ABSTRACT
INTRODUCTION: Distal symmetric polyneuropathy (DSP) is common in HIV and is associated with autonomic impairment. However tools to measure HIV-DSP do not include autonomic indices. We sought to optimize the Total Neuropathy Score (TNS) and the Composite Autonomic Severity Score (CASS) for use in HIV. METHODS: HIV-infected adults (n = 102) underwent neurologic examination, quantitative sensory testing (QST), nerve conduction studies, and autonomic testing. Modifications of the TNS and CASS were assessed for validity based on correlation with the original measure and internal consistency. RESULTS: The TNS version commonly used in HIV-DSP is valid, but it is improved by elimination of QST and addition of autonomic indices. A modified version of the CASS (M-CASS) which was designed for sensitivity to milder impairment was also valid. CONCLUSIONS: A modified TNS that excludes QST and includes autonomic indices is optimal for HIV-DSP. The M-CASS is a valid measure of autonomic impairment in HIV.
Subject(s)
AIDS-Associated Nephropathy/diagnosis , Peripheral Nerves/pathology , Peripheral Nerves/physiopathology , AIDS-Associated Nephropathy/complications , Adult , Female , Humans , Male , Middle Aged , Neural Conduction/physiology , Neurologic Examination , Pain/etiology , Severity of Illness IndexABSTRACT
Akinetic mutism is a wakeful state of severe apathy and paucity of volitional movement. Evidence indicates a possible dopaminergic hypofunction within the anterior cingulate cortex. The authors present three cases of acute onset akinetic mutism successfully treated with intramuscular olanzapine.
Subject(s)
Akinetic Mutism/drug therapy , Antipsychotic Agents/administration & dosage , Benzodiazepines/administration & dosage , Aged , Female , Humans , Injections, Intramuscular/methods , Male , Middle Aged , OlanzapineABSTRACT
Despite growing evidence for a mitochondrial localization of nitric oxide (NO) synthase and a broadening spectrum of NO actions on mitochondrial respiration and apoptosis, the basis for interaction between the enzyme and the organelle remain obscure. Here we investigated mitochondrial localization of endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells and human embryonic kidney cells transfected or infected with eNOS expression vectors. Copurification of eNOS with mitochondria was observed in both human umbilical vein endothelial cells and eNOS-expressing human embryonic kidney cells. Immunodetectable eNOS was cleaved from mitochondria by proteinase K treatment, suggesting eNOS association with the outer mitochondrial membrane. Localization of eNOS to a proteinase K-cleavable site on the cytoplasmic face of the outer membrane was confirmed by immunogold labeling of non-permeabilized mitochondria. Markers for mitochondrial subfractions ruled out the possibility of eNOS association with an intramitochondrial site or inverted mitochondrial particles. Denaturation of eNOS did not attenuate association with mitochondria. Mutant eNOS lacking a pentabasic amino acid sequence within the autoinhibitory domain (residues 628-632 of the bovine eNOS) showed dramatically reduced binding to the mitochondrial but not to the plasma membrane, which was associated with increased oxygen consumption. Collectively, these findings argue in favor of eNOS localization to the outer mitochondrial membrane in endothelial cells and identify elements of a novel anchoring mechanism.
