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Biomedical subjects

S Young

Publications and source records attributed to S Young.

At least 37 records · Page 2Linked to original sources

The specificity of clinical characteristics in adults with attention-deficit/hyperactivity disorder: a comparison with patients with borderline personality disorder.

Characteristics of DSM-IV attention-deficit/hyperactivity disorder (ADHD) in adults can also be found as part of other psychiatric disorders. This study investigated the specificity of adult ADHD features in relation to patients with borderline personality disorder (BPD), a syndrome which shares some of its intrinsic features with ADHD and often co-occurs with ADHD. A group of 20 adult patients selected on the basis of a diagnosis of ADHD and 20 patients selected on the basis of a diagnosis of BPD were assessed by the self-report Attention Deficit Scales for Adults (ADSA). The two groups were matched for age, verbal IQ and gender. Of the nine ADSA scales, seven showed significant inter-group differences, in particular involving attention, organisation and persistence. The 'Consistency/Long-Term' scale, which mainly reflects impaired task and goal persistence, was the best discriminator between the groups. Furthermore, ratings on this scale correlated significantly with the error score of a computer-administered task of spatial working memory, the performance of which has been reported to be impaired in patients with ADHD. The results provide further validation for the ADSA scales and support a previous claim that 'long-term consistencies', i.e., related to task and goal persistence, is 'the centrepiece behavioural issue' for adults with ADHD.

Adult↗

Characteristic neurocognitive profile associated with adult attention-deficit/hyperactivity disorder.

BACKGROUND: It is now accepted that attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. However, relative to the considerable literature concerning the profile of neurocognitive deficits associated with this disorder in childhood, equivalent investigations in adult populations have been less common. The current study examined cognitive function in adults diagnosed with ADHD employing well-validated neuropsychological tasks. METHOD: Nineteen adult patients who satisfied DSM-IV criteria for ADHD and 19 matched (gender, age and verbal IQ), non-clinical control subjects were recruited. Patients were either unmedicated or had abstained from a psychostimulant medication regime for at least 24 h prior to neurocognitive assessment. A functionally wide-ranging test battery was administered. RESULTS: Relative to controls, ADHD adults performed significantly worse on spatial working memory, planning, and attentional-set shifting tests and were significantly slower to respond to target stimuli on the go/no-go task. In contrast, the two subject groups performed equivalently on decision-making and pattern/spatial recognition memory assessments. CONCLUSIONS: The demonstration of neuropsychological dysfunction in the adult ADHD cohort provides some support for the validity of this diagnosis in adulthood. In particular, there is broad consistency between the cognitive profile revealed in the current investigation and that previously demonstrated in a study of medication-naïve ADHD children. There is evidence that frontostriatal function is especially disrupted.

Adult↗

Bystander help within a polyepitope DNA vaccine improves immune responses to influenza antigens.

A polyepitope DNA vaccine has the potential to generate protective immune responses to a range of antigens in a single construct. We investigated whether it was possible to obtain responses to individual epitopes from different antigens, directly linked in a string, and whether the response to a given epitope was enhanced by adjacent epitopes within the construct. A polyepitope plasmid was created, which included three Th epitopes (influenza haemagglutinin, moth cytochrome c and ovalbumin), a Tc epitope (ovalbumin) and two B cell epitopes (haemagglutinin and ovalbumin). Mice were immunized with DNA by using a gene gun. Responses to the polyepitope DNA vaccine were compared with those to DNA vaccine comprising only the haemagglutinin Th and B epitopes (HAT(h)B) or with responses to the recombinant protein. These experiments showed that the polyepitope DNA vaccine induced greater antigen-specific responses to HAT(h)B peptide than the HAT(h)B DNA vaccine. Antigen-specific in vivo cytotoxic responses following polyepitope DNA vaccination were also clearly demonstrable. We conclude that a 'naked DNA' polyepitope vaccine generates specific responses to constituent epitopes and that adjacent irrelevant epitopes may enhance these responses.

Animals↗

Impaired spatial working memory in adults with attention-deficit/hyperactivity disorder: comparisons with performance in adults with borderline personality disorder and in control subjects.

OBJECTIVE: This study investigated a previous claim that working memory may be 'particularly impaired' in adult attention-deficit/hyperactivity disorder (ADHD), compared with other psychiatric disorders which affect frontal lobe-mediated executive functions. METHOD: Performance on spatial working memory (SWM) and two additional tasks were investigated for adult patients selected on the basis of DSM-IV ADHD (n = 19), adult patients selected on the basis of borderline personality disorder (BPD) (n = 19), and non-clinical control subjects (n = 19). Groups were matched for age, verbal IQ and gender. RESULTS: Analysis of variance showed that the ADHD group had significant impairment of SWM performance relative to the non-clinical controls. Although there was a trend towards impairment in the BPD group relative to non-clinical controls, this did not reach significance. CONCLUSION: The results are consistent with the claim that aspects of working memory are 'particularly impaired' in adult ADHD. Also, the BPD group had a longer deliberation time for one of the additional tasks, compared with the ADHD group, which indicated that the patient groups may have different patterns of neuropsychological impairments.

Adult↗

Prevalence and service implications of health anxiety in genitourinary medicine clinics.

A comparison of the prevalence of health anxiety in genitourinary medicine (GUM) clinics in two UK centres was carried out using a new rating scale, the Health Anxiety Inventory (HAI). The relationship of health anxiety to demographic and clinical variables, and its impact on service contacts, was also examined in one of these centres. 694 patients were assessed and significant health anxiety was identified in 8-11%. HAI scores were stable over time and high levels persisted in the absence of treatment. Attenders with sexually transmitted infections had significantly lower levels of health anxiety than those with other conditions. Contacts with clinic doctors and health advisors in the nine months before and after assessment were significantly greater in those with high health anxiety, with doctor appointments 37% higher in the high HAI group (P = 0.005). Health anxiety is a source of considerable morbidity in GUM clinics deserving further study.

Adult↗

Analogous pleiotropic effects of insecticide resistance genotypes in peach-potato aphids and houseflies.

We show that single-point mutations conferring target-site resistance (kdr) to pyrethroids and DDT in aphids and houseflies, and gene amplification conferring metabolic resistance (carboxylesterase) to organophosphates and carbamates in aphids, can have deleterious pleiotropic effects on fitness. Behavioural studies on peach-potato aphids showed that a reduced response to alarm pheromone was associated with both gene amplification and the kdr target-site mutation. In this species, gene amplification was also associated with a decreased propensity to move from senescing leaves to fresh leaves at low temperature. Housefly genotypes possessing the identical kdr mutation were also shown to exhibit behavioural differences in comparison with susceptible insects. In this species, resistant individuals showed no positional preference along a temperature gradient while susceptible genotypes exhibited a strong preference for warmer temperatures.

Animals↗

Comparison of parent knowledge, therapy utilization and severity of atopic eczema before and after explanation and demonstration of topical therapies by a specialist dermatology nurse.

BACKGROUND: The failure of patients to take medicines in a way that leads to clinical benefit is a major challenge. A consensus has emerged that, on average, compliance sufficient to obtain therapeutic objectives occurs about half the time, with noncompliance contributing to therapeutic failure in the other half. These figures refer to simple oral regimens. There has been little work assessing compliance/concordance with complex treatment regimens for atopic eczema. Asthma schools led by specialist nurses have been shown to improve knowledge, use of therapies and clinical outcome. OBJECTIVES: To determine the effect of education and demonstration of topical therapies by specialist dermatology nurses on therapy utilization and severity of atopic eczema. METHODS: Fifty-one children with atopic eczema attending a paediatric dermatology clinic were followed for up to 1 year. At each visit the parent's knowledge about atopic eczema and its treatment and therapy utilization was recorded. The severity of the eczema was recorded using the six area, six sign atopic dermatitis severity score (SASSAD) and parental assessment of itch, sleep disturbance and irritability. At the first visit a specialist dermatology nurse explained and demonstrated how to use all of the topical treatments. This education was repeated at subsequent visits depending on the knowledge of the parent. RESULTS: At baseline less than 5% of parents had received/recalled receiving any explanation of the causes of eczema or demonstration of how to apply topical treatments. The eczema was poorly controlled in all children (mean SASSAD 42.9). Of the children, 24% were not being treated with any emollient cream/ointment; the mean use was 54 g weekly. Of the children, 25% were being inappropriately treated with potent or very potent topical steroids. Following repeated education and demonstration of topical therapies by a specialist dermatology nurse, there was an 89% reduction in the severity of the eczema. The main change in therapy utilization was an 800% increase in the use of emollients (to 426 g weekly of emollient cream/ointment) and no overall increase in the use of topical steroids, accounting for potency and quantity used. CONCLUSIONS: This study reinforces the importance of specialist dermatology nurses in the management of atopic eczema. It also confirms the opinion of patients, patient support groups, dermatologists and best practice guidelines that the most important intervention in the management of atopic eczema is to spend time to listen and explain its causes and demonstrate how to apply topical therapies.

Administration, Topical↗

The association of age and semen quality in healthy men.

BACKGROUND: Although the effect of maternal age on fertility is well known, it is unclear whether paternal age also affects fertility. This cross-sectional study sought to characterize the association between age and semen quality, a well-known proxy of fertility status. METHODS: A convenience sample of 97 non-smoking men (aged 22-80 years) without known fertility problems was recruited from a national government laboratory. The men provided semen samples and information relating to lifestyle, diet, medical and occupational details. Semen volume (ml), sperm concentration (x10(6)/ml), total sperm count (x10(6)), motility (%), progressive motility (%) and total progressively motile sperm count (x10(6)) were measured. RESULTS: After adjusting for covariates, semen volume decreased by 0.03 ml per year of age (95% CI: -0.05, -0.01); motility decreased by 0.7% per year (95% CI: -0.92, -0.43); progressive motility decreased by 3.1% per year (95% CI: -4.5, -1.6); and total progressively motile sperm count decreased by 4.7% per year (95% CI: -7.2, -2.2). There was a suggested decrease in sperm concentration and count. The proportion of men with abnormal volume, concentration and motility was significantly increased across the age decades. CONCLUSIONS: In a convenience sample of healthy men from a non-clinical setting, semen volume and sperm motility decreased continuously between 22-80 years of age, with no evidence of a threshold.

Adult↗

Evaluation of high fidelity patient simulator in assessment of performance of anaesthetists.

BACKGROUND: There is increasing emphasis on performance-based assessment of clinical competence. The High Fidelity Patient Simulator (HPS) may be useful for assessment of clinical practice in anaesthesia, but needs formal evaluation of validity, reliability, feasibility and effect on learning. We set out to assess the reliability of a global rating scale for scoring simulator performance in crisis management. METHODS: Using a global rating scale, three judges independently rated videotapes of anaesthetists in simulated crises in the operating theatre. Five anaesthetists then independently rated subsets of these videotapes. RESULTS: There was good agreement between raters for medical management, behavioural attributes and overall performance. Agreement was high for both the initial judges and the five additional raters. CONCLUSIONS: Using a global scale to assess simulator performance, we found good inter-rater reliability for scoring performance in a crisis. We estimate that two judges should provide a reliable assessment. High fidelity simulation should be studied further for assessing clinical performance.

Anesthesia↗

Randomised controlled trial of short bursts of a potent topical corticosteroid versus prolonged use of a mild preparation for children with mild or moderate atopic eczema.

OBJECTIVE: To determine whether a three day burst of a potent corticosteroid is more effective than a mild preparation used for seven days in children with mild or moderate atopic eczema. DESIGN: Randomised, double blind, parallel group study of 18 weeks' duration. SETTING: 13 general practices and a teaching hospital in the Nottingham area. PARTICIPANTS: 174 children with mild or moderate atopic eczema recruited from general practices and 33 from a hospital outpatient clinic. INTERVENTIONS: 0.1% betamethasone valerate applied for three days followed by the base ointment for four days versus 1% hydrocortisone applied for seven days. MAIN OUTCOME MEASURES: Primary outcomes were total number of scratch-free days and number of relapses. Secondary outcomes were median duration of relapses, number of undisturbed nights, disease severity (six area, six sign atopic dermatitis severity scale), scores on two quality of life measures (children's life quality index and dermatitis family impact questionnaire), and number of patients in whom treatment failed in each arm. RESULTS: No differences were found between the two groups. This was consistent for all outcomes. The median number of scratch-free days was 118.0 for the mild group and 117.5 for the potent group (difference 0.5, 95% confidence interval -2.0 to 4.0, P=0.53). The median number of relapses for both groups was 1.0. Both groups showed clinically important improvements in disease severity and quality of life compared with baseline. CONCLUSION: A short burst of a potent topical corticosteroid is just as effective as prolonged use of a milder preparation for controlling mild or moderate atopic eczema in children.

Administration, Topical↗

Isolation and molecular characterization of Musca domestica delta-9 desaturase sequences.

We have isolated fatty acyl-CoA desaturase cDNA (Mdomd9) and genomic sequences from the housefly, Musca domestica. Two approximately 1.66 kb cDNAs were recovered. They had identical coding regions and 3' untranslated regions (UTRs), but differed in their 5' UTRs. The open reading frame encodes a 380 amino acid (aa) protein with 82% identity to Drosophila melanogaster desat1, and significant (> 50%) identity with other insect delta-9 desaturases. Functional analyses in a yeast expression system confirmed the cDNA encodes a delta9 desaturase. Northern analysis indicated two transcripts of 1.7 and 2.9 kb that hybridized specifically to the open reading frame. PCR amplification of genomic templates revealed three intron sites that are conserved among other insect species. Southern analysis of genomic DNA indicated at least two desaturase gene copies per haploid genome. There is a high degree of polymorphism, most of which appears to be due to variable intron sequences; curiously, individual flies had varying morphs of intron II and intron III. Together, the data suggest that there are more delta9 desaturase alleles within the population studied than there are loci within the genome, and support other studies suggesting that insect fatty acyl-CoA desaturases are a dynamically evolving gene family.

Amino Acid Sequence↗

Reduced lung function both before bronchiolitis and at 11 years.

BACKGROUND AND AIMS: We have previously shown an association between reduced premorbid lung function (V'maxFRC) and bronchiolitis. We hypothesised that individuals with bronchiolitis will go on to have reduced lung function and increased respiratory symptoms in childhood. METHODS: V'maxFRC was measured at 1 month of age; individuals with bronchiolitis were prospectively identified. Annual symptom questionnaires were completed from 3 to 6 years. At 11 years of age, children underwent an assessment including questionnaire, lung function, airway response to histamine (AR), and skin prick testing. RESULTS: Eighteen individuals with bronchiolitis were ascertained from 253 cohort members. Children with bronchiolitis had increased viral induced wheeze at 3 (OR 5.8, 95% CI 1.4 to 25.2; n = 103) and 5 years (OR 5.3, 95% CI 1.1 to 25.5; n = 101). At 11 years of age, 194 children were assessed including 16 with past bronchiolitis. These 16 individuals had reduced mean z scores for % V'maxFRC compared with other children (-0.56 and 0.06 respectively) and mean z scores for % FEF(25-75) at 11 years (-0.53 and 0.06 respectively). At 11 years, FEV(1), FVC PEF, AR, atopy, wheeze, and diagnosed asthma were not different between groups. CONCLUSIONS: Reduced lung function is present before and after bronchiolitis; the level of reduction is comparable. The mechanism for wheeze and reduced lung function after bronchiolitis appears to be related to premorbid lung function and not bronchiolitis per se.

Bronchiolitis↗

The Localio approach: a technical note for a large sacral chordoma.

Whenvever possible, radical resection of retrorectal tumours should be performed.(1) We describe the Localio technique (abdominosacral approach) in a case of a large malignant sacral chordoma. We emphasise the necessity to perform such an approach to achieve a radical resection for these tumours which have little chemosensitivity and minimal radiosensitivity. We highlight clinical features which suggest the presence of a spinal tumour and reiterate the absolute importance of rectal examination.

Chordoma↗

Phosphatidylinositol 3 kinase contributes to the transformation of hematopoietic cells by the D816V c-Kit mutant.

Stem cell factor (SCF) binds the receptor tyrosine kinase c-Kit and is critical for normal hematopoiesis. Substitution of valine for aspartic acid 816 (D816V) constitutively actives human c-Kit, and this mutation is found in patients with mastocytosis, leukemia, and germ cell tumors. Immortalized murine progenitor cells (MIHCs) transduced with wild-type c-Kit proliferate in response to SCF, whereas cells expressing D816V c-Kit (MIHC-D816V) are factor-independent and tumorigenic. However, the mechanisms mediating transformation by D816V c-Kit are unknown. The objective of this study was to identify signaling components that contribute to D816V c-Kit-mediated transformation. SCF stimulates association of p85PI3K with phosphorylated tyrosine 721 of wild-type c-Kit. Phosphatidylinositol 3 kinase (PI3K) subsequently contributes to the activation of Akt and Jnks. In contrast, these studies demonstrated that the D816V c-Kit mutant was constitutively associated with phosphorylated p85PI3K, and, downstream of PI3K, Jnk 1 and Jnk 2 were activated but Akt was not. Interestingly, Erks 1 and 2 were not constitutively activated by D816V c-Kit. Thus, D816V c-Kit maintains the activity of PI3K but not of all signaling pathways activated by wild-type c-Kit. Further, all pathways downstream of PI3K are not constitutively active in MIHC-D816V cells. Studies with a PI3K inhibitor and D816V/Y721F c-Kit, a mutant incapable of recruiting PI3K, indicate that constitutive activation of PI3K through direct recruitment by D816V c-Kit plays a role in factor-independent growth of MIHC and is critical for tumorigenicity.

Amino Acid Substitution↗