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.

Delivery of neurturin by AAV2 (CERE-120)-mediated gene transfer provides structural and functional neuroprotection and neurorestoration in MPTP-treated monkeys.

Abstract: Objective We tested the hypothesis that gene delivery of the trophic factor neurturin could preserve motor function and protect nigrostriatal circuitry in hemiparkinsonian monkeys. Methods An adeno-associated virus–based vector encoding human neurturin (AAV2-NTN; also called CERE-120) was injected into the striatum and substantia nigra of monkeys 4 days after a unilateral intracarotid injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rendered them hemiparkinsonian. Control hemiparkinsonian monkeys received either AAV2 encoding green fluorescent protein or formulation buffer. Results Although stable deficits were seen in all control monkeys, AAV2-NTN significantly improved MPTP-induced motor impairments by 80 to 90% starting at approximately month 4 and lasting until the end of the experiment (month 10). AAV2-NTN significantly preserved nigral neurons, significantly preserved striatal dopaminergic innervation, and activated phospho-extracellular signal–regulated kinase, consistent with a mechanism involving a trophic factor–initiated molecular cascade. Histological analyses of numerous brain regions, including the cerebellum, showed normal cytoarchitecture and no aberrant pathology. Interpretation These data demonstrate that AAV2-NTN (CERE-120) can preserve function and anatomy in degenerating nigrostriatal neurons and are supportive of ongoing clinical tests in Parkinson's disease patients. Ann Neurol 2006;60:706–715

Preparation and characterization of toxic Abeta aggregates for structural and functional studies in Alzheimer's disease research.

Abstract: The amyloid cascade hypothesis, supported by strong evidence from genetics, pathology and studies using animal models, implicates amyloid-beta (Abeta) oligomerization and fibrillogenesis as central causative events in the pathogenesis of Alzheimer's disease (AD). Today, significant efforts in academia, biotechnology and the pharmaceutical industry are devoted to identifying the mechanisms by which the process of Abeta aggregation contributes to neurodegeneration in AD and to the identity of the toxic Abeta species. In this paper, we describe methods and detailed protocols for reproducibly preparing Abeta aggregates of defined size distribution and morphology, including monomers, protofibrils and fibrils, using size exclusion chromatography. In addition, we describe detailed biophysical procedures for elucidating the structural features, aggregation kinetics and toxic properties of the different Abeta aggregation states, with special emphasis on protofibrillar intermediates. The information provided by this approach allows for consistent correlation between the properties of the aggregates and their toxicity toward primary neurons and/or cell lines. A better understanding of the molecular and structural basis of Abeta aggregation and toxicity is crucial for the development of effective strategies aimed at prevention and/or treatment of AD. Furthermore, the identification of specific aggregation states, which correlate with neurodegeneration in AD, could lead to the development of diagnostic tools to detect and monitor disease progression. The procedures described can be performed in as little as 1 day, or may take longer, depending on the exact toxicity assays used.

Dexmedetomidine for neurological surgery.

Abstract: Dexmedetomidine is a new intravenous drug gaining popularity in neuroanesthesia and neurocritical care practice. This alpha2-adrenergic receptor agonist offers a unique "cooperative sedation," anxiolysis, and analgesia with no respiratory depression. Cerebral effects are generally consistent with a desirable neurophysiological profile, including neuroprotective characteristics. In addition, sympatholytic and antinociceptive properties allow for hemodynamic stability at critical moments of neurosurgical stimulation. This review will address the neuropharmacology and neurophysiology of alpha2-adrenergic agonists and will specifically consider the rapidly evolving applicability of dexmedetomidine as an adjuvant to neurosurgical case management.

Newer Anesthesia and Rehabilitation Protocols Enable Outpatient Hip Replacement in Selected Patients

Abstract: Advancements in the surgical approach, anesthetic technique, and the initiation of rapid rehabilitation protocols have decreased the duration of hospitalization and subsequent length of recovery following elective total hip arthroplasty. We assessed the feasibility and safety of outpatient total hip arthroplasty in 150 consectutive patients. A comprehensive perioperative anesthesia and rehabilitation protocol including preoperative teaching, regional anesthesia, and preemptive oral analgesia and antiemetic therapy was implemented around a minimally invasive surgical technique. A rapid rehabilitation pathway was started immediately after surgery and patients had the option of being discharged to home the day of surgery if standard discharge criteria were met. All 150 patients were discharged to home the day of surgery, at which time 131 patients were able to walk without assistive devices. Thirty-eight patients required some additional intervention outside the pathway to resolve nausea, hypotension, or sedation prior to discharge. There were no readmissions for pain, nausea, or hypotension yet there was one readmission for fracture and nine emergency room evaluations in the three month perioperative period. This anesthetic and rehabilitation protocol allowed outpatient total hip arthroplasty to be routinely performed in these consectutive patients undergoing primary total hip arthroplasty. With current reimbursement approaches the modest savings to the hospital in length of stay may be outweighed by the additional costs of personnel, thereby making this outpatient system more expensive to implement.

Human polymerized hemoglobin for the treatment of hemorrhagic shock when blood is unavailable: the USA multicenter trial.

Abstract: Background Human polymerized hemoglobin (PolyHeme, Northfield Laboratories) is a universally compatible oxygen carrier developed to treat life-threatening anemia. This multicenter phase III trial was the first US study to assess survival of patients resuscitated with a hemoglobin-based oxygen carrier starting at the scene of injury. Study Design Injured patients with a systolic blood pressure≤90 mmHg were randomized to receive field resuscitation with PolyHeme or crystalloid. Study patients continued to receive up to 6 U of PolyHeme during the first 12 hours postinjury before receiving blood. Control patients received blood on arrival in the trauma center. This trial was conducted as a dual superiority/noninferiority primary end point. Results Seven hundred fourteen patients were enrolled at 29 urban Level I trauma centers (79% men; mean age 37.1 years). Injury mechanism was blunt trauma in 48%, and median transport time was 26 minutes. There was no significant difference between day 30 mortality in the as-randomized (13.4% PolyHeme versus 9.6% control) or per-protocol (11.1% PolyHeme versus 9.3% control) cohorts. Allogeneic blood use was lower in the PolyHeme group (68% versus 50% in the first 12 hours). The incidence of multiple organ failure was similar (7.4% PolyHeme versus 5.5% control). Adverse events (93% versus 88%; p=0.04) and serious adverse events (40% versus 35%; p=0.12), as anticipated, were frequent in the PolyHeme and control groups, respectively. Although myocardial infarction was reported by the investigators more frequently in the PolyHeme group (3% PolyHeme versus 1% control), a blinded committee of experts reviewed records of all enrolled patients and found no discernable difference between groups. Conclusions Patients resuscitated with PolyHeme, without stored blood for up to 6 U in 12 hours postinjury, had outcomes comparable with those for the standard of care. Although there were more adverse events in the PolyHeme group, the benefit-to-risk ratio of PolyHeme is favorable when blood is needed but not available.