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Biomedical subjects

R Goodman

Publications and source records attributed to R Goodman.

At least 37 records · Page 2Linked to original sources

Association between behaviour at age 3 years and adult criminality.

BACKGROUND: The continuity in antisocial behaviour into adulthood from middle childhood is well established but it is not clear whether this is also true of the pre-school period. AIMS: To determine whether pre-school behaviour problems increase the risk of later criminal convictions and add to risk associated with family and social circumstances. METHOD: The records of adult convictions were traced for a general population sample (n=828) initially assessed at age 3 years. RESULTS: The risk of having any adult conviction was related to soiling, daytime enuresis, activity level and management difficulties, and that of having an adult violent offence to recent-onset daytime enuresis, management difficulties and temper tantrums. The only other predictors of later convictions were the child's gender and social competence at age 3 years. CONCLUSIONS: The presence of specific behaviour problems in the pre-school period places the child at increased risk of being convicted of an adult offence. Family and social circumstances at age 3 years did not predict later convictions.

Adult↗

Prevalence of obsessive-compulsive disorder in the British nationwide survey of child mental health.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disorder that appears to be underdiagnosed and undertreated, despite the evidence for effective treatments. There are variable estimates of OCD prevalence in the under-16s and published rates give little indication of age trends. AIMS: To establish the prevalence and associates of OCD in young people aged 5-15 years. METHOD: A nationwide (UK) epidemiological study of rates of psychiatric disorder in 5- to 15-year-olds (1999 British Child Mental Health Survey): 10 438 children were assessed. RESULTS: Twenty-five children with OCD were identified (weighted overall prevalence 0.25%; 95% CI 0.14-0.35), with prevalence rising exponentially with increasing age. Compared with normal controls, children with OCD were more likely to be from lower socio-economic class and of lower intelligence. Only three of these children had been seen by specialist children's services. CONCLUSIONS: Although OCD is rare in young children, the rate increases towards the adult rates at puberty. Children with OCD have additional psychosocial disadvantage. The majority of the childhood cases identified in this survey appear to have been undetected and untreated.

Adolescent↗

The impact of antidepressant discontinuation versus antidepressant continuation on 1-year risk for relapse of bipolar depression: a retrospective chart review.

BACKGROUND: Current treatment guidelines recommend discontinuation of an antidepressant within 3 to 6 months after remission of depression in patients with bipolar illness. Yet few studies directly compare the impact of antidepressant discontinuation versus antidepressant continuation on the risk for depressive relapse in patients with bipolar disorder who have been successfully treated for a depressive episode. METHOD: In a retrospective chart review, patients with DSM-IV bipolar disorder who were treated for an index episode of depression by adding antidepressant medication to ongoing mood stabilizer medications were identified. The risk of depressive relapse in 25 subjects who stopped antidepressant medications after improvement was compared with the risk of depressive relapse in 19 subjects who continued antidepressants after improvement. RESULTS: Termination of antidepressant medication significantly increased the risk of a depressive relapse. Antidepressant continuation was not significantly associated with an increased risk of mania. CONCLUSION: While this study may have been limited by the retrospective nature of the chart review, nonrandomized assignment of treatment, and reliance on unstructured progress notes, it suggests that antidepressant discontinuation may increase the risk of depressive relapse in some patients with bipolar disorder. Further research is needed to clarify whether maintenance antidepressant treatment may be warranted in some patients with bipolar disorder, especially in those with frequent recurrent depressive episodes.

Antidepressive Agents↗

Cytoprotection by electromagnetic field-induced hsp70: a model for clinical application.

A unique approach to clinical application of cytoprotection is offered by electromagnetic (EM) field induction of stress proteins. EM fields are noninvasive and easily applied, as compared with the current hyperthermia protocols. Fertilized dipteran eggs and cultured rodent cardiomyocytes (H9c2 cells) were used as models to test EM fields for their ability to induce increased hsp70 levels for effective cytoprotection. Eggs preconditioned with an 8 microT 60Hz EM field for 30 min had 114% increase in hsp70 levels, and an average 82% increase in survival, following a lethal temperature of 36.5 degrees C. Thermal preconditioning at 32 degrees C was not nearly as effective in dipteran eggs, inducing only a 44% increase in survival. Preconditioning of cultured murine cardiomyocytes (H9c2 cells) with an 8 microT 60 Hz field induced a 77% average increase in hsp70 levels.

Animals↗

ERK1/2 phosphorylation, induced by electromagnetic fields, diminishes during neoplastic transformation.

It has been suggested that electromagnetic (EM) fields can act as co-promoters during neoplastic transformation. To examine this possibility, we studied the effects of 0.8-, 8-, 80-, and 300-microT 60-Hz electromagnetic (EM) fields in INITC3H/10T1/2 mouse fibroblast cells. These cells are transformed carcinogenically by methylcholanthrene, but the neoplastic phenotype can be suppressed indefinitely by the presence of retinyl acetate (RAC) in the culture medium. The effects of EM field exposures were examined at three stages: (1) before initiation of transformation (i.e., RAC in the culture media); (2) early in the transformation process (4 days after withdrawal of RAC); and (3) at full of neoplastic transformation (10 days after withdrawal of RAC). EM field exposures induced significant increases in protein levels for hsp70 and c-Fos and in AP-1 binding activity. EM fields induced phosphorylation of MAPK/ERK1/2 before the onset of transformation, but these increases diminished during the transformation process. No phosphorylation in the other major extracellular stress pathway, SAPK/JNK, was detected in cells exposed to EM fields at any time before, during, or after neoplastic transformation. Human cells HL60, MCF7, and HTB124, exposed to EM fields, also showed MAPK/ERK1/2 phosphorylation. Cells treated with the phorbol ester, TPA, served as positive controls for AP-1 activation, c-Fos protein synthesis, and ERK1/2 phosphorylation. There was no indication that EM fields affected the rate of cell transformation or acted as a co-promoter, under the conditions of this study.

Animals↗

Vagus nerve stimulation (VNS) for treatment-resistant depressions: a multicenter study.

BACKGROUND: Vagus Nerve Stimulation (VNS) delivered by the NeuroCybernetic Prosthesis (NCP) System was examined for its potential antidepressant effects. METHODS: Adult outpatients (n = 30) with nonpsychotic, treatment-resistant major depressive (n = 21) or bipolar I (n = 4) or II (n = 5; depressed phase) disorders who had failed at least two robust medication trials in the current major depressive episode (MDE) while on stable medication regimens completed a baseline period followed by NCP System implantation. A 2-week, single-blind recovery period (no stimulation) was followed by 10 weeks of VNS. RESULTS: In the current MDE (median length = 4.7 years), patients had not adequately responded to two (n = 9), three (n = 2), four (n = 6), or five or more (n = 13) robust antidepressant medication trials or electroconvulsive therapy (n = 17). Baseline 28-item Hamilton Depression Rating Scale (HDRS(28)) scores averaged 38.0. Response rates (> or =50% reduction in baseline scores) were 40% for both the HDRS(28) and the Clinical Global Impressions-Improvement index (score of 1 or 2) and 50% for the Montgomery-Asberg Depression Rating Scale. Symptomatic responses (accompanied by substantial functional improvement) have been largely sustained during long-term follow-up to date. CONCLUSIONS: These open trial results suggest that VNS has antidepressant effects in treatment-resistant depressions.

Adolescent↗

Promoter-targeted selection and isolation of neural progenitor cells from the adult human ventricular zone.

Adult humans, like their nonhuman mammalian counterparts, harbor persistent neural progenitor cells in the forebrain ventricular lining. In the absence of adequate surface markers, however, these cells have proven difficult to isolate for study. We have previously identified and selected neural progenitor cells from both the fetal and adult rodent ventricular zone (VZ), by sorting forebrain cells transfected with plasmid DNA encoding the gene for green fluorescent protein driven by the early neuronal promoter for Talpha1 tubulin (P/Talpha1:hGFP). We have now extended this approach by purifying both P/Talpha1:hGFP tubulin-defined neuronal progenitors, as well as potentially less committed E/nestin:hGFP-defined neural progenitor cells, from the adult human VZ. The ventricular wall of the temporal horn of the lateral ventricle was dissected from temporal lobes obtained from four adult patients undergoing therapeutic lobectomy. These samples were dissociated, and the cultured cells transduced with either P/Talpha1:hGFP or E/nestin:EGFP plasmid DNA. A week later, the cells were redissociated, selected via fluorescence-activated cell sorting (FACS) on the basis of neural promoter-driven GFP expression, and replated. The majority of these cells expressed the early neuronal protein betaIII-tubulin upon FACS; within the week thereafter, most matured as morphologically evident neurons that coexpressed betaIII-tubulin and microtubule-associated protein (MAP)-2. Many of these neurons had incorporated bromodeoxyuridine in vitro in the days before FACS, indicating their mitogenesis in vitro. Thus, the use of fluorescent transgenes under the control of early neural promoters permits the enrichment of neuronal progenitor cells from the adult human ventricular zone. The specific acquisition, in both purity and number, of residual neural progenitor cells from the adult human brain may now permit hitherto unfeasible studies of both their biology and practical application.

Adult↗

The role of MRI in the assessment of scaphoid fracture healing: a pilot study.

Twenty-two patients with fracture of the scaphoid treated by cast immobilisation underwent clinical examination, radiography and MR scanning 6 weeks after injury. On clinical and plain radiographic criteria alone, 12 patients were considered sufficiently healed to warrant mobilisation. The remaining 10 patients were considered unhealed and were immobilised for a further period. A musculoskeletal radiologist, blinded to the clinical diagnosis, reviewed the MRI scans. Of the 10 patients considered unhealed, 5 had the MR appearances of a united fracture, based on normal marrow signal across the fracture line on T1-weighted images. Of the 12 patients deemed to have united, union could be confirmed by MRI criteria in only 5, but all 12 were healed at 1 year. The results suggest that MRI can provide additional information in this group of patients. It can confirm bony union in a high proportion of patients deemed clinically non-united. Its use in this context will allow a more rapid mobilisation and return to normal function. The significance of persistent MR signal abnormalities in patients who have clinical and radiographic signs of healing merits further study.

Adult↗

Predicting type of psychiatric disorder from Strengths and Difficulties Questionnaire (SDQ) scores in child mental health clinics in London and Dhaka.

A computerised algorithm was developed to predict child psychiatric diagnoses on the basis of the symptom and impact scores derived from Strengths and Difficulties Questionnaires (SDQs) completed by parents, teachers and young people. The predictive algorithm generates "unlikely", "possible" or "probable" ratings for four broad categories of disorder, namely conduct disorders, emotional disorders, hyperactivity disorders, and any psychiatric disorder. The algorithm was applied to patients attending child mental health clinics in Britain (N = 101) and Bangladesh (N = 89). The level of chance-corrected agreement between SDQ prediction and an independent clinical diagnosis was substantial and highly significant (Kendall's tau b between 0.49 and 0.73; p < 0.001). A "probable" SDQ prediction for any given disorder correctly identified 81-91% of the children who definitely had that clinical diagnosis. There were more false positives than false negatives, i.e. the SDQ categories were over-inclusive. The algorithm appears to be sufficiently accurate and robust to be of practical value in planning the assessment of new referrals to a child mental health service.

Adolescent↗

Comparing the German versions of the Strengths and Difficulties Questionnaire (SDQ-Deu) and the Child Behavior Checklist.

The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioural screening questionnaire that can be completed in about 5 minutes by the parents and teachers of 4-16 year olds. The scores of the English version correlate well with those of the considerably longer Child Behavior Checklist (CBCL). The present study compares the German versions of the questionnaires. Both SDQ and CBCL were completed by the parents of 273 children drawn from psychiatric clinics (N = 163) and from a community sample (N = 110). The children from the community sample also filled in the SDQ self-report and the Youth Self Report (YSR). The children from the clinic sample received an ICD-10 diagnosis if applicable. Scores from the parent and self-rated SDQ and CBCL/YSR were highly correlated and equally able to distinguish between the community and clinic samples, with the SDQ showing significantly better results regarding the total scores. They were also equally able to distinguish between disorders within the clinic sample, the only significant difference being that the SDQ was better able to differentiate between children with and without hyperactivity-inattention. The study shows that like the English originals, the SDQ-Deu and the German CBCL are equally valid for most clinical and research purposes.

Adolescent↗

The N-terminal domain of p73 interacts with the CH1 domain of p300/CREB binding protein and mediates transcriptional activation and apoptosis.

The newly identified p53 homolog p73 mimics the transcriptional function of p53. We have investigated the regulation of p73's transcriptional activity by p300/CREB binding protein (CBP). p73-p300 complexes were identified in HeLa cell extracts by cofractionation and coimmunoprecipitation assays. The p73-p300 interaction was confirmed in vitro by glutathione S-transferase-protein association assays and in vivo by coimmunoprecipitating the overexpressed p300 and p73 in human p53-free small-cell lung carcinoma H1299 or osteosarcoma Saos-2 cells. The N terminus but not the N-terminal truncation of p73 bound to the CH1 domain (amino acids [aa] 350 to 450) of p300/CBP. Accordingly, this p73 N-terminal deletion was unable to activate transcription or to induce apoptosis. Overexpression of either p300 or CBP stimulated transcription mediated by p73 but not its N-terminally deleted mutant in vivo. The N-terminal fragment from aa 19 to 597, but not the truncated fragment from aa 242 to 1700 of p300, reduced p73-mediated transcription markedly. p73-dependent transcription or apoptosis was partially impaired in either p300- or CBP-deficient human breast carcinoma MCF-7 or H1299 cells, suggesting that both coactivators mediate transcription by p73 in cells. These results demonstrate that the N terminus of p73 directly interacts with the N-terminal CH1 domain of p300/CBP to activate transcription.

Apoptosis↗

Using the Strengths and Difficulties Questionnaire (SDQ) to screen for child psychiatric disorders in a community sample.

BACKGROUND: Child psychiatric disorders are common and treatable, but often go undetected and therefore remain untreated. AIMS: To assess the Strengths and Difficulties Questionnaire (SDQ) as a potential means for improving the detection of child psychiatric disorders in the community. METHOD: SDQ predictions and independent psychiatric diagnoses were compared in a community sample of 7984 5- to 15-year-olds from the 1999 British Child Mental Health Survey. RESULTS: Multi-informant (parents, teachers, older children) SDQs identified individuals with a psychiatric diagnosis with a specificity of 94.6% (95% Cl 94.1-95.1%) and a sensitivity of 63.3% (59.7-66.9%). The questionnaires identified over 70% of individuals with conduct, hyperactivity, depressive and some anxiety disorders, but under 50% of individuals with specific phobias, separation anxiety and eating disorders. Sensitivity was substantially poorer with single-informant rather than multi-informant SDQs. CONCLUSIONS: Community screening programmes based on multi-informant SDQs could potentially increase the detection of child psychiatric disorders, thereby improving access to effective treatments.

Adolescent↗

Parents and GPs at cross-purposes over hyperactivity: a qualitative study of possible barriers to treatment.

BACKGROUND: Although childhood hyperactivity is a common, serious, and treatable disorder, most affected children in Britain do not receive effective treatment. AIM: To investigate the views that parents and GPs hold about hyperactivity, and to explore how far these views, and clashes between these views, influence access to services. METHOD: Qualitative study making use of semi-structured interviews with 10 general practitioners (GPs) and 29 parents of hyperactive children drawn from parents' groups, community services, and specialist clinics. RESULTS: The views of parents and GPs differed markedly. Parents generally saw severe hyperactivity as a long-lasting, biologically-based problem that needed treatment in its own right and that benefited from diagnosis. Most of the GPs were unsure whether hyperactivity was a medical disorder warranting a label and specific treatment, and often saw it as a passing phase related to family stresses. Parents worried that professionals would blame them for their child's problem, whereas many GPs saw the parent's tendency to medicalise as a way to avoid thinking about their own shortcomings in parenting. CONCLUSION: Access to treatment was influenced by the views of parents and GPs, by the clashes between these views, and by each group's perceptions of the other group's beliefs. Clashes between the views of parents and GPs were particularly likely to lead to misunderstandings, dissatisfaction, and lack of access to effective help.

Attention Deficit Disorder with Hyperactivity↗

Variable expression of the autism broader phenotype: findings from extended pedigrees.

Factors influencing the rate, form, and severity of phenotypic expression among relatives of autistic probands are examined. Family history data on 3095 first- and second-degree relatives and cousins from 149 families with a child with autism and 36 families with a child with Down syndrome are studied. The results provide further evidence of an increased risk among autism relatives for the broadly defined autism phenotype. Of proband characteristics, severity of autism and obstetric optimality were confirmed as being related to familial loading for probands with speech. There was little variation in loading among probands lacking speech. The type of phenotypic profile reported in relatives appeared little influenced by characteristics of the relative or the proband, except for variation by degree of relative, parental status of relative, and perhaps proband's birth optimality score. Phenotypic rates among parents suggested reduced fitness for the severest and more communication-related forms of expression but not for the more mild and social forms of expression. Patterns of expression within the families did not support a simple X-linked nor an imprinted X-linked mode of inheritance. The basis for sex differences in rates of expression is discussed.

Autistic Disorder↗

The Development and Well-Being Assessment: description and initial validation of an integrated assessment of child and adolescent psychopathology.

The Development and Well-Being Assessment (DAWBA) is a novel package of questionnaires, interviews, and rating techniques designed to generate ICD-10 and DSM-IV psychiatric diagnoses on 5-16-year-olds. Nonclinical interviewers administer a structured interview to parents about psychiatric symptoms and resultant impact. When definite symptoms are identified by the structured questions, interviewers use open-ended questions and supplementary prompts to get parents to describe the problems in their own words. These descriptions are transcribed verbatim by the interviewers but are not rated by them. A similar interview is administered to 11-16-year-olds. Teachers complete a brief questionnaire covering the main conduct, emotional, and hyperactivity symptoms and any resultant impairment. The different sorts of information are brought together by a computer program that also predicts likely diagnoses. These computer-generated summary sheets and diagnoses form a convenient starting point for experienced clinical raters, who decide whether to accept or overturn the computer diagnosis (or lack of diagnosis) in the light of their review of all the data, including transcripts. In the present study, the DAWBA was administered to community (N = 491) and clinic (N = 39) samples. There was excellent discrimination between community and clinic samples in rates of diagnosed disorder. Within the community sample, subjects with and without diagnosed disorders differed markedly in external characteristics and prognosis. In the clinic sample, there was substantial agreement between DAWBA and case note diagnoses, though the DAWBA diagnosed more comorbid disorders. The use of screening questions and skip rules greatly reduced interview length by allowing many sections to be omitted with very little loss of positive information. Overall, the DAWBA successfully combined the cheapness and simplicity of respondent-based measures with the clinical persuasiveness of investigator-based diagnoses. The DAWBA has considerable potential as an epidemiological measure, and may prove to be of clinical value too.

Adolescent↗

Electromagnetic fields may act directly on DNA.

A wide variety of environmental stimuli induce the expression of stress response genes, including high temperatures, hypoxia, heavy metal ions, and amino acid analogs. Stress genes are also induced by low frequency magnetic fields. The cellular response to magnetic fields is activated by unusually weak stimuli, and involves pathways only partially associated with heat shock stress. Since magnetic fields interact with moving charges, as we have shown in enzymes, it is possible that magnetic fields stimulate the stress response by interacting directly with moving electrons in DNA. In this paper, we review several lines of evidence that support this hypothesis.

Animals↗

A magnetic field-responsive domain in the human HSP70 promoter.

HSP70 gene expression is induced by a wide range of environmental stimuli, including 60-Hz electromagnetic fields. In an earlier report we showed that the induction of HSP70 gene expression by magnetic fields is effected at the level of transcription and is mediated through c-myc protein binding at two nCTCTn sequences at -230 and -160. in the human HSP70 promoter. We report on the identification of a third c-myc binding site (between -158 and -162) that is an important regulator of magnetic field-induced HSP70 expression. We also show that the heat shock element (HSE), lying between -180 and -203, is required for induction of HSP70 gene expression by magnetic fields. The HSE centered at -100 alone is insufficient.

Binding Sites↗

Peer problems of 9- to 11-year-old children with hemiplegia in mainstream schools. Can these be predicted?

Is it possible to predict relatively early in the life of children with disabilities those who are likely to develop peer problems if they get no extra help? This question is examined in our prospective study of a representative sample of children with hemiplegia attending mainstream schools. Hemiplegia is a particularly suitable model for studying integration as it is a relatively homogeneous condition that does not usually preclude mainstream placement. Our aim was to investigate whether the excess of peer problems could be predicted from information obtained some 4 years earlier. A representative sample of 55 children with hemiplegia in mainstream education was followed prospectively from a mean age of 7.1 years (Time 1) to a mean age of 10.7 years (Time 2). Using standardized measures of peer rejection, lack of friends, and victimization, two-thirds of the sample had at least one of these problems at Time 2. A greater number of peer problems was primarily predicted by two Time-1 variables: lower IQ and more teacher-reported externalizing problems (disruptiveness and hyperactivity). A risk index based on these two variables identified a high-risk subgroup that might particularly have benefited from early intervention to reduce behavioural problems, and nurture social skills. As more children with special needs are integrated into mainstream schools, it is increasingly important to remember that supporting these children requires appropriate provision to foster their social as well as their academic and physical development.

Child↗