Trajectories of femoral neck strength in relation to the final menstrual period in a multi-ethnic cohort.

UNLABELLED: The purpose of this study was to describe the evolution of femoral neck strength relative to load across the menopause transition. It declined significantly over the 10 years bracketing the final menstrual period, and the rate of decline was modified by body mass index, race/ethnicity, and smoking status. INTRODUCTION: Composite indices of femoral neck strength, which integrate dual energy X-ray absorptiometry (DXA)-derived bone mineral density and bone size with body size, are inversely associated with hip fracture risk. Our objective was to describe longitudinal trajectories of the strength indices across the menopausal transition. METHODS: Data came from the Study of Women's Health Across the Nation; participants were pre- or early peri-menopausal, ages 42-53 at baseline, and were followed up for 9.1 ± 1.8 years. Composite indices of femoral neck strength in different failure modes (compression, bending, and impact) were created in 921 women who had three or more hip DXA scans and had definable final menstrual period (FMP) dates. We used mixed effects models to fit piecewise linear growth curves to the baseline-normalized strength indices as a function of time to/after the FMP. RESULTS: Compression and impact strength indices did not decline until 1 year prior to the FMP, and declined rapidly thereafter, with some slowing of decline 1 year after the FMP. Bending strength index increased slightly until 2 years prior to the FMP, then plateaued, and began to decline at the FMP. Mean decline in strength indices over 10 years was 6.9 % (compression), 2.5 % (bending), and 6.8 % (impact). Women with higher body mass index had larger declines in two of the three indices. Other major modifiers of rates of decline were race/ethnicity and smoking status. CONCLUSIONS: Femoral neck strength relative to load declines significantly during the menopausal transition, with declines commencing 1 to 2 years prior to the FMP.

A comparison of DXA and CT based methods for estimating the strength of the femoral neck in post-menopausal women.

UNLABELLED: The study goal was to compare simple two-dimensional (2D) analyses of bone strength using dual energy x-ray absorptiometry (DXA) data to more sophisticated three-dimensional (3D) finite element analyses using quantitative computed tomography (QCT) data. DXA- and QCT-derived femoral neck geometry, simple strength indices, and strength estimates were well correlated. INTRODUCTION: Simple 2D analyses of bone strength can be done with DXA data and applied to large data sets. We compared 2D analyses to 3D finite element analyses (FEA) based on QCT data. METHODS: Two hundred thirteen women participating in the Study of Women's Health Across the Nation (SWAN) received hip DXA and QCT scans. DXA BMD and femoral neck diameter and axis length were used to estimate geometry for composite bending (BSI) and compressive strength (CSI) indices. These and comparable indices computed by Hip Structure Analysis (HSA) on the same DXA data were compared to indices using QCT geometry. Simple 2D engineering simulations of a fall impacting on the greater trochanter were generated using HSA and QCT femoral neck geometry; these estimates were benchmarked to a 3D FEA of fall impact. RESULTS: DXA-derived CSI and BSI computed from BMD and by HSA correlated well with each other (R=0.92 and 0.70) and with QCT-derived indices (R=0.83-0.85 and 0.65-0.72). The 2D strength estimate using HSA geometry correlated well with that from QCT (R=0.76) and with the 3D FEA estimate (R=0.56). CONCLUSIONS: Femoral neck geometry computed by HSA from DXA data corresponds well enough to that from QCT for an analysis of load stress in the larger SWAN data set. Geometry derived from BMD data performed nearly as well. Proximal femur breaking strength estimated from 2D DXA data is not as well correlated with that derived by a 3D FEA using QCT data.

Evaluation of new instruments for screening and diagnosis of tics and tic disorders in a well-characterized sample of youth with tics and recruited controls.

Tics and tic disorders can significantly impact children, but limited screening tools and diagnostic challenges may delay access to care. The current study attempted to address these gaps by evaluating sensitivity and specificity of the Motor or Vocal Inventory of Tics (MOVeIT), a tic symptom screener, and the Description of Tic Symptoms (DoTS), a brief diagnostic assessment for tic disorders. Children (n=100, age 6-17 years old) with tic disorders attending a Tourette specialty clinic and a community-recruited sample without tics completed a gold-standard assessment by a tic expert; these evaluations were compared to child self-report and parent and teacher report versions of the MOVeIT, and child and parent versions of the DoTS. The parent and child MOVeIT met or exceeded pre-specified 85% sensitivity and specificity criteria for detecting the presence of tics when compared to a gold-standard tic expert diagnosis. The Teacher MOVeIT had lower sensitivity (71.4%) but good specificity (95.7%) for identifying any tic symptoms compared to gold standard. For determination of the presence or absence of any tic disorder, sensitivity of both parent and child DoTS was 100%; specificity of the parent DoTS was 92.7% and child DoTS specificity was 75.9%. More work may be needed to refine the teacher MOVeIT, but it is also recognized that tic expression may vary by setting. While the MOVeIT and DoTS parent and child questionnaires demonstrated adequate sensitivity and specificity for determining the presence of tics and tic disorders in this well-defined sample, additional testing in a general population is warranted.

Ethnic differences in composite indices of femoral neck strength.

UNLABELLED: Bone mineral density does not explain race/ethnicity differences in hip fracture risk. In this study, we demonstrated that race/ethnicity differences in composite hip strength indices were consistent with documented race/ethnicity differences in hip fracture risk, suggesting that unlike bone density, the composite indices may represent ethnicity-independent measures of bone strength. INTRODUCTION: African-American and Asian women have lower risks of hip fracture than Caucasian women, but such racial/ethnic variation in hip fracture risk cannot be explained by bone mineral density (BMD). The composite indices of femoral neck strength integrate femoral neck and body size with BMD and predict hip fracture risk in Caucasian women. We hypothesize that unlike race/ethnic differences in BMD, race/ethnic differences in the composite strength indices would be consistent with race/ethnic differences in hip fracture risk. METHODS: We studied a community-based sample of Caucasian (n = 968), African-American (n = 512), Chinese (n = 221), and Japanese (n = 239) women, premenopausal or in early perimenopause, from the Study of Women's Health Across the Nation. RESULTS: Unadjusted indices were similar in Caucasian and African-American women but higher in Asian women. After adjusting for age, body mass index, and menopause status, all three minority groups had higher composite strength indices than Caucasian women. Foreign-born Japanese women had higher unadjusted and adjusted composite strength indices than US-born Japanese women, but such differences by nativity were not observed in Chinese women. CONCLUSION: We concluded that composite strength indices have the potential to explain racial/ethnic differences in hip fracture risk, suggesting that composite strength indices may represent ethnicity-independent measures of bone strength. This contention needs to be verified by further research on the fracture predictive ability of composite strength indices in multi-ethnic longitudinal cohorts.

Renal function and nonvertebral fracture risk in multiethnic women: the Women's Health Initiative (WHI).

UNLABELLED: To examine the association between renal function and fracture in multiethnic women, we studied postmenopausal women enrolled in the Women's Health Initiative. Postmenopausal White women with mild renal dysfunction were at increased risk of nonvertebral fracture; this association was at least partially explained by effects of renal dysfunction on chronic inflammation. Reduced renal function appeared to increase fracture risk among Black women, but there was little evidence to support this association among other racial/ethnic groups. INTRODUCTION: The purpose of this study was to determine whether renal function is associated with fracture risk within racial/ethnic groups. METHODS: A nested case-control study was conducted among 93,673 postmenopausal women; incident nonvertebral fractures were identified in 362 Black, 183 Hispanic, 110 Asian, and 45 American-Indian women. A random sample of 395 White women with incident nonvertebral fracture was chosen. One nonfracture control for each case was selected (matched on age, race/ethnicity, and blood draw date). Cystatin C levels were measured using baseline serum, and estimated glomerular filtration rate calculated (eGFR(cys-c)). RESULTS: Each 1 SD increase in cystatin C was associated with a 1.2-fold increased risk of fracture among White women (adjusted odds ratios [OR], 1.23; 95% confidence intervals [CI], 1.04-1.46). The OR of fracture was 1.16 (95% CI, 0.85-1.58) among women with eGFR(cys-c) 60-90 mL/min/1.73 m(2) and 2.46 (95% CI, 1.16-5.21) among those with eGFR(cys-c) <60 mL/min/1.73 m(2) compared to the reference group (eGFR(cys-c) >90 mL/min/1.73 m(2)) (p trend = 0.05). The association was reduced after adjustment for cytokine TNFα soluble receptors (OR, 1.62; 95% CI, 0.59-4.46 for eGFR(cys-c) <60 mL/min/1.73 m(2)). Among Blacks, there was an association between cystatin C and fracture risk (OR per 1 SD increase, 1.15; 95% CI, 1.00-1.32); after adjustment, this association was only modestly attenuated, but no longer statistically significant. There was no evidence of significant associations among Hispanic, Asian, or American-Indian women. CONCLUSION: Postmenopausal White women with mild renal dysfunction are at increased risk of nonvertebral fracture. Effects of renal function on chronic inflammation may mediate this association. Reduced renal function may increase fracture risk among Black women, but there was little evidence to support this association among other racial/ethnic groups.

Electroporation-mediated delivery of a naked DNA plasmid expressing VEGF to the porcine heart enhances protein expression.

Gene therapy is an attractive method for the treatment of cardiovascular disease. However, using current strategies, induction of gene expression at therapeutic levels is often inefficient. In this study, we show a novel electroporation (EP) method to enhance the delivery of a plasmid expressing an angiogenic growth factor (vascular endothelial growth factor, VEGF), which is a molecule previously documented to stimulate revascularization in coronary artery disease. DNA expression plasmids were delivered in vivo to the porcine heart with or without coadministered EP to determine the potential effect of electrically mediated delivery. The results showed that plasmid delivery through EP significantly increased cardiac expression of VEGF compared with injection of plasmid alone. This is the first report showing successful intracardiac delivery, through in vivo EP, of a protein expressing plasmid in a large animal.

Use of a novel technology for presenting screening measures to detect mild cognitive impairment in elderly patients.

BACKGROUND: Available screening tools for mild cognitive impairment (MCI), often a precursor to Alzheimer's disease, are insensitive or not feasible for administration in a busy primary care setting. Display Enhanced TEsting for Cognitive impairment and Traumatic brain injury (DETECT) addresses these issues by creating an immersive environment for the brief administration of neuropsychological (NP) measures. OBJECTIVE: The aim of this study was to determine if the DETECT cognitive subtests can identify MCI patients as accurately as standard pen and paper NP tests. METHODS: Twenty patients with MCI recruited from a memory disorders clinic and 20 age-matched controls were given both a full battery of NP tests (standard NP) and the DETECT screen. Logistic regression models were used to determine whether individual tests were predictive of group membership (MCI or control). Demographic variables including age, race, education and gender were adjusted as covariates. Selection methods were used to identify subset models that exhibited maximum discrimination between MCI patients and controls for both testing methods. RESULTS: Both the standard NP model (C-index = 0.836) and the DETECT model (C-index = 0.865) showed very good discrimination and were not significantly different (p = 0.7323). CONCLUSION: The DETECT system shows good agreement with standard NP tests and is capable of identifying elderly patients with cognitive impairment.

Clinicians' attitudes toward standardized assessment and diagnosis within child and adolescent psychiatry.

BACKGROUND: There is a strong call for clinically useful standardized assessment tools in everyday child and adolescent psychiatric practice. The attitudes of clinicians have been raised as a key-facilitating factor when implementing new methods. An explorative study was conducted aimed to investigate the clinicians' attitudes regarding standardized assessments and usefulness of diagnoses in treatment planning. METHODS: 411 mental health service personnel working with outpatient and inpatient assessment and treatment within the specialist child and adolescent mental health services, Stockholm County Council were asked to participate in the study, of which 345 (84%) agreed answer a questionnaire. The questionnaire included questions regarding Attitudes toward Standardized Assessment and Utility of Diagnosis. Descriptive analyses were performed and four subscales were compared with information from a similar study in US using the same instruments. The demographic and professional characteristics (age, working years, gender, education, profession, management position, involvement in assessment, level of service) in terms of prediction of attitudes were studied by univariate and multivariate linear regressions. RESULTS: Overall, the clinicians had quite positive attitudes and were more positive compared to a similar study conducted in the US earlier. There were differences in attitudes due to several characteristics but the only characteristic predicting all subscales was type of profession (counselor, nurse, psychiatrist, psychologist, other), with counselors being less positive than other groups. CONCLUSION: The overall positive attitudes toward standard assessment are of importance in the development of evidence-based practice and our study implies that clinicians in general value and are willing to use standardized assessment. Nevertheless, there are specific issues such as adequate training and available translated assessment instrument that need to be addressed. When implementing new methods in practice, there are general as well as specific resistances that need to be overcome. Studies in different cultural settings are of importance to further extend the knowledge of what is general and what is specific barriers.

Endovascular treatment of aneurysms: healing mechanisms in a Swine model are associated with increased expression of matrix metalloproteinases, vascular cell adhesion molecule-1, and vascular endothelial growth factor, and decreased expression of tissue inhibitors of matrix metalloproteinases.

BACKGROUND AND PURPOSE: The mechanism of aneurysm healing after coiling remains poorly understood. The purpose of the study was to obtain a better understanding of the cellular and molecular events that are associated with aneurysm healing after endovascular coiling in a swine aneurysm model. MATERIALS AND METHODS: Twenty sidewall aneurysms were created surgically in common carotid arteries in 10 swine. These aneurysms were embolized immediately after creation by using platinum coils by endovascular means. Two and 12 weeks after implantation, aneurysm samples were collected for histologic and biochemical analysis. RESULTS: All aneurysms were completely or nearly completely occluded angiographically at the time of embolization and at follow-up. At 2 weeks, aneurysm cavities were filled with inflammatory cells and myofibroblasts. At 12 weeks, aneurysm cavities were filled with richly vascularized fibrous tissue and disorganized collagen bundles. The expression of matrix metalloproteinase (MMP)-2 and -9 was found to be elevated at 2 weeks. Expression remained greater than that in control tissue at 12 weeks but was significantly decreased compared with the earlier time point. Expression of tissue inhibitors of MMPs (TIMPs) was diminished at both time points. Expression of vascular cell adhesion molecule-1 (VCAM-1) and vascular endothelial growth factor (VEGF) was elevated at both 2 weeks and 12 weeks. Endothelial nitric oxide synthase expression was not different from that in controls. Transforming growth factor-beta expression was elevated at 2 weeks only. CONCLUSION: The coil occlusion in this model that is prone to heal is associated with increased expression of MMP-2, MMP-9, VCAM-1, and VEGF, and decreased expression of TIMPs.

Control of aneurysm volume by adjusting the position of ligation during creation of elastase-induced aneurysms: a prospective study.

BACKGROUND AND PURPOSE: Animal models with appropriate volume are crucial for preclinical assessment of aneurysm therapies. Our purpose was to control the aneurysm volume by adjusting the position of ligation during creation of elastase-induced aneurysms in rabbits. MATERIALS AND METHODS: Sixty elastase-induced aneurysms in rabbits were created. Two different methods were used for creation, including group 1 (n=30) by using a lower ligation (from the origin of the right common carotid artery [RCCA] to the ligation point, 10 mm) and group 2 (n=30) by using a higher ligation (from the origin of the RCCA to the ligation point, 15 mm). Aneurysm sizes (neck diameter, width, and height) and volumes in the 2 groups were measured and calculated, and they were compared by using the Student t test. RESULTS: The mean aneurysm neck diameter, width, and height for group 2 were significantly larger than those of group 1 (3.3 +/- 0.8 versus 2.7 +/- 0.6 mm, P<.001; 3.7 +/- 0.7 versus 2.5 +/- 0.7 mm, P<.001; 9.0 +/- 1.7 versus 7.3 +/- 1.9 mm, P<.001, respectively). The aneurysm volume in group 2 was significantly larger than that in group 1 (102.4 +/- 54.8 mm(3) versus 36.6 +/- 26.8 mm(3), P<.001). CONCLUSION: The aneurysm volume of elastase-induced models in rabbits can be controlled by adjusting the position of the ligation. Using a higher ligation can create relatively more voluminous aneurysms, compared with using a lower ligation.

Design of a Multisite Study Assessing the Impact of Tic Disorders on Individuals, Families, and Communities.

BACKGROUND: Tic disorders, including Tourette syndrome, are complex, multisymptom diseases, yet the impact of these disorders on affected children, families, and communities is not well understood. METHODS: To improve the understanding of the impacts of Tourette syndrome, two research groups conducted independent cross-sectional studies using qualitative and quantitative measures. They focused on similar themes, but distinct scientific objectives, and the sites collaborated to align methods of independent research proposals with the aim of increasing the analyzable sample size. RESULTS: Site 1 (University of Rochester) was a Pediatric Neurology referral center. Site 2 (University of South Florida) was a Child Psychiatry referral center. A total of 205 children with tic disorders were enrolled from both studies. The University of Rochester also enrolled 100 control children in order to clearly isolate impacts of Tourette syndrome distinct from those occurring in the general population. The majority of children with tic disorders (n = 191, 93.1%) had Tourette syndrome, the primary population targeted for these studies. Children with Tourette syndrome were similar across sites in terms of tic severity and the occurrence of comorbid conditions. The occurrence of psychiatric comorbidities in the control group was comparable with that in the general pediatric population of the United States, making this a well-justified comparison group. CONCLUSIONS: Through collaboration, two sites conducting independent research developed convergent research methods to enable pooling of data, and by extension increased power, for future analyses. This method of collaboration is a novel model for future epidemiological research of tic disorders.

A longitudinal immunohistochemical study of the healing of experimental aneurysms after embolization with platinum coils.

BACKGROUND AND PURPOSE: The purpose of this study was to probe the cellular mechanism of healing in aneurysms after platinum coil embolization, by using multiple special stains and immunolabels. METHODS: Elastase-induced aneurysms were created and embolized in 28 rabbits. Aneurysms were excised between 2 and 24 weeks after embolization. Specimens were embedded in paraffin, sectioned, and stained with hematoxylin-eosin, Masson trichrome, and multiple immunostains. RESULTS: At 2 weeks, peripheral sparse spindle-nucleated cells were positive for alpha-smooth muscle actin (SMA), myosin, and vimentin, indicating myofibroblastic differentiation. At 4 weeks, all spindle-nucleated cells in the aneurysm were positive for SMA, myosin, desmin, and vimentin. Ten weeks after embolization, positive immunohistochemical staining in the cells populating the aneurysm significantly decreased. Mean positive SMA cells, per high-powered field were 5 +/- 3, 45 +/- 9, 10 +/- 5, 0 +/- 0, and 0 +/- 0 at 2, 4, 10, 16, and 24 weeks, respectively. Findings of a Kruskal-Wallis test showed these data to be significantly different (P =.0001). Post hoc tests revealed significantly greater amounts of SMA-positive staining in the cells at 4 weeks compared with those at 2, 10, 16, and 24 weeks (P < .05). In addition, the 10-week group had significantly more positive cells than the 16- and 24-week groups (P < .05). There was a 78% decrease in apoptotic cells between 4 (37 +/- 11) and 10 weeks (8 +/- 4) after implantation. Apoptotic cells were completely absent beyond 10 weeks. CONCLUSION: Aneurysm healing, in response to platinum coil embolization, appeared to progress through the stages of thrombus formation, granulated tissue organization, and loose connective tissue formation. Myofibroblasts, the key cellular component involved in healing, appeared within the aneurysm early. They progressively reduced in number with time and finally disappeared through the mechanism of apoptosis.

Can neck size in elastase-induced aneurysms be controlled? A retrospective study.

BACKGROUND AND PURPOSE: Reproducible animal models with appropriate neck size are crucial for preclinical assessment of aneurysm therapies. Our purpose was to determine whether the neck size of elastase-induced aneurysms could be controlled by adjusting the position of the temporary occlusion balloon. METHODS: Seventy-two elastase-induced aneurysms in rabbits were retrospectively analyzed. Three groups (group 1, n = 35; group 2, n = 32; group 3, n = 5) were defined according to different balloon position (lowest, intermediate, and highest, respectively) related to the origin of right common carotid artery (CCA). Aneurysm sizes in different groups were measured and compared; parent artery dilation was assessed as present or absent. The Wilcoxon rank sum test, the Fisher exact test, and the chi(2) test were used for statistics process. RESULTS: The mean aneurysm neck diameter in group 1 was significantly wider than that in group 2 (P = .0001). The proportion of wide-necked (diameter of neck >4 mm) aneurysms in group 1 was significantly higher than that in group 2 (P = .0011). The mean dome/neck ratio in group 1 was smaller than that of group 2 (P = .0031). Aneurysm width and height and the frequency of parent artery dilation were not different in groups 1 and 2 (P = .43, P = .10, and P = .25). No aneurysms formed in group 3. CONCLUSION: The neck size of elastase-induced aneurysms can be controlled by adjusting the position of the inflated balloon, with balloon positioning that bridges from the CCA to the subclavian/brachiocephalic arteries yielding narrow-necked aneurysms.

Intra-arterial digital subtraction angiography through the ear artery for experimental aneurysm imaging.

Digital subtraction angiography through the central artery of the ear was performed to show elastase-induced aneurysms in 34 rabbits. Twenty-eight (82%) aneurysms in which common origins of the bilateral common carotid artery (CCA) were found were well shown. All 6 other aneurysms not well shown had separate origins of the CCAs from the aortic arch (P < .001). This method can be used for angiographic follow-up when there is a common origin of the CCAs.

Long-term patency of elastase-induced aneurysm model in rabbits.

BACKGROUND AND PURPOSE: Long-term patency in untreated experimental aneurysms represents a critical attribute of any system proposed for the testing of aneurysm occlusion devices. Our purpose was to evaluate the long-term patency in elastase-induced saccular aneurysm models in rabbits. METHODS: Serial intravenous digital subtractive angiography (IVDSA) was performed in 20 elastase-induced saccular aneurysm models in rabbits 1, 3, 6, 9, 12, and 24 months after creation. Aneurysm dimensions, including neck diameter, width, and height, were measured and calculated from IVDSA images. Comparisons of the aneurysm sizes across time were performed by using the paired Wilcoxon signed rank test and the Friedman test. RESULTS: None of the 20 aneurysms showed spontaneous thrombosis at any time point. Mean dimensions did not change over time for any parameter. Mean aneurysm neck, width, and height were not significantly changed at interval evaluations of 1, 3, 6, 9, 12, and 24 months (P = .210; P = .413, and P = .405, respectively). CONCLUSION: Long-term patency in elastase-induced saccular aneurysm models in rabbits is excellent. Aneurysm dimensions remain stable for as long as 2 years following creation.

Vitamin D receptor gene polymorphisms, bone turnover, and rates of bone loss in older African-American women.

Bone mineral density (BMD) is under genetic control. Some studies in Caucasian and Asian women suggest that polymorphisms in the vitamin D receptor (VDR) gene are associated with BMD and the rate of postmenopausal bone loss. We determined if similar associations exist in 101 African-American women aged 65 years and older (71 +/- 5 years, mean +/- SD). We also examined the relation between VDR genotype and fractional 45Ca absorption and markers of bone formation (osteocalcin) and resorption (N-telopeptides) in these women. BMD was measured at the proximal femur and whole body at baseline and after 1.9 +/- 0.4 years (femur only) on a Hologic QDR-2000 densitometer using dual-energy X-ray absorptiometry. Calcaneal BMD was measured with single x-ray absorptiometry. VDR gene polymorphisms were defined by the endonucleases BsmI, ApaI, and TaqI. These polymorphisms were not associated with BMD at any skeletal site or with markers of bone turnover. There was a significant interaction between age and VDR genotype where the oldest women (> 70 years) with the TT genotype experienced greater hip bone loss than women with the TT genotype (-2.1%/year vs. -0.4%/year, respectively), whereas heterozygous women experienced an intermediate rate of bone loss (-1.3%/year). Women homozygous for the B allele had 14% lower fractional 45Ca absorption compared with women homozygous for the b allele, although this difference was not statistically significant (p = 0.08). We conclude that VDR gene polymorphisms are not associated with BMD or indices of bone turnover in this population of older African-American women. However, DNA sequence variation in the VDR gene or a nearby locus may influence intestinal calcium transport and the rate of postmenopausal bone loss in African-American women.

Familial resemblance of bone mineral density (BMD) and calcaneal ultrasound attenuation: the BMD in mothers and daughters study.

The familial resemblance in bone mineral density (BMD) and calcaneal broadband ultrasound attenuation (BUA) was examined in 207 mother-daughter pairs. Mothers were participants in the Study of Osteoporotic Fractures. Three groups of daughters were recruited based on their maternal history of "fracture," "low BMD" without fracture (< 0.58 g/cm2, t-score < -2.5), and "normal BMD" without fracture (> 0.67 g/cm2, t-score > -1.6). Data on other potentially heritable factors known to influence BMD and BUA were also collected. BMD was measured at the hip, spine, whole body, and calcaneus. Calcaneal BUA was assessed using the Walker-Sonix UBA 575. Total hip and femoral neck BMD were significantly lower (5.0-8.0%, p < 0.017) among daughters, in particular premenopausal daughters, of mothers with established osteoporosis ("fracture" or "low BMD") compared with daughters of mothers at lower risk of osteoporosis ("normal BMD"). BUA did not differ across daughter groups. Lifestyle characteristics (dietary calcium, smoking, physical activity) were not highly correlated in mothers and daughters. Height, weight, and body composition were significantly correlated within mother-daughter pairs and could be a potential mechanism by which BMD is inherited. Among pre- and postmenopausal daughters, heritability estimates ranged from 50-63% and 34-48%, respectively. Heritability for calcaneal BUA (53%) was evident among postmenopausal daughters only. In conclusion, familial association in BMD was strongest among premenopausal daughters. Estimates of heritability suggest that maternal BMD and BUA are important independent predictors of BMD and BUA among daughters, reinforcing the importance of prevention and early intervention among women with a positive family history of osteoporosis.

Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders: the Health, Aging, and Body Composition Study.

Two factors generally reported to influence bone density are body composition and muscle strength. However, it is unclear if these relationships are consistent across race and sex, especially in older persons. If differences do exist by race and/or sex, then strategies to maintain bone mass or minimize bone loss in older adults may need to be modified accordingly. Therefore, we examined the independent effects of bone mineral-free lean mass (LM), fat mass (FM), and muscle strength on regional and whole body bone mineral density (BMD) in a cohort of 2,619 well-functioning older adults participating in the Health, Aging, and Body Composition (Health ABC) Study with complete measures. Participants included 738 white women, 599 black women, 827 white men, and 455 black men aged 70-79 years. BMD (g/cm2) of the femoral neck, whole body, upper and lower limb, and whole body and upper limb bone mineral-free LM and FM was assessed by dual-energy X-ray absorptiometry (DXA). Handgrip strength and knee extensor torque were determined by dynamometry. In analyses stratified by race and sex and adjusted for a number of confounders, LM was a significant (p < 0.001) determinant of BMD, except in white women for the lower limb and whole body. In women, FM also was an independent contributor to BMD at the femoral neck, and both FM and muscle strength contributed to limb BMD. The following were the respective beta-weights (regression coefficients for standardized data, Std beta) and percent difference in BMD per unit (7.5 kg) LM: femoral neck, 0.202-0.386 and 4.7-5.9%; lower limb, 0.209-0.357 and 2.9-3.5%; whole body, 0.239-0.484 and 3.0-4.7%; and upper limb (unit = 0.5 kg), 0.231-0.407 and 3.1-3.4%. Adjusting for bone size (bone mineral apparent density [BMAD]) or body size BMD/height) diminished the importance of LM, and the contributory effect of FM became more pronounced. These results indicate that LM and FM were associated with bone mineral depending on the bone site and bone index used. Where differences did occur, they were primarily by sex not race. To preserve BMD, maintaining or increasing LM in the elderly would appear to be an appropriate strategy, regardless of race or sex.

Reduction of myocardial reinfarction by the combined treatment with clofibrate and nicotinic acid.

In an ongoing study 558 consecutive survivors of myocardial infarction below 70 years, mean age 59 years, were randomly allocated 4 months after the acute episode into a control group or a chemotherapy group from December 1972 to April 1976. Both groups were given moderate advice about diet and the chemotherapy group was prescribed clofibrate, 1 g twice daily, and nicotinic acid 1 g three times daily. Serum cholesterol and triglycerides were lowered around 15-20% and 30% respectively in the chemotherapy group while only insignificant reductions were observed in the control group. Until December 1976 total mortality and mortality from IHD has been the same in the two groups. The number of non-fatal myocardial infarctions has been 38 in the control and 19 in the chemotherapy group, a statistically significant reduction (P less than 0.01).

Oral cancer chemotherapy in paediatric patients: obstacles and potential for development and utilisation.

Although most cancer chemotherapy in children is administered parenterally, oral formulations are becoming increasingly available for use in patients as young as infants. Incentives for this approach include safety, flexibility, reduced financial cost, improved quality of life, and the potential for improved efficacy. The ability to deliver chemotherapy at home and apply schedules of administration that increase the agent's efficacy because patients do not require hospitalisation or visits to the clinic renders oral chemotherapy particularly attractive. Obstacles to oral chemotherapy in paediatric patients include restrictions in dose size and schedule, uncertain or low bioavailability, adverse effects of malabsorption, and adherence (noncompliance and refusal to take oral chemotherapy). Techniques to overcome most of these limitations are available or can be developed, and lack of an oral formulation can be solved in many instances by the pharmaceutical industry. Future developments in oral chemotherapy should not be limited to adult patient applications.