A Method to Estimate Brain Volume from Head CT Images and Application to Detect Brain Atrophy in Alzheimer Disease.

BACKGROUND AND PURPOSE: Total brain volume and total intracranial volume are important measures for assessing whole-brain atrophy in Alzheimer disease, dementia, and other neurodegenerative diseases. Unlike MR imaging, which has a number of well-validated fully-automated methods, only a handful of methods segment CT images. Available methods either use enhanced CT, do not estimate both volumes, or require formal validation. Reliable computation of total brain volume and total intracranial volume from CT is needed because head CTs are more widely used than head MRIs in the clinical setting. We present an automated head CT segmentation method (CTseg) to estimate total brain volume and total intracranial volume. MATERIALS AND METHODS: CTseg adapts a widely used brain MR imaging segmentation method from the Statistical Parametric Mapping toolbox using a CT-based template for initial registration. CTseg was tested and validated using head CT images from a clinical archive. RESULTS: CTseg showed excellent agreement with 20 manually segmented head CTs. The intraclass correlation was 0.97 (P < .001) for total intracranial volume and 0.94 (P < .001) for total brain volume. When CTseg was applied to a cross-sectional Alzheimer disease dataset (58 with Alzheimer disease patients and 58 matched controls), CTseg detected a loss in percentage total brain volume (as a percentage of total intracranial volume) with age (P < .001) as well as a group difference between patients with Alzheimer disease and controls (P < .01). We observed similar results when total brain volume was modeled with total intracranial volume as a confounding variable. CONCLUSIONS: In current clinical practice, brain atrophy is assessed by inaccurate and subjective "eyeballing" of CT images. Manual segmentation of head CT images is prohibitively arduous and time-consuming. CTseg can potentially help clinicians to automatically measure total brain volume and detect and track atrophy in neurodegenerative diseases. In addition, CTseg can be applied to large clinical archives for a variety of research studies.

A new laboratory device with mathematically based positioning of a frozen tissue block facilitating precise sectioning of large specimens.

Mohs micrographic surgery (MMS) is a treatment method aiming at thorough, personalized eradication of skin cancers by mean of staged excision of tissues surrounding the tumor with complete (100%) histopathological examination of their margins. In many MMS laboratories, the excised tissue is divided, shaped, frozen in a cryostat with a heat extractor and positioned manually (with the block on the object disc) in an articulated cryostat chuck during cutting. However, these activities may be difficult, time-consuming and associated with the risk of imprecise tissue sectioning. Development of a laboratory device allowing for processing of large tissue specimens, with the function of mechanical, mathematically steered positioning of the tissue block surface directly to the microtome knife cutting place, eliminating the need for manual adjustment. The prototype device was designed and manufactured. Its functioning was tested on 513 histological slides produced during 212 operations of skin cancers using MMS. The depth of the first complete sections and the diameter of sections were measured. Complete sections were obtained at an average depth of 81.60 m (min. 20 m, max. 180 m, SD = 29.15), whereas the average diameter of sections was 18.11 mm (min. 4 mm, max. 42 mm, SD = 9.10). The histological processing of large specimens with mathematically based positioning of the tissue surface in relation to the cryotome knife cutting plane is precise, fast and easy. The device can be useful in those MMS centers which continue to employ manual setting of the cryostat chuck or share the cryostat with other users, which prevents fixing the chuck position (including large hospital settings). It may also be helpful in centers using a cryostat with a fixed chuck, for the correction of minimal inaccuracies of its preset position.

Coatings of nanostructured pristine graphene-IrOx hybrids for neural electrodes: Layered stacking and the role of non-oxygenated graphene.

The need to enhance charge capacity in neural stimulation-electrodes is promoting the formation of new materials and coatings. Among all the possible types of graphene, pristine graphene prepared by graphite electrochemical exfoliation, is used in this work to form a new nanostructured IrOx-graphene hybrid (IrOx-eG). Graphene is stabilized in suspension by IrOx nanoparticles without surfactants. Anodic electrodeposition results in coatings with much smaller roughness than IrOx-graphene oxide. Exfoliated pristine graphene (eG), does not electrodeposit in absence of iridium, but IrOx-nanoparticle adhesion on graphene flakes drives the process. IrOx-eG has a significantly different electronic state than graphene oxide, and different coordination for carbon. Electron diffraction shows the reflection features expected for graphene. IrOx 1-2 nm cluster/nanoparticles are oxohydroxo-species and adhere to 10nm graphene platelets. eG induces charge storage capacity values five times larger than in pure IrOx, and if calculated per carbon atom, this enhancement is one order magnitude larger than the induced by graphene oxide. IrOx-eG coatings show optimal in vitro neural cell viability and function as cell culture substrates. The fully straightforward electrochemical exfoliation and electrodeposition constitutes a step towards the application of graphene in biomedical systems, expanding the knowledge of pristine graphene vs. graphene oxide, in bioelectrodes.

Disease course and viral shedding in experimental Norwalk virus and Snow Mountain virus infection.

Norovirus is the most common cause of acute infectious gastroenteritis, causing approximately 21 million cases annually in the USA. The virus is highly contagious and resistant to decontamination, making outbreaks difficult to control. To facilitate the development of better control methods, this study characterized the viral shedding patterns in stools from subjects experimentally infected with genogroup I or II norovirus. Viral stool titers were determined by quantitative real-time RT-PCR for all stools produced in the first 7 days post-challenge and representative stools through day 35 post-challenge. The shedding titers and disease course were analyzed with respect to virus type, illness, and subject demographics. Infection with GII.2 Snow Mountain (SMV) resulted in more symptoms and a higher frequency of painful symptoms compared to GI.1 Norwalk (NV) infection. However, NV infection produced stool viral titers approximately 2 logs higher than those seen in SMV infections. Both NV and SMV were shed in stools for up to 3 weeks after the resolution of symptoms, but long shedding durations were more common in NV infections. For each challenge virus, shedding titers and patterns were not correlated with subject demographics or clinical course. This is the first study to report shedding dynamics in experimental GII norovirus infection.

Nanocomposites of iridium oxide and conducting polymers as electroactive phases in biological media.

Much effort is currently devoted to implementing new materials in electrodes that will be used in the central nervous system, either for functional electrostimulation or for tests on nerve regeneration. Their main aim is to improve the charge capacity of the electrodes, while preventing damaging secondary reactions, such as peroxide formation, occurring while applying the electric field. Thus, hybrids may represent a new generation of materials. Two novel hybrid materials are synthesized using three known biocompatible materials tested in the neural system: polypyrrole (PPy), poly(3,4-ethylenedioxythiophene) (PEDOT) and iridium oxide (IrO2). In particular, PPy-IrO2 and PEDOT-IrO2 hybrid nanocomposite materials are prepared by chemical polymerization in hydrothermal conditions, using IrO2 as oxidizing agent. The reaction yields a significant ordered new hybrid where the conducting polymer is formed around the IrO2 nanoparticles, encapsulating them. Scanning electron microscopy and backscattering techniques show the extent of the encapsulation. Both X-ray photoelectron and Fourier transform infrared spectroscopies identify the components of the phases, as well as the absence of impurities. Electrochemical properties of the final phases in powder and pellet form are evaluated by cyclic voltammetry. Biocompatibility is tested with MTT toxicity tests using primary cultures of cortical neurons grown in vitro for 6 and 9days.

Validation of the exercise addiction inventory in a Danish sport context.

Exercise addiction is characterized by excessive exercise behavior with potential negative consequences. The symptoms consist of salience, mood modification, tolerance, withdrawal symptoms, conflicts, and relapse. The purpose of this study was to test the psychometric properties of the exercise addiction inventory (EAI) and to estimate the prevalence of exercise addiction in a Danish normal weight sport population. A sample of 780 habitual fitness and football exercisers were contacted and 590 completed the EAI and an in-house questionnaire containing questions about variables related to exercise addiction: (a) exercise frequency; (b) continuance despite injuries; and (c) personal perception of addiction. The results demonstrated an overall prevalence of exercise addiction of 5.8%. There was no significant difference between fitness and football prevalences. The internal reliability of EAI was acceptable with a Cronbach's α of 0.66. The criterion validity was tested toward the three variables related to exercise addiction. The dependent group had significantly higher scores on the three variables than the non-dependent group. Exercise addiction seems to exist in both fitness and football. The EAI is a useful screening tool and might be applicable in future screening and prevention of exercise addiction. However, further investigation about the population is needed to understand the phenomenon and to identify the risk group.

Therapeutic potency of IL2-caspase 3 targeted treatment in a murine experimental model of inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) comprises primarily the two disorders - ulcerative colitis and Crohn's disease - that involve deregulated T cell responses. The ever-increasing incidence rate of Crohn's disease and ulcerative colitis during recent decades, combined with the limited efficacy and potential adverse effects of current treatments, explain the real need for seeking more specific and selective methods for treating these diseases. AIM: To investigate the ability of interleukin 2 (IL2)-caspase 3 chimeric protein, designed to target activated T lymphocytes that express the high-affinity IL2 receptor, to ameliorate the clinical symptoms of acute murine experimental colitis, using a mouse model of dextran sodium sulfate (DSS)-induced colitis. METHODS: Mice with DSS-induced colitis were treated with IL2-caspase 3 for 7 days and disease severity was assessed in parallel to control, non-treated mice, receiving only daily injections of phosphate-buffered saline. IL2-caspase 3 was tested both for its ability to prevent the development of colitis, and for its therapeutic potential to cure on-going, active acute disease. In addition, colon tissue samples were used for myeloperoxidase assays and RNA isolation followed by polymerase chain reaction to determine mRNA expression levels of specific genes. RESULTS: Treatment with IL2-caspase 3 dose-dependently ameliorated the disease activity index (DAI) of mice colitis. We achieved up to 78% improvement in DAI with intravenous injections of 15 microg/mouse/day. Furthermore, IL2-caspase 3 decreased neutrophil and macrophage infiltration to the inflamed tissue by up to 57%. IL2-caspase 3 was proven as a therapeutic reagent in another model, where treatment begins only after disease onset. Here we demonstrated a 70% decrease in DAI when compared to non-treated sick mice. A reduction in mRNA expression levels of both IL1 beta and tumour necrosis factor alpha was found in lysates of total colon tissue of treated mice, as compared to sick, untreated mice. We also found that expression levels of Bcl2 were significantly decreased after treatment, while Bax was upregulated in comparison to non-treated mice. Moreover, the Bcl2/Bax ratio, which is elevated in both experimental colitis and in human Crohn's disease, decreased dramatically after treatment. CONCLUSIONS: IL2-caspase 3 chimeric protein may provide a novel approach to the therapy of human IBD, and a possible suggested treatment for other pathological conditions that involve uncontrolled expansion of activated T cells.

Distal infantile neuroaxonal dystrophy--a new familial variant with perineuronal argyrophilic bodies.

We report on two sisters with an infantile onset of dyskinetic movements, tonic spasms, seizures and apneic spells. The condition deteriorated to a hypotonic "burnt out" stage by the age of 3 years in the older sister and to a stable dyskinetic condition by the age of 2.5 years in the younger one. A skin biopsy from the older sister revealed myelinated nerve fibers crowded with neurofilaments. The extensive investigation for neurometabolic disorder, magnetic resonance imaging of the brain, and ophthalmological and neurophysiological examinations were not especially revealing. The older sister died at the age of 3 years. The autopsy revealed no apparent loss of nerve cells in the brain and no sign of storage disease. However, silver-stained coarse granules, immunopositive for neurofilament polypeptide, were found around nerve cell bodies in the cortex and in the basal ganglia. Electron microscopy revealed perineuronal membrane-bound profiles filled with filaments. Silver-stained axonal torpedoes were found in the cerebellum, but there were no spheroids. The substantia nigra, the locus ceruleus and the nucleus basalis of Meynert showed extensive perineuronal and perivascular swelling. Homovanillic acid was severely reduced, while 5-hydroxyindoleacetic acid and hydroxymethylphenyl glycol were normal in the cerebrospinal fluid of the severely affected, autopsied case. The two cases are considered to represent a new form of infantile neuroaxonal dystrophy, characterized by the degeneration of perineuronal terminals in the cerebral cortex and in the basal ganglia, as well as by axonal degeneration in the cerebellum and peripheral nerves.

Evolution of anti-HIV drug candidates. Part 3: Diarylpyrimidine (DAPY) analogues.

The synthesis and anti-HIV-1 activity of a series of diarylpyrimidines (DAPYs) are described. Several members of this novel class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) are extremely potent against both wild-type and a panel of clinically significant single- and double-mutant strains of HIV-1.

Combined magnetic resonance imaging and single-photon emission tomography scanning in the discrimination of Alzheimer's disease from age-matched controls.

OBJECTIVE: To compare the utility of temporal lobe magnetic resonance imaging (MRI) and single-photon emission tomography (SPET) scanning in discriminating between subjects with Alzheimer's disease (AD) and age-matched controls. METHODS: Thirty subjects with NINCDS-ADRDA AD (23 probable AD, 5 possible AD, 2 definite AD) and 22 age- and sex-matched controls underwent T1-weighted coronal MRI scanning (0.3 T) and technetium 99m-HMPAO SPET scanning. MRI scans were analyzed using a digitizer system with volumes of hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, and whole cerebral cortex calculated. From SPET scans, regional cerebral blood flow (rCBF) was assessed in anterior and posterior frontal, parietal, occipital, and mesial temporal cortex using a region of interest analysis with the cerebellum as a reference area. RESULTS: Using MRI, the areas that best separated groups were left hippocampal and left amygdala volume, resulting in correct classification (patient vs. control) in 79% of cases (sensitivity 77%, specificity 82%). Exactly the same proportion of subjects were correctly classified by SPET, with the most discriminating rCBF changes being left parietal and right posterior frontal. Combining information from both scans improved the proportion of correctly classified subjects in a discriminant function to 90% (sensitivity 93%, specificity 86%; only 2 AD and 3 controls misclassified). All AD subjects had abnormalities on MRI and/or SPET (sensitivity for combined examinations 100%), while abnormalities on both MRI and SPET had a positive predictive value of 100% for dementia (including the detection of one control subject who later had dementia). Significant correlations between MRI and SPET measures were seen in control subjects but not in patients. CONCLUSION: Both 0.3 T MRI and single rotating gamma camera SPET were equally useful in separating AD subjects from age-matched controls, although the combination of both significantly enhanced discrimination. In particular, all AD subjects had abnormalities on either MRI or SPET and both techniques may have an important role in assisting with clinical diagnosis, though replication in other centers and examination of differentiation of AD from other causes of dementia need to be examined.

Prevalence [correction of prevalance] of functional blindness, visual impairment, and related functional deficits among elderly Mexican Americans.

BACKGROUND: This report describes the prevalence and correlates of functional blindness and visual impairment among older Mexican Americans, using data on 2800 respondents from the Hispanic Established Populations for the Epidemiological Study of the Elderly. METHODS: Bivariate and multivariate logistic regression analyses were used to examine the associations between corrected bilateral distant vision and sociodemographic characteristics, selected health conditions, self-reported health status, health care utilization, and functional dependence on the basis of assistance needed for basic and instrumental activities of daily living (ADLs). RESULTS: Using a modified Snellen test for distance visual acuity, 5% of older Mexican Americans were found to be functionally blind, and 13.5% were found to be visually impaired. Vision loss was significantly associated with older age, lower education, hypertension, diabetes, poor self-rated health, and hospitalization during the year prior to the interview. Over 50% of functionally blind subjects required assistance with at least one basic ADL, compared with 15% of those who were visually impaired and 8% of those who were not visually impaired. CONCLUSIONS: The prevalence of functional blindness in this sample of elderly Mexican Americans was higher than reported for the general elderly population, yet they also have higher rates of adequate vision because of the low prevalence of visual impairment. The results suggest a need for more research on the prevalence and impact of functional blindness and visual impairment on the health of older Mexican Americans.

The Positively Aging teaching materials improve middle school students' images of older people.

PURPOSE: The Positively Aging program is an innovative set of interdisciplinary teaching materials that uses examples from geriatrics and gerontology to teach sixth through eighth grade curricular elements. The purpose of this study was to determine if use of the Positively Aging teaching materials by regular classroom teachers could change middle school students' images of elders. DESIGN AND METHODS: At the beginning of the 1998-1999 school year, students at two San Antonio, Texas, middle schools were asked to draw a typical older person. These drawings were coded as positive, neutral, or negative portrayals of elders. One school then used the Positively Aging materials as part of the curriculum; the other school served as the control. Second drawings were obtained from the students at the end of the school year and compared to those from baseline. RESULTS: Both drawings were completed by 60% of students at the intervention school and 55% of students at the control school. Of the 782 paired drawings from the intervention school, 34% were more positive at Time 2 compared to 25% of 591 paired drawings from the control school (chi2 = 13.9, p < .001). In addition, only 20% of the second drawings from the intervention school were more negative than the first drawing compared to 27% from the control school (chi2 = 11.3, p < .001). Using a generalized logit model, we adjusted for each student's baseline drawing (positive-neutral-negative), grade level, gender, ethnic group, and socioeconomic status. After adjustment, students in the intervention school were more likely to draw positive (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.13, 1.94) or positive and neutral images (OR 1.58, 95% CI 1.21, 2.19) at follow-up compared to the control school. IMPLICATIONS: This controlled study demonstrated that use of the Positively Aging teaching materials and activities moved middle school students toward a more positive view of elders. Interdisciplinary teaching materials based on geriatrics and gerontology can be successfully developed and tested in public school systems to affect attitudes about aging.

Walking velocity in aged persons: its association with lower extremity joint range of motion.

OBJECTIVE: To measure the association between walking velocity and hip and knee flexion range, ethnic background, anthropometrics, comorbid pathologies, and coimpairments, in a sample of community-dwelling aged persons. METHODS: To reach our objective, we used data from the San Antonio Longitudinal Study of Aging (SALSA), a population-based cohort of Mexican American and European American persons aged 64 to 79. By fitting hierarchical regression models, we measured the variance in the walking velocity over 50 feet explained by hip and knee flexion range, adjusting for the combined influence of demographic and anthropometric variables, coexistent pathologic conditions, impairments, and the examiners who conducted the assessments. RESULTS: The average walking velocity among the 702 subjects for whom data were available was 73.6 meters per minute (range 20 to 121). Bivariate analyses revealed significant associations between walking velocity and age, sex, ethnic background, height, weight, presence of arthritis, diabetes mellitus, stroke, upper leg pain, peripheral vascular disease, left ventricular hypertrophy, and forced expiratory volume at 1 second. The correlation (r) between walking velocity and flexion range of the hip and knee were 0.40 and 0.35, respectively (P < or = 0.001 for each). Multivariate hierarchical models adjusting for demographic and anthropometric characteristics of the subjects, and examiner variation, revealed that hip and knee flexion range explained 6% of the variance in walking velocity. Adjusting for the presence of comorbid conditions and coimpairments reduced the variance attributable to hip and knee flexion range only slightly, to 5%. CONCLUSION: Hip and knee flexion range contribute significantly to walking velocity in the SALSA cohort of community-dwelling aged persons.

Ethnic differences in mini-mental state examination (MMSE) scores: where you live makes a difference.

OBJECTIVES: To examine differences in correlates of the Mini-Mental State Examination (MMSE) in a population-based sample of older Mexican Americans and European Americans and to provide empirical validation of the MMSE as an indicator of cognitive impairment in survey research in older Mexican Americans by comparing MMSE classification against performance on timed tasks with varying levels of cognitive demand. DESIGN: A population-based cross-sectional study. SETTING: Trained bilingual staff administered the MMSE as part of the San Antonio Longitudinal Study of Aging (SALSA) home-based assessment battery. PARTICIPANTS: 827 community-dwelling Mexican Americans and European Americans, 65 and older, residing in three socioeconomically and culturally distinct neighborhoods (barrio, transitional, suburban). MEASUREMENTS: The MMSE was compared against a variety of demographic, biomedical, and sociocultural variables ascertained by self-report and against performance-based measures of functional tasks representing varying levels of cognitive demand (Structured Assessment of Independent Living Skills (SAILS) subscales for food manipulation and money management). RESULTS: Mexican Americans were 2.2 times more likely than European Americans to have MMSE scores <24. Multiple logistic regression analysis revealed that neighborhood was an independent predictor of low MMSE scores in Mexican Americans, with the relationship between ethnic group and MMSE explained by neighborhood. After adjusting for neighborhood type, no differences were noted between Mexican Americans and European Americans. Independent of other factors examined, low education was associated with low MMSE scores in both Mexican Americans and European Americans. Mexican Americans with MMSE scores <24 took significantly longer to complete four out of five performance-based food manipulation tasks and all three money management tasks. CONCLUSIONS: Neighborhood type was a predictor of cognitive impairment. Education affected MMSE scores similarly in both ethnic groups. MMSE scores <24, indicative of cognitive impairment, were uniformly associated with functional impairment in both the Mexican Americans and European Americans. Among older Mexican Americans, MMSE-classified cognitive impairment was significantly associated with poorer performance on timed tasks with varying levels of cognitive demand independent of other correlates. A similar pattern of association was observed in European Americans. Thus, the MMSE appears to be a valid indicator of cognitive impairment in survey research in both older Mexican Americans and European Americans.

Control of nuclear export of hnRNP A1.

mRNA export is mediated by RNA-binding proteins which shuttle between the nucleus and cytoplasm. Using an in vitro unidirectional export assay, we observe that the shuttling mRNA-binding protein, hnRNP A1, is exported only extremely slowly unless incubations are supplemented with snRNA-specific oligonucleotides which inhibit splicing. In vivo microinjection experiments support this conclusion. Like many examples of nucleocytoplasmic transport, export of hnRNP A1 requires energy and is sensitive to the presence of wheat germ agglutinin. It does not, however, require supplementation with cytoplasmic proteins. Although the exportin, Crm1, is needed for export of several varieties of RNA, both the in vitro assay and in vivo assays show that it is not required for export of hnRNP A1. In vitro and in vivo studies also show that inhibition of transcription allows continued shuttling of hnRNP A1 and in fact accelerates its export. Judging from the stimulatory effects of targeted destruction of snRNAs, this is likely to reflect completion of the covalent maturation of the RNAs with which hnRNP A1 associates. These observations therefore provide a simple explanation of why multiple RNA-binding proteins relocate to the cytoplasm upon inhibition of transcription in vivo.

Lower body function and mortality in Mexican American elderly people.

BACKGROUND: The purpose of this analysis was to examine the differential impact of performance-based and self-reported lower body measures on 2-year mortality in Mexican American elderly persons. METHODS: Data employed are from the Hispanic Established Population for Epidemiological Studies of the Elderly, a probability survey of 3050 community-dwelling Mexican Americans aged 65 and older from the five Southwestern states interviewed in 1993 and 1994. Of the baseline sample with complete data, 198 persons were confirmed deceased 2 years later. A three-task, performance-based, lower body function measure consisting of a short walk, balance, and repeated chair stands tests was used. Self-reported lower body function was measured by a 4-item Activities of Daily Living (ADL) measure involving the lower body. RESULTS: The three-task, lower body function measure was a significant predictor of 2-year mortality. The short walk alone was as predictive as the summary measure. The predictive ability of both measures was minimally reduced by the inclusion of the self-reported ADL measure and life-threatening medical conditions. Finally, the ADL measure was not a significant predictor of mortality with all the other variables in the analysis. CONCLUSION: Objective measures of lower body function were significant predicators of mortality in Mexican American elderly persons, as found in the general population. Unlike previous studies, the ADL measure was not an independent predictor of mortality after controlling for the objective measure and other risk factors. Additional research is needed to address why objective measures of function are such strong predictors of death.

Comparison of MRI perfusion imaging and single photon emission computed tomography in chronic stroke.

There have been few direct comparisons between MR perfusion-weighted imaging (PWI) and established perfusion imaging techniques, and none in chronic stroke. We therefore studied 17 chronic hemispheric infarction patients (mean, 90 days) and compared hypoperfusion volumes determined from PWI maps of relative cerebral blood flow (rCBF) and volume (rCBV), and mean transit time (rMTT) with those measured with (99)Tc-HMPAO single photon emission computed tomography (SPECT). Comparisons were also made between infarct size (T(2)-WI) and clinical scales. Correlations were found between lesion location and volume in all three PWI hemodynamic parameter maps with clinical state and lesions on SPECT and T(2)-WI. In 3 patients, rCBF and rCBV lesions extended well beyond the borders of moderate-sized infarctions. We conclude that in chronic stroke, PWI can delineate regions of abnormal perfusion that reflect the degree of functional impairment and structural damage. The finding of peri-infarct hypoperfusion suggests that PWI may have the potential to provide a rapid and non-invasive template against which interventional strategies aimed at promoting functional recovery may be investigated.

New-onset incontinence and markers of frailty: data from the Hispanic Established Populations for Epidemiologic Studies of the Elderly.

BACKGROUND: Urinary incontinence in older adults has many distinct etiologies and is associated with lower self-reported health. However, it is unclear whether the new onset of urinary incontinence marks newly emergent frailty. METHODS: Using a longitudinal population-based survey of older Mexican Americans (N = 2660) across five south-western states, this study compared the strength of association between markers of physical frailty such as activities of daily living (ADLs), instrumental activities of daily living (IADLs), and performance (timed walk, timed chair rise, and tandem balance) with baseline incontinence (prevalent disease) and new-onset incontinence (incident disease). RESULTS: We found that 14.1% of the participants (n = 329) were incontinent at baseline (prevalent cases) and 11.6% (n = 208) were newly incontinent 2 years later (incident cases). Controlling for other covariates, prevalent incontinence was only associated with a 60% increased risk of having difficulty walking 8 ft. Incident incontinence was associated with a twofold increased risk of impairment in ADLs and IADLs, and poor performance on all three physical measures. CONCLUSIONS: Incident incontinence is associated with an increased risk of more global functional impairment. Thus, incident disease may be an important early marker for signaling the onset of frailty among persons who become incontinent after the age of 65 years.

Modeling impairment: using the disablement process as a framework to evaluate determinants of hip and knee flexion.

Elders often present to health care providers with multiple inter-related conditions that determine an individual's ability to function. The disablement process provides a generalized sociomedical framework for investigating the complex pathways from chronic disease to disability. At each stage of the main pathway, associations may exist among primary physical factors and modifying variables that ultimately have downstream effects on the progression toward disability. The purpose of the present analysis is to examine the inter-relationships between a cohesive set of variables primarily at the level of impairment that may affect hip and knee flexion range of motion (ROM). The San Antonio Longitudinal Study of Aging enrolled 833 community dwelling Mexican (MA) and European American (EA) elders aged 64-78 years between 1992 and 1996. Of these, 647 had complete data from both a home-based and performance-based battery of assessments for these analyses. Concerning impairments, hip ROM was measured using an inclinometer, and knee ROM using a goniometer. Pain location and intensity were assessed using the McGill Pain Questionnaire. Peripheral vascular disease was assessed using doppler brachial and ankle systolic blood pressures. Ankle and knee reflexes, and vibratory sensation were assessed by a standardized neurological examination. As to diseases, diabetes was assessed using a combination of blood glucose levels and self-report, and arthritis by self-report. Concerning modifying variables, height and weight were directly measured and used to calculate BMI. Activity level was assessed with the Minnesota Leisure Time Questionnaire. Analgesic use was assessed by direct observation of medications taken within the past two weeks. We used structural equation modeling to test associations between the variables that were specified a priori. These analyses demonstrate the central role of BMI as a determinant of hip and knee flexion ROM. For an increase in level of BMI, the coefficients [SEM] for changes in levels of hip and knee ROM were -0.38 [0.05] and -0.26 [0.05], respectively. A higher BMI resulted in lower hip and knee ROM. BMI was also directly associated with prevalent diabetes (0.10 [0.05]) and arthritis (0.17 [0.05]). However, after adjustment for BMI, diabetes and arthritis did not have direct independent associations with either hip or knee ROM. BMI was also indirectly associated with knee, but not hip, ROM through paths including lower-leg pain, pain intensity, and neurosensory impairments. Diabetes had an indirect association with hip, but not knee ROM, through a path including peripheral vascular disease. In conclusion, BMI is a primary direct determinant of hip and knee ROM. The paths by which diabetes and arthritis lead to physical disability may be mediated, in part, at the level of impairment by BMI's association with joint range of motion. Interventions designed to decrease the impact of diabetes and arthritis on disability should track changes in BMI and joint ROM to measure the paths that account for the intervention's success. The observed associations suggest that interventions targeted to decrease BMI itself may lead to improved function in part through improved joint ROM.

The involvement of physicians in VA home care: results from a national survey.

OBJECTIVES: To examine the role of physicians in the Veteran Affairs (VA) home-based primary care (HBPC) program and to identify variables that predict whether physicians make home visits and volume of home visits made. DESIGN: Descriptive and regression analyses of responses from a mail survey. PARTICIPANTS: Forty-five physicians affiliated with VA HBPC programs. MAIN SURVEY TOPICS: Self-reported work load, attitudes toward home care, reasons for home visits, administrative policies regarding physicians' role in patient care management, and time commitment to home care. RESULTS: A majority of physicians believed strongly in the importance of home care and made home visits for reasons consistent with their training. Physician attitude toward home care and preoccupation with office or hospital practice were related to whether or not physicians made home visits. Degree of preoccupation with office practice and amount of salary support from VA HBPC were significant predictors of the number of visits made (R2 = 0.44). CONCLUSIONS: These findings indicate that most physicians will make home visits if they believe that home care is valuable and if their time commitment is supported financially. Managed care plans that own and operate home care programs and have the capacity to transfer primary care management to physicians who derive financial support from the programs should find this information particularly relevant.