Early development and tissue-specific patterns of insulin binding in chick embryo.

We studied the development of insulin binding to its receptor in chick embryos from days 2-18 of the 21-day incubation period. Using partially purified membrane preparations we found that insulin receptors on both brain and liver of day 18 embryos were typical insulin receptors by multiple criteria. Specific insulin binding to preparations of whole embryos was not detected on day 2, but was present by day 3. Insulin receptors were present on both heads and bodies of embryos by day 4. Binding to liver and brains increased with development between days 8 and 18; however, the patterns of increase in the two tissues were quite distinct. In liver, binding was low on day 8, but increased markedly by day 14 (P less than 0.01). Increases after day 14 were less impressive. In contrast, binding to brain preparations was relatively well established by day 8 and did not change significantly between days 8 and 14. An abrupt increase occurred between days 14 and 16 (P less than 0.01), and a second increase took place between days 16 and 18. We have previously shown that insulin is present in chick embryos before known pancreatic development. The current demonstration that insulin receptors are also present early in embryogenesis makes it possible that insulin may influence the embryo at early stages. In addition, the different patterns of increases in insulin binding in liver and brain during mid- to late development suggest complex and tissue-specific mechanisms of regulation.

Hypothalamic atrophy with progressive hypopituitarism in an adolescent girl.

The present report describes a 19-yr-old female with progressive hypopituitarism and diabetes insipidus. Pneumoencephalography demonstrated gross atrophy of the hypothalamus and a small pituitary gland. In the face of documented hypothyroidism and hypogonadism, basal pituitary trophic hormones were consistently detectable and responded briskly to releasing factor administration. This combination of an atrophic lesion of the hypothalamus with gradually evolving hypopituitarism but detectable and stimulable anterior pituitary hormones appears to represent a unique form of hypothalamic failure.

Insulin binding to erythrocytes of normal infants, children, and adults: variation with age and sex.

The assay of insulin receptors on erythrocytes requires only small amounts of blood and has made it possible to characterize insulin binding in infancy and childhood. To establish normal insulin-binding criteria, we studied 125I binding to insulin receptors on erythrocytes from a large number of normal subjects, including 15 term deliveries, 45 prepubertal children (aged 2 months-12 yr), 15 adult women, and 15 adult men. Insulin binding to cord erythrocytes was significantly higher at tracer and physiological insulin concentrations than binding to cells from any other age group (P less than 0.001). In the prepubertal children after the newborn period, insulin binding was not related to age or sex and did not differ significantly from the binding to cells from adult women. Erythrocytes from adult males, however, bound significantly higher amounts of insulin than did those from adult women or prepubertal children at all insulin concentrations tested (P less than 0.01). Increased binding to cord erythrocytes appeared to be due to an increase in receptor affinity, while the increased binding in adult males was primarily a result of increased receptor concentration. The data confirm previous reports of increased insulin binding to fetal cells and indicate that erythrocyte insulin binding stabilizes at levels similar to those in adult females by the age of 2 months. The increased binding of insulin to erythrocytes from adult males compared to binding to erythrocytes from children or adult females suggests that androgens may increase erythrocyte insulin binding over prepubertal levels.

A matched case-control study of convenience store robbery risk factors.

Convenience store clerks have been shown to be at high risk for assault and homicide, mostly owing to robbery or robbery attempts. Although the literature consistently indicates that at least some environmental designs are effective deterrents of robbery, the significance of individual interventions and policies has differed across past studies. To address these issues, a matched case-control study of 400 convenience store robberies in three metropolitan areas of Virginia was conducted. Conditional logistic regression was implemented to evaluate the significance of various environmental designs and other factors possibly related to convenience store robbery. Findings indicate that numerous characteristics of the surrounding environment and population were significantly associated with convenience store robbery. Results also showed that, on a univariate level, most crime prevention factors were significantly associated with a lower risk for robbery. Using a forward selection process, a multivariate model, which included cash handling policy, bullet-resistant shielding, and numerous characteristics of the surrounding area and population, was identified. This study addressed numerous limitations of the previous literature by prospectively collecting extensive data on a large sample of diverse convenience stores and directly addressing the current theory on the robbers' selection of a target store through a matched case-control design.

Convenience store robberies in selected metropolitan areas. Risk factors for employee injury.

Circumstances of injury were abstracted from police reports for 1835 convenience store robberies that occurred during 1992 or 1993 in selected metropolitan areas of seven eastern states. Subset analyses were performed using the data (758 robberies) from four states with relatively complete risk factor information. The purpose of this study was to estimate the risk of injury in a robbery situation for various risk factors. The overall risk of employee robbery-related injury could not be estimated because the probability of robbery is unknown. Of the 1835 robberies, 59% of the total robberies occurred at nighttime (9 p.m. to 3 a.m.), 47% occurred in stores previously robbed in the study period, 63% involved the use of a firearm, and 12% were associated with an injury to at least one employee. In the subset analysis of 758 robberies in four states, the employee probability of injury in a robbery was lower with firearm use compared with no weapon or use of a blunt instrument, and the probability of severe injury (defined as death, or an injury necessitating a trip to a hospital) was lower with a firearm compared with the use of a blunt instrument. However, all five fatalities were firearm-related. Other factors that were associated with a lower probability of employee injury included robbery occurrence in stores that had been robbed multiple times, compared with stores robbed only once; having 1 to 999 dollars stolen, compared with having no money stolen; and the presence of a customer(s) in the store at the time of the robbery. The employee risk of injury was not significantly different between one- (0.106) and multiple-employee (0.111) stores. Similarly, the employee risk of severe injury was not significantly different between one- (0.029) and multiple-employee stores (0.022). We conclude that there are several potential risk factors for employee injury in convenience store robberies, some of which are amenable to interventions. Further research on these factors and their relationship to employee injury is indicated.

Effectiveness of behavioral safety belt interventions.

A wide variety of approaches have been developed to promote safety belt use. This paper evaluates the relationship of types of behavioral safety belt programs to short- and long-term safety belt use rates. Five types of programs were examined: Law, Incentive, Education, Monitoring, and Prompt. Programs were generally effective in increasing use rates, with a median increase of 17.0% (95% CI = 13.4%, 20.1%). Program type differentially affected use rates, with Law and Incentive producing the highest increase in rates. Length of intervention and number of interventions within one program were not significantly related to use rates. Immediately after intervention ended, safety belt use declined but soon stabilized, with rates remaining significantly higher than baseline.

Ergonomic exposure assessment: an application of the PATH systematic observation method to retail workers. Postures, Activities, Tools and Handling.

This study examined biomechanical stressor variables (physical work exposures) in relation to job title, gender, and back-belt status in 134 retail store workers. The principal concerns were to quantitatively describe physical work exposures and to determine the degrees to which these quantitative variables correlated with job title and with the use of back belts. An additional objective was to assess the inter-rater reliability of the observation method. The systematic observation method employed was based on a modification of the PATH (Postures, Activities, Tools, and Handling) measurement method. Chi-square analysis indicated that the frequencies of bent or twisted postures followed the pattern of unloaders > stockers > department managers. For weight handled per lift, lower, or carry, the pattern was unloaders > department managers > stockers. The mean lifting frequencies per hour were 35.9 for department managers, 48.8 for stockers, and 137.4 for unloaders. Back-belt-wearing percentages were higher for unloaders (63%) compared with stockers (48%) and department managers (25%). Back-belt-wearing workers had higher levels of biomechanical stressor variables, including arm position, twisting, weight handled, and number of lifts per hour. Kappa statistics ranged from 0.5 to 0.63, a level of adequate or good reliability beyond chance. The method employed in this study is applicable in studies that require only fairly crude distinctions among biomechanical stressor variables. Nevertheless, this level of distinction may be sufficient when implementing intervention studies and control strategies for many material-handling-intensive jobs.

Asymptomatic primary hyperparathyroidism in children. Newer methods of preoperative diagnosis.

An asymptomatic 11-year-old boy was found to have primary hyperparathyroid secondary to an isolated parathyroid adenoma. This rare disorder of childhood can have asymptomatic hypercalcemia as its only manifestation. Parathyroid hormone assays and studies of urinary calcium excretion, especially the calcium-creatinine clearance ratio, distinguish parathyroid hormone excess from hypocalciuric forms of hypercalcemia. Real-time ultrasonography and dual-isotope subtraction scanning provide accurate, noninvasive, preoperative localization of abnormal parathyroid tissue. The prognosis of untreated, asymptomatic primary hyperparathyroidism in children is not known, and the indications for surgery are unclear. Diagnostic certainty is, therefore, especially important prior to surgical exploration.

Robbery characteristics and employee injuries in convenience stores.

BACKGROUND: Each year approximately 30,000 convenience store employees are at risk for injuries related to robberies and many are fatal. METHODS: A prospective cohort study of 460 convenience store robberies from 1 February 1995 to 30 September 1996 was conducted to uncover possible associations between injury and pertinent robbery circumstances and work environments. Data collection sources included police reports, employee interviews, store evaluations, and relevant Census data. Rate ratios and correlation statistics were calculated to identify associations with injury and relationships between variables. RESULTS: Injury risk was strongly associated with the following characteristics: employee resistance, robberies without firearms or money taken, daytime and merchandise robberies, stores with limited escape routes and no cash policy or drop safe, older clerks, and surrounding areas with lower valued buildings, less expensive rent, more vacant structures, and younger residents. Numerous intercorrelations between these characteristics were identified. DISCUSSION: Training opportunities, store procedures, and environmental designs are important factors to consider in reducing robbery-related injuries.

Urinary and serum steroid concentrations in the management of congenital adrenal hyperplasia. Lack of physiologic correlations.

Serum concentrations of 17-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, progesterone, testosterone, and androstenedione and 24-hour excretion of 17-ketosteroids and pregnanetriol were measured serially in 18 children with congenital adrenal hyperplasia (21-hydroxylase deficiency) during a two-year period. Correlations were sought between results of measurements of these steroids and clinical progress assessed by physical examination and skeletal maturity to determine if measurement of concentration of these substances at a single point in time could be used to gauge the dose of corticosteroids for optimum treatment. We found that these measurements of steroids were generally not useful indicators of optimum control of the disease. Repeated careful clinical examination and assessment of changes in growth velocity and skeletal maturation seem to be the best criteria on which to base dosage of corticosteroids used for therapy.

Power determination for geographically clustered data using generalized estimating equations.

Study designs in public health research often require the estimation of intervention effects that have been applied to a cluster of subjects in a common geographic area, rather than randomly assigned to individual subjects, and where the outcome is dichotomous. Statistical methods that account for the intracluster correlation of measurements must be used or the standard errors of regression coefficients will be under-estimated. Generalized estimating equations (GEE) can be used to account for this correlation, although there are no straightforward methods to determine sample-size requirements for adequate power. A simulation study was performed to calculate power in a GEE model for a proposed study of the effect of an intervention, designed to reduce lower-back injuries among nursing personnel employed in nursing homes. Nursing homes will be randomly assigned to either an intervention or control group and all employees within a nursing home will be treated alike. Historical injury data indicates that the baseline-injury risk for each home can be reasonably modelled using a beta distribution. It is assumed that the risk for any individual nurse within a nursing home follows a Bernoulli probability distribution expressed as a logit function of fixed covariates, which have values of odds ratios determined from previous studies which represent characteristics of the study population, and a random-intercept term which is specific for each home. Results indicate that failure to account for intracluster correlation can lead to overestimates of power as well as inflation of type I error by as much as 20 per cent. Although the GEE method accounted for the intracluster correlation when present, estimates of the intracluster correlation were negatively biased when no intracluster correlation was present. In addition, and possibly related to the negatively biased estimates of intracluster correlation, we also found inflated type I error estimates from the GEE method.

Unique features of the insulin receptor in rat brain.

We examined the structure of the affinity-labeled insulin receptors in rat brain, rat liver, and human IM-9 lymphocytes using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In gels run under reducing conditions, the alpha-subunit of the insulin receptor in brain had an apparent Mr of 127,000 distinctly lower than that seen in both rat liver and human lymphocytes (apparent Mr = 136,000). Exposure to neuraminidase increased the electrophoretic mobility of the liver receptor, but had no effect on the insulin receptor in brain. The carbohydrate moieties of the insulin receptors in rat brain and liver were further examined by chromatography on wheat-germ agglutinin agarose. The receptors in both tissues adsorbed to the wheat-germ agglutinin; elution with 0.3 M N-acetyl glucosamine resulted in slightly better recovery of the brain than of the liver receptor. Exposure to neuraminidase virtually abolished the interaction of the liver receptor with the lectin, whereas adsorption of the brain receptor was unaffected by neuraminidase. These results indicate that the insulin receptor in brain is distinguished from those in peripheral tissues by structural alterations, including changes in the carbohydrate moiety of the receptor. Such alterations contrast sharply with the previously observed similarities in insulin binding properties between insulin receptors in brain and other tissues. The implications of such structural alterations for the program of insulin action expressed by the receptors in brain remain to be explored.

The insulin receptor of rat brain is coupled to tyrosine kinase activity.

Insulin receptors from rat brain were studied for receptor-associated tyrosine kinase activity. In solubilized, lectin-purified receptor preparations, insulin stimulated the phosphorylation of the beta subunit of its receptor as well as of exogenous substrates. Phosphoamino acid analysis of casein phosphorylated by these preparations revealed that 32P incorporation occurred predominantly on tyrosine residues. Receptor and casein phosphorylations were specific for insulin and analogues that also bind to the insulin receptor. The insulin dose response for phosphorylation of brain receptor resembled that reported for the purified insulin receptor from human placenta (Kasuga, M., Fujita-Yamaguchi, Y., Blithe, D.L., and Kahn, C.R. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 2137-2141), suggesting similar insulin sensitivity and coupling of the brain receptor kinase. Four polyclonal antisera to the insulin receptor were able to bind and immunoprecipitate the brain receptor; however, only two antisera activated the receptor-associated kinase. Thus, the brain insulin receptor, like the well studied non-neural receptor, is coupled to tyrosine kinase activity, making regulation of cellular events by insulin in neural tissue possible.

Screening programs for congenital hypothyroidism. How can they be improved?

High-sensitivity neonatal hypothyroid screening tests are used throughout the country. Because of low specificity, primary care physicians are faced with an abundance of false-positive results that challenge the interpreting physician with clinical, economic, and medicolegal considerations. We surveyed 154 physicians caring for Wisconsin-born infants with the highest newborn-screen thyrotropin values in a two-year period. Our results indicated that (1) confirmation of thyroid normalcy is often delayed beyond 6 weeks of age; (2) there is wide variation among physicians regarding therapeutic goals if hypothyroidism is confirmed; and (3) physicians prefer autonomy in the management of congenital hypothyroidism. Modifications in hypothyroid screening programs may include confirmatory tests by a central laboratory (that distributes filter paper with all abnormal results), provision of a management decision tree for primary care physicians, and a one-time subsidy for a visit to a pediatric endocrinologist. We suggest that these modifications may improve the long-term outcome of hypothyroid infants identified by the screening program.