APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD).

PURPOSE: Inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia is an adult-onset autosomal dominant illness (IBMPFD) caused by mutations in the valosin-containing protein (VCP) on chromosome 9p21.1-p12. The penetrance of the gene is 82% for myopathy, 49% for Paget's disease, but may be as low as 30% for frontotemporal dementia. Modifier genes could account for decreased frontotemporal dementia penetrance. In this study apolipoprotein-E (APOE) was evaluated for this role in IBMPFD families based on its known modifier effect in Alzheimer's disease. METHODS: From a database of 231 members of 15 families, 174 had APOE genotype available for analysis. Logistic regressions on APOE genotype and frontotemporal dementia were performed, using appropriate covariates. RESULTS AND CONCLUSION: FTD was associated with APOE 4 genotype (P=0.0002), myopathy (P=0.0006), and age (P=0.01), but not microtubule associated protein tau (MAPT) H2 haplotype (P=0.5) or gender (0.09) after adjustment for membership in pedigrees with at least one APOE 4 genotype. These data suggest a potential link between APOE 4 genotype and the specific form of frontotemporal dementia found in IBMPFD. The molecular basis of this link bears further investigation. We did not observe an association of frontotemporal dementia and H2 MAPT haplotype.     

Reliability and validity of first metatarsophalangeal joint orientation measured with an electromagnetic tracking device

OBJECTIVE: To establish the reliability and validity of measurements of sagittal plane orientation of the first metatarsophalangeal joint using the Flock of Birds electromagnetic tracking device. DESIGN: Different joint orientations were reproduced on cadaver specimens in a specially designed jig with skin and skeletal application of the sensors. BACKGROUND: The Flock of Birds provides a means for quantifying first metatarsophalangeal joint motion, however, the reliability and validity of such an application has not been determined. METHODS: Joint orientation was measured in five cadaver feet with skin and skeletal sensor application. A specially designed jig allowed simulation of clinical tests of range of motion. Sagittal plane orientation was determined from 3-D, anatomically-based, reference frames embedded in the first metatarsal and proximal hallux. RESULTS: Reliability of all measurements was high for skin and skeletal sensor application. There were no significant differences in joint orientation between either technique for any of the simulated motion tests. CONCLUSIONS: The Flock of Birds provides reliable and valid measures of first metatarsophalangeal joint orientation with the sensors applied to the skin over the first metatarsal and proximal hallux. RELEVANCE: An electromagnetic tracking device is suitable for measuring sagittal plane motion of the first metatarsophalangeal joint. This motion can easily be expressed using 3-D, anatomically-based reference frames.     

Hip strength and hip and knee kinematics during stair descent in females with and without patellofemoral pain syndrome

STUDY DESIGN: Cross-sectional. OBJECTIVE: To determine if females presenting with patellofemoral pain syndrome (PFPS) from no discernable cause other than overuse demonstrate hip weakness and increased hip internal rotation, hip adduction, and knee valgus during stair descent. BACKGROUND: Historically, PFPS has been viewed exclusively as a knee problem. Recent findings have indicated an association between hip weakness and PFPS. Researchers have hypothesized that patients who demonstrate hip weakness would exhibit increased hip internal rotation, hip adduction, and knee valgus during functional activities. To date, researchers have not simultaneously examined hip and knee strength and kinematics in subjects with PFPS to make this determination. METHODS AND MEASURES: Eighteen females diagnosed with PFPS and 18 matched controls participated. Strength measures were taken for the hip external rotators and hip abductors. Hip and knee kinematics were collected as subjects completed a standardized stair-stepping task. Independent t tests were used to determine between-group differences in strength and kinematics during stair descent. RESULTS: Subjects with PFPS generated 24% less hip external rotator (P = .002) and 26% less hip abductor (P =. 006) torque. No between-group differences (P > .05) were found for average hip and knee transverse and frontal plane angles during stair descent. CONCLUSION: Subjects with PFPS had significant hip weakness but did not demonstrate altered hip and knee kinematics as previously theorized. Additional investigations are needed to better understand the association between hip weakness and PFPS etiology.     

Memories that last in old age: motor skill learning and memory preservation

Using an automated test panel, age-associated declines in learning, remembering and performing a novel visuomotor task were assessed in 497 normal adults ranging from 18 to 95 years old. As predicted, task performance times slowed with increasing age in the cross-sectional portion of the study. However in the subsequent longitudinal study, while motor learning was significantly slower in adults over 62 years old, motor memory was pristinely preserved in normal adults from 18 to 95 years old. When tested 2 years after the first training session and without intervening rehearsal, mean performance times were retained and continued to improve by 10% in young adults and 13% in aged adults, reflecting long lasting preservation of motor memories. While the maximum lifetime of an unpracticed, novel motor memory in humans is not known, the present study suggests that new motor memories can be retained for at least 2 years without rehearsal in normal aged adults. This age-resistant component of motor memory stands in contrast to the well-known decrements in other motor and cognitive processes with human aging.     

"Oh, the places you'll go": transformation of the nation's biomedical research enterprise in the 21st century

The postgenomic era and heightened public expectations for tangible improvements in the public health have stimulated a complete transformation of the nation's biomedical research enterprise. The National Institutes of Health (NIH) "Roadmap for Medical Research" has catalyzed this transformation. The NIH roadmap consists of several interrelated initiatives, of which the Clinical and Translational Science Award (CTSA) program is the most relevant for rehabilitation specialists. This article reviews the evolution of this transformation and highlights the unprecedented opportunities the CTSA program provides rehabilitation specialists to play leadership roles in improving the clinical care of their patients.     

Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study

We hypothesize that hydrocortisone infusion in severe community-acquired pneumonia attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications. In a multicenter trial, patients admitted to the Intensive Care Unit (ICU) with severe community-acquired pneumonia received protocol-guided antibiotic treatment and were randomly assigned to hydrocortisone infusion or placebo. Hydrocortisone was given as an intravenous 200-mg bolus followed by infusion at a rate of 10 mg/hour for 7 days. Primary end-points of the study were improvement in Pa(O(2)):FI(O(2)) (Pa(O(2)):FI(O(2)) > 300 or >/= 100 increase from study entry) and multiple organ dysfunction syndrome (MODS) score by Study Day 8 and reduction in delayed septic shock. Forty-six patients entered the study. At study entry, the hydrocortisone group had lower Pa(O(2)):FI(O(2)), and higher chest radiograph score and C-reactive protein level. By Study Day 8, treated patients had, compared with control subjects, a significant improvement in Pa(O(2)):FI(O(2)) (p = 0.002) and chest radiograph score (p < 0.0001), and a significant reduction in C-reactive protein levels (p = 0.01), MODS score (p = 0.003), and delayed septic shock (p = 0.001). Hydrocortisone treatment was associated with a significant reduction in length of hospital stay (p = 0.03) and mortality (p = 0.009).     

Validation studies of the human movement analysis panel for hand/arm performance

The human movement analysis panel (HMAP) measures separable components of arm motion and simple and complex finger coordination. HMAP testing takes 30min to administer. In separate experiments we have validated the HMAP against the standard grooved pegboard and measures of gait speed, and demonstrated important learning effects over both short durations of days, and longer intervals of months to years in normal subjects of different ages. Stepwise regression demonstrated the strongest correlation between the HMAP complex motor times and pegboard both-hand removal (R(2)=0.52, p=0.002 for dominant and R(2)=0.33, p=0.02 for non-dominant hands). The most consistent and sensitive measure of HMAP motor performance overall was the complex motor time. The HMAP is a short-duration, easily administered, objective quantitative test of motor function, with potential applications in aging, and in Parkinson's Disease and related motor disorders. The HMAP has a smaller version used in primates, so that measurements made in primate models of disease and its treatment are directly comparable to analogous clinical measurements made in the corresponding human disease.