients who were suffering from advanced non-small-cell lung cancer. Treatments including two different schedules of cisplatin administration (25 vs 100 mg/m2 on day 1) were compared. At 30 min after the beginning of the cisplatin infusion, blood samples and bronchoscopically obtained biopsy specimens were taken for determinations of platinum concentrations by means of flameless atomic absorption spectrophotometry. The procedure did not induce any complication. Total plasma platinum concentrations at 30 min were significantly lower (P less than 0.01) in patients receiving 25 mg/m2 (0.49 +/- 0.23 microgram Pt/ml) than in those receiving 100 mg/m2 (1.44 +/- 0.62 micrograms Pt/ml), whereas no significant difference was observed in tumor-tissue platinum concentrations (22.49 +/- 53.89 ng Pt/mg in patients receiving 25 mg/m2 vs 51.13 +/- 65.52 ng Pt/mg in those receiving 100 mg/m2). There was a weak correlation between simultaneous plasma and tumor-tissue platinum concentrations at 30 min. Tumor-tissue platinum concentrations seem to be poorly influenced by the cisplatin dose. This finding suggests a great interindividual variability of platinum tumor-diffusion properties in non-small-cell lung cancer.

Adult↗
PubMed1990

Pilot study of neoadjuvant ifosfamide, cisplatin, and etoposide in locally advanced non-small cell lung cancer.

33 patients with locally advanced non-small cell lung cancer entered a study of neoadjuvant chemotherapy to evaluate the response rate with ifosfamide/cisplatin/etoposide and the complete resection rate and safety of surgery following chemotherapy. Chemotherapy with cisplatin 25 mg/m2, ifosfamide 1.5 g/m2, and etoposide 100 mg/m2 was given on days 1-4 of a 21 day cycle and repeated for three cycles. For responders, surgery was done 15-20 days after haematological recovery. Chemotherapy induced 5 complete responses (15%) and 18 partial responses (55%). 77% of the 33 patients had grade 3-4 neutropenia and 60% grade 3-4 thrombocytopenia. 1 patient died with a central nervous system haemorrhage. Thoracotomy was done in 21 patients but resection was only possible in 20 (61%). A complete resection was achieved in 18 patients (55%). Histology was negative for the 5 complete responses. Surgery induced no morbidity. A high response rate may be obtained with ifosfamide, cisplatin and etoposide neoadjuvant chemotherapy allowing a high complete resection rate.

Adult↗