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J K Hewitt

Publications and source records attributed to J K Hewitt.

At least 55 records · Page 3Linked 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↗

A model system for analysis of family resemblance in extended kinships of twins.

The "Virginia 30,000" comprise 29,698 subjects from the extended kinships of 5670 twin pairs. Over 80 unique correlations between relatives can be derived from these kinships, comprised of monozygotic (MZ) and dizygotic (DZ) twins and their spouses, parents, siblings, and children. This paper describes the first application of a fairly general model for family resemblance to data from the Virginia 30,000. The model assesses the contributions of additive and dominant genetic effects in the presence of vertical cultural inheritance, phenotypic assortative mating, shared twin and sibling environments, and within-family environment. The genetic and environmental effects can be dependent on sex. Assortment and cultural inheritance may be based either on the phenotype as measured or on a latent trait of which the measured phenotype is an unreliable index. The model was applied to church attendance data from this study. The results show that the contributions of genes, vertical cultural inheritance, and genotype-environment covariance are all important, but their contributions are significantly heterogeneous over sexes. Phenotypic assortative mating has a major impact on family resemblance in church attendance.

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↗

Environmental and genetic influences on alcohol use in a volunteer sample of older twins.

A growing literature supports genetic contributions to familial resemblance for alcohol use characteristics, but few studies have focused on the mechanisms underlying alcohol use among older persons. We report patterns of alcohol use in a U.S. volunteer sample of 3,049 female and 1,070 male twins aged 50 to 96. Significant gender and age effects were found for self-report measures of current and lifetime alcohol use, with greater intake among males and current and lifetime abstinence more common among older participants. Comparisons with data obtained 4 years previously revealed high stability for quantity and frequency of alcohol consumption. Twin pairs with more frequent social contact tended to be more similar for lifetime and current alcohol use. Biometrical genetic modeling results indicate that use of alcohol is highly familial, with both genetic and shared environmental factors contributing to initiation of alcohol use among men and women. Among drinkers, however, the degree of twin resemblance for consumption behaviors is low to moderate and appears to be regulated by shared genes rather than shared environments. These data are consistent with a multidimensional process, suggesting that the determinants of whether one drinks in older age differ from those underlying how much or how often alcohol is consumed.

Aged↗

Genetic and environmental influences on lifetime alcohol-related problems in a volunteer sample of older twins.

Few studies have employed genetically informative designs to study the causes of alcohol-related problems in nonclinical populations. We report patterns of alcohol abuse in a community-based U.S. volunteer sample of 3,049 female and 1,070 male twins aged 50 to 96. Significant gender and age effects were found for self-report measures of current and lifetime alcohol-related problems, with higher prevalence among males and lower frequency among older birth cohorts. Significant associations were found between severity of alcohol abuse (adapted from Feighner criteria) and age of drinking onset, parental history of alcohol problems and, among males, lower educational attainment. Model-fitting analyses based on data from 650 identical and 479 fraternal twin pairs indicate substantial family resemblance for a variety of definitions of lifetime alcohol abuse and alcohol problems. The median estimate of genetic variance across several definitions of alcohol problems was 38.5%, while that for shared environmental influence was 15.5%. Gender heterogeneity was not found for magnitude of genetic and environmental influences, but these comparisons were limited by low statistical power. Findings are discussed with reference to the literature on alcohol abuse among older adults and the genetic epidemiology of alcoholism.

Aged↗

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↗

Analyzing twin resemblance in multisymptom data: genetic applications of a latent class model for symptoms of conduct disorder in juvenile boys.

A model based on the latent class model is developed for the effects of genes and environment on multivariate categorical data in twins. The model captures many essential features of dimensional and categorical conceptions of complex behavioral phenotypes and can include, as special cases, a variety of major locus models including those that allow for etiological heterogeneity, differential sensitivity of latent classes to measured covariates, and genotype x environment interaction (G x E). Many features of the model are illustrated by an application to ratings on eight items relating to conduct disorder selected from the Rutter Parent Questionnaire (RPQ). Mothers rated their 8- to 16-year-old male twin offspring [174 monozygotic (MZ) and 164 dizygotic (DZ) pairs]. The impact of age on the frequency of reported symptoms was relatively slight. Preliminary latent class analysis suggests that four classes are required to explain the reported behavioral profiles of the individual twins. A more detailed analysis of the pairwise response profiles reveals a significant association between twins for membership of latent classes and that the association is greater in MZ than DZ twins, suggesting that genetic factors played a significant role in class membership. Further analysis shows that the frequencies of MZ pairs discordant for membership of some latent classes are close to zero, while others are definitely not zero. One possible explanation of this finding is that the items reflect underlying etiological heterogeneity, with some response profiles reflecting genetic categories and others revealing a latent environmental risk factor. We explore two "four-class" models for etiological heterogeneity which make different assumptions about the way in which genes and environment interact to produce complex disease phenotypes. The first model allows for genetic heterogeneity that is expressed only in individuals exposed to a high-risk ("predisposing") environment. The second model allows the environment to differentiate two forms of the disorder in individuals of high genetic risk. The first model fits better than the second, but neither fits as well as the general model for four latent classes associated in twins. The results suggest that a single-locus/two-allele model cannot fit the data on these eight items even when we allow for etiological heterogeneity. The pattern of endorsement probabilities associated with each of the four classes precludes a simple "unidimensional" model for the latent process underlying variation in symptom profile in this population. The extension of the approach to larger pedigrees and to linkage analysis is briefly considered.

Adolescent↗

Testing hypotheses about direction of causation using cross-sectional family data.

We review the conditions under which cross-sectional family data (e.g., data on twin pairs or adoptees and their adoptive and biological relatives) are informative about direction of causation. When two correlated traits have rather different modes of inheritance (e.g., family resemblance is determined largely by family background for one trait and by genetic factors for the other trait), cross-sectional family data will allow tests of strong unidirectional causal hypotheses (A and B are correlated "because of the causal influence of A on B" versus "because of the causal influence of B on A") and, under some conditions, also of the hypothesis of reciprocal causation. Possible sources of errors of inference are considered. Power analyses are reported which suggest that multiple indicator variables will be needed to ensure adequate power of rejecting false models in the presence of realistic levels of measurement error. These methods may prove useful in cases where conventional methods to establish causality, by intervention, by prospective study, or by measurement of instrumental variables, are unfeasible economically, ethically or practically.

Adoption↗

Genetic contribution to risk of smoking initiation: comparisons across birth cohorts and across cultures.

Self-report data on smoking initiation (whether the respondent admitted ever having smoked) were obtained from three large adult twin samples (Australia, N = 3,808 pairs; Virginia, N = 2,145 pairs; AARP, N = 3,620 pairs). Data were broken down into birth cohorts, and genetic models were fitted to test whether the decline, in more recent birth cohorts, in the percentage of individuals becoming smokers has led to a change in the relative contributions of genes and environment to risk of becoming a smoker. Despite a marked change in the proportion of male respondents who reported ever having smoked, we found no evidence for cohort differences in genetic and environmental effects (no Genotype x Cohort interaction). Significant differences in genetic and environmental parameters were found between sexes, and between the Australian and the two U.S. samples. In the U.S. samples, estimates of the genetic contribution to risk of becoming a smoker were 60% in men, 51% in women. In the Australian sample, heritability estimates were 33% in men, but 67% in women. Significant shared environmental effects on smoking initiation also were found, accounting for 23% of the variance in U.S. men, 28% of the variance in U.S. women, 39% of the variance in Australian men, and 15% of the variance in Australian women. In models that allowed for the environmental impact of cotwin smoking on a twin's risk of smoking initiation, estimates of the direct genetic contribution to risk of smoking initiation were comparable or higher (49-58% in U.S. women and 71% in Australian women; 58-61% in U.S. men, and 37% in Australian men).

Adult↗

Univariate genetic analysis of oxygen transport regulation in children: the Medical College of Virginia Twin Study.

We investigated the relative contributions of genetic, individual environmental, and shared environmental effects on 2,3-diphosphoglycerate (DPG) regulation in preadolescent children. In a population of 165 early pubescent boy and girl twin pairs (11.4 y old), of whom 63 were passive smokers, we asked: 1) Are there differences in the control of DPG levels between early pubertal boys and girls? 2) If present, are these differences influenced by exposure to passive cigarette smoke? Non-passive-smoking boys and girls had similar DPG levels. With exposure to passive smoke, DPG levels increased in boys (p = 0.02) but not in girls. Analysis of variance on DPG demonstrated a parental smoking effect (p = 0.008) and suggested an interactive effect between parental smoking and sex of the child (p = 0.08). Univariate genetic analyses suggested that genes operated at different magnitudes in boys (9%) and girls (39%) in explaining a significant portion of the variance in DPG. The magnitude of shared environmental influences was greater in boys (62%) than in girls (34%), whereas individual environmental effects were similar in boys (29%) and girls (26%). Early pubertal boys differ from girls in their regulation of DPG. Environmental stressors such as passive cigarette smoke may elicit different responses in males and females, even at an early age. The use of path analysis may provide important insights into the mechanisms and interactions of genetic and environmental effects that underly the childhood antecedents of atherosclerotic heart disease.

2,3-Diphosphoglycerate↗

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↗