CSF Biomarkers in Longitudinal Alzheimer Disease Cohorts: Pre-Analytic Challenges.

Background: The sensitivity of amyloid to pre-analytic factors complicates cerebrospinal fluid (CSF) diagnostics for Alzheimer disease. We report reliability and validity evidence for automated immunoassays from frozen and fresh CSF samples in an ongoing, single-site research program.

Methods: CSF samples were obtained from 2 Wisconsin cohorts (1256 measurements; 727 participants).

Vitamin B6 and vitamin D deficiency co-occurrence in geriatric memory patients.

Introduction: Vitamin B6 and D levels are not assessed routinely in geriatric memory patients. This study examined vitamin levels to determine the potential effects on cognition.

Methods: A chart review was conducted of 203 consecutive patients over a 12-month period.

Trajectory of clinical symptoms in relation to amyloid chronicity.

Introduction: While it is generally appreciated that amyloid precedes symptomatic Alzheimer's disease (AD) by decades, a greater understanding of this timeline may increase prognostic accuracy, planning, and care of persons who are on the AD continuum.

Methods: We examined trajectories of Clinical Dementia Rating-Sum of Boxes (CDR-SB) relative to estimated years of amyloid positivity (A+) in  = 123 participants who were all A+ based on [C-11]Pittsburgh compound B positron emission tomography.

Results: The average amyloid chronicity at CDR-SB of 2.

The Impact of Risk and Resistance Factors on Quality of Life in Caregivers of Individuals with Dementia.

Objectives: The present study investigates the effect of caregiver and care recipient risk and resistance factors on caregiver quality of life (QOL). Risk factors are those characteristics that contribute to psychosocial maladjustment of the caregiver and reduce QOL, while resistance factors promote caregiver adjustment and improve QOL.

Methods: One-hundred and three caregiver/care recipient dyads were recruited from a memory assessment clinic in Midwestern United States.

Rapid correction of low vitamin D status in nursing home residents.

Unlabelled: This prospective study finds that ergocalciferol 50,000 IU three times weekly for four weeks effectively and safely corrects vitamin D inadequacy in nursing home residents.

Introduction: Low vitamin D status is common among nursing home residents and contributes to bone loss, falls and fractures. The objective of this study was to evaluate the efficacy and safety of short course, high dose, oral vitamin D(2) (ergocalciferol) treatment.

A randomized, single-blind, increasing dose safety trial of an oxygen-carrying plasma expander (Hemospan) administered to orthopaedic surgery patients with spinal anaesthesia.

The objective of this study was to further explore the safety of Hemospan (Sangart Inc., San Diego, CA, USA), an oxygen-carrying plasma expander. The aim of this study was to determine if Hemospan is well tolerated in orthopaedic surgery patients with spinal anaesthesia in doses up to 1 L.

Kenosha County falls prevention study: a randomized, controlled trial of an intermediate-intensity, community-based multifactorial falls intervention.

Objectives: To decrease the rate of falls in high-risk community-dwelling older adults.

Design: Randomized, controlled trial.

Setting: Community-based.

Is vitamin D important for preserving cognition? A positive correlation of serum 25-hydroxyvitamin D concentration with cognitive function.

This study investigates the association of vitamin D status with cognitive function and discusses potential mechanisms for such an effect. The relationship of vitamin B12 with cognition was also assessed. A retrospective review of older adults presenting to a university-affiliated clinic providing consultative assessments for memory problems was performed.

A multicenter clinical study of the safety and activity of maleimide-polyethylene glycol-modified Hemoglobin (Hemospan) in patients undergoing major orthopedic surgery.

Background: Hemospan (Sangart Inc., San Diego, CA), a polyethylene glycol-modified hemoglobin with unique oxygen transport properties, has successfully completed a phase I trial in healthy volunteers. Because adverse events are expected to increase with age, the authors conducted a phase II safety study of Hemospan in elderly patients undergoing elective hip arthroplasty during spinal anesthesia.

A phase I single blind clinical trial of a new oxygen transport agent (MP4), human hemoglobin modified with maleimide-activated polyethylene glycol.

Background And Objectives: MP4 (Hemospan), a hemoglobin-based oxygen carrier, has been designed to deliver oxygen to hypoxic tissues without causing vasoconstriction. A phase I clinical trial of MP4 was undertaken to evaluate whether MP4 elicits the clinical side effects associated with previous hemoglobin-based solutions.

Design And Methods: Twelve volunteers were studied.

Diaspirin-crosslinked hemoglobin reduces blood transfusion in noncardiac surgery: a multicenter, randomized, controlled, double-blinded trial.

Unlabelled: In this randomized, prospective, double-blinded clinical trial, we sought to investigate whether diaspirin-crosslinked hemoglobin (DCLHb) can reduce the perioperative use of allogeneic blood transfusion. One-hundred-eighty-one elective surgical patients were enrolled at 19 clinical sites from 1996 to 1998. Selection criteria included anticipated transfusion of 2-4 blood units, aortic repair, and major joint or abdomino-pelvic surgery.

Effect of diaspirin crosslinked hemoglobin (DCLHb HemAssist) during high blood loss surgery on selected indices of organ function.

Background: The safety of the hemoglobin based oxygen carrier diaspirin crosslinked hemoglobin (DCLHb) has been reported only in the low (50-200 mg/kg) dose range [Przybelski. R.J.

Falls in the geriatric patient.

Falls are common in the geriatric and older adult population, often causing significant morbidity or mortality. The geometry of the human body in motion requires a highly functional individual to remain balanced and upright under a variety of conditions and perturbations. Balance in this population is adversely affected by intrinsic and extrinsic factors.

A safety assessment of diaspirin cross-linked hemoglobin (DCLHb) in the treatment of hemorrhagic, hypovolemic shock.

Objective: To determine the safety and possible efficacy of diaspirin cross-linked hemoglobin (DCLHb) in the treatment of patients in Class II-IV hemorrhagic, hypovolemic shock.

Design: Multicenter, randomized, normal saline-controlled, dose-escalation study.

Setting: Eleven hospitals in the U.

Randomized trial of diaspirin cross-linked hemoglobin solution as an alternative to blood transfusion after cardiac surgery. The DCLHb Cardiac Surgery Trial Collaborative Group.

Background: Risks associated with transfusion of allogeneic blood have prompted development of methods to avoid or reduce blood transfusions. New oxygen-carrying compounds such as diaspirin cross-linked hemoglobin (DCLHb) could enable more patients to avoid allogeneic blood transfusion.

Methods: The efficacy, safety, hemodynamic effects, and plasma persistence of DCLHb were investigated in a randomized, active-control, single-blind, multicenter study in post-cardiac bypass surgery patients.

Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke.

Background And Purpose: Diaspirin cross-linked hemoglobin (DCLHb) is a purified, cell-free human hemoglobin solution. In animal stroke models its use led to a significant reduction in the extent of brain injury. The primary objective of this study was to evaluate the safety of DCLHb in patients with acute ischemic stroke.

Effect of diaspirin cross-linked hemoglobin on endothelin-1 and blood pressure in acute ischemic stroke in man.

Objective: For almost 50 years it has been known that hemolysed blood can increase blood pressure. Although preclinical studies suggest that this pressor response is due to an interaction of hemoglobin with endothelium-derived vasoactive substances, its mechanism in humans is unknown. We investigated the involvement of endothelin-1 in the blood pressure response to the oxygen carrier diaspirin cross-linked hemoglobin (DCLHb) in stroke patients.

The effects of diaspirin-crosslinked hemoglobin on the assessment of immunohematology profiles.

Background: Extensive studies have been conducted on the in vitro effects of diaspirin-crosslinked hemoglobin (DCLHb) in biochemical, hematologic, hemostatic, and blood banking (immunohematologic) methods. The absence of red cell antigens or plasma and/or serum antibodies allows DCLHb to be used as "universal-donor" material. This study evaluates the effects of DCLHb on the accurate assessment of the immunohematologic profile (ABO and Rh blood grouping, antibody screen, and crossmatching).

Initial evaluation of diaspirin cross-linked hemoglobin (DCLHb) as a vasopressor in critically ill patients.

Objective: To evaluate the hemodynamic effects and any toxicologic effects of diaspirin cross-linked hemoglobin (DCLHb) in critically ill patients.

Design: A prospective, observational study.

Setting: A seven-bed intensive care unit (ICU) in a University teaching hospital.

Phase I study of the safety and pharmacologic effects of diaspirin cross-linked hemoglobin solution.

Objective: To evaluate the safety, pharmacokinetics, and pharmacodynamics of diaspirin cross-linked hemoglobin solution (DCLHb) in normal, healthy volunteers.

Design: Randomized, double-blind, controlled, crossover study.

Setting: Phase I research facility of a contract research organization.

Pharmacologic profile of diaspirin cross-linked hemoglobin in hemodialysis patients.

Various hemoglobin compounds have been evaluated as potential oxygen-carrying, blood volume expanders, but toxicity has prevented clinical application. Diaspirin cross-linked hemoglobin (DCLHb) represents a modified hemoglobin compound that is derived from human red blood cells and maintained in a tetrameric configuration by cross-linkages between the two alpha chains of the hemoglobin molecule. In a randomized, placebo-controlled, single-blind, cross-over trial, DCLHb's safety and pharmacologic parameters were evaluated in 18 subjects receiving chronic hemodialytic therapy.

Diaspirin crosslinked hemoglobin (DCLHb) does not affect the anesthetic potency of isoflurane in rats.

Hemoglobin solutions are being developed as oxygen carrying fluids for multiple clinical indications. Despite an early report of accentuation of ether anesthesia, the effect of hemoglobin on anesthetic potency has not been assessed. We assessed the effect of alpha-alpha diaspirin crosslinked hemoglobin (DCLHb) on the anesthetic requirement of isoflurane necessary to keep rats unresponsive to noxious stimuli (1.

Focal cerebral ischemia in rats: effect of hemodilution with alpha-alpha cross-linked hemoglobin on CBF.

Hemodilution has had limited success as a treatment of cerebral ischemia. When using a nonoxygen binding fluid, the therapeutic efficacy of hemodilution-induced increases in CBF are offset by concomitant decreases in oxygen content. The effect of hemodilution, with diaspirin alpha-alpha cross-linked hemoglobin (DCLHb), on CBF during middle cerebral artery occlusion was assessed.

The effects of alpha-alpha cross-linked hemoglobin on the feeding and locomotor activity of rats.

The feeding and locomotor activities of rats were used as an assay for the potentially toxic effects of an oxygen-carrying blood substitute. Rats lived in individual cages where they could feed ad lib by pressing a lever once for each small food pellet, drink water, or run in a wheel; a 12-h light/dark cycle was continuously in effect. After being anesthetized and hemorrhaged one-third of their total blood volume, individual rats were resuscitated with one of the following fluids: their own shed blood (OB), bis(3,5-dibromosalicylfumarate) alpha-alpha cross-linked hemoglobin (HbXL), human serum albumin (HSA), or Ringer's lactate (RL).