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1.
Nat Med ; 27(10): 1825-1835, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34621052

RESUMEN

Nonalcoholic steatohepatitis (NASH), a chronic liver disease without an approved therapy, is associated with lipotoxicity and insulin resistance and is a major cause of cirrhosis and hepatocellular carcinoma. Aramchol, a partial inhibitor of hepatic stearoyl-CoA desaturase (SCD1) improved steatohepatitis and fibrosis in rodents and reduced steatosis in an early clinical trial. ARREST, a 52-week, double-blind, placebo-controlled, phase 2b trial randomized 247 patients with NASH (n = 101, n = 98 and n = 48 in the Aramchol 400 mg, 600 mg and placebo arms, respectively; NCT02279524 ). The primary end point was a decrease in hepatic triglycerides by magnetic resonance spectroscopy at 52 weeks with a dose of 600 mg of Aramchol. Key secondary end points included liver histology and alanine aminotransferase (ALT). Aramchol 600 mg produced a placebo-corrected decrease in liver triglycerides without meeting the prespecified significance (-3.1, 95% confidence interval (CI) -6.4 to 0.2, P = 0.066), precluding further formal statistical analysis. NASH resolution without worsening fibrosis was achieved in 16.7% (13 out of 78) of Aramchol 600 mg versus 5% (2 out of 40) of the placebo arm (odds ratio (OR) = 4.74, 95% CI = 0.99 to 22.7) and fibrosis improvement by ≥1 stage without worsening NASH in 29.5% versus 17.5% (OR = 1.88, 95% CI = 0.7 to 5.0), respectively. The placebo-corrected decrease in ALT for 600 mg was -29.1 IU l-1 (95% CI = -41.6 to -16.5). Early termination due to adverse events (AEs) was <5%, and Aramchol 600 and 400 mg were safe, well tolerated and without imbalance in serious or severe AEs between arms. Although the primary end point of a reduction in liver fat did not meet the prespecified significance level with Aramchol 600 mg, the observed safety and changes in liver histology and enzymes provide a rationale for SCD1 modulation as a promising therapy for NASH and fibrosis and are being evaluated in an ongoing phase 3 program.


Asunto(s)
Ácidos Cólicos/administración & dosificación , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Estearoil-CoA Desaturasa/genética , Alanina Transaminasa , Biopsia , Ácidos Cólicos/efectos adversos , Método Doble Ciego , Femenino , Humanos , Hígado/metabolismo , Hígado/patología , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/patología , Triglicéridos/metabolismo
2.
J Stomatol Oral Maxillofac Surg ; 119(2): 122-128, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29246755

RESUMEN

INTRODUCTION: To describe the relationship and impact of age group, gender and skin complexion on the prevalence and clinical distribution of oral mucosal alterations of developmental origin (OMA-DO) among school children aged 5-13 years. METHODS: A randomized representative national survey of Jordanian school children including all Country geographic areas was performed. Cut-off age that significantly correlated with presence and distribution of OMA-DO was identified (ROC curve). Skin complexion was classified into light/fair, intermediate/tan, dark/brown based on skin complexion index. Chi square test with P value≤0.05 was used for significance of correlations. RESULTS: Two thousand two hundred and fifty one children were clinically examined. The average age that significantly correlated with prevalence and distribution of OMA-DO was 9.9 years. Female gender was significantly correlated with four OMA-DO: leukoedema (L), linea Alba (LA), Fordyce's granules (FG), commissural lip pits (CLP) and wider distribution of racial pigmentations (RP) (P<0.05, χ2 test). Older age group (9.9-13 years) was significantly correlated with 7 OMA-DO: L, LA, FG, frenal tag, CLP, mandibular and maxillary tori (MT) as well as wider clinical distribution of RP, FG, L (P<0.05 χ2 test). Dark skin complexion significantly correlated with 5 OMA-DO: L, LA, FG, RP, MT and wider clinical distribution of RP (P<0.02, χ2 test). CONCLUSIONS: Increased prevalence and wider clinical distribution of OMA-DO are significantly associated with older age group of 9.9-13 years, female gender, and dark skin complexion. Oral health care provides are encouraged to be familiar with these correlations. This knowledge is expected to improve OMA-DO diagnosis and clinical management. Continuous education programs in this field are recommended.


Asunto(s)
Sistemas de Distribución en Hospital , Enfermedades de la Boca , Adolescente , Anciano , Distribución de Chi-Cuadrado , Niño , Preescolar , Femenino , Humanos , Mucosa Bucal , Prevalencia
3.
Aliment Pharmacol Ther ; 46(3): 282-291, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28543263

RESUMEN

BACKGROUND: Previous studies have reached conflicting conclusions regarding the efficacy of mesalazine in the prevention of recurrent diverticulitis. AIM: To investigate the efficacy and safety of mesalazine granules in the prevention of recurrence of diverticulitis after acute uncomplicated diverticulitis. METHODS: Two phase 3, randomised, placebo-controlled, double-blind multicentre trials (SAG-37 and SAG-51) investigated mesalazine granules in patients with prior episodes (<6 months) of uncomplicated left-sided diverticulitis. Patients were randomised to receive either 3 g mesalazine once daily or placebo (SAG-37, n=345) or to receive either 1.5 g mesalazine once daily, 3 g once daily or placebo for 96 weeks (SAG-51, n=330). The primary endpoint was the proportion of recurrence-free patients during 48 weeks (SAG-37 and SAG-51) or 96 weeks (SAG-51) of treatment. RESULTS: Mesalazine did not increase the proportion of recurrence-free patients over 48 or 96 weeks compared to placebo. In SAG-37, the proportion of recurrence-free patients during 48 weeks was 67.9% with mesalazine and 74.4% with placebo (P=.226). In SAG-51, the proportion of recurrence-free patients over 48 weeks was 46.0% with 1.5 g mesalazine, 52.0% with 3 g mesalazine and 58.0% with placebo (P=.860 for 3 g mesalazine vs placebo) and over 96 weeks 6.9%, 9.8% and 23.1% respectively (P=.980 for 3 g mesalazine vs placebo). Patients with only one diverticulitis episode in the year prior to study entry had a lower recurrence risk compared to >1 episode. Safety data revealed no new adverse events. CONCLUSION: Mesalazine was not superior to placebo in preventing recurrence of diverticulitis.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Diverticulitis/prevención & control , Mesalamina/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Resultado del Tratamiento
4.
Int Nurs Rev ; 63(1): 50-9, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25756927

RESUMEN

AIM: This study explored Jordanian mothers' knowledge of infants' childrearing practices and developmental milestones, the socio-demographic variables of relevance to knowledge, and sources of information that guide childrearing practices. BACKGROUND: Parents' knowledge is considered the frame of reference for parents' interpretations of their children's behaviors and provides the basis for having the appropriate expectation of the child's developmental stage. Parents' knowledge of childrearing is essential for children's physical, cognitive and emotional development. METHODS: A cross-sectional design using a modified version of MacPhee's 'Knowledge of Infant Development Inventory' was used to assess 400 mothers' knowledge of infants' childrearing and developmental milestones, in Amman, Jordan. RESULTS: Mothers were found to be more knowledgeable in physical and safety skills and less in cognitive, emotional, and parent-infant interaction skills. Parental age, education, parity and planned pregnancy had limited influence on developmental milestones knowledge. Formal and informal sources of information were used conforming to traditional societies. DISCUSSION AND CONCLUSION: Results were congruent with findings from other studies in the region and similar traditional societies. Results allude to conclusion that mothers resort to informal sources and traditional practices to replace formally structured programmes when absent. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Healthcare professionals, nursing schools and healthcare policy makers are encouraged to develop and institute a holistic approach encompassing physical, cognitive, emotional and parent-infant interaction domains in childrearing educational programmes. Structured parenting programmes for mothers and culturally accepted sources of information for fathers are essential to enhance parenting skills among Jordanian couples.


Asunto(s)
Desarrollo Infantil , Crianza del Niño/psicología , Conocimientos, Actitudes y Práctica en Salud , Relaciones Madre-Hijo , Madres/psicología , Responsabilidad Parental/psicología , Adolescente , Adulto , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Recién Nacido , Jordania , Masculino , Persona de Mediana Edad , Factores Socioeconómicos , Adulto Joven
5.
Neurogastroenterol Motil ; 27(1): 99-104, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25484196

RESUMEN

BACKGROUND: Constipation is a common disorder. Because the prevalence is high and the satisfaction level with currently available treatment is low, there is an unmet need for innovative treatment. We assessed the safety and efficacy of the Vibrant Capsule, a non-pharmacological device that is assumed to induce a normal peristaltic wave in the large intestine to alleviate constipation. METHODS: Two animal safety studies and a safety study on healthy volunteers were conducted, followed by a prospective, non-randomized, open-label, single group assignment, safety and efficacy study. The latter was conducted among 26 patients who ingested the capsule twice weekly for a study period of 7.5 weeks, after a run-in period of 2 weeks without usual treatment for constipation. KEY RESULTS: In the studies on animals and healthy volunteers, there were no adverse events. Twenty-eight patients began the clinical trial and 26 completed it (25 women). The mean age was 47.0 ± 12.6 years (range: 19-65). The two dropouts, who completed the safety phase, and the 26 who completed the entire study expelled the capsule without difficulty. Twelve participants reported 27 adverse events, none serious, and all transient. There was a significant increase of 1.60 ± 1.09 in the mean number of bowel movements/week from 2.19 ± 0.67 to 3.79 ± 1.31 (p < 0.001). This increase was seen in 23 of the 26 patients (88.5%). The mean number of spontaneous bowel movements for the study group increased in each treatment week compared to baseline. CONCLUSIONS & INFERENCES: The Vibrant Capsule is safe and potentially effective in the treatment of constipation, justifying randomized controlled studies.


Asunto(s)
Estreñimiento/terapia , Vibración/efectos adversos , Vibración/uso terapéutico , Adulto , Animales , Cápsulas , Enfermedad Crónica , Perros , Femenino , Humanos , Masculino , Estudios Prospectivos , Resultado del Tratamiento , Adulto Joven
6.
J Viral Hepat ; 19(10): 732-43, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22967105

RESUMEN

Patients with decompensated cirrhosis owing to chronic hepatitis B viral (HBV) infection have a high morbidity/mortality rate, and the treatment remains a challenge. We studied the safety and efficacy of telbivudine and lamivudine in such patients. This noninferiority, double-blind trial randomized 232 treatment-naive patients with decompensated HBV (1:1) in 80 academic hospitals to receive once-daily telbivudine 600 mg or lamivudine 100 mg for 104 weeks. Primary composite endpoint was proportion of patients with HBV DNA <10 000 copies/mL, normal alanine aminotransferase (ALT) and Child-Turcotte-Pugh score improvement/stabilization at week 52. Response rates using a post hoc modified endpoint (HBV DNA <300 copies/mL [57 IU/mL] and ALT normalization) in intent-to-treat analysis (missing = failure) were 56.3%vs 38.0% after 76 weeks (P = 0.018) and 45.6%vs 32.9% after 104 weeks (P = 0.093) for telbivudine vs lamivudine. Telbivudine treatment was an independent predictive factor for HBV DNA <300 copies/mL and ALT normalization (P = 0.037). Response rates with protocol-defined composite endpoint in intent-to-treat analysis (M = F) were 56.2 vs 54.0% (noninferiority not achieved) and 39.1%vs 36.4% (noninferiority achieved) in telbivudine and lamivudine groups at 52 and 104 weeks. Telbivudine treatment was associated with a significant improvement in glomerular filtration rate compared to lamivudine treatment and was also associated with a trend for improvement in survival (87%vs 79%). No cases of lactic acidosis were reported. Telbivudine compared to lamivudine was associated with a higher rate of patients with both viral suppression and ALT normalization, a trend towards a higher rate of survival and significant improvement in glomerular filtration.


Asunto(s)
Antivirales/administración & dosificación , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/administración & dosificación , Cirrosis Hepática/complicaciones , Fallo Hepático , Nucleósidos/administración & dosificación , Pirimidinonas/administración & dosificación , Adolescente , Adulto , Anciano , Alanina Transaminasa/sangre , Antivirales/efectos adversos , ADN Viral/sangre , Método Doble Ciego , Femenino , Humanos , Lamivudine/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Nucleósidos/efectos adversos , Estudios Prospectivos , Pirimidinonas/efectos adversos , Índice de Severidad de la Enfermedad , Telbivudina , Timidina/análogos & derivados , Resultado del Tratamiento , Adulto Joven
7.
East Mediterr Health J ; 18(3): 205-12, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22574472

RESUMEN

This cross-sectional, descriptive, correlational study evaluated the mental health consequences of abuse among Jordanian women. Standard tools were used to collect data from 93 abused women seeking help at a welfare centre in relation to forms of abuse, depression, coping, suicidal ideation, substance use, social support and self-efficacy. The most commonly reported form of abuse was psychological abuse. Applying the Beck Depression Inventory showed that 38.7% of the abused women had moderate to severe levels of depression. Although half the women had a low level of perceived social support, abused Jordanian women reported moderate to very high levels of self-efficacy and used approach coping more frequently than avoidance coping strategies. Using the Modified Scale for Suicide Ideation, 15.7% of the women reported that the desire for death was stronger than the desire for life. Abused women in Jordan face mental health and psychosocial risks that could compromise their quality of life.


Asunto(s)
Adaptación Psicológica , Mujeres Maltratadas/psicología , Trastornos Mentales/etiología , Adolescente , Adulto , Estudios Transversales , Depresión , Femenino , Humanos , Entrevistas como Asunto , Jordania , Trastornos Mentales/diagnóstico , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Autoeficacia , Apoyo Social , Trastornos Relacionados con Sustancias , Ideación Suicida , Adulto Joven
8.
(East. Mediterr. health j).
en Inglés | WHO IRIS | ID: who-118297

RESUMEN

This cross-sectional, descriptive, correlational study evaluated the mental health consequences of abuse amongjordanian women. Standard tools were used to collect data from 93 abused women seeking help at a welfare centre in relation to forms of abuse, depression, coping, suicidal ideation, substance use, social support and self-efficacy. The most commonly reported form of abuse was psychological abuse. Applying the Beck Depression Inventory showed that 38.7% of the abused women had moderate to severe levels of depression. Although half the women had a low level of perceived social support, abused Jordanian women reported moderate to very high levels of self-efficacy and used coping more frequently than avoidance coping strategies. Using the Modified Scale for Suicide ldeation, 15.7% of the women reported that the desire for death was stronger than the desire for life. Abused women in mental health and psychosocial risks that could compromise their quality of life


Asunto(s)
Salud Mental , Estudios Transversales , Depresión , Autoeficacia , Maltrato Conyugal , Mujeres Maltratadas
9.
Int Nurs Rev ; 58(4): 420-7, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22092319

RESUMEN

AIMS: The study aims to describe nursing students' changing perception of nursing over 4 years of the nursing programme and examine whether perception differed by gender, previous study or choice of nursing education. METHODS: A descriptive cross-sectional design was used, with a probability sample of 606 students. Respondents were a random sample of 50% of each of the four educational cohorts studying within the academic year 2008-2009 in one baccalaureate nursing programme at a Jordanian public university. A specifically designed tool of statements of nursing definitions based on nursing theories, the nursing literature and sociocultural beliefs was used to identify student nurses' perception of nursing. FINDINGS: Student perceptions changed from lay altruistic beliefs of nursing to theoretical medical technological views of the profession denoting a theory-practice gap. Perceptions also differed by gender, having a previous associate degree in nursing and a priority choice to study nursing. CONCLUSION: Such results delineated the importance of revising nursing schools' curricula and the universities' admission policies into the nursing profession.


Asunto(s)
Bachillerato en Enfermería , Enfermería , Percepción , Estudiantes de Enfermería/psicología , Selección de Profesión , Femenino , Humanos , Jordania , Masculino , Criterios de Admisión Escolar , Encuestas y Cuestionarios
10.
Clin Exp Immunol ; 157(1): 155-64, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19659781

RESUMEN

Hepatic fibrosis is the end-stage consequence of chronic liver disease, affecting many people worldwide. Unlike the anti-fibrotic effect of natural killer (NK) cells, CD8 and NK T subsets are considered as profibrogenic subsets. Padma Hepaten is a multi-compound herbal preparation derived from Tibetan medicine and has proven efficacy in some clinical trials and tests at the cellular level. In this study, we evaluate the immune efficacy of Padma Hepaten administered intraperitoneally (i.p.) and/or orally in a mice model of hepatic fibrosis. Hepatic fibrosis was induced by 6 weeks of biweekly i.p. carbon tetrachloride (CCl4) injections in male C57Bl6 mice. There were four groups, including naive mice, non-treated fibrotic mice and fibrotic mice treated by Padma Hepaten at weeks 5-6 of fibrosis induction either orally or by i.p. injections. Padma Hepaten was prepared at 10 mg/ml in saline and 250 microl (2.5 mg) were administered four times per week. After week 6, animals were killed. To isolate a Padma Hepaten-associated effect on lymphocytes, splenocytes were harvested from either naive or Padma Hepaten-treated non-fibrotic donors. Isolated splenocytes were therefore reconstituted into two groups of irradiated recipients. Recipients were then administered the same CCl4 regimen. Hepatic fibrosis was determined by sirius red staining of liver sections and by assessment of alpha smooth muscle actin expression compared with beta-actin (both by mRNA as well as the protein liver extract western blotting). Hepatic fibrosis and alanine aminotransferase serum levels were decreased significantly in both Padma Hepaten-treated groups compared with the non-treated fibrotic group. Padma Hepaten treatment was associated with attenuation of lymphocyte subsets in both treated groups. Using a chemiluminescence technique to assess total anti-oxidant capacities (TAC), it was found that both the plasmas and livers of mice treated by CCl4 had significantly higher TAC compared with controls. However, the levels of TAC in animals treated either by CCl4 alone or CCl4 with Padma Hepaten were similar. Adoptive transfer of Padma Hepaten-treated lymphocytes was associated with fibrosis amelioration compared with recipients with naive lymphocytes. CCl4 generates higher levels of anti-oxidant capacities, probably as a response to oxidative stress. Padma Hepaten administration attenuated hepatic fibrogenesis significantly, accompanied by attenuation of lymphocyte but not anti-oxidant capacities.


Asunto(s)
Cirrosis Hepática/inmunología , Cirrosis Hepática/terapia , Hígado/inmunología , Células T Asesinas Naturales/inmunología , Fitoterapia/métodos , Extractos Vegetales/administración & dosificación , Actinas/análisis , Actinas/genética , Traslado Adoptivo , Animales , Biomarcadores/análisis , Western Blotting , Tetracloruro de Carbono , Citometría de Flujo/métodos , Hígado/química , Hígado/patología , Cirrosis Hepática/patología , Linfocitos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Irradiación Corporal Total
11.
Community Dent Health ; 25(1): 50-4, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18435235

RESUMEN

OBJECTIVE: To assess the coronal caries experience and associated risk indicators among a sample of Jordanian adults. PARTICIPANTS AND METHODS: A random sample of 1,096 dentate Jordanian adults in Irbid region were interviewed and clinically examined for coronal caries using the DMFS index. Descriptive summary statistics, bivariate, and regression analyses were employed. RESULTS: Findings revealed that the mean numbers of coronal decayed surfaces (DS), missing surfaces because of caries (MS), filled surfaces (FS), decayed and filled surfaces (DFS) and DMFS were 6.3, 20.6, 8.0, 14.3 and 34.9 respectively. All subjects had coronal caries experience and 93% had untreated lesions. Subjects of older age, with less education, urban residence, lower incomes, no dental insurance, a smoking habit and irregular oral hygiene practices had a significantly higher coronal caries experience (p < 0.05). Age, income, education, residence, smoking, brushing and flossing collectively explained 45% of the variance for the mean number of coronal DMFS. CONCLUSIONS: This study provided useful information on the coronal caries status of Jordanian adults. Modifications of several social factors could potentially reduce coronal DMFS, to improve oral health status and function in adults.


Asunto(s)
Índice CPO , Caries Dental/epidemiología , Corona del Diente/patología , Adolescente , Adulto , Factores de Edad , Anciano , Dispositivos para el Autocuidado Bucal/estadística & datos numéricos , Restauración Dental Permanente/estadística & datos numéricos , Escolaridad , Femenino , Humanos , Renta/estadística & datos numéricos , Seguro Odontológico/estadística & datos numéricos , Jordania/epidemiología , Masculino , Persona de Mediana Edad , Higiene Bucal/estadística & datos numéricos , Fumar/epidemiología , Pérdida de Diente/epidemiología , Cepillado Dental/estadística & datos numéricos , Salud Urbana/estadística & datos numéricos
12.
Clin Exp Immunol ; 152(1): 163-73, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18279442

RESUMEN

Tissue-type plasminogen activators (tPA) and urokinase-type plasminogen activators (uPA) are involved in liver repair. We examined the potential immunomodulatory actions of uPA, tPA and uPA-receptor (uPAR) in carbon-tetrachloride-induced hepatic fibrosis in wild-type (WT), tPA-/-, uPA-/- and uPAR-/- mice. Carbon-tetrachloride treatment increased fibrosis in four groups but significantly less in three knock-out models. Serum cytokines and intrahepatic T cells elevated significantly following fibrosis process in WT animals but not in the knock-out groups. In culture, uPA increased lymphocyte proliferation significantly in WT and uPA-/- but not uPAR-/- animals. Following uPA exposure in vivo, there was CD8 predominance. To isolate uPA's effect on lymphocytes, WT mice were irradiated sublethally and then reconstituted with WT or uPA-/- lymphocytes. In these animals fibrosis was decreased and T cells were reduced in the uPA-/- recipients. Based on these data we postulate that plasminogen activators affect fibrosis in part by liver-specific activation of CD8 subsets that govern the fibrogenic activity of hepatic stellate cells.


Asunto(s)
Cirrosis Hepática Experimental/inmunología , Activadores Plasminogénicos/inmunología , Animales , Tetracloruro de Carbono , Comunicación Celular/inmunología , Proliferación Celular , Células Cultivadas , Citocinas/sangre , Hepatocitos/inmunología , Cirrosis Hepática Experimental/inducido químicamente , Cirrosis Hepática Experimental/patología , Activación de Linfocitos/inmunología , Transfusión de Linfocitos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Activadores Plasminogénicos/genética , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/inmunología , Receptores del Activador de Plasminógeno Tipo Uroquinasa , Subgrupos de Linfocitos T/inmunología , Irradiación Corporal Total
13.
Haemophilia ; 14(2): 336-42, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18205802

RESUMEN

Treatment with pegylated interferon (Peg-IFN) and ribavirin, now the standard of care, has been shown to achieve sustained viral response (SVR) in up to 60% of patients with hepatitis C (HCV). Studies of response to this combination in HCV-infected haemophilia patients are scarce. The aim of the study was to report the results and safety of interferon/ribavirin treatment in HCV and HCV-/HIV-infected patients at the Israeli National Hemophilia Center. A retrospective observational cohort study was conducted on haemophilia patients infected with HCV or HCV/HIV. Patients received combination of Peg-IFN and ribavirin. Few were still treated with standard interferon. The primary end-point was sustained viral response (SVR). The secondary end-point was safety, with emphasis on increased bleeding episodes. Some 18/43 (42%) HCV mono-infected haemophilia patients achieved SVR. Relapse occurred in 14 (33%), while 11 patients (25%) were non-responders. SVR was achieved among 17/37 (46%) naïve patients receiving Peg-IFN and ribavirin. Among patients with genotype-1, SVR was achieved in 12/36 (33%) and 11/30 (37%) in the whole group and Peg-IFN treated naïve patients, respectively. In HCV/HIV co-infected patients only 1 patient achieved SVR. Severe anaemia occurred in 14/50 (28%) patients, four received erythropoietin. None maintained stable haemoglobin levels. Two patients had significant bleeding episodes. In our cohort of haemophilia patients, SVR was achieved in a lower than expected rates. A relatively high relapse rate in the HCV mono-infected patients and a very high non-response rate in the HCV/HIV co-infected patients were observed as anticipated. Anaemia was a major side effect and the use of growth factors seemed unrevealing.


Asunto(s)
Hemofilia A/virología , Hepacivirus , Hepatitis C/complicaciones , Adulto , Anemia/inducido químicamente , Antivirales/uso terapéutico , Quimioterapia Combinada , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Hemofilia A/tratamiento farmacológico , Hemofilia A/patología , Hemorragia , Hepatitis C/tratamiento farmacológico , Hepatitis C/patología , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Interferón-alfa/uso terapéutico , Israel , Hígado/patología , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes , Estudios Retrospectivos , Ribavirina/efectos adversos , Ribavirina/uso terapéutico , Resultado del Tratamiento , Carga Viral
14.
Clin Exp Immunol ; 148(2): 338-47, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17437422

RESUMEN

Recent functional research studies suggest an anti-fibrotic role for natural killer (NK) cells coupled with a profibrotic role for CD8 cells. However, the morphological cellular interplay between the different cell types is less clear. To investigate lymphocyte/hepatic stellate cell (HSC) interactions, hepatic fibrosis was induced by administering carbon tetrachloride (CCl4) intraperitoneally (i.p.) for 4 weeks in C57Bl/6 mice. Animals were killed at 0, 1, 2, 3 and 4 weeks. Liver sections were stained for Sirius red. Confocal microscopy was used to evaluate alpha smooth-muscle actin (alphaSMA) and lymphocyte subsets in liver sections. At weeks 0 and 4, liver protein extracts were assessed for alphaSMA by Western blotting and isolated liver lymphocytes as well as HSC were analysed by fluorescence activated cell sorter (FACS). Similar to the results obtained from classical Sirius red staining and alphaSMA blotting, analysis of liver sections by confocal microscopy revealed a marked and continuous accumulation of alphaSMA staining along sequential experimental check-points after administering CCl4. Although the number of all liver lymphocyte subsets increased following fibrosis induction, FACS analysis revealed an increase in the distribution of liver CD8 subsets and a decrease of CD4 T cells. Confocal microscopy showed a significant early appearance of CD8 and NK cells, and to a lesser extent CD4 T cells, appearing only from week 2. Lymphocytes were seen in proximity only to HSC, mainly in the periportal area and along fibrotic septa, suggesting a direct interaction. Notably, lymphocyte subsets were undetectable in naive liver sections. Freshly isolated HCS show high expression of major histocompatibility complex (MHC) class II and CD11c. In the animal model of hepatic fibrosis, lymphocytes infiltrate into the liver parenchyma and it is thought that they attach directly to activated HSC. Because HSCs express CD11c/class II molecules, interactions involving them might reflect that HSCs have an antigen-presenting capacity.


Asunto(s)
Hepatocitos/inmunología , Cirrosis Hepática Experimental/inmunología , Subgrupos Linfocitarios/inmunología , Actinas/metabolismo , Animales , Antígeno CD11c/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Tetracloruro de Carbono , Adhesión Celular/inmunología , Comunicación Celular/inmunología , Antígenos de Histocompatibilidad Clase II/metabolismo , Células Asesinas Naturales/inmunología , Cirrosis Hepática Experimental/inducido químicamente , Cirrosis Hepática Experimental/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal
15.
Bone Marrow Transplant ; 35(2): 191-7, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15558045

RESUMEN

Natural killer T (NKT) lymphocyte cells are a subset of regulatory lymphocytes with important immunemodulatory effects. Our aim was to evaluate the effect of transplantation of NKT lymphocytes on graft versus host disease (GVHD) in a murine model of semiallogeneic BMT. GVHD was generated by infusion of 2 x 107 splenocytes from C57BL/6 donor mice into irradiated (C57BL/6 x Balb/c)F1 recipient mice. Adoptive transfer of increasing numbers of DX5+ cells was performed. Recipient mice were followed for histological parameters of GVHD-associated liver, bowel, and cutaneous injury. Intrahepatic and intrasplenic lymphocytes were isolated and analyzed by FACS for CD4+ and CD8+ subpopulations. It was seen that adoptive transfer of 4.5 x 106 DX5+ cells significantly alleviated GVHD-related hepatic, bowel, and cutaneous injury, and improved survival (85% survival on day 28). In contrast, depletion of DX5+ cells led to severe GVHD-associated multiorgan injury and 100% mortality. A direct correlation with the number of transplanted DX5+ cells was noted (maximal effect with transplantation of 4.5 x 106 DX5+ cells). Tolerance induction was associated with an increased peripheral CD4/CD8 ratio, intrahepatic trapping of CD8 lymphocytes and a shift towards a Th2-type cytokine profile, manifested by decreased IL-12/IL10, IL-12/IL-4, IFNgamma/IL-10, and IFNgamma/IL-4 ratios. Transplantation of DX5+ cells holds promise as a novel therapeutic measure for GVHD.


Asunto(s)
Traslado Adoptivo/métodos , Trasplante de Médula Ósea/efectos adversos , Enfermedad Injerto contra Huésped/prevención & control , Células Asesinas Naturales/trasplante , Animales , Trasplante de Médula Ósea/métodos , Relación CD4-CD8 , Citocinas/análisis , Femenino , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/patología , Tolerancia Inmunológica , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Modelos Animales , Bazo/citología , Linfocitos T , Células Th2 , Trasplante Homólogo
16.
Liver Int ; 24(6): 547-51, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15566503

RESUMEN

BACKGROUND: Experience with lamivudine treatment of immunocompetent patients with acute hepatitis B is limited. AIM OF STUDY: To evaluate the safety and efficacy of lamivudine for the treatment of acute severe hepatitis B virus (HBV) infection in immunocompetent adults. PATIENTS AND METHODS: Fifteen patients (10 men, 5 women, mean age 34.3+/-7.3 years) with severe acute HBV infection were treated with lamivudine 100 mg daily for 3-6 months, starting 3-12 weeks after onset of infection. Prior to treatment, 5 patients had grade 1-4 encephalopathy; all patients had severe coagulopathy (mean INR was 4.5+/-6.4), and all patients had evidence of severe hepatocyte lysis (mean alanine aminotransferase 3738+/-1659 U/L, and mean total serum bilirubin 18+/-6.8 mg/dl). All patients had evidence of highly replicative HBV (mean HBV DNA 13.5 x 10(6)+/-11 x 10(6) copies/ml). RESULTS: Thirteen patients (86.6%) responded to treatment. Encephalopathy disappeared within 3 days of treatment and coagulopathy improved within 1 week. Serum HBV DNA was undetectable (by polymerase chain reaction) within 4 weeks, and serum liver enzyme levels normalized within 8 weeks. Two patients in whom lamivudine therapy was delayed developed fulminant hepatitis and underwent urgent liver transplantation. (One died of vascular complications 1 month later). The 11 patients who were serum HBeAg-positive before treatment seroconverted, and HBeAb developed within 12 weeks in 9 of them; HBsAg was undetectable in all 11 tested patients, and protective titer of HBsAb developed within 12-16 weeks in 9 of them. Therapy was well tolerated in all cases. CONCLUSIONS: These data indicate that lamivudine induces a prompt clinical, biochemical, serological and virological response in immunocompetent patients with de novo HBV infection. Lamivudine may prevent the progression of severe acute disease to fulminant or chronic hepatitis and should be considered for use in selected patients. A large randomized controlled, double-blind prospective study is needed.


Asunto(s)
Hepatitis B/tratamiento farmacológico , Huésped Inmunocomprometido , Lamivudine/administración & dosificación , Enfermedad Aguda , Adulto , ADN Viral/análisis , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Hepatitis B/diagnóstico , Humanos , Masculino , Proyectos Piloto , Reacción en Cadena de la Polimerasa/métodos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
17.
Health Phys ; 86(5 Suppl): S120-3, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15069303

RESUMEN

The traditional approach to treatment of certain malignant brain tumors involves permanent implantation of I seeds sequential to tumor's resection. This approach has recently been changed for patients with unifocal recurrent gliomas. What began during the 1990's as a large clinical trial utilizing GliaSite Radiotherapy System, is currently becoming standard of care. This radiotherapy system consists of an inflatable balloon catheter, 2, 3, or 4 cm diameter, which is surgically placed in the tumor resection cavity; its positioning and the level of conformity within the cavity are verified via MRI imaging with contrast. The balloon is then filled with appropriate volume of I in the liquid form. Radiation treatment prescription dose ranges from 40 to 60 Gy (4,000 to 6,000 rads). This is accomplished by allowing 2.77 to 16.6 GBq (75 to 450 mCi) of I to remain in the balloon for 3-5 d. Numerous technical, dosimetric, and logistical considerations arise when handling large quantities of iodine necessary to perform GliaSite procedures. They require coordination of efforts of several hospital departments and the institution's RSO-in our case, two RSOs, at the University of Colorado Hospital and University of Colorado Health Sciences Center hold separate radioactive materials licenses. Based on our experiences and those of others, we conclude that, with appropriate guidance and care, these procedures can be performed safely without excessive restrictions.


Asunto(s)
Braquiterapia/métodos , Braquiterapia/normas , Neoplasias Encefálicas/radioterapia , Cateterismo/métodos , Radioisótopos de Yodo/uso terapéutico , Protección Radiológica/métodos , Administración de la Seguridad/métodos , Administración de la Seguridad/organización & administración , Cateterismo/instrumentación , Humanos , Radioisótopos de Yodo/análisis , Exposición Profesional/análisis , Grupo de Atención al Paciente/organización & administración , Guías de Práctica Clínica como Asunto , Traumatismos por Radiación/prevención & control , Protección Radiológica/normas , Radiometría/métodos , Dosificación Radioterapéutica , Administración de la Seguridad/normas , Estados Unidos
18.
Health Phys ; 86 Suppl 2: S120-S123, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-28121704

RESUMEN

The traditional approach to treatment of certain malignant brain tumors involves permanent implantation of I seeds sequential to tumor's resection. This approach has recently been changed for patients with unifocal recurrent gliomas. What began during the 1990's as a large clinical trial utilizing GliaSite Radiotherapy System, is currently becoming standard of care. This radiotherapy system consists of an inflatable balloon catheter, 2, 3, or 4 cm diameter, which is surgically placed in the tumor resection cavity; its positioning and the level of conformity within the cavity are verified via MRI imaging with contrast. The balloon is then filled with appropriate volume of I in the liquid form. Radiation treatment prescription dose ranges from 40 to 60 Gy (4,000 to 6,000 rads). This is accomplished by allowing 2.77 to 16.6 GBq (75 to 450 mCi) of I to remain in the balloon for 3-5 d. Numerous technical, dosimetric, and logistical considerations arise when handling large quantities of iodine necessary to perform GliaSite procedures. They require coordination of efforts of several hospital departments and the institution's RSO-in our case, two RSOs, at the University of Colorado Hospital and University of Colorado Health Sciences Center hold separate radioactive materials licenses. Based on our experiences and those of others, we conclude that, with appropriate guidance and care, these procedures can be performed safely without excessive restrictions.

20.
Eur J Clin Pharmacol ; 57(6-7): 461-5, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11699610

RESUMEN

OBJECTIVE: We previously found that, compared with healthy subjects. asymptomatic hepatitis-B virus (HBV) carriers displaying slow acetylator phenotype demonstrate a significant prolongation of the elimination half-life of 4-methylaminoantipyrine (MAA) and a decrease in the clearance of formation of 4-aminoantipyrine (AA) and 4-formylaminoantipyrine (FAA). However, the formation of 4-acetylaminoantipyrine (AAA) was unchanged. The present study was designed to examine the effect of the asymptomatic HBV carrier state on the metabolism of dipyrone. as a model drug, in rapid acetylators. METHODS: The plasma and urine concentrations of the metabolites of dipyrone were measured in eight asymptomatic HBV carriers and eight healthy subjects who had normal liver function tests, all displaying the rapid acetylation phenotype and genotype, after the administration of a 1.0-g oral dose of dipyrone. RESULTS: The following pharmacokinetic parameters were evaluated: peak plasma concentration, time to peak plasma concentration, elimination rate constant, area under the plasma concentration-time curve (0-->infinity), amount excreted (0-->infinity), renal and non-renal clearances for MAA and the clearances of formation for AA, FAA and AAA. No significant differences were found between the two subject groups. CONCLUSION: The effect of hepatic viral carrier state on drug metabolism may vary according to metabolic pathways and genetic polymorphism.


Asunto(s)
Aminopirina/análogos & derivados , Aminopirina/farmacocinética , Ampirona/análogos & derivados , Ampirona/farmacocinética , Antiinflamatorios no Esteroideos/farmacocinética , Dipirona/análogos & derivados , Dipirona/farmacocinética , Virus de la Hepatitis B/metabolismo , Pirazolonas , Acetilación , Adulto , Algoritmos , Aminopirina/sangre , Ampirona/sangre , Antiinflamatorios no Esteroideos/sangre , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/orina , Área Bajo la Curva , Portador Sano/sangre , Dipirona/sangre , Dipirona/química , Dipirona/orina , Femenino , Semivida , Humanos , Masculino , Tasa de Depuración Metabólica , Modelos Biológicos
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