Liver transplantation as a therapeutic option for hepatocellular carcinoma

Better outcomes of the patients receiving liver transplantation for viral hepatitis and hepatocellular carcinoma (HCC) are achieved by improved patient selection and perioperative treatment with antiviral agents including lamivudine, ribavirin and interferon. Patient selection is accomplished by high-quality imaging as well as exclusion of patients with large tumors, obvious extrahepatic disease or macroscopic vascular invasion. Using such criteria, a 5-year survival of 92% has been reached in the Queensland Liver Transplant Service on a small number of highly selected patients with HCC. The treatment algorithm of Makuuchi has guided us in recommending resection, estimating to what extent the liver resection can be performed safely, and timing liver transplantation when it is the only option. Adult-to-adult living-donor liver transplantation is being performed safely in many centers worldwide. The transplantation of liver from living donors to HCC patients, when standard criteria for the likelihood of good outcomes are fulfilled, will increase in Japan in the near future. Copyright (C) 2002 S. Karger AG, Basel.

Treatment of non-resectable hepatocellular carcinoma with autologous tumor-pulsed dendritic cells

Background: The response of hepatocellular carcinoma (HCC) to therapy is often disappointing and new modalities of treatment are clearly needed. Active immunotherapy based on the injection of autologous dendritic cells (DC) co-cultured ex vivo with tumor antigens has been used in pilot studies in various malignancies such as melanoma and lymphoma with encouraging results. Methods: In the present paper, the preparation and exposure of patient DC to autologous HCC antigens and re-injection in an attempt to elicit antitumor immune responses are described. Results: Therapy was given to two patients, one with hepatitis C and one with hepatitis B, who had large, multiple HCC and for whom no other therapy was available. No significant side-effects were observed. The clinical course was unchanged in one patient, who died a few months later. The other patient, whose initial prognosis was considered poor, is still alive and well more than 3 years later with evidence of slowing of tumor growth based on organ imaging. Conclusions: It is concluded that HCC may be a malignancy worthy of DC trials and sufficient details in the present paper are given for the protocol to be copied or modified. (C) 2002 Blackwell Publishing Asia Pty Ltd.

In vivo and in vitro models demonstrate a role for caveolin-1 in the pathogenesis of ischaemic acute renal failure

Caveolae and their proteins, the caveolins, transport macromolecules; compartmentalize signalling molecules; and are involved in various repair processes. There is little information regarding their role in the pathogenesis of significant renal syndromes such as acute renal failure (ARF). In this study, an in vivo rat model of 30 min bilateral renal ischaemia followed by reperfusion times from 4 h to 1 week was used to map the temporal and spatial association between caveolin-1 and tubular epithelial damage (desquamation, apoptosis, necrosis). An in vitro model of ischaemic ARF was also studied, where cultured renal tubular epithelial cells or arterial endothelial cells were subjected to injury initiators modelled on ischaemia-reperfusion (hypoxia, serum deprivation, free radical damage or hypoxia-hyperoxia). Expression of caveolin proteins was investigated using immunohistochemistry, immunoelectron microscopy, and immunoblots of whole cell, membrane or cytosol protein extracts. In vivo, healthy kidney had abundant caveolin-1 in vascular endothelial cells and also some expression in membrane surfaces of distal tubular epithelium. In the kidneys of ARF animals, punctate cytoplasmic localization of caveolin-1 was identified, with high intensity expression in injured proximal tubules that were losing basement membrane adhesion or were apoptotic, 24 h to 4 days after ischaemia-reperfusion. Western immunoblots indicated a marked increase in caveolin-1 expression in the cortex where some proximal tubular injury was located. In vitro, the main treatment-induced change in both cell types was translocation of caveolin-1 from the original plasma membrane site into membrane-associated sites in the cytoplasm. Overall, expression levels did not alter for whole cell extracts and the protein remained membrane-bound, as indicated by cell fractionation analyses. Caveolin-1 was also found to localize intensely within apoptotic cells. The results are indicative of a role for caveolin-1 in ARF-induced renal injury. Whether it functions for cell repair or death remains to be elucidated. Copyright (C) 2003 John Wiley Sons, Ltd.

Avalia����o do programa de alimenta����o do trabalhador, no Estado de Pernambuco, Brasil

Foi avaliado o Programa de Alimenta����o do Trabalhador (PAT), no que se refere a implanta����o, funcionamento e resultados em empresas, no Estado de Pernambuco, Brasil. O universo pesquisado abrangeu um total de 130 empresas, sendo 85 inscritas no PAT entre 1977 e 1980 e 45 n��o inscritas. Neste grupo, a coleta de dados limitou-se ao ano de 1980 e teve como finalidade o estabelecimento de par��metros para avaliar os indicadores de impacto do Programa. A an��lise dos card��pios sugere que um reduzido percentual de empresas fornece refei����es conforme as exig��ncias m��nimas de energia e prote��na estabelecidas pela Lei 6.321/76, isto ��, um m��nimo de 1.400 cal e NDpCal% superior a 6. O exame dos indicadores de impacto nas empresas dos dois grupos sugere que o PAT n��o modificou o n��mero de acidentes de trabalho, condi����es de sa��de e rotatividade dos trabalhadores; tendo apenas influ��do no absente��smo.

Body composition, muscle strength, functional capacity, and physical disability risk in liver transplanted familial amyloidotic polyneuropathy patients

Abstract: Background: Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disease leading to sensory and motor polyneuropathies, and functional limitations. Liver transplantation is the only treatment for FAP, requiring medication that negatively affects bone and muscle metabolism. The aim of this study was to compare body composition, levels of specific strength, level of physical disability risk, and functional capacity of transplanted FAP patients (FAPTx) with a group of healthy individuals (CON). Methods: A group of patients with 48 FAPTx (28 men, 20 women) was compared with 24 CON individuals (14 men, 10 women). Body composition was assessed by dual-energy X-ray absorptiometry, and total skeletal muscle mass (TBSMM) and skeletal muscle index (SMI) were calculated. Handgrip strength was measured for both hands as was isometric strength of quadriceps. Muscle quality (MQ) was ascertained by the ratio of strength to muscle mass. Functional capacity was assessed by the six-minute walk test. Results: Patients with FAPTx had significantly lower functional capacity, weight, body mass index, total fat mass, TBSMM, SMI, lean mass, muscle strength, MQ, and bone mineral density. Conclusion: Patients with FAPTx appear to be at particularly high risk of functional disability, suggesting an important role for an early and appropriately designed rehabilitation program.

A case-control study on the association of hepatitis B virus infection and hepatocellular carcinoma in Northeast Brazil

Hepatitis B virus (HBV) serological markers were investigated in 40 incident cases of hepatocellular carcinoma (HCC) and in two age and sex matched control groups, comprising 40 patients with other cancers and 80 healthy individuals, resident in Bahia, Brazil. Serologic tests were done by radioimmunoassay. The study observed high proportion of seropositivity to HBsAg (42.5%) and of those presenting HBsAg or antiHBc (65.0%) among HCC cases, higher in men than women and in those aged 17 to 30 years old. HBsAg seropositivity among HCC patients was greater than in the control group with other cancers (7.5%) and in healthy controls (2.5%), corresponding to odds ratio estimates of 15.0 (95% CI 3.29, 68.30) and 33.0 (95% CI 9.13, 119.28), both statistically significant. HBeAg was not observed and antiHBe was present in 41.2% of cases, suggesting the absence of viral replication, possibly with viral DNA intergration into the hepatocyte genome. The presence of cirrhosis was associated with HBsAg seropositivity among HCC cases. A history of chronic alcoholism is shown to be more frequently related to those cases with cirrhosis. This study highlights the relevant association between HCC and HBV in Northeast Brazil, particularly for young individuals, and the high risk of development of HCC for HBsAg carriers.

Surto alimentar por Salmonella Enteritidis no Noroeste do Estado de S��o Paulo, Brasil

Em 1993 ocorreu um surto alimentar em escola, com 211 afetados. Os dados epidemiol��gicos levantados por entrevista de amostragem de afetados e n��o afetados mostraram que os sintomas predominantes foram diarr��ia, febre (77,7%), dor abdominal (67,7%), v��mito (65,8%), calafrios (54,5%) e cefal��ia (44,5%). A mediana de incuba����o foi de 17 horas, com limites entre 3 e 29 horas. A dura����o da doen��a foi de 3 a 4 dias. O alimento consumido foi um tipo de pat��, mistura de molho de maionese preparada com ovos crus com batata cozida, passado em p��o. A an��lise de material biol��gico (3 coproculturas) e de restos de alimentos revelou a presen��a do mesmo microrganismo, a Salmonella Enteritidis. No caso dos alimentos, o n��mero encontrado desta bact��ria por gramo de produto era compat��vel com a quantidade de c��lulas necess��ria para desencadear a doen��a (10(4)e 10(5)/g). O antibiograma de todas as cepas isoladas revelou o mesmo padr��o de sensibilidade. As falhas no preparo do alimento relacionadas com o levantamento indicam a possibilidade de contamina����o end��gena dos ovos; contamina����o cruzada - o surto afetou tr��s per��odos escolares, sendo que para cada um o alimento foi preparado em separado - e as condi����es de manuten����o do alimento ap��s preparo e at�� o consumo. A observa����o por uma semana seguida das 3 merendeiras envolvidas, atrav��s de coprocultura, n��o indicaram que as mesmas fossem portadoras assintom��ticas desta bact��ria ou que tivessem sido envolvidas no surto em quest��o.

Novel method using a laser scanning cytometer for detection of Mycobacteria in clinical samples

In order to evaluate the capacity of laser scanning cytometry (LSC) to detect acid-fast bacilli directly on clinical samples, a comparison between Kinyoun-stained smears analyzed under light microscopy and propidium iodide-auramine-stained smears analyzed by LSC was performed. The results were compared with those for culture on BACTEC MGIT 960. LSC is a new, reliable methodology to detect Mycobacteria.

Grupos de simetria: identifica����o de padr��es no patrim��nio a��oriano

Disserta����o de Mestrado, Matem��tica para Professores, 3 de Abril de 2014, Universidade dos A��ores.

Differential expression of the eukaryotic release factor 3 (eRF3/GSPT1) according to gastric cancer histological types

Background: There are now several lines of evidence to suggest that protein synthesis and translation factors are involved in the regulation of cell proliferation and cancer development. Aims: To investigate gene expression patterns of eukaryotic releasing factor 3 (eRF3) in gastric cancer. Methods: RNA was prepared from 25 gastric tumour biopsies and adjacent non-neoplastic mucosa. Real time TaqMan reverse transcription polymerase chain reaction (RT-PCR) was performed to measure the relative gene expression levels. DNA was isolated from tumour and normal tissues and gene dosage was determined by a quantitative real time PCR using SYBR Green dye. Results: Different histological types of gastric tumours were analysed and nine of the 25 tumours revealed eRF3/GSPT1 overexpression; moreover, eight of the 12 intestinal type carcinomas analysed overexpressed the gene, whereas eRF3/GSPT1 was overexpressed in only one of the 10 diffuse type carcinomas (Kruskal-Wallis Test; p , 0.05). No correlation was found between ploidy and transcript expression levels of eRF3/GSPT1. Overexpression of eRF3/GSPT1 was not associated with increased translation rates because the upregulation of eRF3/GSPT1 did not correlate with increased eRF1 levels. Conclusions: Overexpression of eRF3/GSPT1 in intestinal type gastric tumours may lead to an increase in the translation efficiency of specific oncogenic transcripts. Alternatively, eRF3/GSPT1 may be involved in tumorigenesis as a result of its non-translational roles, namely (dis)regulating the cell cycle, apoptosis, or transcription.

Translation termination and protein folding pathway genes are not correlated in gastric cancer

Background: The eukaryotic release factor 3 (eRF3) has been shown to affect both tubulin and actin cytoskeleton, suggesting a role in cytoskeleton assembly, mitotic spindle formation and chromosome segregation. Also, direct interactions between eRF3 and subunits of the cytosolic chaperonin CCT have been described. Moreover, both eRF3a and CCT subunits have been described to be up-regulated in cancer tissues. Our aim was to evaluate the hypothesis that eRF3 expression levels are correlated with the expression of genes encoding proteins involved in the tubulin folding pathways. Methods: Relative expression levels of eRF1, eRF3a/GSPT1, PFDN4, CCT2, CCT4, and TBCA genes in tumour samples relative to their adjacent normal tissues were investigated using real time-polymerase chain reaction in 20 gastric cancer patients. Results: The expression levels of eRF3a/GSPT1 were not correlated with the expression levels of the other genes studied. However, significant correlations were detected between the other genes, both within intestinal and diffuse type tumours. Conclusions: eRF3a/GSPT1 expression at the mRNA level is independent from both cell translation rates and from the expression of the genes involved in tubulin-folding pathways. The differences in the patterns of expression of the genes studied support the hypothesis of genetically independent pathways in the origin of intestinal and diffuse type gastric tumours.

Fat intake interacts with polymorphisms of Caspase9, FasLigand and PPARgamma apoptotic genes in modulating Crohn's disease activity

Background & aims: Crohn���s disease (CD) is a multifactorial disease where resistance to apoptosis is one major defect. Also, dietary fat intake has been shown to modulate disease activity. We aimed to explore the interaction between four single nucleotide polymorphisms (SNPs) in apoptotic genes and dietary fat intake in modulating disease activity in CD patients. Methods: Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) techniques were used to analyze Caspase9��93C/T, FasLigand-843C/T, Peroxisome Proliferator-Activated Receptor gamma��161C/T and Peroxisome Proliferator-Activated Receptor gamma Pro12Ala SNPs in 99 patients with CD and 116 healthy controls. Interactions between SNPs and fat intake in modulating disease activity were analyzed using regression analysis. Results: None of the polymorphisms analyzed influenced disease susceptibility and/or activity, but a high intake of total, saturated and monounsaturated fats and a higher ratio of n-6/n-3 polyunsaturated fatty acids (PUFA), was associated with a more active phenotype (p < 0.05). We observed that the detrimental effect of a high intake of total and trans fat was more marked in wild type carriers of the Caspase9��93C/T polymorphism [O.R (95%CI) 4.64 (1.27e16.89) and O.R (95%CI) 4.84 (1.34e17.50)]. In the Peroxisome Proliferator-Activated Receptor gamma Pro12Ala SNP, we also observed that a high intake of saturated and monounsaturated fat was associated to a more active disease in wild type carriers [OR (95%CI) 4.21 (1.33e13.26) and 4.37 (1.52e12.51)]. Finally, a high intake of n-6 PUFA was associated with a more active disease in wild type carriers for the FasLigand-843C/T polymorphism [O.R (95%CI) 5.15 (1.07e24.74)]. Conclusions: To our knowledge, this is the first study to disclose a synergism between fat intake and SNPs in apoptotic genes in modulating disease activity in CD patients.

Risk of colorectal cancer associated with the C677T polymorphism in 5,10-methylenetetrahydrofolate reductase in Portuguese patients depends on the intake of methyl-donor nutrients

Background: Polymorphisms located in genes involved in the metabolism of folate and some methyl-related nutrients are implicated in colorectal cancer (CRC). Objective: We evaluated the association of 3 genetic polymorphisms [C677T MTHFR (methylene tetrahydrofolate reductase), A2756G MTR (methionine synthase), and C1420T SHMT (serine hydroxymethyltransferase)] with the intake of methyl-donor nutrients in CRC risk. Design: Patients withCRC(n 196) and healthy controls (n 200) matched for age and sex were evaluated for intake of methyl-donor nutrients and the 3 polymorphisms. Results: Except for folate intake, which was significantly lower in patients (P 0.02), no differences were observed in the dietary intake of other methyl-donor nutrients between groups. High intake of folate ( 406.7 g/d) was associated with a significantly lower risk of CRC (odds ratio: 0.67; 95% CI: 0.45, 0.99). The A2756G MTR polymorphism was not associated with the risk of developing CRC. In contrast, homozygosity for the C677TMTHFRvariant (TT) presented a 3.0-fold increased risk of CRC (95% CI: 1.3, 6.7). Similarly, homozygosity for the C1420T SHMT polymorphism also had a 2.6-fold increased risk (95% CI: 1.1, 5.9) of developing CRC. When interactions between variables were studied, low intake of all methyl-donor nutrients was associated with an increased risk ofCRC in homozygous participants for the C677T MTHFR polymorphism, but a statistically significant interaction was only observed for folate (odds ratio: 14.0; 95% CI: 1.8, 108.5). No significant associations were seen for MTR or SHMT polymorphisms. Conclusion: These results show an association between the C677T MTHFR variant and different folate intakes on risk of CRC.

A efic��cia entre duas interven����es na S��ndrome do Canal C��rpico

A S��ndrome do Canal C��rpico (SCC) �� a neuropatia compressiva mais comum do membro superior, causada pela compress��o direta sobre o nervo mediano no interior do canal c��rpico.Os resultados deste estudo mostram em cada um dos grupos, ap��s a interven����o, uma melhoria estatisticamente significativa da sintomatologia no G-AFN (p=0,02) e no GTRN/ EAA (p=0,004) e uma melhoria estatisticamente significativa do estado funcional no G-AFN (p=0,022). Verificamos tamb��m em cada um dos grupos, ap��s a interven����o, uma melhoria estatisticamente significativa na ���For��a de preens��o��� (p=0,005), na ���Pin��a polegar/dedo indicador��� (p=0,021), na ���Pin��a polegar/dedo m��dio��� (p=0,026) e ���Pin��a polegar/dedo anular��� (p=0,026) no G-AFN, e uma melhoria estatisticamente significativa na ���Pin��a polegar/indicador��� (p=0,016), na ���Pin��a polegar/dedo m��dio��� (p=0,035), na ���Pin��a polegar/dedo anular��� (p=0,010), na ���Pin��a tr��pode��� (p=0,005) e na ���Pin��a lateral��� (p=0,051) no G-TRN/EAA. Ap��s a interven����o, n��o verificamos diferen��as estatisticamente significativas nos valores das escalas de gravidade de sintomas (p=0,853) e de estado funcional (p=0,148) entre os grupos, mas diferen��as estatisticamente significativas nos valores dos testes neurofisiol��gicos (p=0,047) e for��a de preens��o da m��o (p=0,005). Do estudo, conclu��mos que a utiliza����o da interven����o articular/fascial/neural (AFN) e a interven����o com tala de repouso noturna e exerc��cios de auto alongamento (TRN/EAA), beneficia os indiv��duos com SCC n��o severa, como nos casos incipientes, ligeiros ou moderados. Os indiv��duos com esta condi����o cl��nica apresentam sintomatologia carater��stica de dor, parestesia, especialmente noturna e disfun����o muscular da m��o. Tais manifesta����es originam perda funcional com implica����es nas ��reas de desempenho ocupacional, nomeadamente, nas atividades da vida di��ria, produtivas e de lazer. O tratamento conservador na SCC n��o severa, como nos casos incipientes, ligeiros e moderados, apesar de controverso, �� recomendado. O tema suscita o nosso interesse, raz��o pela qual nos propomos realizar um estudo experimental em indiv��duos com o diagn��stico cl��nico de SCC n��o severa e aplicar num grupo a interven����o articular, fascial e neural (AFN) e noutro grupo a interven����o com tala de repouso noturna e exerc��cios de auto alongamento (TRN/EAA). O estudo tem como principais objetivos, por um lado, verificar o impacto das interven����es em cada um dos grupos e, por outro lado, comparar o seu impacto entre os grupos, no que respeita �� gravidade de sintomas, ao estado funcional, �� for��a de preens��o da m��o e for��a de pin��as finas. Fomos tamb��m comparar os resultados dos testes neurofisiol��gicos (Velocidade de Condu����o Motora) antes e depois da interven����o AFN e da interven����o com TRN/EAA, e averiguar o seu impacto nos valores da lat��ncia motora distal e da velocidade de condu����o sensitiva, entre os grupos. Identificamos tamb��m quais as vari��veis s��cio demogr��ficas e as que caraterizam a patologia que est��o relacionadas com o problema em estudo e com os valores obtidos com as escalas do Boston Carpal Tunnel Questionnaire (BCTQ), no grupo articular, fascial e neural (G-AFN) e no grupo com tala de repouso noturna e exerc��cios de auto alongamento (G-TRN/EAA). Para a concretiza����o do estudo, recorremos a uma amostra de 23 indiv��duos de ambos os sexos do Hospital Curry Cabral, Empresa P��blica Empresarial -Centro Hospitalar de Lisboa Central (HCC, EPE -CHLC).