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Biomedical subjects

J Turnbull

Publications and source records attributed to J Turnbull.

At least 19 recordsLinked to original sources

Developing a standard short questionnaire for the assessment of patient satisfaction with out-of-hours primary care.

BACKGROUND: Governmental reviews of out-of-hours services in England and Scotland have recommended that a standard questionnaire should be used to assess patient satisfaction. This is important because of the rapid introduction of new forms of care. OBJECTIVE: To produce a brief, reliable and valid measure of patient satisfaction for use by a wide variety of providers of out-of-hours primary care. METHODS: The Short Questionnaire for Out-of-Hours care was designed and compared with a longer questionnaire which had been validated and used in earlier research. Questionnaires were sent to 1906 people contacting an out-of-hours GP co-operative. Three versions of the short questionnaire were used with different formats. Analysis compared the response rates, measurement properties, concurrent and construct validity of the short and long questionnaires, and of different versions of the short questionnaire. RESULTS AND CONCLUSIONS: There was no significant difference in the overall response rates obtained from the short or long questionnaires (45.7% versus 41.9%; P = 0.17). The effective response rate of questionnaires from which all satisfaction scales could be calculated was higher for the short questionnaire (43.0% versus 36.4%; P = 0.01). There were no significant differences in response rates or distribution of responses between different versions of the short questionnaire. There was moderate agreement between items on the short questionnaire and corresponding scales on the long questionnaire. Scores using the short questionnaire showed anticipated relationships with the age and sex of patients and with characteristics of how the service was delivered. The SQOC is valid and reliable for routine service use.

After-Hours Care↗

14C activity and global carbon cycle changes over the past 50,000 years.

A series of 14C measurements in Ocean Drilling Program cores from the tropical Cariaco Basin, which have been correlated to the annual-layer counted chronology for the Greenland Ice Sheet Project 2 (GISP2) ice core, provides a high-resolution calibration of the radiocarbon time scale back to 50,000 years before the present. Independent radiometric dating of events correlated to GISP2 suggests that the calibration is accurate. Reconstructed 14C activities varied substantially during the last glacial period, including sharp peaks synchronous with the Laschamp and Mono Lake geomagnetic field intensity minimal and cosmogenic nuclide peaks in ice cores and marine sediments. Simulations with a geochemical box model suggest that much of the variability can be explained by geomagnetically modulated changes in 14C production rate together with plausible changes in deep-ocean ventilation and the global carbon cycle during glaciation.

Journal Article↗

Reviewing emergency care systems I: insights from system dynamics modelling.

OBJECTIVES: To describe the components of an emergency and urgent care system within one health authority and to investigate ways in which patient flows and system capacity could be improved. METHODS: Using a qualitative system dynamics (SD) approach, data from interviews were used to build a conceptual map of the system illustrating patient pathways from entry to discharge. The map was used to construct a quantitative SD model populated with demographic and activity data to simulate patterns of demand, activity, contingencies, and system bottlenecks. Using simulation experiments, a range of scenarios were tested to determine their likely effectiveness in meeting future objectives and targets. RESULTS: Emergency hospital admissions grew at a faster annual rate than the national average for 1998-2001. Without intervention, and assuming this trend continued, acute hospitals were likely to have difficulty sustaining levels of elective work, in reaching elective admission targets and in achieving bed occupancy targets. General practice admissions exerted the greatest influence on occupancy rates. Prevention of emergency admissions for older people (3%-6% each year) reduced bed occupancy in both hospitals by 1% per annum over five years. Prevention of emergency admissions for patients with chronic respiratory disease affected occupancy less noticeably, but because of the seasonal pattern of admissions, had an effect on peak winter occupancy. CONCLUSIONS: Modelling showed the potential consequences of continued growth in demand for emergency care, but also considerable scope to intervene to ameliorate the worst case scenarios, in particular by increasing the care management options available in the community.

Bed Occupancy↗

Reviewing emergency care systems 2: measuring patient preferences using a discrete choice experiment.

OBJECTIVE: To investigate patients' strength of preferences for attributes associated with modernising delivery of out of hours emergency care services in Nottingham. METHODS: A discrete choice experiment was applied to quantify preferences for key attributes of out of hours emergency care. The attributes reflected the findings of previous research, current policy initiatives, and discussions with local key stakeholders. A self complete questionnaire was administered to NHS Direct callers and adults attending accident and emergency, GP services and NHS walk-in centre. Regression analysis was used to estimate the relative importance of the different attributes. RESULTS: Response was 74% (n = 457) although 61% (n = 378) were useable. All attributes were statistically significant. Being consulted by a doctor was the most important attribute. This was followed by being consulted by a nurse, being kept informed about waiting time, and quality of the consultation. Respondents were prepared to wait an extra 2 hours 20 minutes to be consulted by a doctor. There were no measurable preference differences between patients surveyed at different NHS entry points. Younger respondents preferred single telephone call access to health care out of hours. Although having services provided close to home and making contact in person were generally preferred, they were less important than others, suggesting that a range of service locations may be acceptable to patients. CONCLUSIONS: This study showed that local solutions for reforming emergency out of hours care should take account of the strength of patient preferences. The method was acceptable and the results have directly informed the development of a local service framework for emergency care.

Adolescent↗

Creatine supplementation and riluzole treatment provide similar beneficial effects in copper, zinc superoxide dismutase (G93A) transgenic mice.

This study investigated the effects of riluzole (Ril), creatine (Cr) and a combination of these treatments on the onset and progression of clinical signs and neuropathology in an animal model of familial amyotrophic lateral sclerosis, the G93A transgenic mouse (n=13-17 per group). The onset of clinical signs was delayed (P<0.05) by about 12 days in all treatment groups compared with control; however, no differences occurred between treatments. All animals were killed at 199 days of age. At the end of the experimental period the severity of clinical signs was less (P<0.05) with all treatments compared with control. Again no differences between treatments were observed. The treatments had no effect on the number of neurons in ventral horns of the lumbar region of the spinal cord. Transgenic mice ingesting Cr displayed elevated (P<0.05) total Cr levels in cerebral hemispheres (5%) and spinal cord (8%), but not skeletal muscles. These data demonstrate that treatment with Ril and Cr were both effective in delaying disease onset and clinical disability. To the age of killing, no additional benefit was conferred by co-administration of Ril and Cr.

Age of Onset↗

Heparan sulphate sulphotransferase expression in mice and Caenorhabditis elegans.

Heparan sulphate (HS) acts as a multifunctional cell regulator, with specific sulphated saccharide sequences designed for selective interactions with many proteins. Functionally, these interactions result in regulation of the protein activities, and there is growing evidence that cells can dynamically alter the structure of HS sequences that they display. HS biosynthesis involves the action of a complex set of enzymes with polymerase, epimerase and sulphotransferase (ST) activities. In higher organisms, multiple isoforms of STs decorate the nascent HS chains with specific patterns of sulphation that confer selective biological functions. The study of HSSTs in model organisms provides a valuable opportunity to examine the expression of these enzymes in relation to the structure and activities of the HS produced. Here we describe that, in mice, there are stage-specific combinations of HSST isoenzymes that underlie the synthesis of different HS species at different times in the developing brain. This differential expression of HSSTs results in the synthesis of structurally variant HS species that form functional signalling complexes with specific fibroblast growth factors and their receptors. Regulated synthesis of specific HS species could be a mechanism for the regulation of proliferation and differentiation in the developing brain. We also describe evidence that a Caenorhabditis elegans orthologue of the mammalian 2OST enzyme, called HST-2, is essential for the normal development of this nematode. Together, these studies emphasize the importance of HSSTs in the biosynthesis of functionally variant HS proteoglycans, and demonstrate the importance of these complex regulatory molecules in developmental processes.

Animals↗

Genetic mapping of a new Lafora progressive myoclonus epilepsy locus (EPM2B) on 6p22.

BACKGROUND: Lafora disease is a progressive myoclonus epilepsy with polyglucosan accumulations and a peculiar neurodegeneration with generalised organellar disintegration. It causes severe seizures, leading to dementia and eventually death in early adulthood. METHODS: One Lafora disease gene, EPM2A, has been identified on chromosome 6q24. Locus heterogeneity led us to search for a second gene using a genome wide linkage scan in French-Canadian families. RESULTS: We mapped a second Lafora disease locus, EPM2B, to a 2.2 Mb region at 6p22, a region known to code for several proteins, including kinesins. Kinesins are microtubule dependent motor proteins that are involved in transporting cellular components. In neurones, they play a major role in axonal and dendritic transport. CONCLUSION: Analysis of the present locus in other non-EPM2A families will reveal whether there is further locus heterogeneity. Identification of the disease gene will be of major importance towards our understanding of the pathogenesis of Lafora disease.

Chromosome Mapping↗

Histological assessment of intermediate- and long-term creatine monohydrate supplementation in mice and rats.

Creatine monohydrate (CrM) supplementation appears to be relatively safe based on data from short-term and intermediate-term human studies and results from several therapeutic trials. The purpose of the current study was to characterize pathological changes after intermediate-term and long-term CrM supplementation in mice [healthy control and SOD1 (G93A) transgenic] and rats (prednisolone and nonprednisolone treated). Histological assessment (18-20 organs/tissues) was performed on G93A mice after 159 days, and in Sprague-Dawley rats after 365 days, of CrM supplementation (2% wt/wt) compared with control feed. Liver histology was also evaluated in CD-1 mice after 300 days of low-dose CrM supplementation (0.025 and 0.05 g x kg-1x day-1) and in Sprague-Dawley rats after 52 days of CrM supplementation (2% wt/wt) with and without prednisolone. Areas of hepatitis were observed in the livers of the CrM-supplemented G93A mice (P < 0.05), with no significant inflammatory lesions in any of the other 18-20 tissues/organs that were evaluated. The CD-1 mice also showed significant hepatic inflammatory lesions (P < 0.05), yet there was no negative effect of CrM on liver histology in the Sprague-Dawley rats after intermediate-term or long-term supplementation nor was inflammation seen in any other tissues/organs (P = not significant). Dietary CrM supplementation can induce inflammatory changes in the liver of mice, but not rats. The observed inflammatory changes in the murine liver must be considered in the evaluation of hepatic metabolism in CrM-supplemented mice. Species differences must be considered in the evaluation of toxicological and physiological studies.

Animals↗

Specialist practice for UK community mental health nurses: the 1998--99 survey of course leaders.

Surveys of the leaders of the UK's post-qualifying education courses for community mental health nurses have taken place, on an annual basis, for over 10 years. In this paper, findings from the survey undertaken in the 1998--99 academic year are reported. These findings include: that most course leaders do not personally engage in clinical practice; that interprofessional education takes place at a minority of course centres, and that course philosophies and aims are characterised by an emphasis on both outcomes (in terms of, for example, skills acquisition, knowledge development and the ability to engage in reflective practice), and process (adult learning).

Attitude of Health Personnel↗

Heparan sulfate: decoding a dynamic multifunctional cell regulator.

The heparan sulfates are a family of cell-surface and matrix polysaccharides with an incredible degree of structural diversity that are distributed widely in virtually all metazoan organisms. Recent genetic, biochemical and cell-biological studies have led to increased understanding of the biosynthetic mechanisms that produce these complex molecules, as well as their functional versatility in regulating protein activities. The dynamic expression of heparan sulfates with differing sugar sequences suggests a new concept in which the repertoire of sequences produced by a particular cell or tissue is designated its 'heparanome'. This review discusses recent developments and surveys emerging experimental strategies that hold promise for revealing the functional specificity and mechanisms of action of heparan sulfates as multifunctional cell regulators.

Animals↗

Dynamic biosynthesis of heparan sulphate sequences in developing mouse brain: a potential regulatory mechanism during development.

Over recent years our understanding of the functions of the heparan sulphate (HS) family of complex polysaccharides has shifted dramatically. Once seen as simply structural scaffolding in the extracellular matrix, they are now viewed as critical players in the regulatory network of cells. They are strategically located at the cell surface and in the extracellular matrix, and there has been an increasing realization that specific sequences in the HS chains are designed for selective interactions with many proteins. Functionally, these interactions result in regulation of the protein activities. It is becoming clear that HS functions as a new class of multifunctional cell regulator. There is also growing evidence that cells can dynamically alter the structure of HS sequences that they express. Here we review recent developments and describe evidence for regulated changes in the synthesis and structure of HS chains expressed during early mouse brain development. The data suggest a new concept in which dynamic changes in biosynthesis of different HS sequences create distinct cellular HS repertoires, the heparanome. Their expression, in specific spatio-temporal patterns, is likely to endow organisms with novel regulatory mechanisms for controlling the activity of specific HS-binding proteins.

Animals↗

Lasting impact in families after death from ALS.

INTRODUCTION: ALS severely affects families, who have to cope after the patient's death. There is no information on ongoing needs or concerns of families surviving the death of the ALS patient. We wished to survey these needs. METHOD: We developed a written questionnaire which we distributed at a single point in time to 32 patients' families. All patients had been followed in the McMaster University ALS clinic, and had died months to years earlier from ALS. RESULTS: The response rate was excellent (85%). ALS caused lasting emotional and financial hardship in families, and 37% of respondents felt they were coping poorly, sometimes years after the patient's death. This did not clearly relate to the bereavement period, nor to the physical or financial impact of the disease during life. In most cases the disease led to a strengthening of family ties. However, 15% of chief caregivers felt blamed by in-laws for contributing to the death of the patient; in these cases family ties weakened. Less than half of families were still receiving ALS information, although 75% still wished to. About two-thirds of families had ongoing questions about the disease, and a small number remained concerned that they, or their children, would develop the disease. Only a third of families were actively involved in ongoing fund-raising activities. CONCLUSIONS: It is possible to survey ongoing family needs after the death of the ALS patient. ALS causes lasting impact in surviving family members. There are ongoing needs that could be met by ALS clinics, ALS organizations, and healthcare systems, and opportunities for greater involvement of family members in volunteer activities, awareness, and fundraising. Generalization across other healthcare systems, and comparison with other disease states, could be important.

Aged↗

Beneficial effect of ginseng root in SOD-1 (G93A) transgenic mice.

Many patients with amyotrophic lateral sclerosis (ALS; motor neuron disease) use natural or traditional therapies of unproven benefit. One such therapy is ginseng root. However, in some other disease models, ginseng has proven efficacious. Ginseng improves learning and memory in rats, and reduces neuronal death following transient cerebral ischemia. These effects of ginseng have been related to increases in the expression of nerve growth factor and its high affinity receptor in the rat brain, and antioxidant actions, inter alia. Since such actions could be beneficial in ALS as well, we studied the effect of ginseng (Panax quinquefolium), 40 and 80 mg/Kg, in B6SJL-TgN(SOD1-G93A)1Gur transgenic mice. The ginseng was given in drinking water, from age 30d onwards. We measured the time to onset of signs of motor impairment, and survival. There was no difference between the two ginseng groups (n=6, 6) in either measure. However, compared to controls (n=13), there was a prolongation in onset of signs (116d vs. 94d, P<0.001), and survival (139d vs. 132d, P<0.05). These experiments lend support to the use of ginseng root in ALS. Future experiments using this model could examine for symptomatic effects of ginseng, measure the effect of specific ginsenosides (which differ between ginseng species), and elucidate their mechanisms of action.

Amyotrophic Lateral Sclerosis↗

Sequencing of 3-O sulfate containing heparin decasaccharides with a partial antithrombin III binding site.

Heparin- and heparan sulfate-like glycosaminoglycans (HLGAGs) represent an important class of molecules that interact with and modulate the activity of growth factors, enzymes, and morphogens. Of the many biological functions for this class of molecules, one of its most important functions is its interaction with antithrombin III (AT-III). AT-III binding to a specific heparin pentasaccharide sequence, containing an unusual 3-O sulfate on a N-sulfated, 6-O sulfated glucosamine, increases 1,000-fold AT-III's ability to inhibit specific proteases in the coagulation cascade. In this manner, HLGAGs play an important biological and pharmacological role in the modulation of blood clotting. Recently, a sequencing methodology was developed to further structure-function relationships of this important class of molecules. This methodology combines a property-encoded nomenclature scheme to handle the large information content (properties) of HLGAGs, with matrix-assisted laser desorption ionization MS and enzymatic and chemical degradation as experimental constraints to rapidly sequence picomole quantities of HLGAG oligosaccharides. Using the above property-encoded nomenclature-matrix-assisted laser desorption ionization approach, we found that the sequence of the decasaccharide used in this study is DeltaU(2S)H(NS,6S)I(2S)H(NS, 6S)I(2S)H(NS,6S)IH(NAc,6S)GH(NS,3S,6S) (+/-DDD4-7). We confirmed our results by using integral glycan sequencing and one-dimensional proton NMR. Furthermore, we show that this approach is flexible and is able to derive sequence information on an oligosaccharide mixture. Thus, this methodology will make possible both the analysis of other unusual sequences in HLGAGs with important biological activity as well as provide the basis for the structural analysis of these pharamacologically important group of heparin/heparan sulfates.

Antithrombin III↗

Manganese superoxide dismutase levels are elevated in a proportion of amyotrophic lateral sclerosis patient cell lines.

The most frequent genetic causes of amyotrophic lateral sclerosis (ALS) determined so far are mutations occurring in the gene for copper/zinc superoxide dismutase (CuZnSOD). The mechanism may involve inappropriate formation of hyroxyl radicals, peroxynitrite or malfunctioning of the SOD protein. We hypothesized that undiscovered genetic causes of sporadically occurring amyotrophic lateral sclerosis might be found in the mechanisms that create and destroy oxygen free radicals within the cell. After determining that there were no CuZnSOD mutations present, we measured superoxide production from mitochondria and manganese superoxide dismutase (MnSOD), glutathione peroxidase, NFkappaB, Bcl-2 and Bax by immunoblot. Of the ten sporadic patients we tested we found three patients with significantly increased concentrations of MnSOD. These patients also had lower levels of superoxide production from mitochondria and decreased expression of Bcl-2. No mutations were found in the cDNA sequence of either MnSOD in any of the sporadic patients. A patient with a CuZnSOD mutation (G82R) used as a positive control showed none of these abnormalities. The patients displaying the MnSOD aberrations showed no specific distinguishing features. This result suggests that the cause of ALS in a subgroup of ALS patients (30%) is genetic in origin and can be identified by these markers. The alteration in MnSOD and Bcl-2 are likely epiphenomena resulting from the primary genetic defect. It suggests also that the oxygen free radicals are part of the cause in this subgroup and that dysregulation of MnSOD or increased endogenous superoxide production might be responsible.

Adult↗

Cost analysis of nurse telephone consultation in out of hours primary care: evidence from a randomised controlled trial.

OBJECTIVE: To undertake an economic evaluation of nurse telephone consultation using decision support software in comparison with usual general practice care provided by a general practice cooperative. DESIGN: Cost analysis from an NHS perspective using stochastic data from a randomised controlled trial. SETTING: General practice cooperative with 55 general practitioners serving 97 000 registered patients in Wiltshire, England. SUBJECTS: All patients contacting the service, or about whom the service was contacted during the trial year (January 1997 to January 1998). MAIN OUTCOME MEASURES: Costs and savings to the NHS during the trial year. RESULTS: The cost of providing nurse telephone consultation was 81 237 pound sterling per annum. This, however, determined a 94 422 pound sterling reduction of other costs for the NHS arising from reduced emergency admissions to hospital. Using point estimates for savings, the cost analysis, combined with the analysis of outcomes, showed a dominance situation for the intervention over general practice cooperative care alone. If a larger improvement in outcomes is assumed (upper 95% confidence limit) NHS savings increase to 123 824 pound sterling per annum. Savings of only 3728 pound sterling would, however, arise in a scenario where lower 95% confidence limits for outcome differences were observed. To break even, the intervention would have needed to save 138 emergency hospital admissions per year, around 90% of the effect achieved in the trial. Additional savings of 16 928 pound sterling for general practice arose from reduced travel to visit patients at home and fewer surgery appointments within three days of a call. CONCLUSIONS: Nurse telephone consultation in out of hours primary care may reduce NHS costs in the long term by reducing demand for emergency admission to hospital. General practitioners currently bear most of the cost of nurse telephone consultation and benefit least from the savings associated with it. This indicates that the service produces benefits in terms of service quality, which are beyond the reach of this cost analysis.

Acute Disease↗

Negotiating the boundaries: the experience of the mental health nurse at the interface with the criminal justice system.

Community mental health nurses working within the criminal justice system undertake an important function with regard to the strategic intent that wherever possible, mentally disordered persons should receive care and treatment from health and social services. Their precise role, and the particular function of court diversion/assessment schemes, is still being defined. This takes place within a broader context of reorientation of mental health nursing within the move to community care and exposure to the complexity of multidisciplinary working. Examining the experience of mental health nurses in court diversion schemes reveals the intensity of the experience of working in an inter-professional setting without the benefit of preparation or training, and without the frame of reference of a structured health environment. Adaptation of the language of mental health nursing was necessary to effect mutual understanding with other professional groups, and there was a recognition that the competences needed to operate in this environment had not previously been identified as part of their skills base. The result was to bring into question their professional practice and identity as mental health nurses. The handling of patient information in the context of an inter-professional setting remains an issue requiring clarification.

Community Mental Health Services↗