RESUMO
The naturally occurring oncolytic virus (OV), reovirus, replicates in cancer cells causing direct cytotoxicity, and can activate innate and adaptive immune responses to facilitate tumour clearance. Reovirus is safe, well tolerated and currently in clinical testing for the treatment of multiple myeloma, in combination with dexamethasone/carfilzomib. Activation of natural killer (NK) cells has been observed after systemic delivery of reovirus to cancer patients; however, the ability of OV to potentiate NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) is unexplored. This study elucidates the potential of oncolytic reovirus for the treatment of chronic lymphocytic leukaemia (CLL), both as a direct cytotoxic agent and as an immunomodulator. We demonstrate that reovirus: (i) is directly cytotoxic against CLL, which requires replication-competent virus; (ii) phenotypically and functionally activates patient NK cells via a monocyte-derived interferon-α (IFNα)-dependent mechanism; and (iii) enhances ADCC-mediated killing of CLL in combination with anti-CD20 antibodies. Our data provide strong preclinical evidence to support the use of reovirus in combination with anti-CD20 immunotherapy for the treatment of CLL.
Assuntos
Citotoxicidade Celular Dependente de Anticorpos/imunologia , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/imunologia , Orthoreovirus Mamífero 3/imunologia , Vírus Oncolíticos/imunologia , Rituximab/imunologia , Rituximab/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/imunologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Efeito Citopatogênico Viral , Feminino , Humanos , Imunidade Inata , Fatores Imunológicos/imunologia , Fatores Imunológicos/uso terapêutico , Imunofenotipagem , Imunoterapia , Células Matadoras Naturais/imunologia , Leucemia Linfocítica Crônica de Células B/diagnóstico , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Replicação ViralRESUMO
A case of classical colliquative amoebic hepatitis, documented with aspiration of abundant amoebic pus by means of hepatocentesis and treated with chloroquine and haematin, is reported. This type of amoebiasis is rare nowadays, it is pointed out. Present-day clinico-epidemiological features are outlined: reduction in official cases, reversal of the ratio between colitis and hepatitis (the latter is on the increase), disappearance of acute dysenteric forms, less tendency to colliquative development in cases where the liver is involved, an involvement which is seen most frequently with an atypical chronic-type imprint. Mention is finally made of the reasons behind this cliniqo-epidemiological shift.
Assuntos
Abscesso Hepático Amebiano/fisiopatologia , Cloroquina/uso terapêutico , Colite/epidemiologia , Hemina/uso terapêutico , Humanos , Itália , Abscesso Hepático Amebiano/tratamento farmacológico , Abscesso Hepático Amebiano/epidemiologia , Masculino , Pessoa de Meia-IdadeRESUMO
A comparison between a BCG antigen and various batches of an antigen extracted at different times from leishmania cultures in the fixation of complement reaction is reported. A better response was obtained with BCG (further confirmation on a larger series is being sought), whereas the leishmania antigens were difficult to prepare and their batch titres were not constant.
Assuntos
Antígenos , Leishmaniose/imunologia , Animais , Testes de Fixação de Complemento , Cães , Humanos , Leishmania/imunologia , Mycobacterium bovis/imunologiaRESUMO
The serum zinc concentration seems unlikely to be an important factor influencing immune response to hepatitis B vaccination in hemodialysis patients, on the basis of the following results: the absence of statistically significant differences in serum zinc concentrations between patients with absence of post-vaccine seroconversion or non protective seroconversion and patients with excellent seroconversion (anti-HBs concentrations over 124.6 mUI/ml); the association of protective antibody responses in 50% of non responders after an additional dose of HBV vaccine, without preliminary corrections of zinc balance.
Assuntos
Anticorpos Anti-Hepatite B/análise , Diálise Renal , Vacinas contra Hepatite Viral/imunologia , Zinco/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Avaliação como Assunto , Vacinas contra Hepatite B , Humanos , Pessoa de Meia-Idade , Vacinas contra Hepatite Viral/administração & dosagemRESUMO
The case of a patient who developed hepatitis during treatment with clofibrate is reported. The first attack of hepatitis, which resolved after the drug was suspended, was followed by another at rechallenge with a similar drug, fenofibrate.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Clofibrato/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Feminino , Fenofibrato/efeitos adversos , Humanos , Pessoa de Meia-Idade , Fatores de TempoRESUMO
Early diagnosis of PHC development in cirrhosis is sometimes difficult through common tests excluding invasive diagnostic procedures; liver biopsy as a routine periodical control during the course of the disease is not advisable and AFP monitoring as a diagnostic test is preferable. The present study shows the results of a screening for AFP levels in a series of 113 cirrhotic patients aged over 50. 11.5% of them presented increased levels of serum AFP, indicating development of PHC. AFP elevated values resulted in 76.5% of cases associated with a previous HBV infection, and the risk of PHC development resulted sixfold greater in anti-HBc positive male cirrhotic patients. In patients with elevated AFP levels the prevalence of complications of cirrhosis resulted up to tenfold greater than in AFP negative patients.
Assuntos
Carcinoma Hepatocelular/diagnóstico , Hepatite B/imunologia , Cirrose Hepática/sangue , Neoplasias Hepáticas/diagnóstico , alfa-Fetoproteínas/análise , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Antígenos do Núcleo do Vírus da Hepatite B/análise , Humanos , Cirrose Hepática/imunologia , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
Objective of the study was to identify predictive factors of response to treatment with interferon in patients with anti-HCV positive chronic liver disease. 92 anti-HCV positive patients, 51 with chronic hepatitis and 41 with active cirrhosis, were treated for 12 months with recombinant alpha 2a interferon at a starting dose of 6 MU TIW/6 months, followed by 3 MU TIW/6 months. Patients were considered responders (RS) when they presented normal serum ALT values both at the end of treatment and after 6 months of follow-up; relapsers (RC) those with normal ALT values at the end of treatment but with increase during the 6 months of follow-up and non-responders (NR) patients who had no beneficial effect on ALT levels during treatment. 21 patients were RS, 11 RC and 60 cases NR. Univariate analysis of pre-treatment factors showed that response to interferon was associated with absence of cirrhosis and lower gamma-GT levels in RS than in RC. Multiple logistic regression of these variables showed that gamma-GT levels and absence of cirrhosis were the only independent factors associated with response to treatment. In conclusion, in our series of patients, only two factors were confirmed useful in predicting response to interferon treatment and it is concluded that they must always be evaluated before starting treatment with interferon which is not without side effects and may not have beneficial effect.
Assuntos
Anticorpos Anti-Hepatite C/imunologia , Hepatite C/tratamento farmacológico , Hepatite Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Adulto , Análise de Variância , Formação de Anticorpos/efeitos dos fármacos , Feminino , Hepatite C/imunologia , Hepatite Crônica/imunologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , PrognósticoAssuntos
Aviação , Cólera/epidemiologia , África , Aeronaves , Ásia , Sudeste Asiático , Cólera/transmissão , Desinfecção , Europa (Continente) , Humanos , Higiene , Saneamento , Viagem , VacinaçãoAssuntos
Colestase/induzido quimicamente , Cirrose Hepática/complicações , Antipirina/efeitos adversos , Antipirina/análogos & derivados , Transtornos de Ansiedade/tratamento farmacológico , Barbitúricos/efeitos adversos , Cafeína/efeitos adversos , Colestase/patologia , Quimioterapia Combinada , Feminino , Haloperidol/efeitos adversos , Humanos , Cirrose Hepática/patologia , Maprotilina/efeitos adversos , Pessoa de Meia-Idade , Recidiva , Temazepam/efeitos adversos , Fatores de TempoRESUMO
The complement fixation test with an antigen from commercially lyophilized BCG and the immunofluorescence test were carried out on serum samples from patients with visceral leishmaniasis, oriental sore and tbc. The IFT positivity was obtained only in patients with visceral leishmaniasis. The CFT with BCG showed positive results in 3 on 5 serum samples from patients with visceral leishmaniasis, in 2 with oriental sore, at low titres, and in 5 serum samples from patients with tbc. The AA. confirm the high specificity of the IFT, but suggest that the CFT with BCG can be used as a convenient screening test.
Assuntos
Vacina BCG , Testes de Fixação de Complemento , Imunofluorescência , Leishmaniose/diagnóstico , Mycobacterium bovis/imunologia , Formação de Anticorpos , Antígenos , Humanos , MétodosRESUMO
The utility of complement-fixation test with an antigen from commercially lyophilized BCG was investigated in the diagnosis of leishmaniasis. The following results were obtained: Visceral leishmaniasis: 4 positivity on 5 cases; Oriental sore: 3 positivity on 6 cases; Canine leishmaniasis: 6 positivity, at high level, and 2 negativity; Other diseases: 5 positivity, on 17 sera of tbc; No positivity in sera from patients with various diseases, in control and in normal dogs. The results are compared with those quoted in medical literature and discussed. The meaning of the reaction is also briefly discussed, and the hypothesis of the presence of partigens between BCG and leishmania, or presence of autoantibodies is prospected.
Assuntos
Vacina BCG , Testes de Fixação de Complemento/métodos , Leishmaniose/diagnóstico , Mycobacterium bovis/imunologia , Animais , Autoanticorpos , Reações Cruzadas , Doenças do Cão/diagnóstico , Cães , Epitopos , Humanos , Leishmaniose/veterinária , Leishmaniose Mucocutânea/diagnóstico , Leishmaniose Visceral/diagnósticoRESUMO
A clinical and electrophysiological study was carried out on 19 selected patients with chronic liver disease. Clinical signs of peripheral nerve involvement were found in 4 patients (21%); while electrophysiological impairment was present in 11 patients (57.8%). These abnormalities were mostly limited to the sensory and motor fibers of the tibialis posterior nerve. Our data confirm the presence of peripheral nerve involvement in chronic liver disease, and that it may be evidenced by careful electrophysiological examination.
Assuntos
Hepatopatias/complicações , Doenças do Sistema Nervoso Periférico/fisiopatologia , Adulto , Idoso , Doença Crônica , Feminino , Hepatite Crônica/complicações , Hepatite Crônica/fisiopatologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Doenças do Sistema Nervoso Periférico/complicaçõesRESUMO
To determine whether platelet prostaglandin production in patients with liver cirrhosis was as impaired as platelet aggregation, serum thromboxane production was studied in 52 patients with liver cirrhosis; 12 patients had consumed more than 80 gr of alcohol/day, for more than ten years; 13 patients had also had diabetes mellitus for more than two years. A reduced thromboxane synthesis by platelets of liver disease patients was observed; the parallel decrease of both platelet thromboxane and serum PGE2 formation may also suggest a decrease in arachidonic acid availability for prostaglandin and thromboxane production. A smaller reduction of thromboxane and PGE2 formation in cirrhotics with diabetes mellitus or chronic alcohol intake was also observed.
Assuntos
Plaquetas/metabolismo , Cirrose Hepática/sangue , Tromboxanos/sangue , Adulto , Idoso , Complicações do Diabetes , Diabetes Mellitus/sangue , Dinoprostona , Feminino , Humanos , Cirrose Hepática/complicações , Cirrose Hepática Alcoólica/sangue , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária , Prostaglandinas E/sangue , Tromboxano B2/sangueRESUMO
A very simplified method of crossed over electrophoresis (CIEP) was employed with a lyophilized commercially produced antigen (previously submitted to several freezing and thawing) and cellulose acetate membrane, for the diagnosis of human hydatidosis. Results are as follows: active hydatidosis (surgically confirmed): number of sera tested 35; positive 32 (91%). Sera of patients with parasitic and non parasitic illnesses (especially malignancies of liver and lung) did not show any precipitin lines. The pattern of immunoprecipitation is characteristically in the form of an "upper lip" or a thick and undulating "streak". The very thin arcs of precipitation which are occurring in some control sera, are to be considered negative. These results indicate that with regard to the rule of the "three S" (specificity, sensitivity and simplicity) the method appears sufficiently satisfactory.
Assuntos
Contraimunoeletroforese/métodos , Equinococose/diagnóstico , Imunoeletroforese/métodos , Formação de Anticorpos , Antígenos , Equinococose/imunologia , Equinococose Hepática/diagnóstico , Equinococose Hepática/imunologia , Equinococose Pulmonar/diagnóstico , Equinococose Pulmonar/imunologia , Epitopos , Congelamento , Humanos , Testes de PrecipitinaRESUMO
Aim of this study was to evaluate the diagnostic value of serum MAO activity (sMAO) in chronic liver disease. sMAO has been assayed by benzylamine colorimetric method. No statistically significant differences of sMAO values have been found between controls and acute viral hepatitis or various diseases patients. Differences instead between controls and patients sMAO values (chronic persistent hepatitis, chronic active hepatitis and liver cirrhosis) were statistically significant (p less than 0.005).
Assuntos
Hepatopatias/diagnóstico , Monoaminoxidase/sangue , Doença Aguda , Doença Crônica , Colorimetria , Diagnóstico Diferencial , Hepatite Crônica/diagnóstico , Hepatite Viral Humana/diagnóstico , Humanos , Cirrose Hepática/diagnóstico , Hepatopatias/enzimologiaRESUMO
Prevalence of HBV infection markers and its association with some risk factors has been studied on hospital staff of the University Polyclinic of Palermo. The results show that male sex, job category (technicians, nurses, cleaners) and age are significantly associated with a higher prevalence of HBV infection markers; length of service and working in departments with a presumably higher exposure to blood did not result as a risk factor of higher prevalence of HBV infection when submitted to multiple regression logistic analysis. It is suggested that results of this study may be affected by the elevated spread of HBV infection in this area, and extra risk associated to hospital exposure is too small to be demonstrated.