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Resume Introduction Les associations d’allergies alimentaires et de pollinoses sont nombreuses, elles impliquent les pollens d’arbres, de graminees et d’herbacees, d’une part, et de nombreux vegetaux comestibles, d’autre part, dont l’ingestion provoque soit un syndrome oral, soit des manifestations plus severes telles qu’urticaire, œdeme de Quincke, asthme, voire choc anaphylactique. Etat des connaissances Les bases moleculaires des allergies croisees pollens–aliments sont de mieux en mieux connues : les principaux allergenes croisants sont les allergenes de la famille de Bet v 1, allergene majeur du pollen de bouleau, qui sont presents dans de nombreux fruits mais aussi dans des graines, les profilines presentes dans tous les pollens, les fruits et certains legumes. Ces deux familles d’allergenes sont denaturees par le chauffage et les enzymes gastriques, a l’inverse des LTP presentes seulement dans les pollens d’herbaces et de certains arbres mais aussi dans les fruits et les legumes. D’autres molecules sont des candidates a des reactions croisees : Bet v 6 (une isoflavone reductase), les 1,3-β glucanases, les proteines thaumatines-like . Les experiences d’inhibition in vitro ont confirme que l’epitope ayant induit la sensibilisation provient le plus souvent d’un allergene pollinique ; le support moleculaire de la reaction croisee varie en fonction de l’environnement geographique. Conclusion Les applications pratiques sont soulignees : explications des cosensibilisations diagnostiquees par les tests cutanes, explications de l’insuffisance de certains extraits, utilite du diagnostic moleculaire in vitro, soit par le dosage unitaire des IgE vis-a-vis d’un allergene croisant suspecte, soit par la technique des biopuces multiallergeniques, prediction de la gravite potentielle des symptomes lies a certaines sensibilisations, apport de la desensibilisation aux pollens dans les allergies alimentaires associes.

Resume Introduction Les acariens de la famille des Pyroglyphidae sont la plus importante source des allergenes des acariens. Depuis 1988, leurs connaissances moleculaires se sont considerablement enrichies, leurs structures et leurs fonctions ont pu etre precisees pour la majorite d’entre eux. Etat des connaissances Vingt-deux allergenes ont ete identifies. Les groupes 1 et 2 ont une homologie de sequence en AA de 85 % et sont des allergenes majeurs. Les groupes 4, 5, 7, 11, 14 et 15 sont egalement des groupes importants. La liaison aux IgE des groupes 3, 8, 10, 20 est faible. Les groupes 1, 2, 3 ont un polymorphisme eleve. Nombre d’allergenes ont une fonction biochimique : cysteine proteases pour les allergenes du groupe 1 par exemple. Der p 2 a une homologie de structure et de fonction avec MD-2, corecepteur du recepteur TLR4, dont les LPS sont le ligand. Des reactions croisees ont ete mises en evidence : majeures au sein d’une meme famille, plus faibles entre allergenes de familles differentes. Conclusion Les applications pratiques sont soulignees : explications des cosensibilisations, interet de l’epidemiologie moleculaire, permettant le choix des allergenes a utiliser pour le diagnostic, enfin utilisation future dans les desensibilisations specifiques.

Resume La taxonomie, la morphologie, le cycle biologique et l’ecologie des acariens Pyroglyphides (dont font partie les Dermatophagoides) et des acariens de stockage (Acaridae, Glycyphagidae et Blomia tropicalis) sont rappeles. L’anatomie des acariens Pyroglyphides et des acariens de stockage est voisine : octopodes, munis d’un gnathosome caracteristique, sens du toucher developpe assure par des poils sensoriels. Les glandes salivaires et l’intestin moyen secretent la majorite des allergenes qui sont des enzymes proteolytiques. La fecondite des acariens de stockage est nettement superieure a celle des Pyroglyphides. L’humidite relative est le parametre crucial qui regule la proliferation des acariens. De 60 a 80 % pour les Pyroglyphides, il doit approcher ou depasser 80 % pour les acariens de stockage. La literie est la niche ecologique des Pyroglyphides qui se nourrissent de squames humaines. L’ecosysteme des acariens de stockage qui se nourrissent de denrees alimentaires est proche de celui des moisissures. Initialement consideres comme des acariens du secteur agricole, les acariens de stockage sont egalement des acariens de l’habitat citadin. B. tropicalis dans les regions tropicales est un veritable acarien de la poussiere de maison. En plus des manifestations allergiques respiratoires, les acariens de stockage peuvent provoquer des dermatoses de contact professionnelles.

Resume La connaissance des allergies moleculaires des vegetaux comestibles a beaucoup progresse au cours des dernieres annees. Les auteurs rappellent l’interet que presente l’identification des allergenes d’un point de vue moleculaire : lien avec des manifestations cliniques plus ou moins severes, approche moleculaire de l’epidemiologie des sensibilisations, interpretation de multisensibilisations. Les allergenes moleculaires des differentes familles de sources allergeniques vegetales comestibles sont rappeles, avec cette distinction : (1) les familles a forte prevalence de sensibilisation : les prolamines, 2S-albumine, LTP, inhibiteurs d’alpha-amylase, les cupines (7S et 11S globulines), les profilines, les proteines Bet v 1-like, et (2) les familles d’allergenes vegetaux a faible prevalence de sensibilisation tels que les 1-3s-glucanases, les 1-endochitinases, les isoflavones reductases… Chaque fois que cela etait possible, les auteurs ont indique quels etaient les composants moleculaires qui etaient disponibles pour le diagnostic in vitro. Des exemples de diagnostic par association de composants moleculaires sont donnes et montrent l’amelioration de l’efficacite du diagnostic dans certains cas precis.

Summary Borna Disease virus and its antigens have been assayed by the fluorescence antibody technique. A focus-immunoassay, termed PELISA, was established. It is based on fixation of the cells with 3% formaldehyde, treatment with 1% Triton X-100, incubation with antibodies and the corresponding species-specific antibodies coupled to horseradish peroxidase followed by the enzyme/substrate (3-amino-9-ethyl-carbazole, H202) reaction. This assay can be applied to detect antigens. It allows quantitation of virus as well as titration of antibodies. It greatly facilitates studies on Borna Disease virus and its antigens and is approx. 10 to 100-fold more sensitive than the fluorescence antibody test used previously. Zusammenfassung Focus-Immuntest zum Nachweis von virus-spezifischen Antigenen bei der Borna Krankheit Eine Borna Virus Infektion sowie Borna Virus-spezifische Antigene wurden bisher mittels der Fluoreszenzantikorper-Technik nachgewiesen. Es wird uber einen empfindlichen Focus-Immuntest, genannt PELISA, berichtet. Er basiert auf der Fixation von Zellen mit 3% Formaldehyd, Behandlung mit 1% Triton X-100, Inkubation mit Antikorpern und den entsprechenden speziesspezifischen, Peroxidase markierten Antikorpern. Die Antikorperbindung wird durch eine Enzym/Substrat (3-Amino-9-Ethyl-Carbazol, H202) Reaktion nachgewiesen. Dieser Test kann zur Antigendarstellung genutzt werden. Er erlaubt die Quantifizierung von Virus ebenso wie die Titration von Antikorpern und ist etwa 10–100fach empfindlicher als der bis jetzt verwendete Fluoreszenzantikorpertest. Untersuchungen am Virus der Borna Krankheit sowie seiner Antigene werden mit diesem Test erheblich vereinfacht. Resumen La prueba inmunitaria focal para los antigenos especificos del virus de la enfermedad de Borna Hasta la fecha se ponian en evidencia una infeccion por virus Borna y los antigenos especificos del mismo virus mediante la tecnica de anticuerpos fluorescentes. Se informa sobre una prueba inmunitaria focal sensible, llamada PELISA. Esta tecnica se basa en la fijacion de celulas con un 3% de aldehido metilico, tratamiento con 1% de Triton X-100, incubacion con anticuerpos y con los anticuerpos correspondientes especificos de especie, marcados con peroxidasa de rabano rusticano. La fijacion de anticuerpos se pone en evidencia por medio de una reaccion de enzima/substrato (3-amino-9-etil-carbazol, H202). Esta prueba se puede utilizar para detectar antigenos. Permite cuantificar virus, titular anticuerpos y es de 10–100 veces mas sensible que la prueba de anticuerpos fluorescentes que se venia utilizando hasta ahora. Con esta prueba se han simplificado mucho los estudios referentes al virus de la enfermedad de Borna y a sus antigenos.

Resume Les allergenes rares de l’environnement interieur sont insuffisamment reconnus. La prevalence de la sensibilisation a ces allergenes depend des caracteristiques geographiques et climatiques de l’habitat, ainsi que du mode de vie de ses habitants. Leurs sources sont diverses : allergenes d’origine animale (acariens, insectes, mammiferes…) ou d’origine vegetale. La sensibilisation aux allergenes rares doit etre confirmee par une histoire clinique documentee, par des tests immunologiques et par l’effet benefique de l’eviction. Une revue generale des allergenes rares et/ou des nouveaux aeroallergenes de l’environnement interieur est presentee.

Resume La mise au point de nouvelles techniques de desensibilisation utilisant des produits issus de la biologie moleculaire necessite le controle de leur efficacite par des essais cliniques appropries. Un apercu des principales molecules proposees par les recherches fondamentales au cours des dernieres annees est delivre : allergenes recombinants correspondant a des molecules d’allergenes pertinents du fait de leur forte prevalence de sensibilisation, derives hypoallergeniques d’allergenes recombinants (polymeres, fragments, molecules avec des mutations ou des deletions d’acides amines), molecules hybrides, epitopes T, epitopes B, molecules conjuguees a des CpG ou d’autres co-stimulateurs. L’activite biologique d’un grand nombre de ces molecules a ete demontree in vivo. La selection de molecules candidates pour l’immunotherapie a d’abord comporte des etudes preliminaires effectuees en ouvert sur un nombre restreint de patients. Les auteurs rapportent ici les resultats de cinq etudes de desensibilisations effectuees par injection, realisees en double insu, le groupe temoin etant un placebo et/ou un groupe traite par l’extrait naturel (dans deux etudes). Les resultats cliniques les plus significatifs sur le plan statistique ont ete observes avec des allergenes recombinants non modifies, sans survenue d’accidents systemiques severes. Dans les cinq etudes, on releve une augmentation importante des IgG specifiques vis-a-vis de l’allergene naturel et vis-a-vis des allergenes recombinants. La reduction des tests cutanes dans les groupes traites par rapport au groupe placebo est significative dans deux etudes sur trois. Des etudes comportant un nombre de patients plus important sont maintenant souhaitables pour repondre aux exigences reglementaires du developpement clinique des allergenes recombinants.

Resume Les progres des techniques de biologie moleculaire ont conduit a la production d’allergenes sous forme recombinante, disponible pour une trentaine d’entre eux pour les dosages in vitro. Ils correspondent a un variant moleculaire defini et leur activite biologique doit etre evaluee par rapport a l’allergene naturel correspondant. Les avantages des allergenes recombinants sont essentiellement l’obtention de preparations allergeniques ayant des qualites pharmaceutiques constantes, permettant la determination des IgE specifiques dirigees contre les differents composants moleculaires d’une source allergenique tels que les pollens, les acariens…Les principales consequences de ces avancees biologiques sont rappelees : evaluation des sensibilisations vis-a-vis d’allergenes moleculaires dans differentes populations (epidemiologie moleculaire), amelioration des extraits utilises pour le diagnostic en selectionnant les sources allergeniques les plus pertinentes et en quantifiant leur contenu en allergenes majeurs, definition du spectre de reconnaissance des IgE specifiques vis-a-vis des differents composes moleculaires (spectrotype), evaluation quantitative des reponses IgE, etablissement des bases moleculaires des reactions croisees entre allergenes inhales, entre allergenes alimentaires, entre allergenes inhales et allergenes alimentaires. Sur le plan de la pratique allergologique, ce nouvel outil diagnostique permet une meilleure interpretation des polysensibilisations mises en evidence par les tests cutanes et les tests in vitro. Des exemples de tableaux cliniques particuliers associes a des sensibilisations specifiques vis-a-vis de certains allergenes recombinants sont presentes.

In an attempt to find better criteria for the evaluation of prophylactic treatment of asthma, we have studied the significance and the correlations of the 3 parameters usually measured: symptoms, bronchodilator requirements, changes in Peak Expiratory Flow (PEF). We have collected these data daily over a 16 week period in 13 adult asthmatics allergic to Dermatophagoides pteronyssinus. For each patient, the 3 scores were compared graphically. Linear regression was used to analyze the individual relationship between 2 daily scores. Incomplete cards mostly revealed unexpected behaviour (e.g. normal lung function but many symptoms recorded) and cannot of course be taken into account in a trial protocol. We found a good correlation between PEF and symptom scores in 10 out of 13 patients and we could point out the poor correlation between medication score and the other scores. To our knowledge, it is the first time such an objective result has been shown in asthmatic adults. Our analysis provides data which should improve the studies of prophylactic treatment efficacy in asthma.

Resume La notion d'allergie croisee s'impose desormais a l'allergologue comme un element indispensable de sa demarche diagnostique et therapeutique. En effet, la connaissance des proteines et des mecanismes impliques dans ce type de phenomene presente non seulement un interet physiopathologique, mais aide egalement le praticien a interpreter certaines donnees anamnestiques et les resultats des tests cutanes ou biologiques. Elle rend par ailleurs plus rationnelle la prise en charge des patients, et aura probablement des applications therapeutiques a l'avenir dans le cadre d'une utilisation plus large des allergenes recombinants.

Resume L'eventail des allergies croisees pollens–aliments s'est elargi au cours de la derniere decennie, les tableaux cliniques sont mieux precises selon les allergenes impliques, et les bases moleculaires sont determinees pour certaines. Les outils diagnostiques englobent les tests cutanes, la recherche d'IgE specifiques et les tests de provocation orale ouverts et en double insu. Les allergies croisees ont d'abord ete fondees uniquement sur des techniques immunologiques d'inhibition avec des extraits naturels, elles ont beneficie de l'apport de la biologie moleculaire. De nombreux allergenes homologues d'allergenes des pollens ont ete sequences, la structure tridimensionnelle est determinee pour Pru av 1, permettant des etudes a l'echelle submoleculaire. Les allergenes croisant entre pollens et aliments, dont la pertinence clinique est la mieux etablie, concernent les allergenes de la famille de Bet v 1 et Bet v 2. Ces allergenes sont presents dans de nombreux fruits et vegetaux comestibles. Les identites de sequence pour Bet v 1 varient de 38 a 67 %, elles sont plus importantes pour les profilines (70 a 80 %). Les sensibilisations croisees liees a Bet v 1 et a la profiline peuvent etre muettes sur le plan clinique, ce qui est particulierement frequent pour la profiline. Les autres molecules candidates a des reactions croisees entre pollens et allergenes alimentaires sont Bet v 6, allergene mineur du bouleau, les lipotransferases retrouvees dans certains pollens de composees, les 1,3-β-glucanases correspondant a un allergene majeur de l'olivier. La signification de la detection d'IgE specifiques dirigees contre les determinants carbohydrates reste discutee. Le probleme majeur pour le clinicien est celui de la non-signification clinique des reactions croisees mises en evidence in vitro et in vivo.

An epizootic infection was observed in a colony of 80 New World monkeys consisting of various species including a group of marmosets and Saguinus species. During the summer and autumn of 2002, 30 animals died of unknown diseases. Six animals were sent to the German Primate Center for investigation of the cause of death. A complete pathologic and histologic investigation was carried out. The animals exhibited erosive-ulcerative lesions of the oral mucous membranes. Advanced stages of the disease were characterised by hemorrhagic lesions on the skin distributed randomly over the body, but principally on the face, scrotal region, soles, and palms. Electron microscopy revealed virus particles with orthopox-like morphology within intracytoplasmic inclusions in epithelial cells. The DNA samples from various tissues were analyzed by use of a set of orthopox virus-specific, real-time polymerase chain reaction assays. Amplification products were sequenced to define the virus more precisely. Sequencing confirmed the presence of an orthopox virus. Sequence data indicated that all six animals were infected with the same virus. Propagation of the virus on Vero cells resulted in a rapidly progressive cytopathogenic effect. Preliminary phylogenetic analyses of two genes revealed closest homology to cowpox viruses. The origin of this poxvirus outbreak remains unexplained, and the strain and genus of the virus need to be determined in detail.

1 An enzymatic activity is described in oleate-grown cells of E. coli, which has the cofactor requirements of a long chain acid: CoA ligase (AMP). This enzyme is at least partially membrane bound and activates saturated and mono- and polyunsaturated fatty acids. It is inactive with butyrate and hexanoate. The enzyme is induced by oleate under similar conditions, but at different relative rates, as three other enzymes of fatty acid degradation (thiolase, crotonase, hydroxyacyl-CoA dehydrogenase) which are under coordinate control. 2 A mutant lacking acyl-CoA synthetase synthesizes the other three enzymes at the basal rate of the wild type in the presence or absence of oleate in the medium. This suggests that the fatty acyl-CoA derivatives rather than the fatty acids serve as inducers. The same mutant is unable to incorporate fatty acids into bacterial lipids. The acyl-CoA synthetase is therefore required for lipid synthesis from exogenous fatty acids in vivo. 3 The isolation and properties of mutants unable to degrade oleate are described. A pleiotropic mutant lacking thiolase, crotonase and hydroxyacyl-CoA dehydrogenase still contains the inducible acyl-CoA synthetase. Mutants lacking thiolase and hydroxyacyl-CoA dehydrogenase have inducible wild type levels of the other enzymes. 4 Mutants affecting the synthesis of thiolase, hydroxyacyl-CoA dehydrogenase or crotonase map between the loci metE and rha on the E. coli-chromosome and are probably closely linked. The mutant lacking acyl-CoA synthetase is not linked to the other mutants and maps near the his-locus. 5 Only fatty acids with more than twelve carbon atoms serve as inducers or can be used as sole carbon source by the wild type. This specificity is therefore typical for the abolition of repression by the interaction with the fatty acids. 6 Spontaneous mutants can be isolated which grow on decanoate. These are constitutive for the synthesis of all four enzymes investigated and can only grow on fatty acids with more than eight carbon atoms. Thus, after destruction of the repression mechanism the growth behavior is a reflection of the substrate specificity of the acyl-CoA synthetase. 7 Starting with the constitutive mutants, spontaneous mutants have been isolated which can grow on butyrate. These fall into two classes: (a) One class grows on butyrate and poorly on long chain fatty acids. It makes all four enzymes constitutively but has twenty times more thiolase activity than the parent. This thiolase activity is not due to a gene linked to metE. (b) The other class can grow on butyrate and fatty acids with more than eight carbon atoms. It synthesizes the enzymes constitutively. 8 The data suggest that the expression of the linked structural genes of crotonase, hydroxy-acyl-CoA dehydrogenase and thiolase and the unlinked gene of the acyl-CoA synthetase from a regulon which is controlled by a common regulator gene.

The φπ + /ωπ + ratio from n ¯ p annihilations on a liquid hydrogen target, for n ¯ momenta between 64 and 297 MeV/ c , was measured using the OBELIX spectrometer at LEAR. The ratio R ( ϕ π / ω π ) = σ ( n ¯ p → ϕ π + ) / σ ( n ¯ p → ω π + ) turned out 0.110±0.015 stat ±0.006 syst . Implications of this result on the OZI rule are discussed.

Resume Les auteurs rapportent l’observation d’un homme de 53 ans pris en charge pour pneumopathie hypoxemiante. Le lavage alveolaire objectivait une alveolite neutrophilique et les recherches d’agents infectieux etaient negatives. Une biopsie pulmonaire objectivait un discret œdeme endo-alveolaire et un infiltrat polymorphe dans les parois alveolaires moderement epaissies. Une antibiotherapie inefficace etait remplacee, apres 17 jours, par une corticotherapie. La symptomatologie clinique et radiologique s’ameliorait alors en quelques jours et la pneumopathie ne recidivait pas a l’arret des corticoides. A l’origine de cette pneumopathie, les auteurs incriminent la minocycline que recoit ce patient depuis 2 ans pour un rhinophyma. Ce traitement avait ete suspendu pendant quelques semaines et c’est apres sa reprise qu’etait apparue la pneumopathie. Les differentes manifestations cliniques des pneumopathies a la minocycline sont ensuite passes en revue : pneumopathies a eosinophiles, BOOP, pneumopathies d’hypersensibilite. Un seul cas de polynucleaires neutrophiles au lavage a ete anterieurement rapporte.

First results on n annihilations on nucleons and nuclei measured by the OBELIX spectrometer are reported. Interesting new results on meson spectroscopy were obtained. Furthermore n-p and n - Nucleus (C, Al, Cu, Sn, Pb) annihilation cross sections between 100 and 300 MeV/c were measured.

Summary Background Ash, a wind-pollinated tree belonging to the family Oleaceae, is distributed world-wide and has been suggested as a potent allergen source in spring time. Objective The aim of this study was to determine the profile of allergen components in ash pollen in order to refine diagnosis and therapy for patients with sensitivity to ash pollen Methods The IgE reactivity profile of 40 ash pollen-allergic patients was determined by immunoblotting. Antibodies raised to purified pollen allergens from tree and grass pollens were used to identify cross-reactive structures in ash pollen extract. IgE immunoblot inhibition studies were performed with recombinant and natural pollen allergens to characterize ash pollen allergens and to determine the degree of cross-reactivity between pollen allergens from ash, olive, birch, grasses and weeds. Results The allergen profile of ash pollen comprises Fra e 1, a major allergen related to the major olive allergen, Ole e 1, and to group 11 grass pollen allergens, the panallergen profilin, a two EF-hand calcium-binding protein, a pectinesterase-like molecule and an allergen sharing epitopes with group 4 grass pollen allergens. Thus, the relevant allergens of ash are primarily allergens that share epitopes with pollen allergens from other tree, grass and weed species. Conclusions Allergic symptoms to ash pollen can be the consequence of sensitization to cross-reactive allergens from other sources. The fact that ash pollen-allergic patients can be discriminated on the basis of their specific IgE reactivity profile to highly or moderately cross-reactive allergens has implications for the selection of appropriate forms of treatment.

Resume Les reactions immediates aux produits de contraste iodes sont bien connues et largement decrites. Cependant, leur mecanisme physiopathologique reste controverse et plusieurs hypotheses ont ete avancees : hyperosmolalite, histaminoliberation non specifique, activation du complement, anaphylaxie. Les auteurs rapportent deux observations personnelles de chocs anaphylactoides survenus lors de coronarographies apres injection d’ioxaglate (Hexabrix 320®). Les tableaux cliniques s’apparentent a des manifestations anaphylactiques, compte tenu de la chronologie des manifestations cliniques, de la positivite des tests cutanes en immediat et dans l’un des deux cas rapportes de la survenue d’une nouvelle reaction severe malgre la premedication par antihistaminiques H1 et corticoides. Une evaluation allergologique est indiquee apres toute reaction severe a un produit de contraste iode afin de prevenir les accidents ulterieurs ; la premedication peut etre une fausse securite ; elle n’a pas empeche la survenue d’une reaction severe dans une des observations rapportees.

Resume La desensibilisation specifique a besoin de criteres objectifs pour affirmer son efficacite et son utilite. L'essai clinique en double insu parait necessaire mais pose des problemes concernant certains criteres tels que le choix des malades retenus, le choix du placebo, le choix des criteres d'efficacite clinique, la connaissance precise des modalites du traitement de desensibilisation. Il n'existe pas pour l'instant suffisamment de donnees pour introduire la mesure de parametres immunologiques dans la surveillance et l'appreciation de l'efficacite de l'immunotherapie.

Resume L’observation rapportee est celle d’un patient presentant des symptomes de pollinose avec multisensibilisations a differents pollens et des allergies alimentaires se manifestant sous la forme d’urticaire, de syndrome oral et d’anaphylaxie a l’effort. Les etiologies des allergies respiratoires et alimentaires sont discutees au vu des resultats de dosages d’IgE specifiques avec la technique ISAC. Les sensibilisations respiratoires sont de type mediterraneen ; l’anaphylaxie d’effort est tres vraisemblablement liee aux LTP de la tomate ; les etiologies du syndrome oral et de l’urticaire sont liees aux LTP de peche mais les proteines de stockage qui sont des allergenes des lentilles et du soja doivent aussi etre evoquees.

The influence of pretreatment serum levels of lactate dehydrogenase (LDH) and neuron-specific enolase (NSE) on survival was investigated in a series of 263 consecutive patients with small-cell lung cancer. LDH was elevated in one-half of the patients, NSE in 79%. Both were significantly higher when the disease was considered extensive than when it was limited. The markers were significantly correlated (r= 0.54, P=1.03 x 10(-20)), and both had a significant impact on survival in the univariate analysis. The multivariate survival analysis of the entire population showed that LDH, along with performance status, extent of disease, and albumin, was a more important prognostic factor than NSE. Only when LDH was removed from the model did NSE become an independent prognostic factor. In the separate multivariate survival analyses of limited and extensive disease, LDH remained an independent prognostic factor. For extensive disease, NSE did not even appear in the model when LDH was excluded; for limited stage disease, NSE did become a weak independent prognostic factor when LDH was excluded. In conclusion, LDH, which is less expensive to assay than NSE, is also a stronger independent prognostic factor for small-cell lung cancer and should be part of the initial work-up. In clinical trials, stratification for LDH levels should be considered because of its prognostic weight.

A study of 215 Berlin dentists and 108 dental assistants recruited at the 1997 Berlin Dental Society meeting assessed their occupational risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, HBV vaccine coverage, and barrier prevention methods used. Among dentists, 7% (95% CI 4–11) and 0·5% (95% CI 0–3) had serological evidence of previous HBV and HCV infection, respectively. Similar figures for dental assistants were 1% (95% CI 0–5) and 0% (95% CI 0–4). Only 74% of dentists and 63% of dental assistants reported HBV vaccination. Approximately half always used gloves, eye glasses, or face masks. HBV unvaccinated dentists whose patients had HBV risk factors had a greater risk of HBV infection; those who always wore face masks were at lower risk (OR 0·2, 95% CI 0·02–0·98). These data indicate that among Berlin dentists, the HCV risk was lower than that of HBV and that face masks may have lowered the risk of HBV. The use of eye glasses or gloves did not appear to lower the risk of HBV acquisition in this population.

During the 20th century medical education has been largely preoccupied with discussions of the venues and methods for teaching. Little attention has been paid to what should be learned about the scientific paradigm underlying research and practice. A 17th century model has gradually produced an increasingly narrow, monocausal, reductionistic view of health and disease. Much good has resulted, but this "belief system" fails to accommodate or explain the meaning and impact on patients' health of diverse internal and external experiences and influences. During this period quantum mechanics and its ever-expanding capacity to accommodate new information and enhance understanding have superseded Newtonian physics in much scientific thinking.A broad range of historical and contemporary scientific literature is examined in support of four central questions in this three-part series: (1) Are there reasons to examine these matters now? (2) How is medical scientific thinking influenced by the general reorientation of science during the 20th century? (3) Are there reasons now to examine the impact of these changes on medicine? (4) Will a change of paradigm affect medical practice, research, and education?The extraordinarily productive contemporary biomedical model should be expanded beyond the physical and biological to incorporate meaningful information about how each patients experiences impinge on health status.Family and other primary care physicians together with collaborators in the biological and behavioral sciences and other health professions should undertake rigorous research to establish the validity of the expanded paradigm espoused. Its impact on practice, research, education, and policies could be profound.

BACKGROUND: During the 20th century medical education has been largely preoccupied with discussions of the venues and methods for teaching. Little attention has been paid to what should be learned about the scientific paradigm underlying research and practice. A 17th century model has gradually produced an increasingly narrow, monocausal, reductionistic view of health and disease. Much good has resulted, but this "belief system" fails to accommodate or explain the meaning and impact on patients' health of diverse internal and external experiences and influences. During this period quantum mechanics and its ever-expanding capacity to accommodate new information and enhance understanding have superseded Newtonian physics in much scientific thinking. METHODS: A broad range of historical and contemporary scientific literature is examined in support of four central questions in this three-part series: (1) Are there reasons to examine these matters now? (2) How is medical scientific thinking influenced by the general reorientation of science during the 20th century? (3) Are there reasons now to examine the impact of these changes on medicine? (4) Will a change of paradigm affect medical practice, research, and education? RESULTS: The extraordinarily productive contemporary biomedical model should be expanded beyond the physical and biological to incorporate meaningful information about how each patient's experiences impinge on health status. CONCLUSIONS: Family and other primary care physicians together with collaborators in the biological and behavioral sciences and other health professions should undertake rigorous research to establish the validity of the expanded paradigm espoused. Its impact on practice, research, education, and policies could be profound.

The results of a study of the annihilation reactions n p → θπ + and n p → ωπ + are reported; the data were collected by the OBELIX apparatus, with antineutrons annihilating in flight (momenta from ∼ 50 MeV/ c to 405 MeV/ c ). Annihilation frequencies and annihilation cross sections have been deduced, for both channels, as a function of antineutron momentum. From the cross section ratio, a substantial deviation from OZI rule expectations is observed. An s s quark content in the nucleon offers a fairly plausible explanation for such an effect.

We report the study of light baryon production in two-prong annihilation reactions due to antiprotons stopping in gaseous deuterium and detected by the OBELIX spectrometer (LEAR, CERN). A clear signal of the Δ(1232) production in binary reactions was found in both annihilation channels: p d→π − Δ + (Δ + →π 0 p) and p d→π 0 Δ 0 (Δ 0 →π − p) . The annihilation probabilities for these reactions turned out to be Y=(1.01±0.08)×10−5 and Y=(1.12±0.20)×10−5, respectively. In addition, the annihilation probability for the prototype Pontecorvo reaction p d→π − p was measured with the best world statistics: Y=(1.46±0.08)×10−5.

Resume L'allergie au pollen est tres frequente. Les etudes epidemiologiques ont montre que la prevalence des maladies allergiques et des rhinites allergiques polliniques sont en augmentation. Les sensibilisations aux pollens sont plus frequentes en milieu urbain que rural, dans les pays europeens de l'Ouest par rapport aux pays europeens de l'Est, et a proximite des axes routiers. Des experimentations chez l'animal et chez l'homme ont montre que les particules de diesel pouvaient favoriser une reponse immune specifique de type IgE. Des particules de petite taille, inhalables, portant les allergenes des pollens, ont ete retrouvees dans l'atmosphere par de nombreux auteurs. La nature et la provenance de ces particules n'est pas totalement elucidee : relargage a partir des pollens de granules inhalables, fragments de plantes, et/ou transfert des allergenes des pollens vers des particules presentes dans l'atmosphere. L'observation microscopique des pollens en milieu pollue a montre la presence d'agregats particulaires a leur surface. Ainsi, a cote des conditions meteorologiques, les polluants atmospheriques pourraient intervenir en modifiant la biodisponibilite des allergenes des pollens.

The reaction p p→K + K − π 0 was analysed for antiproton annihilations at rest at three hydrogen target densities. A strong dependence of the p p→φπ 0 yield on the quantum numbers of the initial state is observed. The branching ratio of the φπ0 channel from the 3S1 initial state is more than 15 times larger than the one from the 1P1 state. A large apparent violation of the OZI rule for tensor meson production from p p -annihilations from the P-waves (1+++2++) is observed: Rexp(f′2π0/f2π0)=(149±20)·10−3, significantly exceeding the OZI-rule prediction R=16·10−3.

The study of the I =1, J PC =0 ++ states with the OBELIX detector in the channel p p→K ± K 0 S π ∓ at three different target densities is reported. The data show the evidence for an extra scalar state with mass 1.29±0.01 GeV/ c 2 and width 0.080±0.005 GeV/ c 2 .

We performed a prospective study in order: 1) to determine whether a correlation could be found between serum eosinophil cationic protein (ECP) levels and clinical and functional status in perennial asthmatics during a 5 month prospective study; and 2) to evaluate the relationship between allergic exposure and ECP levels in periodic asthmatics. Two groups of asthmatic patients were selected: a group of acutely ill perennial asthmatics and a group of periodic asthmatics. The acutely ill perennial asthmatics (n=22, mean age=39.4 yrs) were included on the basis of hospitalization for acute asthma. At the end of the hospitalization, there was a 5 month follow-up of clinical, functional and medication scores, as well as eosinophil counts and ECP levels. The periodic asthmatic group was composed of asthmatics sensitized to birch and tree pollens (n=10, mean age=33.8 yrs). The same measurement were performed on this group, before, during and after the pollen season. Under corticosteroid treatment in the acutely ill patients, there was a significant decrease in serum ECP levels between the first day of hospitalization and the day of discharge (mean: 23.2 microg x L(-1) and 9.5 microg x L(-1), respectively; p=0.006). No correlation was found between the clinical status, functional status and serum ECP levels during the 5 month follow-up. A significant increase in ECP levels was found in periodic asthmatics during the pollen season. Our results suggest that serum eosinophil cationic protein is a useful marker of allergen exposure and of acute asthma treatment. This could be of importance in the prevention and follow-up of allergic asthma; the value of serum eosinophil cationic protein measurements in the day-to-day management of adult asthmatics needs to be further clarified.

Resume La mise en evidence de plus en plus nombreuse d'allergies croisees a un interet primordial en allergologie, a la fois sur le plan clinique, biologique et therapeutique. Des a present, leur connaissance enrichit la semeiologie des maladies allergiques : par exemple en confirmant le diagnostic etiologique d'une allergie respiratoire par l'existence d'une allergie croisee associee, ou encore par une meilleure identification d'un allergene alimentaire du fait d'une sensibilisation concomitante a certains pneumallergenes. La notion d'allergenes croisants est essentielle pour l'interpretation des tests cutanes et des tests biologiques : les communautes de familles pour des allergenes d'origine vegetale ou animale, tres proches sur le plan taxonomique, peuvent expliquer certaines polysensibilisations. Des discordances peuvent exister entre sensibilisations immunologiques aux allergenes croisants et manifestations cliniques, ce qui souligne la necessite absolue de confronter les resultats biologiques a la clinique. En cas d'allergie alimentaire, la substitution par des produits ne contenant pas l'allergene croisant peut etre interessante. Sur le plan fondamental, les allergenes croisants sont parfois des proteines ayant des fonctions communes : cysteines proteases, proteines de transport, proteines du cytosquelette. Les allergenes croisants ont en general une forte homologie de sequences d'acides amines. Dans le futur, la production d'allergenes recombinants correspondant aux allergenes croisants peut avoir des consequences interessantes pour le diagnostic de certaines sensibilisations ; elle devrait permettre un dosage quantitatif des IgE specifiques dirigees contre les allergenes croisants. Elle pourrait egalement modifier les techniques de desensibilisation en n'ayant qu'a un nombre limite d'allergenes croisants recombinants.

The spin-parity analysis of the $\mathrm{n\ifmmode \bar{}\else \={}\fi{}}\stackrel{\ensuremath{\rightarrow}}{p}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}$ exclusive reaction in flight is presented. The main aim is to study the $({\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}})$ invariant mass spectrum in the region around 1500 MeV. The analysis was performed with a Breit-Wigner parametrization for all the resonant states and, for the scalar sector in the mass region below 1.2 GeV, by means of a K-matrix-like treatment. It clearly shows the need for two states, a scalar one ${(0}^{++})$ with mass and width $(1522\ifmmode\pm\else\textpm\fi{}25) \mathrm{MeV}$ and $(108\ifmmode\pm\else\textpm\fi{}33) \mathrm{MeV}$, and a tensorial one ${(2}^{++})$ with mass $(1575\ifmmode\pm\else\textpm\fi{}18) \mathrm{MeV}$ and width $(119\ifmmode\pm\else\textpm\fi{}24) \mathrm{MeV}$, respectively. In addition, the analysis requires the presence of a scalar state at $(1280\ifmmode\pm\else\textpm\fi{}55) \mathrm{MeV}$, $(323\ifmmode\pm\else\textpm\fi{}13) \mathrm{MeV}$ broad, and of a second vectorial one, in addition to the ${\ensuremath{\rho}}^{0}(770)$ signal, with mass and width $(1348\ifmmode\pm\else\textpm\fi{}33) \mathrm{MeV}$ and $(275\ifmmode\pm\else\textpm\fi{}10) \mathrm{MeV}$, respectively.

The results of the spin-parity analysis of annihilations at very low momentum (≈ 50 MeV/c) are reported. To describe the data the production of the ϱ, f2, a2 and a1 mesons and the presence of the ππ interaction in S-wave (the σ term) in the final state are necessary. The best fit solution requires also the presence of a ϱ′ state of mass and width M = 1.282 ± 0.037, Γ = 0.236 ± 0.036 GeV/c2 and of a heavy pion π(1300) of mass and width M = 1.275 ± 0.015, Γ = 0.218 ± 0.100 GeV/c2. The measured fraction of the annihilation cross section into 2π+2π− is (7.61 ± 0.35) · 10−2.

We measured the in flight annihilation frequencies and cross sections of reactions n p → π + π 0 ,π + η and K+KS in the antineutron momentum range between 50 and 400 MeV/c. The annihilation frequencies of these channels from the different allowed initial states were calculated and some information about the n p annihilation dynamics were obtained. The first determination of the D-wave contribution in this momentum range was also obtained.

The partial wave analysis of the reaction p p → π + π − π 0 at rest has been performed for the first time by using high-statistics data sets collected in hydrogen targets at three different densities. The different mixtures of partial waves corresponding to our samples allow a reliable determination of each contribution. This technique is crucial in the identification of the exotic candidate f2(1565) which can be produced by 1S0, 3P1 and 3P2 initial states. The amplitude analysis was performed in the frame of the K-Matrix and P-Vector approach. It requires presence of the exotic candidates f0(1500) and f2(1565) with the following masses and total widths: (1449 ± 20)MeV, (114 ± 30)MeV and (1507 ± 15)MeV, (130 ± 20)MeV respectively. In addition to f0(980), f0(1300) f2(1270) and ϱ(770), a clear evidence of I = 1, JP = 1− signal, which we identify with ϱ(1450), is obtained.

New experimental results on p d annihilation at rest into pions plus a high momentum proton in the final state are discussed. The data sample was collected using the OBELIX spectrometer at the LEAR facility (CERN). The annihilation probabilities, or more precisely the yields (Y) via channels p d → 2π − π + π 0 p and p d → 3π − 2π + π 0 p with proton momenta p > 400 MeV/c have been measured for the first time: Y = (93.2 ± 1.6) × 10−4 and Y = (52.2 ± 1.4) × 10−4, respectively. The signal in the invariant mass distribution of the pπ+ system in the region of the well-known Δ++(1232)-isobar is clearly seen in reactions p d → 2π − π + p , p d → 2π − π + π 0 p , p d → 3π − 2π + p and p d → 3π − 2π + π 0 p . The upper limit on reaction p (Δ − Δ ++ ) → 2π − π + p in the p d annihilation at rest, which could be interpreted as a manifestation of the ΔΔ component of the deuteron, was found to be Y ≤ 6.5 × 10−5 with a 90% confidence level.

New measurements of the pp total annihilation cross-section at very low momenta (around 50 MeV/c) confirm the previous results obtained by the OBELIX collaboration. The measured values are in general agreement with a scattering length approximation of the annihilation cross-section where the pp scattering lengths are obtained from measurement of the protonium shifts and widths and which accounts for the Coulomb interaction. Partial annihilation cross-sections and annihilation frequencies for some channels have been measured too. The values of the total and partial cross sections at the lowest p momentum show an unexpected behaviour

The study of the I = 1, 0 ++ states with the OBELIX detector in the channel pp → K ±K 0 sπ ∓ at three different target densities is reported. We discuss in particular the results about a o (980) and the evidence of an extra scalar state with mass 1.29 ± 0.01 GeV/c 2 and width 0.080 ± 0.005 GeV/c 2