Pooled genome-wide linkage data on 424 ADHD ASPs suggests genetic heterogeneity and a common risk locus at 5p13.
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Attention Deficit Disorder with Hyperactivity↗
Biomedical subjects
P Pearson
Publications and source records attributed to P Pearson.
Lung function and blood levels of copper, selenium, vitamin C and vitamin E in the general population.
BACKGROUND: Increased dietary intake of antioxidants has been associated with higher lung function, but few studies have used biological markers of antioxidant intake. OBJECTIVE: This study aimed to determine if antioxidant status, as measured by blood levels, influences lung function. DESIGN: Using a random subsample of 479 participants, aged 18-65 y old, from a larger cross-sectional observational study, the association of forced expiratory volume in 1 s (FEV1) with plasma copper, vitamin C, vitamin E and serum selenium was assessed. RESULTS: An s.d. increase in blood copper level was associated with a difference in FEV1 of -48 ml (95% confidence intervals: -95, -2 ml, P = 0.04), vitamin C +49 ml (+4, +94, P = 0.03), vitamin E -15 ml (-62, +32, P = 0.53) and selenium +52 ml (+7, +96, P = 0.02). The sizes of association were not appreciably altered in a mutually adjusted model. CONCLUSIONS: Higher levels of serum vitamin C and selenium appear to be associated with higher FEV1. The association between higher serum copper and lower FEV1 requires further study in view of the ubiquitous exposure to this mineral.
Adult↗
A school based study of children with learning disability indicates poor levels of genetic investigation.
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Adolescent↗
A novel CBFA2 single-nucleotide mutation in familial platelet disorder with propensity to develop myeloid malignancies.
Hereditary mutations associated with hematologic malignancies are rare. Heterozygous mutations affecting the hematopoietic transcription factor CBFA2 (also AML1/RUNX1) were recently reported to be associated with familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML, MIM 601399). A new 3-generation family with FPD/AML with a novel CBFA2 mutation is described. In this family, AML was diagnosed in a second-generation male. After allogeneic stem cell transplantation from his human leukocyte antigen-identical sister, a donor-derived, genetically identical leukemia developed in the recipient and the donor. Sequencing analysis identified a G-to-T transition within the CBFA2 gene, which involves codon 198, encoding a conserved aspartic acid within the DNA- binding Runt domain. Three of 5 siblings affected with the FPD/AML trait harbored the mutation in a heterozygous form. This experience underscores the necessity of performing mutation analysis of the CBFA2 gene before sibling allogeneic transplantation in families with FPD/AML.
Acute Disease↗
Chromatic and achromatic defects in patients with progressing glaucoma.
To evaluate the pattern of losses associated with glaucomatous injury in patients with progressing glaucoma, functional losses were examined in 14 patients with progressing glaucoma using tests for which detection should be selectively mediated by one of three psychophysical mechanisms. Red-on-white increments, blue-on-white increments and critical flicker frequency were used to isolate the responses of the red-green chromatic mechanism, the blue-on chromatic mechanism, and the high-frequency flicker achromatic mechanism. For our 3.1 degrees circular stimuli, chromatic defects were found in a greater number of the patients with glaucoma than were achromatic defects. We evaluated these defects in terms of two existing hypotheses: preferential loss and reduced redundancy. The greater sensitivity to glaucomatous injury of chromatic tests, compared to achromatic tests, found in this and other studies and the apparent discrepancy between anatomical and psychophysical studies can be parsimoniously explained by differences in cortical summation of ganglion cell responses for the chromatic and achromatic pathways.
Aged↗
A Rett syndrome patient with a ring X chromosome: further evidence for skewing of X inactivation and heterogeneity in the aetiology of the disease.
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, characterised by regression of development in young females. Recently, mutations in the MECP2 gene were found to be present in 80% of sporadic cases, but in much lower frequency (< 30%) among familial cases. Several reports claim that the pattern of X chromosome inactivation (XCI) relates to the penetrance of RTT; in some cases skewed XCI is seen in Rett patients, and in others it is observed among normal carriers. We present here a case of RTT with a 46,X,r(X) in which complete skewed inactivation of the ring was demonstrated. Further, no mutations were found in the MECP2 gene present on the intact X. Our data, in conjunction with two previously published cases of X chromosome abnormalities in RTT, indicate that X chromosome rearrangements are sporadically associated with RTT in conjunction with extreme skewing of X inactivation. Based on our case and reported data, we discuss the evidence for a second X-linked locus for RTT associated with lower penetrance, and a different pattern of XCI, than for MECP2. This would result in a larger proportion of phenotypically normal carrier women transmitting the mutation for this putative second locus, and account for the minority of sporadic and majority of familial cases that are negative for MECP2 mutations.
Dosage Compensation, Genetic↗
Going home from hospital: the carer/patient dyad.
AIMS: This study aimed to provide an in-depth understanding of the process of hospital discharge experienced by the carers of patients 'at risk' of unsuccessful discharge from medical wards in three hospitals in the North of England. BACKGROUND: The Community Care Act and the Carers Recognition and Services Act placed responsibility on service providers to ensure the smooth discharge of patients from hospital making sure that appropriate community services are in place to support the patient and their informal carer following discharge from hospital. The study, from which this paper is taken, identified patients at risk of unsuccessful discharge and tracked the experiences of the patient and their carer through the discharge process. For the purpose of the study unsuccessful discharge is defined as unplanned readmission within 6 weeks of discharge or extended length of stay. DESIGN: The study combined qualitative and quantitative methods to identify factors leading to unsuccessful discharge. Logistic regression was used retrospectively with the records of 1500 patients to identify factors predicting unsuccessful discharge. A sample of medical patients predicted to be at risk of unsuccessful discharge, their formal and informal carers, were followed through the discharge process using qualitative techniques to look at decision-making and outcomes related to discharge. FINDINGS: This paper presents findings relating to patient/carer experiences of the discharge process. It explores the obligate moral climate in which the role of carer is negotiated between professionals, patients, family members, friends and neighbours and the differing assumptions about duty associated with caring roles in hospital and in family and community settings. CONCLUSION: The discussion adopts a critical theory perspective to examine the contradictions confronting practitioners, patients and carers arising from hospital policies which promote cost-effective and efficient use of expensive technical resources while simultaneously seeking to identify and meet the needs of patients and carers for care.
Adolescent↗
Defining the genetic contribution of type 2 diabetes mellitus.
Type 2 diabetes mellitus is a common multifactorial genetic syndrome, which is determined by several different genes and environmental factors. It now affects 150 million people world wide but its incidence is increasing rapidly because of secondary factors, such as obesity, hypertension, and lack of physical activity. Many studies have been carried out to determine the genetic factors involved in type 2 diabetes mellitus. In this review we look at the different strategies used and discuss the genome wide scans performed so far in more detail. New technologies, such as microarrays, and the discovery of SNPs will lead to a greater understanding of the pathogenesis of type 2 diabetes mellitus and to better diagnostics, treatment, and eventually prevention.
Animals↗
Managing patient demand: a qualitative study of appointment making in general practice.
BACKGROUND: Managing patients' requests for appointments is an important general practice activity. No previous research has systematically observed how patients and receptionists negotiate appointments. AIM: To observe appointment making and investigate patients' and professionals' experiences of appointment negotiations. DESIGN OF STUDY: A qualitative study using participant observation. SETTING: Three general practices on Tyneside; a single-handed practice, a practice comprising three doctors, and a seven-doctor practice. METHOD: Participant observation sessions, consisting of 35 activity recordings and 34 periods of observation and 38 patient and 15 professional interviews, were set up. Seven groups of patients were selected for interview. These included patients attending an 'open access' surgery, patients who complained about making an appointment, and patients who complimented the receptionists. RESULTS: Appointment making is a complex social process. Outcomes are dependent on the process of negotiation and factors, such as patients' expectations and appointment availability. Receptionists felt that patients in employment, patients allocated to the practice by the Health Authority, and patients who did not comply with practice appointment rules were most demanding. Appointment requests are legitimised by receptionists enforcing practice rules and requesting clinical information. Patients volunteer information to provide evidence that their complaint is appropriate and employ strategies, such as persistence, assertiveness, and threats, to try and persuade receptionists to grant appointments. CONCLUSION: Appointment making is a complex social process where outcomes are negotiated. Receptionists have an important role in managing patient demand. Practices should be explicit about how appointments are allocated, including publishing practice criteria.
Adolescent↗
Genotype-phenotype correlations in families with deletions in the von Hippel-Lindau (VHL) gene.
Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome characterized by predisposition for bilateral and multi-centric hemangioblastoma in the retina and central nervous system, pheochromocytoma, renal cell carcinoma, and cysts in the kidney, pancreas, and epididymis. We describe five families for which direct sequencing of the coding region of the VHL gene had failed to identify the family-specific mutation. Further molecular analysis revealed deletions involving the VHL gene in each of these families. In four families, partial deletions of one or more exons were detected by Southern blot analysis. In the fifth family, FISH analysis demonstrated the deletion of the entire VHL gene. Our results show that (quantitative) Southern blot analysis is a sensitive method for detecting germline deletions of the VHL gene and should be implemented in routine DNA diagnosis for VHL disease. Our data support the previously established observation that families with a germline deletion have a low risk for pheochromocytoma. Further unraveling of genotype-phenotype correlations in VHL disease has revealed that families with a full or partial deletion of the VHL gene exhibit a phenotype with a preponderance of central nervous system hemangioblastoma.
Adolescent↗
The required role of the psychiatric-mental health nurse in primary health-care: an augmented Delphi study.
An augmented Delphi study was employed to elicit the perceptions of CPNs, GPs, social workers, managers of psychiatric nursing services and health service purchasers in England, on the role required of a psychiatric (mental health) nurse in primary health care. In the final stage of the study, users of mental health service were enlisted in a verification study of the emergent findings. A broad consensus emerged that a gap existed in mental health services in primary care. This was perceived as placing a large burden on GPs, which might be reduced by the appropriate development of community psychiatric-mental health nursing. The study suggested the possibilities for development of a 'mental health nurse consultant' role, which might augment the current CPN role, within which the nurse might offer not only direct patient care, but also support to members of the primary care team.
Attitude of Health Personnel↗
Osteosarcoma in preadolescent patients.
The medical records of boys younger than 11 years and girls younger than 10 years of age with osteosarcoma of the pelvis or extremity were reviewed. Thirty patients were identified who were newly diagnosed but untreated for osteosarcoma. None of these patients had pulmonary metastases. The same four protocols were used to treat the patients in the current study as were used to treat adolescents. The event-free and overall survival was calculated and prognostic factors were assessed. The median followup time was 8 years (range, 6-14 years). The results were compared with the results of older patients treated with the same protocols and with published results. Fourteen patients had pulmonary metastases (47%); among these patients, four also had skeletal metastases (in two of the latter, skeletal metastases appeared before the pulmonary metastases). Event-free survival was 53% and overall survival was 57%. This result is comparable with current survival results in adolescent and older patients. Serum alkaline phosphatase and serum lactic dehydrogenase levels before treatment, height percentile greater than 50%, chemotherapy-induced tumor necrosis, surgical procedure, tumor site, tumor histologic features, and patient gender were not prognostic indicators. The prognosis for prepubertal patients with osteosarcoma is similar to the prognosis of their adolescent and older counterparts. There does not seem to be any indication to treat preadolescent patients with osteosarcoma using alternate therapies.
Antineoplastic Combined Chemotherapy Protocols↗
Non-Indian childhood cirrhosis.
Copper is an essential trace element for sustaining life. However, copper in excess is highly toxic and elevated copper concentrations in cells have been associated with several diseases, including non-Indian childhood cirrhosis (NICC) in man and copper toxicosis in Bedlington terriers. NICC and copper toxicosis in Bedlington terriers are phenotypic very similar to Wilson disease and Indian childhood cirrhosis. Recently, the gene underlying Wilson disease (ATP7B) as well as copper transport genes hCTR1, hCTR2 and ATOX1 have been excluded as candidates for NICC in man and copper toxicosis in Bedlington terriers. Currently, a genome wide screen is being carried out to localize the NICC gene. Isolation of the NICC gene and defining its pathophysiology will significantly expand our insight into copper metabolism in man, which, at present, is largely limited. The availability of a dog mutation with phenotypic similarities to NICC will open up new lines of research for studying the disease if it proves to be homologous to NICC but will still represent an important addition to the list of genes determining copper disease in mammals if it doesn t.
Animals↗
Differential effects of alcohol on rod and cone temporal processing.
OBJECTIVE: One of the more reliable effects of alcohol on sensory processing is the reduction of the critical flicker fusion frequency (CFF). To gain a better understanding of the mechanisms through which alcohol influences the processing of temporal information, we explored the effects of alcohol on CFF at a high level of illumination when performance is mediated by the cones (photopic), and at a lower level when performance is dominated by the rods (low mesopic). METHOD: Measurements of CFF were made under placebo and alcohol conditions (0.06% blood alcohol concentration) in six subjects (three men, three women). Assessments were obtained in both the rising and falling phases of absorption for both light levels at several retinal locations. RESULTS: Alcohol was found to reduce CFF by approximately the same amount at all retinal locations for photopic viewing levels. Mesopic CFF was lower than photopic, as expected. However, it was only minimally affected by alcohol, showing only a slight decline for central viewing. CONCLUSIONS: These results imply a selective effect on alcohol on cone function. In considering the possible mechanisms of such a selective action, we suggest that this effect may be an indirect one. That is, the poorer performance under photopic conditions may be a consequence of an alcohol-induced reduction in the inhibitory interactions that are more prevalent at photopic light levels.
Adult↗
Resistance to antibiotics. Prescribing of antibiotics needs to be rational.
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Advertising↗
Effects of moderate blood alcohol concentrations on spatial and temporal contrast sensitivity.
OBJECTIVE: In order to gain a more complete picture of the influence of alcohol on visual performance, we measured contrast sensitivity for a range of spatial and temporal frequencies in individuals with moderate blood alcohol concentrations (BACs). METHOD: Subjects were tested at blood alcohol concentrations of 0.06% in both the rising and falling phases of absorption. In the first part of the study, the performance of two men and four women on a number of simple screening measures and static contrast sensitivity was measured. In the second part (four men and three women), the grating patterns were contrast reversed at four different rates, allowing us to assess the effects of alcohol on temporal processing. The second study examined the relationship between blood alcohol concentrations and contrast sensitivity. RESULTS: Although few significant changes in performance were found on the simple screening tests, we observed a significant reduction (43%) in stationary contrast sensitivity at the 0.06% BAC. This change in performance was greater at low and high spatial frequencies than at moderate ones. At high temporal frequencies, the reduction in sensitivity was 2.5 times that seen for lower temporal frequencies. With higher blood alcohol concentrations, the decrease in performance was found to be greatest for the high and low spatial frequencies. CONCLUSIONS: These data suggest that alcohol produces visual deficits that are not attributable to pursuit eye movements. It is suggested that these visual deficits, combined with changes in ocular-motor control and attentional deficits, may have a strong effect on performance under the influence of alcohol.
Adult↗
Guidelines for human gene nomenclature (1997). HUGO Nomenclature Committee.
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Alleles↗
The vexed question of authorship: views of researchers in a British medical faculty.
OBJECTIVE: To assess knowledge, views, and behaviour of researchers on criteria for authorship and causes and control of gift authorship. DESIGN: Interview survey of stratified sample of researchers. SETTING: University medical faculty. SUBJECTS: 66 staff (94% response rate) comprising several levels of university academic and research appointments. MAIN OUTCOME MEASURES: Awareness and use of criteria for authorship, views on which contributions to research merit authorship, perceptions about gift authorship and strategies for reducing it, and experiences of authorship problems. RESULTS: 50 (76%) respondents supported criteria for authorship, but few knew about or used available criteria. Of the five people who could specify all three criteria of the International Committee of Medical Journal Editors, only one knew that all criteria had to be met. Forty one respondents (62%) disagreed with this stipulation. A range of practical and academic contributions were seen as sufficient for authorship. Gift authorship was perceived as common, promoted by pressure to publish, to motivate research teams, and to maintain working relationships. A signed statement justifying authorship and a published statement of the contribution of each author were perceived as practical ways of tackling gift authorship. Most researchers had experienced problems with authorship, most commonly the perception that authorship had been deserved but not awarded (49%). CONCLUSION: There seems to be a gap between editors' criteria for authorship and researchers' practice. Lack of awareness of criteria is only a partial explanation. Researchers give more weight than editors to practical research contributions. Future criteria should be agreed by researchers and not be imposed by editors.
Attitude↗