Sex differences on anxiety and depression in older adults and their relationship with cognitive impairment / Diferencias por sexo en ansiedad y depresión en personas adultas mayores y su relación con el deterioro cognitivo

Introduction Subjective memory complaints (SMCs) in elderly adults could express cognitive decline in the future. A consensus has been reached about how these SMC relate to mood variables, but further research is required to determine which socio-demographic, cognitive, functional and occupational factors will act as predictors in elderly adults. Objetivo To analyze, through a descriptive observational study, the relationship between anxiety/depression and sex, age and occupation, with cognitive/functional performance in 367 older adults with SMC, but without objective cognitive impairment in a primary healthcare center. Methods The cognitive variables were measured by applying the Spanish version of Mini-Mental State Examination (MEC-35) and Set-test for verbal fluency. To measure functional level, the Barthel index and Lawton and Brody scales were employed. Physical occupational status and mental occupational status were measured based on three levels, low, medium and high, according to the American Occupational Therapy Association. Results Low educational and occupational physical and mental levels were related to anxiety and depression. In addition, differences by sex were found on anxiety and depression related to different factors. In men, anxiety was related to higher cognitive level, and in women to higher functional performance in IADLs. On the contrary, depression in men was related to lower cognitive level and higher performance in ADLs. Conclusions It is important to maintain a sex-gender perspective on the study of anxiety and depression in elderly, taking into account social roles and the traints of the work environment, in order to avoid cognitive and functional impairment (AU)

Introducción Las quejas subjetivas de memoria (SMC) en adultos mayores podrían expresar un daño cognitivo en el futuro. Existe consenso sobre la relación de estas SMC con variables del estado de ánimo pero se necesita más investigación para determinar qué factores sociodemográficos, cognitivos, funcionales y ocupacionales serían los predictores en los adultos mayores. Objetivo Analizar la relación entre ansiedad y depresión con el sexo, edad y ocupación, así como con el desempeño cognitivo y funcional en 367 adultos mayores con SMC en un centro de atención primaria. Métodos Las variables cognitivas se midieron mediante la version Española del Mini-Mental State Examination (MEC-35) y Set-Test para la fluidez verbal. Para medir el nivel funcional se utilizaron el índice de Barthel y la escala de Lawton y Brody. El estado ocupacional físico y mental fueron medidos en base a tres niveles (bajo, medio y alto) según la American Occupational Therapy Association. Resultados Los niveles educativos y ocupacionales físicos y mentales bajos se relacionaron con ansiedad y depresión. Además, se encuentran diferencias por sexo en los factores relacionados con la ansiedad y depresión. En los hombres, la ansiedad se relacionó con un mayor nivel cognitivo y en las mujeres con mayor desempeño funcional en las actividades instrumentales de la vida diaria (AIVD). Por el contrario, la depresión en los hombres se relacionó con menor nivel cognitivo y un mayor desempeño en las actividades básicas de la vida diaria (ABVD). Conclusiones Es importante mantener la perspectiva sexo-género en el análisis de la ansiedad y depresión en personas mayores, teniendo presentes los roles sociales y características del entorno laboral, para evitar el deterioro cognitivo y funcional (AU)

Sex differences on anxiety and depression in older adults and their relationship with cognitive impairment.

INTRODUCTION: Subjective memory complaints (SMCs) in elderly adults could express cognitive decline in the future. A consensus has been reached about how these SMC relate to mood variables, but further research is required to determine which socio-demographic, cognitive, functional and occupational factors will act as predictors in elderly adults. OBJETIVE: To analyze, through a descriptive observational study, the relationship between anxiety/depression and sex, age and occupation, with cognitive/functional performance in 367 older adults with SMC, but without objective cognitive impairment in a primary healthcare center. METHODS: The cognitive variables were measured by applying the Spanish version of Mini-Mental State Examination (MEC-35) and Set-test for verbal fluency. To measure functional level, the Barthel index and Lawton and Brody scales were employed. Physical occupational status and mental occupational status were measured based on three levels, low, medium and high, according to the American Occupational Therapy Association. RESULTS: Low educational and occupational physical and mental levels were related to anxiety and depression. In addition, differences by sex were found on anxiety and depression related to different factors. In men, anxiety was related to higher cognitive level, and in women to higher functional performance in IADLs. On the contrary, depression in men was related to lower cognitive level and higher performance in ADLs. CONCLUSIONS: It is important to maintain a sex-gender perspective on the study of anxiety and depression in elderly, taking into account social roles and the traints of the work environment, in order to avoid cognitive and functional impairment.

Análisis del efecto de un programa de estimulación cognitiva en adultosmayores con cognición normal: ensayo clínico aleatorizado / Analysis of the effect of cognitive stimulation program in older adults with normal cognition: randomized clinical trial

Fundamento:Los programas de estimulación cognitiva en adultos mayores persiguen mejorías cognitivas y emocionales. Existen escasos programas adaptados por niveles cognitivos y ocupacionales en mayores sin deterioro cognitivo. El objetivo fue analizar la efectividad de una intervención de estimulación cognitiva adaptada a dos niveles cognitivos en adultos mayores sobre la cognición y el estado de ánimo.Material y métodos:Ensayo clínico aleatorizado (CONSORT) en un centro de salud, que incluyó 201 participantes ≥ 65 años (101 intervención y 100 control) evaluados tras la intervención, a los seis meses y al año. Los instrumentos de evaluación fueron el mini-examen cognoscitivo (MEC), la escala de ansiedad abreviada de Goldberg y la escala de depresión geriátrica de Yesavage (GDS-15). La intervención se efectuó mediante un programa de estimulación cognitiva de dos niveles cognitivos según MEC (nivel alto: 32-35; nivel bajo: 28-31) con diez sesiones de 45 minutos. El análisis estadístico se realizó mediante t-Student.Resultados:La diferencia de las medias de puntuación MEC entre los grupos control e intervención fue estadísticamente significativa en las tres valoraciones; estas diferencias se observaron independientemente del sexo, edad, nivel cognitivo, y estado de ánimo. Al año se incrementó 1,48 puntos la puntuación MEC en el grupo de nivel alto y 2,03 en el de nivel bajo. Las puntuaciones MEC no variaron según ansiedad y depresión en ninguna de las valoraciones.Conclusiones:El programa de estimulación cognitiva, adaptado por niveles cognitivos, muestra beneficios cognitivos en personas mayores sin deterioro cognitivo que viven en la comunidad, independientemente del sexo, edad y nivel educativo.(AU)

Background: Cognitive stimulation programs in older adults seek cognitive and emotional improvements.The literature makes no reference to programs adapted according to cognitive and occupational levels in older adults with no cognitive impairment. The objective of this study was to analyze the effectiveness of level-adapted cognitive stimulation intervention in older adults in terms of cognition and mood. Methods: Randomized clinical trial (CONSORT) at a health center, which included 201 participants ≥65 years (101 intervention and 100 control) evaluated immediately after the intervention, then at six months and finally at one year. The assessment instruments were the cognitive mini-exam (CME), the abbreviated Goldberg anxiety scale and the Yesavage geriatric depression scale (GDS-15). The intervention was carried out through a cognitive stimulation program with two cognitive levels according to CME (high: 32-35; low: 28-31) with ten sessions of 45 minutes. Statistical analysis was performed by Student’s t-test. Results: The difference observed in the averages between control and intervention groups was statistically significant in the three assessments; these differences were observed regardless of gender, age, cognitive level, and mood. One year after the intervention, CME score reached an increase of 1.48 points in the in the high level group and 2.03 points in the low level. However, no significant differences in CME score were observed in any of the assessments for anxiety or depression. Conclusion: A cognitive stimulation program, cognitive level-adapted, has shown cognitive benefits in older adults without cognitive impairment living in the community, regardless of sex, age and educational level.(AU)

[Analysis of the effect of cognitive stimulation program in older adults with normal cognition: randomized clinical trial].

BACKGROUND: Cognitive stimulation programs in older adults seek cognitive and emotional improvements. The literature makes no reference to programs adapted according to cognitive and occupational levels in older adults with no cognitive impairment. The objective of this study was to analyze the effectiveness of level-adapted cognitive stimulation intervention in older adults in terms of cognition and mood. METHODS: Randomized clinical trial (CONSORT) at a health center, which included 201 participants =?65 years (101 intervention and 100 control) evaluated immediately after the intervention, then at six months and finally at one year. The assessment instruments were the cognitive mini-exam (CME), the abbreviated Goldberg anxiety scale and the Yesavage geriatric depression scale (GDS-15). The intervention was carried out through a cognitive stimulation program with two cognitive levels according to CME (high: 32-35; low: 28-31) with ten sessions of 45 minutes. Statistical analysis was performed by Student's t-test. RESULTS: The difference observed in the averages between control and intervention groups was statistically significant in the three assessments; these differences were observed regardless of gender, age, cognitive level, and mood. One year after the intervention, CME score reached an increase of 1.48 points in the in the high level group and 2.03 points in the low level. However, no significant differences in CME score were observed in any of the assessments for anxiety or depression. CONCLUSION: A cognitive stimulation program, cognitive level-adapted, has shown cognitive benefits in older adults without cognitive impairment living in the community, regardless of sex, age and educational level.

FMD empty capsids combined with the Immunostant Particle Adjuvant -ISPA or ISA206 induce protective immunity against foot and mouth disease virus.

Foot and Mouth Disease Virus (FMDV) causes economy losses and is controlled by vaccination in many countries. Vaccine formulations based on empty capsids or Virus-Like Particles (VLPs) have the advantage of avoiding the biological hazard of using infectious FMDV, albeit are poorly immunogenic. Recently, we have described that ISPA a new Immune Stimulating Complex adjuvant, is useful to improve the response against FMD of vaccines that use inactivated virus. Now, the adjuvant effects of ISPA and ISA 206 (water/oil/water) on a VLPs-based FMD vaccine were evaluated. VLPs (strain A/Argentina/2001) were obtained in mammalian cell cultures and their elicitation of an immune response against FMDV with and without ISPA or ISA 206 was evaluated in mice as a first approach. Notably, VLPs-ISPA and VLPs-ISA 206 vaccines induced protection against viral challenge in 100 % of mice, while protection induced by VLPs alone was of 40 %. Total and neutralizing FMDV antibodies were higher in the VLPs-ISPA and VLPs-ISA 206 groups compared to the VLPs group. VLPs-ISPA induced significantly higher (p < 0.001) IgG1, IgG2a, IgG2b and IgG3 titers than the VLPs vaccine. Moreover, in comparison with non-adjuvanted VLPs, VLPs-ISPA and VLPs-ISA 206 elicited an increased virus-specific T response, including higher IFNγ+/CD8 + lymphocyte production in mice. When these vaccines were tested in calves, antibody titers reached an Expected Percentage of Protection (EPP) above 90 % in the case of the VLPs-ISPA and VLPs-ISA 206 vaccines, while, in the VLPs group, EPP reached 25 %. IFNγ levels secreted by mononuclear cells of VLP-ISPA-vaccinated cattle were significantly higher than in the VLPs group. Overall, the results demonstrate that VLPs-ISPA or VLPs-ISA 206 are promising formulations for the development of a novel FMD vaccine.

Efficacy of cognitive intervention programs in amnesic mild cognitive impairment: A systematic review.

BACKGROUND: Amnesic mild cognitive impairment (aMCI) is considered a prodromal stage of Alzheimer's disease. Given the absence of an effective pharmacological treatment for aMCI, increasing numbers of studies are attempting to understand how cognitive interventions could benefit aMCI patients. The aim of this systematic review was to evaluate the current evidence regarding the efficacy on cognition of cognitive intervention programs in older adults with aMCI. METHODS: We searched for randomized controlled trials and clinical trials published until March 2020 on PubMed, Web of Science, Cochrane Library, SCOPUS, and OTseeker. A total of 454 works were identified and 7 studies that met the inclusion criteria, were included in this review. PRISMA guidelines were followed and PEDro scale was included for the measurement of the quality of the selected studies. RESULTS: Cognitive interventions showed positive effects on cognition. Cognitive training programs considerably enhanced the Mini Mental State Examination scores. However, no relevant differences in global cognition were found using other assessment tools as DRS-2 or ADAS-Cog Scale. Cognitive training and cognitive rehabilitation programs seemed to improve several cognitive domains as memory, language or executive function in aMCI patients in both post-training and at follow-up analysis. CONCLUSIONS: Our findings support that cognitive interventions can be an effective option for people with aMCI. Cognitive interventions improved global cognitive function post-intervention, but also seemed to enhance some cognitive domains post-intervention and at follow-up. However, more studies are needed to analyze the potential benefits of cognitive intervention on aMCI.

Immune Response and Partial Protection against Heterologous Foot-and-Mouth Disease Virus Induced by Dendrimer Peptides in Cattle.

Synthetic peptides mimicking protective B- and T-cell epitopes are good candidates for safer, more effective FMD vaccines. Nevertheless, previous studies of immunization with linear peptides showed that they failed to induce solid protection in cattle. Dendrimeric peptides displaying two or four copies of a peptide corresponding to the B-cell epitope VP1 [136-154] of type O FMDV (O/UKG/11/2001) linked through thioether bonds to a single copy of the T-cell epitope 3A [21-35] (termed B2T and B4T, resp.) afforded protection in vaccinated pigs. In this work, we show that dendrimeric peptides B2T and B4T can elicit specific humoral responses in cattle and confer partial protection against the challenge with a heterologous type O virus (O1/Campos/Bra/58). This protective response correlated with the induction of specific T-cells as well as with an anamnestic antibody response upon virus challenge, as shown by the detection of virus-specific antibody-secreting cells (ASC) in lymphoid tissues distal from the inoculation point.

Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice.

BACKGROUND: Polymerized allergoids coupled to nonoxidized mannan (PM-allergoids) may represent novel vaccines targeting dendritic cells (DCs). PM-allergoids are better captured by DCs than native allergens and favor Th1/Treg cell responses upon subcutaneous injection. Herein we have studied in mice the in vivo immunogenicity of PM-allergoids administered sublingually in comparison with native allergens. METHODS: Three immunization protocols (4-8 weeks long) were used in Balb/c mice. Serum antibody levels were tested by ELISA. Cell responses (proliferation, cytokines, and Tregs) were assayed by flow cytometry in spleen and lymph nodes (LNs). Allergen uptake was measured by flow cytometry in myeloid sublingual cells. RESULTS: A quick antibody response and higher IgG2a/IgE ratio were observed with PM-allergoids. Moreover, stronger specific proliferative responses were seen in both submandibular LNs and spleen cells assayed in vitro. This was accompanied by a higher IFNγ/IL-4 ratio with a quick IL-10 production by submandibular LN cells. An increase in CD4+ CD25high FOXP3+ Treg cells was detected in LNs and spleen of mice treated with PM-allergoids. These allergoids were better captured than native allergens by antigen-presenting (CD45+ MHC-II+ ) cells obtained from the sublingual mucosa, including DCs (CD11b+ ) and macrophages (CD64+ ). Importantly, all the differential effects induced by PM-allergoids were abolished when using oxidized instead of nonoxidized PM-allergoids. CONCLUSION: Our results demonstrate for the first time that PM-allergoids administered through the sublingual route promote the generation of Th1 and FOXP3+ Treg cells in a greater extent than native allergens by mechanisms that might well involve their better uptake by oral antigen-presenting cells.

Abdomen agudo durante la gestación y el puerperio / Acute abdomen during pregnancy and the puerperium

El abdomen agudo en la gestación y el puerperio constituye un diagnóstico complejo y un reto terapéutico. Nuestro objetivo es realizar una revisión bibliográfica de esta patología a propósito de un caso de peritonitis secundaria a absceso tubárico con apendicitis por helmintos concomitante. Principalmente, su sintomatología se resume en el dolor y la distensión abdominal, las náuseas y/o los vómitos. Estos síntomas se encuentran presentes en el embarazo normal, dificultando el diagnóstico diferencial. El abdomen agudo es relativamente infrecuente durante la gestación y el puerperio, siendo la apendicitis aguda la principal causa de origen no obstétrico. Asocia una elevada morbimortalidad materno-fetal, que aumenta a medida que la gestación avanza, requiriendo un manejo multidisciplinar para alcanzar un diagnóstico precoz y un tratamiento efectivo. Fundamentalmente, el abordaje terapéutico es quirúrgico debido, en gran medida, al diagnóstico tardío con frecuente asociación de complicaciones. Un manejo temprano será primordial para minimizar riesgos para la madre y el feto

Acute abdomen in pregnancy and the postpartum period is a complex diagnostic and therapeutic challenge. We review the literature on this topic and report a case of peritonitis secondary to tubal abscess with concomitant helminth appendicitis. The main symptoms of this entity are pain and bloating, nausea and/or vomiting. These symptoms are present in normal pregnancy, which hampers the differential diagnosis. Acute abdomen is relatively uncommon during pregnancy and the postpartum, and the main obstetric cause is acute appendicitis. Maternal and fetal morbidity and mortality are high and increase as the pregnancy progresses, requiring multidisciplinary management to achieve early diagnosis and effective treatment. The therapeutic approach is mainly surgical, largely due to late diagnosis and associated complications. Early management is essential to minimize the risks to the mother and fetus

[A twelve-year-old teenager with bone pain and white papules]. / Douleurs osseuses et papules blanchâtres chez un adolescent de 12 ans.

Here we present a case report in which a teenager, with papules on the arm and back since the infancy, complained of back and right knee pain at the age of 12 years. The radiological examination led to the diagnosis of osteopoikilosis and melorheostosis. The Buschke-Ollendorff syndrome (BOS) associates osteopoikilosis (asymptomatic bone dysplasia) and disseminated dermatofibrosis. The BOS is rare, and its association with melorheostosis (another bone dysplasia in which pain and deformity may occur) makes the prognosis uncertain. This case report highlights the diagnosis problems related with bone pain in paediatrics. The purpose of this manuscript is to present the characteristics of two bone dysplasias: osteopoikilosis and melorheostosis, and to discuss the involvement of each one in the clinical picture of our patient.

Hepatic encephalopathy: nomenclature, pathogenesis and treatment.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome in patients with liver failure and/or a portal-systemic bypass. Since 2002 a new nomenclature of HE exists, that classifies HE in encephalopathy type A (associated with acute liver failure), type B (associated with portal-systemic bypass), and type C (associated with liver cirrhosis). HE type A is characterized by a rapid development to coma, cerebral edema, and a poor short-term prognosis. Therefore, these patients should be referred to a liver transplantation center. Standard treatment of HE consists of non absorbable disaccharides, non absorbable antibiotics, and a diet with an appropriate amount of proteins. In addition, the possibility of performing a liver transplantation should be evaluated. In patients with intractable HE other alternative treatments adjunct to standard treatment, like zinc, sodium benzoate, ornithine aspartate, branched chain amino acids, flumazenil, and bromocriptine should be considered.

La encefalopatía hepática: terminología, etiología y tratamiento / Hepatic encephalopathy: nomenclature, pathogenesis and treatment

La encefalopatía hepática (EH) es un síndrome neuropsiquiátrico que aparece como complicación en pacientes con una insuficiencia hepática y/o con una derivación portosistémica. A partir de 2002 existe una nueva terminología de la EH, que la organiza en encefalopatía de tipo A (asociada con una insuficiencia hepática aguda), de tipo B (asociada con una derivación portosistémica), y de tipo C (asociada con una cirrosis hepática). La encefalopatía de tipo A se caracteriza por una rápida evolución a coma, edema cerebral y un mal pronóstico a corto plazo, por lo que estos pacientes deben ser referidos a un centro de trasplante hepático. El tratamiento estándar de la EH consiste en disacaridasas no absorbibles, antibióticos no absorbibles, una dieta con una cantidad adecuada en proteínas, y también se deben evaluar la posibilidad de un trasplante hepático. En pacientes con una EH refractaria se deben considerar otros tratamientos alternativos, junto con el tratamiento estándar, como el zinc, el benzoato de sodio, la ornitina aspartato, los aminoácidos de cadena ramificada, el flumazenilo, y la bromocriptina (AU)

Estudio descriptivo de los pacientes ambulatorios con enfermedad hepática por alcohol en nuestro medio / Descriptive study of outpatients with alcohol liver disease in our population

Objetivo: Nos propusimos describir las características demográficas y los hábitos de consumo de alcohol de un grupo de pacientes ambulatorios. Intentamos discernir la influencia de la edad, sexo, habitat y nivel socioeconómico sobre el hábito enólico. Diseño experimental: Nuestro estudio es retrospectivo, de base institucional. Pacientes: 164 pacientes ambulatorios, en seguimiento en nuestras consultas externas de la unidad de Hepatología por enfemedad hepática alcohólica. Resultados: La edad media de inicio fue 18,6 (7,36) años; los años de enolismo medio fueron de 35,4 (13,5) años y el consumo medio de alcohol de 161,2 (116,7) gramos de alcohol/día. Solo en 16 hombres (8 por ciento) se observó un consumo menor de 60 gramos de alcohol al día, y 5 mujeres (35,7 por ciento) consumían menos de 40 gramos de alcohol al día. El consumo de alcohol a lo largo de la vida estuvo correlacionado con el índice de Maddrey al final del estudio (r=+0,407). De igual forma el consumo diario de gramos de alcohol estuvo correlacionado con el aspecto ecográfico del hígado(r=+0,283), apreciándose también correlación de dicha técnica de imagen (r=+0,301) con el Tiempo de Protrombina al inicio del estudio. El porcentaje de pacientes que presentaron al menos un episodio de descompensación de su cirrosis fue del 39 por ciento. Conclusiones: La edad de inicio ronda la mayoría de edad . El consumo de alcohol a lo largo de la vida, estuvo correlacionado con el tiempo de protrombina en la última visita y el aspecto ecográfico del hígado (AU)

[Descriptive study of ambulatory patients with alcohol-related liver disease in our setting]. / Estudio descriptivo de los pacientes ambulatorios con enfermedad hepática por alcohol en nuestro medio.

AIMS: We tried to show the demographic characteristic and alcohol intake habits among our outpatients. We study the influence of age, sex, habitat and socioeconomical status on alcoholic habit. DESIGN: Retrospective and institution based study. Patients. 164 patients who were followed up for alcohol liver disease in our outpatient section. RESULTS: Average age to start drinking alcohol was 18.6 (7.36) years, years of alcoholism were 35.4 (13.5) years, average daily alcohol intake was 161.2 (116.7) grams of pure alcohol. Only 16 men (8%) drank less than 60 grams a day. 5 (35.7%) women drank less than 40 grams a day. Life-cumulative alcohol intake was correlated with Maddrey's score at the end of the study (r = +0.407). Average daily alcohol intake was correlated with ultrasonographic features of the liver (r = +0.283), we appreciated that Prothrombin Time was also correlated with ultrasonographic features of the liver (r = +0.301). The percentage of patients who suffer, at least one decompensation of their disease was 39%. CONCLUSIONS: Average age to start drinking is about legal age. Life-cumulative alcohol intake was related to Prothrombin Time and ultrasonographic features of the liver.

Effect of food on the pharmacokinetics and bioavailability of oral imiquimod relative to a subcutaneous dose.

OBJECTIVES: The present study, the first clinical pharmacokinetic report of the immune response modifier imiquimod, was conducted to assess the effect of food on the oral absorption of imiquimod, to characterize its pharmacokinetics, and to estimate its oral bioavailability. SUBJECTS AND METHODS: Sixteen healthy male volunteers completed this open-label, randomized, three-period crossover study. Subjects received a 100 mg oral dose of imiquimod after fasting in one period, after a standarized, high fat meal in another, and a 30 mg subcutaneous dose in the third period. RESULTS: The oral bioavailability of imiquimod was on average 47%, and independent of whether imiquimod was administered with or without food. Oral imiquimod was absorbed in both fasted and non-fasted states with an absorption half-life of approximately 1 hour. However, there seemed to be a delay in the initiation of the absorption process when food was administered, which translated in to a Tmax of approximately 2.6 hours while fasting and one hour later in the non-fasted state. Imiquimod was rapidly eliminated with a half-life of approximately 2.5 hours and a total body clearance of approximately 970 ml/hxkg. Although equivalence could not be established due to the large intersubject variability, no significant differences in rate (Cmax) and extent (AUC) of oral absorption were observed between the fasted and non-fasted states. In addition, the Cmax, AUC and bioavailability values for individual subjects were consistent between both oral treatments. CONCLUSION: This study suggests that food does not have a major effect on the rate, extent of absorption or bioavailability of oral imiquimod, and thus, it is suitable to administer imiquimod orally in either the fasted or non-fasted states.

Ausencia de efecto antiviral del tratamiento con altas dosis de interferón-ß natural subcutáneo en los pacientes con hepatitis crónica C infectados por el genotipo 1 / Absence of antiviral activity of high-dose subcutaneous beta-interferon in patients with chronic infection by genotype 1 virus C hepatitis

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