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Biomedical subjects

R Harrington

Publications and source records attributed to R Harrington.

At least 55 records · Page 3Linked to original sources
PubMed1999

In vivo transduction of mouse epidermis with recombinant retroviral vectors: implications for cutaneous gene therapy.

Gene-based therapies may provide a way to treat inherited skin disorders but current approaches suffer serious limitations. The surgical procedures required to transplant ex vivo modified keratinocytes are likely to result in scarring and contracture, thereby limiting the area that can be treated. In addition, none of the methods currently available for in vivo gene transfer to epidermis leads to long-term transgene expression. The goal of this study was to develop a means for in vivo gene transfer to epidermis that would result in long-term transgene expression. We report here the first successful in vivo gene transfer that results in sustained transgene expression in epidermis. Hyperplastic mouse skin was transduced by direct injection of VSV-G pseudotyped retroviral vectors encoding the LacZ reporter gene. In mice tolerant to beta-galactosidase (beta-gal), transgene expression was noted in hair follicles and interfollicular epidermis for the duration of the experiment (16 weeks after transduction). Based on the kinetics of epidermal turnover in mouse skin, expression for this length of time strongly suggests stem cell transduction. In immunocompetent mice intolerant to beta-gal, transgene expression was lost by 3 weeks after transduction, concurrent with the onset of host immune responses to the transgene product.

Animals↗
PubMed1999

Minimal myocardial damage during coronary intervention is associated with impaired outcome.

AIMS: Studies on the glycoprotein IIb-IIIa receptor blocker abciximab in patients undergoing percutaneous coronary intervention consistently show a reduction in procedure-related myocardial infarction. Some such infarcts are characterized by elevated creatine kinase or creatine kinase-MB, without apparent clinical symptoms. The clinical relevance of such 'creatine kinase leaks' has been questioned. Therefore we investigated the relationship between post-procedural creatine kinase-MB elevation and outcome at the 6 month follow-up. METHODS AND RESULTS: Creatine kinase-MB, or total creatine kinase values were analysed in 5025 out of 6156 patients enrolled in the CAPTURE, EPIC and EPILOG studies. A consistent gradual increase in 6 month mortality was observed as creatine kinase-MB or creatine kinase levels increased: 1.1%, 2.1%, 1.8%, 3. 6% and 6.7% for creatine-MB or creatine ratios (relative to upper limit of normal) <1, 1-3, 3-5, 5-10 and >/=10, respectively. Also the incidence of death or (recurrent) myocardial infarction was related to creatine kinase-MB or creatine kinase ratios. Subsequent revascularization was not related to periprocedural myocardial infarction. By multivariable analysis, correcting for clinical and angiographic characteristics, mortality at 6 months was related to the enzyme (creatine kinase, creatine kinase-MB) ratio, a history of heart failure and age. The combined end-point of death and myocardial infarction was also related to these factors, as well as to a history of bypass surgery and unstable angina. CONCLUSION: Modest elevation of cardiac enzymes (creatine kinase-MB, creatine kinase) after percutaneous coronary intervention is associated with an increased risk of mortality and reinfarction during the 6 month follow-up. Measures to reduce such periprocedural infarcts are warranted.

Abciximab↗
PubMed1999

The MacArthur Three-City Outcome Study: evaluating multi-informant measures of young children's symptomatology.

OBJECTIVE: Three sites collaborated to evaluate the reliability and validity of 2 measures, developed in tandem to assess symptomatology and impairment in 4- to 8-year-old children: the Berkeley Puppet Interview Symptomatology Scales (BPI-S) and the Health and Behavior Questionnaire (HBQ). METHOD: In this case-control study, mothers, teachers, and children reported on multiple dimensions of children's mental health for 120 children (67 community and 53 clinic-referred children). RESULTS: The BPI-S and the parent and teacher versions of the HBQ demonstrated strong test-retest reliability and discriminant validity on a majority of symptom scales. Medium to strong effect sizes (Cohen d) indicated that children in the clinic-referred group were viewed by all 3 informants as experiencing significantly higher levels of symptomatology than nonreferred, community children. CONCLUSION: The availability of a set of multi-informant instruments that are psychometrically sound, developed in tandem, and developmentally appropriate for young children will enhance researchers' ability to investigate and understand symptomatology or the emergence of symptomatology in middle childhood.

Case-Control Studies↗
PubMed1999

Cost-effectiveness analysis of a home-based social work intervention for children and adolescents who have deliberately poisoned themselves. Results of a randomised controlled trial.

BACKGROUND: Little evidence exists regarding the effectiveness or cost-effectiveness of alternative treatment services in the field of child and adolescent psychiatry. AIMS: To assess the cost-effectiveness of a home-based social work intervention for young people who have deliberately poisoned themselves. METHOD: Children aged < or = 16 years, referred to child mental health teams with a diagnosis of deliberate self-poisoning were randomly allocated to either routine care (n = 77) or routine care plus the social work intervention (n = 85). Clinical and resource-use data were assessed over six months from the date of trial entry. RESULTS: No significant differences were found between the two groups in terms of the main outcome measures or costs. In a sub-group of children without major depression, suicidal ideation was significantly lower in the intervention group at the six-month follow-up (P = 0.01), with no significant differences in cost. CONCLUSIONS: A family-based social work intervention for children and adolescents who have deliberately poisoned themselves is as cost-effective as routine care alone.

Adolescent↗
PubMed1999

Genetic basis of attention deficit and hyperactivity.

BACKGROUND: Hyperkinetic disorder or attention-deficit hyperactivity disorder (ADHD) is an important clinical condition. AIMS: The research evidence for a genetic contribution to ADHD is reviewed. METHOD: Measurement of the phenotype, the extent to which attention deficit and hyperactivity are heritable and molecular genetic findings are discussed. Future research directions are also considered. RESULTS: ADHD is a familial disorder. Available adoption evidence suggests genetic influences are important. Twin studies have primarily focused on trait measures which have consistently been found to be highly heritable Molecular genetic studies of clinical disorder so far have suggested the involvement of the dopamine DRD-4 receptor gene and dopamine transporter gene (DAT1). However, these findings await further replication. CONCLUSIONS: Advances in psychiatric genetics and current research interest in the genetics of ADHD should improve our understanding of aetiological factors and have an impact on treatment.

Attention Deficit Disorder with Hyperactivity↗
PubMed1999

On diagnosing rare disorders rarely: appropriate use of screening instruments.

The main aim of this study was to determine whether child mental health professionals who regularly use questionnaires to screen for mental disorders know that these questionnaires have a low predictive value when the base rate of a disorder is low. The study was based on a representative sample of professionals who used questionnaires regularly to screen for mental disorders. They were set a problem in which a clinic sample was screened with a questionnaire that, at a certain cut-point, had 80 % sensitivity and 80 % specificity, and in which the true base rate of disorder was 10%. Only 10% (5/48) of respondents answered correctly that just 30 % of individuals who scored above this cut-point would actually have the disorder and more than half of respondents believed that 80 % would have the disorder. Both users and designers of questionnaires need to be more aware of and explicit about their drawbacks as screens for mental disorders.

Child↗
PubMed1998

Systematic review of efficacy of cognitive behaviour therapies in childhood and adolescent depressive disorder.

OBJECTIVE: To determine whether cognitive behaviour therapy is an effective treatment for childhood and adolescent depressive disorder. DESIGN: Systematic review of six randomised trials comparing the efficacy of cognitive behaviour therapy with inactive interventions in subjects aged 8 to 19 years with depressive disorder. MAIN OUTCOME MEASURE: Remission from depressive disorder. RESULTS: The rate of remission from depressive disorder was higher in the therapy group (129/208; 62%) than in the comparison group (61/168; 36%). The pooled odds ratio was 3.2 (95% confidence interval 1.9 to 5.2), suggesting a significant benefit of active treatment. Most studies, however, were based on relatively mild cases of depression and were of only moderate quality. CONCLUSIONS: Cognitive behaviour therapy may be of benefit for depressive disorder of moderate severity in children and adolescents. It cannot, however, yet be recommended for severe depression. Definitive large trials will be required to determine whether the results of this systematic review are reliable.

Adolescent↗
PubMed1998

Prevention and early intervention for depression in adolescence and early adult life.

Over the past decade there has been increasing interest in the possibility that early intervention might prevent mental disorders later in life. Indeed, in the United Kingdom the Department of Health recommends that health promotion should be one of the main functions of child mental health services, a suggestion that has been endorsed by professional bodies. It is easy to see why both purchasers and providers of mental health services would be interested in prevention, but will preventive interventions work in practice? This paper discusses the possibility of preventing depressive disorder in late adolescence and early adult life by intervening in childhood and early adolescence. The paper begins with a description of the phenomenology of depression and its risk factors. It then goes on to describe a framework of prevention and within this framework explores whether there is an adequate knowledge base. The general perspective that is presented is one of cautious scepticism. It is argued that difficulties in defining depression and identifying risk factors that can easily be remedied make it unlikely that within the foreseeable future primary prevention programmes will prove to be more effective than treatment and rehabilitation of affected individuals. The possibility that preventive programmes could do harm will also be discussed. The paper concludes with some proposals about appropriate targets for prevention. It is suggested that apart from a few policy areas where there are some relatively harmless measures that could protect from later depression, a balanced preventive programme will give higher priority to treatment services than to those concerned with early intervention.

Adolescent↗
PubMed1998

Retrovirus-mediated transduction of porcine keratinocytes in organ culture.

Direct transfer of new genetic information to keratinocytes in epidermis may prove effective in treating certain genodermatoses; however, current methods for in vivo gene transfer to skin do not lead to persistence of the transgene. The goal of this study was to explore direct gene transfer using retrovirus-mediated transduction. Retroviral vectors integrate a DNA copy of their genome into the host chromosome and therefore have the potential to effect a permanent gene therapy. To facilitate development of methods for in vivo transduction with retroviral vectors, a porcine skin organ culture model was constructed in which the denuded surface was repopulated with replicating keratinocytes from hair follicles and epidermal remnants. In situ transduction was carried out by topical application of two retrovirus vectors, MFGlacZ (10(7) blue forming units per ml) and LZRN pseudotyped with the G protein of vesicular stomatitis virus (VSV) (10(9) colony forming units per ml), each encoding the beta-galactosidase reporter gene and the latter encoding the neomycin phosphotransferase selectable gene. Beta-galactosidase expressing cells were observed more frequently with LZRN than with MFGlacZ; however, transduction efficiency remained low in both instances. At equivalent titers, the VSV-G pseudotyped retroviral vector was shown to transduce porcine keratinocytes more efficiently than a similar vector with the amphotropic envelope. The number of beta-gal+ cells in organ culture could be increased by selection of LZRN-transduced cells in situ with G418. To achieve transduction of epidermis in vivo, these studies point out the importance of high titer retroviral vectors, pseudotyping with VSV-G protein, and in situ selection.

Animals↗
PubMed1998

Which depressed patients respond to cognitive-behavioral treatment?

OBJECTIVE: To identify predictors of remission from major depression in adolescent patients given cognitive-behavioral therapy (CBT). METHOD: The study was based on 50 patients aged between 10 and 17 years who were obtained from two studies of CBT. A wide range of possible predictors was examined. RESULTS: Sixty percent remitted by the end of treatment. In multivariate analyses remission was associated with younger age and less social impairment. CONCLUSIONS: Depressed patients who respond to CBT tend to be younger and less severely impaired than those who do not respond.

Adolescent↗
PubMed1998

Lowering the burden of suffering from child psychiatric disorder: trade-offs among clinical, targeted, and universal interventions.

OBJECTIVE: To examine the trade-offs among clinical, targeted, and universal interventions aimed at lowering the burden of suffering from child psychiatric disorders. METHOD: Data from clinical and research studies were organized to show the advantages and disadvantages of the three strategies. RESULTS: Important trade-offs exist among these three approaches. The strategy to reduce the burden of suffering from child psychiatric disorder should consist of a number of concurrent steps. First, effective universal programs should be in place. Targeted programs should follow for those not helped sufficiently by the universal programs. Finally, for those unaffected by the targeted programs, clinical services should be available. CONCLUSION: An optimal mix of universal, targeted, and clinical programs is needed. The nature of the combination will change as knowledge accumulates, and there will always be trade-offs among these three. Acad.

Child↗
PubMed1998

Surgical management of giant nonmelanoma skin neoplasia.

BACKGROUND: Management of advanced integumentary malignancy has been controversial. We have evaluated and treated 10 patients with giant nonmelanoma skin neoplasias more than 8 cm in diameter. METHODS: Aggressive surgical ablation was prospectively recommended to treat giant basal cell or mixed basosquamous tumors and two purely squamous cell tumors. Radiation therapy was given in three surgical patients. Our data are analyzed retrospectively. RESULTS: Survival of the two patients who refused surgery was measured in weeks. One patient who refused adequate surgery survived 9 months before dying. All of the adequately treated surgical patients are alive as of this writing, including one who had subsequent resection of pulmonary metastases. Three patients required free tissue transfer. The average survival of surgically treated patients was 2.7 years. CONCLUSION: An aggressive surgical approach to the management of advanced/giant skin neoplasia is justifiable and the only treatment that may produce long-term survivability.

Aged↗
PubMed1998

Psychological treatment of depression in children and adolescents. A review of treatment research.

BACKGROUND: This paper reviews research on the psychological treatment of depression in children. METHOD: Manual and computer literature searches were performed. RESULTS: The most promising psychological interventions for depression in children are individual rather than family therapies. Cognitive--behavioural therapy seems to be an effective treatment for depressive symptoms and mild depressive disorders. It may also be a useful preventive intervention, though this remains to be conclusively demonstrated. There have been no systematic studies comparing psychological treatments with medication. CONCLUSIONS: Studies comparing psychological treatments and medication are now required.

Adolescent↗
PubMed1998

Randomized trial of a home-based family intervention for children who have deliberately poisoned themselves.

OBJECTIVE: To establish whether an intervention given by child psychiatric social workers to the families of children and adolescents who had attempted suicide by taking an overdose reduced the patients' suicidal feelings and improved family functioning. METHOD: One hundred sixty-two patients, aged 16 or younger, who had deliberately poisoned themselves were randomly allocated to routine care (n = 77) or routine care plus the intervention (n = 85). The intervention consisted of an assessment session and four home visits by the social workers to conduct family problem-solving sessions. The control group received no visits. Both groups were assessed at the time of recruitment and 2 and 6 months later. The primary outcome measures were the Suicidal Ideation Questionnaire, the Hopelessness Scale, and the Family Assessment Device. RESULTS: There were no significant differences in the primary outcomes between the intervention and control groups at either of the outcome assessments. Parents in the intervention group were more satisfied with treatment (mean difference 1.4 [95% confidence interval 0.6 to 2.1]). A subgroup without major depression had much less suicidal ideation at both outcome assessments (analysis of covariance p < .01) compared with controls. CONCLUSIONS: The home-based family intervention resulted in reduced suicidal ideation only for patients without major depression.

Adolescent↗
PubMed1997

Genotypic variation among different phenotypes within aphid clones.

Most aphid species Hemiptera: Aphididae are parthenogenetic between periods of sexual reproduction. They are also highly polyphenic, with different adult morphs occurring in the life cycle, piz. winged, wingless, asexual and sexual. It is assumed that aphids born in a parthenogenetic clonal lineage are genetically identical regardless of the final adult form with the exception of sexual forms). Using the randomly amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) we have found that different asexual adult phenotypes winged and wingless of some clones of two cereal aphid species (the grain aphid, Sitobion avenae (F.) and the bird-cherry aphid. Rhopalosiphum padi (L.) may be distinguished by the presence or absence of one or more RAPD-PCR bands. In three of nine clones examined, such differences were found, and Southern blotting and hybridization of the discriminating bands confirmed these to be of aphid origin, rather than due to endosymbiotic bacteria or contaminating fungi. The main 248 and 296 bp bands, in the two species respectively, were sequenced and found to be A/T rich. The smaller band showed 57% homology with white striated muscle over a stretch of 90 bp. Genomic DNA treated with dimethyl sulphoxide to remove secondary structures still showed differences in RAPD-PCR profiles between winged and wingless morphs within the unusual clones. This discovery may be widespread and therefore it is important to understand the phenomenon in relation to clonal organisms.

Animals↗
PubMed1997

Psychiatric disorders in the relatives of depressed probands. I. Comparison of prepubertal, adolescent and early adult onset cases.

Research with adults suggests that early onset of depression is associated with increased rates of depression among relatives. This paper presents results, of a family study that tested the hypothesis that prepubertal depression was associated with a greater familial loading of depression than the postpubertal form, which in turn had a greater familial loading than adult onset depression. Probands were from a child to adult longitudinal study. Psychiatric disorders among relatives were assessed with family interview and family history methods 'blind' to all findings regarding the proband. Contrary to expectation, familial rates of depression did not differ significantly between the groups. However, manic disorders tended to be more common among the relatives of postpubertal depressed cases than among the relatives of adult onset cases. Moreover, relatives of prepubertal depressed subjects had higher rates of criminality and family discord than postpubertal subjects. Prepubertal onset depressive disorders appear to be relatively distinct from postpubertal forms.

Adolescent↗