Jacques Prignot

Studies on the proteins of human bronchial secretions.

Abstract Four samples of normal human bronchial secretions, collected without admixture of saliva, and a pool of sputum obtained from 10 patients with non-purulent chronic bronchitis, were analyzed by electrophoretic and immuno-electrophoretic methods. The sputum was, in addition, submitted to chromatographic fractionation on DEAE-cellulose and the fractions thus obtained were further characterized by electrophoresis, immuno-electrophoresis and tested for the presence of amylase and lysozyme. Albumin and γA-immunoglobulin were the main plasma proteins identified in all samples, whereas γG-immunoglobulin was present only in negligible amounts. The proteins specific for saliva were identified in the sputum samples, but four of them, viz. lysozyme, lactoferrin, salivary β 1 -globulin and (probably) salivary α 2 -globulin, were also identified in bronchial samples uncontaminated by saliva.

Cost effectiveness of varenicline in Belgium, compared with bupropion, nicotine replacement therapy, brief counselling and unaided smoking cessation: a BENESCO Markov cost-effectiveness analysis.

AbstractBackground and Objective: Varenicline is a nicotinic acetylcholine receptor partial agonist that is approved for use as an aid to smoking cessation. Randomized clinical trials show that its efficacy is superior to that of other current smoking cessation therapies. This study set out to determine the cost effectiveness of varenicline relative to other smoking cessation interventions (bupropion and nicotine replacement therapy [NRT]) as well as brief counselling alone and unaided cessation in a cohort of Belgian adult smokers making a one-time quit attempt, from the perspective of the healthcare payer (public and private). Methods: A Markov model, the Benefits of Smoking Cessation on Outcomes (BENESCO) model, was applied to calculate the long-term health and economic benefits of smoking cessation. Cost effectiveness was expressed as cost per life-year (LY) gained and cost per quality-adjusted life-year (QALY) gained. Clinical and economic model inputs were obtained from the literature and public healthcare databases. Costs were discounted at 3% and health outcomes at 1.5%. A probabilistic sensitivity analysis and a one-way sensitivity analysis were performed to test the robustness of the results. Results: Varenicline is associated with a reduction of smoking-related morbidity and mortality as well as with a decrease in healthcare costs compared with the pharmacological agents bupropion and NRT. Varenicline also leads to additional LYs and QALYs compared with brief counselling alone and unaided cessation over a lifetime period. Varenicline is a dominant strategy compared with bupropion and NRT. Compared with brief counselling alone and unaided cessation, varenicline presents a cost/QALY of €240 and €1656, respectively. Conclusion: Varenicline is a cost-effective alternative to brief counselling and unaided cessation, and is a cost-saving treatment in comparison with bupropion and NRT, in a Belgian population of smokers willing to quit.

Immunodetection of small cell lung cancer metastases in bone marrow using three monoclonal antibodies

Detection of bone marrow metastases by indirect immunofluorescence methods was investigated using three monoclonal antibodies (MoAbs) raised against small cell lung cancer (SCLC). These antibodies, designated anti-LCA1, -LCA2 and -LCA3, recognize three different antigens on the surface of SCLC cells. Eighty-four bone marrow samples from 74 different patients were studied. Whereas tumor cells were found in 32 (38%) by MoAb staining, only 10 (12%) were positively identified using conventional morphological methods. Nine out of the morphologically positive specimens showed reactivity with at least two monoclonal antibodies. Among the 32 samples proven positive by immunofluorescence, an important antigenic variability was noted. Anti-LCA1 recognized tumor cells in 62%, anti-LCA2 and anti-LCA3 in 53%. Due to the recognition of bone marrow involvement by fluorescence methods in 26% of the 34 patients classified as limited disease, a new subgroup of limited disease patients was defined whose prognosis remains undetermined. Our results confirm the utility of immunodetection in the diagnosis of SCLC bone marrow metastases and emphasize the advantage of using a panel of MoAbs with different antigenic specificities. Further study is needed to determine the prognostic significance of bone marrow involvement established by immunodetection.

Immunohistochemical localization of the iron-binding protein lactoferrin in human bronchial glands

Les techniques immunohistochimiques ont permis de localiser la lactoferrine dans les cellules séreuses des acini des glandes bronchiques.

Early Bronchodilating Effect of Oxitropium Bromide in Comparison with Ipratropium Bromide

The bronchodilating effects of a metered aerosol dose of 40 micrograms ipratropium bromide and of 200 micrograms oxitropium bromide are similar 15 min. after administration. The bronc hodilating activity of ipratropium bromide appears earlier (i.e., 75-90 s after administration) than that of oxitropium bromide but later than that of ibuterol, a beta2-agonist. Ipratropium bromide administered at the close of 80 micrograms provokes a bronchodilation about double of that obtained with 40 micrograms. An adaptation of the usual dosage should be considered.

An economic evaluation based on a randomized placebo-controlled trial of varenicline in smokers with cardiovascular disease: results for Belgium, Spain, Portugal, and Italy.

Background: An estimated 17.2% of patients continue to smoke following diagnosis of cardiovascular disease (CVD). To reduce the risk of further morbidity or mortality in cardiovascular patients, smoking cessation has been shown to reduce the risk of mortality by 36% and myocardial infarction by 32%. The objective of this study was to evaluate the long-term health and economic consequences of smoking cessation in patients with CVD. Design and methods: Results of a randomized clinical trial comparing varenicline plus counselling vs. placebo plus counselling were extrapolated using a Markov model to simulate the lifetime costs and health consequences of smoking cessation in patients with stable CVD. For the base case, we considered a payer’s perspective including direct costs attributed to the healthcare provider, measuring cumulative life years (LY) and quality adjusted life (QALY) years as outcome measures. Secondary analyses were conducted from a societal perspective, evaluating lost productivity due to premature mortality. Sensitivity and subgroup analyses were also undertaken. Results were analysed for Belgium, Spain, Portugal, and Italy. Results: Varenicline plus counselling was associated with a gain in LY and QALY across all countries; relative to placebo plus counselling. From a payer’s perspective, incremental cost effectiveness ratios were €6120 (Belgium), €5151 (Spain), €5357 (Portugal), and €5433 (Italy) per QALY gained. From a societal perspective, varenicline in addition to counselling was less costly than placebo and counselling in all cases. Sensitivity analyses showed little sensitivity in outcomes to model assumptions or uncertainty in model parameters. Conclusions: Varenicline in addition to counselling is cost-effective compared to placebo and counselling in smokers with CVD.

Recent contributions of air- and biomarkers to the control of secondhand smoke (SHS): a review.

Since the publication of the US Surgeon General Reports in 1996 and 2006 and the report of the California Environmental Protection Agency in 1999, many reports have appeared on the contribution of air and biomarkers to different facets of the secondhand smoke (SHS) issue, which are the targets of this review. These recent studies have allowed earlier epidemiological surveys to be biologically validated, and their plausibility demonstrated, quantified the levels of exposure to SHS before the bans in various environments, showed the deficiencies of mechanical control methods and of partial bans and the frequently correct implementation of the efficient total bans. More stringent regulation remains necessary in the public domain (workplaces, hospitality venues, transport sector, etc.) in many countries. Personal voluntary protection efforts against SHS are also needed in the private domain (homes, private cars). The effects of SHS on the cardiovascular, respiratory and neuropsychic systems, on pregnancy and fertility, on cancers and on SHS genotoxicity are confirmed through experimental human studies and through the relationship between markers and prevalence of disease or of markers of disease risk.

Controlled trial of the effect of repeated administration of ipratropium bromide on ventilatory function of patients with severe chronic airways obstruction

A trial was designed to assess whether repeated administration of ipratropium bromide for two weeks produced greater improvement than was obtained after a single dose. The effect of ipratropium bromide was compared with that of a placebo during a double-blind cross-over randomized trial in patients with advanced chronic airways disease in a stable state. Ipratropium bromide and placebo were both administered by metered dose inhaler for 14 days. There was a slight statistically significant improvement of conductance, thoracic gas volume, FEV1 and VC after inhalation of ipratropium bromide, but repeated doses of the drug did not produce progressive improvement.

Adriamycin and adriamycin—DNA in inoperable bronchogenic carcinoma. A randomized study with cyclophosphamide vinblastine

Abstract In a randomized study on 59 patients with inoperable bronchogenic carcinoma, the chemotherapeutic efficacy and toxicity of ADM-DNA was compared with that of free ADM and that of the association cyclophosphamide-vinblastine. No significant differences in initial chemotherapeutic response could be observed between the groups of patients treated respectively with cyclophosphamide-vinblastine, free adriamycin or adriamycin—DNA. The cardiotoxicity of ADM seems however reduced by its combination with DNA, since no signs of cardiotoxicity were observed, even in the 15 patients who received a total dosage of adriamycin—DNA exceeding 500 mg/m 2 .

Carboplatin in combination with etoposide in inoperable non-small-cell lung cancer (NSCLC).

Carboplatin, a second generation platinum complex, is less nephrotoxic and emetogenic than its parent compound. We have tested the objective response to and the toxicity of the combination carboplatin 330 mg m-2 on day 1 with etoposide 120 mg m-2 on days 1, 3 and 5, administered every 3 weeks in histologically proven inoperable non-small-cell lung cancer (NSCLC) patients with a good performance status. Thirty-one patients entered the study; 29 were evaluable for response, 24 after 3 courses and 5 after 2 courses of chemotherapy. An overall response rate of 21% was found including zero complete response and 6 partial responses. In addition, 3 minor responses (10%), 12 stable diseases (38%), and 9 progressive diseases (39%) were observed. The median survival was 48 weeks, including 68 weeks for non-metastatic (M0) patients and 27 weeks for metastatic (M + ) patients. This regimen was well tolerated. Gastrointestinal toxicity never exceeded WHO grade II and renal function remained in the normal range for all cases. Haematological toxicity was low in the majority of the cases; nevertheless it proved to be the dose limiting toxicity as illustrated by two grade III anemia, one grade III leucopenia, one grade III and one grade IV thrombocytopenia. Carboplatin-etoposide combination is not more active, but clearly much less toxic than cisplatin-etoposide in NSCLC.