RESUMO
Red blood cell exchange (RBCEx) has become a standard therapy to remove abnormal red blood cells (RBCs) in patients with sickle cell disease (SCD). In the last few decades, numerous RBCEx procedures have been performed chronically during regular programs, while numerous procedures have also been performed in an emergency for several indications, this therapeutic option being very efficient in vital and emergency situations. In both groups of indications, large amounts of sickle RBCs have to be removed, which requires great precision and the setting of specific hematological targets. The aim of this review is to discuss the aims, clinical and biological targets, and the requirements and precautions when performing RBCEx in an emergency. Moreover, we analyze how improvement of the techniques as well as the clinical and biological targets has led to optimization of the procedures in emergency settings. We also consider the outstanding issues that require additional investigation.
Assuntos
Anemia Falciforme/terapia , Transfusão de Eritrócitos/métodos , Eritrócitos/metabolismo , HumanosRESUMO
Red blood cell exchange (RBCX) has become a standard therapy to remove abnormal red blood cells (RBC) in patients with sickle cell disease (SCD). In the last few decades, RBCX techniques have gradually improved, allowing sickle RBCs to be removed with greater precision and enabling specific hematological targets to be set. Improved knowledge of the techniques as well as the clinical and biological targets has led to optimization of the procedures. The aim of this review is to summarize the current technique, methods, targets and schedules of RBCX and to consider the outstanding issues that require additional investigation.
Assuntos
Transfusão de Eritrócitos/métodos , Eritrócitos/metabolismo , HumanosRESUMO
Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.
Assuntos
Anemia/diagnóstico , Aorta/metabolismo , Aneurisma da Aorta Abdominal/diagnóstico , Biomarcadores/metabolismo , Eritrócitos/fisiologia , Hemoglobinas/metabolismo , Ferro/metabolismo , Idoso , Anemia/complicações , Anemia/mortalidade , Aorta/patologia , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/mortalidade , Feminino , Ferritinas/metabolismo , Hepcidinas/metabolismo , Humanos , Masculino , Prognóstico , Receptores da Transferrina/metabolismo , Fatores de Risco , Análise de Sobrevida , Transferrina/metabolismoRESUMO
OBJECTIVE: Maternal and fetal risk is often high during pregnancy in sickle cell disease. Our objective was to evaluate the benefits of a transfusion program adapted to each pregnant patient, either by red cell transfusion or by automated red cell exchange, in sickle cell patients with a history of serious obstetrical and/or sickling complications. STUDY DESIGN: We managed 18 pregnancies in 14 patients (12 SS, 1 SC, 1 S/b-thalassemia), seven of whom had a history of one or more pregnancies, with severe maternofetal complications in nine out of 10 cases. The other seven patients were pregnant for the first time and were in care because of a history of severe sickling complications. The aim was to achieve a proportion of abnormal hemoglobin (hemoglobin S or S+C) below 50% and a hemoglobin level between 9 and 11 g/dL. The choice between transfusion and red cell exchange was made in the light of the hemoglobin level. Red cell exchange was done using a Fresenius Com. Tec blood cell separator. Patients had red cell exchange in 10 cases, and transfusions in five cases. In three cases, patients had successive transfusions and red cell exchange. RESULTS: No serious maternal complication was observed. No fetal or perinatal death occurred. In one case, delivery was induced at 36 weeks of gestation because of fetal distress and hypotrophy. CONCLUSIONS: Our study suggests that women with severe sickle cell disease, even if they have a serious obstetrical history, can carry their pregnancy to term, without major obstetric complications, through a combination of early management by a multidisciplinary team and a suitable policy of prophylactic transfusion or automated red cell exchange.
Assuntos
Anemia Falciforme/terapia , Transfusão de Eritrócitos , Transfusão Total , Complicações Hematológicas na Gravidez/terapia , Adulto , Automação , Feminino , Hemoglobina Falciforme/análise , Humanos , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Bacillus thuringiensis subsp. kurstaki BUPM255 secretes a chitobiosidase Chi255 having an expected molecular weight of 70.665 kDa. When the corresponding gene, chi255, was expressed in E. coli, the active form, extracted from the periplasmic fraction of E. coli/pBADchi255, was of about 54 kDa, which suggested that Chi255 was excessively degraded by the action of E. coli proteases. Therefore, in vitro progressive C-terminal Chi255 deleted derivatives were constructed in order to study their stability and their activity in E. coli. Interestingly, when the chitin binding domain (CBD) was deleted from Chi255, an active form (Chi2555Delta5) of expected size of about 60 kDa was extracted from the E. coli periplasmic fraction, without the observation of any proteolytic degradation. Compared to Chi255, Chi255Delta5 exhibited a higher chitinase activity on colloidal chitin. Both of the enzymes exhibit activities at broad pH and temperature ranges with maximal enzyme activities at pH 5 and pH 6 and at temperatures 50 degrees C and 40 degrees C, respectively for Chi255 and Chi255Delta5. Thus, it was concluded that the C-terminal deletion of Chi255 CBD might be a nice tool for avoiding the excessive chitinase degradation, observed in the native chitinase, and for improving its activity.
Assuntos
Bacillus thuringiensis/enzimologia , Quitina/metabolismo , Quitinases/biossíntese , Hexosaminidases/biossíntese , Proteínas Recombinantes/biossíntese , Bacillus thuringiensis/genética , Quitinases/química , Quitinases/genética , Estabilidade Enzimática , Escherichia coli/genética , Hexosaminidases/química , Hexosaminidases/genética , Temperatura Alta , Concentração de Íons de Hidrogênio , Estrutura Terciária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Deleção de SequênciaRESUMO
AIMS: The present work aims to study a new chitinase from Bacillus thuringiensis subsp. kurstaki. METHODS AND RESULTS: BUPM255 is a chitinase-producing strain of B. thuringiensis, characterized by its high chitinolytic and antifungal activities. The cloning and sequencing of the corresponding gene named chi255 showed an open reading frame of 2031 bp, encoding a 676 amino acid residue protein. Both nucleotide and amino acid sequences similarity analyses revealed that the chi255 is a new chitinase gene, presenting several differences from the published chi genes of B. thuringiensis. The identification of chitin hydrolysis products resulting from the activity, exhibited by Chi255 through heterologous expression in Escherichia coli revealed that this enzyme is a chitobiosidase. CONCLUSIONS: Another chitinase named Chi255 belonging to chitobiosidase class was evidenced in B. thuringiensis subsp. kurstaki and was shown to present several differences in its amino acid sequence with those of published ones. The functionality of Chi255 was proved by the heterologous expression of chi255 in E. coli. SIGNIFICANCE AND IMPACT OF THE STUDY: The addition of the sequence of chi255 to the few sequenced B. thuringiensis chi genes might contribute to a better investigation of the chitinase 'structure-function' relation.
Assuntos
Bacillus thuringiensis/enzimologia , Quitinases/genética , Sequência de Aminoácidos , Bacillus thuringiensis/genética , Proteínas de Bactérias/genética , Sequência de Bases , Cromatografia Líquida de Alta Pressão/métodos , Clonagem Molecular/métodos , Meios de Cultura , Expressão Gênica/genética , Genes Bacterianos/genética , Hexosaminidases/genética , Hidrólise , FilogeniaRESUMO
The authors report a case of a young patient with a recent decrease in unilateral vision. He had homozygote sickle cell disease with multiple general complications. Fundus examination was normal apart from a mild alteration of the macular reflect in the left eye, but fluorescein angiography showed multiple arteriolar macular occlusions, explaining the decrease in vision in the left eye. After erythropheresis, vision acuity improved and fluorescein angiography showed reperfusion. This case suggests that transfusional exchange may improve acute macular ischemia secondary to sickle cell disease.
Assuntos
Anemia Falciforme/complicações , Degeneração Macular/etiologia , Visão Monocular , Doença Aguda , Adolescente , Transfusão de Sangue , Eritropoese , Angiofluoresceinografia , Humanos , Degeneração Macular/diagnóstico , Degeneração Macular/terapia , MasculinoRESUMO
The aims of the study were to evaluate the impact of a written information about treatment related risks in patient receiving blood derived or recombinant medications. Haemophiliac patients and patients with constitutional or acquired immune deficiencies are concerned by this treatment and these information. Our objectives are to evaluate the efficacy of the written information, the knowledge of the patients about these medications and the psychological, emotional impact if these information. The study is based on questionnaires which specified how the patient treat bleeding episodes, their knowledge about viral safety of blood products, the patient's perception of his or her health status and relationship with the physician. Psychological and emotional status are evaluated with the Hospital Anxiety and Depression Scale. The results show the difficulty to inform patients: if the information generate only limited anxiety in patients with haemophilia or immune deficiencies, we observe that the delivery of a written information got a mediocre effect on overall knowledge. We think that this information must be appropriate for patients and be communicated orally within the patient-physician relationship.
Assuntos
Coagulantes/uso terapêutico , Fator VIII/uso terapêutico , Hemofilia A/terapia , Imunoglobulinas/uso terapêutico , Educação de Pacientes como Assunto/normas , Ansiedade/etiologia , Atitude Frente a Saúde , Depressão/etiologia , Humanos , Proteínas Recombinantes , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: C-reactive protein (CRP), a marker of systemic inflammation, is a powerful predictor of adverse cardiovascular events. Respiratory impairment is also associated with cardiovascular risk. Although some studies have found an inverse relationship between lung function and markers of systemic inflammation, only one study has reported a relationship between lung function and CRP levels. In contrast, little is known about the relationship between bronchial hyperresponsiveness (BHR) and systemic inflammation. The association between lung function and CRP and between BHR and CRP has been investigated. METHODS: As part of the European Community Respiratory Health Survey follow up study serum CRP levels, forced expiratory volume in 1 second (FEV(1)), and BHR to methacholine (>/=20% decrease in FEV(1) to <4 mg methacholine) were measured in 259 adults aged 28-56 years free of cardiovascular disease or respiratory infection. RESULTS: Mean (SD) FEV(1) (adjusted for age, sex, height, and smoking status) was lower in subjects with a high CRP level (high tertile) (3.29 (0.44) l/s v 3.50 (0.44) l/s; p<0.001) and BHR was more frequent (41.9% v 24.9%; p = 0.005) than in subjects with lower CRP levels (low+middle tertiles). Similar results were obtained when the potential confounding factors were taken into account. Similar patterns of results were found in non-smokers and in non-asthmatic subjects. CONCLUSIONS: Increased CRP levels are strongly and independently associated with respiratory impairment and more frequent BHR. These results suggest that both respiratory impairment and BHR are associated with a systemic inflammatory process.
Assuntos
Hiper-Reatividade Brônquica/fisiopatologia , Proteína C-Reativa/metabolismo , Adulto , Biomarcadores , Hiper-Reatividade Brônquica/metabolismo , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Capacidade Vital/fisiologiaRESUMO
BACKGROUND/AIMS: This controlled study aimed to evaluate the efficacy and potential side effects of hepatitis B virus (HBV) vaccination as active immunotherapy in HBV-related chronic hepatitis. METHODS: The 118 included patients were 'naive' subjects who had never received any previous anti-HBV therapy, showed detectable serum HBV DNA and had biopsy-proven chronic hepatitis. In a 12-month follow-up they were given either five intramuscular injections of 20 microg of a preS2/S (GenHevac B, Pasteur-Mérieux) (n = 46) or an S vaccine (Recombivax Merck & Co.) (n = 34) or no treatment as a control (n = 37). The efficacy of vaccination was evaluated by testing for serum HBV DNA negativation using a standard liquid hybridization assay. RESULTS: Three months after the first three vaccine injections, the percentage of serum HBV DNA negativation was higher in the vaccine groups (16.3%) than in the control group (2.7%) (P = 0.033, by the chi2 Pearson test) and was more frequently observed in patients who had pretreatment viremia >200 pg/ml (none in the control group vs. 16.7% in the vaccinated groups) (P = 0.025). After 12 months follow-up and five vaccine injections, there was no difference in the rate of serum HBV DNA negativation between vaccinated and unvaccinated subjects but HBV vaccines significantly decreased the HBV viral load between the sixth and twelfth months (P = 0.04) in contrast with the control group. The rate of HBe/anti-HBe seroconversion after 6 months of follow-up occurred only in eight (13.3%) vaccinated patients and in one (3.6%) of the controls. Disappearance of serum HBsAg was not observed in any of the patients. CONCLUSIONS: This controlled study offers direct evidence that the HBV vaccine may decrease HBV replication in chronic hepatitis B patients. It also emphasizes the need for reinforced immunization strategies as well as combination therapies.
Assuntos
Hepatite B Crônica/terapia , Imunoterapia Ativa/métodos , Adulto , DNA Viral/sangue , Feminino , Vacinas contra Hepatite B/efeitos adversos , Vacinas contra Hepatite B/uso terapêutico , Vírus da Hepatite B/isolamento & purificação , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Humanos , Imunoterapia Ativa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/uso terapêutico , Replicação ViralRESUMO
Interaction between neutrophils and endothelial cells is one of the first steps in the functional response of polymorphonuclear neutrophils (PMN), and is necessary for their migration toward damaged tissues. PMN activation, leading to their adhesion to and migration between endothelial cells, is part of a complex phenomenon that can be altered in pathological situations such as the ischemia-reperfusion syndrome, in which large numbers of PMN are recruited to the tissue and release reactive oxygen species (ROS) near the vessel wall. ROS have been implicated in the pathogenesis of various inflammatory diseases. The increased adhesion of PMN to ROS-stimulated endothelial cells involves an increase in tyrosine phosphorylation of a tyrosine kinase focal adhesion kinase (p125FAK) and several cytoskeleton proteins, including paxillin and p130 cas. We examined the role of glutathione (GSH) in the regulation of this adhesion phenomenon and in the increased tyrosine phosphorylation induced by ROS. For this purpose we used anethole dithiolthione (ADT), which increases the glutathione synthesis by activating gamma-glutamyl-cysteine synthetase. We found that ADT reduced both PMN adhesion to ROS-stimulated human umbilical vein endothelial cells (HUVEC) and tyrosine phosphorylation of p125FAK and paxillin. ADT increased redox status by increasing intracellular GSH content in oxidized cells. These results show that GSH can reverse the effect of oxidation on tyrosine kinase activation and phosphorylation, and thus plays an important role in cell signaling. They also confirm the antioxidant activity of ADT.
Assuntos
Anetol Tritiona/farmacologia , Antioxidantes/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/enzimologia , Proteínas Tirosina Quinases/metabolismo , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Proteínas do Citoesqueleto/metabolismo , Ativação Enzimática/efeitos dos fármacos , Quinase 1 de Adesão Focal , Proteína-Tirosina Quinases de Adesão Focal , Glutationa/metabolismo , Humanos , Hipoxantina/farmacologia , Técnicas In Vitro , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Oxirredução , Estresse Oxidativo , Paxilina , Fosfoproteínas/metabolismo , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Xantina Oxidase/farmacologiaRESUMO
BACKGROUND: A new intravenous lipid emulsion (ILE) prepared from a mixture of soybean and olive oils contains only long-chain triacylglycerols, with a low proportion (20%) of polyunsaturated fatty acids and 60% monounsaturated fatty acids. OBJECTIVE: The goal of this randomized, double-blind clinical trial was to assess in children the efficacy and safety of this new ILE compared with a control group receiving a soybean-oil emulsion. DESIGN: Eighteen children received for 2 mo 24% of nonprotein energy (1.80 g kg (-)(1) d(-)(1)) either as the new ILE or a soybean oil-based emulsion. Assessments were performed on days -30, 0, 30, and 60 and the changes (day 60 - day 0) assessed by analysis of variance. RESULTS: There were no significant differences in triacylglycerol, apolipoproteins A-I and B, or HDL cholesterol between the 2 groups, whereas total and LDL cholesterol were higher in the soybean oil group on day 60. The pattern of 20:4n-6 in erythrocyte membranes did not change significantly, nor did the ratio of 20:3n-9 to 20:4n-6. On day 60, 18:1n-9 was significantly higher in the olive oil group, the ratio of Sigma(n)-6 > C(18) + 18:3n-6 to 18:2n-6 was 2.20 +/- 0.09 in the olive oil group and 1.33 +/- 0.16 in the soybean-oil group, and Sigma(n)-3 > C(18) was 3.83 +/- 0.30 in the olive oil group and 4. 03 +/- 0.33 in the soybean-oil group. The peroxidation index was lower after the olive oil treatment. CONCLUSIONS: The olive oil-based emulsion was well tolerated, maintained a normal EFA status, and may be more suitable for prevention of lipid peroxidation than the soybean-oil-based emulsion.
Assuntos
Gorduras Insaturadas na Dieta/farmacologia , Emulsões Gordurosas Intravenosas/farmacologia , Nutrição Parenteral , Óleos de Plantas/farmacologia , Criança , Pré-Escolar , Gorduras Insaturadas na Dieta/efeitos adversos , Método Duplo-Cego , Emulsões Gordurosas Intravenosas/efeitos adversos , Feminino , Humanos , Lactente , Masculino , Azeite de Oliva , Óleos de Plantas/efeitos adversosRESUMO
In a pilot study, it was established that specific therapy by standard anti-hepatitis B virus (HBV) vaccination may be effective in reducing HBV replication and canceling the immune tolerance to hepatitis B surface antigen (HBsAg) particles in about 50% of persons with chronic active HBV replication. In the present study, the vaccine-induced immune responses were analyzed during an ongoing controlled multicenter vaccine trial. Vaccination elicited peripheral blood mononuclear cell proliferative responses specific for envelope antigen in 7 of 27 subjects given HBsAg. The responses induced by the vaccines were mediated by CD4+ T lymphocytes, and at least three different epitopes were recognized. HBV-specific CD4+ T lymphocytes produced high levels of interferon-gamma [corrected] and belonged to a T helper 1 subset. Reduction of serum HBV DNA in some of these persons suggests that induction of CD4+ T cell responses could be important in controlling viremia during vaccine therapy of chronic HBV carriers.
Assuntos
Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/uso terapêutico , Hepatite B Crônica/terapia , Linfócitos T/imunologia , Vacinação , Epitopos , Vacinas contra Hepatite B/imunologia , Antígenos E da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Humanos , Interferon-alfa/biossíntese , Interferon gama/biossíntese , Ativação Linfocitária , Projetos Piloto , Células Th1/imunologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/uso terapêutico , Replicação Viral/efeitos dos fármacosRESUMO
Gender, menstrual cycle and oral contraceptives may have influence on mechanical properties of Red Blood Cell (RBC) and particularly on RBC deformability. So cell transit parameters have been assessed by filtration with the Cell Transit Analyser (CTA) for a large healthy adult population (seventy-nine males and one-hundred-fifteen females). The CTA provides the distribution of cell transit times of 5000 red blood cells, the mean transit time of the population and different percentiles such as p50, p75, p90 and p95. No effect of oral contraceptives was found. Nevertheless, influence of sex and menstrual cycle were demonstrated. A significant increase of the filtration parameters measured in the female population with respect to the male population and during menstruation, preovulation and post-ovulation periods was observed. During ovulation, the CTA parameters are comparable to the same parameters found in males.
Assuntos
Anticoncepcionais Orais/farmacologia , Deformação Eritrocítica/efeitos dos fármacos , Ciclo Menstrual , Adulto , Índices de Eritrócitos , Feminino , Filtração , França , Humanos , Masculino , Ciclo Menstrual/efeitos dos fármacos , Filtros Microporos , Pessoa de Meia-Idade , Ovulação/fisiologia , Fatores SexuaisAssuntos
Altitude , Fenômenos Fisiológicos da Nutrição Animal , Dieta , Cães/fisiologia , Esforço Físico/fisiologia , Trabalho de Resgate , Animais , Eritrócitos/metabolismo , Ácidos Graxos/sangue , Óleos de Peixe/administração & dosagem , França , Frequência Cardíaca , Hemólise , Peroxidação de Lipídeos , Espécies Reativas de Oxigênio/metabolismo , Vitamina E/administração & dosagem , Vitamina E/sangueAssuntos
Hepatite B/epidemiologia , Hepatite C/epidemiologia , Transplante de Rim , Complicações Pós-Operatórias/epidemiologia , Biópsia , Causas de Morte , Distribuição de Qui-Quadrado , DNA Viral/sangue , Hepacivirus/isolamento & purificação , Hepatite B/complicações , Vírus da Hepatite B/isolamento & purificação , Hepatite C/complicações , Anticorpos Anti-Hepatite C/sangue , Humanos , Transplante de Rim/mortalidade , Transplante de Rim/patologia , Complicações Pós-Operatórias/mortalidade , RNA Viral/sangue , Estudos RetrospectivosRESUMO
Vaccine therapy is now used in various infectious diseases. The hepatitis B virus (HBV) leads to chronic infection in around 5% of patients with a high risk of chronic active hepatitis which may result in cirrhosis and hepatocellular carcinoma. The partial efficacy of antiviral therapies (40% of sustained inhibition of HBV replication), their cost, their possible side effects and the immune-mediated pathology of HBV infection explain the need of new immune therapies in treating HBV infection. Experimental and clinical evidences suggest the usefulness of vaccine therapy in HBV chronic infection. In a pilot and opened study, forty-six consecutive chronic HBsAg carriers with chronic hepatitis and detectable serum HBV DNA were given 3 standard injections of the GenHevac B vaccine at one month interval. Six months after the first injection, 12 patients (26.1%) had undetectable HBV DNA while 8 others showed significant decrease (more than 50%) in HBV DNA titers. Six of these 12 responders received a standard course of alpha-Interferon (5 MU thrice weekly subcutaneously for 4 months) and all six had still undetectable HBV replication at the end of follow-up. Among the 34 non responders to vaccine, 20 were given alpha-interferon and 2 the monophosphate derivate of Vidarabine: 12 of these 22 patients stopped HBV replication and in all 12, vaccine therapy had induced a significant decrease of HBV replication before the antiviral treatment with a decrease of mean serum HBV DNA from 392 pg/ml before to 217 pg/ml after vaccine therapy. In an ongoing controlled study, using the same vaccine schedule, serum HBV DNA disappeared more frequently after 6 months, in patients who were given a preS2/S vaccine (7/35) than in patients who received a S vaccine (1/21) or no vaccine (1/32). In responders to vaccine, an induction of specific proliferative responses was observed and this may contribute to the potential efficacy of anti-HBV vaccine therapy. No side-effect or vaccine-induced escape-mutants occurred during the follow-up. In summary, serum HBV DNA disappeared in 28 of the 46 patients (60.9%) who were given vaccine therapy, with (64.2%) or without (55.6%) Interferon. These results are not different at 6 months and at the end of follow-up from those of 43 HBsAg chronic carriers who were given only an antiviral treatment. Active immune therapy against HBV appears efficient and less expensive than antiviral therapies in stopping HBV replication. Such results need to be confirmed by the completed results of our controlled, randomized trial which is now conducted in our unit.
Assuntos
Anticorpos Anti-Hepatite B/análise , Vacinas contra Hepatite B/administração & dosagem , Hepatite B Crônica/terapia , Imunoterapia , Adulto , Esquema de Medicação , Feminino , Hepatite B Crônica/imunologia , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Resultado do TratamentoRESUMO
Influence of viral liver diseases on the occurrence of azathioprine hepatitis was evaluated in 21 kidney transplant recipients. Diagnosis of azathioprine hepatitis was always based on jaundice, which disappeared after azathioprine withdrawal in 18 patients and after azathioprine dose reduction in 3 patients. Histopathological diagnosis of azathioprine toxicity was ascertained in 14 patients. Rechallenge with azathioprine performed in 4 patients, within 2-4 months after the first jaundice episode, resulted in relapse of jaundice in all cases. Viral hepatitis B virus and hepatitis C markers were present in all 20 tested patients (serum hepatitis B surface antigen in 6 patients and anti-HCV antibodies in 17 patients). Biopsy-proven chronic hepatitis was observed in 18 patients, including 14 chronic active hepatitis, 3 chronic persistent hepatitis and cirrhosis in 1. In kidney transplant recipients, azathioprine hepatitis seems to be facilitated or induced by hepatitis B virus or hepatitis C virus chronic hepatitis. Azathioprine reduction or withdrawal should therefore be combined with the diagnostic evaluation and the treatment of viral liver diseases.
Assuntos
Azatioprina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Hepatite Viral Humana/fisiopatologia , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Adulto , Doença Crônica , Ensaio de Imunoadsorção Enzimática , Feminino , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: A pilot study was conducted to evaluate the efficiency of alpha-interferon treatment in chronic active hepatitis B in anti-HIV-positive patients. METHODS: Twenty-five patients with chronic active hepatitis (23 men and 2 women, mean age: 33 years) were included in the study. Viral infections were acquired by intravenous drug addiction in 2, homosexual relations in 22, and multiple heterosexual contacts in one. The mean CD4 cell count was 480 +/- 234/mL, 7 patients had p24 antigenemia, but none belonged to class C of the CDC classification. All patients were serum HBs Ag and HBV DNA-positive, and delta antigen and antibody negative. Patients received a 6-month course of alpha-interferon 2a, 6 MU subcutaneously three times per week. The mean follow-up after treatment was 15 months. Eighteen patients with serum anti-HIV antibodies, HBsAg and HBV DNA-positive, and chronic active hepatitis, who were not treated with interferon, were included as controls (mean follow-up: 29 months). RESULTS: Nine of the 25 patients (36%) lost serum HBV DNA (1, 2, 4, 6, and 8 months after the beginning of treatment in 1, 4, 1, 2 and 1 cases, respectively), and were considered responders. Only one of the responders developed serum anti-HBe during follow-up, despite the disappearance of HBe Ag in 2 and of HBs Ag in one. Loss of HBV DNA was not clearly associated with the immune status, since 3 of the 9 responders had p24 antigenemia and the 9 responders had a lower mean CD4 count (283 +/- 246/mm3) than non responders (454 +/- 437/mm3, NS). Three of the 18 patients (16.7%) in the control group had spontaneous loss of serum HBV DNA during follow-up. Thus, there was a 2.15-fold increase in HBV DNA loss in the anti-HIV-positive patients who received alpha-interferon, compared to those who did not. CONCLUSION: In HIV-positive patients treated with alpha-interferon, the rate of HBV DNA loss was not clearly different from that reported in immunocompetent patients. As severe HBV-related liver disease has previously been described in anti-HIV positive patients, at least in drug users, these results suggest that this treatment may be proposed whatever the immune status, at least in the absence of AIDS.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepatite B/terapia , Hepatite Crônica/terapia , Interferon-alfa/uso terapêutico , Adulto , Biomarcadores/análise , Feminino , Infecções por HIV/fisiopatologia , Infecções por HIV/terapia , Hepatite B/etiologia , Hepatite B/fisiopatologia , Hepatite Crônica/etiologia , Hepatite Crônica/fisiopatologia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Fatores de TempoRESUMO
OBJECTIVES: The possibility of "community-acquired" viral infection has been suggested in alcoholics. In order to assess this hypothesis, we evaluated the prevalence of antibodies against hepatitis A virus, a oro-fecally transmitted virus, in heavy drinkers. PATIENTS AND METHODS: We retrospectively studied 258 heavy drinkers, 188 males and 70 females, divided into sub-groups of increasing age, and compared them to 277 similarly classified blood donors. RESULTS: The prevalence of serum anti-hepatitis A antibodies was significantly higher in alcoholics than in controls (64.7 vs 52.3%, P < 0.01). The difference was particularly marked in patients younger than 45 years old (56.2 vs 39.1%, P < 0.01). In the alcoholics, there was no correlation between the prevalence of anti-hepatitis A antibodies and the socioeconomic level, the quantity of alcohol ingested, or the severity of the underlying liver disease. CONCLUSION: These results suggest that alcoholism is, per se, a risk factor for viral infections.