Tratamiento del Linfoma Difuso de Célula Grande B en la era Rituximab: Experiencia de un Centro.

Hemos analizado la supervivencia global (SG) y el tiempo libre de enfermedad (TLE) de los pacientes afectos de un linfoma difuso de célula grande en la era Rituximab. Describimos los resultados de los que recibieron un trasplante alogénico (aloTPH) en los últimos 13 años. La supervivencia global (SG) en los tratados con Rituximab fue de 59% y el tiempo libre de enfermedad (TLE) de 54%. La supervivencia por IPI fue de IPI bajo=82%, intermedio-bajo=54%, intermedio-alto=51%, alto=33%. En el trasplante autólogo la SG fue de 65% y con TLE 54%. La SG para los que recibieron un aloTPH fue de 49% a los 78 meses.

CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation.

CARMA1 is a lymphocyte-specific member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, which coordinate signaling pathways emanating from the plasma membrane. CARMA1 interacts with Bcl10 via its caspase-recruitment domain (CARD). Here we investigated the role of CARMA1 in T cell activation and found that T cell receptor (TCR) stimulation induced a physical association of CARMA1 with the TCR and Bcl10. We found that CARMA1 was constitutively associated with lipid rafts, whereas cytoplasmic Bcl10 translocated into lipid rafts upon TCR engagement. A CARMA1 mutant, defective for Bcl10 binding, had a dominant-negative (DN) effect on TCR-induced NF-kappa B activation and IL-2 production and on the c-Jun NH(2)-terminal kinase (Jnk) pathway when the TCR was coengaged with CD28. Together, our data show that CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation and CD28 costimulation-dependent Jnk activation.

Detection of Hepatitis B Virus Antigens in Paraffin-embedded Liver Specimens from the Amazon Region, Brazil

Hepatic viscerotomy of paraffin-preserved old specimens, collected in the period from 1934 to 1967, were analyzed by immunohistochemical assays to detect hepatitis B, hepatitis D, dengue and yellow fever virus antigens. The material belongs to the Yellow Fever Collection, Department of Pathology, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil and the cases were diagnosed at that time according to clinical aspects and histopathological findings reporting viral hepatitis, yellow fever, focal necrosis and hepatic atrophy. From the 79 specimens, 69 were collected at the Labrea Region and the other 10 in different other localities in the Amazon Region. The five micra thick histological slices were analyzed for the presence of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) by immunoperoxidase technique. An immunofluorescence assay was applied to the detection of hepatitis D, yellow fever and dengue virus antigens. Nine (11.4%) histological samples were HBsAg reactive and 5 (6.3%) were HBcAg reactive. The oldest reactive sample was from 1934. Viral antigens related to the other pathologies were not detected in this study. Our results confirm that the methodology described may be used to elucidate the aetiology of hepatitis diseases even after a long time of conservation of the specimens.

Relation between Hepatitis B Carrier Status and Antibody against Synthetic Plasmodium falciparum Erythrocyte Surface (pf155 - RESA) Antigen

A survey on Plasmodium infection was carried out in gold mine camps located in the Brazilian Amazon. Antibody against P. falciparum ring-infected erythrocyte surface antigen (RESA) was quantified by an enzyme-immunoassay in order to assess P. falciparum exposure. Hepatitis B, a common infection in this area, was also investigated by serologic markers. Among 520 sampled subjects, 517 (99.4%) admitted previous symptomatic malaria, 106 (20.4%) had positive thick smears for malaria, 82.9% had HBV markers, and 7.1% were HBsAg positive. Anti-RESA titers was significantly lower in HBV carriers than in people with resolved HBV infection suggesting that the anti-RESA immune response could be supressed by HBV carrier status. Moreover, immunedeficient responses to both infections may take place in some subjects causing concomitant lower anti-RESA response and incapacity to clear HBV.

Tractament amb EPOCH a dosi ajustada i Rituximab en pacients no tractats amb LNH-B de cèl.lula gran de mal pronòstic

Aquest estudi multicèntric, fase IV analitza l’eficàcia i la seguretat del tractament amb dosi ajustada d’EPOCH amb Rituximab en infusió continua, en pacients no tractats prèviament amb mal pronòstic diagnosticats de limfomes B de cèl.lula gran. Material i mètodes. S’inclogueren 81 pacients, 68 d’aquests diagnosticats de Limfoma B difús de cèl.lula gran, 7 de Limfoma fol.licular grau III i 6 de Limfoma B primari de mediastí. Eren pacients de mal pronòstic segons IPI≥2 o IPIae≥1, ECOG/PS 0-4, estadi II-IV (estadi I si malaltia voluminosa al diagnòstic). Resultats. La edat mitjana era de 52 anys (rang, 21-77 anys), 92,5% d’alt risc segons l’IPIae. Es va obtenir resposta completa (RC i RCi) en el 79% dels pacients, la supervivència global i la supervivència lliure d’esdeveniment, a la mediana del temps de seguiment (34,3 mesos) va ser de 68% i 63,2%, respectivament. La supervivència lliure de malaltia als 5 anys va ser de 72,2% pels pacients que van assolir RC/RCi. Cap dels factors de risc de l’IPI o IPIae, ni els índexs per ells mateixos van resultar amb associació estadísticament significativa a la OS o PFS. Només es va obtenir associació entre els nivells de ß2 microglobulina (&3,5mg/l) i la PFS i OS (p=0,075 i p=0,015, respectivament). Es van reportar 54 episodis de neutropènia febril (11,5% dels cicles); i es van morir 27 pacients, 15 (55,5%) degut a progressió de la malaltia i 9 (33,3%) degut a sepsi o infecció grau 4. Conclusions. Els resultats aconseguits amb la combinació de Rituximab i DA-EPOCH mostren uns resultats prometedors i amb nivells de toxicitat molt acceptables en els pacients d’alt risc diagnosticats de Limfomes B de cèl.lula gran no tractats prèviament.

Isolation and Identification of 9-methylgermacrene-B as the Putative Sex Pheromone of Lutzomyia cruzi (Mangabeira, 1938) (Diptera: Psychodidae)

Lutzomyia (Lutzomyia) cruzi has been named as a probable vector of Leishmania chagasi in Corumbá, Mato Grosso do Sul, Brazil. Taxonomically L. cruzi is closely related to the L. longipalpis species complex. Females of L. cruzi and L. longipalpis are morphologically indistinguishable and associated males must be examined carefully to confirm identifications. Chemical analysis hexane extracts of male L. cruzi has revealed the presence of a 9-methylgermacrene-B (C16), a homosesquiterpene (mw 218) previously shown to be the sex pheromone of one of the members of the L. longipalpis species complex.

Longitudinal Study on the Natural Infection of Biomphalaria straminea and B. glabrata by Schistosoma mansoni in an Endemic Area of Schistosomiasis in Pernambuco, Brazil

The abundance of snail hosts and the rates of infection with Schistosoma mansoni were monitored monthly for four years in two representative localities subjected to repeated chemotherapy of infected persons. Snail abundance varied from 1.0 to 4.4 collected per person/minute/station for Biomphalaria straminea and from 0.1 to 7.0 for B. glabrata. Infection rates of snails in nature varied from 0% to 15% for the former and from 0% to 70% for the latter species. Human infection increased from 35.5% to 61.9% in the locality occupied by B. straminea, and decreased from 40.3% to 20.8% in that occupied by B. glabrata. No relationship could be detected between human infection and the snail variables. Despite seasonal variations, natural infection persisted throughout the monitoring period in both snail species. It reached remarkably high levels in B. straminea when compared to those obtained by other authors probably because of differences in methodology. It is recommended that longitudinal studies should be carried out focally and periodically to avoid underestimating the prevalence of schistosome infection in snails.

The changing preference of T and B cells for partners as T-dependent antibody responses develop.

Recirculating virgin CD4+ T cells spend their life migrating between the T zones of secondary lymphoid tissues where they screen the surface of interdigitating dendritic cells. T-cell priming starts when processed peptides or superantigen associated with class II MHC molecules are recognised. Those primed T cells that remain within the lymphoid tissue move to the outer T zone, where they interact with B cells that have taken up and processed antigen. Cognate interaction between these cells initiates immunoglobulin (Ig) class switch-recombination and proliferation of both B and T cells; much of this growth occurs outside the T zones B cells migrate to follicles, where they form germinal centres, and to extrafollicular sites of B-cell growth, where they differentiate into mainly short-lived plasma cells. T cells do not move to the extrafollicular foci, but to the follicles; there they proliferate and are subsequently involved in the selection of B cells that have mutated their Ig variable-region genes. During primary antibody responses T-cell proliferation in follicles produces many times the peak number of T cells found in that site: a substantial proportion of the CD4+ memory T-cell pool may originate from growth in follicles.

Hepatitis C and hepatitis B virus infection in different hemodialysis units in Belo Horizonte, Minas Gerais, Brazil

The prevalence, virological and epidemilogical aspects of the hepatitis C virus (HCV) and the hepatitis B virus (HBV) infections vary among hemodialysis patients in different countries. Aiming at analyzing these aspects of HCV and HBV infections in hemodialysis patients in Belo Horizonte, MG, Brazil, we studied three hemodialysis units including 434 patients. Serology was used to detect anti-HCV and HBsAg. Reverse trancriptase nested polymerase chain reaction (RT-nested-PCR) of the 5'-noncoding region was used to detect circulating HCV RNA and restriction fragment length polymorphism analysis for genotyping. Seroprevalence varied from 26.5% to 11.1% for hepatitis C and from 5.9% to 0% for hepatitis B. Risk factors observed for HBV and/or HCV infections were the number of patients per dialysis unit, duration of treatment, number of clinics attended, number of blood units transfused, and lower level scholarity. Alanine aminotransferase levels were altered with a higher frequency in HBV or HCV seropositive patients. Half of ten patients, negative for anti-HCV, had detectable viremia by RT-nested-PCR, indicating that this technique should be used to confirm infections in this group of patients. The HCV genotype 1 was the most frequently observed, followed by the genotype 2, but no correlation was detected between genotype and clinical or epidemiological data.

B-cell infiltration and frequency of cytokine producing cells differ between localized and disseminated human cutaneous leishmaniases

Biopsies from human localized cutaneous lesions (LCL n = 7) or disseminated lesions (DL n = 8) cases were characterized according to cellular infiltration,frequency of cytokine (IFN-<FONT FACE=Symbol>gfont>, TNF-alpha) or iNOS enzyme producing cells. LCL, the most usual form of the disease with usually one or two lesions, exhibits extensive tissue damage. DL is a rare form with widespread lesions throughout the body; exhibiting poor parasite containment but less tissue damage. We demonstrated that LCL lesions exhibit higher frequency of B lymphocytes and a higher intensity of IFN-gamma expression. In both forms of the disease CD8+ were found in higher frequency than CD4+ T cells. Frequency of TNF-alpha and iNOS producing cells, as well as the frequency of CD68+ macrophages, did not differ between LCL and DL. Our findings reinforce the link between an efficient control of parasite and tissue damage, implicating higher frequency of IFN-gamma producing cells, as well as its possible counteraction by infiltrated B cells and hence possible humoral immune response in situ.

Seroprevalence of Hepatitis B virus infection among an afro-descendant community in Brazil

Furnas dos Dionísios is an Afro-Brazilian black community whose descendants were mainly fugitive slaves that established themselves in the State of Mato Grosso do Sul (MS), Brazil. The population is comprised mainly of low socioeconomic individuals who are engaged in agricultural activities. The objective of this study was to investigate the prevalence of hepatitis B (HB) and its correlation with epidemiological data obtained from the community. The studied population totaled 260 individuals with ages varying from 1 to 79 years (median 20). One hundred thirty-three (51.2%) were females and 127 (48.8%) were males. A high prevalence for anti-HBc was observed (42.7%), with present infection detected in 9.2% of the subjects who were also HB surface antigens (HBs Ag) positive; 27.3% were anti-HBc and anti-HBs reactive, and 6.2% had anti-HBc as only marker. The prevalence for anti-HBc was proportional to age, reaching its highest peak in age categories greater than 50. No serological marker was detected in children under the age of 2 years, however anti-HBc was present in 12 subjects with ages between 2 and 14 years, of these 8 (7.4%) were HBsAg positive. Among individuals over the age of 15 years, 99 were anti-HBc reactive, of these 16 (10.5%) were also HBsAg positive, thus suggesting an increased prevalence of HBV carriers among children and adolescents. The risk factors observed in this community that were significantly associated with anti-HBc positivity were age (over 20 years) and having an anti-HBc positive mother. Both HBeAg and anti-HBe were detected in 44.4% of the samples tested. HBsAg subtypes found in the studied population were adw2 (77.7%) and ayw2 (23.3%). While intrafamilial transmission was most likely responsible for HBV infection among children, other routes such as sexual contact might be considered for individuals with ages over 15 years.

Supplementary Report of the HIA to the Minister for Health, in accordance with Section 7E(1)(b) of the Health Insurance Acts, 1994-2009 (Redacted Version)

The purpose of this Supplementary Report is to advise on how the budgetary measures impact on the conclusions in relation to tax credits and stamp duty included in the Authority’s November 2011 Report. in doing so, we will assess the direct impacts and we will discuss some scenarios. However, the Authority’s advice in this area relies on projections of the health insurance market and, in light of the above, there is considerable uncertainty surrounding any projections of how claims inflation or the market size may develop, even in the short and medium terms. Supplementary Report of the HIA to the Minister for Health, in accordance with Section 7E(1)(b) of the Health Insurance Acts, 1994-2009 (Redacted Version) Click here to download PDF 3.2mb

Report of the HIA to the Minister for Health, in accordance with Section 7E(1)(b) of the Health Insurance Acts, 1994-2009 (Redacted Version)

The Authority has been asked by the Minister for Health to prepare a Report under Section 7E (1) (b) of the Health Insurance Acts 1994-2009 (“the Health Insurance Acts”). For the purposes of the legislation, the relevant period is 1 July 2010 to 30 June 2011. The basis of the Report is specified in the legislation   Click here to download PDF 7.3mb Click here to download the supplementary document PDF 3.2mb

Report of the Expert Group on the Judgment in A, B and C V Ireland

In December 2009 the European Court of Human Rights (ECtHR) heard a case brought by three women in respect of the alleged breach of their rights under the European Convention for the Protection of Human Rights and Fundamental Freedoms (the Convention) in regard to abortion in Ireland (the A, B and C v Ireland case).   Click here to download PDF 929kb