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Significant progress in the diagnosis and classification of pleural mesothelioma has been made in the past 5 years. Novel biomarkers are now entering more widespread use following major advances in understanding the genomic landscape of the malignancy. As the diagnosis and management of mesothelioma becomes more multidisciplinary together with the increasing role of histopathology in providing additional prognostic information to guide downstream management, we review herein newly proposed prognostic variables, diagnostic biomarkers, utility of pleural effusion cytology in diagnosis, and mesothelioma surgery. A section on the upcoming WHO classification on malignant pleural mesothelioma is also included.

AIMS: Nuclear grade has been recently validated as a powerful prognostic tool in epithelioid malignant pleural mesothelioma (E-MPM). In other studies histological parameters including pleomorphic features and growth patterns were also shown to exert prognostic impact. The primary aims of our study are (1) externally validate the prognostic role of pleomorphic features in E-MPM and (2) investigate if evaluating growth pattern in addition to 2-tier nuclear grade improves prognostication. METHODS AND RESULTS: 614 consecutive cases of E-MPM from our institution over a period of 15 years were retrospectively reviewed, of which 51 showed pleomorphic features. E-MPM with pleomorphic features showed significantly worse overall survival compared those without (5.4 months vs 14.7 months). Tumours with predominantly micropapillary pattern showed the worst survival (6.2 months) followed by solid (10.5 months), microcystic (15.3 months), discohesive (16.1 months), trabecular (17.6 months) and tubulo-papillary (18.6 months). Sub-classification of growth patterns into high grade (solid, micropapillary) and low grade (all others) led to good separation of overall survival (10.5 months vs. 18.0 months) but did not predict survival independent of 2-tier nuclear grade. A composite score comprised of growth pattern and 2-tier nuclear grade did not improve prognostication compared with nuclear grade alone. Intra-tumoural heterogeneity in growth patterns is ubiquitous. CONCLUSIONS: Our findings support the incorporation of E-MPM with pleomorphic features in the epithelioid subtype as a highly aggressive variant distinct from 2-tier nuclear grade. E-MPM demonstrates extensive heterogeneity in growth pattern but its evaluation does not offer additional prognostic utility to 2-tier nuclear grade.

SummaryLung Carcinoids (L-CDs) are uncommon low-grade neuroendocrine tumours that are only recently becoming characterised at the molecular level. Notably data on the molecular events that precipitate altered gene expression programmes are very limited. Here we have identified two discrete L-CD subtypes from transcriptomic and whole-genome DNA methylation data, and comprehensively defined their molecular profiles using Whole-Exome Sequencing (WES) and Single Nucleotide Polymorphism (SNP) genotyping. Subtype (Group) 1 features upregulation of neuronal markers (L-CD-NeU) and is characterised by focal spindle cell morphology, peripheral location (71%), high mutational load (P=3.4×10−4), recurrent copy number alterations and is enriched for Atypical Lung Carcinoids. Group 2 (L-CD-PanC) are centrally located and feature upregulation of pancreatic and metabolic pathway genes concordant with promoter hypomethylation of beta cell and genes related to insulin secretion (P−6). L-CD-NeU tumours harbour mutations in chromatin remodelling and in SWI/SNF complex members, while L-CD-PanC tumours show aflatoxin mutational signatures and significant DNA methylation loss genome-wide, particularly enriched in repetitive elements (P−16). Our findings provide novel insights into the distinct mechanisms of epigenetic dysregulation in these lung malignancies, potentially opening new avenues for biomarker selection and treatment in L-CD patients.

Connective tissue diseases (CTDs) are a heterogeneous group of disorders, acquired or hereditary, involving an autoimmune-mediated inflammation of connective tissues in the whole body. Lung involvement is common with CTDs, and associated with significant morbidity and mortality. Each compartment of the lung may be affected, often simultaneously, depending on the type of CTD. In addition, the lung may show pathological changes related to treatment, such as infection, drug reaction, and neoplasia. A multidisciplinary approach to diagnose these patients is essential and incorporates radiological and clinical as well as pathological data. In this review we describe the patterns of lung disease associated with common CTDs, lung disease in pediatric CTD patients, and newly recognized conditions.

Nuclear grading systems for epithelioid malignant pleural mesothelioma (MPM) have been proposed but it remains uncertain if they could be applied in a biopsy-heavy setting. Using the proposed system, we conducted an independent, external validation study using 563 consecutive cases of epithelioid MPM diagnosed at our institution between 2003 and 2017, of which 87% of patients underwent biopsies only. The median number of sites sampled was 1, with a median maximum tissue dimension of 17 mm (biopsy) and 150 mm (resection). The median overall survival (OS) was 14.7 months. The frequencies of grade I, II, and III tumors were 31% (132/563), 52% (292/563), and 17% (94/563). Grade I tumors were associated with the most favorable median OS (24.7 mo) followed by grades II (12.7 mo) and III (7.2 mo). The 2-tier nuclear grade separated tumors into low grade (19.3 mo) and high grade (8.9 mo). In multivariate analysis, 3-tier nuclear grade, 2-tier nuclear grade, and mitosis-necrosis score predicted OS independent of age, procedural type, solid-predominant growth pattern, necrosis, and atypical mitosis (all P

Summary The objective of reservoir characterization is to understand the reservoir rocks and fluids through accurate measurements: in this context seismic inversion plays a dominant role in providing the structural framework and an estimation of rock properties. The advent of the Controlled-Source EM methodology, producing an estimate of the subsurface resistivity, brought the multiphysics data into the characterization workflow traditionally dominated by seismic and significantly enhanced the accuracy of the estimated rock and fluid properties. This work constitutes a first step towards the generalization of a framework that can exploit all the available geophysical measurements and properties for an improved understanding of reservoir uncertainties. We introduce two approaches to for the multigeophysical reservoir characterization: the first one is deterministic while the second is statistical. The two workflows have in common the rock-physics model that computes the geophysical properties from the petrophysical ones while they differ in the way the inversion step for the estimation of the reservoir properties from the observations is implemented. We evaluate the workflows on an offshore oil field where 3D seismic, 3D CSEM data and well logs are available.

The use of biodegradable polymers has aroused academic and technological interest directed to the replacement of conventional polymers aiming at reducing the environmental impact caused by these materials. Vegetable fibres as reinforcement elements provide gains in mechanical, thermal and degradation properties to polymer composites. The buriti fibre (Mauritia flexuosa) is an abundant crop of easy cultivation in tropical countries and its use in composites with poly(lactic acid) (PLA), can provide the development of a material with specific features, combining good mechanical properties and excellent degradation potential to the obtained composites. In this research, PLA and buriti fibre composites were developed with the use of triacetin as coupling agent. For a 30% content by mass of fibre, the results showed that the mechanical properties of the composites were similar to those of neat PLA. This was attributed to the fibre/matrix interaction observed by the SEM analysis and to an increase in crystallinity assessed by thermal properties.

Introduction There is limited evidence regarding the optimal number of sampling sites and specimen dimension in histological diagnosis of malignant pleural mesothelioma (MPM). Previously we have validated 2-tier nuclear grade as an independent predictor of survival in epithelioid MPM. This study evaluates the association between sampling parameters and the performance of 2-tier nuclear grade and growth pattern as survival predictors using a biopsy-heavy cohort. Methods Clinicopathological information including the number of sampling sites, tissue dimension, 2-tier nuclear grade, predominant growth pattern and overall survival (OS) were retrieved from an institutional mesothelioma database comprising 614 consecutive cases of epithelioid MPM over a 15 year period. Survival analysis was performed using Kaplan-Meier method. Association between categorical variables was analysed using Fisher exact test, and was assessed in relation to biopsy size and number. Statistical significance was defined as p Results The mean age was 69.1 years, with male preponderance (75.6%). 87.0% (534/614) received biopsy only. The median number of sites sampled was 1 (range 1–20). The median maximum tissue dimension was 18 mm for biopsies (range 2–140 mm) and 145 mm for resections (range 40–350 mm). 17.7% of all biopsies (95/534) were taken from a single site with a maximum dimension of ≤10 mm (median: 8 mm). Low grade tumours showed significantly prolonged OS compared with high grade (19.3 months vs. 8.9 months, p Conclusions We propose an optimal sampling standard of 3 sites or a maximum tissue dimension of ≥20 mm from a single site. This then allows a 2-tier nuclear grading system to provide prognostic stratification for clinical care and research of epithelioid MPM.

BACKGROUND Tuberculosis prevention has been based on generalized BCG vaccination in France since 1949. The aim of this cross-sectional survey was to assess the impact of the change in BCG administration (in January 2006) and the end of compulsory vaccination (in July 2007). METHOD A self-administered postal questionnaire was sent to a random sample of 2248 physicians practicing in 6 departments in the Rhone-Alpes region in 2008. RESULTS Overall, 923 questionnaires were analyzed. The median age of the respondents was 52 years, 67 % were male, 93 % were general practitioners, and 91 % practiced in private practice offices. The median number of BCG vaccines administered on a quarterly basis was 5 (interquartile range [IQR], 3-10) before January 2006, one (IQR, 0-3) between January 2006 and July 2007, and zero (IQR, 0-1) after July 2007 (P

The objective of this study was to assess the efficacy and safety of moxifloxacin versus amoxicillin-clavulanate plus roxithromycin (comparator) in adult community-acquired pneumonia (CAP) patients with risk factors. In this comparative, randomized, multicenter, open-label study, patients hospitalized for CAP received a 10-day oral treatment with either moxifloxacin (400 mg o.d.) or amoxicillin-clavulanate (1,000/125 mg t.i.d.) plus roxithromycin (150 mg b.i.d.). Clinical and bacteriological outcomes were assessed during test of cure and follow-up visits (5-7 days and 21-28 days after the end of treatment, respectively). Of 349 randomized patients, 346 were included in the intent-to-treat analysis and 289 in the per-protocol analysis. Their baseline characteristics were comparable. The most frequent risk factors for mortality were age >65 years (50.0%), alcoholism (23.1%), and comorbidities (50.6%); chronic obstructive pulmonary disease (COPD) (25.4%) and diabetes mellitus (13.6%) were the most common associated comorbidities. A causative pathogen was documented in 66 of 346 (19.1%) of the patients (including 21 with positive blood cultures). Respective per-protocol clinical success rates at test-of-cure (primary efficacy endpoint) for moxifloxacin and comparator were 131 of 151 (86.8%) and 120 of 138 (87.0%), with a 95% confidence interval (CI) of -8.0-7.6 for the difference. Bacteriological success rates (eradication) were 23 of 30 (76.7%) and 23 of 31 (74.2%); rates for patients with positive blood cultures were 10 of 14 and 4 of 6. Persistent clinical success rates at follow-up were 118 of 120 (98.3%) and 102 of 106 (96.2%), with a 95%CI of -2.2-6.4 for the difference. The intent-to-treat analysis confirmed these results. Adverse events associated with moxifloxacin and the comparator drug were reported for 42 of 171 (24.6%) and 50 of 175 (28.6%) of the patients, respectively, and comprised predominantly digestive disorders, which occurred in 9.4% and 21.1%. On the basis of these results, once-daily oral moxifloxacin alone is as effective as amoxicillin-clavulanate plus roxithromycin for the treatment of CAP in patients with risk factors.

Acute hypersensitivity reactions are adverse events potentially associated with antineoplastic drug infusions. Their occurrence can be particularly relevant in an outpatient environment where time of administration and subsequent observation is limited to a short period of time. In addition, concern about the onset of more severe hypersensitivity reactions can limit subsequent use of crucial drugs.During a 3-year observational period, we collected a total of 240 infusional acute hypersensitivity reactions out of 56,120 administrations performed, with an overall incidence of 0.4%.In order of frequency, platinum derivatives, taxanes and monoclonal antibodies accounted for the highest incidences. Their relative frequency was: oxaliplatin, 2.5%; carboplatin, 0.4%; paclitaxel, 1.2%; docetaxel, 1.2%; trastuzumab, 1.2%, and rituximab, 1.2%.Since the number of chemotherapeutic agents is steadily increasing, much attention should be paid to such reactions, particularly when several administrations are performed daily, and where management of the potential risk associated with specific drugs is mandatory. Their occurrence represents an unpredictable, unexpected and often hard to manage contingency, and our opinion is that observation and consciousness of this issue are fundamental for its appropriate management. We describe our experience, emphasizing the role of this toxicity and explaining how this awareness allowed us to define some empirical rules to handle acute hypersensitivity reactions.

The aim of this study was to assess the effects of PM10 daily concentrations in urban ambient air on bronchial reactivity and on two indices of respiratory function (FEV1 and PEF) of healthy control (n = 20) and of mild asthmatic adults (n = 20). The study took place over two periods of a month and a half, during summer 1996 and winter 1997. Each volunteer underwent two methacholine challenge tests, one during a weekday, the other early on the next Monday morning, after a weekend of lower exposure. They also monitored their FEV1 and PEF twice daily with an electronic peak flow meter. The respiratory function decreased among asthmatic subjects a few days after daily PM10 levels had increased (−1.25% for FEV1, 95% CI = [−0.58, −1.92]; and −0.87% for PEF [−0.1, −1.63], for a daily 10 μg m−3 variation of PM10 in summer; −0.25% [−0.51, 0.02] for FEV1 only in winter). No association between daily variations of respiratory function and PM10 was observed among control subjects. Bronchial reactivity was not significantly different between the two days of methacholine tests among asthmatic and control subjects, either in summer or in winter. This study confirms the greater sensitivity of asthmatic adults, compared with healthy subjects, to short-term variations of ambient air concentrations of particles. However, bronchial reactivity is not modified by small short-term variations of particulate pollution among mild asthmatics or healthy subjects. Copyright © 1999 John Wiley & Sons, Ltd.

Resume Un essai multicentrique, comparatif, randomise, en ouvert pour chaque groupe traite a ete mene en ville, avec un plan statistique visant a mettre en evidence l'equivalence de deux types de strategies de traitement (josamycine 5 jours — azithromycine 5 jours). Compte tenu de la demonstration faite de l'equivalence entre les therapeutiques etudiees, une analyse complementaire a ete realisee. Pour cette analyse economique, la strategie envisagee est, a duree de traitement egale (5 jours), celle de la minimisation de cout : on cherche a mettre en evidence la strategie pour laquelle les couts induits sont les moins importants. Le cout moyen direct pour l'Assurance Maladie (consommations de soins) s'eleve a 221 F dans le groupe josamycine 5 jours et a 258 F dans le groupe azithromycine 5 jours (p

Resume L'objectif de cette etude multicentrique, prospective, randomisee, en double aveugle, etait de comparer l'efficacite et la tolerance du cefotiam hexetil (CTM) a la dose de 400 mg matin et soir avec celles de l'amoxicilline/acide clavulanique (AAC) a la dose de 1 g matin et soir sur une periode de dix jours de traitement au cours d'une exacerbation de bronchite chronique. Cent cinquante sept patients adultes souffrant d'une exacerbation de bronchite chronique ont ete inclus par des pneumologues. Les deux populations etaient comparables a l'inclusion en ce qui concerne les donnees demographiques et la clinique. En fin de traitement, 92 % des patients du groupe cefotiam hexetil et 88 % du groupe amoxicilline/acide clavulanique etaient gueris apres analyse en intention de traiter, respectivement 96 % versus 94 % apres analyse en per protocol. Le nombre d'effets secondaires a ete moins frequent dans le groupe cefotiam hexetil (9 % versus 21 %). Cette difference etait statistiquement significative (p = 0,03). En conclusion, le cefotiam hexetil 400 mg matin et soir peut etre considere comme une bonne alternative therapeutique dans le traitement des exacerbations de bronchite chronique de l'adulte avec une efficacite equivalente et une tolerance meilleure que l'amoxicilline/acide clavulanique 1 g matin et soir.

Resume Cette etude d'equivalence randomisee en ouvert a compare l'efficacite et la tolerance cliniques d'une nouvelle forme galenique de josamycine, comprime dispersible dose a 1 g, administree a la posologie de 2 g/j en deux prises pendant 5 jours ou pendant 10 jours, a celles d'azithromycine administree a la posologie de 500 mg le premier jour en une seule prise puis de 250 mg pendant les 4 jours suivants, au cours de la bronchite aigue survenant chez l'adulte sain (n = 472) et chez le sujet presentant une bronchite chronique (n = 51). En intention de traiter, 523 patients inclus ont ete analyses pour l'efficacite clinique en fin de traitement (J7 ou J12) (JOS 5 jours = 174; AZI 5 jours = 175; JOS 10 jours = 174), 466 ont ete analyses a distance du traitement (J30). L'analyse de la tolerance a concerne 521 patients. En fin de traitement, le pourcentage de succes cliniques a ete de 90,2 % (157/174) dans le groupe JOS 5 jours, de 91,4 % (160/175) dans le groupe AZI 5 jours et de 92,5 % (161/174) dans le groupe JOS 10 jours (resultats equivalents). A distance, il y a eu 2 rechutes sur 152 patients (1,3 %) dans le groupe JOS 5 jours, 3/158 (1,9 %) dans le groupe AZI 5 jours et 5/156 (3,2 %) dans le groupe JOS 10 jours (resultats equivalents). Un effet indesirable a ete note chez 30/173 patients du groupe JOS 5 jours, chez 24/175 patients du groupe AZI 5 jours et chez 38/173 patients du groupe JOS 10 jours (p = 0,12). Chez 10 patients seulement, l'apparition d'un evenement intercurrent a motive l'arret du traitement. L'efficacite clinique de la josamycine comprime dispersible pendant 5 jours a ete equivalente a celle de l'azithromycine pendant 5 jours et a celle de la josamycine comprime dispersible pendant 10 jours au cours de la bronchite aigue de l'adulte. Que ce soit pendant 5 jours ou pendant 10 jours, la josamycine comprime dispersible a ete aussi efficace et bien toleree que l'azithromycine pendant 5 jours.

The expression of oncogenes c-myc, c-jun and c-raf and tumour suppressor gene p53 was assessed by northern blot analysis of 42 tumours and p53 protein expression by immunohistochemistry on paraffin-embedded sections from 36 specimens of squamous cell carcinoma of the head and neck (SCCHN) obtained before therapy. Of the 42 tumours, 89, 100 and 100% expressed c-myc, c-jun and c-raf oncogenes, respectively. These oncogene expressions did not correlate with sex, age or clinical stage of the disease. However, an association was found between low c-myc expression (P = 0.0001) and high c-jun expression (P = 0.0001) and absence of tumoral response to neoadjuvant chemotherapy. On the other hand, c-raf overexpression was observed in patients resistant to radiation therapy (P = 0.0494). Forty-two per cent of the tumours showed p53 protein overexpression, which did not correlate with any clinical parameter. This p53 protein overexpression was associated with high p53 mRNA levels (REL) (P = 0.0223). A correlation was found between increased c-myc RNA expression and lack of p53 protein expression (P = 0.0407). In addition, a lack of p53 protein expression was indicative of tumour relapse (P = 0.05). None of these biological parameters were associated with disease-free survival (Cox-Mantel test). In conclusion, the overexpression of c-myc, c-jun and c-raf may be independently associated to tumoral response to chemotherapy or radiotherapy, or to tumour relapse, but fail to predict long-term survival.

Item does not contain fulltext BACKGROUND: In a European multicenter prospective study patients with lung cancer were interviewed for smoking history and biological samples centrally collected. The aim of this study was to compare KRAS mutation analysis with smoking status at the time of diagnosis. METHODS: A nested case-study was performed on 233 non-small cell lung carcinomas. Cases were selected on the basis of progressive disease or disease-free post surgery based on specific criteria. KRAS mutation analysis was performed with the point-EXACCT method. RESULTS: KRAS mutations were found in 39 adenocarcinomas and 1 squamous cell carcinoma in the 233 NSCLC. The median quitting smoking time (QST) for patients with and without KRAS mutations was 9 years, interquartile range [IQR 16-38] and 3 years, IQR [13-50], respectively (p=0.039). No difference was found for age at initiation of smoking, duration of smoking, average tobacco consumption, and smoking status at the time of diagnosis. CONCLUSION: The QST was longer for patients with KRAS mutations, supporting the notion that the presence of a KRAS mutation is a dominant early effect, supporting its role as a driver oncogen. 01 februari 2012

Resume Au cours d'une etude ouverte, multicentrique, menee par 400 pneumologues francais, 1383 patients presentant une poussee aigue de surinfection de BPCO ont ete traites par cefpodoxime-proxetil a raison de 200 mg × 2/jour. Une gazometrie arterielle et une spirometrie ont ete pratiquees, en debut et en fin de traitement, chez respectivement 32 % et 22 % des patients dans le but d'obtenir un critere objectif d'evaluation de la guerison. La majorite des patients presentaient, lors de l'inclusion, des facteurs de risques multiples : exacerbation aigue de type 1 d'apres la classification d'Anthonisen (78 %), plus de 3 poussees de surinfection dans l'annee (58 %), âge ≥ 65 ans (50 %) et des indices fonctionnels de gravite a l'inclusion : VEMS 2 de 6 (± 9) mmHg dans le groupe des guerisons et de 3 (± 10) mmHg dans le groupe des echecs (p = 0,008). La variation moyenne de pourcentage du VEMS theorique entre l'inclusion et la fin du traitement a ete de 7 ± 11 (p = 10 −4 ). L'incidence des effets secondaires (principalement digestifs) imputables au traitement et ayant entraine un arret de traitement a ete de 3,5 %. Cette etude, conduite sur une large cohorte de patients, confirme l'efficacite et la bonne tolerance du cefpodoxime-proxetil dans le traitement des poussees aigues de surinfection de BPCO. Le cefpodoxime-proxetil peut etre recommande en traitement de premiere intention dans les poussees aigues de surinfection de BPCO.

Increased vascular calcification is a major cause of cardiovascular events in patients with chronic kidney disease (CKD). It is the result of an active ossification process counteracted by ''bone'' proteins such as osteopontin, alkaline phosphatase, osteoprotegerin, and osteocalcin. Chronic kidney disease - mineral and bone disorder (CKD-MBD) is a systemic disorder of mineral and bone metabolism that occurs in CKD. In addition to abnormalities in the serum calcium and phosphate profile, CKD-MBD is characterized by abnormalities of bone turnover, mineralization, volume and growth as well as vascular calcification. Considering that the presence and extent of vascular calcification in CKD portend a poor prognosis, many efforts have been made to shed light on this complicated phenomenon to prevent vascular calcium deposition and its progression. Indeed, careful control of calcium load, serum phosphate and parathyroid hormone along with the use of calcium-free phosphate binders and vitamin D receptor activators represent a new therapeutic armamentarium to improve quality of life and reduce mortality in CKD.

Despite progress in tobacco control, at least in industrialised countries, lung cancer will remain the leading killer among cancers for the next decade. However, translation of molecular carcinogenesis discoveries to the clinical setting gives realistic hope of major improvements in early diagnosis and will, furthermore, enable therapy to be tailored thus reducing the mortality rate. Tobacco exposure accounts for 85–90% of lung cancer deaths 1. This range corresponds to 16,000–24,000 lung cancer deaths in the USA that are not attributable to tobacco carcinogens. Lung cancer in nonsmokers could, therefore, rank among the seven to nine most fatal cancers in the USA 2. An important study, of more than 630,000 people for incidence and 1.8 million people for mortality, has highlighted the major role of tobacco in lung cancer as its primary result and showed neither a temporal trend in favour of an increased incidence of lung cancer in nonsmokers nor a higher incidence in females, but supported claims that the death rate in males is higher than that in females; it also showed that further studies into the high incidence of lung cancer among females in Pacific Rim countries are necessary 2. If tobacco exposure remains the main cause, lung …

Resume Dans une etude ouverte, randomisee et multicentrique conduite en medecine liberale, cinquante medecins generalistes ont assure le recrutement prospectif de 356 patients presentant un episode de surinfection de broncho-pneumopathie chronique obstructive. Cent soixante-quatorze ont ete repartis dans un groupe de traitement par le cefadroxil, 2 g par jour en deux prises quotidiennes; et 182 autres patients ont recu l'association amoxicilline — acide clavulanique, 1,5 g par jour en trois prises quotidiennes. La duree de traitement etait de 10 j. Sur 333 patients analysables, l'analyse de l'efficacite clinique a montre qu'il n'existait pas de difference significative entre les deux groupes de traitement en terme d'evolution des symptomes de J1 a J10, et de leur presence a J10. Treize patients (7,5%) dans le groupe cefadroxil et 49 (27%) dans le groupe amoxicilline — acide clavulanique ont presente au moins un effet indesirable. La tolerance clinique globale a ete jugee bonne chez 92,5% des patients dans le groupe cefadroxil et 72,3% dans le groupe amoxicilline — acide clavulanique, cette difference etait hautement significative (p = 10−4). L'efficacite clinique du cefadroxil comparable a celle de l'association amoxicilline — acide clavulanique, et sa meilleure tolerance observee au cours de cette etude, suggerent que le cefadroxil est un antibiotique adapte au traitement des surinfections de BPCO.

Resume Un essai multicentrique, ouvert, randomise sur 2 groupes paralleles de traitement a ete realise en medecine communautaire dans le but de comparer l'efficacite clinique et la tolerance du cefadroxil administre a la posologie de 2 g/j et de l'association amoxicilline-acide clavulanique 1,5 g/j, dans le traitement par voie orale des pneumopathies aigues de l'adulte presumees a pneumocoque, sur des criteres cliniques et radiologiques. Les patients etaient revus au 4e jour du traitement puis a la fin de celui-ci, au douzieme jour ± 2. Une visite facultative avait lieu vers le 30e jour de l'essai. Sur les 87 patients inclus dans l'etude, 75 etaient analysables pour l'evaluation de l'efficacite a J12. Les 2 groupes de traitement etaient homogenes a l'inclusion sur l'ensemble des parametres cliniques et demographiques etudies. L'evolution de la symptomatologie etait comparable dans les 2 groupes ; mais la tolerance clinique s'est revelee statistiquement meilleure dans le groupe cefadroxil, le pourcentage de patients ayant presente au moins un effet indesirable etant de 5 % dans ce groupe, versus 26 % dans le groupe oppose, la survenue d'effets indesirables digestifs ayant entraine la sortie d'essai de 3 patients. Dans le traitement de premiere intention des pneumopathies aigues de l'adulte presumees a pneumocoque, le cefadroxil et l'association amoxicilline — acide clavulanique sont apparus avoir une efficacite comparable.

Summary We report the identification of a novel HLA-DRB1*04, officially named DRB1*0460. It was detected during performing HLA-DRB1 high resolution typing by DNA sequencing-based method. The exon 2 nucleotide sequence of DRB1*0460 is identical to that of DRB1*040301 except at codon 63 (AGCAAC), changing the encoded serine to asparagine.

Les resultats obtenus a ce jour dans le traitement du cancer du poumon restent decevants. La faible survie s’explique par une prise en charge a un stade souvent localement avance ou metastatique, qui ne releve parfois que d’un traitement palliatif.

Summary Hospitalized tuberculosis cases were observed, in the years 1982 and 1992. The number of cases decreased, from 148 in 1982 to 57 in 1992. This decrease was correlated to the decrease of the incidence rate in the area : 24,42/100 000 in 1982, 9,74/100 000 in 1992. The cases, according the age group, presented a bimodal distribution in 1992 with two peaks : before 34 years-old and after 65 years old. This kind of repartition did not exist in 1982. The importance of AIDS is, by now, minor (only 3 cases in 1992, none in 1992). The antibiotic resistance is not a problem (only 3 cases of combined resistance : streptomycin + isoniazid) and is not increasing since 1982. Those epidemiological datas should be reevaluated regularly, in order to observe a real evolution.

The gestational age of 302 neonates whose obstetric gestational age was known was assessed at birth using the Dubowitz method; it was obtained from Dubowitz score both graphically from a nomogram and by calculation from the corresponding equation. The values obtained graphically differed to a lesser extent from the obstetric gestational age than did the gestation derived algebraically. With infants small for gestational age (SGA) the difference between the methods was smaller and not significant. It is concluded that the concurrent knowledge of obstetric gestational age introduced a bias in the graphic step; this did not happen in SGA infants probably because in these cases the available information is sometimes less certain. These data demonstrate that even simple procedures are influenced by concurrent information; as a philosophical point about the interpretation of data in general, this study provides an empirical example of the 'theory-ladenness of facts' in medicine.

To report on two consecutive Phase II cooperative trials in which we evaluated the combination of alternating hyperfractionated accelerated radiotherapy and cisplatin-based chemotherapy in inoperable Stage III non-small cell lung cancer (NSCLC).Between February 1986 and September 1989, 65 patients were entered in the first trial (GOTHA I), and between December 1989 and October 1992 67 were enrolled in the second trial (GOTHA II). In both protocols, radiotherapy (RT) was administered twice daily, at 6 h intervals, 5 days a week, to a total dose of 63 Gy in 42 fractions of 1.5 Gy. RT was given during weeks 2, 3, 6, and 7, over an elapsed time of 6 weeks. In GOTHA I, three cycles of cisplatin, 60 mg/m2 day 1, mitomycin, 8 mg/m2 day 1, and vindesin 3 mg/m2 day 1 and the first day of the following week, were given during weeks 1, 5, and 9; in GOTHA II, cisplatin 70 mg/m2 day 1 and vinblastin 5 mg/m2 day 1 and the first day of the following week were given during weeks 1, 5, 9, 13, 17, and 21.With a minimum follow-up of 3 years, the 1-, 2-, 5-, and 8-year overall survival probability was 56% (95% CI 47-64%), 27% (20-35%), 12% (7-18%) and 9% (3-16%), respectively, with a median survival of 13.6 months (11.4-16.8). Median follow-up for survivors was 6 years (3.3-9.9). There were no survival differences between Stages IIIA and IIIB (p = 0.84), performance status 0, 1, 2 (p = 0.87), sex (p = 0.45) or between the two treatment protocols. At this time, 14 patients are alive, and 118 have died: 102 from NSCLC, 4 from acute toxicity, 2 from secondary surgery, 4 from other medical causes, and 6 from unknown causes. Correlation between response and long-term survival was poor, since of the 24 patients who survived 3 years or more, only 6 (25%) were classified as having a complete response; the remainder having either a partial response (11, 46%), no change (6, 25 %), or "progressive disease" (1, 4 %). First site of relapse was local in 31% of these cases, distant in 43%, local and distant in 15 %, and unknown in 11%. Main grade 3-4 acute toxicities were nausea-vomiting (17%), mucositis (15%), leukopenia (41%), and thrombocytopenia (11%). Eight patients presented with grade 3-4 symptomatic lung radiation pneumopathy.Based on this experience with 132 patients, this combination of alternated RT and chemotherapy (CT) for inoperable Stage III NSCLC is feasible with acceptable toxicity, and long-term results suggest a gain in survival when compared to those obtained with conventional RT alone. However, the still high local and distant failure rates indicate that both local and systemic therapies need to be improved.