Use of the second-generation antipsychotic, risperidone, and secondary weight gain are associated with an altered gut microbiota in children.

The atypical antipsychotic risperidone (RSP) is often associated with weight gain and cardiometabolic side effects. The mechanisms for these adverse events are poorly understood and, undoubtedly, multifactorial in etiology. In light of growing evidence implicating the gut microbiome in the host's energy regulation and in xenobiotic metabolism, we hypothesized that RSP treatment would be associated with changes in the gut microbiome in children and adolescents. Thus, the impact of chronic (>12 months) and short-term use of RSP on the gut microbiome of pediatric psychiatrically ill male participants was examined in a cross-sectional and prospective (up to 10 months) design, respectively. Chronic treatment with RSP was associated with an increase in body mass index (BMI) and a significantly lower ratio of Bacteroidetes:Firmicutes as compared with antipsychotic-naïve psychiatric controls (ratio=0.15 vs 1.24, respectively; P<0.05). Furthermore, a longitudinal observation, beginning shortly after onset of RSP treatment, revealed a gradual decrease in the Bacteroidetes:Firmicutes ratio over the ensuing months of treatment, in association with BMI gain. Lastly, metagenomic analyses were performed based on extrapolation from 16S ribosomal RNA data using the software package, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Those data indicate that gut microbiota dominating the RSP-treated participants are enriched for pathways that have been implicated in weight gain, such as short-chain fatty acid production.

Effects of life-long fluoride intake on bone measures of adolescents: a prospective cohort study.

Controversy persists concerning the impact of community water fluoridation on bone health in adults, and few studies have assessed relationships with bone at younger ages. Ecological studies of fluoride's effects showed some increase in bone mineral density of adolescents and young adults in areas with fluoridated water compared with non-fluoridated areas. However, none had individual fluoride exposure measures. To avoid ecological fallacy and reduce bias, we assessed associations of average daily fluoride intake from birth to age 15 yr for Iowa Bone Development Study cohort members with age 15 yr dual-energy x-ray absorptiometry (DXA) bone outcomes (whole body, lumbar spine, and hip), controlling for known determinants (including daily calcium intake, average daily time spent in moderate-to-vigorous intensity physical activity, and physical maturity). Mean (SD) daily fluoride intake was 0.66 mg (0.24) for females and 0.78 mg (0.30) for males. We found no significant relationships between daily fluoride intake and adolescents' bone measures in adjusted models (for 183 females, all p values ≥ .10 and all partial R(2) ≤ 0.02; for 175 males, all p values ≥ .34 and all partial R(2) ≤ 0.01). The findings suggest that fluoride exposures at the typical levels for most US adolescents in fluoridated areas do not have significant effects on bone mineral measures.

Subjective and objective measures of physical activity in relationship to bone mineral content during late childhood: the Iowa Bone Development Study.

OBJECTIVE: This study compared accelerometry to self-report for the assessment of physical activity (PA) in relation to bone mineral content (BMC). In addition, we compared the ability of these measures to assess PA in boys versus girls. METHODS: Participants in this cross-sectional study included 449 children (mean age 11 years) from the Iowa Bone Development Study. PA was measured via 3-5 days of accelerometry using the Actigraph and 7 day self-report questionnaire using the Physical Activity Questionnaire for Children (PAQ-C). Hip, spine, and whole body BMC were measured via dual energy x ray absorptiometry (DXA). RESULTS: Partial correlation analysis (controlling for height, weight, and maturity) showed the Actigraph was significantly associated with hip (r = 0.40), spine (r = 0.20), and whole body (r = 0.33) BMC in boys, as was the PAQ-C (r = 0.28 hip, r = 0.19 spine, and r = 0.22 whole body). Among girls, only the Actigraph was significantly associated with hip (r = 0.18) and whole body (r = 0.16) BMC. Both the Actigraph and PAQ-C were significant in hip, spine, and whole body multivariable linear regression models (after controlling for body size and maturity) in boys. Only the Actigraph entered hip BMC regression model in girls. CONCLUSIONS: Our study supports previous work showing associations between everyday PA and BMC in older children. These associations are more likely to be detected with an objective versus subjective measure of PA, particularly in girls.

A meta-analytic investigation of linkage and association of common leptin receptor (LEPR) polymorphisms with body mass index and waist circumference.

METHODS: We analyzed data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R and K656N) of LEPR with body mass index (BMI; kg/m(2)) and waist circumference (WC). A total of 3263 related and unrelated subjects from diverse ethnic backgrounds including African-American, Caucasian, Danish, Finnish, French Canadian and Nigerian were studied. We tested effects of individual alleles, joint effects of alleles at multiple loci, epistatic effects among alleles at different loci, effect modification by age, sex, diabetes and ethnicity, and pleiotropic genotype effects on BMI and WC. RESULTS: We found that none of the effects were significant at the 0.05 level. Heterogeneity tests showed that the variations of the non-significant effects are within the range of sampling variation. CONCLUSIONS: We conclude that, although certain genotypic effects could be population-specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or WC in the overall population.

Pooling analysis of genetic data: the association of leptin receptor (LEPR) polymorphisms with variables related to human adiposity.

Analysis of raw pooled data from distinct studies of a single question generates a single statistical conclusion with greater power and precision than conventional metaanalysis based on within-study estimates. However, conducting analyses with pooled genetic data, in particular, is a daunting task that raises important statistical issues. In the process of analyzing data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R, and K656N) of LEPR with body mass index (BMI; kilograms divided by the square of the height in meters) and waist circumference (WC), we encountered the following methodological challenges: data on relatives, missing data, multivariate analysis, multiallele analysis at multiple loci, heterogeneity, and epistasis. We propose herein statistical methods and procedures to deal with such issues. With a total of 3263 related and unrelated subjects from diverse ethnic backgrounds such as African-American, Caucasian, Danish, Finnish, French-Canadian, and Nigerian, we tested effects of individual alleles; joint effects of alleles at multiple loci; epistatic effects among alleles at different loci; effect modification by age, sex, diabetes, and ethnicity; and pleiotropic genotype effects on BMI and WC. The statistical methodologies were applied, before and after multiple imputation of missing observations, to pooled data as well as to individual data sets for estimates from each study, the latter leading to a metaanalysis. The results from the metaanalysis and the pooling analysis showed that none of the effects were significant at the 0.05 level of significance. Heterogeneity tests showed that the variations of the nonsignificant effects are within the range of sampling variation. Although certain genotypic effects could be population specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or waist circumference in the general population.

Long-term survival after mitral valve replacement in children aged <5 years: a multi-institutional study.

BACKGROUND: Short- and long-term outcomes after prosthetic mitral valve replacement (MVR) in children aged <5 years are ill-defined and generally perceived as poor. The experience of the Pediatric Cardiac Care Consortium (45 centers, 1982 to 1999) was reviewed. METHODS AND RESULTS: MVR was performed 176 times on 139 patients. Median follow-up was 6.2 years (range 0 to 20 years, 96% complete). Age at initial MVR was 1.9+/-1.4 years. Complications after initial MVR included heart block requiring pacemaker (16%), endocarditis (6%), thrombosis (3%), and stroke (2%). Patient survival was as follows: 1 year, 79%; 5 years, 75%; and 10 years, 74%. The majority of deaths occurred early after initial MVR, with little late attrition despite repeat MVR and chronic anticoagulation. Among survivors, the 5-year freedom from reoperation was 81%. Age-adjusted multivariable predictors of death include the presence of complete atrioventricular canal (hazard ratio 4.76, 95% CI 1.59 to 14.30), Shone's syndrome (hazard ratio 3.68, 95% CI 1.14 to 11.89), and increased ratio of prosthetic valve size to patient weight (relative risk 1.77 per mm/kg increment, 95% CI 1.06 to 2.97). Age- and diagnosis-adjusted prosthetic size/weight ratios predicted a 1-year survival of 91% for size/weight ratio 2, 79% for size/weight ratio 3, 61% for size/weight ratio 4, and 37% for size/weight ratio 5. CONCLUSIONS: Early mortality after MVR can be predicted on the basis of diagnosis and the size/weight ratio. Late mortality is low. These data can assist in choosing between MVR and alternative palliative strategies.

Usefulness of the Framingham risk score and body mass index to predict early coronary artery calcium in young adults (Muscatine Study).

The value of a coronary artery disease prediction algorithm, the Framingham risk score (score), for detecting coronary artery calcium (CAC) was examined in 385 men and 472 women, aged 29 to 43 years. Scores were compared in subjects with and without CAC and were also used to predict presence of CAC. Receiver-operating characteristic curves were computed to compare different prediction models. The score model was compared with age only, natural logarithm of body mass index (lnBMI) only, and score plus lnBMI models. CAC was detected in 30% of men and 16% of women. The mean score was significantly higher in men and women with CAC. For every 2-point increase in the score, the odds of CAC increased by 30% in women and 20% in men. Significant associations between CAC status and risk factors were observed for age in women, and high- density lipoprotein cholesterol and blood pressure in men and women. The area under the receiver-operating characteristic curve for the score was 0.67 and 0.57 for women and men, respectively. When lnBMI was added to the score model, the area increased to 0.76 in women (lnBMI p <0.0001, score p <0.005). For men, the area increased from 0.57 to 0.67, and the score was no longer significant (p >0.60) in the model with lnBMI (p <0.0001). Score predicts CAC in asymptomatic young adults. Inclusion of lnBMI in the score model adds significantly to the prediction of CAC in women and men. The lnBMI model has a greater predictive value than the score in this young population.

Physical activity and bone measures in young children: the Iowa bone development study.

OBJECTIVES: Physical activity has a beneficial effect on bone development in circumpubertal children, although its effect on younger children is uncertain. In this cross-sectional study, we examined associations between physical activity and bone measures in 368 preschool children (mean age: 5.2 years, range: 4-6 years). DESIGN: Physical activity was measured using 4-day accelerometry readings, parental report of children's usual physical activity, and parental report of children's hours of daily television viewing. Total body and site-specific bone mineral content and area bone mineral density (BMD) were measured by dual energy radiograph absorptiometry. RESULTS: After adjustment for age and body size, accelerometry measures of physical activity and parental report of usual physical activity were consistently and positively associated with bone mineral content and BMD in both boys and girls (r = 0.15-0.28). Television viewing was inversely associated with hip BMD in girls (r = -0.15). The proportion of variance in bone measures explained by physical activity in linear regression models ranged from r(2) = 1.5% to 9.0%. In all of these models except total body BMD, at least 1 and often several of the physical activity variables entered as independent predictors. Activity variables most likely to enter the regression models were vigorous physical activity (as determined by accelerometry) and parental ranking of child's usual physical activity. CONCLUSIONS: Findings indicate that there are statistically significant and, perhaps important, associations between physical activity and bone measures during early childhood, well ahead of the onset of peak bone mass. This would suggest that intervention strategies to increase physical activity in young children could contribute to optimal bone development.

Reproducibility of left ventricular measurements with acoustic quantification: the influence of training.

Acoustic quantification (AQ) of two-dimensional (2-D) echocardiograms provides online estimation of left ventricular (LV) size and function. However, edge detection with AQ is influenced by gain settings and is therefore operator dependent. Our purpose was to compare AQ and conventional 2-D echo measurements of LV size and function obtained by different operators and to evaluate the influence of training on these measurements. A cardiac sonographer without previous experience with the AQ system was trained by an experienced operator. Twenty-two normal males (age, 28 +/- 4 years) participated in the study. Images were recorded with conventional 2-D and AQ echo from the short-axis and apical four-chamber views. During the initial training period, five subjects were imaged by the sonographer under the supervision of the trainer. At the initial study session, 12 subjects were imaged independently by the two operators. Following a second training period with five different subjects, the same initial 12 subjects were again imaged at a second study session. LV cavity areas were traced from the conventional 2-D echocardiograms and measured from the AQ waveforms at end-diastole and end-systole. Volumes were calculated using the single-plane area-length method. Ejection fraction (EF) was calculated from volumes. Reproducibility was determined by comparing the variability of AQ and conventional 2-D echo measurements obtained at the two sessions. A second training session reduced the operator variability only of the short-axis end-diastolic area measurement (17 +/- 11% vs 6 +/- 5%, P < 0.025). We conclude that a single training session may be adequate for the reproducible estimation of ventricular volumes with the AQ method.

Osteocalcin: genetic and physical mapping of the human gene BGLAP and its potential role in postmenopausal osteoporosis.

Osteocalcin is an abundant, highly conserved bone-specific protein that is synthesized by osteoblasts. Temporally, osteocalcin appears in embryonic bone at the time of mineral deposition, where it binds to hydroxyapatite in a calcium-dependent manner. A role for osteocalcin in bone resorption has been suggested because of its ability to influence recruitment and differentiation of osteoclasts at the bone surface. The human osteocalcin gene has been mapped to 1q25-1q31 by somatic cell hybridization. In this paper, we refine both the genetic map and the physical map of osteocalcin and describe a new microsatellite (CA) marker, D1S3737, which is tightly linked to the gene. This marker and two other closely linked markers were used to identify alleles of the osteocalcin gene in case and control samples of postmenopausal white Iowans with low and high bone mineral density (BMD), respectively. A significant difference (P = 0.007) was observed between allele frequency distributions of case and control women with one of the markers, D1S3737. Further, logistic regression analysis determined one allele of D1S3737 as associated with BMD status in this population (P = 0.03). Our data suggest that genetic variation at the osteocalcin locus impacts BMD levels in the postmenopausal period and may predispose some women to osteoporosis.

The lack of integration of clinical audit and the maintenance of medical dominance within British hospital trusts.

Concerns have been expressed repeatedly about the effectiveness of clinical audit. Some have argued that this is limited by the lack of integration within day-to-day practice and with other NHS policy initiatives. We aimed to explore what mechanisms were being used to develop annual clinical audit programmes within NHS Trusts, and to describe the influence of other initiatives on this; to understand how such influences are exerted; and to understand the role of key players, in order to inform future programme development. Semi-structured face-to-face interviews were performed with Chairs of Clinical Audit Committees, Clinical Audit Managers and Co-ordinators (N = 15) in the former Yorkshire Region of the NHS in England. Concerns about the development, planning and integration of clinical audit focused upon an almost exclusive medical dominance and upon how audit leadership could be delivered within the context of hospital management structures. The lack of an overall plan for the development of clinical audit in most sites was seen as enabling the doctors' agenda to dominate. Purchasing authorities were recognized as being important, but often with limited influence. Other influences on the audit agenda, such as research and development (R&D) and clinical risk management, were rarely well co-ordinated. These findings concur with previous studies in identifying a wide range of constraints on the progress of audit. Several of these constraints operate within the internal environment, for example the doctors' agenda, and concerns about management involvement. Such constraints require resolution in order to facilitate the integration of audit with other initiatives and to achieve the goals of audit effectively. Clinical effectiveness and clinical governance may offer a means of facilitating this integration.

Regression diagnostics for the class A regressive model with quantitative phenotypes.

Regression diagnostic methods are developed and investigated under the Class A regressive model proposed by Bonney [(1984) Am J Med Genet 18:731-749]. We call a family whose phenotypic distribution does not conform to the same genetic model as the majority of the families an etiotic family. The exact case-deletion approach for identifying etiotic families, based on examining the changes in each model parameter estimate by excluding one family at a time, is very time-consuming. We proposed three alternative diagnostic methods: the empirical influence function (EIF), the one-step approximation, and the approximated one-step approach. These methods can be computed efficiently and were incorporated into the existing software package S.A.G.E. A thorough Monte-Carlo investigation of the performance of the diagnostic methods was conducted and generally supports the EIF approach as the recommended alternative. The phenotypic variance is the parameter whose associated regression diagnostic most frequently and correctly identified etiotic families in the models that were examined. An analysis of body mass index data from 402 individuals in 122 Muscatine, Iowa families is used to illustrate the methods. A Class A regressive model with a recessive major locus and equal mother-offspring and father-offspring correlations provided the best-fitting model. The proposed regression diagnostics identified up to 7.4% of the 122 families as etiotic. As a result of this investigation, case-deletion diagnostic assessment is now a practical component in the analysis of quantitative family data.

Candidate genes for nonsyndromic cleft lip and palate and maternal cigarette smoking and alcohol consumption: evaluation of genotype-environment interactions from a population-based case-control study of orofacial clefts.

Previous studies suggest that the relationship between genes and nonsyndromic cleft lip +/- cleft palate (CLP) or cleft palate only (CP) may be modified by the environment. Using data from a population-based case-control study, we examined allelic variants for three genes, i.e., transforming growth factor alpha (TGFA), transforming growth factor beta 3 (TGFB3), and Msh (Drosophila) homeobox homolog 1 (MSX1), and their interactions with two exposures during pregnancy (maternal cigarette smoking and alcohol consumption) as risk factors for CLP and CP. For each cleft phenotype, risk estimates associated with most allelic variants tended to be near unity. Risk estimates for maternal smoking (> or = 10 cigarettes/day) were significantly elevated for CP and were most elevated among infants with allelic variants at the TGFB3 or MSX1 sites. By comparison, risk estimates for maternal alcohol consumption (> or = 4 drinks/month) were significantly elevated for CLP and were most elevated among infants with allelic variants at the MSX1 site. Our results suggest that development of CLP and CP may be influenced independently by maternal exposures but more significantly by interaction of such exposures and specific allelic variants.

Longitudinal analysis of scaling VO2 for differences in body size during puberty: the Muscatine Study.

PURPOSE: The purpose of this study was to determine an appropriate method to "normalize" oxygen uptake (VO2) for body size in children and adolescents. METHODS: We examined allometric scaling factors for a cohort of 126 children (mean age at baseline = 10.3 yr) participating in a 5-yr follow-up study. Each year for 5 yr we measured peak VO2, submaximal VO2, body mass, height, body composition, and sexual maturation. We sorted the 5-yr data set by sexual maturation and gender and then used the generalized estimating equation method to estimate regression parameters that described the influence of log transformed body mass on log transformed VO2. All analyses were repeated using log transformed fat-free body mass (FFM) in lieu of log transformed body mass. RESULTS: Models using FFM appeared better at eliminating the effect of body size on VO2. In boys a univariate model with a FFM exponent of 0.91 and in girls a univariate model with a FFM exponent of 0.87 satisfactorily normalized peak VO2. However, we could not identify a common body size exponent for both boys and girls. CONCLUSIONS: Results support the use of allometric scaling of VO2 as a function of FFM for maturing boys and girls but indicate that the effects of maturation on the relationship between VO2 and body size differ between boys and girls.

Asthma and allergic rhinitis in adoptees and their adoptive parents.

BACKGROUND: Since the highest risk for the development of atopic disease is in early life, environmental risk factors need to be separated from the genetic component in this high risk period. Adoptees removed at birth and placed in adoptive families present a way to separate environmental and genetic factors at this early susceptible age. METHOD: An opportunity for a pilot study of asthma and allergic rhinitis in adoptive families was presented when a psychiatrist (RC) was planning a behavioral study of young adult adoptees and their adoptive parents. A detailed questionnaire about allergic rhinitis and asthma was added after the psychiatrists' interview. Placement was not influenced by a history of allergy in adoptive or natural parents. The adoptee and at least one adoptive parent completed questionnaires in 367 families. The adoptees had been removed at birth and placed in the adoptive family within 3 months (83% within 1 month). RESULTS: Compared with adoptive families without asthma or allergic rhinitis, an adoptive mother with asthma or rhinitis, when the adoptive father was not affected, increased the risk for asthma in the adoptee (OR = 3.2, P < .0005). Asthma in the adoptive mother alone (OR = 3.2, P < .005) and allergic rhinitis alone (OR = 3.4, P < .005) increased the risk for asthma in the adoptee. Adoptive father asthma or allergic rhinitis showed a trend toward increased asthma in the adoptee (OR = 1.9, P < .1). CONCLUSION: This should be considered a pilot or feasibility study since subjects could not be examined or tested. Finding a risk for atopic respiratory disease or asthma associated with adoption by parents with asthma or allergic rhinitis suggests that further well planned adoptee studies should be made.

The effect of follow-up on limiting non-participation bias in genetic epidemiologic investigations.

The use of a comprehensive follow-up strategy to limit non-participation bias was evaluated in a population-based case-control study of orofacial clefts. Birth parents were requested to provide exposure data, and index children and parents were asked to provide blood specimens. Follow-up included telephone or postal reminders every two weeks for up to three months. Consent to participate was received from 281 (76.6%) case mothers and 246 (72.4%) case fathers. The corresponding totals for controls were 279 (54.7%) and 245 (49.8%). Evaluation of participation rates by intensity of follow-up showed that 23% of case and 18% of control families consented without reminders (first stage); 81% of cases and 83% of controls agreed following one or two reminders (second stage); and the remainder of participants consented following three or more reminders (final stage). Cumulative distributions of sociodemographic characteristics differed little between second and final stage participants. Odds ratios for maternal multivitamin use were similar between second and final stage participants, whereas those for maternal and paternal smoking tended to decline. Although follow-up measures were necessary to enroll most families, use of more than two reminders did not appear to increase the representativeness of the sample; however, termination of recruitment after only two reminders would have led to different conclusions. Future studies require data collection protocols that encourage participation from all population subgroups, and one alternative is presented.

Feasibility of collecting disease reports from relatives for genetic epidemiologic investigations.

Self-reports of disease from relatives are generally believed to be more detailed than those received from a family informant, although differential participation may exist among the relatives who provide information. To investigate the potential for differential participation, we requested permission to contact relatives of mothers (informants) who had provided family history information for a population-based case-control study of orofacial clefts. Birth defect and cancer self-reports were received from 345 (65.6%) case and 380 (68.8%) control relatives. Participants and nonparticipants differed little by type (maternal or paternal) or degree of relationship. Informants, however, were more likely to permit contact with relatives who were maternal, first-degree and female. Relatives appeared willing to provide self-reports, although the potential for differential selection introduced by informants should be considered.

Maternal interview reports of family history of birth defects: evaluation from a population-based case-control study of orofacial clefts.

Accurate family histories of birth defects are critical for risk assessment and etiologic investigations. Typically, information about family history of birth defects is ascertained from interviews with birth mothers of index children; however, the quality of these interviews is rarely assessed. We evaluated family history information provided by case (n = 28) and control (n = 29) mothers who participated in a population-based, case-control study of orofacial clefts. Interview responses from mothers were compared to questionnaire reports collected by mail from first- and second-degree parental relatives. A total of 345 case and 380 control adult relatives completed questionnaires. These relatives also provided reports for 130 case and 169 control offspring. To examine the quality of birth defect reports, the sensitivity and specificity of birth mother responses were calculated. Sensitivity for presence (yes/no) of a birth defect was 31% for case mothers and 9% for control mothers. Specificity for case and control mothers was 98% and 97%, respectively. Interview responses from mothers who participate in family genealogy were more likely to be concordant with relative reports than were responses from mothers who do not participate in family genealogy. Case mother responses were more likely to be concordant than control mother responses. These results suggest that reliance on interview reports from birth mothers may lead to an underestimation of the occurrence of birth defects in relatives. Future investigations should explore methods to improve the quality of informant reports about family histories of birth defects. One alternative approach is discussed.

Determinants of bone mineral density in postmenopausal white Iowans.

BACKGROUND: Osteoporosis is a major health problem for older individuals. For women, development of osteoporosis is a function of the accretion of "peak" bone mass in the third decade, age at menopause, and rate of bone loss with aging. Low bone mineral density (BMD) is a major risk factor for osteoporosis and fracture. The purpose of this study was to identify life style, nutritional, medical, and genetic predictors of low BMD in postmenopausal Iowa women. METHODS: One hundred thirty-four postmenopausal White women ranging in age from 57 to 81 years were included in this case-control study. Bone mineral density was measured at the femoral neck, using dual photon X-ray absorptiometry (Hologic 2000 QDR). Sixty-six women with BMD measurements below 0.68 g/cm2 (the bottom quartile of the BMD distribution in the population from which participants were recruited), and 68 women with values at or above 0.83 g/cm2 (the top quartile of the BMD distribution in the same population) were included. Information about environmental, nutritional, medical, and life style modifiers of BMD was obtained by written questionnaire and telephone interview. To assess familial factors that might influence BMD, we obtained a detailed family history for each participant. In addition, we tested the hypothesis that allelic variation at the Vitamin D receptor (VDR), and the type I collagen gene (COL1A1 and COL1A2) loci influence BMD. RESULTS: Weight, loss of height, age, and age at menopause were strong predictors of BMD in our population. After adjustment for these differences, we found no effect of genotype at the COL1A1, COL1A2, and VDR loci on BMD. CONCLUSIONS: Bone mineral density is a complex trait that is influenced by several different modifiers; in the present study, weight was the best predictor of postmenopausal BMD. While several studies suggest that VDR genotype is an important determinant of BMD, we did not find this association in our population, nor did we identify an association between allelic variation at the type I collagen gene loci and BMD. Identification of genes that determine body mass index may provide additional insight into risk factors for low BMD, and osteoporotic fractures.

Evaluation of color kinesis, a new echocardiographic method for analyzing regional wall motion in patients with dilated left ventricles.

The recently developed echocardiographic technology of color kinesis (CK) displays endocardial motion in color layers on a single end-systolic 2-dimensional echocardiographic frame. Previous work using this method is promising for quantitation of regional function, but there is limited experience in patients with severely reduced left ventricular function. Twenty patients (age 59 +/- 10 years) with dilated cardiomyopathy (left ventricular ejection fraction 22 +/- 8%) underwent CK imaging. Endocardial motion was quantitated by measuring the distance of endocardial motion during the systolic interval and also by calculating the endocardial velocity. CK measurements were compared among 4 wall motion grades (i.e., normal, hypokinetic, akinetic, and dyskinetic) assessed by qualitative wall motion scoring. There was a significant overall difference (p < 0.0001) in the mean systolic endocardial inward motion (i.e., contraction) and outward motion (i.e., expansion) among wall motion grades. The mean endocardial outward distance was significantly greater for the dyskinetic segments than for the other grades (p < 0.001). There were also differences in the mean velocity of endocardial motion among the wall motion grades. In the presence of left bundle branch block, there was no difference in the mean endocardial inward distance of the hypokinetic, akinetic, and dyskinetic septal segments. We conclude that in the absence of left bundle branch block, normal, hypokinetic, akinetic, and dyskinetic ventricular wall segments may be distinguished in patients with dilated cardiomyopathy on the basis of endocardial motion measured with CK.