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Slower Progression (slower + progression)
Selected AbstractsProgression through early drinking milestones in an adolescent treatment sampleADDICTION, Issue 3 2010Kristina M. Jackson ABSTRACT Aims Research using nationally representative and community samples demonstrates a robust association between early onset of drinking and increased likelihood of numerous adverse outcomes. However, little is known about the subsequent drinking that occurs early in the drinking career. The present study dissects the transition from any alcohol use to treatment entry by taking a fine-grained approach to examining the attainment and progression of drinking events in a sample of adolescents in substance use treatment. Design/Setting Data were taken from the Drug Abuse Treatment Outcome Study for Adolescents (DATOS-A), a multi-site, community-based study of adolescents entering treatment. Participants Respondents included 3331 youth aged 12,18 years (mean = 15.75) admitted to treatment in 1993,95 (74% male, 52% white, 24% African American, 20% Hispanic). Measurements Age of attainment was obtained for five drinking-related milestones, including first drink of alcohol, first time drunk, first monthly drinking, first drank five or more drinks/day on a weekly basis and first drank five or more drinks/day on a daily basis. Findings Most milestones were attained at a very early age, and average progression through adjacent drinking events was relatively swift, Movement through early drinking milestones was accelerated in girls and white youth. Youth who reported their first drink at an early age (age 10 or younger) showed slower progression, suggesting the existence of distinct processes underlying early use and drinking transitions within an individual. Conclusions This study provides data relevant to understanding drinking progression/natural history in a large clinical sample, especially for differences by gender and ethnicity. The findings have implications for the identification of intermediate stages that might benefit from selected intervention programs. [source] Axonal integrity in the absence of functional peroxisomes from projection neurons and astrocytesGLIA, Issue 13 2010Astrid Bottelbergs Abstract Ablation of functional peroxisomes from all neural cells in Nestin-Pex5 knockout mice caused remarkable neurological abnormalities including motoric and cognitive malfunctioning accompanied by demyelination, axonal degeneration, and gliosis. An oligodendrocyte selective Cnp-Pex5 knockout mouse model shows a similar pathology, but with later onset and slower progression. Until now, the link between these neurological anomalies and the known metabolic alterations, namely the accumulation of very long-chain fatty acids (VLCFA) and reduction of plasmalogens, has not been established. We now focused on the role of peroxisomes in neurons and astrocytes. A neuron-specific peroxisome knockout model, NEX-Pex5, showed neither microscopic nor metabolic abnormalities indicating that the lack of functional peroxisomes within neurons does not cause axonal damage. Axonal integrity and normal behavior was also preserved when peroxisomes were deleted from astrocytes in GFAP-Pex5,/, mice. Nevertheless, peroxisomal metabolites were dysregulated in brain including a marked accumulation of VLCFA and a slight reduction in plasmalogens. Interestingly, despite minor targeting of oligodendrocytes in GFAP-Pex5,/, mice, these metabolic perturbations were also present in isolated myelin indicating that peroxisomal metabolites are shuttled between different brain cell types. We conclude that absence of peroxisomal metabolism in neurons and astrocytes does not provoke the neurodegenerative phenotype observed after deleting peroxisomes from oligodendrocytes. Lack of peroxisomal metabolism in astrocytes causes increased VLCFA levels in myelin, but this has no major impact on neurological functioning. © 2010 Wiley-Liss, Inc. [source] Impact of pegylated interferon and ribavirin on morbidity and mortality in patients with chronic hepatitis C and normal aminotransferases in France,HEPATOLOGY, Issue 5 2009Sylvie Deuffic-Burban Clinicians continue to raise questions concerning the necessity of treating chronic hepatitis C virus (HCV)-infected patients with normal alanine aminotransferase (N-ALT), in light of their slower progression to cirrhosis than patients with elevated alanine aminotraferase (E-ALT). This study was undertaken to predict the impact of pegylated interferon (IFN) and ribavirin on HCV-related morbidity and mortality in patients with N-ALT. A previous Markov model was adapted to separately simulate patients with N-ALT (30%) and those with E-ALT (70%). The model estimates fibrosis progression rates according to age, sex, and whether ALT levels are normal or elevated, assuming that patients with E-ALT have a 2.6 times higher progression than those with N-ALT. It takes into account improvement in HCV screening and treatment and competitive mortality. We assumed that N-ALT patients were treated 80% less frequently between 2002 and 2004 and 70% less frequently from 2005 on, as obtained in real life from three multicentric cohorts (Hepatys, Adequation, Persee). Antiviral treatment of HCV-infected populations might reduce 2008-2025 HCV-related morbidity and mortality by 34,200 cases of cirrhosis (36%, 33,000-35,000), 22,400 complications (28%, 21,000-23,000) and 17,500 deaths (25%, 17,000-18,000), including 3000 cases of cirrhosis (22%, 2000-5000), 1200 complications (15%, 1000-1700), and 1000 deaths (14%, 900-1300) in the N-ALT population, despite a probability of receiving treatment that is three to five times less in this population. If N-ALT patients are treated at the same proportions as those with E-ALT, morbidity and mortality could be further reduced by 1400 cases of cirrhosis (13%, 1200-2200), 600 complications (9%, 600-1000), and 500 deaths (9%, 500-800). Conclusion: Treatment of N-ALT patients would decrease HCV morbidity and mortality. These patients should be considered candidates for treatment just as others are. (HEPATOLOGY 2009.) [source] Fanconi's syndrome and subsequent progressive renal failure caused by a Chinese herb containing aristolochic acidNEPHROLOGY, Issue 3 2004SANGHO LEE SUMMARY: Chinese herb nephropathy contains a variety of clinical features of progressive renal failure (indicated by studies conducted in Belgium) to the variant type of Fanconi's syndrome. Fanconi's syndrome has mostly been reported in Asian countries, and is characterized by proximal tubular dysfunction and slower progression to end-stage renal disease (ESRD); it also often revealed a reversible clinical course. We describe a 43-year-old woman who presented with polyuria and polydipsia caused by Fanconi's syndrome. The cause of Fanconi's syndrome was not identified because the patient denied the intake of the Chinese herbal mixture at first. Fanconi's syndrome seemed to be reversible in its early stage, but it rapidly progressed to renal failure after 3 months, despite the interruption of Chinese mixture use. A renal biopsy revealed typical findings of aristolochic acid-induced nephropathy. Aristolochic acids were also detected in the Chinese herbs that were consumed. This case highlights the variety of the clinical spectrum of aristolochic acid induced nephropathy (AAN). We emphasize that AAN should be suspected in all patients with Fanconi's syndrome, even if patients deny the intake of any Chinese herbal preparation. [source] How much phenotypic variation can be attributed to parkin genotype?ANNALS OF NEUROLOGY, Issue 2 2003Ebba Lohmann MD To establish phenotype,genotype correlations in early-onset parkinsonism, we have compared the phenotype of a large series of 146 patients with and 250 patients without parkin mutations. Although no single sign distinguished the groups, patients with mutations had significantly earlier and more symmetrical onset, dystonia more often at onset and hyperreflexia, slower progression of the disease, and a tendency toward a greater response to levodopa despite lower doses. After forward stepwise multiple logistic regression analysis, dystonia at onset and brisk reflexes were not longer significantly different but were correlated with age at onset rather than the presence of the parkin mutation. Age at onset in carriers of parkin mutations varied as did the rate of progression of the disease: the younger the age at onset the slower the evolution. The genotype influenced the phenotype: carriers of at least one missense mutation had a higher United Parkinson's Disease Rating Scale motor score than those carrying two truncating mutations. The localization of the mutations was also important because missense mutations in functional domains of parkin resulted in earlier onset. Patients with a single heterozygous mutation had significantly later and more asymmetrical onset and more frequent levodopa-induced fluctuations and dystonia than patients with two mutations. Ann Neurol 2003 [source] Face down posturing for macular hole surgery.ACTA OPHTHALMOLOGICA, Issue 2009Is it really required? Purpose Background: In macular hole surgery pars plana vitrectomy and intravitreal gas injection with or without inner limiting membrane peel, is considered the mainstay of treatment. The requirement for face down posturing is generally regarded as part of the traditional postoperative routine. Several mechanisms have been postulated to explain the action of the gas bubble including exertion of a large floatation force on the macula and prevention of the macular hole exposure to vitreous fluid. Recently the need to face down has been chalenged since this regime compromises patients' postoperative quality of life and it makes macular hole surgery almost impossible for individuals with mental or physical limitations. Methods Review of personal data and systermatic literature review of studies investigating macular hole surgery with shortened or eliminated face down posturing. Results There is considerable body of evidence suggesting successful anatomical and functional outcome in patients with shorter duration of posturing or no posturing at all following macular hole surgery. The pros and cons of each technique will be presented in detail. Conclusion Prone posturing following macular hole surgery provides no functional or anatomic benefit but it is associated with slower progression of cataract. Combined phacovitrectomy without face down positioning may be considered for phakic patients undergoing macular hole surgery. [source] |