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J Holmes

Publications and source records attributed to J Holmes.

At least 19 recordsLinked to original sources
PubMed2003

The Multi-Source Interference Task: validation study with fMRI in individual subjects.

Dorsal anterior cingulate cortex (dACC) plays critical roles in cognitive processing, but group-averaging techniques have generally been required to obtain significant dACC activation in functional neuroimaging studies. Development of a task that reliably and robustly activates dACC within individuals is needed to improve imaging studies of neuropsychiatric disorders and localization of dACC in normal volunteers. By combining sources of cognitive interference (Stroop, Eriksen and Simon) with factors known to increase dACC activity, the Multi-Source Interference Task (MSIT) maximally taxes dACC, making it possible to reliably activate dACC within individuals using functional magnetic resonance imaging (fMRI). In this study, eight normal adult volunteers performed the MSIT during fMRI. We compared fMRI responses and performance data between interference and control trials. Significant dACC activation (P < 1.7 x 10(-4)) was observed in all eight individuals and in the group-averaged fMRI data. In addition to dACC activation, group data also showed activation of presumably networked regions including dorsolateral prefrontal, premotor, and parietal cortices. The MSIT's reaction time interference effect (overall mean 312 +/- 61 ms) was up to 10 times greater than that of its component predecessors and temporally stable over hundreds of trials. The robustness, reliability and stability of the neuroimaging and performance data should make the MSIT a useful task with which to study normal human cognition and psychiatric pathophysiology.

Adult↗
PubMed2001

Susceptibility genes for a trait measure of attention deficit hyperactivity disorder: a pilot study in a non-clinical sample of twins.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder, and molecular genetic studies are underway, with most researchers focusing on identifying susceptibility genes in clinical samples with ADHD. An alternative approach is to search for quantitative trait loci underlying the trait measure of ADHD in non-clinical samples. Positive findings of association of the dopamine transporter DAT1 480 bp allele (allele 10) and the DRD4 7 repeat allele with clinical ADHD have been previously reported. In this pilot study, we examined these polymorphisms in a selected population-based sample of twins (50 high scoring pairs, 42 low scoring pairs). There was a trend for an increase in the frequency of the dopamine receptor DRD4 7 repeat allele in the high-scoring concordant monozygotic twins (odds ratio=1.4). Although this result was not statistically significant, the frequency of the 7 repeat allele was similar to that reported for our clinic sample of ADHD patients drawn from the same geographical area. There was a non-significant trend for an increased frequency of the DAT1 allele 10 (odds ratio=1.3). These results suggest that a molecular genetic study based on a questionnaire-derived measure of ADHD in a non-clinical sample is feasible and the results appear to be comparable with those from studies of clinical cases. However, sample size and power are key issues to consider when using this approach.

Adolescent↗
PubMed2001

No association between CHRNA7 microsatellite markers and attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable, common psychiatric disorder of childhood that probably involves several genes. There are several lines of evidence suggesting that the nicotinic system may be functionally significant in ADHD. First, nicotine promotes the release of dopamine and has been shown to improve attention in adults with ADHD, smokers, and nonsmokers. Second, ADHD is a significant risk factor for early initiation of cigarette smoking in children and maternal cigarette smoking appears to be a risk factor for ADHD. Finally, animal studies in rats and monkeys also suggest that nicotine may be involved in attentional systems and locomotor activity. The nicotinic system has previously been studied in schizophrenia where the neuronal nicotinic acetylcholine receptor alpha 7 subunit gene (CHRNA7) has been implicated in decreased P50 inhibition and attentional disturbances in patients with schizophrenia and in many of their nonschizophrenic relatives. Three known microsatellite markers (D15S165, D15S1043, and D15S1360) near the nicotinic acetylcholine alpha 7 receptor gene, CHRNA7, were studied in 206 ADHD parent-proband trios of children aged 5-16 with ADHD according to DSM-IV criteria. Children with known major medical or psychiatric conditions or mental retardation (IQ < 70) were excluded from the study. Markers D15S165 and D15S1360 were in linkage disequilibrium. The extended Transmission Disequilibrium Test analyses demonstrated no evidence that variation at the microsatellite markers D15S1360, D15S1043, and D15S165 influences susceptibility to ADHD. However, it remains possible that the CHRNA7 gene and other nicotinic system genes may be involved in conferring susceptibility to ADHD.

Adolescent↗
PubMed2001

Examining for association between candidate gene polymorphisms in the dopamine pathway and attention-deficit hyperactivity disorder: a family-based study.

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable childhood-onset psychiatric condition characterized by developmentally inappropriate inattention, hyperactivity, and impulsiveness. The pathophysiology of ADHD is currently unknown. However, the therapeutic effects of stimulant medication together with findings from animal and neuroimaging studies as well as from several molecular genetic studies of the dopamine receptor D4 gene and dopamine transporter gene have implicated involvement of the dopaminergic system. To test the dopaminergic hypothesis further, we have looked for association between ADHD and alleles of seven dopamine-related candidate genes using a family-based association approach in a sample of 150 children diagnosed with ADHD. We tested polymorphisms in genes encoding three dopamine receptors (DRD3, DRD4, and DRD5) and four dopamine-relevant enzymes: tyrosine hydroxylase [tyrosine hydroxylase (TH)], dopamine beta hydroxylase (DbetaH), catechol-O-methyltransferase (COMT), and monoamine oxidase A (MAOA). We were unable to detect a significant association with any of the polymorphisms genotyped, although there was a trend for preferential transmission of the DRD5 148 bp marker allele and the MAOA 122 bp marker allele. We conclude that none of the alleles we have tested makes a major contribution to ADHD, although much larger samples are required to exclude small effects.

Adolescent↗
PubMed2001

Psychiatric illness and mortality after hip fracture.

People with dementia or delirium have increased mortality in the 6 months after hip fracture, but depression might take longer to have an effect. We assessed the psychiatric status of 731 participants with hip fracture and analysed the effect of psychiatric illness on mortality during the next 2 years. We found that dementia, delirium, and depression all increased the risk of mortality (p<0.0001, p<0.0001, and p=0.0359, respectively), and that mortality differed significantly between hospitals (p=0.0003). We suggest that psychiatric interventions should be asssessed in hip-fracture patients with adequate follow up of outcome measures.

Aged↗
PubMed2001

The behavior of oxygen as a collision-induced dissociation target gas.

The unusual and unique ability of O2 as target gas in kV collision-induced dissociations, to enhance a specific fragmentation of a mass selected ion, has been examined in detail. The affected dissociations studied were the loss of CH3* from CH3CH+X (X = OH, CH3, NH2, SH); CH3* and C1* loss from CH3C+(C1)CH3; C2H5* loss from CH3CH2CH+X (X = OH and NH2); H* loss from +CH2OH and +CH2NH2; O loss from 1,2-, 1,3-, and 1,4-C6H4(NO2)2+*; CH3NO+*; C6HsNO2+*; C5H5NO+* (pyridine N-oxide); 3- and 4-CH3C5H4NO+*. A general explanation of the phenomena, which was semiquantitatively tested in the present work, can be summarized as follows: the ion - O2 encounter excites the target molecules to their 3sigma(g)- state which resonantly return this energy to electronic state(s) in the ion. The excited ion now contains a sharp excess of a narrow range of internal energies, thus significantly and only enhancing fragmentations whose activation energies lie within this small energy manifold.

Journal Article↗
PubMed2001

Modeling emotion and behavior in animated personas to facilitate human behavior change: the case of the HEART-SENSE game.

The goal of this research is to determine whether a computer based training game (HEART-SENSE) can improve recognition of heart attack symptoms and shift behavioral issues so as to reduce pre-hospitalization delay in seeking treatment. Since treatment delay correlates with adverse outcomes, this research could reduce myocardial infarction mortality and morbidity. In Phase I we created and evaluated a prototype virtual village in which users encounter and help convince synthetic personas to deal appropriately with a variety of heart attack scenarios and delay issues. Innovations made here are: (1) a design for a generic simulator package for promoting health behavior shifts, and (2) algorithms for animated pedagogical agents to reason about how their emotional state ties to patient condition and user progress. Initial results show that users of the game exhibit a significant shift in intention to call 9-1-1 and avoid delay, that multi-media versions of the game foster vividness and memory retention as well as a better understanding of both symptoms and of the need to manage time during a heart attack event. Also, results provide insight into areas where emotive pedagogical agents help and hinder user performance. Finally, we conclude with next steps that will help improve the game and the field of pedagogical agents and tools for simulated worlds for healthcare education and promotion.

Algorithms↗
PubMed2001

Platelet activation and function after trauma.

BACKGROUND: Abnormal hemostasis is associated with many of the complications of trauma-associated morbidity and mortality. Platelets are integral in the maintenance of hemostasis. METHODS: Samples were obtained from 100 trauma patients on arrival at the emergency room (initial time) and at 24, 48, and 72 hours later. Samples were also obtained from 10 healthy controls at the same time intervals. Using flow cytometry, three parameters were used to measure platelet activation: platelet microparticles, expression of P-selectin (CD62P), and expression of the activated conformation of glycoprotein IIb-IIIa (PAC-1 binding). Platelet function was measured using a platelet function analyzer (PFA-100, Dade International Inc., Miami, FL). RESULTS: One hundred trauma patients were enrolled. The average age was 40 years, 75% were men, and 84% had blunt injuries. The mean Injury Severity Score was 22.3 +/- 10.9 (mean +/- SD) and the average Glasgow Coma Scale score was 11 +/- 4. All three platelet activation parameters were increased in trauma patients versus controls for all time periods (p < 0.001). Trauma patients had a trend toward a shorter initial collagen/epinephrine closure time versus controls (p = 0.096). Compared with the 24-, 48-, and 72-hour time intervals, initial collagen/epinephrine closure times were shortened (p < 0.001, p < 0.001, and p < 0.001). Platelet function returned to normal reference ranges within 24 hours but platelet activation parameters remained elevated at least 72 hours after initial trauma. In contrast, when trauma patients with and without brain injury were compared, brain injury patients had increased platelet activation but decreased platelet function (increased collagen/epinephrine closure times). In addition, there was a significant prolongation in collagen/epinephrine closure times for the 24-, 48-, and 72-hour time points in nonsurviving patients versus survivors. There was no association between platelet activation and function and other adverse outcomes including pulmonary embolism, deep venous thrombosis, and disseminated intravascular coagulation. CONCLUSION: Severe injury usually results in increased platelet activation and function. However, the combination of increased platelet activation with decreased function was associated with increased mortality.

Adult↗
PubMed2000

Untied

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Journal Article↗
PubMed2000

A series of outbreaks of food poisoning?

A series of independently occurring episodes which were notified individually as 'food poisoning' were, after investigation, linked to a common source water supply.

Caliciviridae Infections↗
PubMed2000

Follicle-stimulating hormone or human menopausal gonadotropin for ovarian stimulation in in vitro fertilization cycles: a meta-analysis.

OBJECTIVE: To reanalyze the results of using FSH alone and hMG during IVF treatment, taking into account the different protocols of administration of superactive GnRH agonist analogs. DESIGN: Meta-analysis. SETTING: The London Women's Clinic. PATIENT(S): Women undergoing IVF treatment. INTERVENTION(S): A meta-analysis of published randomized controlled trials from 1985 to 1999 of the use of FSH versus hMG for ovarian stimulation during IVF treatment. The common Peto odds ratio was calculated with use of a fixed effect model. The overall log odds ratio was estimated after demonstrating the consistency or homogeneity of the study results. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate per cycle of IVF. RESULT(S): The results suggested that in the "long and short GnRH agonists protocol" of IVF, FSH, and hMG were equally effective in achieving ovarian stimulation, and there were no differences in the clinical pregnancy rates per cycle of IVF. However, in protocols where no pituitary desensitization was used, FSH alone was more efficacious. CONCLUSION(S): The optimum choice of gonadotropin preparation for ovarian stimulation during IVF treatment is influenced by the regimen of pituitary desensitization used. The optimum gonadotropin to be used when GnRH antagonists are used has yet to be determined.

Clinical Protocols↗
PubMed2000

Psychiatric illness predicts poor outcome after surgery for hip fracture: a prospective cohort study.

BACKGROUND: Hip fracture is common in the elderly. Previous studies suggest that psychiatric illness is common and predicts poor outcome, but have methodological weaknesses. Further studies are required to address this important issue. METHODS: We prospectively recruited 731 elderly participants with hip fracture in two Leeds hospitals. Psychiatric diagnosis was made within 5 days of surgery using the Geriatric Mental State schedule and other standardized instruments, and data on confounding factors was collected. Main study outcomes were length of hospital stay, and mortality over 6 months after fracture. RESULTS: Fifty-five per cent of participants had cognitive impairment (dementia in 40% and delirium in 15%), 13% had a depressive disorder, 2% had alcohol misuse and 2% had other psychiatric diagnoses. Participants were likely to remain in hospital longer if they suffered from dementia, delirium or depression. The relative risks of mortality over 6 months after hip fracture were increased in dementia and delirium, but not in depression. CONCLUSIONS: Psychiatric illness is common after hip fracture, and has significant effects on important outcomes. This suggests a need for randomized, controlled trials of psychiatric interventions in the elderly hip fracture population.

Aged↗
PubMed2000

A family-based and case-control association study of the dopamine D4 receptor gene and dopamine transporter gene in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable psychiatric condition of early childhood onset characterised by marked inattention, hyperactivity and impulsiveness. Molecular genetic investigations of ADHD have found positive associations with the 480-bp allele of a VNTR situated in the 3' untranslated region of DAT1 and allele 7 of a VNTR in exon 3 of DRD4. A number of independent studies have attempted to replicate these findings but the results have been inconsistent. We used both family-based and case control approaches to examine these polymorphisms in a sample of 137 children diagnosed with ICD-10, DSM-IV or DSM-III-R ADHD. We found no evidence of association with the DAT1 polymorphism, despite a sample size that has up to 80% power to detect a previously reported effect size. We observed a significant increase in the DRD4 7 repeat allele amongst ADHD probands (21.7%) and their parents (18.9% in mothers, 22.3% in fathers), compared to ethnically matched controls (12.8%). However TDT analysis showed no preferential transmission of allele 7 to ADHD probands.

Adult↗
PubMed2000

The links between joint damage and disability in rheumatoid arthritis.

OBJECTIVE: The characteristic joint damage and disability of rheumatoid arthritis (RA) increase slowly over 10-20 yr. Although it is generally believed that persisting inflammatory synovitis causes joint damage and subsequent disability, the strength of their relationship has not been systematically evaluated. This review describes their progression and interrelationship in treated RA. METHODS: MEDLINE and Current Contents databases were searched for the combined terms of rheumatoid arthritis AND X-rays, Health Assessment Questionnaire, slow-acting anti-rheumatic drugs and all identifiable synonyms. This search identified 1303 articles and from these we evaluated in detail 23 reports on the progression of joint damage, 12 reports on the progression of disability and 25 reports dealing with their interrelationship. Additional information was obtained from four data sets comprising 725 RA patients studied cross-sectionally and 33-126 cases followed prospectively for 1-5 yr. X-ray damage was primarily assessed by Larsen and Sharp indices, and disability by the Health Assessment Questionnaire (HAQ). RESULTS: Joint damage and disability both increase throughout the duration of RA. Although disability (HAQ score) is correlated with disease duration (correlation coefficients between 0.27 and 0.30), the link between X-ray damage and disability is stronger (correlation coefficients between 0.30 and 0.70). In the earliest phases of RA, X-ray damage and HAQ scores are not related. By 5-8 yr, there are significant correlations with correlation coefficients between 0.30 and 0.50. In late RA (>8 yr), most studies show highly significant correlations between 0.30 and 0.70. CONCLUSIONS: Joint damage progresses constantly over the first 20 yr of RA. It accounts for approximately 25% of disability in established RA. The link between damage and disability is strongest in late (>8 yr) RA. However, avoiding or reducing joint damage in both early and established/late RA is likely to maintain function.

Arthritis, Rheumatoid↗
PubMed2000

Use of out-of-hospital interventions for the pediatric patient in an urban emergency medical services system.

OBJECTIVE: To determine appropriateness of out-of-hospital interventions by emergency medical services (EMS) personnel on children with respiratory illnesses. METHODS: A retrospective, cross-sectional study was performed on a random sample of 304 children transported by an urban EMS system during 1994. Data were abstracted from EMScan (a computerized database of all EMS dispatches) and the EMS narrative records. Appropriate utilization of interventions was determined by comparison with the standard EMS protocol for respiratory complaints in this system. An assessment of whether interventions were inappropriately underutilized or inappropriately overutilized was made. Effect of severity of illness, patient age, transport times, and use of medical command on the use of interventions was evaluated. RESULTS: Two hundred three patients (67%) were classified as having respiratory distress. Overall, 56% of the patients received appropriate interventions, 39% received one or two inappropriate interventions, and 5% received three or more inappropriate interventions. Rates of inappropriate utilization with 95% CI for each intervention were: oxygen 16% (95% CI = 12 to 20), assisted ventilation 2% (95% CI = 0.5 to 4), medication use 9% (95% CI = 6 to 13), vascular access 11% (95% CI = 7 to 14), phlebotomy 9% (95% CI = 6 to 13), and cardiac monitoring 18% (95% CI = 14 to 22). Oxygen and medications were underutilized (p < 0.005), whereas vascular access, cardiac monitoring, and phlebotomy were overutilized (p < 0.005). Online medical command (used in 9% of transports) improved appropriate use of vascular access [OR 8.3 (95% CI = 3 to 25) (p < 0.001)] and cardiac monitoring [OR = 3 (95% CI = 1 to 8) (p < 0.05)]. CONCLUSIONS: Emergency medical services personnel underutilized oxygen and medications and overutilized vascular access, phlebotomy, and cardiac monitoring in children with respiratory illness in this urban setting. Increasing patient age, transport times, and illness severity tend to increase the use of certain interventions, while contact with online medical direction seems to improve appropriate use of interventions.

Adolescent↗
PubMed2000

The burden of personality disorder: a district-based survey.

Patients with a clinical diagnosis of personality disorder (PD) often suffer prolonged distress. They are a considerable burden on psychiatric services and they are experienced as difficult to manage by their keyworkers. This paper describes the creation of a community-based case register of patients suffering from PD. It explores the relationship between psychological distress, personality dysfunction, service utilisation and keyworker stress. Mental Health workers were asked to identify those patients on their caseload whose primary problem was PD. This list provided the basis for the case register. Patients completed the revised Personality Diagnostic Questionnaire IV (PDQ 4); the General Health Questionnaire (GHQ); and the Beck Depression Inventory - 21 item (BDI). A brief, semi-structured interview was conducted by Community Psychiatric Nurses to estimate service utilisation and keyworker stress. The mean GHQ was 14.58; the mean BDI score was 28.22. The mean number of PDs per patient was 4.5. One quarter of patients (21/80) had been admitted at least once to a psychiatric ward in the previous year and 17% (13/80) had presented to casualty at least once in the previous two months. 57% of the patients had weekly or more contacts with a helping agency. The number of PD diagnoses per patient as measured by the PDQ 4 was not found to be predictive of stress experienced by CPNs, whereas high BDI and GHQ scores were strongly correlated. Similarly, the number of admissions to a psychiatric ward was associated with high BDI and GHQ scores but not with number of PDs per patient. It is feasible to establish a case register of all patients in the district with PD. There are high levels of depression and distress amongst patients with PD being treated as outpatients. Service utilisation and keyworker stress are not predicted by number of PDs per patient but are strongly associated with distress as measured by the GHQ and BDI. The implications of these findings are discussed.

Adolescent↗