Phenylketonuria (PKU; OMIM 261600) is an autosomal recessive inborn error of phenylanaline metabolism. PKU is characterized by deficient or defective phenylalanine hydroxylase activity and persistantly increased levels of the essential amino acid phenylalanine in the circulation. The present article examines current understanding of the etiology of PKU, along with a meta-analysis examining neuropsychological and intellectual presentations in continuously treated adolescents and adults. Patients with PKU differed significantly from controls on Full-Scale IQ, processing speed, attention, inhibition, and motor control. Future research utilizing an integrative approach and detailed analysis of specific cognitive domains will assist both the scientist and clinician, and ultimately the patient.
Iron is implicated in the pathogenesis of liver injury and insulin resistance (IR) and thus phlebotomy has been proposed as a treatment for nonalcoholic fatty liver disease (NAFLD). We performed a prospective 6-month randomized, controlled trial examining the impact of phlebotomy on the background of lifestyle advice in patients with NAFLD. Primary endpoints were hepatic steatosis (HS; quantified by magnetic resonance imaging) and liver injury (determined by alanine aminotransaminase [ALT] and cytokeratin-18 ). Secondary endpoints included insulin resistance measured by the insulin sensitivity index (ISI) and homeostasis model of assessment (HOMA), and systemic lipid peroxidation determined by plasma F2-isoprostane levels. A total of 74 subjects were randomized (33 phlebotomy and 41 control). The phlebotomy group underwent a median (range) of 7 (1-19) venesection sessions and had a significantly greater reduction in ferritin levels over 6 months, compared to controls (2148 6 114 vs. 238 6 89 ng/mL; P < 0.001). At 6 months, there was no difference between phlebotomy and control groups in HS (17.7% vs. 15.5%; P 5 0.4), serum ALT (36 vs. 46 IU/L; P 5 0.4), or CK-18 levels (175 vs. 196 U/L; P 5 0.9). Similarly, there was no difference in end-of-study ISI (2.5 vs. 2.7; P 5 0.9), HOMA (3.2 vs. 3.2; P 5 0.6), or F2-isoprostane levels (1,332 vs. 1,190 pmmol/L; P 5 0.6) between phlebotomy and control groups. No differences in any endpoint were noted in patients with hyperferritinemia at baseline. Among patients undergoing phlebotomy, there was no correlation between number of phlebotomy sessions and change in HS, liver injury, or IR from baseline to end of study. Conclusion: Reduction in ferritin by phlebotomy does not improve liver enzymes, hepatic fat, or IR in subjects with NAFLD. (HEPATOLOGY 2015;61:1555-1564
Background and Purpose-The previous decade has witnessed increasing application of Guglielmi detachable coils (GDCs) for the treatment of intracranial aneurysms. However, the midterm angiographic and clinical outcomes are not well documented. We report here the angiographic and clinical outcomes of patients treated with GDCs over an 8-year period . Methods-Between 1992 and 1998, 144 patients with 160 intracranial aneurysms were treated with GDCs. Clinical follow-up data were obtained from medical records, questionnaires, and telephone interviews. Angiographic studies were reviewed by 2 neuroradiologists to obtain consensus regarding the degree of aneurysm occlusion. Results-Eighty-one patients had ruptured aneurysms; 63 had unruptured aneurysms. Technical success was achieved in 91% of patients, with complete aneurysm occlusion in 46%, neck remnants in 16%, and residual body filling in 38%. Angiographic follow-up revealed that residual body filling in some aneurysms was resolved, small neck remnants were stable, and the recanalization rate decreased with time. All 63 patients with unruptured aneurysms were discharged from hospital with independent clinical status (Glasgow Outcome Score, 1 or 2). For patients with ruptured aneurysms, discharge clinical status correlated with the Hunt & Hess clinical grade at the time of treatment. Clinical follow-up for a minimum of 2 years was available in 98.5% of patients. Ninety-four percent of patients treated for unruptured aneurysms were independent at 2 years, and 82% of Hunt & Hess grade I to II patients were independent. Conclusions-Coil embolization is a safe and effective treatment for both ruptured and unruptured aneurysms. Increasing angiographic stability is demonstrated in treated aneurysms up to 3 years from coil embolization. Therefore, follow-up angiography until this time is advisable. (Stroke. 2002;33:210-217.)
RNA polymerase III is essential for the transcription of non-coding RNAs, including tRNAs. Mutations in the genes encoding its largest subunits are known to cause hypomyelinating leukodystrophies (HLD7) with pathogenetic mechanisms hypothesised to involve impaired availability of tRNAs. We have identified a founder mutation in the POLR3A gene that leads to aberrant splicing, a premature termination codon and partial deficiency of the canonical full-length transcript. Our clinical and imaging data showed no evidence of the previously reported white matter or cerebellar involvement; instead the affected brain structures included the striatum and red nuclei with the ensuing clinical manifestations. Our transcriptome-wide investigations revealed an overall decrease in the levels of Pol III-transcribed tRNAs and an imbalance in the levels of regulatory ncRNAs such as small nuclear and nucleolar RNAs (snRNAs and snoRNAs). In addition, the Pol III mutation was found to exert complex downstream effects on the Pol II transcriptome, affecting the general regulation of RNA metabolism.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.