Rush University Medical Center

About: Rush University Medical Center is a healthcare organization based out in Chicago, Illinois, United States. It is known for research contribution in the topics: Population & Dementia. The organization has 13915 authors who have published 29027 publications receiving 1379216 citations. The organization is also known as: Rush Presbyterian St. Luke's Medical Center.

Functional fetal nigral grafts in a patient with Parkinson's disease: Chemoanatomic, ultrastructural, and metabolic studies

Abstract: A patient with Parkinson's disease received bilateral fetal human nigral implants from six donors aged 6.5 to 9 weeks post-conception. Eighteen months following a post-operative clinical course characterized by marked improvement in clinical function, this patient died from events unrelated to the grafting procedure. Post-mortem histological analyses revealed the presence of viable grafts in all 12 implant sites, each containing a heterogeneous population of neurons and glia. Approximately 210,146 implanted tyrosine hydroxylase-immunoreactive (TH-ir) neurons were found. A greater number of TH-ir grafted neurons were observed in the right (128,162) than the left (81,905) putamen. Grafted TH-ir neurons were organized in an organotypic fashion. These cells provided extensive TH-ir and dopamine transporter-ir innervation to the host striatum which occurred in a patch-matrix fashion. Quantitative evaluations revealed that fetal nigral grafts reinnervated 53% and 28% of the post-commissural putamen on the right and left side, respectively. Grafts on the left side innervated a lesser area of the striatum, but optical density measurements were similar on both sides. There was no evidence that the implants induced sprouting of host TH-ir systems. Electron microscopic analyses revealed axo-dendritic and occasional axo-axonic synapses between graft and host. In contrast, axo-somatic synapses were not observed. In situ hybridization for TH mRNA revealed intensely hybridized grafted neurons which far exceeded TH mRNA expression within residual host nigral cells. In addition, γ-amino butyric acid (GABA)-ergic neurons were observed within the graft that formed a dense local neuropil which was confined to the implant site. Serotonergic neurons were not observed within the graft. Cytochrome oxidase activity was increased bilaterally within the grafted post-commissural putamen, suggesting increased metabolic activity. In this regard, a doubling of cytochrome oxidase activity was observed within the grafted post-commissural putamen bilaterally relative to the non-grafted anterior putamen. The grafts were hypovascular relative to the surrounding striatum and host substantia nigra. Blood vessels within the graft stained intensely for GLUT-1, suggesting that this marker of blood-brain barrier function is present within human nigral allografts. Taken together, these data indicate that fetal nigral neurons can survive transplantation, functionally reinnervate the host putamen, establish synaptic contacts with host neurons, and sustain many of the morphological and functional characteristics of normal nigral neurons following grafting into a patient with PD. © 1996 Wiley-Liss, Inc.

Gait impairments in Parkinson's disease.

Abstract: Summary Gait impairments are among the most common and disabling symptoms of Parkinson's disease. Nonetheless, gait is not routinely assessed quantitatively but is described in general terms that are not sensitive to changes ensuing with disease progression. Quantifying multiple gait features (eg, speed, variability, and asymmetry) under natural and more challenging conditions (eg, dual-tasking, turning, and daily living) enhanced sensitivity of gait quantification. Studies of neural connectivity and structural network topology have provided information on the mechanisms of gait impairment. Advances in the understanding of the multifactorial origins of gait changes in patients with Parkinson's disease promoted the development of new intervention strategies, such as neurostimulation and virtual reality, aimed at alleviating gait impairments and enhancing functional mobility. For clinical applicability, it is important to establish clear links between specific gait impairments, their underlying mechanisms, and disease progression to foster the acceptance and usability of quantitative gait measures as outcomes in future disease-modifying clinical trials.

Fragile X-associated tremor/ataxia syndrome: clinical features, genetics, and testing guidelines.

Abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder with core features of action tremor and cerebellar gait ataxia. Frequent associated findings include parkinsonism, executive function deficits and dementia, neuropathy, and dysautonomia. Magnetic Resonance Imaging studies in FXTAS demonstrate increased T2 signal intensity in the middle cerebellar peduncles (MCP sign) in the majority of patients. Similar signal alterations are seen in deep and subependymal cerebral white matter, as is general cortical and subcortical atrophy. The major neuropathological feature of FXTAS is the presence of intranuclear, neuronal, and astrocytic, inclusions in broad distribution throughout the brain and brainstem. FXTAS is caused by moderate expansions (55-200 repeats; premutation range) of a CGG trinucleotide in the fragile X mental retardation 1 (FMR1) gene, the same gene which causes fragile X syndrome when in the full mutation range (200 or greater CGG repeats). The pathogenic mechanism is related to overexpression and toxicity of the FMR1 mRNA per se. Although only recently discovered, and hence currently under-diagnosed, FXTAS is likely to be one of the most common single-gene disorders leading to neurodegeneration in males. In this report, we review information available on the clinical, radiological, and pathological features, and prevalence and management of FXTAS. We also provide guidelines for the practitioner to assist with identifying appropriate patients for DNA testing for FXTAS, as well as recommendations for genetic counseling once a diagnosis of FXTAS is made.

Costs of an emergency department-based accelerated diagnostic protocol vs hospitalization in patients with chest pain a randomized controlled trial

Abstract: Context.-More than 3 million patients are hospitalized yearly in the United States for chest pain. The cost is over $3 billion just for those found to be free of acute disease. New rapid diagnostic tests for acute myocardial infarction (AMI) have resulted in the proliferation of accelerated diagnostic protocols (ADPs) and chest pain observation units. Objective.-To determine whether use of an emergency department (ED)-based ADP can reduce hospital admission rate, total cost, and length of stay (LOS) for patients needing admission for evaluation of chest pain. Design.-Prospective randomized controlled trial comparing admission rate, total cost, and LOS for patients treated using ADP vs inpatient controls. Total costs were determined using empirically measured resource utilization and microcosting techniques. Setting.-A large urban public teaching hospital serving a predominantly African American and Hispanic population. Patients.-A sample of 165 patients was randomly selected from a larger consecutive sample of 429 patients with chest pain concurrently enrolled in an ADP diagnostic cohort trial. Eligible patients presented to the ED with clinical findings suggestive of AMI or acute cardiac ischemia (ACI) but at low risk using a validated predictive algorithm. Main Outcome Measures.-Primary outcomes measured for each subject were LOS and total cost of treatment. Results.-The hospital admission rate for ADP vs control patients was 45.2% vs 100% (P<.001). The mean total cost per patient for ADP vs control patients was $1528 vs $2095 (P<.001). The mean LOS measured in hours for ADP vs control patients was 33.1 hours vs 44.8 hours (P<.01). Conclusions.-In this trial, ADP saved $567 in total hospital costs per patient treated. Use of ED-based ADPs can reduce hospitalization rates, LOS, and total cost for low-risk patients with chest pain needing evaluation for possible AMI or ACl.

The voltage dependence of NADPH oxidase reveals why phagocytes need proton channels

Abstract: The enzyme NADPH oxidase in phagocytes is important in the body's defence against microbes: it produces superoxide anions (O2-, precursors to bactericidal reactive oxygen species1). Electrons move from intracellular NADPH, across a chain comprising FAD (flavin adenine dinucleotide) and two haems, to reduce extracellular O2 to O2-. NADPH oxidase is electrogenic2, generating electron current (Ie) that is measurable under voltage-clamp conditions3,4. Here we report the complete current–voltage relationship of NADPH oxidase, the first such measurement of a plasma membrane electron transporter. We find that Ie is voltage-independent from -100 mV to >0 mV, but is steeply inhibited by further depolarization, and is abolished at about +190 mV. It was proposed that H+ efflux2 mediated by voltage-gated proton channels5,6 compensates Ie, because Zn2+ and Cd2+ inhibit both H+ currents7,8,9 and O2- production10. Here we show that COS-7 cells transfected with four NADPH oxidase components11, but lacking H+ channels12, produce O2- in the presence of Zn2+ concentrations that inhibit O2- production in neutrophils and eosinophils. Zn2+ does not inhibit NADPH oxidase directly, but through effects on H+ channels. H+ channels optimize NADPH oxidase function by preventing membrane depolarization to inhibitory voltages.