Genome-wide linkage scan for quantitative trait loci underlying normal variation in heel bone ultrasound measures.

Quantitative ultrasound (QUS) traits are correlated with bone mineral density (BMD), but predict risk for future fracture independent of BMD. Only a few studies, however, have sought to identify specific genes influencing calcaneal QUS measures. The aim of this study was to conduct a genome-wide linkage scan to identify quantitative trait loci (QTL) influencing normal variation in QUS traits. QUS measures were collected from a total of 719 individuals (336 males and 383 females) from the Fels Longitudinal Study who have been genotyped and have at least one set of QUS measurements. Participants ranged in age from 18.0 to 96.6 years and were distributed across 110 nuclear and extended families. Using the Sahara ® bone sonometer, broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (QUI) were collected from the right heel. Variance components based linkage analysis was performed on the three traits using 400 polymorphic short tandem repeat (STR) markers spaced approximately 10 cM apart across the autosomes to identify QTL influencing the QUS traits. Age, sex, and other significant covariates were simultaneously adjusted. Heritability estimates (h²) for the QUS traits ranged from 0.42 to 0.57. Significant evidence for a QTL influencing BUA was found on chromosome 11p15 near marker D11S902 (LOD = 3.11). Our results provide additional evidence for a QTL on chromosome 11p that harbors a potential candidate gene(s) related to BUA and bone metabolism.

Longitudinal changes in calcaneal quantitative ultrasound measures during childhood.

UNLABELLED: This longitudinal study examined how calcaneal quantitative ultrasound (QUS) measures change during childhood while taking into account skeletal maturation, body mass index (BMI), and physical activity. The study reported sex differences in QUS growth curves and an inverse relationship between BMI and speed of sound (SOS) measures. INTRODUCTION: The aim of this study was to examine how calcaneal QUS parameters change over time during childhood and to determine what factors influence these changes. METHODS: The study sample consisted of a total of 192 Caucasian children participating in the Fels Longitudinal Study. A total of 548 calcaneal broadband ultrasound attenuation (BUA) and SOS observations were obtained between the ages of 7.6 and 18 years. The best fitting growth curves were determined using statistical methods for linear mixed effect models. RESULTS: There are significant sex differences in the pattern of change in QUS parameters (p < 0.05). The relationship between QUS measures and skeletal age is best described by a cubic growth curve in boys and a linear pattern among girls. Boys experience their most rapid growth in BUA and SOS in early and late adolescence, while girls experience constant growth throughout childhood. Adiposity levels were significantly associated with the changes in SOS among boys (p < 0.001) and girls (p < 0.01), indicating that children with higher BMI are likely to have lower SOS over time compared to children with lower BMI. For girls, physical activity levels showed positive associations with changes in QUS measures (p < 0.05). CONCLUSION: This study documents significant sex differences in the pattern of change in QUS measures over childhood and adolescence. Our study also shows significant influences of adiposity and physical activity on the pattern of change in QUS measures during childhood.

Sleep disturbance in relation to health-related quality of life in adults: the Fels Longitudinal Study.

OBJECTIVE: Sleep disturbances are prevalent problems in the general population. Symptoms of insomnia can impact various physical and mental conditions. Furthermore, sleep disturbances may worsen the quality of life independently of co-occurring medical conditions. In this study, we examined the relationships between self-reported sleep disturbance symptoms and health-related quality of life measures in the Fels Longitudinal Study. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 397 adults (175 men and 222 women) aged 40 years and older were included in the present study. MEASUREMENTS: Three self-reported sleep disturbance measures (difficulty falling asleep, nocturnal awakenings and maintaining sleep, and daytime tiredness) were collected between 2003 and 2006. Health-related quality of life measures were assessed using the Medical Outcomes Survey Short Form (SF)-36. Socio-demographic status (marital status, employment status, and education) and current medical conditions were collected from participants during study visits. RESULTS: Individuals who reported frequent sleep disturbances showed significantly worse quality of life on all SF-36 subscales examined. The odds ratio (OR) ranged from 1.71 to 18.32 based on symptoms of insomnia across seven SF-36 domains in analyses adjusted for significant covariates influencing quality of life. Participants with severe sleep disturbances (both sleep problems and daytime impairment) showed generally higher odds of reporting poor SF-36 scores (adjusted ORs; 5.88 - 17.09) compared to participants with no problems. CONCLUSION: Sleep disturbance is comprehensively and independently associated with poor health-related quality of life in middle-aged and older adults.

The first seriatim study into old age for weight, stature and BMI: the Fels Longitudinal Study.

PURPOSE: To document the serial status of measures of weight, stature and BMI from birth into old age. METHODS: Longitudinal measures of weight, stature and BMI were taken from birth to 76 years of age for 5 men and 7 women as part of the Fels Longitudinal Study. RESULTS: Sex-specific plots of means for weight, stature and BMI are presented that describe the changes and sex differences in these measurements between birth (or the first year of life) into old age. These serial data demonstrate a continuous increase in body weight through much of adulthood and a small decline in stature starting in late middle age. The plots for BMI indicate the early onset of overweight and subsequent obesity early in adulthood and its continuance into old age for men and women. CONCLUSIONS: These are the first plots of serial means for weight, stature and BMI measured from the same group of individuals from birth into old age. These findings demonstrate the changes in these measurements through childhood and maturity into old age. Similar data are needed for individuals from other racial/ethnic groups and countries in order to understand the aging process better.

Fetal age: methods of estimation and effects of pathology.

Accurate identification of fetal age is important in a wide variety of circumstances. Seventeen anthropometric and radiographic measurements were taken on fetuses between 15 and 42 weeks of gestational age, both with and without pathologic conditions. A full evaluation including radiographic, karyotypic, gross anatomic, and histologic examination of the fetus and placenta identified 72 individuals as nondysmorphic with no signs of chronic uterovascular insufficiency. These specimens served as the control group. Based on least-squares regressions of this group, age-estimation equations were calculated for all variables. Six models were adequately described by linear equations; the remaining 11 required a quadratic term. Based on standard error of the estimate (S(y:x)), skeletal measures proved the most accurate age estimators. Pathologic conditions were shown to have an influence on age estimation indicated by high levels of inaccuracy and, in some instances, significant bias.

The vomeronasal organ in the human embryo, studied by means of three-dimensional computer reconstruction.

The human vomeronasal organ is of interest because of its potential role in sex pheromone detection. Due to the scarcity of early human material, studies of its development have concentrated on fetal rather than embryonic stages. The availability of embryonic specimens in the Walmsley Collection has enabled us to study the development of the vomeronasal organ (VNO) in human embryos between Carnegie Stages 17 and 23. Embryos at Carnegie Stage 17 or below showed no evidence of a VNO. One embryo with characteristics intermediate between Carnegie stages 17 and 18 was the earliest to show evidence of a VNO, in the form of a shallow indentation. All embryos at Carnegie Stages 18 or later had VNOs. Three-dimensional computer reconstructions were made of the VNO in each specimen where this was possible. This in part depended on the plane of section. The total volume and lumen volume were measured from these reconstructions and the volume of the vomeronasal epithelium was calculated by subtraction. A generally consistent increase in total volume and epithelial volume was observed with increasing developmental stage. The lumen contributed rather little to the total volume at these stages.

Measurement of specific gravity as a surrogate for urinary flow rate--a singular study.

About two hundred and fifty urine samples were collected some years ago in the course of experimental exposure of one individual to benzene vapor. Phenol concentrations and specific gravities were recorded, together with the volume of urine samples and the times of voiding. Review of this data shows that the reciprocal of specific gravity minus unity (SG-1) measured by refractometer correlated closely with urinary flow rate, while those using the traditional urinometer correlated much less closely. If this is valid for all workers, then refractometer measurement of specific gravity may be used as a surrogate for flow rate. More consistent interpretation of spot urine sampling results as a measure of intake of hazardous substances through occupational exposure is then possible. This is particularly the case if used in conjunction with the formula developed and tested by Araki et al. for flow rate adjustment.

Pneumatic processes in the temporal bone of chimpanzee (Pan troglodytes) and gorilla (Gorilla gorilla).

The ontogeny of human temporal bone pneumatization has been well studied from both comparative and clinical perspectives. While a difference in the extent of air cell distribution has been noted in our closest living relatives, chimpanzees and gorillas, the processes responsible have been relatively unexplored. To examine these processes, a large, age-graded series of hominoid skulls was radiographed and the progress of pneumatization recorded. Additionally, a subsample of 30 chimpanzees and 12 gorillas was subjected to high-resolution CT scanning. Neonatal specimens show a well-developed mastoid antrum, as well as a capacious hypotympanum extending into the petrous apex. In African apes, as in humans, the mastoid antrum serves as the focus for air cell expansion into the mastoid and immediately adjacent areas. In chimpanzees and gorillas, however, a pronounced lateral structure, described as the squamous antrum, serves as the focus of pneumatization for anterior structures such as the squamous and zygomatic. The diminution of this structure in Homo sapiens explains the difference in air cell distribution in these regions.

Structure and validation of a pharmacokinetic model for benzene.

A pharmacokinetic model for benzene has been developed and validated for the inhalation aspects of its operation. The validation shows reasonable agreement between the model outputs and human biological data for phenol in urine, benzene in alveolar air, and benzene in mixed exhaled air.

New PBPK model applied to old occupational exposure to benzene.

An intensive program of benzene monitoring using new techniques was undertaken in Western Europe in the late 1960s and early 1970s. Significant exposure was found in the transport of benzene and gasoline, particularly during the loading of barges, and during the loading and operation of sea-going vessels. The ceiling threshold limit value of 25 ppm recommended at that time generated problems in assessing exposure, so alternative criteria were proposed. During that period some shore-based exposures were reported, and their significance was discussed in several articles. The information gained at that time is reexamined by physiologically based pharmacokinetic (PBPK) modeling and is used to help validate an improved PBPK model, which is described and tested on results from experimental exposure in a companion article. The old field data, comprising five specific studies, confirm the relevance of modeling to assessment of occupational exposure, and demonstrate its value for interpretation of field data, which is seldom as complete, systematic, or accurate as that obtained in experimental work. The model suggests that metabolism of benzene in humans may not be restricted to the liver. Sites and processes of metabolism merit further investigation.

Pattern and process of growth of the abnormal human fetus.

Identifying patterns of fetal growth alteration benefits both the clinician and the researcher. Twenty-four measurements in three variable sets (anthropometric measures, organ weights, and long-bone measures from radiographs) were taken on fetuses both with and without pathological conditions that are suspected to result in growth alteration. In addition, radiographs of each case were examined for the presence or absence of ossification centers. Based on least-squares regressions of the normal group, we calculated standardized residuals for the affected group to identify patterns of growth alteration. A large sample of fetuses between 15 and 42 weeks of gestational age with a variety of pathological conditions is described and evaluated for growth alterations. Symmetric and asymmetric growth alteration was detected in a small part of the sample and was predominantly isolated to fetuses in the late third trimester. Although patterns of growth alteration have been suggested as a means for noninvasive diagnoses of syndromes (such as trisomy 21), no consistent patterns are discernible in the current group. The sample provides a unique opportunity to evaluate fetal growth in terms of the interaction between genetic and environmental influences.

The relationships between urinary elimination, airborne concentration, and radioactive hand contamination for workers exposed to uranium.

The purposes of this study were to estimate the proportional contribution of uranium dust exposure to urinary excretion of the metal, and to examine the influence of hand contamination on the elimination of uranium from the urine of workers who performed different jobs. The study was based on records taken from a gaseous diffusion plant in 1956. Regression techniques were used to investigate the relationship between uranium concentration in urine and exposure variables, including the concentration of uranium dust and the incidence of hand contamination. The proportional contribution of airborne to urinary uranium was estimated by the slope of this relationship. It is concluded that the workers eliminated uranium at relatively constant rates per unit air concentration (0.67 to 1.27 micrograms/L per micrograms/m3). In addition to airborne uranium, hand contamination significantly contributed to the elimination among maintenance crew, but not among production workers. Furthermore, the production index was shown to be a useful surrogate for airborne and urinary uranium.

Standardized residuals as a means for detection of growth alteration in the pathologic human fetus.

This paper introduces and discusses the use of standardized residuals as a technique for comparing the growth of normal and pathologic human fetuses. Anthropometric measures, radiographic measures, and organ weights were regressed on known gestational age of second- and third-trimester fetuses. Standardized residuals were calculated for a group of potentially growth-impaired fetuses. Use of residuals aids in identification of patterns of growth alteration in specific pathologies. Most important, studying the response of developing organ systems to a variety of insults may elucidate mechanisms of growth regulation in the fetus. We emphasize the special quality of the multivariate measures of the core sample of fetuses from the Akron Children's Hospital collection.

Cause and control: education and training of professional industrial hygienists for 2020.

By the year 2020, the environmental movement will have established a recognized profession, expert at studying deleterious effects in the working and public domains. Environmental science practitioners will be better able to identify and relate ill effects to the presence of adverse agents in the environment; they will not, however, necessarily be skilled at developing systems for control. Industrial hygienists should provide the unique and special skills required to establish economically optimum control systems. Industrial hygiene should by then have been redefined to emphasize this critical role of its professional members. A new orientation for education is therefore proposed to provide a sound basis for the professional needs of industrial hygienists who should be at the peak of their careers in 2020. Members of the profession should then be the leaders in research on, and practice of, the science and engineering of design, installation, and monitoring of control systems for occupational and environmental hazards. The preferred educational background for entry to the profession should be some branch of engineering, which by then must have recovered its lost status and be divided into fewer specialized compartments than it is today. Engineering should provide a broader base for students entering professional education in this field, who will be more concerned with prevention and engineering control of both occupational and environmental hazards, rather than with measurement and epidemiology of the biological and toxicologic sciences. Preparation for professional work in industrial hygiene will call for the specialized education of engineers required to design and maintain processes that minimize the use, production, or generation of hazardous substances.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment outcomes of Vietnam veterans with Posttraumatic Stress Disorder.

This study examined changes on the Millon Clinical Multiaxial Inventory for 45 Vietnam veterans who completed a specialized inpatient treatment program. The average length of stay for these veterans was 140 days. Patients' scores on the Millon decreased on 12 of the 20 scales and increased on 8, and their Posttraumatic Stress Disorder-related symptoms of anxiety and dysthymia decreased significantly. Posttraumatic Stress Disorder-related character styles, schizoid, avoidant, and passive-aggressive, also showed significant decreases.

Adapted character styles of Vietnam veterans with Posttraumatic Stress Disorder.

A total of 189 male Vietnam veterans who were admitted to a specialized inpatient treatment program were evaluated using the Millon Clinical Multiphasic Personality Inventory to assess character styles. The veterans were assessed for Posttraumatic Stress Disorder by using a subscale of the Minnesota Multiphasic Personality Inventory (MMPI) and 72% of the patients were classified as having Posttraumatic Stress Disorder. The character styles of passive-aggressive, schizoid, avoidant, and borderline were significantly associated with these patients. The most common 2-point profile was passive-aggressive and avoidant (8-2 or 2-8) and was significantly related to the diagnosis. While drug and alcohol abuse were common problem areas for the entire sample, the profile of patients with Posttraumatic Stress was different from those of substance abusers. These results indicate that treating Vietnam veterans with this disorder requires adopting strategies which include a character style focus as well as a symptom focus.

Pharmacokinetics of benzene in a human after exposure at about the permissible limit.

This limited range of experimental human exposure indicates that: 1. In the single experimental subject, the amount of benzene retained in the body 10 hours and more after exposure depends on the multiple of the concentration and duration of exposure. 2. At concentrations about the threshold limit value, the presence of other hydrocarbons does not affect the retention or elimination of benzene. 3. The amount of benzene retained in the body for 10 or more hours is dependent on the energy expenditure of the subject during exposure. There is reason to think that elimination after exposure is similarly affected. 4. While the principal route for elimination of benzene is the metabolite, conjugated phenol, in urine, the proportion eliminated in breath depends on the duration of exposure in the 1- to 8-hour range. 5. Three or four distinct compartments for retaining benzene are apparent and these may be identified with specific groups of organs in the body. 6. Mathematical modelling of the system can provide a reasonably accurate representation of benzene behavior in the body, and should enable dosage to individual or groups of organs to be estimated after occupational exposure. 7. Diurnal variation in the elimination of benzene after exposure may introduce a factor of uncertainty of about two into the prediction of exposure from biological monitoring. 8. Patterns of retention and elimination of toluene are very similar to those of benzene, though the principal metabolite in urine is different, and there may be a limit to the maximum amount that can be excreted by that route due to the relatively low solubility of hippuric acid in aqueous solutions.