PubMed Health⌕ Search

Biomedical subjects

D A Mrazek

Publications and source records attributed to D A Mrazek.

At least 19 recordsLinked to original sources
PubMed2001

Pigment epithelium-derived factor supports normal Müller cell development and glutamine synthetase expression after removal of the retinal pigment epithelium.

In conditions in which the retinal pigment epithelium (RPE) is dystrophic, carries a genetic mutation, or is removed physically, Müller cells undergo degenerative changes that contribute to the retinal pathology. We previously demonstrated that pigment epithelium-derived factor (PEDF), a glycoprotein secreted by the RPE cells with neuroprotective and differentiation properties, protects against photoreceptor degeneration induced by RPE removal. The purpose of the present study was to analyze the putative gliosupportive activity of PEDF on Müller cells of RPE-deprived retinas and assess whether protection of Müller cells was correlated with improved photoreceptor outer segment assembly. Eyes were dissected from Xenopus laevis tadpoles, and the RPE was removed before culturing in medium containing purified PEDF, PEDF plus anti-PEDF, or medium alone. Control eyes matured with an adherent RPE or in medium containing PEDF plus nonimmune serum. Müller cell ultrastructure was examined. Glial fibrillary acidic protein (GFAP) and glutamine synthetase were localized immunocytochemically, and the corresponding protein levels were quantified. In control retinas, Müller cells were structurally intact and formed adherens junctions with neighboring photoreceptors. In addition, they did not express GFAP, whereas glutamine synthetase expression was high. RPE removal dramatically altered the ultrastructure and biosynthetic activity of Müller cells; Müller cells failed to form adherens junctions with photoreceptors and glutamine synthetase expression was suppressed. PEDF prevented the degenerative glial response; Müller cells were ultrastructurally normal and formed junctional complexes with photoreceptors. PEDF also preserved the expression of glutamine synthetase at near-normal levels. The morphogenetic effects of PEDF were blocked by the anti-PEDF antibody. Our study documents the glioprotective effects of PEDF and suggests that maintenance of the proper Müller cell ultrastructure and expression of glutamine synthetase may be necessary to support the proper assembly of photoreceptor outer segments.

Animals↗
PubMed2001

Depression in adolescence.

Major depression is a common mental health disorder in adolescents that predicts a significant risk for recurrence in adulthood. Suicide is the third most frequent cause of deaths in this age group, and depression is a significant risk factor for suicidal ideation and attempts. Risks for depression and suicidal ideation are reviewed, and subtypes of depression are discussed. Difficulties associated with identification of depression and suicidal ideation in adolescents and biologic therapies for adolescent depression are reviewed.

Adolescent↗
PubMed2001

Genetic and environmental influences on the associations between attention problems and other problem behaviors.

Problem behavior in children shows a high degree of co-occurrence, both within the domains of internalizing and externalizing behaviors and across domains. Maternal ratings of 207 same- and opposite-sex twin pairs on the Child Behavior Checklist (CBCL/4-18; Achenbach, 1991) were used to determine the etiology of these associations. In the current sample of 4- to 11-year-old children (mean age: 7.6 years) phenotypic correlations were .68 between Internalizing and Externalizing, between .41 and .66 within the internalizing scales, and between .58 and .71 within the externalizing scales. Correlations across domains on the scale level were of similar magnitude. Genetic and shared environmental correlations were generally high, with the exception of the somatic complaints scale which showed low genetic correlations with other scales. These findings of uniformly high shared etiology was seen within and across domains. For example, Attention Problems showed genetic correlations of .65 with Delinquent Behavior and .76 with Aggressive Behavior; the genetic correlations of Attention Problems with internalizing scales were .71 for Anxious/Depressed and .79 for Withdrawn; a low genetic correlation was only shown for the Somatic Complaints scale (r(g) = .16). Although the magnitude of shared environmental contributions was lower, the environmental correlations were close to unity, indicating that the same family environmental factors were involved in aspects of problem behavior when assessed across domains. Results for the Attention Problems scale were similar to other disruptive behavior, justifying its inclusion with the externalizing scales.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Onset and persistence of childhood asthma: predictors from infancy.

OBJECTIVE: In a prospective study of children with a family history of asthma, asthma onset by 3 years of age was found previously to be positively associated with variables from the first year of life, including elevated total immunoglobulin E (IgE), frequent respiratory infections, and parenting difficulties. We followed this cohort of genetically at-risk children to investigate the relationship between factors assessed in infancy and asthma, allergy, and psychological status at school age. METHODS: A cohort of 150 children who were at risk for developing asthma were identified prenatally on the basis of the mothers' having asthma. For 28 children, the father had asthma as well, putting them at bilateral genetic risk. Families primarily were middle and upper middle class Caucasians. Parents came to the clinic during the third trimester of pregnancy for assessments of medical and psychosocial functioning. A home visit took place when the infant was 3 weeks old, when parenting risk was assessed before the onset of any asthma symptoms. Parenting difficulties included problems with infant caregiving as well as components of maternal functioning, such as postpartum depression and inadequate marital support. Blood was drawn for serum IgE at 6 months of age. Parents and offspring subsequently came to the clinic multiple times, with the last clinic visit during the child's sixth year. Follow-up at age 6 involved a clinic visit for allergy and psychosocial evaluations, consisting of interviews and a behavior questionnaire. Seventy-seven children received the allergy and psychosocial evaluation, 26 received the psychosocial evaluation in the clinic, and 30 families received telephone interviews and mailed in questionnaires. Additional monitoring of families by telephone and mail was maintained over the next 2 years, until the children were 8, to ensure accurate characterization of the course of illness. Comprehensive medical records were obtained and reviewed for all health care contacts. Children were designated as having asthma when there was documentation in medical records of physician-diagnosed asthma, observed wheezing, and/or prescription of asthma medications during the time period when the child was between 6 and 8 years of age. Parental reports of the occurrence of asthma corroborated the medical record data. RESULTS: Data regarding asthma status were available for 145 children through 8 years of age. Forty (28%) of the children manifested asthma between 6 and 8 years of age. Among variables previously reported to predict asthma onset by age 3, 3 proved to have significant univariate relationships with asthma between ages 6 and 8: elevated IgE levels measured when the children were 6 months of age, global ratings of parenting difficulties measured when infants were 3 weeks old, and higher numbers of respiratory infections in the first year of life. Among these offspring of mothers with asthma, paternal asthma showed a significant association with asthma between ages 6 and 8. Eczema in the first year was not significantly related to later asthma. Multiple logistic regression showed that the model that best predicted asthma at ages 6 to 8 from infancy variables included 2 main effects. The adjusted odds ratio for 6-month IgE was 2.15 (1.51, 3.05) and for parenting difficulties was 2.07 (1.15, 3.71). Although socioeconomic status (SES) was not associated with asthma at ages 6 to 8, families of lower SES were more likely to be rated as having parenting difficulties early in the child's life. The mothers of lower SES breastfed for a shorter period of time and were more likely to smoke during their infant's first year. There were more respiratory infections during the first year of life among infants whose mother was rated as having more parenting difficulties. Mothers who reported smoking breastfed their infants for a shorter length of time. Male gender was significantly associated with higher IgE levels when infants were 6 months of age. Laboratory testing was completed for 77 children at age 6. Total serum IgE levels were significantly higher for the children with asthma between ages 6 and 8. Skin-prick testing showed that the children with asthma had significantly more positive skin test reactions than did the children without asthma. Psychosocial interview data at 6 years of age were available for 103 families, and behavioral questionnaires were available for 133 families. On the basis of 6-year interviews, children with asthma were rated as being at greater psychological risk than were the children without asthma. Mothers' Child Behavior Checklist (CBCL) ratings of their children's behavior indicated higher internalizing scores for the children with asthma as compared with the children without asthma. Like the 6-month IgE, 6-year IgE was higher for boys. IgE levels measured at 6 months of age were significantly correlated with 6-year IgE levels. Parenting difficulties measured at 3 weeks were significantly correlated with 6-year measures of maternal depression, CBCL Internalizing score, and Child Psychological Risk (CPR) score. There also were significant correlations among the psychosocial variables assessed when the children were 6 years of age; maternal depression was significantly associated with child CBCL Internalizing score and CPR score, and the last 2 also were significantly correlated. Multiple logistic regression showed that 2 concurrently measured variables entered the model showing the strongest associations with asthma at ages 6 to 8. The adjusted odds ratio for CPR score was 3.21 (1.29-7.96) and for 6-year IgE was 1.71 (1.04-2.80). CONCLUSIONS: This study of the natural history of childhood asthma focused on the development of asthma into the school-age years in a genetically at-risk group of children. The relationships between biological and psychosocial variables in the first year and school-age asthma support the formulation of asthma as beginning early in life, with the developing immune system interacting with environmental influences. The data provide support for the possible contribution of psychosocial factors to asthma onset and persistence into childhood.

Adult↗
PubMed2000

Pigment epithelium-derived factor supports normal development of photoreceptor neurons and opsin expression after retinal pigment epithelium removal.

Dysfunction of the retinal pigment epithelium (RPE), its loss, or separation from the underlying neural retina results in severe photoreceptor degeneration. Pigment epithelium-derived factor (PEDF) is a glycoprotein with reported neuroprotective and differentiation properties that is secreted in abundance by RPE cells. The "pooling" of PEDF within the interphotoreceptor matrix places this molecule in a prime physical location to affect the underlying neural retina. The purpose of this study was to analyze the morphogenetic activity of PEDF in a model of photoreceptor dysmorphogenesis induced by removal of the RPE. Eyes were dissected from embryonic Xenopus laevis, and the RPE was removed before culturing in medium containing PEDF, PEDF plus anti-PEDF antibodies, or medium alone. Control retinas were maintained with an adherent RPE. Light and electron microscopic analysis was used to examine retinal ultrastructure. Opsin was localized immunocytochemically and quantified as an index of outer segment membranous material and photoreceptor protein expression. Removal of the RPE resulted in an aberrant assembly of photoreceptor outer segments, loss of fine subcellular ultrastructure in photoreceptors, and a reduction in opsin protein levels when compared with control retinas. The addition of PEDF prevented the dysmorphic photoreceptor changes induced by RPE removal. In particular, photoreceptor ultrastructure, outer segment membrane assembly, and steady-state levels of opsin were equivalent to control conditions. Anti-PEDF antibodies completely blocked the morphogenetic activity of PEDF. These results indicate that PEDF is able to mimic the supportive role of the RPE on photoreceptors during the final stages of retinal morphogenesis.

Animals↗
PubMed2000

Psychiatric diagnoses in adolescents seropositive for the human immunodeficiency virus.

OBJECTIVE: To provide a descriptive analysis of the prevalence of past and current psychiatric disorders in adolescents positive for the human immunodeficiency virus (HIV). DESIGN: Structured interview in a convenience sample in a primary care urban adolescent clinic in Washington, DC. PARTICIPANTS: Thirty-four HIV-seropositive adolescents ranging in age from 16 to 21 years. MAIN OUTCOME MEASURES: The Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition (SCID-P) was administered by a child psychiatrist or a clinical child psychologist. Extensive review of medical records was also conducted. RESULTS: A majority of the HIV-infected adolescents in our sample had received psychiatric diagnoses prior to their treatment at the clinic (53%), had a documented history of sexual abuse (50%), and had a history of substance use (82%). Psychiatric diagnoses determined by the SCID-P indicated that 85% of the sample had a current Axis I disorder, with 44% reporting ongoing depressive disorders. CONCLUSIONS: The majority of subjects in this sample had had a previous psychiatric diagnosis, and almost half had a current affective disorder. Psychiatric disorders, especially affective disorders, may be a risk factor for high-risk sexual behaviors and substance use that increases the risk for HIV infection in adolescent populations.

Adolescent↗
PubMed2000

Maternal characteristics and toddler temperament in infantile anorexia.

OBJECTIVE: To explore the association between specific maternal characteristics, maternal perceptions of toddler temperament, and infantile anorexia. METHOD: Three groups of toddlers (aged 12-37 months) participated in this study: toddlers with infantile anorexia (n = 34), picky eaters (n = 34), and healthy eaters (n = 34). Mothers completed questionnaires that assessed their own eating attitudes, marital satisfaction, and their toddlers' temperament, and an interview that explored their attachment representations. Mothers and toddlers were videotaped during a feeding session, and toddlers were weighed and measured. RESULTS: Temperament ratings differentiated between infantile anorexics and healthy eaters (p < .0001), with infantile anorexics receiving higher difficulty, irregularity, negativity, dependence, and unstoppable ratings. Mothers of anorexics showed greater attachment insecurity than mothers of healthy eaters (p < .05), but they demonstrated neither overt eating pathology nor less marital satisfaction than the other groups. Thirty-nine percent of variance in feeding conflict was explained by toddlers' diagnoses, temperament ratings, and maternal characteristics. Twenty-one percent of variance in toddlers' weights was explained by temperament ratings and feeding conflict. CONCLUSION: Maternal characteristics and perceptions of their toddlers' temperament characteristics should be addressed in treatment for infantile anorexia.

Anorexia↗
PubMed1999

Prediction of early-onset asthma in genetically at-risk children.

The W.T. Grant Foundation Asthma Risk Study was designed to prospectively examine children who were considered at a genetically increased risk for the development of asthma. The respective contributions of 11 potential risk factors, both environmental and biological, were assessed in order to determine their relative roles in affecting the early onset of asthma. This is a report of an inception cohort of children born to asthmatic mothers and followed for a 3-year period. All 150 families were recruited from the general community and living within 2 h of the National Jewish Center for Immunology and Respiratory Medicine (Denver, CO). Mothers in the index risk sample had been previously diagnosed with asthma and were recruited during their pregnancy through physician referrals and media solicitation. The index sample of 150 families was 92% Caucasian and predominantly middle class. The mean age of mothers was 29.3 years, and of fathers, 31.1 years. The main outcome was the determination of the early onset of asthma and its association with quantified risk factors. By age 3 years, 14 of the 150 children had developed asthma. Frequent illness, IgE levels at age 6 months, parenting difficulties, and early eczema were significantly associated with the onset of asthma (P = 0.003, P = 0.006, P = 0.01, and P = 0.03, respectively). Only frequent illness, elevated serum IgE levels, and parenting difficulties entered a predictive model where they were independently related to the development of asthma.

Age of Onset↗
PubMed1999

Developmental models of infant and childhood temperament.

The developmental courses of specific temperamental constructs were explored by using structural equation model fitting. Maternal ratings were obtained from either 2 or 3 different temperament questionnaires for 180 children at 3, 6, 12, 18, 24, 36, and 48 months of age. Several formal structural models were fit in infancy (3-18 months), in the toddler-preschooler period (24-48 months), and across all measurement occasions. In infancy, the autoregressive simplex model fit well for all 4 composites considered: Positive Emotionality, Distress-Anger, Fear, and Activity Level. In contrast to the considerable change in temperament during infancy, temperament appears to be very stable from 24 to 48 months of age, and a common factor model fits well with these data. Across all measurement occasions, models that allowed for stability in temperament to be at least partially mediated through intermediate forms of the trait fit best.

Age Factors↗
PubMed1998

Early asthma onset: risk of emotional and behavioral difficulties.

The relationship between age of asthma onset and behavioral adjustment was analyzed using data from a longitudinal prospective investigation of 150 children identified prenatally as at genetic risk for developing asthma (the W. T. Grant Asthma Risk Study). The children's development and asthma status were monitored regularly for 6 years. Mothers were interviewed yearly using the Behavioral Screening Questionnaire (BSQ). Children who had an early onset of asthma (by 3 years of age) had significantly more behavior problems at age 4 than children who developed asthma later (between 3 and 6 years of age). Furthermore, the early-onset group had significantly more problems at age 6 than both children who developed asthma later and children who never developed asthma. Children with early asthma onset were compared to children who were asthma free on individual problem items of the BSQ, revealing a profile of behavior problems that included waking at night, depressed mood, and some indication of increased fearfulness. This profile is consistent with an earlier report of behavior problems among severely asthmatic preschool children (Mrazek, Anderson, & Strunk, 1984), who displayed the same internalizing behavior problems on the BSQ. These results suggest that early asthma onset may have predictable negative influences on behavioral adjustment over a wider range of asthma severity than has previously been reported.

Affective Symptoms↗
PubMed1995

Clinical assessment of parenting.

OBJECTIVE: This report describes the Parenting Risk Scale and reviews previous approaches to the systematic assessment of parenting. Five key dimensions of parenting are described as well as the method for rating the occurrence of difficulties and concerns about parenting using a semistructured interview methodology. METHOD: The Parenting Risk Scale was developed with two cohorts of young children. One cohort consisted of 150 children at increased genetic risk for developing asthma but who were physically healthy during the initial periods of assessment of parenting. A second cohort of healthy children at no elevated risk for asthma was similarly studied. RESULTS: Reliability of the parenting ratings was found to be acceptable with appropriate training, and both concurrent and predictive validity were demonstrated to be excellent. High stability in the ratings of adequacy of parenting was documented. Specifically, ratings made during the prenatal assessment were highly significantly associated with completely independent ratings of parenting made more than 4 years after the birth of the index child (r = .42, p < .0001). The appropriateness of this method for the assessment of the quality of parenting in clinical settings is highlighted. CONCLUSIONS: The Parenting Risk Scale is a reliable and valid measure for the systemic assessment of five key dimensions of parenting.

Asthma↗
PubMed1995

Problem behavior in early and middle childhood: an initial behavior genetic analysis.

Twin samples were used to estimate the relative importance of genetic and environmental influences on problem behavior in children, assessed by the Child Behavior Checklist (CBCL). For the younger cohort, mothers completed the CBCL/2-3, while for the older cohort the CBCL/4-18 was used. Nearly half of the older sample had also been assessed with the questionnaire for younger children at a prior date, providing tentative answers regarding continuity and change in the etiology of problem behavior. Results suggested that shared environmental influences may be more important in early childhood than in middle childhood, while the reverse holds for genetic influences.

Child↗
PubMed1994

Genetic and environmental influences on early childhood behavior.

The Child Behavior Checklist for Ages 2-3 (Adelbach et al., J. Abnorm. Child Psychol. 15;629-650; 1987) was completed by mothers of 229 pairs of twins (mean age = 33 months). Using the two broad-band groupings of Internalizing and Externalizing described by Achenbach et al. (1987), various models to estimate genetic and environmental parameters were fitted using LISREL 7. Model-fitting results showed that the genetic components to the observed phenotypical variation were small and not necessary in the model. Influences from the shared environment, however, could not be dropped from the model without a deterioration in fit. Parameter estimates were not significantly different in boys and girls.

Child Behavior↗
PubMed1994

Early asthma onset: the interaction between family stressors and adaptive parenting.

It has been repeatedly noted by clinicians that psychological stressors appear to be associated with the expression of asthma in individuals who have a genetic vulnerability for developing the disease. While retrospective evidence has supported this clinical observation (Levitan 1985; Teiramaa 1986), the association between emotional stressors and illness onset can only be convincingly demonstrated using a longitudinal design (Mrazek 1988; Steinhausen et al. 1983). In 1985 the W. T. Grant Asthma Risk Study was designed to identify which physiological and psychological risk factors for asthma were most highly associated with eventual expression of the disease. Young infants who were genetically at risk for asthma were evaluated and their development was prospectively monitored. The primary objective of the longitudinal study was to identify risk factors for illness expression. If this were possible, these risk factors could then be targeted for intervention efforts designed to delay the initial onset of asthmatic symptoms. The ultimate objective of an effective intervention would be that for some children, the illness could be prevented completely.

Adult↗
PubMed1992

Quality of marital relationship: a clinical rating scale.

Clinical research requires the measurement of complex variables in a manner that is as simple as possible while still being precise. This paper presents a clinical rating scale that was developed as a global measure of the quality of couples' relationships. These couples participated in a study that investigated asthma onset in children at genetic risk for developing this illness. The ratings of marital quality at the prenatal point were significantly related to the number of behavior problems the children were reported to have at 2 years of age. The use of the scale is outlined, together with descriptive data for this group. Reliability data and evidence for predictive and construct validity are presented.

Adaptation, Psychological↗
PubMed1992

Marriages with children at medical risk: the transition to parenthood.

Prior studies suggest that the birth of a new baby causes a modest but reliable drop in marital satisfaction. The present study replicates and extends this finding in couples with children at medical risk and probes the mechanisms behind this effect. Longitudinal data on marital satisfaction, family structure, infant illness and temperament, and family life events were collected at prenatal, 6, 12, and 18 month periods. Family structural burdens and family stress burdens had a significant negative effect on marital satisfaction. Child-related burdens were less reliably related. Results are discussed in the context of stress and coping as well as developmental psychopathology.

Asthma↗
PubMed1992

Psychiatric complications of pediatric asthma.

Asthma is the most common chronic illness of childhood. An increased prevalence of psychopathology has been shown repeatedly to occur in severely asthmatic children, but little evidence exists to suggest that this is true for children with mild asthma. A major problem in interpreting the psychological literature addressing asthma has been the absence of studies of children with specified subtypes of the disease and the analysis of heterogeneous samples including children with a wide range of ages and poorly defined disease characteristics. Depression and anxiety disorders occur at a greater prevalence in severely asthmatic children and may be exacerbated by antiasthmatic medications. Vocal cord dysfunction may be misdiagnosed as asthma and is suggested to be associated with an increased risk of psychiatric disturbance. The presence of depressive illness in very severe asthmatic patients is associated with greater asthma mortality and requires intervention. Treatment considerations include the need for a high level of suspicion for noncompliance in patients who are nonresponsive to antiasthmatic medications, judicious use of antidepressant medication, referral of children with co-occurring psychiatric symptoms for psychiatric assessment and management, and consideration of early intervention strategies to minimize the initial expression of asthmatic symptoms.

Asthma↗