RESUMO
OBJECTIVE: The aim of this study was to explore a possible association between the pattern of serum cytokines with the virological and biochemical status of hepatitis C virus (HCV)-seropositive blood donors. METHODS: 23 non-viremic and 33 viremic HCV-seropositive blood donors based on HCV-RNA tests, and 29 healthy individuals were included. Cytometric bead array assays were performed to detect cytokines. RESULTS: The subjects were classified as low, medium or high cytokine producers based on the tertile distribution. The absence of detectable viremia was associated with high IL-1ß and IL-8 producers. Conversely, elevated levels of IL-6, IL-10 and IL-12 were associated with detectable viremia. An increased frequency of high IL-1ß producers was observed frequently in the non-viremic recombinant immunoblot assay (RIBA)-indeterminate subjects, while the high IL-4, IL-6, IL-8, IL-10 and IL-12 producers were more frequent in the non-viremic RIBA-positive subjects. Furthermore, the levels of IL-1ß and IL-8 were higher in viremic subjects with a low level of alanine-aminotransferase (ALT), whereas the level of IFN-γ was increased among viremic subjects with a high ALT level. CONCLUSION: IL-1ß and IL-8 were more likely to be associated with a non-viremic or less severe HCV infection, whereas IL-2 and IFN-γ levels correlated with a high ALT level.
Assuntos
Doadores de Sangue , Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Hepatite C/virologia , Interferon gama/sangue , Interleucina-8/sangue , Viremia/diagnóstico , Adulto , Feminino , Hepacivirus/imunologia , Hepatite C/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangueRESUMO
BACKGROUND/AIMS: Killer cell immunoglobulin-like receptors (KIR) are involved in the activation/inhibition of NK cells through an interaction with HLA class I molecules on target cells. Our study aimed to evaluate the association between KIR gene polymorphisms and the response of patients with CHC to antiviral therapy. METHODS: We compared the frequency of KIR genes, as well as that of compound KIR/HLA-C genotypes, between groups of patients with CHC who presented a sustained virological response (n=66) and who were non-responders to a combination of pegylated or standard interferon and ribavirin (n=101). KIR and HLA-C genotyping were performed using commercial kits. RESULTS: We detected a greater frequency of the KIR2DL5 gene among non-responders to antiviral therapy compared with sustained virological responders (68.3 vs. 40.9%) (P<0.001). We used multiple logistic regression analysis to determine the association between therapy response and the presence of KIR2DL5, after a control for potentially confounding variables (genotype, alcohol, fibrosis, gender, age, ethnic background and route of HCV infection). The results confirmed the strong association between the presence of KIR2DL5 and the non-response to antiviral treatment (P=0.001). CONCLUSIONS: Host genetic factors may be associated with a non-response to antiviral therapy. KIR2DL5 is a candidate gene involved in immunomodulation associated with non-response to antiviral therapy.
Assuntos
Antivirais/uso terapêutico , Antígenos HLA-C/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Polimorfismo Genético , Receptores KIR2DL5/genética , Adulto , Idoso , Estudos de Coortes , Farmacorresistência Viral/genética , Quimioterapia Combinada , Feminino , Frequência do Gene , Antígenos HLA-C/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/diagnóstico , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Valor Preditivo dos Testes , Probabilidade , Prognóstico , Receptores KIR2DL5/efeitos dos fármacos , Receptores de Células Matadoras Naturais/efeitos dos fármacos , Receptores de Células Matadoras Naturais/genética , Proteínas Recombinantes , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Ribavirina/uso terapêutico , Estatísticas não Paramétricas , Falha de Tratamento , Resultado do Tratamento , Carga Viral/efeitos dos fármacosRESUMO
A detailed phenotypic analysis of major and minor circulating lymphocyte subsets is described in potential blood donors with markers of hepatitis C virus (HCV), including non-viremic and viremic groups. Although there were no changes in the hematological profile of either group, increased the levels of pre-NK cells (CD3-CD16+CD56-) and a lower frequency of mature NK cells (CD3-CD16+CD56+) characterized innate immunity in the non-viremic group. Both non-viremic and viremic groups displayed significantly increased levels of CD56(Bright) NK cells. Furthermore, this subset was significantly elevated in the viremic subgroup with a low viral load. In addition, an increase in the NKT2 subset was observed only in this subgroup. An enhanced frequency of activated CD4+ T-cells (CD4+HLA-DR+) was a characteristic feature of the non-viremic group, whereas elevated CD19+ B-cells and CD19+CD86+ cell populations were the major phenotypic features of the viremic group, particularly in individuals with a low viral load. Although CD4+CD25High T-cells were significantly elevated in both the viremic and non-viremic groups, it was particularly evident in the viremic low viral load subgroup. A parallel increase in CD4+CD25High T-cells, pre-NK, and activated CD4+ T-cells was observed in the non-viremic group, whereas a parallel increase in CD4+CD25High T-cells and CD19+ B-cells was characteristic of the low viral load subgroup. These findings suggest that CD56Bright NK cells, together with pre-NK cells and activated CD4+ T-cells in combination with CD4+CD25High T-cells, might play an important role in controlling viremia. Elevated CD56(Bright) NK cells, B-cell responses and a T-regulated immunological profile appeared to be associated with a low viral load.
Assuntos
Antígenos CD/análise , Linfócitos B/imunologia , Doadores de Sangue , Linfócitos T CD4-Positivos/imunologia , Hepatite C Crônica/imunologia , Células Matadoras Naturais/imunologia , Subpopulações de Linfócitos/imunologia , Adulto , Feminino , Hepacivirus/isolamento & purificação , Humanos , Células Matadoras Naturais/química , Masculino , Pessoa de Meia-Idade , Carga Viral , Viremia/imunologiaRESUMO
UNLABELLED: Patients with chronic hepatitis C can have variable clinical progression. Hepatic histological alterations appear to be milder in asymptomatic subjects who have persistently normal ALT levels. AIMS: To evaluate the severity of histological liver alterations in blood donors with normal and elevated ALT levels. METHODS: We evaluated volunteer blood donors from the main blood bank of the city of Salvador-Brazil. Those who were anti-HCV positive were invited to participate in the study. Serum ALT and AST levels were measured at two time points, two months apart. Donors were divided into two groups: group I, individuals with ALT > 1.5 times the upper limit of normal in at least one time point and group II, individuals with normal or near normal ALT, at both time points RESULTS: We evaluated 30,232 blood donors and 528 (1.7%) of them were anti-HCV positive. Eighty-two attended our service and HCV infection was confirmed in 66 individuals. Male gender predominated in both groups; the mean age was 36 for group I, and 33 for group II. Tattoos and intravenous illicit drug use were frequently-encountered risk factors. Liver biopsy was done in 43 subjects. Among donors with elevated ALT, two (10%) had minimum alterations, while in group II normal liver or minimum alterations were observed in six (26%) subjects. Chronic hepatitis or cirrhosis was encountered in 35 (81%) individuals: three (15%) and five (21%) subjects had chronic hepatitis without inflammatory activity, 10 (50%) and 11 (48%) had minimum to moderate activity and five (25%) and one (4.3%) had cirrhosis, in groups I and II, respectively (P was not significant). CONCLUSIONS: The prevalence of anti-HCV among this population of volunteer blood donors was 1.7%, and these subjects had few liver histological alterations or chronic hepatitis and cirrhosis. Liver injury severity was significant in patients with elevated ALT, however subjects with normal levels may also present chronic hepatitis and cirrhosis.
Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Hepacivirus/imunologia , Hepatite C Crônica/patologia , Fígado/patologia , Doadores de Sangue , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/enzimologia , Hepatite C Crônica/epidemiologia , Humanos , Masculino , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
The objective of the present study was to analyze HCV serological and virological parameters from hemophiliacs in the State of Bahia. Anti-HCV was investigated by ELISA in a cohort of 268 hemophiliacs A/B who were followed-up in a reference unit for hemotherapy in the State of Bahia. HCV viremia and genotypes were also determined from a subset of 66 anti-HCV seropositive hemophiliacs. Seroprevalence among hemophiliacs was 42.2% (95% CI 36.5-48.1) and was significantly higher (p<0.05) according to age > or =10 years, presence of factor VIII/IX inhibitory antibodies and other infection markers. None of the hemophiliacs less than 5 years of age were anti-HCV seropositive. Viremia was detectable in 77.3% (51/66). HCV genotype 1 (74%) was the most prevalent followed by genotype 3 (22%) and genotype 2 (4%). Our results indicate that HCV prevalence is still high among hemophiliacs, although HCV transmission was not observed in young hemophiliacs.
Assuntos
Hemofilia A/virologia , Hemofilia B/virologia , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/sangue , Hepatite C/epidemiologia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Fatores de Coagulação Sanguínea/imunologia , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Hemofilia A/sangue , Hemofilia B/sangue , Hepacivirus/genética , Hepatite C/diagnóstico , Hepatite C/virologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
UNLABELLED: Hepatitis B virus (HBV) can be classified into at least eight genotypes, A-H. We evaluated the distribution HBV genotypes among patients with chronic infection. METHODS: We consecutively evaluated adult patients with chronic HBV infection from Salvador, Brazil. Patients were classified according to HBV infection chronic phases based on HBV-DNA levels and presence of serum HBV markers. HBV-DNA was qualitatively and quantitatively detected in serum by polymerised chain reaction (PCR). Isolates were genotyped by comparison of amino acid mutations and phylogenetic analysis. RESULTS: One-hundred and fourteen patients were evaluated. HBV-DNA was positive in 96 samples. HBV genotype was done in 76. Mean age was 36 +/- 11.3. In 61 of 76 cases subjects were classified as inactive HBsAg carriers. Their mean HBV serum level was 1760 copies/ml and 53 of 61 were infected with HBV genotype A, seven with HBV genotype F and one with genotype B. Twelve of the 76 patients had detectable hepatitis B e-antigen (HBeAg) in serum. Ten were infected with HBV genotype A and two with genotype F; most had increased alanine aminotransferase and high HBV-DNA levels. Three patients were in the immunotolerant phase, two were infected with HBV genotype A and one with genotype F. HBV subtyping showed subtypes adw2 and adw4. CONCLUSIONS: HBV genotype A adw2 and genotype F adw4 were the most prevalent isolates found. We could not find differences in genotype distribution according to HBV clinical phases and DNA levels. We did not detect HBV genotype D in contrast to a previous study in our center with acute hepatitis B. All inactive HBsAg carriers had low HBV-DNA levels.
Assuntos
Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Adolescente , Adulto , Idoso , Sequência de Aminoácidos , Sequência de Bases , Brasil , DNA Viral/sangue , DNA Viral/genética , Feminino , Genes Virais , Genótipo , Vírus da Hepatite B/classificação , Vírus da Hepatite B/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Homologia de Sequência de Aminoácidos , Proteínas Virais/genéticaRESUMO
Patients with chronic hepatitis C can have variable clinical progression. Hepatic histological alterations appear to be milder in asymptomatic subjects who have persistently normal ALT levels. AIMS: To evaluate the severity of histological liver alterations in blood donors with normal and elevated ALT levels. METHODS: We evaluated volunteer blood donors from the main blood bank of the city of Salvador-Brazil. Those who were anti-HCV positive were invited to participate in the study. Serum ALT and AST levels were measured at two time points, two months apart. Donors were divided into two groups: group I, individuals with ALT > 1.5 times the upper limit of normal in at least one time point and group II, individuals with normal or near normal ALT, at both time points RESULTS: We evaluated 30,232 blood donors and 528 (1.7 percent) of them were anti-HCV positive. Eighty-two attended our service and HCV infection was confirmed in 66 individuals. Male gender predominated in both groups; the mean age was 36 for group I, and 33 for group II. Tattoos and intravenous illicit drug use were frequently-encountered risk factors. Liver biopsy was done in 43 subjects. Among donors with elevated ALT, two (10 percent) had minimum alterations, while in group II normal liver or minimum alterations were observed in six (26 percent) subjects. Chronic hepatitis or cirrhosis was encountered in 35 (81 percent) individuals: three (15 percent) and five (21 percent) subjects had chronic hepatitis without inflammatory activity, 10 (50 percent) and 11 (48 percent) had minimum to moderate activity and five (25 percent) and one (4.3 percent) had cirrhosis, in groups I and II, respectively (P was not significant). CONCLUSIONS: The prevalence of anti-HCV among this population of volunteer blood donors was 1.7 percent, and these subjects had few liver histological alterations or chronic hepatitis and cirrhosis. Liver injury severity was significant in patients with elevated ALT, however subjects with normal levels may also present chronic hepatitis and cirrhosis.
Assuntos
Feminino , Humanos , Masculino , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Hepacivirus/imunologia , Hepatite C Crônica/patologia , Fígado/patologia , Doadores de Sangue , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/enzimologia , Hepatite C Crônica/epidemiologia , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
O objetivo deste estudo foi analisar parâmetros sorológicos e virológicos em hemofílicos no Estado da Bahia. O anti-VHC foi investigado por ELISA em uma coorte de 268 hemofílicos A/B sob acompanhamento em uma unidade de referência do Estado da Bahia. A viremia do VHC e genótipos foram determinados em um subgrupo de 66 hemofílicos soropositivos para o anti-VHC. A soroprevalência do anti-VHC entre os hemofílicos foi de 42,2% (IC 95% 36,5-48,1) e foi associada significativamente (p<0,05) a idade >10 anos, presenca de anticorpos antifator VIII/IX e outros marcadores sorológicos de infeccão. Nenhum dos hemofílicos com idade inferior a 5 anos foram anti-VHC positivos. A viremia foi detectada em 77,3% (51/66), sendo o genótipo 1 do VHC (74%) o mais prevalente, seguido pelos genótipos 3 (22%) e 2 (4%). Nossos resultados indicam que a prevalência do VHC é ainda alta entre os hemofílicos, muito embora a transmissão não tenha sido observada entre os menores de 5 anos.
Assuntos
Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Hemofilia A/virologia , Hemofilia B/virologia , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/sangue , Hepatite C/epidemiologia , Biomarcadores/sangue , Fatores de Coagulação Sanguínea/imunologia , Brasil/epidemiologia , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Genótipo , Hemofilia A/sangue , Hemofilia B/sangue , Hepacivirus/genética , Hepatite C/diagnóstico , Hepatite C/virologia , Prevalência , Fatores de Risco , RNA Viral/sangue , Estudos Soroepidemiológicos , Índice de Gravidade de Doença , ViremiaRESUMO
BACKGROUND: Hepatitis C infection in hemodialysis units has been evaluated in different geographic regions. AIMS: The prevalence of anti-HCV in patients undergoing hemodialysis program in the city of Salvador, State of Bahia, Brazil, was studied and its association with transfusions, duration of hemodialysis and ALT elevation. METHOD: During a period of 17 months, all patients undergoing dialytic treatment, were evaluated. The total number of patients was 395, all of whom completed a questionnaire and provided serum samples for laboratory analysis. Serological levels were measured for ALT and the samples were tested for anti-HCV using ELISA II with a further confirmation using RIBA III. RESULTS: Anti-HCV was positive in 23.8 per cent (94/395). The presence of transfusions was associated with anti-HCV and as the number of transfusions used increased, so did the frequency of anti-HCV. Of the patients who never received transfusions, 12.5 per cent (6/48) were anti-HCV positive. The duration of dialytic treatment lasted from 53.44 +/- 36.45 months in the anti-HCV positive group and 22.10 +/- 22.75 months for the group testing negative. ALT elevation was more frequent in the anti-HCV positive group. Positivity for the RIBA III fractions was 79.8 per cent, 100 per cent, 80.9 per cent and 52.1 per cent, for c100-3, c33, c22 and NS5, respectively. The anti-NS5 was even less frequent in the group with elevated ALT. CONCLUSIONS: The prevalence of anti-HCV in patients undergoing chronic hemodialysis in Salvador, Bahia, is elevated and it is associated with transfusions, a longer duration of dialytic treatment and ALT elevation.
Assuntos
Humanos , Masculino , Feminino , Adulto , Adolescente , Pessoa de Meia-Idade , Alanina Transaminase/sangue , Hepacivirus/isolamento & purificação , Anticorpos Anti-Hepatite C/sangue , Hepatite C/epidemiologia , Diálise Renal/efeitos adversos , Idoso de 80 Anos ou mais , Doadores de Sangue , Transfusão de Sangue/efeitos adversos , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática , Unidades Hospitalares de Hemodiálise , Hepacivirus/imunologia , Hepatite C/imunologia , Immunoblotting , Prevalência , Estudos Soroepidemiológicos , Fatores de TempoRESUMO
Helicobacter pylori plays an important role in the etiology of peptic ulcer disease. Its prevalence appears to be higher in developing countries. We evaluated the seroprevalence of H. pylori and risk factors associated with infection in voluntary blood donors who attended the main blood center of the city of Salvador, Brazil. The subjects responded to an epidemiological questionnaire, with information about sex, age, race, lifestyle, social-economic level indicators, and residence and hygiene conditions. Anti-H. pylori antibody was determined by ELISA (Cobas Core, Roche). Three hundred and seven subjects were included in the study. Anti-H. pylori antibody results were indeterminate in 33 individuals (10.8 percent), who were excluded from analysis. Among the remaining 274 subjects, 187 (68.2 percent) were anti-H. pylori positive. Based on multivariate logistic regression analysis three variables were found to be significantly associated with a higher prevalence of H. pylori infection: absence of plumbing in the residence during childhood, a history of rainwater invading the dwelling during childhood, and low ingestion of milk.
Assuntos
Humanos , Masculino , Feminino , Infecções por Helicobacter , Helicobacter pylori , Anticorpos Antibacterianos , Doadores de Sangue , Brasil , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Infecções por Helicobacter , Modelos Logísticos , Análise Multivariada , Prevalência , Fatores de Risco , Estudos SoroepidemiológicosRESUMO
O vírus da hepatite C, recentemente descoberto, é o principal agente etiológico das hepatites pós-transfusionais, com percentual elevado de cronificação e evolução para carcinoma hepatocelular. Vários estudos têm se dedicado à compreensão da epidemiologia, evolução clínica e formas de apresentação da hepatite C. Desde 1990, a triagem de doadores de sangue com marcadores positivos para este vírus (antiVHC) reduziu, sensivelmente, a incidência de hepatite pós-transfusional, entretanto, criou dificuldades na interpretação clínica dos doadores de sangue antiVHC positivos...
Assuntos
Humanos , Hepacivirus/imunologia , Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Hepatite C/imunologia , Hepatite C/patologia , Hepatite C/prevenção & controle , Hepatite C/sangueRESUMO
Estudo restrospectivo de 2.464 exames retossigmoidoscópicos realizados no Hospital Universitário da Universidade Federal de Sergipe, no Hospital governador Joäo Alves Filho e em Clínicas Particulares de Aracaju - sergipe, no período compreendido entre Janeiro de 1991 a dezembro de 1999. em 442 exames foram observados processos inflamatórios, dos quais houve comprovaçäo de retocolite esquistossomótica em 55 casos. Foram analisadas variáveis como idade, sexo, manifestações clínicas procedência, localizaçäo das alterações, patologias associadas e impressäo dianóstica ao exame endoscópico. Houve predomínio do sexo masculino com 76 por cento do total. A idade variou de 9 a 77 anos, com média de 37. A terceira década de vida foi a mais acometida no sexo feminino, enquanto que no masculino foi a quinta Cerca de 44 por cento da populaçäo provinha do interior de Sergipe. Foi observada predominância das manifestações da retocolite ulcerativa exclausivamente na porçäo retal, com 80 por cento. O sangramento foi a principal indicaçäo para a realizaçäo dos exames (355). Num total de 47 patologias associadas encontradas, as mais freqüentes foram hemorróida, papilite e plicoma. Em 76 por cento dos pacientes näo houve suspeita de parasitose como etiologia da retocolite ao exame retossigmoidoscópico. Os resultados deste trabalho demonstraram que a esquistossomose deve ser pesquisada, em sergipe e em regiões onde esta seja endêmica, como importante diagnóstico diferencial em pacientes com processo inflamatórios intestinais
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Proctocolite , Esquistossomose mansoni , Proctocolite , Estudos Retrospectivos , Esquistossomose mansoni , SigmoidoscopiaRESUMO
Foram analisados retrospectivamente 11 casos de pacientes com procidência retal, submetidos a operaçäo de Delorme com cerclagem a Thiersch modificada, no período de 1990 a 1996. Os autores observaram que a técnica foi bem tolerada pelos pacientes, evitou a anestesia geral na maioria dos casos e o risco de laparotomia em idosos e debilitados; o acesso perineal foi seguro, a morbidade mínima, mortalidade nula, alta hospitalar precoce e custos reduzidos
Assuntos
Humanos , Masculino , Feminino , Prolapso Retal/cirurgia , Ampicilina/uso terapêutico , Antibacterianos/uso terapêutico , Antitricômonas/uso terapêutico , Cloranfenicol/uso terapêutico , Gentamicinas/uso terapêutico , Metronidazol/uso terapêutico , Penicilinas/uso terapêuticoRESUMO
Neste estudo retrospectivo, testamos a qualidade da analgesia pós-operatória com morfina peridural em cirurgias orificiais, confrontando com os efeitos colaterais apresentados. Selecionamos 36 pacientes que utilizaram morfina-epidural (1,0 a 1,5 mg), analisando as incidências de prurido, depressäo respiratória, náuseas e vômitos, retençäo urinária, uso de analgésicos no pós-operatório imediato (POI) e a permanência hospitalar. Dividimos os pacientes em dois grupos, segundo a prescriçäo de analgésicos no POI: Grupo I (diclofenaco sódico, 75 mg, IM, SOS), Grupo II (diclofenaco sódico 75 mg, IM, 12/12h). A idade mínima e máxima foi respectivamente 21 e 57 anos com idade média de 34,5 anos com desvio padräo igual a 7,1. Resultados mostraram: ausência de depressäo respiratória; incidência relevante de retençäo urinária (47 por cento), com predominância masculina; e diferença na qualidade da analgesia pela potencializaçäo do diclofenaco associado à morfina, tendo 100 por cento de pacinentes sem dor no Grupo II contra 62,5 por cento no Grupo I (p < 0,05). Prurido (5 por cento) e náuseas e vômitos (25 por cento) foram inferiores a outros trabalhos descritos. O tempo de internamento foi 2-3 dias (94,4 por cento). A analgesia foi efetiva, contudo a incidência elevada de efeitos colaterais e o adequado controle da dor com outros métodos sistêmicos, talvez reservem o uso da morfina-peridural para casos de dor mais severa. Atualmente a associaçäo de agonista-antagonista ou antagonista com a morfina dá uma excelente analgesia com poucos efeitos colaterais