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Biomedical subjects

J K Hewitt

Publications and source records attributed to J K Hewitt.

At least 19 recordsLinked to original sources

Are vaginal and rectal pressures equivalent approximations of one another for the purpose of performing subtracted cystometry?

OBJECTIVE: To determine if rectal and vaginal pressures are clinically equivalent to one another for the purpose of calculating subtracted detrusor pressure during routine filling cystometry and pressure-flow voiding studies. METHODS: A total of 140 consecutive filling and voiding cystometrograms were performed at separate sessions on 127 female patients undergoing routine clinical cystometry for a variety of clinical indications, usually urinary incontinence. In all cases, intravaginal as well as intrarectal pressures were measured simultaneously using microtip transducer pressure catheters, and two subtracted detrusor pressures were calculated throughout each study. Rectal and vaginal pressure measurements from the same patient were compared with the patient in the supine position with an empty bladder, in the erect position with a full bladder, and in the sitting position during voiding at the point of maximum urinary flow. RESULTS: The mean pressures were similar in all cases. Although there was no statistical difference in the mean differences between the rectal and vaginal pressures in the supine-empty position (P = .5528), significant differences were noted between them in the erect-full and sitting-voiding positions (P = .0016 and P = .0033, respectively). Linear regression analysis of the data obtained in each position was carried out, plotting vaginal pressure on the x axis and rectal pressure on the y axis. The corresponding r values for each position were 0.431 for the supine-empty position, 0.547 for the erect-full position, and 0.478 for the sitting-voiding position, indicating poor correlation between pressures in individual patients. In nine patients (6.5%) with significant vaginal relaxation and large cystoceles, a steady rise in vaginal pressure was noted during bladder filling. In six patients (4.4%), one or more spontaneous vaginal contractions were noted during the course of the study, whereas in 68 (48.9%), spontaneous rectal contractions were present. Of the 68 cases where spontaneous rectal contractions were noted, these contractions faded away in 53 cases (77.9%) as the study progressed. CONCLUSIONS: Rectal pressure and vaginal pressure are not the same during filling and voiding cystometry. Although they are reasonable approximations of each other for most qualitative clinical diagnostic purposes, potentially significant differences in subtracted detrusor pressure may occur, depending on which pressure is used as the approximation of intra-abdominal pressure. This may affect clinical management decisions in individual patients. The technique used for approximating abdominal pressure must be stated clearly in any report or publication dealing with subtracted cystometry.

Adult

Urodynamic characteristics of women with complete posthysterectomy vaginal vault prolapse.

OBJECTIVES: To review the symptoms and lower urinary tract function in women with posthysterectomy vaginal vault prolapse. METHODS: A retrospective review was carried out of the urodynamic records of 19 women with posthysterectomy vaginal vault prolapse who had been evaluated in the Bladder Function Laboratory of the Department of Obstetrics and Gynecology at Duke University Medical Center. RESULTS: A full urodynamic evaluation was carried out on 19 women who had had a hysterectomy and who had subsequently experienced complete prolapse of the vaginal vault. Vaginal eversion produced massive distortion of the lower urinary tract and was associated with complex symptoms. Among the cystometric findings in these patients was an early average first desire to void (94 mL) and a reduced average cystometric capacity (370 mL). Symptoms of voiding difficulty were common. During noninstrumented uroflowmetry, the average peak and mean flow rates were reduced in these women (16.5 mL/s and 8.1 mL/s, respectively), suggestive of functional obstruction of the outlet due to the prolapse. Pressure-flow voiding studies showed a reduced peak flow rate (11 mL/s) with an increased detrusor pressure at peak flow (50 cm H2O), also indicative of functional obstruction. All women underwent urethrocystoscopy, and no patient had a urethral stricture or urethral stenosis. Although symptoms of urgency (79%) and urge incontinence (63%) were common, detrusor instability was confirmed by urodynamic studies in only 3 women (16%), suggesting that urge-related symptoms in these women may often be due to anatomic distortion of the lower urinary tract rather than to detrusor overactivity. "Genuine" stress incontinence was documented in only 2 women (11%) during cystometry; however, when these patients were examined with full bladders with their prolapses reduced and returned to a normal anatomic position with a single-bladed speculum, the physical sign of stress incontinence was demonstrated in all 9 women (47%) who had a complaint of stress incontinence. This suggests that massive vaginal prolapse may mask an incompetent continence mechanism, which may then be revealed after surgical repair of the prolapse. CONCLUSIONS: Women with posthysterectomy vaginal vault prolapse present complicated reconstructive problems for the pelvic surgeon. The same pathophysiological process may produce both voiding dysfunction and stress incontinence. These patients should be evaluated carefully before surgical repair is undertaken. Stress incontinence may not be demonstrated in these patients unless they are examined with a full bladder with their prolapse carefully reduced to a normal anatomic position. Women who demonstrate stress incontinence with the vaginal prolapse reduced and the urethra supported normally should be suspected of having "type III" incontinence (demonstrable stress incontinence in the presence of normal urethral support). Women with these findings may require a suburethral sling procedure if they are to remain continent after correction of posthysterectomy vaginal vault eversion.

Adult

The application of structural equation modeling to maternal ratings of twins' behavioral and emotional problems.

The application of structural equation modeling to twin data is used to assess the impact of genetic and environmental factors on children's behavioral and emotional functioning. The models are applied to the maternal ratings of behavior of a subsample of 515 monozygotic and 749 dizygotic juvenile twin pairs, ages 8 through 16, obtained through mailed questionnaires as part of the Medical College of Virginia Adolescent Behavioral Development Twin Project. The importance of genetic, shared, and specific environmental factors for explaining variation is reported for both externalizing and internalizing behaviors, as well as significant differences in the causes of variation in externalizing behaviors among young boys and girls. The usefulness of applying structural equation models to data on monozygotic and dizygotic twins and the potential implications for addressing clinically relevant questions regarding the causes of psychopathology are discussed.

Adolescent

The analysis of parental ratings of children's behavior using LISREL.

A common procedure for assessing children's behavior is to obtain parental ratings of the child. Since the ratings obtained are a function of both parent and child, disentangling the child's phenotype from that of the rater becomes an important methodological problem. For the analysis of genetic and environmental contributions to children's behavior, solutions to this are available when multiple raters, e.g., two parents, rate multiple children, e.g., twins. This paper describes and illustrates simple LISREL models for the analysis of parental ratings of children's behavior. We show how the assumption that mothers and fathers are rating the same behavior in children can be contrasted with the weaker alternative that parents are rating correlated behaviors. Given the stronger assumption, which appears adequate for ratings of children's internalizing behavior problems, the contribution of rater bias and unreliability may be separated from the shared and nonshared environmental components of variation in a behavior genetic analysis.

Adolescent

Childhood behavior problems: a comparison of twin and non-twin samples.

This study compares standardized measures of childhood behavior problems in a community-based twin sample with those for normative samples from the general population. Maternal parent ratings on the Child Behavior Checklist (CBCL) for 1824 twins were compared with the CBCL normative sample. The results indicated that twins showed small but consistently higher levels of problem behaviors. These elevations were significant for older children on both internalizing and externalizing behaviors; for younger children the elevations were significant for externalizing but not internalizing behaviors.

Adolescent

Multivariate genetic analysis of blood pressure and body size. The Medical College of Virginia Twin Study.

BACKGROUND: In subjects of all ages, those who weigh the most often have the highest blood pressure. Thus, in epidemiological studies, weight is the most important correlate of blood pressure. Using the data from the Medical College of Virginia Twin Study, we asked these questions: 1) Do the same genetic paths that regulate body size also regulate systolic and diastolic blood pressure? 2) Are there distinct genetic pathways that regulate each of these variables? 3) Does environment play a major regulatory role? 4) Are the correlations among these variables mainly due to genetic or environmental effects? 5) Do genetic paths that regulate body size mediate the correlation between systolic blood pressure and diastolic blood pressure? METHODS AND RESULTS: We ascertained 253 Caucasian twin pairs living in the Commonwealth of Virginia. The average age was 11.2 +/- 0.2 years. We used multivariate path analyses to investigate the genetic relations among systolic blood pressure, diastolic blood pressure, and body size. We found that there was a highly significant genetic relation between systolic blood pressure and body size and between systolic and diastolic blood pressure. There are genetic paths that are shared within these two sets of variables, but in each case, the paths for each pair appear to be separate from one another. CONCLUSIONS: These analyses provide a method to partition correlation coefficients found in epidemiological studies into genetic and environmental components. The correlations found among these three variables are in large part due to these genetic relations. We found no genetic relation between diastolic blood pressure and body size.

Blood Pressure

Evidence for independent genetic influences on obesity in middle age.

The National Heart, Lung, and Blood Institute (NHLBI) Twin Study provided longitudinal data on a cohort of 514 pairs of adult male twin pairs who were examined at approximate ages of 48, 57, and 63 years. Because the sample was selected from military veterans, height and weight data were also available from their induction physical examinations when they were approximately 20 years of age. From the total NHLBI Twin Study cohort, 124 monozygotic and 119 dizygotic male twin pairs had complete data available for both members of the pair at induction and three examinations spanning 43 years of adult life. Using these data, the contributions of genetics and shared and non-shared environmental factors to BMI over the 43 year period were estimated by model fitting procedures. Model fitting included both a factor decomposition of these effects as well as a developmental path model. Results from the decomposition procedure indicate significant genetic effects at each examination cycle. Fitting a developmental path model, two independent genetic contributions to the variability of BMI were found: one at, or prior to, the induction examination about age 20, and a second between ages 20 and 48. Significant non-shared environmental contributions at each examination were also indicated, but shared environmental effects were not significant. We conclude that cumulative genetic effects explain most of the tracking in obesity over time; non-shared environmental effects, although significant at each age, are relatively short-lived and make only a minor contribution to tracking.

Adult

Bivariate genetic analysis of left ventricular mass and weight in pubertal twins (the Medical College of Virginia twin study).

Left ventricular (LV) hypertrophy in adults is a recognized risk factor for the subsequent development of cardiovascular morbidity. To make informed preventive health decisions it is important to understand the interaction of genes and environment on LV mass. In both children and adults, weight is a strong correlate of LV mass. We hypothesized that genetic influences common to both of these variables could in part explain the strong relation between weight and LV mass in children. In a population of 341 twins (11 years old), these questions were asked: (1) How much of the total variance of LV mass is under genetic control? (2) After accounting for weight and weight adjusted for sexual maturity, how much of the remaining variance is genetic? (3) Of the total genetic variance, what proportion is specific for LV mass and what proportion is common to both weight and LV mass? (4) How much of the correlation between these 2 variables is explained by genes common to both LV mass and weight? Univariate genetic analyses documented that genes operating at different magnitudes in boys (63%) and girls (71%) explain a significant proportion of the variance of LV mass. After removing the effect of weight and sexual maturity by regression methods, genes remain an important influence. Bivariate genetic analyses confirmed that genes common to LV mass and weight significantly influence the covariation of these variables and that greater than 90% of the correlation of LV mass and weight is due to common genes.

Body Mass Index

Genetic analysis of cerebellar foliation patterns in mice (Mus musculus).

Four inbred strains of mice, DBA/2J, C57BL/10J, BALB/cJ, and SJL/J, were mated in a diallel cross. The cerebella of the F1 generation were examined for the presence (Type I) or absence (Type II) of an intraculminate fissure between vermian lobule IV and vermian lobule V (the ventral and dorsal lobules of the culmen). One strain (DBA/2J) consistently expressed the Type I pattern. Another strain (SJL/J) expressed predominantly the Type II pattern. The other two strains (C57BL/10J and BALB/cJ) and many of the hybrids exhibited variability in their expression of the foliation patterns. The results were analyzed using biometrical genetic procedures and showed significant additive and dominance genetic effects and a maternal effect. Correlations of these cerebellar anatomical variants with the development of behavior are discussed.

Animals

Genetics of Type A behavior in two European countries: evidence for sibling interaction.

Young male twins in The Netherlands and England completed the Jenkins Activity Survey (Dutch and English versions, respectively), a measure of Type A behavior. Separate model fitting analysis revealed a similar pattern of variance estimates and associated goodness of fit across the two countries. The data were then analyzed concurrently, with a scalar parameter included to account for differences in variance due to the disparity of the measurement scales. A model including additive genetic and individual environmental effects gave a good explanation to the data. The heritability estimate was 0.28. Models of social interaction and dominance explained the data even better, the former being preferred. The twins' parents were included in the analysis to examine population variation for Type A behavior intergenerationally. There was evidence for individual environmental experiences having a greater influence on Type A behavior in the older generation.

Adolescent

The structure of schizotypy: a pilot multitrait twin study.

This report of a pilot study examines 29 pairs of twins from a population-based registry on whom four domains of schizotypy have been measured: personal interview using the Structured Interview for Schizotypy, self-report questionnaire formed from eight published self-report scales, attentional battery of eight individual tests, and root mean square error on smooth pursuit eye tracking. Analyzing the twins as individuals revealed two independent dimensions of clinically rated schizotypy (positive symptom schizotypy and negative symptom schizotypy) and two independent dimensions of self-rated schizotypy (positive trait schizotypy and trait anhedonia). Positive symptom schizotypy was highly correlated with positive trait schizotypy, but not with attentional dysfunction or eye-tracking error. By contrast, negative symptom schizotypy was significantly related to trait anhedonia, attentional dysfunction, and eye-tracking error. Correlations in monozygotic and dizygotic twins suggested that genetic factors were important in all four domains of schizotypy. Except for eye-tracking error, the results are more consistent with a dimensional than a "disease" model of schizotypy. Replication of these results with a larger group of subjects is needed.

Adult

A twin study approach towards understanding genetic contributions to body size and metabolic rate.

The genetic and environmental determinants of a brief assessment of metabolic rate at rest and under psychological stress were studied in 40 pairs of monozygotic and 40 pairs of dizygotic young adult male twins. Height, weight and age were employed as covariates. Univariate analyses showed a high heritability for height and weight and moderate heritability for metabolic rate. Classical twin analyses and multivariate genetic modeling indicated that genetic influences on resting metabolic rate were entirely explained by body weight: there was no independent genetic contribution to resting metabolic rate. Metabolic rate under psychological stress, on the other hand, showed a significant genetic effect. The exponent (3/4) in the power function relating body weight to resting metabolic rate was the same as that found in a wide variety of animal species, a value that has been proposed as defining a body weight set point. We speculate that an adult body weight set point is genetically transmitted. Independent genetic effects on resting metabolic rate would be observed only when the normal equilibrium between body weight and metabolic rate is unbalanced during development, aging or disease. The study illustrates the use of multivariate genetic analyses of twin data which may be readily applied to widely used metabolic rate assessments.

Adolescent

Personality and reproductive fitness.

The relationship between reproductive success (number of biological children) and personality was explored in 1101 postmenopausal females from the Australian twin registry. The quadratic response surface relating fitness to extraversion (E) and neuroticism (N) showed a saddle point at intermediate levels of E and N. Selection was shown to be stabilizing, i.e., having an intermediate optimum, along the axis low E, low N-high E, high N and more mildly disruptive, having greater fitness in the extremes, along the axis low N, high E-high N, low E. Neither dimension of personality considered by itself showed a significant linear or quadratic relationship to reproductive success. Sections through the fitness surface, however, show selection tends to favor high neuroticism levels in introverts and low neuroticism levels in extroverts.

Family Characteristics

Lipoprotein and oxygen transport alterations in passive smoking preadolescent children. The MCV Twin Study.

We investigated the cardiovascular effects of lifelong passive cigarette smoke exposure in preadolescent children and examined the following questions: 1) Is systemic oxygen transport altered? 2) Are coronary heart disease risk factors adversely affected? We recruited 216 families from the MCV Twin Study; 105 had at least one smoking parent. Serum thiocyanate and cotinine levels were used as measures of smoke exposure in the children and thiocyanate was proportional to the number of parental cigarettes smoked each day (p = 0.0001). Paternal smoking had no effect on these measures. Whole blood 2,3-diphosphoglycerate was higher in smoke-exposed than unexposed children (p less than 0.01) and was related to the thiocyanate level (p less than 0.02). High density lipoprotein (HDL) cholesterol was lower in passive smoking children (p less than 0.05); the HDL2 subfraction was reduced in passive smoking boys, while the HDL3 subfraction was reduced in passive smoking girls. Significant adverse alterations in systemic oxygen transport and lipoprotein profiles are already present in preadolescent children exposed to long-term passive cigarette smoke, primarily from maternal smoke. Children with long-term exposure to passive smoke may be at elevated risk for the development of premature coronary heart disease.

2,3-Diphosphoglycerate

Genetic analysis of anthropometric measures in 11-year-old twins: the Medical College of Virginia Twin Study.

We have conducted a cross-sectional analysis of the genetic and environmental contributions to the variance of anthropometric measurements in children during early adolescence. Univariate path analysis was used to estimate the relative contributions of genes, individual environment, and family environment to measures of childhood obesity in 259 11-y-old Caucasian twin pairs. Triceps, subcapular, and suprailiac skinfold thicknesses, as well as waist circumferences, ht, and wt were measured in a standardized protocol. In this sample, a parsimonious model that included only additive genetic effects and environmental factors unique to the individual provided an adequate explanation for the variation in ht, wt, quetelet index, and subscapular and triceps skinfolds. In this largely preadolescent population, different magnitudes of genetic effects were seen in males and females for waist circumference, biiliac diameter, and suprailiac skinfold.

Anthropometry

Univariate genetic analysis of blood pressure in children (the Medical College of Virginia Twin Study).

The relative contributions of genetic, individual environmental and shared environmental effects on resting blood pressure (BP) and heart rate (HR) were studied in prepubescent twins. The study population consisted of 251 caucasian 11-year-old twin pairs. Correlations were higher for all variables in monozygotic twins compared to dizygotic twins; this is consistent with a significant genetic effect. Path analysis revealed that the model of additive genetic and individual environmental effects fit systolic BP, diastolic BP and HR. In boys and girls, sex-specific genetic effects controlled systolic BP. The magnitudes of the sex-specific genetic effects on systolic BP were similar in both boys and girls and accounted for 66% of the variance. In boys, for diastolic BP, genetic effects accounted for 64% of the variance while in girls they accounted for 51%. These results provide no evidence for different genetic effects on HR in boys or girls. No shared environmental effects were detected. The large sample size and design, using different-sex dizygotic twins of the same age, establish that genes play an important role in the influence of resting BP and HR and that there are sex-specific genetic contributions in early pubertal children.

Blood Pressure

Testing structural equation models for twin data using LISREL.

Simple genetic models can be fitted to twin data using software packages such as LISREL (Jöreskog and Sörbom, 1986a). After discussion of data preparation and routine checks on possible violation of assumptions of the twin method, we illustrate univariate, bivariate, and multivariate genetic models which can be tested in cross-sectional twin data using LISREL. These include models for cohort or cohabitation effects, genotype x sex interaction, and certain types of genotype x environment interaction and genotype-environment correlation.

Computer Simulation