RESUMEN
OBJECTIVES: To evaluate the impact of an information booklet on HIV clinical trials, Clinical Trials in HIV and AIDS: Information For People Who Are Thinking About Joining a Trial, in addition to the standard trial information (SI) on patients' knowledge; understanding and attitudes about clinical trials; and to investigate patients' motivations and reasons for enrolling or not enrolling in a clinical trial. METHODS: Fifty HIV-1 positive patients who attended the HIV clinic at a west London hospital were randomized to receive either SI alone (n = 27) or SI and a 16 page information booklet explaining the principles and procedures of HIV clinical trials (n = 23). A self-administered questionnaire was used at baseline to assess past experience and attitudes to clinical trials (10 questions), knowledge and understanding of HIV treatments (8 questions) and clinical trials (11 questions). At 2-6 months after randomization, a second interviewer-administered questionnaire addressed the patient's assessment of the usefulness and comprehensiveness of the information provided by the SI and information booklet, whether or not the patient had enrolled in a clinical trial and reasons for enrolling/not enrolling, knowledge of specific aspects of the trial protocol the patient was eligible to join (13 questions) and general knowledge of clinical trial procedures (repeat of 11 baseline questions). Changes in the attitudes and scores on knowledge and understanding of clinical trials were compared for the two groups. RESULTS: In both groups, patient knowledge of clinical trial procedures improved significantly over the study period. The median score increased from 30 at baseline to 35/44 at follow-up (SI only) vs. 24-31/44 (SI plus booklet), but this did not differ significantly between the two groups. However, knowledge of the specific trial protocol was poor [median score 13/25, interquartile range (IQR) 8-14], and there was no difference in the scores for the two groups. The prime motivations for joining a clinical trial were to benefit personal health and to gain access to new treatments. Potential side-effects were the main concern of prospective trial participants. CONCLUSIONS: This small trial shows that, while the patients' general knowledge and understanding of clinical trials improved over time, this was not improved by the information booklet and recollection of the details of the relevant trial protocol remained poor.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Ensayos Clínicos como Asunto , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/psicología , Conocimientos, Actitudes y Práctica en Salud , Folletos , Aceptación de la Atención de Salud/psicología , Educación del Paciente como Asunto/métodos , Selección de Paciente , Materiales de Enseñanza/normas , Adulto , Fármacos Anti-VIH/efectos adversos , Escolaridad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Motivación , Aceptación de la Atención de Salud/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
This study investigated the contribution of psychological factors to disease progression among long-term HIV-1 infected gay men. Participants completed self-report measures including coping strategies, life events, social support, personality and psychological morbidity and were followed clinically for up to 30 months. Cox proportional hazards survival analyses were carried out to CD4<200 x 106/1 and AIDS-related complex (ARC) or AIDS diagnosis controlling for viral load, antiretroviral drug use and CD4 count. Only acceptance coping was a significant predictor of time to ARC or AIDS diagnosis: the risk of ARC or AIDS was almost 5 times greater for those scoring within the lowest tertile compared with those scoring in the highest tertile (HR=4.7, 95% CI 1.8-12.3).
Asunto(s)
Infecciones por VIH/psicología , Complejo Relacionado con el SIDA/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Adaptación Psicológica , Adulto , Anciano , Recuento de Linfocito CD4 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Personalidad , Apoyo Social , Factores de TiempoRESUMEN
The role of polymorphisms in genes encoding chemokines and their receptors (CCR2B, SDF-1, and the promoter region of CCR5) in human immunodeficiency virus (HIV) disease progression was studied in 132 white HIV type 1 (HIV-1)-infected participants from a United Kingdom cohort study. Genotyping was done by use of amplification refractory mutation system-polymerase chain reaction with sequence-specific primers, and Cox proportional hazards models were used to examine the impact of polymorphisms on time to a CD4 cell count <200x106/L and to CDC stage IV disease. The results confirm a significant association of the CCR2B-64I mutant genotype with slower progression to a CD4 count <200 (hazards ratio [HR], 0.39; 95% confidence interval [CI], 0.17-0.91) but not with the SDF-1alpha 3' UTR homozygous mutation. The effects of the CCR5 and CCR2 mutations were genetically independent and similar in the magnitude of their protective effect on progression to a CD4 count <200 cells. A novel finding was an association of borderline significance between homozygosity for C at nucleotide position 59353 in the CCR5 promoter region and a slower rate of CD4 cell decline to <200x106/L (HR, 0. 58; 95% CI, 0.34-0.996).
Asunto(s)
Infecciones por VIH/genética , Infecciones por VIH/fisiopatología , VIH-1 , Polimorfismo Genético , Receptores CCR5/genética , Receptores de Quimiocina/genética , Receptores de Citocinas/genética , Bisexualidad , Estudios de Casos y Controles , Intervalos de Confianza , Cartilla de ADN , Progresión de la Enfermedad , Genotipo , Anticuerpos Anti-VIH/sangre , Infecciones por VIH/inmunología , Homosexualidad Masculina , Humanos , Masculino , Mutación Puntual , Reacción en Cadena de la Polimerasa , Pronóstico , Regiones Promotoras Genéticas , Modelos de Riesgos Proporcionales , Receptores CCR2 , Factores de TiempoRESUMEN
nef alleles derived from a large number of individuals infected with human immunodeficiency virus type 1 (HIV-1) were analyzed to investigate the frequency of disrupted nef genes and to elucidate whether specific amino acid substitutions in Nef are associated with different stages of disease. We confirm that deletions or gross abnormalities in nef are rarely present. However, a comparison of Nef consensus sequences derived from 41 long-term nonprogressors and from 50 individuals with progressive HIV-1 infection revealed that specific variations are associated with different stages of infection. Five amino acid variations in Nef (T15, N51, H102, L170, and E182) were more frequently observed among nonprogressors, while nine features (an additional N-terminal PxxP motif, A15, R39, T51, T157, C163, N169, Q170, and M182) were more frequently found in progressors. Strong correlations between the frequency of these variations in Nef and both the CD4(+)-cell count and the viral load were observed. Moreover, analysis of sequential samples obtained from two progressors revealed that several variations in Nef, which were more commonly observed in patients with low CD4(+)-T-cell counts, were detected only during or after progression to immunodeficiency. Our results indicate that sequence variations in Nef are associated with different stages of HIV-1 infection and suggest a link between nef gene function and the immune status of the infected individual.
Asunto(s)
Productos del Gen nef/genética , Variación Genética , Infecciones por VIH/virología , VIH-1/genética , Síndrome de Inmunodeficiencia Adquirida/virología , Secuencia de Aminoácidos , Secuencia de Bases , Recuento de Linfocito CD4 , Estudios de Cohortes , ADN Viral , Progresión de la Enfermedad , Productos del Gen nef/química , Genes Virales , Infecciones por VIH/inmunología , Humanos , Datos de Secuencia Molecular , Conformación Proteica , Homología de Secuencia de Aminoácido , Carga Viral , Productos del Gen nef del Virus de la Inmunodeficiencia HumanaRESUMEN
Identification of the reasons for long-term survival in HIV infection is an area of current intense research. The objective of this study was to determine the perceptions among patients with different rates of disease progression as to the reasons for a good outcome with HIV. In a case-control study of 134 long-term (> or = 8 years) HIV-infected participants, 62 were defined as non-progressors; current CD4 cell count > or = 500 x 10(6)/L and asymptomatic or only mildly symptomatic. Two groups of control patients were identified: intermediate progressors who also had been HIV-infected for > or = 8 years, but whose current CD4 cell count was < 500 x 10(6)/L (n = 61), and a group of rapid progressors who had developed AIDS within 5 years of HIV infection (n = 11). Non-progressors were asked 'what do you feel are the reasons for your good outcome with HIV-infection?' and intermediate and rapid progressors were asked 'what do you feel are the reasons for a good outcome with HIV infection?'. Mental attitude, and in particular a positive outlook was the reason most frequently given for a good outcome among both non-progressors (NP) 42%, and progressors (P) 40%, followed by lifestyle measures and personal action (NP 31%, P 35%). Medical treatments such as anti-retroviral drugs were rarely suggested (< 3%). No significant differences were observed in the frequency of the different reasons given by non-progressors and progressors. The belief among our long-term HIV-infected individuals, that a positive outlook, lifestyle and personal action are important determinants of a good prognosis, is in sharp contrast to the biomedical model of disease progression that prevails among the medical and scientific research community.
Asunto(s)
Actitud Frente a la Salud , Infecciones por VIH/psicología , Sobrevivientes/psicología , Síndrome de Inmunodeficiencia Adquirida/psicología , Adulto , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Estilo de Vida , Masculino , Factores de TiempoRESUMEN
Cytotoxic T lymphocytes (CTLs) are thought to play a crucial role in the termination of the acute primary HIV-1 syndrome, but clear evidence for this presumption has been lacking. Here we demonstrate positive selection of HIV-1 proviral sequences encoding variants within a CTL epitope in Nef, a gene product critical for viral pathogenicity, during and after seroconversion. These positively selected HIV-1 variants carried epitope sequence changes that either diminished or escaped CTL recognition. Other proviruses had mutations that abolished the Nef epitope altogether. These results provide clear evidence that CTLs exert selection pressure on the viral population in acute HIV-1 infection.
Asunto(s)
Productos del Gen nef/inmunología , Antígenos VIH/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Linfocitos T Citotóxicos/inmunología , Adulto , Secuencia de Aminoácidos , Células Clonales , Clonación Molecular , Epítopos/química , Epítopos/inmunología , Productos del Gen nef/química , Productos del Gen nef/genética , Genotipo , Antígenos VIH/química , Antígenos VIH/genética , Infecciones por VIH/virología , VIH-1/genética , Antígenos HLA/genética , Antígenos HLA/inmunología , Humanos , Masculino , Datos de Secuencia Molecular , Péptidos/química , Péptidos/inmunología , Reacción en Cadena de la Polimerasa , Provirus/genética , Provirus/inmunología , Selección Genética , Análisis de Secuencia , Productos del Gen nef del Virus de la Inmunodeficiencia HumanaRESUMEN
Inadvertent subarachnoid injection of a local anesthetic during the conduct of epidural anesthesia may have a devastating effect on the patient. The incidence of dural puncture with an epidural catheter has been reported to range from 0.5% to 0.9%. This case report demonstrates that, despite negative aspiration of cerebral spinal fluid from the catheter, subarachnoid injection of a local anesthetic can occur.
Asunto(s)
Anestesia Epidural/efectos adversos , Espacio Subaracnoideo , Succión/métodos , Adulto , Anestesia Epidural/métodos , Femenino , HumanosRESUMEN
The water soluble benzodiazepine derivative, midazolam, is used almost exclusively at our institution to produce sedation for numerous surgical procedures. Mild arterial oxygen desaturation has been reported in patients who have received as little as .04 mg/kg. A time series design study was undertaken to determine if there was any correlation between the decline in arterial oxygen percent saturation (SaO2) and the time at which sedation occurred and to establish the presence of any statistical significance in this decline. Thirty-one ASA I and II patients consisting of 8 females and 23 males requiring various minor orthopedic and general surgical procedures were studied. The total mean age of the population was 32.29 +/- 12.43 years (mean +/- SD). Fourteen patients had a smoking history, while 15 patients did not (2 patients were eliminated from the study for failure to demonstrate sedation, as characterized by either Verrill's sign or thickened speech following intravenous administration of midazolam). All patients arrived in the operating room unpremedicated and were administered .04 mg/kg midazolam intravenously. Arterial oxygen saturation was measured over a 10-minute period using pulse oximetry. Results were analyzed using regression analysis, a t-test for independent groups, and a one-way analysis of variance. There was no statistically significant difference in the decline in SaO2 between smokers and nonsmokers. Our study has shown that the mean onset of sedation using a dose of .04 mg/kg occurred between 3 and 4 minutes, with the peak fall in SaO2 occurring at the 3-minute interval irrespective of smoking history. The greatest mean drop in SaO2 was 95.84%. Midazolam, like its parent drug, diazepam, alters ventilatory mechanics.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Midazolam/farmacología , Oximetría , Respiración/efectos de los fármacos , Adulto , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Midazolam/administración & dosificación , Midazolam/farmacocinéticaRESUMEN
Medical records of 131 dogs with external ocular diseases were reviewed. Bacteriologic culture of swab specimens from 151 eyes revealed 100 eyes (66.2%) were considered positive for potentially pathogenic microorganisms. Of 127 species of microorganisms (bacterial and fungal) isolated, 50 (39.3%) were Staphylococcus spp (S intermedius, 17.3%). Streptococcus spp were the next most frequently isolated organism at 32 (25.2%), (Str canis, 16.5%). beta-Hemolytic streptococci (17%) were isolated more frequently than were alpha-hemolytic streptococci (9%), and coagulase-positive staphylococcal species (29%) were isolated almost 3 times as often as were coagulase-negative species (11%). Fungal and yeast organisms were isolated from 4.6% of the eyes. In vitro, most Staphylococcus spp were susceptible to cephalothin, bacitracin, and gentamicin, whereas most Streptococcus spp were susceptible to chloramphenicol, erythromycin, carbenicillin, and cephalothin. Pseudomonas spp were sensitive to tobramycin, gentamicin, and amikacin.