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Early Therapeutic Interventions (early + therapeutic_intervention)
Selected AbstractsPotential role for Interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection,HEPATOLOGY, Issue 4 2010Jason Grebely Polymorphisms in the IL28B (interleukin-28B) gene region are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. We evaluated the role of IL28B in spontaneous and treatment-induced clearance following recent HCV infection. The Australian Trial in Acute Hepatitis C (ATAHC) was a study of the natural history and treatment of recent HCV, as defined by positive anti-HCV antibody, preceded by either acute clinical HCV infection within the prior 12 months or seroconversion within the prior 24 months. Factors associated with spontaneous and treatment-induced HCV clearance, including variations in IL28B, were assessed. Among 163 participants, 132 were untreated (n = 52) or had persistent infection (infection duration ,26 weeks) at treatment initiation (n = 80). Spontaneous clearance was observed in 23% (30 of 132 participants). In Cox proportional hazards analysis (without IL28B), HCV seroconversion illness with jaundice was the only factor predicting spontaneous clearance (adjusted hazards ratio = 2.86; 95% confidence interval = 1.24, 6.59; P = 0.014). Among participants with IL28B genotyping (n = 102 of 163 overall and 79 of 132 for the spontaneous clearance population), rs8099917 TT homozygosity (versus GT/GG) was the only factor independently predicting time to spontaneous clearance (adjusted hazard ratio = 3.78; 95% confidence interval = 1.04, 13.76; P = 0.044). Participants with seroconversion illness with jaundice were more frequently rs8099917 TT homozygotes than other (GG/GT) genotypes (32% versus 5%, P = 0.047). Among participants adherent to treatment and who had IL28B genotyping (n = 54), sustained virologic response was similar among TT homozygotes (18 of 29 participants, 62%) and those with GG/GT genotype (16 of 25, 64%, P = 0.884). Conclusion: During recent HCV infection, genetic variations in IL28B region were associated with spontaneous but not treatment-induced clearance. Early therapeutic intervention could be recommended for individuals with unfavorable IL28B genotypes. (HEPATOLOGY 2010;) [source] Early therapeutic intervention in females with Fabry disease?ACTA PAEDIATRICA, Issue 2008Derralynn A Hughes Abstract Anderson,Fabry disease is an X-linked lysosomal storage disorder resulting from deficiency of ,-galactosidase A. The subsequent accumulation of globotriaosylceramide (Gb3) in cells and tissues of the body has multisystemic effects and significantly impacts upon quality of life and survival of individuals with this condition. In general, Anderson,Fabry disease is more severe in male patients; however, despite X-linkage, females may develop severe signs and symptoms of the disease, although there is considerable phenotypic heterogeneity, which correlates most closely with age. Histological analyses of biopsies have shown evidence of Gb3 storage in the kidney and heart in female patients. Gb3 levels are also elevated in the urine of females, although plasma Gb3 levels are not reliably elevated. The efficacy of enzyme replacement therapy (ERT) with recombinant human ,-galactosidase A has been demonstrated in females in a clinical trial and in observational studies, including those using data from outcome surveys. Benefits include a reduction in left ventricular mass, stabilization of renal function and improvements in pain and quality of life. Conclusion: If early intervention with ERT in females is to be advocated, it is necessary to demonstrate not only that females with Anderson,Fabry disease have clinical and biochemical features of ,-galactosidase A deficiency and respond to ERT, but also that early intervention prevents the onset of the later manifestations of the disorder. Any strategy for early therapy should also balance future advantages against any impact on quality of life. [source] Relating therapeutic process to outcome: are there predictors for the short-term course in anorexic patients?EUROPEAN EATING DISORDERS REVIEW, Issue 4 2005Almut Zeeck Abstract Objective The aim of the study was to explore if process aspects of the first 12 individual psychotherapy sessions of anorexic patients (6 weeks of treatment) are associated with a good or bad outcome at discharge. Method N,=,38 patients with anorexia nervosa (DSM-IV) were treated in a multimodal setting. Process measures were available from the perspectives of both patients and therapists for N,=,344 sessions. Results 79% of the successful patients (discharge BMI,>,17.5) and 68% of the failures could be correctly identified by process variables measured in the initial treatment phase. Patients' experience of negative emotions re therapy between sessions was associated with a bad outcome, whereas a frequent and intense process of ,recreating the therapeutic dialogue' was found to be associated with a good outcome. Early therapeutic interventions with a focus on symptoms and interpersonal relationships were related to a positive outcome, whereas a focus on self-concept was related to a bad outcome. Copyright © 2005 John Wiley & Sons, Ltd and Eating Disorders Association. [source] Modulation of sulfur mustard induced cell death in human epidermal keratinocytes using IL-10 and TNF-,,,JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2005Aziz Qabar Abstract We compared the effects of overexpressing a tightly regulated anti-inflammatory cytokine, interleukin 10 (IL-10), and the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-,) on sulfur mustard induced cytotoxicity in human epidermal keratinocytes. Both cytokines were overexpressed when compared with the cells transfected with the empty vector as determined by quantitative ELISA. Cells overexpressing interleukin 10 suppressed the pro-inflammatory cytokines interleukin 8 and interleukin 6 following exposure to 50,300 ,M sulfur mustard. These cells exhibited delayed onset of sulfur mustard induced cell death. On the other hand, cells overexpressing tumor necrosis factor alpha induced a sustained elevation in both interleukin 6 and 8 expression following exposure to 50,300 ,M sulfur mustard. These cells were sensitized to the effects of sulfur mustard that resulted in an increased sulfur mustard induced cell death. Normal human epidermal keartinocytes treated with sulfur mustard exhibited elevated levels of tumor necrosis factor alpha expression and increased activity of nuclear factor kappa B. Gene array data indicated that cells overexpressing interleukin 10 induced several genes that are involved in growth promotion and cell-fate determination. We, therefore, identify IL-10 and TNF-, signal transduction pathways and their components as possible candidates for early therapeutic intervention against sulfur mustard induced cell injury. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:213,225, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20089 [source] Congenital diaphragmatic hernia: review of the literature in reflection of unresolved dilemmasACTA PAEDIATRICA, Issue 12 2009S Grisaru-Granovsky Abstract Background:, Congenital diaphragmatic hernia (CDH) is a rare but clinically and scientifically challenging condition. The introduction of ultrasound has enabled early prenatal detection and consequently, hope of early therapeutic intervention. Aim:, We undertook the task to review the recent developments in understanding the pathology of CDH as well as the history and current management strategies to aid perinatologists in consultations with parents of CDH-affected foetuses. Study design:, A Medline search was undertaken of all reports and reviews published between 1980 and 2008 using MeSH search terms ,diaphragmatic hernia', ,congenital' and ,newborn'. Results:, The true incidence of CDH is still difficult to estimate because of the high incidence of hidden mortality of CDH. Complete case ascertainment also poses difficulties in assessment of the impact of new therapeutic modalities on overall survival. Recent improvements in prenatal detection are a milestone in affording time for re-assessments and parental counselling. The true benefit of antenatal therapy is circumscribed and should be offered only in selected cases of isolated severe CDH as defined by existing guidelines. Postnatal intensive respiratory supportive therapy and innovative surgical techniques within specialized tertiary centres has had a major impact on survival of babies with CDH. Conclusion:, The high survival of ,selected cases' that are live births and benefit from optimal care will be difficult to improve by antenatal interventions. The multidisciplinary approach to basic research and randomized clinical trials will further define the best approach to the foetus and neonate with CDH. [source] Plasticity of the visual system after early brain damageDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 10 2010ANDREA GUZZETTA The aim of this review is to discuss the existing evidence supporting different processes of visual brain plasticity after early damage, as opposed to damage that occurs during adulthood. There is initial evidence that some of the neuroplastic mechanisms adopted by the brain after early damage to the visual system are unavailable at a later stage. These are, for example, the ability to differentiate functional tissue within a larger dysplastic cortex during its formation, or to develop new thalamo-cortical connections able to bypass the lesion and reach their cortical destination in the occipital cortex. The young brain also uses the same mechanisms available at later stages of development but in a more efficient way. For example, in people with visual field defects of central origin, the anatomical expansion of the extrastriatal visual network is greater after an early lesion than after a later one, which results in more efficient mechanisms of visual exploration of the blind field. A similar mechanism is likely to support some of the differences found in people with blindsight, the phenomenon of unconscious visual perception in the blind field. In particular, compared with people with late lesions, those with early brain damage appear to have stronger subjective awareness of stimuli hitting the blind visual field, reported as a conscious feeling that something is present in the visual field. Expanding our knowledge of these mechanisms could help the development of early therapeutic interventions aimed at supporting and enhancing visual reorganization at a time of greatest potential brain plasticity. [source] Natural history of hepatic fibrosis progression in chronic hepatitis C virus infection in IndiaJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2009Syed S Hissar Abstract Background and Aim:, The rate of fibrosis progression per year can predict the time for the development of cirrhosis in chronic hepatitis C (CHC). We assessed the rate of fibrosis progression and the predictors of disease severity in Indian CHC patients. Methods:, Of the 355 treatment-naïve, histologically-proven CHC patients, the precise duration of infection (from the time of exposure to HCV until liver biopsy) could be determined in 213 patients (age = 41.6 ± 14.7 years, male : female = 139 : 74, genotype 3 = 75%). The rate of fibrosis progression per year was calculated. The correlation of the advanced degree of fibrosis and age, duration of infection, age at the onset of infection, sex, mode of infection, hepatitis C virus (HCV) genotype, histological activity index (HAI), and the presence of diabetes mellitus were studied. Results:, The median rate of fibrosis progression per year was 0.25 (0.0,1.5) fibrosis units. The fibrosis progression rate was higher in patients who acquired infection at > 30 years of age, those < 30 years (0.33 vs 0.15; P < 0.001), and those who acquired HCV infection with a history of blood transfusion than with other modes of transmission (0.25 vs 0.19; P = 0.04). The median time to progress to cirrhosis was 16 years. The multivariate analysis found that the HAI score (odds ratio [OR]= 14.03; P < 0.001) and the duration of infection > 10 years (OR = 4.83; P < 0.001) correlated with severe liver disease (fibrosis , 3). Conclusion:, The median rate of fibrosis progression per year in Indian CHC patients is 0.25 fibrosis units. A higher HAI and longer duration of infection are associated with a significant risk of advanced liver disease, and merit early therapeutic interventions. [source] Cardiac troponin T Arg92Trp mutation and progression from hypertrophic to dilated cardiomyopathyCLINICAL CARDIOLOGY, Issue 5 2001Noboru Fujino M.D. Abstract Background: Mutations in the cardiac troponin T gene causing familial hypertrophic cardiomyopathy (HCM) are associated with a very poor prognosis but only mild hypertrophy. To date, the serial morphologic changes in patients with HCM linked to cardiac troponin T gene mutations have not been reported. Hypothesis: The aim of this study was to determine the long-term course of patients with familial HCM caused by the cardiac troponin T gene mutation, Arg92Trp. Results: The Arg92Trp missense mutation was present in 10 individuals from two unrelated pedigrees. They exhibited different cardiac morphologies: three had dilated cardiomyopathy-like features, five had asymmetric septal hypertrophy with normal left ventricular systolic function, one had electrocardiographic abnormalities without hypertrophy, and one had the disease-causing mutation but did not fulfill the clinical criteria for the disease. The mean maximum wall thickness was 14.1 ± 6.0 mm. The three patients with dilated cardiomyopathy-like features had progressive left ventricular dilation. Three individuals underwent right ventricular endomyocardial biopsy. There was a modest degree of myocardial hypertrophy (myocyte diameter: 18.9 ± 5.2 m,m), and minimal myocardial disarray and mild fibrosis were noted. Conclusion: The Arg92Trp substitution in the cardiac troponin T gene shows a high degree of penetrance, moderate hypertrophy, and early progression to dilated cardiomyopathy in Japanese patients. Early identification of individuals with this mutation may provide the opportunity to evaluate the efficacy of early therapeutic interventions. [source] | ||||||||||