classification criteria for scleroderma
Citations
All
Search in:AllTitleAbstractAuthor name
Publications
(56)
Patents
Grants
Pathways
Clinical trials
Publication
Journal: Neurology
January/28/2004
Abstract
OBJECTIVE
To assess whether changes in antemortem MRI brain volume measurements are valid predictors of subsequent Alzheimer disease (AD) pathology.
METHODS
Thirty-nine subjects, 15 nondemented and 24 with cognitive impairment, were followed until death. Regional postmortem measures of senile plaque (SP) and neurofibrillary tangle (NFT) severity were examined in relationship to cross-sectional and longitudinal volumetric measurements obtained from antemortem MRI.
RESULTS
Total brain volume change over time was related to the accumulation of cortical NFT. The rate of ventricular CSF volume increase was related to both cortical NFT and SP. The last hippocampal volume prior to death was related to hippocampal NFT burden; the rate of hippocampal volume atrophy was not related to hippocampal NFT pathology. These significant relationships continue to exist when all nondemented subjects are excluded from analysis. In subjects with cognitive impairment, the best predictor of cortical NFT and SP is the rate of ventricular volume increase. Excluding subjects with long duration between MRI and death did not appreciably alter results.
CONCLUSIONS
MRI volumes measured over time are valid biomarkers of pathologic progression of AD across a range of antemortem clinical states. The rate of ventricular volume enlargement can be used to monitor disease progression or response to treatment in future clinical trials that are targeted at NFT and SP pathology.
Publication
Journal: Journal of Clinical Endocrinology and Metabolism
April/30/2006
Abstract
BACKGROUND
Testosterone and estradiol levels decline with age in men. This change may affect multiple clinical outcomes, but there have been few reports of the distribution and correlates of testosterone and estradiol concentrations in elderly men.
OBJECTIVE
The purpose of these studies was to assess sex steroid levels in a large cohort of older men.
METHODS
We conducted a cross-sectional cohort evaluation.
METHODS
Community-dwelling men were studied at six academic medical centers in the United States.
METHODS
The Osteoporotic Fractures in Men Study is a prospective cohort of men aged at least 65 yr. In these studies, a randomly selected stratified subsample of 2623 participants was analyzed.
METHODS
We assessed levels of total and free testosterone and estradiol and SHBG.
RESULTS
Age was inversely associated with free testosterone and free estradiol levels (P for trend = 0.001 for both). Notably, at any age, there was substantial variation in levels of each hormone. Free testosterone levels were lower in men with greater body mass index, lower SHBG, and poorer self-reported health status and in those of Asian race. Free estradiol concentrations were lower in men with lower body mass index and higher SHBG levels. Free estradiol and free testosterone were modestly correlated (r = 0.20; P < 0.001), but at any level of free testosterone, there was considerable variation in free estradiol levels.
CONCLUSIONS
This is the largest cohort of older men in which sex steroid levels are available, and it demonstrates that testosterone and estradiol, and their free fractions, tend to decline with age even among older men. However, substantial variation is also present. The relationships between sex steroid levels and their consequences in aging are likely to be complex.
Publication
Journal: Journal of Bone and Mineral Research
March/12/2007
Abstract
In a prospective study of 5384 older men, hip BMD was a very strong predictor of hip fracture, much stronger than spine BMD. The relationship between hip BMD and hip fracture risk seemed to be stronger than observed in a large prospective study of women. Hip BMD is an excellent test for predicting fracture risk in men.
BACKGROUND
There have been few studies of the relationship between BMD and risk of fractures in men and none for the association between lumbar spine BMD and risk of hip and nonvertebral fractures. There is also controversy about whether the associations between BMD and risk of fracture are the same in men and women.
METHODS
We measured proximal femur and lumbar spine BMD in 5384 men, 5384 men,>>or= 65 years of age. We compared the results to the very similar cohort of 7871 women>>or=65 of age. During 4.4 years of 99% complete follow-up, we validated 317 nonvertebral (59 hip) fractures in men and 1169 nonvertebral (208 hip) fractures in women.
RESULTS
Total hip BMD was very strongly associated with risk hip fracture in men (3.2-fold increased risk per sex-specific SD decrease in BMD; 95% CI, 2.4-4.1). The association was stronger than observed in SOF (2.1; 95% CI, 1.8, 2.4; p < 0.001 for interaction). Among the men, lumbar spine BMD was weakly associated with risk of hip fracture (relative risk [RR] per sex-specific SD decrease in BMD: 1.5; 95% CI, 1.2, 2.0). The association between total hip BMD and risk of nonvertebral fractures was somewhat stronger for men (RR = 1.6; 95% CI, 1.5, 1.8) than found for women (p = 0.01 for interaction). The risk of nonvertebral fracture was substantially higher in women than in men for all T scores of hip BMD, regardless of whether sex-specific or female reference values were used.
CONCLUSIONS
Hip BMD is strongly associated with risk of nonvertebral, and especially hip fracture, in older men. These associations are at least as strong as in women. As in women, lumbar spine BMD in men is only weakly associated with risk of hip fracture. Regardless of whether sex-specific or female reference values were used, T scores indicated different risks of fractures in men than in women.
Publication
Journal: Journal of Clinical Endocrinology and Metabolism
November/12/2006
Abstract
BACKGROUND
The clinical value of measuring testosterone and estradiol in older men with osteoporosis and of measuring bone mineral density (BMD) in older men with testosterone or estradiol deficiency is uncertain.
OBJECTIVE
The objective of the study was to examine the association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men.
METHODS
This study was a cross-sectional and longitudinal analysis.
METHODS
The study was conducted at six U.S. centers of the Osteoporotic Fractures in Men study.
METHODS
The study population consisted of 2447 community-dwelling men aged 65 yr or older.
METHODS
Total testosterone deficiency was defined as less than 200 ng/dl. Total estradiol deficiency was defined as less than 10 pg/ml. Osteoporosis was defined as femoral neck or total hip BMD T-score of -2.5 or less. Rapid bone loss was defined as 3%/yr or more.
RESULTS
Prevalence of osteoporosis in men with deficient and normal total testosterone was 12.3 and 6.0% (P = 0.003) and 15.4 and 2.8% (P < 0.0001) in those with deficient and normal total estradiol. Among osteoporotic men and those with normal BMD, prevalence of total testosterone deficiency was 6.9 and 3.2% (P = 0.01), and prevalence of total estradiol deficiency was 9.2 and 2.4% (P = 0.0001). Incidence of rapid hip bone loss in men with deficient and normal total testosterone was 22.5 and 8.6% (p = 0.007) and in those with deficient and normal total estradiol was 14.3 and 6.3% (p = 0.08).
CONCLUSIONS
Older men with total testosterone or estradiol deficiency were more likely to be osteoporotic. Those with osteoporosis were more likely to be total testosterone or estradiol deficient. Rapid hip bone loss was more likely in men with total testosterone deficiency. BMD testing of older men with sex steroid deficiency may be clinically warranted.
Publication
Journal: American Journal of Physiology - Heart and Circulatory Physiology
October/15/2008
Abstract
Idiopathic dilated cardiomyopathy (IDC) is characterized by left ventricular (LV) enlargement with systolic dysfunction, other causes excluded. When inherited, it represents familial dilated cardiomyopathy (FDC). We hypothesized that IDC or FDC would show with cardiac magnetic resonance (CMR) increased myocardial accumulation of gadolinium contrast at steady state and decreased baseline myocardial blood flow (MBF) due to structural alterations of the extracellular matrix compared with normal myocardium. CMR was performed in nine persons affected with IDC/FDC. Healthy controls came from the general population (n = 6) or were unaffected family members of FDC patients (n = 3) without signs or symptoms of IDC/FDC or any structural cardiac abnormalities. The myocardial partition coefficient for gadolinium contrast (lambda(Gd)) was determined by T1 measurements. LV shape and function and MBF were assessed by standard CMR methods. lambda(Gd) was elevated in IDC/FDC patients vs. healthy controls (lambda(Gd) = 0.56 +/- 0.15 vs. 0.41 +/- 0.06; P = 0.002), and correlated with LV enlargement (r = 0.61 for lambda(Gd) vs. end-diastolic volume indexed by height; P < 0.01) and with ejection fraction (r = -0.80; P < 0.001). The extracellular volume fraction was higher in IDC patients than in healthy controls (0.31 +/- 0.05 vs. 0.24 +/- 0.03; P = 0.002). Resting MBF was lower in IDC patients (0.64 +/- 0.13 vs. 0.91 +/- 0.22; P = 0.01) than unaffected controls and correlated with both the partition coefficient (r = -0.57; P = 0.012) and the extracellular volume fraction (r = -0.56; P = 0.019). The expansion of the extracellular space correlated with reduced MBF and ventricular dilation. Expansion of the extracellular matrix may be a key contributor to contractile dysfunction in IDC patients.
Publication
Journal: Clinical and Translational Science
October/24/2010
Abstract
BACKGROUND
More than 20 genes have been reported to cause idiopathic and familial dilated cardiomyopathy (IDC/FDC), but the frequency of genetic causation remains poorly understood.
RESULTS
Blood samples were collected and DNA prepared from 313 patients, 183 with FDC and 130 with IDC. Genomic DNA underwent bidirectional sequencing of six genes, and mutation carriers were followed up by evaluation of additional family members. We identified in 36 probands, 31 unique protein-altering variants (11.5% overall) that were not identified in 253 control subjects (506 chromosomes). These included 13 probands (4.2%) with 12 beta-myosin heavy chain (MYH7) mutations, nine probands (2.9%) with six different cardiac troponin T (TNNT2) mutations, eight probands (2.6%) carrying seven different cardiac sodium channel (SCN5A) mutations, three probands (1.0%) with three titin-cap or telethonin (TCAP) mutations, three probands (1.0%) with two LIM domain binding 3 (LDB3) mutations, and one proband (0.3%) with a muscle LIM protein (CSRP3) mutation. Four nucleotide changes did not segregate with phentoype and/or did not alter a conserved amino acid and were therefore considered unlikely to be disease-causing. Mutations in 11 probands were assessed as likely disease-causing, and in 21 probands were considered possibly disease-causing. These 32 probands included 14 of the 130 with IDC (10.8%) and 18 of 183 with FDC (9.8%)
CONCLUSIONS
Mutations of these six genes each account for a small fraction of the genetic cause of FDC/IDC. The frequency of possible or likely disease-causing mutations in these genes is similar for IDC and FDC.
Publication
Journal: Journal of the International Neuropsychological Society
July/14/2008
Abstract
The objective was to identify the trajectories of onset of memory and other cognitive loss in persons destined to develop mild cognitive impairment (MCI) or dementia. Healthy, community dwelling, cognitively intact elders (n = 156, mean age at entry = 83 years) were examined annually for an average of greater than 7 years. Those who developed at least two consecutive Clinical Dementia Ratings>>or= 0.5 were classified as having MCI. Longitudinal mixed effects models with a change point were used to model the aging process in those with and without an MCI diagnosis during follow-up and to model the rate of change relative to the age of onset of MCI. MCI had a preclinical stage of accelerated cognitive loss that was observed 3 to 4 years before the diagnosis of MCI on tests of verbal memory, animal fluency, and visuospatial constructions. Evidence from memory performance before the change point suggests that a slow decline in memory precedes the period of accelerated decline in the development of MCI. Aging transitions leading to MCI and dementia are characterized by unique linear and nonlinear cognitive changes in several domains that precede the diagnosis of MCI and dementia by at least several years.
Publication
Journal: Clinical Neurosurgery
January/26/2000
Abstract
OBJECTIVE
Deep brain stimulation (DBS) of the globus pallidus internus (GPi) and subthalamic nucleus (STN) has been reported to be effective in alleviating the symptoms of advanced Parkinson's disease (PD). Although recent studies suggest that STN stimulation may be superior to GPi stimulation, a randomized, blinded comparison has not been reported. The present study was designed to provide a preliminary comparison of the safety and efficacy of DBS at either site.
METHODS
Ten patients with idiopathic PD, L-dopa-induced dyskinesia, and response fluctuations were randomized to implantation of bilateral GPi or STN stimulators. Neurological condition was assessed preoperatively with patients on and off L-dopa and on DBS at 10 days and 3, 6, and 12 months after implantation. Patients and evaluating clinicians were blinded to stimulation site throughout the study period. Complete follow-up data were analyzed for four GPi patients and five STN patients.
RESULTS
When off-L-dopa, both GPi and STN groups demonstrated a similar response, with approximately 40% improvement in Unified PD Rating Scale motor scores after 12 months of DBS. Rigidity, tremor, and bradykinesia improved in both groups. In combination with L-dopa, Unified PD Rating Scale motor scores were more improved by GPi stimulation than by STN stimulation. On-L-dopa axial symptoms were clinically improved in the GPi but not the STN group. L-Dopa-induced dyskinesia was reduced by DBS at either site, although medication requirement was reduced only in the STN group. There were no serious intraoperative complications among patients in either group.
CONCLUSIONS
Pallidal and STN stimulation appears to be safe and efficacious for the management of advanced PD. A larger study is needed to investigate further the differences in symptom response and the interaction of L-dopa with stimulation at either site.
Publication
Journal: Hepatology
September/28/2004
Abstract
Chronic liver disease has been shown to be associated with diminished humoral and cellular immune function. Although antigen-presenting cells (APC) that initiate immune responses include various cells (B cells, endothelial cells, macrophages, etc.), the dendritic cell (DC) is a professional APC that activates naive T cells most efficiently. To examine the frequency and function of DCs in chronic liver disease, we studied circulating DCs from a cohort of 112 subjects (23 normal subjects, 29 subjects who had spontaneously recovered from hepatitis C virus [HCV] infection, 30 chronically infected HCV patients, and 30 patients with liver disease unrelated to HCV infection). Our analyses revealed significant reduction in both circulating myeloid (mDC) and plasmacytoid dendritic cells (pDC) in patients with liver disease. In contrast, examination of subjects with spontaneously resolved HCV infection revealed no significant difference in either circulating mDCs or pDCs. We found an inverse correlation with serum alanine aminotransferase (ALT) levels and both mDCs and pDCs frequency. In a subset of patients for whom intrahepatic cells were available, paired analysis revealed enrichment for DCs within the intrahepatic compartment. Interferon alfa (IFN-alpha) production in response to influenza A and poly (I:C) correlated with the frequency of circulating DCs, although IFN-alpha production was comparable on a per-DC basis in patients with liver disease. In conclusion, patients with liver disease exhibit a reduction in circulating DCs. Considering that DCs are essential for initiation and regulation of innate and adaptive immunity, these findings have implications for both viral persistence and liver disease.
Publication
Journal: Nature Medicine
November/7/2005
Abstract
Approximately 50% of the US population received smallpox vaccinations before routine immunization ceased in 1972 for civilians and in 1990 for military personnel. Several studies have shown long-term immunity after smallpox vaccination, but skepticism remains as to whether this will translate into full protection against the onset of orthopoxvirus-induced disease. The US monkeypox outbreak of 2003 provided the opportunity to examine this issue. Using independent and internally validated diagnostic approaches with>>or=95% sensitivity and>>or=90% specificity for detecting clinical monkeypox infection, we identified three previously unreported cases of monkeypox in preimmune individuals at 13, 29 and 48 years after smallpox vaccination. These individuals were unaware that they had been infected because they were spared any recognizable disease symptoms. Together, this shows that the US monkeypox outbreak was larger than previously realized and, more importantly, shows that cross-protective antiviral immunity against West African monkeypox can potentially be maintained for decades after smallpox vaccination.
Publication
Journal: Urology
November/7/2006
Abstract
OBJECTIVE
To describe the prevalence, severity, and health correlates of lower urinary tract symptoms (LUTS) in older community-dwelling U.S. men.
METHODS
We performed a cross-sectional analysis from a cohort study recruited from six U.S. clinical centers. This analysis included 5284 men without a history of prostate cancer who were at least 65 years of age. Participants completed questionnaires regarding the presence and severity of LUTS, including the American Urological Association Symptom and Bother indexes. Health status measures included the Medical Outcomes Survey SF-12 and self-rated health and instrumental activities of daily living.
RESULTS
LUTS were absent in 2.3%, mild in 51.6%, moderate in 39.6%, and severe in 6.6%. Dissatisfaction with the urinary symptoms increased with LUTS severity (P <0.001); 19.8% of moderate and 58.1% of men with severe LUTS reported feeling mostly unsatisfied to terrible with their present urinary symptoms. The prevalence, severity, and dissatisfaction with LUTS increased with age. Men reporting moderate or severe LUTS were 1.41-fold (95% confidence interval 1.23 to 1.61) and 1.51-fold (95% confidence interval 1.23 to 1.85) more likely to rate their overall health quality as fair to very poor for their age instead of good to excellent, even after controlling for age and comorbid conditions. Increased LUTS also was independently associated with increased impairment in instrumental activities of daily living and poorer SF-12 scores.
CONCLUSIONS
Moderate-to-severe LUTS is common in community-dwelling elderly U.S. men. In this study, LUTS severity was associated with poorer health quality and a greater prevalence of an inability to perform activities of daily living. The association of LUTS severity with poor health warrants increased clinical attention.
Publication
Journal: Folia Neuropathologica
April/20/2006
Abstract
Neurodegeneration with brain iron accumulation (NBIA) describes a group of progressive extrapyramidal disorders with radiographic evidence of focal iron accumulation in the brain, usually in the basal ganglia. Patients previously diagnosed with Hallervorden-Spatz syndrome fall into this category. Mutations in the PANK2 gene account for the majority of NBIA cases and cause an autosomal recessive inborn error of coenzyme A metabolism called pantothenate kinase-associated neurodegeneration (PKAN). PKAN is characterized by dystonia and pigmentary retinopathy in children or speech and neuropsychiatric disorders in adults. In addition, a specific pattern on brain MRI, called the eye-of-the-tiger sign, is virtually pathognomonic for the disease. Pantothenate kinase is essential to coenzyme A biosynthesis, and the PANK2 protein is targeted to the mitochondria. Hypotheses of PKAN pathogenesis are based on the predictions of tissue-specific coenzyme A deficiency and the accumulation of cysteine-containing substrates. Identification of the major NBIA gene has led to more accurate clinical delineation of the diseases that comprise this group, a molecular diagnostic test for PKAN, and hypotheses for treatment.
Publication
Journal: Journal of Immunology
August/5/2004
Abstract
As with most herpesviruses, CMVs encode viral genes that inhibit Ag presentation to CD8 T cells (VIPRs). VIPR function has been assumed to be essential for CMV to establish its characteristic lifetime infection of its host. We compared infection of C57BL/6 mice with wild-type murine CMV (MCMV) and a virus lacking each of MCMV's three known VIPRs: m4, m6, and m152. During acute infection, there was very little difference between the two viruses with respect to the kinetics of viral replication and clearance, or in the size and kinetics of the virus-specific CD8 T cell response. During chronic infection, a large, effector memory, virus-specific CD8 T cell population (CD8(low)CD62L(-)CD11c(+)NKG2A(+)) was maintained in both infections; the size and phenotype of the CD8 T cell response to both viruses was remarkably similar. The characteristic effector memory phenotype of the CD8 T cells suggested that both wild-type and Deltam4+m6+m152 virus continued to present Ag to CD8 T cells during the chronic phase of infection. During the chronic phase of infection, MCMV cannot be isolated from immunocompetent mice. However, upon immunosuppression, both Deltam4+m6+m152 and wild-type virus could be reactivated from mice infected for 6 wk. Thus, restoring the ability of CD8 T cells to detect MCMV had little apparent effect on the course of MCMV infection and on the CD8 T cell response to it. These results challenge the notion that VIPR function is necessary for CMV persistence in the host.
Publication
Journal: Neurobiology of Aging
October/3/2004
Abstract
Studies have found that emotionally evocative stimuli are better remembered than neutral stimuli, an effect called "emotional enhancement". Researchers have also found that the elderly experience an overall decline in memory relative to the young. We hypothesized that the elderly may experience diminished emotional enhancement, and that this may be one factor contributing to overall memory decline in the elderly. We tested elderly and young subjects on tasks of emotional memory for words and faces. In both the elderly and young, a shift in memory favoring positive stimuli (as opposed to negative and neutral stimuli) was evident, this effect being slightly more marked in the elderly. We suggest that the effects seen in both groups may be due to a shift from the amygdala-hippocampal system to the prefrontal cortex over time. We suggest that the more marked response in the elderly may be due to age-related changes in these brain systems, causing a further shift towards memory for positive material.
Publication
Journal: Behavioural Brain Research
October/31/2006
Abstract
Human tests designed to mirror rodent tests of object recognition and spatial navigation were administered to adult cognitively healthy humans. Facial recognition was also assessed. There was no sex difference in facial recognition, consistent with earlier studies. In the object recognition test, the test-retest NINL total scores during the same visit were highly correlated, comparable to the test-retest correlations obtained in the established facial recognition test. There were no effects of sex on object recognition. However, in the spatial navigation test, there were effects of sex on spatial learning and memory during the session with the hidden, but not visible, target. These tests might be useful to compare assessments of object recognition and spatial learning and memory in humans and animal models.
Publication
Journal: New England Journal of Medicine
August/13/1982
Publication
Journal: Menopause
June/20/2007
Abstract
OBJECTIVE
To examine how menopausal symptoms and estrogen therapy (ET)-induced symptom relief affect cognition in early menopause.
METHODS
There were two components. Part 1 was a cross-sectional study of 37 healthy, recently postmenopausal women with diverse menopausal symptoms. Women were categorized as having low (n=20) or high symptoms (n=17) based on a validated symptom questionnaire. Women completed mood and sleep questionnaires and underwent cognitive testing, which included verbal memory, visual memory, emotional memory, and verbal fluency. Thirty-two of these women went on to part 2 of the study. Fourteen were randomly assigned to receive ET and 18 to receive placebo for 8 weeks. Before treatment and at 4 and 8 weeks, women completed the same measures as in part 1 of the study.
RESULTS
High symptom women had more negative mood (P=0.01) and lower quality sleep (P<0.001) than low symptom women. Despite suffering from more menopausal symptoms, worse mood, and poorer sleep, women in the high symptom group performed the same on cognitive testing as women in the low symptom group. Women receiving ET had greater improvements in menopausal symptoms and sleep compared with those receiving the placebo (P<or=0.05). ET did not improve mood compared with placebo. Women receiving ET did not have any improvement in cognitive performance compared with those receiving the placebo.
CONCLUSIONS
Menopausal symptoms do not impair cognition. ET does not improve cognition despite alleviating symptoms and improving sleep in recently naturally menopausal women with diverse menopausal symptoms.
Publication
Journal: Journal of Clinical and Experimental Neuropsychology
June/7/2010
Abstract
Expectancy or placebo effects on cognitive function have not been well studied. To determine the effect of taking pills on cognitive function, 40 participants were randomly assigned to a pill or no-pill condition. Healthy seniors who took a 2-week supply of methylcellulose pills, which they were told was an experimental cognitive enhancer, were compared to seniors not taking any pills. There were 2 primary outcome measures defined prior to the study-Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List delayed recall and Stroop color word task time-as well as 7 other cognitive outcome measures. There was a significant effect of pill taking on the 2 primary outcome measures. There was also an effect of pill taking on choice reaction time and Word List immediate recall but not on the other 5 secondary cognitive outcome measures. In an exploratory analysis of potential predictors of the expectancy effect, perceived stress and self-efficacy but not personality traits interacted with the pill-taking effect on cognitive function. Further characterizing and understanding this observed expectancy effect is important to maximize cognitive health and improve clinical trial design.
Publication
Journal: Dialogues in Clinical Neuroscience
January/8/2008
Abstract
The finding that bright light can suppress melatonin production led to the study of two situations, indeed, models, of light deprivation: totally blind people and winter depressives. The leading hypothesis for winter depression (seasonal affective disorder, or SAD) is the phase shift hypothesis (PSH). The PSH was recently established in a study in which SAD patients were given low-dose melatonin in the afternoon/evening to cause phase advances, or in the morning to cause phase delays, or placebo. The prototypical phase-delayed patient, as well as the smaller subgroup of phase-advanced patients, optimally responded to melatonin given at the correct time. Symptom severity improved as circadian misalignment was corrected. Circadian misalignment is best measured as the time interval between the dim light melatonin onset (DLMO) and mid-sleep. Using the operational definition of the plasma DLMO as the interpolated time when melatonin levels continuously rise above the threshold of 10 pg/mL, the average interval between DLMO and mid-sleep in healthy controls is 6 hours, which is associated with optimal mood in SAD patients.
Publication
Journal: Journal of Bone and Mineral Research
January/3/2006
Abstract
The influence of fall orientation on femur strength has important implications for understanding hip fracture risk. A new image analysis technique showed that the strength of the femoral neck in 37 males varied significantly along the neck axis and that bending strength varied by a factor of up to 2.8 for different loading directions.
BACKGROUND
Osteoporosis is associated with decreased BMD and increased hip fracture risk, but it is unclear whether specific osteoporotic changes in the proximal femur lead to a more vulnerable overall structure. Nonhomogeneous beam theory, which is used to determine the mechanical response of composite structures to applied loads, can be used along with QCT to estimate the resistance of the femoral neck to axial forces and bending moments.
METHODS
The bending moment [My(theta)] sufficient to induce yielding within femoral neck sections was estimated for a range of bending orientations (theta) using in vivo QCT images of 37 male (mean age, 73 years; range, 65-87 years) femora. Volumetric BMD, axial stiffness, average moment at yield (M(y,avg)), maximum and minimum moment at yield (M(y,max) and M(y,min)), bone strength index (BSI), stress-strain index (SSI), and density-weighted moments of resistance (Rx and Ry) were also computed. Differences among the proximal, mid-, and distal neck regions were detected using ANOVA.
RESULTS
My(theta) was found to vary by as much as a factor of 2.8 for different bending directions. Axial stiffness, M(y,avg), M(y,max), M(y,min), BSI, and Rx differed significantly between all femoral neck regions, with an overall trend of increasing axial stiffness and bending strength when moving from the proximal neck to the distal neck. Mean axial stiffness increased 62% between the proximal and distal neck, and mean M(y,avg) increased 53% between the proximal and distal neck.
CONCLUSIONS
The results of this study show that femoral neck strength strongly depends on both fall orientation and location along the neck axis. Compressive yielding in the superior portion of the femoral neck is expected to initiate fracture in a fall to the side.
Publication
Journal: Journal of the American Dietetic Association
May/6/2010
Abstract
Mediation analysis is a newer statistical tool that is becoming more prominent in nutrition research. Its use provides insight into the relationship among variables in a potential causal chain. For intervention studies, it can define the influence of different programmatic components and, in doing so, allows investigators to identify and refine a program's critical aspects. We present an overview of mediation analysis, compare mediators with other variables (confounders, moderators, and covariates), and illustrate how mediation analysis permits interpretation of the change process. A framework is outlined for the critical appraisal of articles purporting to use mediation analysis. The framework's utility is demonstrated by searching the nutrition literature and identifying articles citing mediation cross referenced with the terms "nutrition," "diet," "food," and "obesity." Seventy-two articles were identified that involved human subjects and behavior outcomes, and almost half mentioned mediation without tests to define its presence. Tabulation of the 40 articles appropriately assessing mediation demonstrates an increase in these techniques' appearance and the breadth of nutrition topics addressed. Mediation analysis is an important new statistical tool. Familiarity with its methodology and a framework for assessing articles will allow readers to critically appraise the literature and make informed independent evaluations of works using these techniques.
Publication
Journal: Molecular Genetics and Metabolism
November/12/2000
Abstract
Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive condition with multiple malformations, mental retardation, and growth failure, results from markedly reduced activity of the final enzyme in the cholesterol biosynthetic pathway, 7-dehydrocholesterol reductase (DHCR7). Clinical signs vary in severity, ranging from fetal loss to holoprosencephaly with multiple malformations to isolated syndactyly. The biochemical defect in SLOS is a deficiency of DHCR7, which results in an abnormally low cholesterol level, and increased amounts of intermediates of sterol biosynthesis. Animal models currently exist through the use of cholesterol biosynthesis inhibitors, from which a great deal has been learned. Pregnant rats treated with inhibitors of DHCR7 yield pups that have abnormal sterol profiles and craniofacial abnormalities characteristic of severe SLOS. Biochemical testing of human patients can be performed using gas chromatography/mass spectroscopy (GC/MS) to analyze the sterol content of tissues, amniotic fluid, or cell culture lysate. Numerous mutations have been identified in DHCR7 but seven individual mutations account for 67% of the total mutations reported in the literature. Clinical trials with SLOS are underway, with the goal of increasing the cholesterol concentration in the plasma and tissues through the administration of dietary cholesterol. Thus far, this approach has shown limited efficacy. Nevertheless, the recent identification of the biochemical and molecular genetic basis for SLOS is reason for optimism that the condition may one day yield to treatment.
Publication
Journal: Neurobiology of Aging
April/27/2008
Abstract
The ability to maintain cognitive function during aging is a complex process subject to genetic and environmental influences. Alzheimer's disease (AD) is the most common disorder causing cognitive decline among the elderly. Among those with AD, there is broad variation in the relationship between AD neuropathology and clinical manifestations of dementia. Differences in expression of genes involved in neural processing pathways may contribute to individual differences in maintenance of cognitive function. We performed whole genome expression profiling of RNA obtained from frontal cortex of clinically non-demented and AD subjects to identify genes associated with brain aging and cognitive decline. Genetic mapping information and biological function annotation were incorporated to highlight genes of particular interest. The candidate genes identified in this study were compared with those from two other studies in different tissues to identify common underlying transcriptional profiles. In addition to confirming sweeping transcriptomal differences documented in previous studies of cognitive decline, we present new evidence for up-regulation of actin-related processes and down-regulation of translation, RNA processing and localization, and vesicle-mediated transport in individuals with cognitive decline.
Publication
Journal: Urology
December/12/2010
Abstract
OBJECTIVE
To determine the effect of acupuncture on hot flash frequency and intensity, quality of life, and sleep quality in patients undergoing hormonal therapy for prostate cancer. Hot flashes are a common adverse effect of hormonal therapy for prostate cancer.
METHODS
Men who had a hot flash score>> 4 who were receiving androgen deprivation therapy for prostate cancer underwent acupuncture with electrostimulation biweekly for 4 weeks, then weekly for 6 weeks, using a predefined treatment plan. The primary endpoint was a 50% reduction in the hot flash score after 4 weeks of therapy, calculated from the patients' daily hot flash diaries. The hot flash-related quality of life and sleep quality and biomarkers potentially related to hot flashes, including serotonin, calcitonin gene-related peptide, and urinary 5-hydroxyindoleacetic acid, were examined.
RESULTS
A total of 25 men were enrolled from September 2003 to April 2007. Of these, 22 were eligible and evaluable. After 4 weeks, 9 (41%, 95% confidence interval 21%-64%) of 22 patients had had a>> 50% reduction in the hot flash score. Of the 22 patients, 12 (55%, 95% confidence interval 32%-76%) met this response definition at any point during the therapy course. No patient had a significant increase in hot flash score during therapy. A reduced hot flash score was associated with improvement in the hot flash-related quality of life and sleep quality.
CONCLUSIONS
Multiple placebo-controlled trials have demonstrated a 25% response rate to placebo treatment for hot flashes. Of the 22 patients, 41% had responded by week 4 and 55% overall in the present pilot study, providing evidence of a potentially meaningful benefit. Additional studies of acupuncture for hot flashes in this population are warranted.
load more...