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Biomedical subjects

M Egan

Publications and source records attributed to M Egan.

At least 19 recordsLinked to original sources
PubMed2006

Impact of complex genetic variation in COMT on human brain function.

Catechol-O-methyltransferase (COMT) has been shown to be critical for prefrontal dopamine flux, prefrontal cortex-dependent cognition and activation. Several potentially functional variants in the gene have been identified, but considerable controversy exists regarding the contribution of individual alleles and haplotypes to risk for schizophrenia, partly because clinical phenotypes are ill-defined and preclinical studies are limited by lack of adequate models. Here, we propose a neuroimaging approach to overcome these limitations by characterizing the functional impact of ambiguous haplotypes on a neural system-level intermediate phenotype in humans. Studying 126 healthy control subjects during a working-memory paradigm, we find that a previously described risk variant in a functional Val158Met (rs4680) polymorphism interacts with a P2 promoter region SNP (rs2097603) and an SNP in the 3' region (rs165599) in predicting inefficient prefrontal working memory response. We report evidence that the nonlinear response of prefrontal neurons to dopaminergic stimulation is a neural mechanism underlying these nonadditive genetic effects. This work provides an in vivo approach to functional validation in brain of the biological impact of complex genetic variations within a gene that may be critical for its clinical association.

Adult↗
PubMed2006

EMTs and GPs: what do we think of each other?

BACKGROUND: Ireland's health services are undergoing dramatic reorganisation. The establishment of general practitioner (GP) out of hours cooperatives and the integration of current ambulance services into a national ambulance service are among the issues that will impact on prehospital care of emergencies. The study aimed to explore the perceptions of GPs and emergency medical technicians (EMTs) of their own and each other's roles in the context of such reforms. METHODS: A census of all GPs (511) and EMTs (301) in three of Ireland's eight health board regions was undertaken. A questionnaire containing 31 statements asked respondents to indicate their agreement (or lack of it) in areas such as general relationships, care, and training, roles in emergencies and future developments. RESULTS: Of the personnel contacted, 72% of GPs and 75% of EMTs responded. They report excellent working relationships, agree that the ambulance service is of high quality, and that GPs are willing to provide care in emergencies. However, working links are less satisfactory for EMTs, who report a far higher perception of GP use of emergency ambulances than reported by GPs. Both groups are interested in innovative future links. DISCUSSION: Convergence between the professional groups in different geographic areas and between the disciplines across the areas is striking. They include areas of satisfaction and dissatisfaction. The need for improved liaison between the disciplines is clear.

Attitude of Health Personnel↗
PubMed2005

Consideration of environmental change in performance assessments.

Depending on the particular circumstances in which a post-closure performance assessment of a radioactive waste repository is made, it may be appropriate to follow simple or more complex approaches in characterising the biosphere. Several different Example Reference Biospheres were explored in BIOMASS Theme 1 to address a range of issues that arise. Here, consideration is given to Example Reference Biospheres relevant to representing the implications of changes that may occur within the biosphere system during the period over which releases of radionuclides from a disposal facility might take place. Mechanisms of change considered include those extrinsic and intrinsic to the system of interest. An overall methodology for incorporating environmental change into assessments is proposed. This includes screening of primary mechanisms of change; identification of possible time sequences of change; development of a coherent description of the regional landscape response for each time sequence; integration of source term and geosphere-biosphere interface information; identification and description of one or more time series of assessment biospheres; and evaluation of the advantages and disadvantages of simulating the effects of sequences of biosphere systems and the transitions between them, or of defining a set of biosphere systems to be represented individually in a non-sequential analysis. The usefulness of the methodology is explored in two site-specific examples and one generic example.

Climate↗
PubMed2001

Splints/orthoses in the treatment of rheumatoid arthritis.

BACKGROUND: Splints/orthoses are often recommended to patients with rheumatoid arthritis (RA) to decrease pain, decrease swelling and/or prevent deformity. These orthoses include resting hand splints, wrist supports, finger splints and special shoes and shoe inserts. OBJECTIVES: To assess the effectiveness of splints/orthoses in relieving pain, decreasing swelling and/or preventing deformity and determine the impact of splints/orthoses on strength, mobility and function in people with RA. SEARCH STRATEGY: We searched MEDLINE, EMBASE, the PEDro data base and Current Contents up to January 2002, and the Cochrane Controlled Trials Register to Issue 4, 2001 using the search strategy developed by the Cochrane Collaboration. Unpublished studies were sought by hand searching conference proceeding and contacting key experts. SELECTION CRITERIA: All randomized control trials (RCTs) and controlled clinical trials (CCTs), case-control and cohort studies comparing the use of specific orthoses against placebo, another active intervention (including another type of orthoses) or regular treatment were selected, according to an a priori protocol. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected the studies and abstracted data. The methodological quality of the RCTs and CCTs was assessed using a validated scale. MAIN RESULTS: Twelve papers reporting on 10 studies met the inclusion criteria. These studies dealt with the following: working wrist splints (5), resting hand and wrist splints (2), special shoes and insoles (3). There is evidence that wearing working wrist splints statistically significantly decreases grip strength and does not affect pain, morning stiffness, pinch grip, quality of life after up to 6 months of regular wear. We found no evidence that resting wrist and hand splints change pain, grip strength, Ritchie Index or number of swollen joints. However, patients who wore these splints for 2 months reported that they preferred use to non-use and padded resting splints to unpadded ones. The one study of special shoes provided evidence of significant benefits of wearing extra-depth shoes for 2 months including less pain on walking and stair climbing and more minutes pain free walking time. Extra-depth shoes with semi-rigid insoles provided better pain relief than extra-depth shoes alone when worn over 12 weeks. Posted insoles prevented progression of hallux valgus angle but did not affect pain or function. REVIEWER'S CONCLUSIONS: There is insufficient evidence to make firm conclusions about the effectiveness of working wrist splints in decreasing pain or increasing function for people with RA. Potential adverse effects such as decreased range of motion do not seem to be an issue, although some of these splints decrease grip strength and dexterity. Similarly, preliminary evidence suggests that resting hand and wrist splints do not seem to affect range of motion or pain, although patients preferred wearing a resting splint to not wearing one. There is evidence that extra-depth shoes and molded insoles decreases pain on weight-bearing activities such as standing, walking and stair-climbing. Posted insoles may be effective in preventing progression of hallux abductus angle but do not appear to have an impact on pain.

Arthritis, Rheumatoid↗
PubMed2001

Ethical dilemmas in home health care: a social work perspective.

The survey in this article examined several factors related to the frequency and difficulty of resolving four ethical conflicts in a national sample of 364 home health care social workers. Ethical conflicts regarding the assessment of mental competence, self-determination, and access to services were moderately frequent and difficult to resolve, whereas conflicts over implementing advance directives were infrequent and not difficult to resolve. Each ethical conflict involved multiple stakeholders. Multiple regression analyses revealed significant predictors of the frequency and difficulty of resolving the ethical conflicts. Implications for practice and administration in home health care and social work education are discussed.

Advance Directives↗
PubMed2001

Physicians' perceptions and responses to patient emotion: implications for social work practice in health care.

Physicians serve a pivotal role in today's health systems, as they are often the first professional patients must contact for emotion problems. This study surveyed 225 practicing physicians to understand how they perceive patient emotion and the actions they would then take in response to these perceived emotions. In reply to nondescript "emotion complaints" from a patient vignette, these physicians perceived the patient as experiencing anxiety, followed by fear, anger and sadness. Physicians had distinct preferences for psychosocial oriented responses (e.g., explore, reassure, and rationalize) and were least likely to avoid, distract, and ignore. Overall, anxiety and fear generated the greatest number of possible responses from physicians, anger and sadness the fewest.

Adult↗
PubMed2001

Attachment styles and personality disorders as predictors of symptom course.

Adult attachment styles and personality disorders (PDs) show some conceptual and empirical overlap and both may complicate the course of symptoms among psychiatric patients. In this naturalistic prospective study, 149 patients with affective, anxiety, substance use, and other disorders were interviewed shortly after entering treatment, which included psychotherapy, pharmacotherapy, or both. Follow-up interviews were conducted 6 and 12 months later. Attachment styles, DSM-III-R PDs, and symptoms were assessed using structured interviews and consensus ratings. At intake, borderline, avoidant, and dependent PD features correlated consistently with symptom severity and secure attachment correlated inversely with two of four symptom scales. Secure attachment was linked with greater relative improvement in global functioning and a more benign course of anxiety symptoms over 6 months. Borderline PD features predicted less relative improvement of depressive symptoms over 6 months. These findings clarify the relations between attachment styles and PD features and they point to potential mediators of treatment response.

Adult↗
PubMed2000

Do patient factors alter the relationship between physician characteristics and use of long-acting benzodiazepines?

Despite known hazards associated with their use, long-acting benzodiazepines are frequently used in the treatment of older adults. While such use has been linked to physician characteristics, the effect of patient factors has not been considered. To investigate this, data from 1423 Quebec community-dwelling subjects of the Canadian Study of Health and Aging were linked to records of prescriptions billed to the provincial health insurance program during the year following study entry. The standardized one-year period prevalence of any use of long-acting benzodiazepines was 12.2%. Among benzodiazepine users, long-acting benzodiazepine use was more common among male patients and patients of earlier graduating prescribers and specialist prescribers. However, the effect of the latter two factors were modified by patient self-reported anxiety. This study demonstrates that consideration of patient factors may be necessary to obtain an accurate estimate of the association between at least some physician factors and use of long-acting benzodiazepines.

Aged↗
PubMed2000

Long-term continuous use of benzodiazepines by older adults in Quebec: prevalence, incidence and risk factors.

OBJECTIVE: To determine the prevalence and incidence of long-term use of benzodiazepines and to assess patient-, prescriber-, and drug-related risk factors. DESIGN: Cohort study. PARTICIPANTS: 1,423 community-dwelling older adults in Quebec who participated in the Canadian Study of Health and Aging (CSHA1). MEASUREMENTS: Patient characteristics were obtained from the CSHA1 database. These were linked to provincial health insurance data to ascertain benzodiazepine use and prescriber characteristics. MAIN OUTCOME MEASURE: Use of benzodiazepines for at least 135 of the first 180 days following initiation of use. RESULTS: Twelve-month prevalence of long-term continuous use, standardized by age and gender to the Quebec population, was 19.8%. Twelve-month cumulative incidence of long-term continuous use was 1.9%. Older patients were more likely to proceed to long-term continuous use. CONCLUSIONS: Risk of long-term continuous use of benzodiazepines seems to increase with age. This association was found to be independent of gender, health status, anxiety, cognitive status, benzodiazepine type, and physician characteristics.

Adult↗
PubMed2000

The transplant experience of liver recipients: ethical issues and practice implications.

The transplant experience of 20 liver organ transplant recipients was investigated in a longitudinal study. Five primary themes were identified from analysis of recipients' interviews including concerns about: (1) quality of life, (2) quality of health care, (3) economic factors, (4) social support factors, and (5) psychological factors. These findings are analyzed within the current context of social work in health care characterized by three interactive trends: advances in medical technology, changing health care economics, and a shift in the locus of health care delivery from institutions to the community. All five themes reflect the impact of these trends and give rise to ethical issues with practice implications.

Adolescent↗
PubMed1999

A novel sulfonylurea receptor family member expressed in the embryonic Drosophila dorsal vessel and tracheal system.

Sulfonylurea receptors (SURx) are required subunits of the ATP-sensitive potassium channel. SURx alone is electrophysiologically inert. However, when SURx is combined with an inward rectifier Kir6.2 subunit, ATP-sensitive potassium channel activity is generated. We report the identification, characterization, and localization of Dsur, a novel Drosophila gene that is highly related to the vertebrate SUR family. The Dsur coding sequence contains structural features characteristic of the ABC transporter family and, in addition, harbors 1.7 kilobases of a distinctive sequence that does not share homology with any known gene. When Dsur alone is expressed in Xenopus oocytes glibenclamide-sensitive potassium channel activity occurs. During Drosophila embryogenesis, the Dsur gene is specifically expressed in the developing tracheal system and dorsal vessel. Studies of the Drosophila genome support that only a single Dsur gene is present. Our data reveal conservation of glibenclamide-sensitive potassium channels in Drosophila and suggest that Dsur may play an important role during Drosophila embryogenesis. The lack of gene duplication in the Drosophila system provides a unique opportunity for functional studies of SUR using a genetic approach.

ATP-Binding Cassette Transporters↗
PubMed1999

The relationship between dorsolateral prefrontal N-acetylaspartate measures and striatal dopamine activity in schizophrenia.

BACKGROUND: Pathology of dorsolateral prefrontal cortex and dysregulation of dopaminergic neurons have been associated with the pathophysiology of schizophrenia, but how these phenomena relate to each other in patients has not been known. It has been hypothesized that prefrontal cortical pathology might induce both diminished steady-state and exaggerated responses of dopaminergic neurons to certain stimuli (e.g., stress). We examined the relationship between a measure of prefrontal neuronal pathology and striatal dopamine activity in patients with schizophrenia and in a nonhuman primate model of abnormal prefrontal cortical development. METHODS: In the patients, we studied in vivo markers of cortical neuronal pathology with NMR spectroscopic imaging and of steady-state striatal dopamine activity with radioreceptor imaging. In the monkeys, we used the same NMR technique and in vivo microdialysis. RESULTS: Measures of N-acetyl-aspartate concentrations (NAA) in dorsolateral prefrontal cortex strongly and selectively predicted D2 receptor availability in the striatum (n = 14, rho = -.64, p < .01), suggesting that the greater the apparent dorsolateral prefrontal cortex pathology, the less the steady-state dopamine activity in these patients. A similar relationship between NAA measures in dorsolateral prefrontal cortex and steady-state dopamine concentrations in the striatum was found in the monkeys (n = 5, rho = .70, p < .05). We then tested in the same monkeys the relationship of prefrontal NAA and striatal dopamine overflow following amphetamine infusion into dorsolateral prefrontal cortex. Under these conditions, the relationship was inverted, i.e., the greater the apparent dorsolateral prefrontal cortex pathology, the greater the dopamine release. CONCLUSIONS: These data demonstrate direct relationships between putative neuronal pathology in dorsolateral prefrontal cortex and striatal dopamine activity in human and nonhuman primates and implicate a mechanism for dopamine dysregulation in schizophrenia.

Adult↗
PubMed1999

Quality procedures in non-gynaecological cytology laboratories in England and Wales.

All non-gynaecological cytology laboratories in England and Wales (n = 212) were surveyed by telephone. The aim was to investigate what concepts of quality applied in this context and to establish what tools and techniques of quality improvement were used. The overall response was 146 (69%). The respondents mainly comprised NHS Trusts and University Departments. The study showed that there was a diverse approach to quality. All types of quality assurance and customer focus procedure questioned were undertaken but to a varied extent; three laboratories (2%) used a complete range and three (2%) used no procedure at all. Accreditation was associated with staffing adequacy and use of surveys, but not quality assurance (QA) or user focus. Laboratories with a high priority for quality performed more QA and reported a higher staffing adequacy. Critical incident analysis was dependent on workload. Computerization did not affect quality procedures and involvement in the Breast Screening Programme did not result in different quality measures. The time since last update was independent of all factors and external quality assurance (EQA) was not widely available. The study suggested that an integrated approach to quality had not been adopted in English and Welsh cytology laboratories and that there may be a need for a more strategic approach with greater availability of EQA, guidelines on quality tools, closer linkage of accreditation and quality procedures and the production of minimum and ideal standards. The ideal standard could be the complete range of procedures, and the minimum standard could comprise those processes in most frequent use, i.e. critical incident analysis, correlation methods, action on information, analysis of what is done with diagnostic information, a complaints procedure and customer surveys.

Consumer Behavior↗
PubMed1999

The social worker in the emerging field of home care: Professional activities and ethical concerns.

Although home care is one of the fastest growing segments of the health care delivery system, there is little empirical data on the professional functions or ethical concerns of social workers employed in home care. To provide this information 118 social workers in proprietary and nonprofit agencies in one midwestern and one southern state were surveyed. The results indicated that social workers performed a wider array of professional functions with a more diverse population of patients than had been documented previously. Workers experienced ethical concerns related to self-determination, barriers to access of services, implementing advance directives, and assessment of mental competence most often. Workers in proprietary agencies rated the ethical concern of barriers to access of services as occurring significantly more often than workers in nonprofit agencies.

Adolescent↗
PubMed1999

CFTR is functionally active in GnRH-expressing GT1-7 hypothalamic neurons.

We have demonstrated the expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, mRNA, and protein within the rat and human brains, in areas regulating sexual differentiation and function. We have found that GT1-7, a gonadotropin-releasing hormone (GnRH)-secreting hypothalamic neuronal cell line, expresses the CFTR gene, mRNA, and protein and cAMP-dependent (36)Cl efflux. A linear 7-pS Cl- conductance, which is stimulated by ATP and cAMP analogs and inhibited by glibenclamide, consistent with CFTR activity, has been identified in GT1-7 cells. Antisense oligo(dN) generated against exon 10 of the CFTR gene transcript (mRNA) inhibit GnRH secretion into media [312 +/- 73, 850 +/- 150, 963 +/- 304, and 912 +/- 74 pg GnRH/4 x 10(6) cells for antisense, sense, missense, and no oligo(dN), respectively; P < 0. 029 for antisense oligo(dN)-treated vs. normal cells]. No changes in intracellular synthesis of GnRH were noted [1,400 +/- 371 and 1,395 +/- 384 pg GnRH/4 x 10(6) cells for antisense and sense oligo(dN), respectively]. Antisense oligo(dN), but not sense or missense oligo(dN), inhibited cAMP-dependent 36Cl efflux. The expression of CFTR protein, detected by Western blotting, was also inhibited 68% by preincubation of cells with antisense oligo(dN). GT1-7 hypothalamic neurons express the CFTR gene, mRNA, and protein, which modulate neurosecretion. Abnormal neuropeptide vesicle trafficking by mutant CFTR may help to explain some of the diverse manifestations of cystic fibrosis.

3T3 Cells↗
PubMed1999

Comparison of ketamine-induced thought disorder in healthy volunteers and thought disorder in schizophrenia.

OBJECTIVE: This study sought to determine whether thought disorder induced in healthy volunteers by the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine resembles the thought disorder found in patients with schizophrenia. METHOD: The Scale for the Assessment of Thought, Language, and Communication was used to assess thought disorder in healthy volunteers (N = 10) who received subanesthetic doses of ketamine and in a group of clinically stable inpatients with schizophrenia (N = 15) who did not receive ketamine. RESULTS: Mean scores on the Scale for the Assessment of Thought, Language, and Communication for patients with schizophrenia and healthy volunteers receiving ketamine did not differ significantly. Moreover, three of the four highest rated test items in both groups were the same. CONCLUSIONS: These data suggest that ketamine-induced thought disorder in healthy volunteers is not dissimilar to the thought disorder in patients with schizophrenia and provide support for the involvement of the NMDA receptor in a cardinal symptom of schizophrenia.

Adult↗