RESUMO
Respecto del tratamiento con fármacos opioides se discuten algunas de las dificultades que tienen los médicos para valorar los síntomas en pacientes con dolor moderado a severo, y para implementar estrategias terapéuticas para aliviarlos. Dentro de las conductas médicas englobadas como ôopiofobiaõ se describen el miedo a que el paciente desarrolle depresión respiratoria (que no llega al 1% de riesgo de ocurrencia luego de la vía parenteral) y a que se vuelva adicto. Se repasan los conceptos de adicción, dependencia, tolerancia y se resumen las principales series de pacientes que proveen evidencia científica sobre la seguridad de los opioides utilizados en forma apropiada y en el marco de cuidados médicos.
Assuntos
Dor/tratamento farmacológico , Dor/terapia , Tratamento Farmacológico , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Morfina/administração & dosagem , Morfina/efeitos adversosRESUMO
As the chimpanzee, the only reliable animal model for hepatitis C virus (HCV) infection, is impractical for early stage testing of HCV vaccine candidates, we have evaluated the immune response in mice to an experimental plasmid based HCV vaccine. We used this system because DNA vaccines can be rapidly constructed without the necessity of large scale protein production and purification. In this preliminary study we tested the immune response in mice to HCV envelope glycoprotein, E2, induced by a eukaryotic expression plasmid. Protein expression was monitored by immunofluorescence in transfected tissue culture cells. Each mouse was inoculated intramuscular with 100 microg plasmid DNA and some mice were boosted after 5 weeks. Among 12 BALB/C mice inoculated, 10 developed antibody to E2 by the second week. The antibody levels increased steadily before reaching a plateau in mice receiving the booster, but in the nonboosted mice the antibody declined over time. The serum from one mouse was tested against a series of overlapping peptides covering most of E2. This serum contained antibodies recognizing two distinct epitopes beginning at amino acid 57 and amino acid 113 but no antibody was directed against peptides representing the hypervariable region of E2, antibody to which is thought to be important in HCV neutralization. We have shown that the use of plasmid based vaccines can induce a specific immune response in mice against HCV antigens. This system should be useful as the first step in vaccine development.
Assuntos
DNA Viral/imunologia , Plasmídeos/imunologia , Proteínas do Envelope Viral/imunologia , Animais , DNA Viral/análise , Epitopos/imunologia , Células HeLa/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Músculo Esquelético/química , Plasmídeos/genética , Especificidade da Espécie , Transfecção , Proteínas do Envelope Viral/metabolismoRESUMO
OBJECTIVES: To determine the frequency of heterozygous carriers of the Tay-Sachs disease gene in an asymptomatic Ashkenazi Jewish population and to compare the acceptability of different community testing strategies. DESIGN: Pilot survey of carrier rates and community attitudes. SETTING: Sydney, February 1993 to November 1994. PARTICIPANTS: 147 self- or medically referred people of Ashkenazi Jewish origin were tested. Jewish religious, medical and community organisations and leaders were consulted. OUTCOMES: Prevalence of HEXA mutations, client and community preference for different testing and reporting strategies. RESULTS: Frequency of heterozygous carriers was 1 in 18, with a relative frequency of the three major allelic variants similar to that in overseas studies. Most subjects were medically referred and preferred individual reporting of their carrier status. Community representatives had serious reservations about this strategy and few orthodox Jews participated in the study. An alternative strategy was developed for future testing. CONCLUSIONS: Frequency of heterozygous carriers of the Tay-Sachs disease gene was higher than found among Ashkenazi Jews in other countries, possibly because of ascertainment bias. A testing strategy with medical referral and individual reporting of carrier status may not be appropriate for all the community at risk and a modified strategy is necessary.
Assuntos
Testes Genéticos/organização & administração , Programas Nacionais de Saúde , Doença de Tay-Sachs/prevenção & controle , Heterozigoto , Humanos , Judeus , New South Wales , Aceitação pelo Paciente de Cuidados de Saúde , Projetos Piloto , Doença de Tay-Sachs/etnologiaRESUMO
OBJECTIVE: To assess the clinical significance of antibody to hepatitis C virus (anti-HCV) in volunteer blood donors. DESIGN: Prospective cohort study. SETTING: National Institutes of Health Clinical Center, a tertiary referral research hospital. PATIENTS: 60 anti-HCV-positive blood donors, divided into three groups of 20 persons each: Group I had normal alanine aminotransferase levels, group II had levels elevated to values less than twice the normal range, and group III had levels elevated to values greater than twice the normal range. MEASUREMENTS: Medical history, results of laboratory and virologic testing, and percutaneous liver biopsy findings. RESULTS: Participants with normal alanine aminotransferase levels were older and more often female than those with abnormal levels. The source of infection, duration of disease, symptom score, and amount of alcohol consumed were similar in the three groups. Hepatitis C virus RNA was detectable in 85% of participants, more commonly in the groups with elevated alanine aminotransferase levels (95%) than in the group with normal levels (65%); however, titers were similar in all groups. Examination of liver biopsy specimens showed chronic hepatitis in 54 participants (90%) and cirrhosis in 1 participant. The only normal liver biopsy specimens (n = 3) were those from participants who were HCV RNA negative and had normal alanine aminotransferase levels. CONCLUSIONS: Most blood donors with anti-HCV have chronic hepatitis C regardless of their serum alanine aminotransferase levels. Donors with normal alanine aminotransferase levels and no HCV RNA in their serum generally have normal liver histologic findings or minimal changes and have probably recovered from HCV infection.