Biomedical subjects

A Pickles

Publications and source records attributed to A Pickles.

At least 73 records · Page 4Linked to original sources

PubMed1996

The effects of S-nitrosoglutathione on platelet activation, hypertension, and uterine and fetal Doppler in severe preeclampsia.

OBJECTIVE: To determine the effects of the platelet-specific nitric oxide donor S-nitrosoglutathione on women with severe preeclampsia. METHODS: Ten women with severe preeclampsia or preeclampsia with severe fetal compromise at 21-33 weeks' gestation each received a 60-90-minute intravenous infusion of 50-250 micrograms/minute of S-nitrosoglutathione. Each was hypertensive, despite conventional oral antihypertensive therapy in eight. Maternal blood pressure, heart rate, platelet activation, uterine artery, and fetal Doppler indices were measured during the infusion. RESULTS: A dose-dependent reduction in mean arterial pressure from 125 mmHg (95% confidence interval [CI] 117-133) to 103.5 (95% CI 97-111) (P < .005) and an increase in pulse rate from 73.7 beats per minute (95% CI 64.3-84.5) to 89.1 (95% CI 81.2-97.8) (P < .02) was observed during the infusion. Mean uterine artery resistance index fell from 0.76 (95% CI 0.73-0.81) to 0.70 (95% CI 0.65-0.75) (P < .009). Platelet activation measured by P-selectin expression was reduced from 3.02% (95% CI 2.09-4.36) to 1.22% (95% CI 0.94-1.58) (P < .01). Fetal Doppler indices (umbilical artery, middle cerebral artery, and thoracic aorta) showed no significant changes during the infusion. CONCLUSION: S-nitrosoglutathione infusion reduced material mean arterial pressure, platelet activation, and uterine artery resistance without further compromising fetal Doppler indices. This study suggests that platelet-specific nitric oxide donors may prove beneficial in the management of severe preeclampsia.

Adult↗

PubMed1996

Language level and nonverbal social-communicative behaviors in autistic and language-delayed children.

OBJECTIVE: To explore the relationship of general expressive language delay to nonverbal social-communicative deficits and repetitive behaviors associated with autism in preschool children. METHOD: Interviews of the parents of 51 autistic and 43 nonautistic 3- to 5-year-olds with language impairments were compared. RESULTS: Main effects of the children's language level occurred for the majority of social and nonverbal communication items but not for restricted, repetitive behaviors or showing and directing attention, socially directed gaze, or range of facial expression. CONCLUSIONS: In addition to the specific impairments of autism, a broader conceptualization of communication handicap is urged for preschool children with developmental delays.

Attention↗

PubMed1996

Reading problems and antisocial behaviour: developmental trends in comorbidity.

Samples of poor and normal readers were followed through adolescence and into early adulthood to assess continuities in the comorbidity between reading difficulties and disruptive behaviour problems. Reading-disabled boys showed high rates of inattentiveness in middle childhood, but no excess of teacher-rated behaviour problems at age 14 and no elevated rates of aggression, antisocial personality disorder or officially recorded offending in early adulthood. Increased risks of juvenile offending among specifically retarded-reading boys seemed associated with poor school attendance, rather than reading difficulties per se. Reading problems were associated with some increases in disruptive behaviour in their teens in girls.

Adolescent↗

PubMed1996

A broader phenotype of autism: the clinical spectrum in twins.

The diagnostic boundaries of the behavioural phenotype for autism were examined in 28 MZ pairs and 20 DZ same-sex twin pairs, where one or both twins had autism. In the non-autistic cotwin (i.e. in twin pairs discordant for autism) it was common to find language impairments in childhood and social deficits persisting into adulthood. Concordance for this broader phenotype was much greater in MZ pairs than DZ pairs, indicating a strong genetic component. Behavioural and cognitive manifestations of autism were compared both within and between MZ twin pairs. The variation was as great within MZ twin pairs as between pairs, suggesting that it does not index genetic heterogeneity (although aetiological heterogeneity probably exists). Current diagnostic practices need re-evaluation.

Activities of Daily Living↗

PubMed1996

Genetic and environmental influences on the covariation between hyperactivity and conduct disturbance in juvenile twins.

Structural equation models were applied to the maternal ratings of 265 MZ and 163 DZ male-male, 347 MZ and 160 DZ female-female, and 262 male-female twin pairs, aged 8-16 years, who participated in the Virginia Twin Study of Adolescent Behavioral Development (VTSABD). Substantial additive genetic influences and contrast effects were found for hyperactivity, and additive genetic and shared environmental effects or positive comparison effects (particularly for the girls) for oppositional/ conduct disturbance. Bivariate model fitting showed that the covariation between hyperactivity and oppositional/conduct problems in both younger and older boys and girls is almost entirely attributable to genetic factors. However, whereas in the younger males and females the same set of genes explain all the variation in hyperactivity and conduct disturbance, in the older cohort at least some of the genetic effects are behavior- and gender-specific.

Adolescent↗

PubMed1995

A comparison of frailty models for multivariate survival data.

This paper reviews some of the main approaches to the analysis of multivariate censored survival data. Such data typically have correlated failure times. The correlation can be a consequence of the observational design, for example with clustered sampling and matching, or it can be a focus of interest as in genetic studies, longitudinal studies of recurrent events and other studies involving multiple measurements. We assume that the correlation between the failure or survival times can be accounted for by fixed or random frailty effects. We then compare the performance of conditional and mixture likelihood approaches to estimating models with these frailty effects in censored bivariate survival data. We find that the mixture methods are surprisingly robust to misspecification of the frailty distribution. The paper also contains an illustrative example on the times to onset of chest pain brought on by three endurance exercise tests during a drug treatment trial of heart patients.

Angina Pectoris↗

PubMed1995

Multiple raters of disruptive child behavior: using a genetic strategy to examine shared views and bias.

Most research on child behavior incorporates information from different individuals. While agreement between informants is generally only modest, there is little understanding of the processes underlying disagreement. In twin studies, differential agreement among raters for MZ and DZ twins is of particular concern. The processes underlying differences among mother, father, and child ratings of oppositional and conduct disorder symptoms are explored. Evidence in favor of a shared parental view of behavior is presented. Parental ratings give higher intrapair correlations, which could be due to either parents rating their twins more similarly or twins contrasting themselves. Rater bias and situational specificity are among the possible explanations of differential ratings. The effects of incorporating multiple raters of behavior on estimates of genetic and environmental effects are explored. These suggest that genetic influences are greater for the shared (multiple-rater) phenotype than for individual ratings; reduction in measurement error is only a partial explanation.

Adolescent↗

PubMed1995

The Adult Personality Functioning Assessment (APFA): factors influencing agreement between subject and informant.

The Adult Personality Functioning Assessment (APFA) provides ratings of interpersonal and social role performance in six domains over substantial periods of time. Ratings based on subject and informant accounts using the APFA were compared. There was good agreement for estimates of levels of dysfunction, and moderate agreement for type of dysfunction. An anticipated under-reporting of difficulties by subjects was not found. The extent of personality dysfunction was predictive of whether a close informant was available; however, closeness of informant was not consistently associated with subject-informant agreement.

Adaptation, Psychological↗

PubMed1995

Mother-child interaction and the cognitive and behavioural development of four-year-old children with poor growth.

A whole population inner-city survey identified 23 stunted, otherwise healthy, children with persistently poor growth from infancy to 4 years. Their cognitive development was significantly retarded relative to a matched comparison group. Unstructured home observations were used to create transcripts of verbal and nonverbal mother-child interactions. In both groups child behavioural adjustment was linked to maternal negativity, and cognitive performance was correlated with quality of stimulation. The developmental delay associated with chronic failure to thrive appeared more likely to arise from other influences, perhaps a previous biological insult, than to contemporaneous parenting practices.

Adult↗

PubMed1995

Screening for stratification in two-phase ('two-stage') epidemiological surveys.

Screening is undertaken not only for the purpose of giving therapeutic treatment to those among screen positive subjects found to be diagnosis positive, but it is also used in epidemiology as the first phase of multi-phase sampling designs. We review the use of such designs in epidemiology, and in psychiatric epidemiology in particular, focusing on two-phase or double sampling. We then compare a variety of approaches to the statistical analysis of data from such designs including the use of sampling weights, Gibbs sampling, full maximum likelihood for random effects logistic regression and a simple E-M algorithm for incomplete data. The methods are illustrated using data from a recent multi-phase study of psychiatric morbidity in northern Spain.

Humans↗

PubMed1995

Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error: a twin and family history study of autism.

The use of the family history method to examine the pattern of recurrence risks for complex disorders such as autism is not straightforward. Problems such as uncertain phenotypic definition, unreliable measurement with increased error rates for more distant relatives, and selection due to reduced fertility all complicate the estimation of risk ratios. Using data from a recent family history study of autism, and a similar study of twins, this paper shows how a latent-class approach can be used to tackle these problems. New findings are presented supporting a multiple-locus model of inheritance, with three loci giving the best fit.

Autistic Disorder↗

PubMed1994

Survival models for developmental genetic data: age of onset of puberty and antisocial behavior in twins.

The use of survival analysis for developmental genetic data is discussed. The main requirements for models based on the decomposition of frailty distributions into shared and unshared components are outlined for the simple case of twins. Extending the earlier work of Clayton, Oakes, and Hougaard, among others, three forms of hazard model are presented, all of which can be applied to pedigree data with flexible baseline hazards without the use of numerical integration. The first two models use an additive decomposition of frailty, with either gamma or positive stable law distributed (PSL) components. The third model previously described by Hougaard involves a multiplicative PSL decomposition. The models are applied to data on the onset of puberty in male twins and illustrate the importance of correct specification of the baseline hazard for correct inference about genetic effects. The difficulty of assessing model specification using information only on the margins is also noted. Overall, the new model with additive PSL components appeared to fit these data best. A second application illustrates the use of a time-varying covariate in examining the impact of puberty on the onset of conduct disorder symptomotology.

Adolescent↗

PubMed1994

A simple method for censored age-of-onset data subject to recall bias: mothers' reports of age of puberty in male twins.

Genetic analysis of variation in age of onset of development milestones or psychopathological behaviors has been little researched, owing largely to the computational difficulty of dealing with "censored" observations. Censored observations arise when the only information on individuals is that they have reached a particular age but without onset having occurred. This paper shows how models can be simply fitted to such data using programs that can perform genetic analysis of categorical data by maximum likelihood. The method is illustrated using the program Mx with data on maternal report of the onset of puberty in twin sons from the Virginia Twin Study of Adolescent Behavioral Development. Frequently, data on age of onset is collected by retrospective recall. This can pose a variety of measurement problems. Suggestions are made for models that account for some of these problems or are robust to their presence. Substantial evidence for "telescoping" of onset dates is found for the puberty data. If left unaccounted for, these effects can artifactually inflate estimates of common environment effects.

Adolescent↗

PubMed1994

Adult outcomes of childhood and adolescent depression. III. Links with suicidal behaviours.

This study followed up into adulthood a group of child psychiatric patients suffering from depressive disorders and a closely matched nondepressed child psychiatric control group. Depression in childhood was a strong predictor of attempted suicide in adulthood. This predictive power was not due to the association between childhood depression and other childhood risk factors such as conduct disorder or suicidality. Rather, it seemed mostly to reside in the association between depression in childhood and major depression in adult life. These findings suggest that the pathways from childhood psychopathology to adult outcomes can be complex, and depend crucially on what happens later.

Adolescent↗

PubMed1994

Postnatal growth and mental development: evidence for a "sensitive period".

For many years it has been suspected that severely impaired somatic growth during early postnatal life can be associated with the subsequent impairment of mental abilities. This study aimed to test that hypothesis on the basis of data gathered from a prospective whole population survey of infant development in south London. A year's birth cohort of 1558 full-term singletons was monitored; 47 otherwise healthy cases with serious growth faltering in the first year were recruited. Mental and psychomotor abilities were assessed at 15 months. Potentially confounding psychosocial variables, including cognitive stimulation received at home, were measured contemporaneously. A statistical model was constructed that enabled the timing, duration and severity of growth faltering to be used as predictors of mental functioning. Up to 37% of the variance in cognitive and psychomotor outcome at 15 months can be explained by the model. The first few postnatal months appear to constitute a "sensitive period" for the relationship between growth and mental development.

Anemia↗

PubMed1994

A case-control family history study of autism.

Family history data on 99 autistic and 36 Down's syndrome probands are reported. They confirmed a raised familial loading for both autism and more broadly defined pervasive developmental disorders in siblings (2.9% and 2.9%, respectively, vs 0% in the Down's group) and also evidence for the familial aggregation of a lesser variant of autism, comprising more subtle communication/social impairments or stereotypic behaviours, but not mental retardation alone. Between 12.4 and 20.4% of the autism siblings and 1.6% and 3.2% of the Down's siblings exhibited this lesser variant, depending on the stringency of its definition. Amongst autistic probands with speech, various features of their disorder (increased number of autistic symptoms; reduced verbal and performance ability) as well as a history of obstetric complications, indexed an elevation in familial loading. No such association was seen in the probands without speech, even though familial loading for the lesser variant in this subgroup, was significantly higher than in the Down's controls. The findings suggest that the autism phenotype extends beyond autism as traditionally diagnosed; that aetiology involves several genes; that autism is genetically heterogeneous; and that obstetric abnormalities in autistic subjects may derive from abnormality in the foetus.

Adolescent↗

PubMed1994

Generalizations and applications of frailty models for survival and event data.

A variety of survival models with both discrete and continuously distributed frailty is considered within a framework that involves the specification of three sub-models. An intensity sub-model specifies how the intensity is related to values of covariates and frailty; a measurement sub-model specifies how fallible measures of frailty are related to it; and an exposure sub-model specifies how frailty is distributed within the population. The models include those in which frailty is due to omitted covariates and those where it represents a covariate that has been measured subject to error. Multivariate frailty is also considered, with particular emphasis on models suitable for application to genetically related individuals, notably twins. A numerical example illustrates the use of a model with multivariate frailty for data on repeated exercise times.

Angina Pectoris↗

PubMed1993

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↗