RESUMEN
The induction of functional memory cytotoxic T lymphocytes (CTLs) is a major goal of vaccination against intracellular pathogens. Interleukin (IL)-12 is critical for the generation of memory CTLs, and inhibition of mammalian target of rapamycin (mTOR) by rapamycin can effectively enhance the memory CTL response. Yet, the role of IL-12 in mTOR's regulation of memory CTL is unknown. Here we hypothesized that the immunostimulatory effects of mTOR on memory CTLs requires IL-12 signaling. Our results revealed that rapamycin increased the generation of memory CTLs in vaccinia virus infection, and this enhancement was dependent upon the IL-12 signal. Furthermore, IL-12 receptor deficiency diminished the secondary expansion of rapamycin-regulated memory and resultant secondary memory CTLs were abolished. Rapamycin enhanced IL-12 signaling by upregulating IL-12 receptor ß2 expression and signal transducer and activator of transcription factor 4 phosphorylation in CTLs during early infection. In addition, rapamycin continually suppressed T-bet expression in both wild-type and IL-12 receptor knockout CTLs. These results indicate an essential role for IL-12 in the regulation of memory CTLs by mTOR and highlight the importance of considering the interplay between cytokines and adjuvants during vaccine design.
Asunto(s)
Memoria Inmunológica/inmunología , Interleucina-2/inmunología , Linfocitos T Citotóxicos/inmunología , Serina-Treonina Quinasas TOR/inmunología , Virus Vaccinia/inmunología , Vaccinia/inmunología , Traslado Adoptivo , Animales , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Células Cultivadas , Citometría de Flujo , Interacciones Huésped-Patógeno/inmunología , Inmunosupresores/inmunología , Inmunosupresores/farmacología , Interleucina-2/farmacología , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Receptores de Interleucina-12/deficiencia , Receptores de Interleucina-12/genética , Receptores de Interleucina-12/inmunología , Factor de Transcripción STAT4/inmunología , Factor de Transcripción STAT4/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Sirolimus/inmunología , Sirolimus/farmacología , Proteínas de Dominio T Box/inmunología , Proteínas de Dominio T Box/metabolismo , Linfocitos T Citotóxicos/efectos de los fármacos , Linfocitos T Citotóxicos/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Vaccinia/genética , Vaccinia/virología , Virus Vaccinia/fisiologíaRESUMEN
AIMS: To evaluate current trainers' attitudes and practices for informing patients about the trainee participation in cataract surgery within the United Kingdom. METHODS: An anonymous online survey was distributed to current cataract surgery trainers via all Royal College of Ophthalmologists' tutors within the United Kingdom. Trainers were asked specific questions about their current consent practice regarding trainee participation in the cataract surgery. Questions also targeted experiences of patient complaints about training. RESULTS: One hundred and twenty-three trainers completed the survey. Ninety-three percent (n=114) of responders were consultants and 7% (n=8) were non-consultant career-grade doctors or other grades. A total of 34% (n=42) of responders stated that consent was usually taken by themselves or the trainee assigned to the list, whereas 26% (n=32) always took consent themselves. Sixty percent of responders (n=74) stated that consent is taken on the day of surgery; 59% (n=73) indicated consent is taken where listing takes place. Thirty-three percent (n=41) of trainers indicated that they had experienced patient dissatisfaction or complaints. Surgical complications, length of surgery, and discussions during surgery were the leading causes of complaints. Thirty-nine percent (n=48) would operate themselves if patients requested no trainee participation. CONCLUSIONS: There is a wide variety in the current practice of disclosure and level of information given regarding trainee participation in surgery. This will influence patients' expectations, experiences, and satisfaction.
Asunto(s)
Extracción de Catarata/educación , Educación de Postgrado en Medicina , Consentimiento Informado/estadística & datos numéricos , Internado y Residencia , Oftalmología/educación , Participación del Paciente , Revelación de la Verdad , Actitud del Personal de Salud , Encuestas Epidemiológicas , Humanos , Satisfacción del Paciente , Encuestas y Cuestionarios , Enseñanza/métodos , Reino UnidoRESUMEN
BACKGROUND: Sensory neuropathy (SN) is common in patients with HIV. Hepatitis C (HCV) coinfection is often cited as an HIV-SN risk factor, but data to support this are lacking. This collaboration aimed to examine the association between HCV serostatus and SN risk among ambulatory HIV-positive patients. METHODS: Patients with HIV were assessed in cross-sectional studies in Baltimore, Jakarta, Johannesburg, Kuala Lumpur, Melbourne, and Sydney for SN (defined by both supportive symptoms and signs). HCV seropositivity was assessed as an SN risk using a chi(2) test, followed by logistic regression modeling to correct for treatment exposures and demographics. RESULTS: A total of 837 patients of African, Asian, and Caucasian descent were studied. HCV seroprevalence varied by site (Baltimore n = 104, 61% HCV+; Jakarta 96, 51%; Johannesburg 300, 1%; Kuala Lumpur 97, 10%; Melbourne 206, 16%; Sydney 34, 18%). HCV seropositivity was not associated with increased SN risk at any site, but was associated with reduced SN risk in Melbourne (p = 0.003). On multivariate analyses, the independent associations with SN were increasing age, height, and stavudine exposure. HCV seropositivity was not independently associated with an increased SN risk at any site, but associated independently with reduced SN risk in Baltimore (p = 0.04) and Melbourne (p = 0.06). CONCLUSIONS: Hepatitis C (HCV) seropositivity was not associated with increased sensory neuropathy risk among HIV-positive patients at any site. While we were unable to assess HCV RNA or liver damage, the data suggest that HCV coinfection is not a major contributor to HIV-SN. HCV = hepatitis C; SN = sensory neuropathy.
Asunto(s)
Infecciones por VIH/epidemiología , Hepatitis C/sangre , Hepatitis C/epidemiología , Enfermedades del Sistema Nervioso Periférico/epidemiología , Adulto , Factores de Edad , Anciano , Estatura , Estudios de Cohortes , Comorbilidad , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/virología , Inhibidores de la Transcriptasa Inversa/efectos adversos , Factores de Riesgo , Estudios Seroepidemiológicos , Estavudina/efectos adversos , Adulto JovenRESUMEN
The medical facility at Camp Bastion continues to evolve as a consequence of the increased throughput of battlefield trauma patients. There is a requirement for rapid and accurate diagnosis of haemodynamic instability and continued haemodynamic monitoring throughout the peri-operative period. Transoesophageal echocardiography (TOE) has been used for this purpose in the arena of cardiac anaesthesia since the mid 1980s. It is being introduced to other peri-operative settings where severe haemodynamic instability is expected. The old proverb: 'There are none so blind as those who cannot see' (Jeremiah 5:21) is applicable to this topic, in that TOE is proven to be a rapid, portable, safe and effective tool in the assessment of the haemodynamically unstable patient. This paper explores the application of TOE for the assessment of the major causes of haemodynamic instability in the trauma population.
Asunto(s)
Enfermedades Cardiovasculares/diagnóstico por imagen , Ecocardiografía Transesofágica , Heridas y Lesiones/cirugía , Acreditación , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades Cardiovasculares/etiología , Ecocardiografía Transesofágica/instrumentación , Válvulas Cardíacas/fisiología , Humanos , Hipovolemia/diagnóstico por imagen , Periodo Perioperatorio , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Derecha/diagnóstico por imagen , Obstrucción del Flujo Ventricular Externo/diagnóstico por imagen , Heridas y Lesiones/complicaciones , Heridas y Lesiones/diagnóstico por imagenRESUMEN
OBJECTIVE: Sensory neuropathy is a common problem in HIV-infected patients and is the dose-limiting toxicity of stavudine. Affordable methods of predicting neuropathy risk are needed to guide prescribing in countries where some use of stavudine remains an economic necessity. We therefore aimed to identify factors predictive of neuropathy risk before antiretroviral use. METHODS: A total of 294 patients attending clinics in Melbourne, Kuala Lumpur, and Jakarta were enrolled in a cross-sectional neuropathy screening program in 2006. Neuropathy was defined by the presence of symptoms and signs on the AIDS Clinical Trials Group Brief Peripheral Neuropathy Screen. Demographic, laboratory, and treatment details were considered as possible risk factors for neuropathy. The role of patient demographics in predicting stavudine neuropathy were then assessed in 181 patients who reported that they were free of neuropathy symptoms when first prescribed this drug. RESULTS: The prevalence of neuropathy was 42% in Melbourne (n = 100), 19% in Kuala Lumpur (n = 98), and 34% in Jakarta (n = 96). In addition to treatment exposures, increasing age (p = 0.002) and height (p = 0.001) were independently associated with neuropathy. Age and height cutoffs of > or=170 cm or > or =40 years predicted neuropathy. Among 181 patients who were asymptomatic before stavudine exposure, the risk of neuropathy following stavudine was 20% in younger, shorter patients, compared with 66% in older, taller individuals. CONCLUSIONS: Stavudine neuropathy risk increases with patient age and height. Prioritizing older and taller patients for alternative agents would be an inexpensive strategy to reduce neuropathy rates in countries where the burden of HIV disease limits treatment options.
Asunto(s)
Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/epidemiología , Estavudina/efectos adversos , Adolescente , Adulto , Factores de Edad , Anciano , Envejecimiento/metabolismo , Antropometría , Estatura/fisiología , Causalidad , Países en Desarrollo , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Valor Predictivo de las Pruebas , Prescripciones/normas , Medición de Riesgo/métodos , Factores de Riesgo , Adulto JovenRESUMEN
SETTING: Kisenyi slum in peri-urban Kampala, Uganda. OBJECTIVES: Using chronic cough (> or = 2 weeks) inquiry as a screening tool to identify undetected smear-positive tuberculosis (TB) cases and to describe the characteristics of smear-positive TB cases detected by active case finding. DESIGN: A house-to-house survey was conducted in five randomly selected villages in Kampala between June and August 2005. A sample of households was visited; adults aged > or = 15 years were consecutively interviewed to identify those with chronic cough. Three sputum specimens were collected and examined by smear microscopy. RESULTS: Among 930 individuals, we identified 189 (20%) chronic coughers. Of these, we found 33 (18%) undiagnosed smear-positive cases. The newly detected cases had an even sex distribution (P = 0.47), a median age of 30 years, a median cough duration of 1 month and 55% had acid-fast bacilli 1+ sputum smear grade. CONCLUSION: These findings suggest that active case finding could supplement DOTS to yield additional smear-positive TB cases, lead to early diagnosis and thus shorten the duration of infectiousness before effective chemotherapy is initiated. In communities such as Kisenyi, this is a feasible strategy that may prove useful for TB control, but its cost-effectiveness needs to be evaluated. Early health care seeking for cough should be emphasized.
Asunto(s)
Tos/diagnóstico , Áreas de Pobreza , Tuberculosis/diagnóstico , Adolescente , Adulto , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/microbiología , UgandaRESUMEN
OBJECTIVES: The aim of the study was to describe the prevalence of and risk factors for HIV-associated sensory neuropathy (HIV-SN) in 2006 [the era of stavudine, didanosine and zalcitabine (dNRTI)-sparing highly active antiretroviral therapy (HAART)] and to compare our findings with data obtained in the same clinic in 1993 (pre-HAART) and 2001 (frequent use of dNRTI-containing HAART). METHODS: This was a cross-sectional comparative study using convenience sampling. HIV-positive adults attending a tertiary referral clinic over a 2-week period were screened for HIV-SN using the AIDS Clinical Trials Group screening tool. HIV-SN was defined as present if the patient had both neuropathic symptoms and abnormal signs. Demographic, clinical, laboratory and treatment data were considered as possible risk factors for HIV-SN, and results were compared with data obtained in the same clinic in 1993 and 2001. RESULTS: One hundred patients were screened. The prevalence of HIV-SN was 42%, which was unchanged since 2001 (44%) despite a significant reduction in the use of dNRTIs. HIV-SN remained much more common than in 1993 (42% vs 13%; P<0.0001). The only independent associations with HIV-SN in 2006 were increasing patient age and a history of exposure to either stavudine or indinavir. This compares with 1993 when neuropathy was increased in those with Mycobacterium avium complex infection, and 2001 when patient age and use of stavudine and didanosine were the independent associations with HIV-SN in this clinic. CONCLUSIONS: HIV-SN remained common among ambulatory patients in 2006 (42% prevalence) despite a significant reduction in the use of dNRTIs. In addition to patient age and stavudine exposure, indinavir use may be a risk factor for HIV-SN.
Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Polineuropatías/etiología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Estavudina/uso terapéutico , Adolescente , Adulto , Anciano , Terapia Antirretroviral Altamente Activa/métodos , Australia/epidemiología , Estudios Transversales , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Inhibidores de la Transcriptasa Inversa/farmacología , Factores de Riesgo , Estavudina/farmacologíaAsunto(s)
Carcinoma de Células Renales/secundario , Chalazión/patología , Neoplasias de los Párpados/secundario , Neoplasias Renales , Carcinoma de Células Renales/diagnóstico por imagen , Chalazión/diagnóstico , Diagnóstico Diferencial , Neoplasias de los Párpados/diagnóstico , Humanos , Neoplasias Renales/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Radiografía , RecurrenciaRESUMEN
Based on the vulnerability model of depression, this study tested the hypothesis that caregivers with prior depression are more likely to be depressed during caregiving than caregivers without prior depression. We further hypothesized an interaction effect in which caregivers with prior depression would be affected more by care-recipient dependency in activities of daily living and care-recipient depressive symptoms than those without prior depression. In a sample of 111 caregivers of persons with Alzheimer's disease, in an additive regression model, neither 'prior depressive symptoms' nor the clinically more serious 'prior depressive syndrome' was related to depressive symptoms during caregiving. In an interaction model, for caregivers with either 'no prior depression' or 'prior depressive symptoms,' the greater the care-recipient dependencies in instrumental activities of daily living (IADL), the greater were the depressive symptoms during caregiving. For caregivers with a 'prior depressive syndrome', however, the greater the IADL dependency, the fewer were the depressive symptoms during caregiving. This unexpected finding suggests that caregivers with a history of clinically significant depression are not necessarily more prone to depressive symptoms when caregiving responsibilities, at least for instrumental activities, are high. This result questions the vulnerability model of depression when applied to older caregivers.
Asunto(s)
Actividades Cotidianas/psicología , Enfermedad de Alzheimer , Cuidadores/psicología , Depresión/diagnóstico , Trastorno Depresivo/fisiopatología , Atención Domiciliaria de Salud/psicología , Estrés Psicológico/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/enfermería , Enfermedad de Alzheimer/psicología , Actitud Frente a la Salud , Síntomas Conductuales , Depresión/etiología , Trastorno Depresivo/terapia , Femenino , Predicción , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Ohio , Factores de Riesgo , Autoimagen , Factores SexualesRESUMEN
OBJECTIVE: To assess whether linkage of tuberculosis (TB) and HIV/AIDS increases the perception of stigma among TB patients on Community-Based Directly Observed Therapy (CB-DOT) compared to similar TB patients on self-administered therapy (SAT). DESIGN: A Cross-sectional study. SETTING: Kiboga (CB-DOT) and Mubende (SAT) districts, Uganda in 2000. SUBJECTS: One hundred and five tuberculosis patients on CB-DOT and 202 patients on SAT. One hundred and twenty one (39%) of these patients agreed to be tested for HIV. RESULTS: Patients on CB-DOT and patients on SAT were similar on most of the domains used to assess stigma associated with a TB diagnosis, except for the domain of TB diagnosis and general belief that TB and HIV/AIDS are linked. Patients on CB-DOT were more likely to believe that neighbours knew they had TB compared to patients on SAT (91% vs. 62%, p < 0.001), but the groups did not differ in their perception that neighbours thought they have HIV because of TB (46% vs. 46%, p = 0.954). HIV prevalence was similar in both groups. CONCLUSION: The study demonstrates that TB patients on CB-DOT did not differ from SAT patients in their perception of stigma as a result of TB. Therefore, HIV-related stigma may not limit wide implementation of CB-DOT in countries like Uganda.
Asunto(s)
Servicios de Salud Comunitaria/estadística & datos numéricos , Terapia por Observación Directa/psicología , Terapia por Observación Directa/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Prejuicio , Percepción Social , Tuberculosis/terapia , Adolescente , Adulto , Estudios Transversales , Análisis Factorial , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/terapia , Humanos , Masculino , Población Rural/estadística & datos numéricos , Autoadministración/psicología , Tuberculosis/etiología , UgandaRESUMEN
OBJECTIVE: To investigate the association between Alzheimer disease (AD) and worker functions and traits associated with occupations. BACKGROUND: Studies have reported that occupational attainment is related to AD. However, most have not identified specific worker functions and traits (i.e., occupational demands) of occupations that may explain the association, nor have they accounted for changing occupational demands over time. METHODS: Within- and between-group differences in mental, motor, physical, and social occupational demands of 122 AD cases and 235 control subjects were compared across four decades of life (20s, 30s, 40s, and 50s) using repeated-measures analyses of covariance adjusted for race, gender, year of birth, and education. RESULTS: Overall, mental occupational demands were significantly lower and physical occupational demands were significantly higher for cases than for control subjects. Case/control differences in mental demand scores were not found in their 20s but only in later decades. Differences in physical demands were found in all decades but their 30s. Social and motor demands did not differ between cases and control subjects. Among cases only, there were no significant occupational demand score differences across decades. In contrast, mental and social demand scores of control subjects increased in later decades, and motor demand scores declined. Like cases, physical demand scores of control subjects remained stable across the decades. CONCLUSIONS: The authors' results may indicate a relatively early influence of Alzheimer disease neuropathology on capacity to pursue mentally demanding occupations. However, results also are consistent with the notion that mentally demanding occupations have a direct influence on Alzheimer disease neuropathology.
Asunto(s)
Logro , Enfermedad de Alzheimer/epidemiología , Ocupaciones , Factores de Edad , Anciano , Enfermedad de Alzheimer/psicología , Estudios de Casos y Controles , Escolaridad , Femenino , Humanos , Relaciones Interpersonales , Perfil Laboral , Masculino , Competencia Mental , Procesos Mentales , Persona de Mediana Edad , Actividad Motora , Examen Neurológico , Pruebas Neuropsicológicas , Ocupaciones/clasificación , Ohio , Competencia ProfesionalRESUMEN
OBJECTIVE: To examine the presence and extent of bias introduced by using surrogate respondents for healthy controls in a case-control study of Alzheimer's disease (AD). DESIGN: Comparative study of matched responses to questionnaire ascertaining lifestyle issues. SETTING: University Hospitals/Case Western Reserve University Alzheimer Center. PARTICIPANTS: Controls (n = 50) were identified through the Research Registry. Surrogates (n = 50) were their healthy relatives or friends. MEASUREMENTS: Answers in the areas of demographic and occupational history, smoking habits, medical history, dietary intake, and leisure and work activities were recorded. The analysis was based on methods for paired data. Continuous variables were analyzed, focusing on paired differences between self and surrogate responses. RESULTS: For occupations and exposures, over 80% of the surrogates agreed with the subjects on over 80% of the questions. On smoking history, over 90% of the surrogates agreed with the subjects on over 70% of the questions. On leisure and work activities, over 70% of the surrogates agreed with the subjects on over 50% of the questions. There was less agreement regarding medical history. For continuous variables, most paired t-tests of zero mean difference between self and surrogate responses resulted in nonrejection of this hypothesis. Computed mean differences were not always positive or always negative. CONCLUSION: We did not find systematic under- or overreporting by the surrogates of the controls. Therefore, if there are biases in the responses of surrogates of the AD cases in our case-control study, they would not be canceled out by using surrogates for the controls.
Asunto(s)
Enfermedad de Alzheimer/etiología , Sesgo , Estudios de Casos y Controles , Estilo de Vida , Anamnesis/normas , Proyectos de Investigación/normas , Encuestas y Cuestionarios/normas , Anciano , Enfermedad de Alzheimer/epidemiología , Interpretación Estadística de Datos , Escolaridad , Exposición a Riesgos Ambientales/estadística & datos numéricos , Ejercicio Físico , Femenino , Humanos , Actividades Recreativas , Masculino , Anamnesis/métodos , Ocupaciones/estadística & datos numéricos , Características de la Residencia/estadística & datos numéricos , Factores de Riesgo , Fumar/efectos adversosRESUMEN
The purpose of this study was to examine the effects, over time, of depressive symptoms in persons with Alzheimer's disease on depression in their family caregivers. In a sample of 353 patients and caregivers, multilevel longitudinal analysis was used to accommodate an observational design in which the number of observation points and the intervals between points varied across caregivers. The rate of change (increase) in caregiver depression was predicted by the rate of change (increase) in patient depressive symptoms and by increase in patient dependency in instrumental activities of daily living (ADLs). Acceleration of the increase in caregiver depression was predicted by acceleration in patient dependency in instrumental and basic ADLs but not by acceleration in patient depressive symptoms. These findings indicate the importance of measuring the rate and acceleration of change in patient characteristics in order to understand caregiver depression. They also support early interventions for caregivers.
Asunto(s)
Enfermedad de Alzheimer/epidemiología , Cuidadores/psicología , Depresión/epidemiología , Actividades Cotidianas/clasificación , Actividades Cotidianas/psicología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/psicología , Comorbilidad , Depresión/diagnóstico , Depresión/psicología , Femenino , Evaluación Geriátrica , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Ohio/epidemiologíaRESUMEN
The development of Alzheimer's disease (AD) later in life may be reflective of environmental factors operating over the course of a lifetime. Educational and occupational attainments have been found to be protective against the development of the disease but participation in activities has received little attention. In a case-control study, we collected questionnaire data about 26 nonoccupational activities from ages 20 to 60. Participants included 193 people with probable or possible AD and 358 healthy control-group members. Activity patterns for intellectual, passive, and physical activities were classified by using an adaptation of a published scale in terms of "diversity" (total number of activities), "intensity" (hours per month), and "percentage intensity" (percentage of total activity hours devoted to each activity category). The control group was more active during midlife than the case group was for all three activity categories, even after controlling for age, gender, income adequacy, and education. The odds ratio for AD in those performing less than the mean value of activities was 3.85 (95% confidence interval: 2.65-5.58, P < 0.001). The increase in time devoted to intellectual activities from early adulthood (20-39) to middle adulthood (40-60) was associated with a significant decrease in the probability of membership in the case group. We conclude that diversity of activities and intensity of intellectual activities were reduced in patients with AD as compared with the control group. These findings may be because inactivity is a risk factor for the disease or because inactivity is a reflection of very early subclinical effects of the disease, or both.
Asunto(s)
Actividades Cotidianas , Enfermedad de Alzheimer/epidemiología , Adulto , Enfermedad de Alzheimer/psicología , Estudios de Casos y Controles , Femenino , Estado de Salud , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Ohio/epidemiología , Encuestas y CuestionariosRESUMEN
The "reserve" hypothesis suggests that education should affect the clinical expression of Alzheimer's disease (AD), but results from studies examining this idea are not consistent. In a single study, we evaluated the effects of educational attainment on three aspects of the clinical expression of AD: age at symptom onset, rate of cognitive decline, and survival. Subjects were 258 persons with mild- or moderate-stage Alzheimer's, drawn from our AD Research Registry. With statistical adjustment for confounding variables present in a clinic-based design, we found that higher educational attainment was associated with slightly earlier reports of symptom onset and a slower rate of cognitive decline on the Mini-Mental State Exam (MMSE). Education did not affect time of survival until death. We conclude that, for subjects in our sample, education had modest effects on aspects of the clinical expression of AD. These effects were not fully consistent with predictions derived from the "reserve" hypothesis.
Asunto(s)
Enfermedad de Alzheimer/epidemiología , Sistema de Registros , Enseñanza , Anciano , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/epidemiología , Femenino , Humanos , Masculino , Índice de Severidad de la EnfermedadRESUMEN
Malathion resistance has been shown to be the result of a single point mutation in the LcalphaE7 gene in four independently isolated chromosomes of Lucilia cuprina. The resultant amino acid substitution specifies high malathion carboxylesterase (MCE) activity. We have assayed MCE activities and resistance to malathion in three sets of field-derived samples, two sets of isogenic lines and five mass populations, and show that resistance to malathion in these samples is associated with high MCE activity in both sets of isogenic lines and four of the five mass populations. Additional mechanisms contributing to MCE activity or malathion resistance may be present in one of the mass populations. A second point mutation in LcalphaE7 is responsible for conferring diazinon resistance by encoding an increased organophosphate (OP) hydrolase activity. We also assayed diazinon resistances from the same three samples and show that diazinon and malathion resistances were in complete disequilibrium, with two exceptions. One exception involves the mass population with additional resistance mechanism(s) and the other involves three isogenic lines that are resistant to both insecticides. The molecular data for these lines suggest that they carry a duplication of the LcalphaE7 gene.