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Biomedical subjects

J Wicks

Publications and source records attributed to J Wicks.

At least 19 recordsLinked to original sources

Enhanced upregulation of smooth muscle related transcripts by TGF beta2 in asthmatic (myo) fibroblasts.

BACKGROUND: Transforming growth factor beta (TGF beta) upregulates a number of smooth muscle specific genes in (myo)fibroblasts. As asthma is characterised by an increase in airway smooth muscle, we postulated that TGFbeta(2) favours differentiation of asthmatic (myo)fibroblasts towards a smooth muscle phenotype. METHODS: Primary fibroblasts were grown from bronchial biopsy specimens from normal (n = 6) and asthmatic (n = 7) donors and treated with TGF beta2 to induce myofibroblast differentiation. The most stable genes for normalisation were identified using RT-qPCR and the geNorm software applied to a panel of 12 "housekeeping" genes. Expression of alpha-smooth muscle actin (alpha SMA), heavy chain myosin (HCM), calponin 1 (CPN 1), desmin, and gamma-actin were measured by RT-qPCR. Protein expression was assessed by immunocytochemistry and western blotting. RESULTS: Phospholipase A2 and ubiquitin C were identified as the most stably expressed and practically useful genes for normalisation of gene expression during myofibroblast differentiation. TGF beta2 induced mRNA expression for all five smooth muscle related transcripts; alpha SMA, HCM and CPN 1 protein were also increased but desmin protein was not detectable. Although there was no difference in basal expression, HCM, CPN 1 and desmin were induced to a significantly greater extent in asthmatic fibroblasts than in those from normal controls (p = 0.041 and 0.011, respectively). CONCLUSIONS: Although TGF beta2 induced the transcription of several smooth muscle related genes, not all were translated into protein. Thus, while TGF beta2 is unable to induce a bona fide smooth muscle cell phenotype, it may "prime" (myo)fibroblasts for further differentiation, especially if the cells are derived from asthmatic airways.

Adult↗

Relationship between specific adverse life events and psychiatric disorders.

This study examines whether certain psychiatric disorders are associated more closely with adverse life events than other disorders are, and whether some adverse life events are associated with a specific group of disorders (e.g., depressive disorders), but not with other disorders (e.g., anxiety disorders). A probability sample of youth aged 9-17 at 4 sites is used (N = 1,285). Univariate and multivariate logistic regressions identify specific relationships between 25 adverse life events and 9 common child and adolescent psychiatric disorders, measured by the Diagnostic Interview Schedule for Children. Conduct Disorder, Oppositional Defiant Disorder, Major Depressive Disorder, and Dysthymia are significantly associated with many of the adverse life events examined, whereas Attention Deficit/Hyperactivity Disorder, Agoraphobia, and Social Phobia are related to very few. This study suggests that certain psychiatric disorders may be more closely associated with adverse life events than other psychiatric disorders are, and that some adverse life events seem to be related to specific types of disorders.

Adolescent↗

Association between allergy and anxiety disorders in youth.

OBJECTIVE: Studies have documented associations between anxiety disorders and allergy in adults, but these associations have not been studied extensively in children. The objective of this study is to examine the associations between allergy and six anxiety disorders (AD) in youth. METHOD: This is a data analysis of two epidemiologic-services studies: (i) alternative service use patterns of youth with serious emotional disturbance (n = 936), and (ii) methods for the epidemiology of child and adolescent mental disorders (n = 1285). Child psychiatric diagnoses were measured by the diagnostic interview schedule for children. Allergy was assessed by the service utilization and risk factors interview. RESULTS: Among ADs, the strongest association found was between allergy and panic disorder (adjusted odds ratio 5.0; p < or = 0.001). Associations of allergy and the other ADs do not seem to be clinically significant. CONCLUSIONS: Findings suggest that in some patients panic disorder may be associated with hypersensitivity of immune system. Panic disorder should be considered in anxious children reporting allergy when no organic cause of allergy is found, and likewise allergy should considered in children with panic disorder.

Adolescent↗

Comparison of MPEG-1 digital videotape with digitized sVHS videotape for quantitative echocardiographic measurements.

Digital format is rapidly emerging as a preferred method for displaying and retrieving echocardiographic studies. The qualitative diagnostic accuracy of Moving Pictures Experts Group (MPEG-1) compressed digital echocardiographic studies has been previously reported. The goals of the present study were to compare quantitative measurements derived from MPEG-1 recordings with the super-VHS (sVHS) videotape clinical standard. Six reviewers performed blinded measurements from still-frame images selected from 20 echocardiographic studies that were simultaneously acquired in sVHS and MPEG-1 formats. Measurements were obtainable in 1401 (95%) of 1486 MPEG-1 variables compared with 1356 (91%) of 1486 sVHS variables (P <.001). Excellent agreement existed between MPEG-1 and sVHS 2-dimensional linear measurements (r = 0.97; MPEG-1 = 0.95[sVHS] + 1.1 mm; P <.001; Delta = 9% +/- 10%), 2-dimensional area measurements (r = 0.89), color jet areas (r = 0.87, p <.001), and Doppler velocities (r = 0.92, p <.001). Interobserver variability was similar for both sVHS and MPEG-1 readings. Our results indicate that quantitative off-line measurements from MPEG-1 digitized echocardiographic studies are feasible and comparable to those obtained from sVHS.

Echocardiography↗

Gas chromatography-mass spectrometry confirmation of Cozart RapiScan saliva methadone and opiates tests.

The object of this study was to determine the sensitivity and specificity of the Cozart RapiScan onsite saliva test for methadone and opiates versus laboratory-based enzyme immunoassay (EIA) and gas chromatography-mass spectrometry (GC-MS) confirmation. Fifty saliva specimens were obtained from 28 volunteers among persons entering a substance abuse clinic. Specimens were tested onsite using the Cozart RapiScan Saliva test and Cozart RapiScan Reader. Specimens were retested by Cozart Microplate EIA assays on receipt at the laboratory and then frozen for later confirmation by GC-MS. For GC-MS, deuterated internal standards were added to specimen aliquots which were extracted using solid-phase columns at pH 6 and eluted with dichloromethane/isopropanol/ammonia (80:19:2). The dry residues were derivatized with PFOH and PFPA and dried, and the reconstituted extract was injected and quantitated by GC-MS. The Cozart RapiScan Methadone Saliva Assay was found to have a sensitivity and specificity of 100% +/- 12% versus GC-MS (2-ng/mL cutoff) and a sensitivity of 100% +/- 11% and a specificity of 95% +/- 2.4% versus the Microplate EIA for methadone (30-ng/mL cutoff). The Cozart RapiScan Saliva Opiate test had a sensitivity of 100% +/- 12% and a specificity of 92% +/- 3.2% versus GC-MS (2-ng/mL cutoff) and a sensitivity of 96% +/- 2.2% and specificity of 95% +/- 2.4% versus the Microplate EIA for opiates (30-ng/mL cutoff).

Gas Chromatography-Mass Spectrometry↗

Factors associated with use of mental health services for depression by children and adolescents.

OBJECTIVE: This study examined patterns of mental health service use among depressed children and adolescents and factors associated with help seeking and treatment modalities. METHODS: The sample consisted of 206 children and adolescents aged 9 to 17 years who were assessed as part of a larger survey of mental health service use in five service systems and in the community and who met DSM-III-R criteria for depressive disorders (major depression or dysthymia). RESULTS: Among the 206 children, 75 (36 percent) never received professional help for depressive symptoms. Among the 131 children who received professional help for depression, antidepressants were prescribed for 40 (31 percent) in the year before the interview. The findings indicate possible undertreatment of depression among children and adolescents, especially among African Americans. Socioeconomic factors, such as the mother's education and the child's health insurance, were not associated with receiving professional help for depressive symptoms but were associated with receiving antidepressants. Parental perception of a child's mental health service need was associated with receiving professional help but not with receiving antidepressants. Also, depressed children were more likely to receive antidepressants when they had life-threatening or severe symptoms, such as a suicide attempt or drug abuse. CONCLUSIONS: Whether a depressed child receives mental health services and the types of treatment received are influenced by different individual and family factors and by the type of symptoms exhibited. Better understanding of these factors will help in meeting the service needs of depressed children and adolescents.

Adolescent↗

Seasonal variations in internalizing, externalizing, and substance use disorders in youth.

Seasonal variations were assessed in symptoms of internalizing (anxiety and mood), externalizing (attention-deficit/hyperactivity and oppositional defiant disorders), and substance use disorders in youth. This study is based on secondary data analysis of two NIMH-funded epidemiologic-services studies: (a) Alternative Service Use Patterns by Youth with Serious Emotional Disturbance (N=936, ages 9-17); and (b) Methods for the Epidemiology of Child and Adolescent Mental Disorders (N=1285, ages 9-17). Child psychiatric diagnoses were measured by the Diagnostic Interview Schedule for Children. Variables that indicate site of the interview and service system, as well as age, gender, and ethnicity, were used as covariates. Significant annual variations were found in symptom counts of overanxious disorder, obsessive-compulsive disorder, separation anxiety disorder, social phobia, and major depressive disorder, with the estimated nadir in August-October. There may be weak seasonal variations in attention-deficit/hyperactivity disorder with estimated nadir in August, oppositional defiant disorder with estimated nadir in August-September, and marijuana use with estimated zenith in August-September. Significant seasonality in alcohol, other substance use, agoraphobia, and panic disorder was not found. There may be an instrument-specific bias in estimated nadir. Real nadirs may be up to 3 months prior to the estimated nadirs specified above. Findings suggest that seasonality in symptoms should be considered when assessment instruments of childhood psychiatric disorders are developed, as well as when epidemiological and clinical data are collected and analyzed.

Adolescent↗

Exploiting excess sharing: a more powerful test of linkage for affected sib pairs than the transmission/disequilibrium test.

The transmission/disequilibrium test (TDT) is a popular, simple, and powerful test of linkage, which can be used to analyze data consisting of transmissions to the affected members of families with any kind pedigree structure, including affected sib pairs (ASPs). Although it is based on the preferential transmission of a particular marker allele across families, it is not a valid test of association for ASPs. Martin et al. devised a similar statistic for ASPs, Tsp, which is also based on preferential transmission of a marker allele but which is a valid test of both linkage and association for ASPs. It is, however, less powerful than the TDT as a test of linkage for ASPs. What I show is that the differences between the TDT and Tsp are due to the fact that, although both statistics are based on preferential transmission of a marker allele, the TDT also exploits excess sharing in identity-by-descent transmissions to ASPs. Furthermore, I show that both of these statistics are members of a family of "TDT-like" statistics for ASPs. The statistics in this family are based on preferential transmission but also, to varying extents, exploit excess sharing. From this family of statistics, we see that, although the TDT exploits excess sharing to some extent, it is possible to do so to a greater extent-and thus produce a more powerful test of linkage, for ASPs, than is provided by the TDT. Power simulations conducted under a number of disease models are used to verify that the most powerful member of this family of TDT-like statistics is more powerful than the TDT for ASPs.

Alleles↗

Evaluating linkage and linkage disequilibrium: use of excess sharing and transmission disequilibrium methods in affected sib pairs.

Two popular and robust approaches to analysing affected sib pair (ASP) data for linkage are the traditional excess sharing methods and the transmission/disequilibrium test (TDT). Here we derive an overall test of linkage for multi-allelic ASP marker data which comprises two component tests: one for excess sharing and one for transmission disequilibrium. This method has several advantages. Firstly the overall test of linkage is often more powerful than either of the two component tests. Secondly the method makes it possible to determine the contribution of linkage disequilibrium (LD), in addition to linkage, to an overall positive linkage result. This is useful because the presence of LD in addition to linkage may suggest that the marker locus is in very close proximity to a disease susceptibility gene. Thirdly the method provides estimates of the risk associated with transmission of the different marker alleles.

Genetic Diseases, Inborn↗

Modeling linkage and association with evaluation of common sampling schemes.

The probability model of parental transmission (of a multiallelic marker) to affected offspring has been reparameterized in such a way as to distinguish the recombination fraction parameter from the association parameters. The advantage of this reparameterization is that statistical tests can be developed which disentangle linkage and association. It is shown that these tests perform well compared with a standard approach that is commonly used. Further, the simulated data (Problem 2) enable a comparison to be made of the performance of these tests under different family sampling schemes.

Family↗

Measuring resolution in the contrast domain: the small letter contrast test.

BACKGROUND: Recent evidence suggests that small letter contrast sensitivity (CS) is more sensitive than visual acuity (VA) to defocus, luminance, binocular enhancement, and visual differences among pilot trainees. It would be valuable to make this test available for general use. We developed a hard copy (letter chart) version called the Small Letter Contrast Test (SLCT) and evaluated its sensitivity and reliability in comparison to standard vision tests. METHODS: The SLCT has 14 lines of letters with 10 letters per line. The letters are of constant size (20/25 or 4/5 at 4 m), but vary in contrast by line in 0.1 log steps (0.01 log units per letter). Normal room illumination is used. The SLCT was evaluated in 16 subjects under various conditions (spherical and astigmatic blur, low luminance, 2 eyes vs. 1 eye) to determine test sensitivity and reliability, and in patients with clinical conditions. Scores were compared to those obtained with standard tests of VA (Bailey-Lovie) and CS (Pelli-Robson). RESULTS: SLCT scores were similar to previous measures, and retest reliability was one line. The SLCT was more sensitive than VA to spherical and astigmatic blur, low luminance, and vision with two eyes vs. one eye. Greater sensitivity of the SLCT endured despite correction for variability. The SLCT was more sensitive than standard tests to visual loss from early cataract, keratoconus, corneal infiltrates, edema, and amblyopia. CONCLUSIONS: The SLCT is a sensitive, adjunctive test, which complements existing measures of VA. It can reveal subtle visual deficits that may be undetected by standard clinical techniques. The SLCT should prove useful for monitoring vision in refractive surgery, corneal and macular edema, optic neuritis, and for selection and evaluation of candidates for occupations requiring unique visual abilities like aviation.

Contrast Sensitivity↗

Depressive symptoms in women in the six months after miscarriage.

This study, the first systematic investigation of the psychiatric impact of miscarriage, tests whether miscarriage markedly increases depressive symptoms in the 6 months after loss. We interviewed 382 miscarrying women entering the study at 2 weeks, 6 weeks, or 6 months after loss and, for comparison, 283 pregnant women and 318 community women not recently pregnant. Among women interviewed 2 weeks after miscarriage the proportion highly symptomatic on the Center for Epidemiologic Studies-Depression scale was 3.4 times that of pregnant women (95% confidence limits 2.0 and 5.0) and 4.3 times that of community women (95% confidence limits 3.0 and 5.8). Among women first interviewed 6 weeks and 6 months after miscarriage the proportion highly symptomatic was three times that of the community women. Women reinterviewed at 6 weeks and 6 months did not have elevated symptom levels, a result attributed to the unintended therapeutic and test effects of study interviews. Interviews were fully structured, readily administered by telephone by nonmedical personnel. The possibility that such interviews afford miscarrying women substantial psychologic benefits merits future investigation.

Abortion, Spontaneous↗

Determinants of depressive symptoms in the early weeks after miscarriage.

OBJECTIVES: We tested whether and under what conditions miscarriage increases depressive symptoms in the early weeks following loss. METHODS: We interviewed 232 women within 4 weeks of miscarriage and 283 pregnant women and 318 community women who had not recently been pregnant. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression (CES-D) Scale. RESULTS: Among women who had miscarried, the proportion who were highly symptomatic on the CES-D was 3.4 times that of pregnant women and 4.3 times that of community women. Among childless women, the proportion of women who had miscarried who were highly symptomatic was 5.7 times that of pregnant women and 11.0 times that of community women. Women who had miscarried were equally depressed regardless of length of gestation; among pregnant women, depressive symptoms declined with length of gestation. Among women who had miscarried, symptom levels did not vary with attitude toward the pregnancy; among pregnant women, depressive symptoms were elevated in those with unwanted pregnancies. Prior reproductive loss and advanced maternal age (35+ years) were not associated with symptom levels in any cohort. CONCLUSIONS: Depressive symptoms are markedly increased in the early weeks following miscarriage. This effect is substantially modified by number of living children, length of gestation at loss, and attitude toward pregnancy.

Abortion, Spontaneous↗

Determination of vigabatrin in plasma by reversed-phase high-performance liquid chromatography.

A method is described for the determination of vigabatrin in 50 microliters of plasma by isocratic high-performance liquid chromatography using fluorescence detection. The procedure involves protein precipitation with methanol followed by precolumn derivatisation with o-phthaldialdehyde reagent. Separation of the derivatised vigabatrin was achieved on a Microsorb C18 column using a mobile phase of 10 mM orthophosphoric acid:acetonitrile:methanol (6:3:1) at a flow rate of 2.0 ml/min. Assay time is 15 min and chromatograms show no interference from commonly coadministered anticonvulsant drugs. The total analytical error within the range of 0.85-85 micrograms/ml was found to be 7.6% with the within-replicates error of 2.76%. The minimum detection limit was 0.08 micrograms/ml and the minimum quantitation limit was 0.54 micrograms/ml.

Aminocaproates↗

The acetylator phenotypes of Saudi Arabians with coronary arterial atheroma.

The acetylator phenotypes were determined by means of a sulfamethazine test in 101 Saudi Arabian patients with authenticated coronary atheroma; 65 were found to be slow acetylators. This distribution of phenotypes is not significantly different from that in 220 controls, 148 of whom were slow acetylators. This finding makes it unlikely that compounds containing a primary aromatic amino or a hydrazino group are involved in the aetiology or pathogenesis of coronary atheroma.

Acetylation↗

Implications of mainstream classrooms for adolescents with spina bifida.

This study examined the social and academic implications of mainstream, mainstream and special (combined) or special-class education for 31 adolescents with spina bifida, and for their primary caretakers. The Peabody Picture Vocabulary Test and the UCLA Loneliness Scale (adolescents) and the Personality Inventory for Children (caretakers) were administered. Adolescents in mainstream classes had the most normal scores for academic and social skills, those in combined classes had intermediate scores and those in special classes had the lowest scores. Paradoxically, adolescents in combined classes reported the least loneliness. This study suggests that even among students with relatively good social skills, mainstream placement is associated with greater subjective experience of loneliness than is combined placement.

Adolescent↗

Quantification of neonatal cerebral ventricular volume by real-time ultrasonography. Derivation and in vitro confirmation of a mathematical model.

The derivation and in vitro confirmation of a method for the calculation of cerebral ventricular volume determined by cranial ultrasonography is described. The derivation depends on use of the cylindrical coordinate method. Confirmation was performed by construction of ultrasound phantoms from latex balloons embedded in a talc/gelatin matrix. Seventeen phantoms of volumes ranging from 10 to 60 mL were measured. The known volume was then compared to the calculated volume by linear regression analysis. The regression analysis indicated a close correlation between the actual volume of the phantoms and the calculated volume with r = 0.96. Various sources of error in the method are discussed. Our results indicate that the cylindrical coordinate mathematical model when applied to cranial ultrasonography images accurately measures cerebral ventricular volumes.

Analysis of Variance↗