RESUMEN
Recent studies suggest that sound amplification via hearing aids can improve postural control in adults with hearing impairments. Unfortunately, only a few studies used well-defined posturography measures to assess balance in adults with hearing loss with and without their hearing aids. Of these, only two examined postural control specifically in the elderly with hearing loss. The present study examined the impact of hearing aid use on postural control during various sensory perturbations in older adults with age-related hearing loss. Thirty individuals with age-related hearing impairments and using hearing aids bilaterally were tested. Participants were asked to perform a modified clinical sensory integration in balance test on a force platform with and without hearing aids. The experiment was conducted in the presence of a broadband noise ranging from 0.1 to 4 kHz presented through a loudspeaker. As expected, hearing aid use had a beneficial impact on postural control, but only when visual and somatosensory inputs were both reduced. Data also suggest that hearing aid use decreases the dependence on somatosensory input for maintaining postural control. This finding can be of particular importance in older adults considering the reduction of tactile and proprioceptive sensitivity and acuity often associated with aging. These results provide an additional argument for encouraging early hearing aid fitting for people with hearing loss.
Asunto(s)
Sordera , Audífonos , Pérdida Auditiva , Humanos , Anciano , Señales (Psicología) , Pérdida Auditiva/diagnóstico , Equilibrio PosturalRESUMEN
The brain of deaf people is definitely not just deaf, and we have to reconsider what we know about the impact of hearing loss on brain development in light of comorbid vestibular impairments.
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Sordera , Pérdida Auditiva , Vestíbulo del Laberinto , Encéfalo , Mapeo Encefálico , HumanosRESUMEN
Mental imagery can induce audiovisual integration, but whether it can induce interactions in other modalities remains uncertain. It has been demonstrated that audiomotor interaction can be generated following training, but whether such audiomotor interaction can be induced by auditory imagery training remains unknown. The present study aims at determining whether auditory mental imagery could induce a multimodal association with postural control. We examined static postural control in the presence of a frequency-modulated sound in three groups of participants, prior to and following a short period of training designed to create an association between auditory mental imagery of sounds and postural swaying. Results suggest that mental imagery impacted performance, as a significant decrease in postural control was observed in the experimental group following mental imagery training. Results of the control groups confirmed that the effect of mental imagery was not due to response bias, but to a significant multimodal interaction following training. These findings are in accordance with previous studies suggesting that mental imagery stimuli can interact with perceptual stimuli of a different sensory modality and lead to multisensory integration. The results also confirm that audiomotor interaction can be generated a mental imagery training. However, the full extent of mental imagery influence on multimodal interaction remains to be determined.
Asunto(s)
Imágenes en Psicoterapia , Percepción Auditiva , Humanos , Imaginación , SonidoRESUMEN
Functional neuroimaging studies have demonstrated that following deafness, auditory regions can respond to tactile stimuli. However, research to date has not conclusively demonstrated the behavioral correlates of these functional changes, with most studies showing normal-like tactile capabilities in the deaf. It has recently been suggested that more cognitive and complex tactile processes, such as music perception, could help to uncover superior tactile capabilities in the deaf. Indeed, following deafness music seems to be perceived through vibration, but the extent to which they can perceive musical features though the tactile modality remains undetermined. The goal of this study was to investigate tactile identification of musical emotion in the deaf. Participants had to rate melodies based on their emotional perception. Stimuli were presented through an haptic glove. Data suggest that deaf and control participants were comparable in the identification of three of the four emotions tested (sad, fear/threat, peacefulness). However and most importantly, for the simplest emotion (happiness), significant differences emerged between groups, suggesting an improved tactile identification of musical emotion in the deaf. Results support the hypothesis that brain plasticity following deafness can lead to improved complex tactile ability.
Asunto(s)
Sordera/fisiopatología , Emociones/fisiología , Música , Percepción del Tacto/fisiología , Adulto , Femenino , Felicidad , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Elbasvir-grazoprevir is indicated for chronic hepatitis C virus (HCV) genotypes 1 and 4. AIM: To evaluate the utilization and outcomes of chronic HCV patients treated with elbasvir-grazoprevir in the United States. METHODS: We conducted a retrospective cohort study of adults treated with elbasvir-grazoprevir with or without ribavirin for chronic HCV genotypes 1 or 4 infection. Data were collected from healthcare providers and specialty pharmacies through Innervation Platform, a proprietary, cloud-based disease management program from Trio Health. The primary endpoint was per protocol sustained virological response 12 weeks post-treatment (SVR12). RESULTS: Among 470 patients treated in 2016, 95% had HCV genotype 1 infection, 80% (373/468) were HCV treatment naïve and 70% (327/468) had non-cirrhotic disease. Almost 3 quarters (73%) of patients received care in community practices. The majority (89%) of patients received elbasvir-grazoprevir for 12 weeks. Per protocol SVR12 rates were 99% (396/402) for HCV genotype 1 and 95% (21/22) for HCV genotype 4. Among patients with Stage 4 or 5 chronic kidney diseases, 99% (113/114) achieved SVR12. In univariate analyses, variables significantly associated with per protocol SVR12 for the entire sample were therapy duration (P = 0.001), treatment experience (P = 0.016), and cirrhosis status (P = 0.001). However, among HCV genotype 1 patients, no variables were significant. Intent-to-treat SVR12 rates were 89% (396/447) for HCV genotype 1 and 91% (21/23) for HCV genotype 4. CONCLUSION: Elbasvir-grazoprevir is highly effective, and in this 2016 cohort, its use was predominantly in patients with HCV genotype 1 and as a 12-week therapy without ribavirin.
Asunto(s)
Antivirales/uso terapéutico , Benzofuranos/uso terapéutico , Genotipo , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/genética , Imidazoles/uso terapéutico , Quinoxalinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/farmacología , Benzofuranos/farmacología , Estudios de Cohortes , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Hepatitis C Crónica/diagnóstico , Humanos , Imidazoles/farmacología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/genética , Masculino , Persona de Mediana Edad , Quinoxalinas/farmacología , ARN Viral/efectos de los fármacos , ARN Viral/genética , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/genética , Estudios Retrospectivos , Respuesta Virológica SostenidaRESUMEN
BACKGROUND: Treatment of genotype 1 hepatitis C virus (HCV) infection with combination direct acting anti-virals is associated with very high rates of sustained virological response (SVR). Daily combination of ledipasvir and sofosbuvir for 12 weeks is approved for the treatment of genotype 1 HCV patients, though noncirrhotic patients who are naïve to treatment with a baseline HCV RNA <6 million IU/mL can be treated for 8 weeks. This guidance stemmed from a post hoc analysis of the ION 3 clinical trial, which demonstrated similar SVR for patients treated with ledipasvir and sofosbuvir with or without ribavirin for 8 or 12 weeks. AIM: To compare the SVR for 8 weeks vs 12 weeks of ledipasvir and sofosbuvir in HCV infected patients in a real-world setting. METHODS: We performed an observational real-world cohort study of treatment success following 8 or 12 weeks of ledipasvir and sofosbuvir for treatment-naïve genotype 1 HCV patients. RESULTS: A total of 826 patients were treated for either 8 (n=252) or 12 weeks (n=574) with ledipasvir and sofosbuvir and achieved SVR rate of 95.3% and there was no statistical difference in SVR rates in the two groups irrespective of any clinical or virological variables. CONCLUSIONS: In treatment-naïve HCV genotype 1 patients, SVR was 95% in those treated for either 8 weeks or 12 weeks with ledipasvir and sofosbuvir. 8 week ledipasvir and sofosbuvir can reduce costs without compromising outcomes for those patients who qualify for such regimen.
Asunto(s)
Antivirales/administración & dosificación , Bencimidazoles/administración & dosificación , Fluorenos/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Sofosbuvir/administración & dosificación , Anciano , Antivirales/uso terapéutico , Estudios de Cohortes , Femenino , Genotipo , Hepacivirus/genética , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Ribavirina/uso terapéutico , Sofosbuvir/uso terapéutico , Resultado del TratamientoRESUMEN
Early data regarding the "real-world" experience with novel therapies for hepatitis C (HCV) are encouraging. Data are still limited, however, regarding real-world rates of sustained virologic response (SVR) for ledipasvir-sofosbuvir (LDV-SOF), particularly for patients with prior treatment failure. We performed a retrospective cohort study of 1597 patients with chronic genotype 1 HCV who were treated using 12 weeks of the following regimens LDV-SOF±ribavirin (RBV) (n=1521 without RBV, n=76 with RBV). The primary outcome was SVR-determined at 12 weeks in an intention-to-treat design. Prescription according to Food and Drug Administration (FDA) approved labelling (adding RBV for patients with cirrhosis and treatment failure) was assessed in multivariate models. The study population was aged 60 years on average (range 19-89), 60% male, 50% Caucasian, 43% cared for at an academic centre and 30% cirrhotic. Overall, LDV-SOF resulted in a 94% SVR rate. Only 44 (2.9%) patients relapsed. LDV-SOF+RBV yielded SVR in 97% with 0 viral relapses. While cirrhosis and thrombocytopenia were associated with lower odds of SVR, in a multivariable regression model, only treatment at an academic centre and prescriptions contrary to FDA labelling were significantly associated with lower SVR-odds ratios, 0.56 95% CI (0.35-0.87) and 0.29 95% CI(0.12-0.68), respectively. The real-world experience with LDV-SOF mirrors the SVR rates observed in clinical trials. Efforts to promote prescription within FDA recommendations are warranted.
Asunto(s)
Antivirales/uso terapéutico , Bencimidazoles/uso terapéutico , Fluorenos/uso terapéutico , Genotipo , Hepacivirus/clasificación , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Uridina Monofosfato/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hepacivirus/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Ribavirina/uso terapéutico , Sofosbuvir , Respuesta Virológica Sostenida , Resultado del Tratamiento , Uridina Monofosfato/uso terapéutico , Adulto JovenRESUMEN
Despite the clinical success in the real-world of all oral hepatitis C virus (HCV) therapy with response rates approaching that seen in the clinical trials, access has been limited by many payers with discussion of prioritization of treatment based upon AASLD guidelines. We evaluated patients in the TRIO network who were prescribed sofosbuvir (SOF)-based regimens to determine reasons for not starting treatment. Trio Health is a disease management company that works in partnership with academic medical centres, community physicians and specialty pharmacies in the United States to optimize care for HCV. Data for 3841 patients prescribed a sofosbuvir-containing regimen between December 2013 and September 2014 were obtained through this programme. Of the entire group, 315 (8%) patients did not start the prescribed sofosbuvir-containing therapy. A total of 141 (45%) of the nonstart patients had a commercial plan as their primary insurance, 137 (44%) were primarily covered by Medicaid, 17 (5%) were primarily covered by Medicare, and 20 (6%) were either without coverage or coverage was not specified. Reasons for nonstarts were varied and overlapping. Only 15 patients (5% of nonstarts) did not start because they were unreachable or failed to complete required testing. Another 39 patients who did not start (12%) were following their physicians' direction to either wait for new treatment options or to hold treatment for an unspecified reason. Insurance-related processes and financial reasons accounted for 254 (81%) of the 315 nonstarts. The remaining 7 (2%) patients did not have a specified reason for not starting treatment. Nonstart rates were highest in the Medicaid-covered population at 35%. Medicare and Commercial nonstart rates were 2% and 6%, respectively. In a matched comparison, patients with commercial coverage were 6.5 times as likely to start SOF-based therapy compared to patients with Medicaid. Despite high SVR rates of SOF-based regimens in clinical practice, there are still barriers to access to care. In fact, almost half of the nonstart patients had advanced fibrosis scores (F3 or F4) and should have been prioritized to start treatment. As better treatment for HCV with high efficacy and low side effect rates become available, the disparity in access to treatment, as evidenced by the high nonstart rate in the Medicaid-covered group, must be resolved.
Asunto(s)
Antivirales/administración & dosificación , Accesibilidad a los Servicios de Salud , Hepatitis C Crónica/tratamiento farmacológico , Sofosbuvir/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos , Adulto JovenRESUMEN
Sustained virologic response (SVR) is the standard measure for evaluating response to therapy in patients with chronic hepatitis C (CHC). The aim of this study was to prospectively assess the durability of SVR in the pivotal studies of peginterferon (PEG-IFN) α-2b or IFN α-2b. We conducted two phase 3b long-term follow-up studies of patients previously treated for CHC in eight prospective randomized studies of IFN α-2b and/or PEG-IFN α-2b. Patients who achieved SVR [undetectable hepatitis C virus (HCV) RNA 24 weeks after completion of treatment] were eligible for inclusion in these follow-up studies. In total, 636 patients with SVR following treatment with IFN α-2b and 366 with SVR following treatment with PEG-IFN α-2b were enrolled. Definite relapse (quantifiable serum HCV RNA with no subsequent undetectable HCV RNA) was reported in six patients treated with IFN α-2b and three patients treated with PEG-IFN α-2b. Based on these relapses, the point estimate for the likelihood of maintaining response after 5 years was 99.2% [95% confidence interval (CI), 98.1-99.7%] for IFN α-2b and 99.4% (95% CI, 97.7-99.9%) for PEG-IFN α-2b. Successful treatment of hepatitis C with PEG-IFN α-2b or IFN α-2b leads to clinical cure of hepatitis C in the vast majority of cases.
Asunto(s)
Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Quimioterapia Combinada , Estudios de Seguimiento , Hepacivirus/aislamiento & purificación , Humanos , Interferón alfa-2 , Estudios Prospectivos , ARN Viral/sangre , Proteínas Recombinantes/uso terapéutico , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: Adherence to therapeutic regimens affects the efficacy of peginterferon alfa (P) and ribavirin (R) therapy in patients with chronic hepatitis C virus genotype 1. AIM: To determine if medication adherence impacts efficacy [sustained virological response (SVR)] with triple therapy that includes boceprevir (BOC) plus P/R. METHODS: Adherence was determined in two Phase 3 clinical studies with BOC: SPRINT-2 (previously untreated patients) and RESPOND-2 (patients who failed previous therapy with P/R). Adherence to the assigned duration of the dosing regimen and adherence to the three times a day (t.d.s.) dosing interval of 7-9 h for BOC were assessed by the recording of data from patients' dosing diaries and by the amount of study drug dispensed and returned. RESULTS: Most patients (63-71%) adhered to ≥80% of their assigned treatment duration and achieved SVR rates of 86-90%. In contrast, patients who adhered to <80% of their assigned treatment duration achieved SVR rates of 8-32% (P < 0.0001), particularly low in patients who failed previous therapy (SVR = 8-15%). Different rates of adherence (<60% to >80%) to the t.d.s. dosing interval (7-9 h) with BOC did not influence the SVR rates (SVR = 60-83%) with the exception of patients who failed previous treatment and adhered to <60% of the t.d.s. dosing interval with BOC (SVR = 48-50%; P = 0.005). CONCLUSIONS: The achievement of an SVR is more dependent on adherence to the assigned duration of treatment than adherence to the t.d.s. dosing interval with boceprevir. Adherence to >60% of t.d.s. dosing with boceprevir is important in patients who failed previous therapy.
Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Cumplimiento de la Medicación , Polietilenglicoles/uso terapéutico , Prolina/análogos & derivados , Ribavirina/uso terapéutico , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Genotipo , Hepatitis C Crónica/genética , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Prolina/uso terapéutico , ARN Viral/genética , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Carga ViralRESUMEN
We fine mapped two primary biliary cirrhosis (PBC) risk loci, CLEC16A (C-type lectin domain family 16 member A)-suppressor of cytokine signaling 1 (SOCS1) and Spi-B protein (SPIB) and sequenced a locus, sialic acid acetylesterase (SIAE), proposed to harbor autoimmunity-associated mutations. In all, 1450 PBC cases and 2957 healthy controls were genotyped for 84 single-nucleotide polymorphisms (SNPs) across the CLEC16A-SOCS1 and SPIB loci. All 10 exons of the SIAE gene were resequenced in 381 cases and point substitutions of unknown significance assayed for activity and secretion. Fine mapping identified 26 SNPs across the CLEC16A-SOCS1 and 11 SNPs across the SPIB locus with significant association to PBC, the strongest signals at the CLEC16A-SOCS1 locus emanating from a SOCS1 intergenic SNP (rs243325; P=9.91 × 10(-9)) and at the SPIB locus from a SPIB intronic SNP (rs34944112; P=3.65 × 10(-9)). Among the associated SNPs at the CLEC16A-SOCS1 locus, two within the CLEC16A gene as well as one SOCS1 SNP (rs243325) remained significant after conditional logistic regression and contributed independently to risk. Sequencing of the SIAE gene and functional assays of newly identified variants revealed six patients with functional non-synonymous SIAE mutations (Fisher's P=9 × 10(-4) vs controls) We demonstrate independent effects on risk of PBC for CLEC16A, SOCS1 and SPIB variants, while identifying functionally defective SIAE variants as potential factors in risk for PBC.
Asunto(s)
Acetilesterasa/genética , Proteínas de Unión al ADN/genética , Lectinas Tipo C/genética , Cirrosis Hepática Biliar/genética , Proteínas de Transporte de Monosacáridos/genética , Proteínas Supresoras de la Señalización de Citocinas/genética , Factores de Transcripción/genética , Acetilesterasa/metabolismo , Alelos , Estudios de Casos y Controles , Mapeo Cromosómico/métodos , Proteínas de Unión al ADN/metabolismo , Pruebas de Enzimas , Sitios Genéticos , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Lectinas Tipo C/metabolismo , Cirrosis Hepática Biliar/inmunología , Cirrosis Hepática Biliar/metabolismo , Modelos Logísticos , Proteínas de Transporte de Monosacáridos/metabolismo , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Proteína 1 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Injuries at various levels of the auditory system have been shown to lead to functional reorganization of the auditory pathways. In particular, it has recently been shown that such reorganization can occur in callosal agenesis. The pattern of cortical activity following callosotomy is however still unknown, but behavioral results suggest that it could be significantly different from that observed in callosal agenesis. We aimed to confirm this hypothesis by investigating fMRI responses to complex sounds presented binaurally and monaurally in a callosotomized patient. In the binaural condition, the callosotomized subject showed patterns of auditory cortical activation that were similar to those of neurologically intact individuals. However, in both monaural conditions, the callosotomized individual showed a significant increase of the asymmetries favoring the contralateral pathways. Such patterns of cortical responses are only partially consistent with the results obtained from callosal agenesis subjects using the exact same procedure. Indeed, the latter show differences compared with normals in both binaural and monaural conditions. These findings provide neurological evidence that callosotomy could lead to distinctive functional reorganization of the human auditory pathways.
Asunto(s)
Corteza Auditiva/anatomía & histología , Corteza Auditiva/fisiología , Vías Auditivas/anatomía & histología , Vías Auditivas/fisiología , Cuerpo Calloso/cirugía , Adulto , Lateralidad Funcional/fisiología , Humanos , Imagen por Resonancia Magnética/métodos , MasculinoRESUMEN
BACKGROUND: The efficacy of re-treating genotype I hepatitis C virus (HCV) patients who failed combination therapy with interferon/pegylated interferon (PEG-IFN) and ribavirin remains unclear. AIMS: To quantify sustained virological response (SVR) rates with different re-treatment regimens through meta-analysis of randomized controlled trials (RCTs). METHODS: Randomized controlled trials of genotype I HCV treatment failure patients that compared currently available re-treatment regimens were selected. Two investigators independently extracted data on patient population, methods and results. The pooled relative risk of SVR for treatment regimens was computed using a random effects model. RESULTS: Eighteen RCTs were included. In nonresponders to standard interferon/ribavirin, re-treatment with high-dose PEG-IFN combination therapy improved SVR compared with standard PEG-IFN combination therapy (RR=1.49; 95% CI: 1.09-2.04), but SVR rates did not exceed 18% in most studies. In relapsers to standard interferon/ribavirin, re-treatment with high-dose PEG-IFN or prolonged CIFN improved SVR (RR=1.57; 95% CI: 1.16-2.14) and achieved SVR rates of 43-69%. CONCLUSIONS: In genotype I HCV treatment failure patients who received combination therapy, re-treatment with high-dose PEG-IFN combination therapy is superior to re-treatment with standard combination therapy, although SVR rates are variable for nonresponders (≤18%) and relapsers (43-69%). Re-treatment may be appropriate for select patients, especially relapsers and individuals with bridging fibrosis or compensated cirrhosis.
Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Interferones/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Quimioterapia Combinada , Genotipo , Hepacivirus/genética , Hepatitis C/virología , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/uso terapéutico , Interferones/administración & dosificación , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas Recombinantes , Retratamiento , Insuficiencia del Tratamiento , Carga ViralRESUMEN
BACKGROUND: A human betaretrovirus has been characterized in patients with primary biliary cirrhosis (PBC). Uncontrolled studies using combination anti-retroviral therapy have reported significant biochemical and histological improvement. AIM: To conduct a double blind, randomized controlled trial as a proof of principal to link infection with PBC. METHODS: Fifty-nine patients with an alkaline phosphatase level>1.5 upper limits of normal stabilized on ursodeoxycholic acid therapy were randomized to either 300 mg zidovudine and 150 mg lamivudine B.I.D. or placebo for 6 months. RESULTS: None of the patients normalized alkaline phosphatase and no significant differences were observed in normalizing serum aminotransferase levels. Significant differences were observed in the antiviral versus placebo arms with improvements in serial alkaline phosphatase (p<0.04), ALT (p<0.03) and AST (p<0.04) as well as clinical score (p<0.02). After 6 months, 25% of patients in the placebo arm and 4% in the antiviral arm had evidence of virus in serum. CONCLUSIONS: The study endpoints for normalizing hepatic biochemistry were too stringent to show efficacy for zidovudine and lamivudine therapy despite the demonstrable impact on clinical and biochemical improvement. Accordingly, more potent anti-viral regimens will be required to confirm the efficacy of antiviral therapy in PBC patients with human betaretrovirus infection.
Asunto(s)
Antivirales/uso terapéutico , Lamivudine/uso terapéutico , Cirrosis Hepática Biliar/tratamiento farmacológico , Infecciones por Retroviridae/tratamiento farmacológico , Infecciones Tumorales por Virus/tratamiento farmacológico , Ácido Ursodesoxicólico/uso terapéutico , Zidovudina/uso terapéutico , Adulto , Anciano , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Antivirales/efectos adversos , Aspartato Aminotransferasas/sangre , Betaretrovirus/efectos de los fármacos , Colagogos y Coleréticos/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Lamivudine/efectos adversos , Cirrosis Hepática Biliar/sangre , Cirrosis Hepática Biliar/complicaciones , Masculino , Persona de Mediana Edad , Infecciones por Retroviridae/sangre , Infecciones por Retroviridae/complicaciones , Resultado del Tratamiento , Zidovudina/efectos adversosRESUMEN
The present study investigated the functional reorganization of ipsilateral and contralateral auditory pathways in hemispherectomized subjects. Functional reorganization was assessed using functional Magnetic Resonance Imaging (fMRI) and stimulation with complex sounds presented binaurally and monaurally. For neurologically intact control subjects, results showed that binaural stimulations evoked balanced activity in both hemispheres while monaural stimulations induced strong contralateral activity and weak ipsilateral activity. The results obtained from hemispherectomized subjects were substantially different from those obtained from control subjects. Specifically, activity in the intact hemisphere showed a significant decrease in response to contralateral stimulation but, concomitantly, an increase in response to ipsilateral stimulation. The present findings suggest that a substantial functional reorganization takes place in the auditory pathways following an early hemispherectomy. The exact nature of this functional reorganization remains to be specified.
Asunto(s)
Vías Auditivas/fisiología , Mapeo Encefálico , Lateralidad Funcional/fisiología , Hemisferectomía , Plasticidad Neuronal/fisiología , Adaptación Fisiológica , Adulto , Vías Auditivas/anatomía & histología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
The mechanisms responsible for the perception of illusory modal figures are usually studied by presenting entire Kanizsa figures at stimulus onset. However, with this mode of presentation, the brain activity generated by the inducers (the 'pacmen') is difficult to differentiate from the activity underlying the perception of the illusory figure. Therefore, in addition to this usual presentation mode, we used an alternative presentation mode. Inducer disks remained permanently on the screen and the illusory figure was induced by just removing the notches from the disks. The results support the heuristic value of this alternative mode of presentation. The P1 deflection of the visual evoked potentials (VEPs) was found to be greater for the illusory modal figure than for its control and for an amodal figure. This modulation is one of the earliest direct evidences for a low-level processing of illusory forms in the human brain. Meanwhile, larger N1s were obtained for the control figures than for the illusory figures in the notch mode of presentation. While this new type of N1 modulation could shed some light on the stage of processing indexed by this deflection, several propositions are put forward to account for the P1 and N1 variations found.
Asunto(s)
Potenciales Evocados Visuales/fisiología , Ilusiones/fisiología , Percepción de Cercanía/fisiología , Estimulación Luminosa/métodos , Tiempo de Reacción/fisiología , Adulto , Análisis de Varianza , Femenino , Humanos , Masculino , Valores de Referencia , Factores de Tiempo , Percepción Visual/fisiologíaRESUMEN
The present study investigated the spatial properties of cells in the postero-lateral lateral suprasylvian (PLLS) area of the cat and assessed their sensitivity to edges defined by motion. A total of one hundred and seventeen (117) single units were isolated. First, drifting sinusoidal gratings were used to assess the spatial properties of the cells' receptive fields and to determine their spatial frequency tuning functions. Second, random-dot kinematograms were used to create illusory edges by drifting textured stimuli (i.e. a horizontal bar) against a similarly textured but static background. Almost all the cells recorded in PLLS (96.0%) were binocular, and a substantial majority of receptive fields (79.2%) were end-stopped. Most units (81.0%) had band-pass spatial frequency tuning functions and responded optimally to low spatial frequencies (mean spatial frequency: 0.08 c./degree). The remaining units (19.0%) were low-pass. All the recorded cells responded vigorously to edges defined by motion. The vast majority (96.0%) of cells responded optimally to large texture elements; approximately half the cells (57.3%) also responded to finer texture elements. Moreover, 38.5% of the cells were selective to the width of the bar (i.e., the distance between the leading and the trailing edges). Finally, some (9.0%) cells responded in a transient fashion to leading and to trailing edges. In conclusion, cells in the PLLS area are low spatial frequency analyzers that are sensitive to texture and to the distance between edges defined by motion.
Asunto(s)
Potenciales de Acción/fisiología , Sensibilidad de Contraste/fisiología , Percepción de Movimiento/fisiología , Reconocimiento Visual de Modelos/fisiología , Corteza Visual/fisiología , Animales , Gatos , Potenciales Evocados Visuales/fisiología , Femenino , Masculino , Estimulación Luminosa , Especificidad de la Especie , Corteza Visual/anatomía & histología , Campos Visuales/fisiología , Vías Visuales/fisiologíaRESUMEN
Hereditary hemochromatosis type 3 is an iron (Fe)-overload disorder caused by mutations in transferrin receptor 2 (TfR2). TfR2 is expressed highly in the liver and regulates Fe metabolism. The aim of this study was to investigate duodenal Fe absorption and hepatic Fe uptake in a TfR2 (Y245X) mutant mouse model of hereditary hemochromatosis type 3. Duodenal Fe absorption and hepatic Fe uptake were measured in vivo by 59Fe-labeled ascorbate in TfR2 mutant mice, wild-type mice, and Fe-loaded wild-type mice (2% dietary carbonyl Fe). Gene expression was measured by real-time RT-PCR. Liver nonheme Fe concentration increased progressively with age in TfR2 mutant mice compared with wild-type mice. Fe absorption (both duodenal Fe uptake and transfer) was increased in TfR2 mutant mice compared with wild-type mice. Likewise, expression of genes participating in duodenal Fe uptake (Dcytb, DMT1) and transfer (ferroportin) were increased in TfR2 mutant mice. Nearly all of the absorbed Fe was taken up rapidly by the liver. Despite hepatic Fe loading, hepcidin expression was decreased in TfR2 mutant mice compared with wild-type mice. Even when compared with Fe-loaded wild-type mice, TfR2 mutant mice had increased Fe absorption, increased duodenal Fe transport gene expression, increased liver Fe uptake, and decreased liver hepcidin expression. In conclusion, despite systemic Fe loading, Fe absorption and liver Fe uptake were increased in TfR2 mutant mice in association with decreased expression of hepcidin. These findings support a model in which TfR2 is a sensor of Fe status and regulates duodenal Fe absorption and liver Fe uptake.
Asunto(s)
Duodeno/metabolismo , Hemocromatosis/genética , Absorción Intestinal , Hierro/metabolismo , Hígado/metabolismo , Receptores de Transferrina/genética , Animales , Secuencia de Bases , Transporte Biológico , Cruzamientos Genéticos , Cartilla de ADN , Modelos Animales de Enfermedad , Femenino , Ferritinas/metabolismo , Tamización de Portadores Genéticos , Hemocromatosis/metabolismo , Hierro/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones MutantesRESUMEN
Hepatitis C is a global problem with significantly associated morbidity and mortality. Although some recent therapeutic advances have shown rates of sustained virologic remission of 50% or higher, combination therapy with interferon and ribavirin is often not well tolerated and is giving rise to a growing number of nonresponders. As a result, a large number of experimental drugs for the treatment of chronic hepatitis C are in development. As the clinical trial reports are made available, physicians need to become familiar with issues related to the design of these studies and to develop strategies to interpret the evidence they yield. The articles in this supplement describe the issues in clinical trial design and the evaluation of evidence from clinical trials in patients with chronic hepatitis C.
Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/crecimiento & desarrollo , Hepatitis C Crónica/tratamiento farmacológico , Ensayos Clínicos como Asunto , Quimioterapia Combinada , Humanos , Interferones/uso terapéutico , Ribavirina/uso terapéuticoRESUMEN
Re-treatment with interferon-alpha alone for chronic hepatitis C nonresponders to interferon-alpha monotherapy is almost ineffective. This multicentre, randomized, parallel-group, dose-finding study evaluated the efficacy of interferon-beta-1a in the treatment of chronic hepatitis C patients unresponsive to interferon-alpha. A total of 267 patients were randomized to one of four groups: subcutaneous interferon-beta-1a 12 MIU (44 microg) or 24 MIU (88 microg) administered three times weekly or daily. Patients were treated for 48 weeks and then followed up for an additional 24 weeks. There was a trend towards a dose-response relationship regarding virological [loss of detectable serum hepatitis C virus (HCV) RNA] and biochemical response (normalization of serum alanine aminotransferase). Overall, 22 patients (8.3%) had a virological response at the end of treatment; nine patients (3.4%) had a sustained virological response (SVR). Strikingly, 21.7% (5/23) of Chinese patients achieved SVR. Univariate analysis revealed that race was the only variable related to SVR [odds ratio (OR) 16.6; 95% CI 4.1-67.3; P < 0.0001]. Multiple logistic regression analysis also confirmed that more Chinese patients achieved SVR than non-Chinese patients (OR 12.3; 95% CI 2.6-59.3; P = 0.0017). In addition, complete clearance of HCV-RNA occurred earlier in Chinese than in non-Chinese responders (median 2 vs 30 weeks; P = 0.020). Thirty-six patients were withdrawn from treatment because of adverse events. Most adverse events were mild or moderate in severity. In conclusion, interferon-beta-1a provided considerable clinical benefit in Chinese patients with chronic hepatitis C unresponsive to interferon-alpha. The evaluation of interferon-beta-1a in this setting is progressing.