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Resume Contexte et objectifs Dans un contexte de sous-declaration des cancers d’origine professionnelle regulierement soulignee, une etude a ete menee en Ile-de-France sur les cancers de vessie et les cancers naso-sinusiens incidents afin d’evaluer la frequence des expositions a des cancerogenes professionnels, de reperer les secteurs d’activite et les professions concernees, de favoriser les demarches de reconnaissance en maladie professionnelle (MP) le cas echeant et de mettre au point des outils de reperage des expositions utilisables en routine. Methode Etaient eligibles les cas incidents de cancer naso-sinusien residant en Ile-de-France et de cancer de vessie de trois departements d’Ile-de-France pris en charge a 100 % en affection longue duree (ALD30) entre 2005 et 2007 dans le regime general de la Securite sociale, le regime social des independants ou la caisse de coordination aux assurances sociales de la regie autonome des transports parisiens (RATP). Les sujets volontaires ont beneficie d’un questionnaire professionnel detaille. L’exposition aux differents agents cancerogenes pour la vessie (amines aromatiques, hydrocarbures aromatiques polycycliques) ou pour les sinus du nez ou de la face (poussieres de bois, certains derives du chrome ou du nickel) a ete evaluee par deux experts en pathologie professionnelle avec retour d’information vers le medecin traitant et proposition le cas echeant d’une declaration en MP. Les cas ayant fait l’objet d’une declaration et/ou d’une reconnaissance en MP ont ete evalues. Resultats Parmi les 1162 cancers de vessie eligibles qui ont ete reperes 58 % ont accepte de participer. Une proposition de declaration en MP a ete proposee a 7 % des sujets. Seuls 22 % d’entre eux l’ont effectuee. Sur les 151 cancers naso-sinusiens eligibles pour l’etude, 48 % ont participe. Une declaration en MP a ete proposee a 35 % des sujets et seulement 53 % d’entre eux l’ont effectuee. Toutes les demandes de reconnaissance en MP quel que soit le type de cancer considere ont ete acceptees. Conclusion Un nombre notable de patients relevait d’une declaration en MP, mais peu d’entre eux ont effectue cette declaration. Compte tenu des enjeux medico-sociaux de la declaration en MP, pour le patient comme pour la collectivite, il est important de renforcer l’information des professionnels de sante et des patients. Un dispositif de reperage systematique des expositions professionnelles merite d’etre propose a tous les cas incidents de cancer de vessie ou naso-sinusien.

The reasons for the wide variation of incidence and severity of recurrent hepatitis C after liver transplantation are not clear. We have studied liver transplant recipients to assess the impact of hepatitis C virus (HCV) genotype and HCV RNA quantification on HCV recurrence after transplantation. Twenty-two patients received transplants for HCV cirrhosis and were followed up with virological and histological assessments. Mean follow-up was 39 months. HCV genotype was determined with line probe assay (Inno-Lipa). HCV RNA quantity was determined in serum samples by use of polymerase chain reaction nested assay. HCV genotype 1 was detected in 13 patients and other genotypes in 9. Histological recurrence rates were 69% in patients with genotype 1 and 66% in patients with other genotypes. All cases of severe histological injury (chronic active hepatitis or cirrhosis) were observed in patients with genotype 1. HCV RNA quantity was significantly higher in patients with genotype 1 (mean, 2.023 x 10(3) copies/mL) than in patients with other genotypes (mean, 27,403 copies/mL). In conclusion, the severity of histological recurrence after liver transplantation for HCV disease was higher in patients infected by HCV genotype 1 than in those infected with other genotypes. The levels of viral replication were higher in patients with HCV genotype 1 than in those with other genotypes.

Les auteurs decrivent une methode originale de determination de la DL 50 des produits acaricides sur Varroa iacobsoni libre. Cette methode est appliquee a la determination de la DL 50 a 24 h de l'amitraze sous la forme d'Anti-varroa® (Schering) et du coumaphos sous la forme de Perizin® (Bayer). Les DL 50 a 24 h de l'amitraz et du coumaphos dans les conditions experimentales sont respectivement de 2,16 et 3,15 pg/varroa de principe actif. La DL 50 de l'Anti-varroa® (Schering) est de 17,3 pg/varroa, celle de Perizin® (Bayer) est de 98,4 pg/varroa. Les problemes techniques et le choix de specialites pharmaceutiques au lieu de molecules actives sont discutes

The specific aim of this study was to characterize human anti-Rh monoclonal antibodies cross-reacting with self-antigens. We studied supernatants from man-mouse hybridomas and from lymphoblastoid cell lines. Man-mouse hybridomas were established by fusion of peripheral blood lymphocytes from healthy individuals recently immunized against Rh alloantigens, with mouse myeloma (or man-mouse heteromyeloma) cell lines. Lymphoblastoid cell lines were produced by Epstein-Barr virus induction of lymphocytes from identical sources. Of the 55 monoclonal alloantibodies studied, 11 also reacted with intracellular self-antigens as demonstrated by immunofluorescence assay on cryostat sections of human tissues. This cross-reactivity was mainly a property of monoclonal alloantibodies belonging to the IgM isotype (among the 11 cross-reacting mAbs 10 were IgM). The cross-reactivities of these monoclonal antibodies were ascertained by absorption of alloreacting antibodies with red blood cells. Similar results were obtained on a panel of purified cellular antigens by ELISA. The results confirm that during an immune response against a foreign antigen (alloantigen), B cells that produce polyreactive antibodies are not excluded from the pool of responding cells. Therefore, polyreactive autoantibodies present in sera from healthy individuals may be the result of an immune response against foreign antigens.

Hepatitis C virus-specific in vitro antibody production (HCV IVAP) by peripheral blood lymphocytes in 53 HCV antibody-positive patients was investigated in comparison with alanine aminotransferase (ALT) levels and HCV RNA in serum samples. All 29 HCV IVAP-positive patients were HCV RNA positive; 26 had elevated ALT levels. Among the 24 HCV IVAP-negative patients, 16 were HCV RNA negative, with 12 presenting normal ALT values. These data indicate that HCV IVAP results are highly correlated (P < 0.001) with HCV RNA results and ALT levels. Our study indicates that HCV IVAP can be used as a novel assay in the diagnosis and pathogenesis exploration of HCV infection.

Authors describe another case of subcutaneous dirofilariasis due to Dirofilaria (Nochtiella) repens in France. A 26-year-old woman was infected while on vacation in Cap d'Agde on the Mediterranean coast. The patient presented with a subcutaneous nodule in the right subclavicular region. Examination of the nodule after surgical excision revealed the presence of a worm identified as an immature female Dirofilaria repens. Dirofilariasis is a rare anthroponotic disease encountered only in the Old World, particularly in Southeastern France including Corsica which has the second highest number of reported cases after Italy. Since man is a dead-end for the parasite, Dirofilaria repens does not mature and hence most human infections present as isolated subcutaneous nodules. Nodules are usually located in areas exposed to bites by the dipteres, i.e. the face (46 p. 100 of cases reported in the world) and the periocular and palpebral region (30 p. 100). Diagnosis is based mainly on morphological examination of the worm after surgical excision. However promising results in diagnosis of ocular and visceral forms of Dirofilaria repens and understanding of helminthiasis have been achieved thanks to progress in immunological techniques, i.e., ELISA and western blot, and DNA analysis based on polymerase chain reaction.

Distension of the rat intestine causes a capsaicin-sensitive, pressure-dependent depressor response which is indicative of nociception. A hypersensitivity of jejunal distension which possibly involves tachykinin NK2 receptors and is restricted to areas with mast cell hyperplagia is observed in rats infected 30 days previously with Nippostrongylus brasiliensis. This study aimed to further investigate the role of mast cells, tachykinins and kinins in this intestinal hypersensitivity. The activity of a mast cell stabilizer (doxantrazole), kinin antagonists (des-Arg 10-[Leu9]-kallidin, B1, HOE 140, B2) and tachykinin antagonists (CP 99, 994, NK1, SR 142801, NK3) were tested against the distension-induced depressor responses in control and post-infected rats. The 30-day post-infection-induced hypersensitivity was significantly reduced by the mast cell stabilizer doxantrazole. The hypersensitivity had resolved in 90-day post-infected rats when mast cells levels had normalized. Des-Arg 10-[Leu9]-kallidin and HOE 140 did not inhibit the depressor responses in controls but produced a significant inhibition in 30-day post-infected rats. CP 99,994 inhibited the depressor responses in post-infected rats with an equal potency to that in control rats. SR 142801 was inactive in both groups. In conclusion, mast cells and kinin-mediated nociception appear to be involved in post-infection intestinal hypersensitivity whereas tachykinin NK1 and NK3 receptors do not.

The efficacy of moxidectin 2% oral gel (Equest(R), Fort-Dodge) against European worm strains was studied through post-mortem worm counts and feacal egg counts (FECs) in 12 young ponies naturally infected. The animals were allocated in two groups of six ponies each: the first one was treated at 0.4 mg/kg b.w. and the second one received a placebo and served as control. All the ponies were necropsied 14 days post-treatment. The efficacy of moxidectin in reducing strongyle FECs ranged from 99.8% to 100% from 3 to 14 days after treatment. Moxidectin efficacy was 100% against Trichostrongylus axei and Triodontophorus spp., > 99.9% against Cyathostomes adults and L-5, 92% against S. edentatus L-5, 100% against O. equi L-5, 99% against O. equi L-4, and 92% against G. intestinalis. No animal treated with moxidectin was harbouring P. equorum, Habronema spp., G. pecorum nor G. nasalis, while the control group was slightly infected with these parasites. This experiment confirms the post-mortem worm count results obtained in the United States and the FECs results reported in Europe. Moxidectin showed to be safe in young ponies. (C) 1998 Elsevier Science B.V.

A cross sectional survey was carried out on a population of 82 rats (Rattus norvegicus and Rattus rattus alexandrinus) trapped in Marseille. The main histopathological finding was the presence of adults or eggs of Capillaria hepatica in 44% of the animals. 21% were found with fleas (Xenopsylla cheopis). There was no evidence of trichinosis in any of the rats examined. Hepatic capillariasis is a zoonosis seldom described in human beings. About 30 human cases have been reported in the world. Human infestation occurs first by consumption of raw rat liver containing un-embryonated eggs causing only pseudoparasitism without disease. The genuine mode of infestation is the consumption of sullied soil with rats feces containing embryonated eggs. Therefore parasites provoke, true as in rat inflammatory lesions, necrosis and fibrosis of the liver. The treatment associates antiparasitic drugs such as ivermectine, disophenol or pyrantel tartrate. The presence of a large population of infested synanthropic rats requires epidemiological monitoring and extermination of rats. All physicians must be informed of this potential risk.

SUMMARY To study the immunization induced by rHBsAg, we analysed the in vitro antibody production (IVAP) to HBsAg by PBMC from 18 subjects vaccinated by two injections on days 0 and 30. HBsAg-specific IVAP was detectable in all subjects after both the first and the second injection, and lasted for about 10 days and then disappeared. However, when the spontaneous HBsAg-specific IVAP became negative, HBsAg stimulation of PBMC cultures induced again a specific HBsAg IVAP. Cultures of cell populations separated by erythrocyte rosetting or Percoll density centrifugation showed that the cells responsible for spontaneous secretion, after in vivo stimulation, were low-density B lymphocytes. High-density B lymphocytes were involved in anti-HBs production induced by in vitro stimulation when spontaneous secretion disappeared. These data suggest that the IVAP test could be a source of important information along with serologic analysis for exploration of the immune response to hepatitis B vaccine.

A non randomized pilot study has been undertaken to evaluate the feasibility of local immunotherapy (IT) of recurrent glioblastoma multiforme (GM) by continuous intracerebral perfusion of recombinant interleukin-2 (rIL-2, Eurocetus) with and without lymphokine activated killer (LAK) cells. At time of surgical removal of the tumor, a catheter was implanted in the cavity left by tumor debulking allowing continuous perfusion of rIL-2. Five patients received 18 x 10(6) IU/day or rIL-2 for five days. At days 1, 3, and 5 after surgery, rIL-2 perfusion was briefly interrupted for the injection of LAK cells. Eight other patients received rIL-2 alone, either 24 x 10(6) IU/day (five patients) or 54 x 10(6) IU/day (three patients). Capillary leak syndrome, which is the main side effect of systemic infusion of rIL-2, was never observed, but local immunotherapy induced fever, confusion, and cerebral edema in all patients. Despite local IT, tumor progression was diagnosed by CT scan 4 to 12 weeks after the treatment.

Serum specimens from 25 individuals with an isolated human immunodeficiency virus type 1 (HIV-1) core antigen reactivity in a Western immunoblot test were examined for their reactivities with HIV-1 virions, control cellular antigens, HIV-1-Bru p24gag recombinant protein (p24gag), and a panel of 22 p24gag-derived peptides. The results were as follows: (i) serum specimens from eight HIV-1-uninfected subjects did bind to virions but failed to bind to p24gag; (ii) sera from 13 HIV-1-uninfected subjects and from one HIV-2-infected patient reacted with HIV-1 virions and p24gag but failed to bind to any of the peptides expressing major p24gag epitopes, and (iii) 3 serum specimens obtained from one neonate carrying anti-HIV-1 maternal antibody and from two HIV-1-infected subjects who had seroconverted during the study reacted with HIV-1 virions, p24gag, and one or more peptides containing the major p24gag epitopes. Our data suggest that the combination of p24gag and appropriate peptides could be useful for resolution when atypical Western immunoblot results are encountered.

In vivo half-life of a 125I-labeled human anti-D monoclonal antibody (mAb) and that of 131I-labeled Rho-GAM was assessed in a rhesus monkey injected simultaneously with both reagents. The half-life of the mAb was 7.9 days, compared to 17 days of Rho-GAM. Survival of the second dose of mAb, given 34 days after the first injection, was identical to that of the first dose, thus showing that the human mAb did not elicit an immune response. The in vitro produced human mAbs appear to be an alternative, unlimited source of anti-D antibodies for possible use in prevention of feto-maternal Rh immunization.

Introduction Le depistage systematique du VHC n’est pas recommande dans la population generale mais propose a des populations a risque [1]. Le but de notre etude etait de determiner les facteurs associes a la pratique du depistage du virus de l’hepatite C (VHC) chez les femmes jeunes. Patients et Methodes La population d’etude etait issue des 300 femmes enceintes ayant participe a l’etude ALHICE [1] realisee entre 1998 et 2002 dont le critere d’inclusion etait la presence d’une serologie VHC positive, connue ou pas avant leur participation. Le moment de la decouverte du VHC, les antecedents medicaux et les facteurs de risque lies a leur contamination ont ete recueillis par questionnaire realise en entretien. La population cible du depistage a ete identifiee selon les recommandations de l’ANAES (janvier 2001) qui regroupe les populations dites a risque eleve (prevalence VHC > 2 %) et celle a risque faible (prevalence VHC Resultats Le moment de la decouverte du VHC n’etant pas renseigne pour 3 femmes, l’analyse a ete menee chez 297 femmes. Parmi elles, 224 (75 %) avaient ete diagnostiquees avant l’etude ALHICE ; 279 (94 %) presentaient un des criteres definis dans les recommandations (population globale cible), 203 (68 %) appartenaient au groupe de risque eleve et 76 au groupe a risque faible. Parmi les 279 femmes de la population globale cible, 68 (24 %) n’avaient pas ete diagnostiquees avant leur entree dans l’etude. Chez les 18 (6 %) femmes ne reunissant pas un des criteres de depistage, 5 (28 %) ont decouvert leur seropositivite au moment de leur participation a l’etude. Le depistage du VHC avant la grossesse etait significativement associe a un antecedent d’usage de drogues (62 % versus 28 %, p Conclusion Pour ameliorer le depistage du VHC chez la population de femmes jeunes, les efforts devraient etre concentres vers les femmes nees dans une des zones a risque (Afrique, Amerique du Sud, Asie du Sud-Est, Moyen-Orient) ainsi que vers celles en situation de precarite. Remerciements, financements, autres Etude financee par l’ANRS et la Fondation de France.

SUMMARYWe studied the spontaneous in vitro secretion of anti-HIV-1 antibodies by peripheral blood mononuclear cells (PBMC) from HIV-1-infected patients. Specific antibody production was detected in supernatants of PBMC cultures using an ELISA; HIV-1 specificity was confirmed by antigen adsorption and Western blotting. This antibody secretion was found to be an active phenomenon and was not due to a release of plasma antibodies passively adsorbed onto the cell membranes. In all positive supernatants, anti-HIV-1-secreted antibodies were directed against enu-encoded antigens and many supernatants also contained antibodies to pol- and gag-encoded antigens. PBMC from all HIV-1-infected patients tested (140 adults and 18 infants) secreted anti-HIV-1 antibodies. This production was found during all the clinical stages of HIV-1 infection. Our results suggest that this spontaneous HIV-1-specific antibody secretion represents a marker of HIV-1 infection. Detection of these antibodies could be a valuable tool for early confirmation of HIV-1 infection in neonates born to HIV-1-seropositive mothers.

In vitro secretion of antibodies to cytomegalovirus was investigated by analysis of peripheral blood mononuclear cell culture supernatants from subjects infected with cytomegalovirus. Patients with primary or recurrent cytomegalovirus infection showed transient in vitro cytomegalovirus-specific antibody secretion. A high proportion of patients infected with human immunodeficiency virus and sero-positive for cytomegalovirus showed in vitro cytomegalovirus-specific antibody secretion. All peripheral blood mononuclear cell cultures from patients with symptomatic human immunodeficiency virus infection were found to secrete in vitro antibodies to cytomegalovirus, despite the fact that isolation of cytomegalovirus from some of these patients was not achieved. In human immunodeficiency virus-infected patients, in vitro secretion of anti-cytomegalovirus antibodies appeared to be persistent. In vitro cytomegalovirus-specific antibody secretion by peripheral blood lymphocytes probably reflects an in vitro cytomegalovirus-specific B cell activation. This new assay could be considered an interesting method for detecting both acute or chronic cytomegalovirus infection, with potential use in routine laboratory practice.

Le genotype 5 est rare; il represente 1,5 % de tous les cas d’hepatite C. La transfusion est le principal mode de contamination. L’evolution fibrosante parait relativement lente. La reponse soutenue sous bitherapie pegylee est interessante car obtenue chez les 2/3 patients.

In the study of stored serum from 35 transfused open heart surgery patients with post transfusion hepatitis we conclude : the high incidence of the HCV conversion (77 %), elevated frequency of chronic post transfusion hepatitis evolutivity, the limited sensibility of the antiVCH test (Ortho — Elisa), better prognostic of seronegative antiHCV hepatitis.

The authors report a family in which the father is Ax, the mother B, the paternal grandmother Ax; 3 children out of 6 are A2B and the other three Ax. One of A2B children is married to an O subject, and she had a son of phenotype Ax. It was observed that Ax gene in position trans of a B gene behaves phenotypically as an A2.

Summary The authors have studied in particular hepatitis B virus markers and the ratio of OKT4+/OKT8+ cells in two subgroups of 52 deprived asymptomatic drug addicts. In the group 1 (deprived for 19 days on an average), 52% of the subjects showed a ratio of OKT4+/OKT8+ HBV markers were present in 90% of the subjects in each group. We would like to point out the high frequency of the anti-HBc positivity without other markers in these two groups, respectively 20% in the group 1 and 32% in the group 2. These results emphasize the interest in screening systematically this marker in all blood donors.

The Basques were previously shown to present a high frequency of HLA-B18 and BfF1, which are known to be associated with insulin dependent diabetes mellitus (IDDM). During the VIII International Histocompatibility Workshop, we studied HLA-A, B, C, DR; Bf, C4 and GLO.I polymorphisms in 51 unrelated French Basque IDDM patients and in 50 controls. Haplotypes were established by family studies in all controls and some patients. Two haplotypes were frequently found in the controls: HLA-A1, Bw57, BfS, C4 F1S, DR7 and HLA-Aw30, Cw5, B18, Bf F1, C4Fs degree, DR3. The first one was not found in the patients. All the components of the second haplotype had increased frequencies possibly as a consequence of linkage disequilibrium with HLA-DR3: a highly significant association between IDDM and HLA-DR3 was observed (90.2% vs 24.0%, relative risk (RR) = 29.1, P less than 10(-11)). The HLA-DR4 frequency was slightly increased (37.3% vs 16.0%), and HLA-DR2 was not found. The silent allele C4s degree was particularly associated with early diagnosed IDDM (86.7% in patients with age at onset under 20 years vs 57.1% in other patients, P less than 0.02). The high relative risk for HLA-DR3/DR4 heterozygous vs that of individuals, possibly HLA-DR3 homozygous, supported the hypothesis that two HLA-DR linked genetic factors could be involved in the inheritance of IDDM susceptibility.

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Summary Since its creation by Doctor Matte , the Groupamatic concept had been chosen by the Blood Center of Toulouse in order to enable blood typing on the continuously growing number of blood donors. The complete system suggested by the manufacturer presented a serious point of restraint : the use of relatively static and preestablished blood typing logics. We adopted a compromise solution : developing a specific software for the processing of Groupamatic data on our PDP 12 computer which directly controls the electromechanical unit. The various phases of blood group determination of blood donors and of result validation are presented: 1. Control of the electromechanical unit by the PDP 12 : -- First run of samples on Groupamatic : First ABO Rh blood typing with a logic which does not recognize the A subgroups. Memorization of results. -- Second run of samples on Groupamatic. Second ABO Rh blood typing including A1 A2 typing and weak A typing. Memorization of results. 2. Further processing of results : -- Delayed validation of ABO Rh groups ; -- Print out of validated results only of self adhesive labels for the blood units ; -- Print out of documents used by the Laboratory of Erythrocyte Immunology.

We report here the experience of 3 years of irregular antibody automated screening with Groupamatic, that is to say of 661,511 samples tested in Paris and 269, 162 samples tested in Toulouse. The positive reactions in Paris were 16,296 (2.46%) out of which 2,021 irregular antibodies were identified (0.30%). The positive reactions in Toulouse were 8,266 (3.07%) out of which 2,138 irregular antibodies were identified (0,79%). The difference between the number of screened positive reactions and the identified one is due to false positive reactions (half of the cases) and to autoantibodies whose number is roughly the same than the number of identified alloantibodies. During the years 1970, 1971 and 1972, the irregular antibodies were systematically screened in Toulouse on all blood donors with a manual technique on opaline plate using enzyme treated red cell tests (papain). 7,147 positive reactions were detected, out of 240,080 tests (2.98%). 1,954 (0,81%) were alloantibodies and 1,529 (0.64%) autoantibodies; 3.455 were false positive reactions and 209 were non identified antibodies. These figures are superimposed with those obtained with Groupamatic during the following years, thus pointing out the interest of this equipment.

Resume La constatation de discordances dans l'agglutination de certains sujets avec divers anticorps anti-C et anti-CD a ete le point de depart d'une experimentation effectuee sur les donneurs de sang et les malades examines au Centre de Transfusion Sanguine de Toulouse. On a pu demontrer que les sujets porteurs du chromosome Cde associe a cdE etaient agglutines par tous les serums anti-C et anti-CD alors que les sujets CdE n'etaient agglutines que par certains d'entre eux dans les conditions normales. Par contre, ils etaient agglutines par tous apres papainisation ou en utilisant le test de Coombs indirect. Ceci souligne la grande heterogeneite des reactifs anti-C qui sont en realite des melanges de plusieurs types d'anticorps et en particulier d'anti-C et d'anti-Ce. La meconnaissance de ces notions peut entrainer des erreurs dans la determination des phenotypes Rh.

Resume Les auteurs comparent les diverses methodes actuelles de depistage des anticorps d'histocompatibilite. Leur experience porte sur pres de 2000 titrages. La leuco-agglutination sur sang preleve sur sequestrene est la methode qui permet d'obtenir le plus grand nombre de resultats positifs. Chez les polytransfuses, il parait necessaire d'associer plusieurs methodes.

Resume Les auteurs decrivent leur technique personnelle de realisation du test de transformation blastique. Ils insistent sur certaines modalites ou precautions a observer. Ils rapportent ensuite leurs resultats, d'une part dans la recherche de l'allergie medicamenteuse, d'autre part dans celle de l'allergie microbienne (antigene M du streptocoque). Leur interpretation est discutee, ainsi que les correlations entre les resultats du laboratoire et la clinique. Ils soulignent en terminant l'interet que revet la realisation du test de transformation blastique en routine et en recherche.