PubMed Health⌕ Search

Biomedical subjects

J Gray

Publications and source records attributed to J Gray.

At least 19 recordsLinked to original sources

Saccades in presymptomatic and early stages of Huntington disease.

OBJECTIVE: To evaluate quantitative measures of eye movements as possible biomarkers in prediagnostic and early stages of Huntington disease (HD). METHODS: The study sample (n = 215) included individuals both at risk and recently diagnosed with HD. All participants completed a uniform clinical evaluation which included administration of the Unified Huntington's Disease Rating Scale (UHDRS) by a movement disorder neurologist and molecular testing to determine HD gene status. A high resolution, video-based eye tracking system was employed to quantify measures of eye movement (error rates, latencies, SD of latencies, velocities, and accuracies) during a computerized battery of saccadic and steady fixation tasks. RESULTS: Prediagnostic HD gene carriers and individuals with early HD demonstrated three types of significant abnormalities while performing memory guided and anti-saccade tasks: increased error rate, increased saccade latency, and increased variability of saccade latency. The eye movement abnormalities increased with advancing motor signs of HD. CONCLUSIONS: Abnormalities in eye movement measures are a sensitive biomarker in the prediagnostic and early stages of Huntington disease (HD). These measures may be more sensitive to prediagnostic changes in HD than the currently employed neurologic motor assessment.

Eye Movements↗

Genetic nurse counsellors can be an acceptable and cost-effective alternative to clinical geneticists for breast cancer risk genetic counselling. Evidence from two parallel randomised controlled equivalence trials.

This study compared genetic nurse counsellors with standard services for breast cancer genetic risk counselling services in two regional genetics centres, in Grampian region, North East Scotland and in Cardiff, Wales. Women referred for genetic counselling were randomised to an initial genetic counselling appointment with either a genetic nurse counsellor (intervention) or a clinical geneticist (current service, control). Participants completed postal questionnaires before, immediately after the counselling episode and 6 months later to assess anxiety, general health status, perceived risk and satisfaction. A parallel economic evaluation explored factors influencing cost-effectiveness. The two concurrent randomised controlled equivalence trials were conducted and analysed separately. In the Grampian trial, 289 patients (193 intervention, 96 control) and in the Wales trial 297 patients (197 intervention and 100 control) returned a baseline questionnaire and attended their appointment. Analysis suggested at least likely equivalence in anxiety (the primary outcome) between the two arms of the trials. The cost per counselling episode was 11.54 UK pounds less for nurse-based care in the Grampian trial and 12.50 UK pounds more for nurse-based care in Cardiff. The costs were sensitive to the grade of doctor (notionally) replaced and the extent of consultant supervision required by the nurse. In conclusion, care based on genetic nurse counsellors was not significantly different from conventional cancer genetic services in both trial locations.

Adolescent↗

Functional characterization of human NTRK2 mutations identified in patients with severe early-onset obesity.

OBJECTIVE: The neurotrophin receptor TrkB has been implicated in the regulation of energy homeostasis in rodents. We have previously identified four rare missense mutations in the gene encoding TrkB, NTRK2, in 198 severely obese children with developmental delay. We have now undertaken a more detailed analysis of the in vitro functional consequences of the mutations identified: I98V, P660L, T821A and Y722C. DESIGN: Wild-type and mutant TrkB receptor constructs were stably transfected into PC12 cells and the signaling responses to the endogenous ligand, brain-derived neurotrophic factor (BDNF), were examined by Western blotting of cell lysates. In the case of Y722C, PC12 cells stably expressing this mutant were studied for their ability to respond to BDNF by promoting neurite outgrowth and cell survival. RESULTS: Further functional characterization of the previously reported Y722C TrkB mutation reveals impaired activation of mitogen-activated protein kinase, phospholipase C-gamma and Akt, as well as reduced BDNF-induced neurite outgrowth and cell survival in stably transfected PC12 cell lines. However, the signaling properties of I98V, P660L and T821A were all indistinguishable from wild type. CONCLUSION: We provide further evidence for the impairment in signaling by Y722C and show that as well as a loss of signaling, this mutation affects the ability of TrkB to promote neurite outgrowth in response to BDNF. Thus, impaired hypothalamic neurogenesis may contribute to the severe hyperphagia and obesity seen in the individual harboring the Y722C variant. The other three rare TrkB variants do not show reduced autophosphorylation or impaired downstream signaling in vitro and, as yet, it is unclear whether these variants contribute to obesity in these patients.

Age of Onset↗

Incidence-angle dependence of optical reflectivity difference from an ultrathin film on solid surface.

We studied the incidence-angle dependence of the optical reflectivity difference in response to ultrathin films on transparent and opaque substrates. We found that the classical three-layer model reproduces the experimentally obtained angular dependence for a monolayer of xenon on Nb(110) and for a monolayer of protein molecules on functionalized glass. We explore the enhancement of the optical response near the Brewster angle (or its equivalent for opaque substrates) in thin film detection.

Adsorption↗

Changing physician prescribing behaviour.

Didactic approaches to educating physicians and/or other health professionals do not produce changes in learner behaviour. Similarly, printed materials and practice guidelines have not been shown to change prescribing behaviour. Evidence-based educational approaches that do have an impact on provider behaviour include: teaching aimed at identified learning needs; interactive educational activities; sequenced and multifaceted interventions; enabling tools such as patient education programs, flow charts, and reminders; educational outreach or academic detailing; and audit and feedback to prescribers. Dr. Jean Gray reflects over the past 25 years on how there has been a transformation in the types of activities employed to improve prescribing practices in Nova Scotia. The evolution of Continuing Medical Education (CME) has resulted in the creation of the Drug Evaluation Alliance of Nova Scotia (DEANS) program, which is one exemplar of an evidence-based educational approach to improving physician prescribing in that province. Key words: Evidence-based, education, prescribing.

Drug Prescriptions↗

Does cognitive function influence alaryngeal speech rehabilitation?

BACKGROUND: We sought to define the cognitive domains that influence valved speech rehabilitation. METHODS: Sixteen laryngectomees with primary tracheoesophageal punctures were randomly recruited from one head and neck unit. They were assessed by a consultant neuropsychologist and a speech therapist. Speech therapy time was determined from speech therapy notes. RESULTS: The Digit Symbol Substitution Test, assessing learning speed and processing speed, correlated significantly with speech therapy time in the first (p = .002) and third (p = .014) postoperative years, respectively. Categorical fluency assessment correlated positively with speech therapy time in the first year (p = .009). Learning speed (p = .007) and categorical fluency (p = .041) correlated positively with the fall in speech therapy input between the first and third year after laryngectomy. CONCLUSIONS: Learning speed, processing speed, and categorical fluency strongly influence alaryngeal speech rehabilitation. This study highlights the potential for pre-laryngectomy cognitive assessment to help plan alaryngeal speech rehabilitation. This has significant resource implications.

Aged↗

Increased acute GvHD and higher transplant-related mortality in non-caucasians undergoing standard sibling allogeneic stem cell transplantation.

We conducted a retrospective study to compare outcome in Caucasians and non-Caucasians undergoing standard sibling allogeneic SCT. End points of the study were to compare graft-versus-host disease (GvHD) occurrence and transplant-related mortality (TRM). There were 251 patients, 43 non-Caucasian and 208 Caucasian. A higher proportion of non-Caucasian patients developed acute GvHD (aGvHD) grade 2 or greater as compared to the Caucasian group (48 vs 26%, respectively) P = 0.02. With a median follow-up of 27 months, 26% (11/43) of non-Caucasians and 14% (29/208) of Caucasian patients had died from TRM, which accounted for 55% of all deaths in the non-Caucasian group compared to 33% in Caucasians, P = 0.02. Overall survival 12 months post transplant was 64 vs 69% in the non-Caucasian and Caucasian groups, respectively (P = 0.43). Although there were higher numbers of CMV-positive patients in the non-Caucasian group, there were no deaths from CMV reactivation in this subgroup. We conclude that there is increased TRM and aGvHD following standard sibling allograft in the non-Caucasian population and this could be due to either differences in tumour biology or extrinsic factors such as socio-economic factors, nutritional status, post transplant care or presenting with late stage disease.

Acute Disease↗

Performance of a time-resolved fluorescence immunoassay for measuring varicella-zoster virus immunoglobulin G levels in adults and comparison with commercial enzyme immunoassays and Merck glycoprotein enzyme immunoassay.

Highly sensitive and specific, quantitative assays are needed to detect varicella-zoster virus (VZV) immunoglobulin G in human sera, particularly for determining immune status and response following vaccination. A time-resolved fluorescence immunoassay (TRFIA) has been developed, and its performance was compared to that of two commercial enzyme immunoassays (EIAs) and Merck glycoprotein EIA (gpEIA). The TRFIA had equivalent sensitivity (97.8%) and high specificity (93.5%) in relation to gpEIA. A commercial (Behring) EIA compared favorably with TRFIA in terms of sensitivity (98.4%) but had lower specificity (80.7%). Another commercial EIA (Diamedix) had high specificity (97.1%) but low sensitivity (76.4%) compared to TRFIA if equivocal test results were treated as negative for VZV antibody. A novel feature of the TRFIA was that the cutoff was generated using population mixture modeling and was expressed in mIU/ml, as the assay was calibrated using the British standard VZV antibody.

Adult↗

A critical review of foot orthoses in the rheumatoid arthritic foot.

Foot orthoses are commonly prescribed by health professionals as a form of intervention for the symptomatic foot in rheumatoid arthritis. However, there is a limited evidence base to support the use of foot orthoses in this patient group. This article provides a critical review of the use of foot orthoses in the management of rheumatoid arthritic foot pathologies. A search was conducted in the Cochrane Controlled Trials Register (current issue of the Cochrane Library), Physiotherapy evidence database (PEDro), Medline, The Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Allied and Complementary Medicine (AMED) and from reference lists in journal articles. The language was restricted to English. Searching of the databases was undertaken between December 2004 and March 2005. The results indicated there is no consensus of opinion on the choice of foot orthoses used for the management of pathology in the rheumatoid foot, although there is strong evidence that foot orthoses do reduce pain and improve functional ability. The type of foot orthoses used ranged from simple cushioned insoles to custom-made rigid cast devices. Methodological issues raised included small sample size and poor use of valid and reliable outcome measures. There is limited evidence pertaining to cost-effectiveness. The results indicated a need for further investigation into the most clinically and cost-effective foot orthoses to prescribe in the management of the rheumatoid arthritic foot. This review highlights the need to identify the various types of foot orthoses that are most effective in the management of the established rheumatoid arthritic foot.

Arthritis, Rheumatoid↗

Prediction of Charnley femoral stem aseptic loosening by early post-operative radiological features.

We describe the association between immediate post-operative radiological appearances and early aseptic failure of total hip replacement. Sixty-three hips were entered into the aseptic failure group and 138 into the control group. Alignment of the femoral stem was not associated with failure (p=0.283). Thickness of the cement mantle was associated with failure in Gruen zones 6 (p=0.040) and 7 (p=0.003). A significant association for the presence of radiolucent lines was found for Gruen zones 3 (p=0.0001) and 5 (p=0.0001). Grade of cementation was associated with failure for Barrack grades C (p=0.001) and D (p=0.001). This study has demonstrated that easily applied radiological criteria can be used to identify 'hip arthroplasties at risk' from the immediate post-operative radiograph.

Aged↗

A micro costing of NHS cancer genetic services.

This paper presents the first full micro costing of a commonly used cancer genetic counselling and testing protocol used in the UK. Costs were estimated for the Cardiff clinic of the Cancer Genetics Service in Wales by issuing a questionnaire to all staff, conducting an audit of clinic rooms and equipment and obtaining gross unit costs from the finance department. A total of 22 distinct event pathways were identified for patients at risk of developing breast, ovarian, breast and ovarian or colorectal cancer. The mean cost per patient were pound sterling 97- pound sterling 151 for patients at moderate risk, pound sterling 975- pound sterling 3072 for patients at high risk of developing colorectal cancer and pound sterling 675- pound sterling 2909 for patients at high risk of developing breast or ovarian cancer. The most expensive element of cancer genetic services was labour. Labour costs were dependent upon the amount of labour, staff grade, number of counsellors used and the proportion of staff time devoted to indirect patient contact. With the growing demand for cancer genetic services and the growing number of national and regional cancer genetic centers, there is a need for the different protocols being used to be thoroughly evaluated in terms of costs and outcomes.

Costs and Cost Analysis↗

Effects of vibrissae removal on search accuracy in the water maze.

In two experiments, the vibrissae were clipped on either the left, the right, or both sides, and the rats were trained to find a submerged platform in the Morris water maze. In both experiments, animals without vibrissae on both sides or on the left consistently spent significantly more time in the "counter" area twice the platform diameter in size, surrounding the submerged platform, than intact controls. Counter preference was not as consistent across experiments in rats with right vibrissae removed. These results suggest that the vibrissae are required for proprioceptive location of the platform itself, but not for proximal search accuracy. Since ischemic damage to hippocampal CA1 pyramidal cells has also been reported to prolong counter search during training, the results support the suggestion that impaired hippocampal processing of proprioceptive information from the vibrissae may contribute to the increased latency to find the platform shown by ischemic rats.

Analysis of Variance↗

Blood pressure after cardiac transplantation in childhood.

BACKGROUND: There has been little formal study of blood pressure in children after cardiac transplantation. METHODS: Twenty-four-hour and clinical blood pressure (BP) were measured in 28 children (>6 months after transplantation) and compared with a large amount of normal data. RESULTS: Conventional (clinical) systolic BP (SBP) was elevated in 9 (32.1%) of 28 (95% confidence interval [CI] 15.8 to 52.3), and conventional diastolic BP (DBP) was elevated in 5 (17.8%) of 28 (95% CI 6.0 to 36.8). Mean 24-hour BP was >97.5 percentile in 2 (7.7%) of 26 (95% CI 0.9 to 25.1) for SBP and in 7 (28.0%) of 25 (95% CI 12.1 to 49.4) for DBP. In comparison with the control population, mean nighttime SBP was 8.9 mm Hg higher in the transplanted group (95% CI 4.8 to 13.1), but daytime and mean 24-hour SBP were similar. Mean day, night, and 24-hour DBP was significantly higher in the transplanted patients. The nighttime decrease in BP was significantly less than controls for SBP, but not for DBP. Conventional BP measurement was poorly predictive of 24-hour BP. There was a significant association between mean 24-hour SBP and interventricular septal thickness (r(2)=0.35; p=0.01). DBP was not associated with interventricular septal thickness (r(2)=0.07; p=0.20) but was significantly correlated with the time since transplantation (r=0.42; p=0.03 for conventional DBP and r=0.43; p=0.04 for 24-hour DBP). CONCLUSIONS: The elevation of DBP in children after cardiac transplantation is unexplained. The elevation in nighttime SBP has possible important therapeutic implications and is not predicted by conventional (clinical) BP measurement.

Adolescent↗

Repositioning the patient: the implications of being 'at risk'.

In the modern era of biomedical practice, genetic knowledge has redefined the idea of 'the patient' to include those who are 'at risk' of disease alongside those who are already sick. For such individuals, it is risk itself that constitutes the raison d'être of medical intervention. Using data from interviews with 58 users of a UK cancer genetics service together with data derived from clinical consultations, we consider the way such patients or clients make sense of a cancer genetic risk estimate and how they integrate genetic risk information into their lifeworld. In particular, we note that patient-clients who are 'at risk' tend to see themselves in a liminal position betwixt the healthy and the sick, and that such individuals consequently seek recourse to systems of medical surveillance that can continuously monitor their state of health. Our analysis also revealed the fact that many of those deemed by professionals to be at low risk of inheriting cancer-related mutations subsequently strove to be re-categorised as being at moderate or high risk of an adverse outcome. A number of explanations concerning lay health beliefs, lay 'representations' of health and the nature of the patient-client's lifeworld are examined and assessed in order to account for this apparent paradox.

Attitude to Health↗

Molecular characterization of rotaviruses circulating in the population in Turkey.

Of a total of 508 stool specimens from children with acute diarrhoea, mostly under the age of 5 years, collected in nine cities in the western and southeastern regions of Turkey between May 2000 and October 2002, 119 (23.4%) were found positive for rotaviruses (RV) by ELISA. Positive samples were characterized by electropherotyping and G and P genotyping. A subset of G and P types were confirmed by nucleic acid sequencing. The most prevalent types found in this collection included G4P[8], accounting for 27/64 (42.2%) of the fully characterized strains. G1P[8], G2P[4] and G3P[8] were found in 17 (26.6%), 2 (3.1%) and one (1.5%) samples respectively. Less common strains such as G9P[8] were found in two (3.2%) samples and G2P[8], G1P[6], G2P[6] and G4P[6], possible reassortant viruses, were found in five (7.8%), 2 (3.1%), one (1.5%) and four (6.3%) samples respectively. Mixed infections were found in six (7.3%) samples and were associated with combinations of G1 + G2, G1 + G4, G1 + G9 and G4 + G9 strains. This is the first molecular epidemiology study of its kind to be carried out in Turkey and suggests a significant diversity of co-circulating rotavirus strains.

Age Distribution↗

An exploratory comparison of genetic counselling protocols for HNPCC predictive testing.

Most UK genetics centres offering predictive testing for hereditary non-polyposis colorectal cancer (HNPCC) use an extended counselling protocol originally developed for Huntington's disease. Shortened counselling may be more appropriate in the context of treatable genetic conditions such as HNPCC. Twenty-six high-risk individuals were randomized to extended genetic counselling (two sessions of education and reflection held 1 month apart) or shortened genetic counselling (a single educational session) prior to HNPCC testing. Prospective questionnaires, interviews and transcripts of counselling sessions were analysed. Participants were unsure what to expect prior to genetic counselling and had already decided to undergo genetic testing. There was no evidence of psychological harm caused by shortened genetic counselling, with a high level of satisfaction with the counselling received in both groups. Reflective counselling occurred in both groups but was framed in terms of practical action and information. Participants expressed differing preferences for the level of information received. This exploratory study indicates that shortened genetic counselling may be an appropriate means of supporting decisions already made by individuals about HNPCC testing. However, participants would benefit from preparatory information to help them reflect on issues not previously considered, which can then be explored more fully as part of a tailored counselling approach.

Adult↗