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Biomedical subjects

K Turner

Publications and source records attributed to K Turner.

At least 19 recordsLinked to original sources

A multicentre longitudinal observational study of changes in self reported health status in people with Parkinson's disease left untreated at diagnosis.

BACKGROUND: The issue of when to start treatment in Parkinson's disease (PD) remains controversial. Some favour treatment at diagnosis while others opt for a "wait and watch" policy. The effect of the latter policy on the self reported health status of people with PD is unknown. AIMS: To record self reported health status through longitudinal use of a validated PD specific questionnaire (PDQ-39) in untreated PD patients in multiple centres in the UK. To compare patients who were left untreated with those who were offered treatment during follow-up. METHODS: A multicentre, prospective, "real life" observational audit based study addressing patient reported outcomes in relation to self reported health status and other sociodemographic details. RESULTS: 198 untreated PD were assessed over a mean period of 18 months. During two follow-up assessments, the self reported health status scores in all eight domains of the PDQ-39 and the overall PDQ-39 summary index worsened significantly (p<0.01) in patients left untreated. In a comparative group in whom treatment was initiated at or soon after diagnosis, there was a trend towards improvement in self reported health status scores after treatment was started. CONCLUSIONS: This study addresses for the first time self reported health status, an indicator of health related quality of life, in untreated PD. The findings may strengthen the call for re-evaluation of the policy to delay treatment in newly diagnosed patients with PD.

Aged↗

Second trimester placental location as a predictor of an adverse pregnancy outcome.

OBJECTIVE: To determine if the second trimester placental location is associated with perinatal outcomes. MATERIALS AND METHODS: Observational study of placental location and the subsequent risk of an adverse pregnancy outcome. Placental location was divided into three categories, low, high lateral and high fundal. RESULTS: There were 3336 pregnancies analyzed in this study. Low implantation sites had a greater risk of preterm labor (odds ratio (OR) 1.70, 95% confidence interval (CI) 1.38 to 2.90, P<0.001), preterm delivery (OR 1.86, 95% CI 1.36 to 2.54, P<0.001), fewer fetuses with macrosomia (OR 0.56, 95% CI 0.38 to 0.83, P=0.010) and reduced risk of postpartum hemorrhage (OR 0.56, 95% CI 0.46 to 0.95, P=0.026). High lateral implantations had a greater risk of low 1-min (OR 1.80, 95% CI 1.11 to 2.93, P=0.017) and 5-min (OR 3.49, 95% CI 1.46 to 8.36, P=0.005) Apgar scores. CONCLUSIONS: Low placental implantation was associated with an increased risk of preterm labor, preterm delivery and a reduced risk of postpartum hemorrhage, and of a macrosomic fetus. High lateral implantation was associated with low Apgar scores.

Adolescent↗

The role of formative courses in the professional integration of patients with epilepsy. An Italian experience.

The aim of the present paper was to describe some formative projects on work integration of patients with epilepsy and mild cognitive deficits, so that similar initiatives may be promoted. The different phases of the formative projects were described: the inclusion criteria, the selection of participants, the assessment instruments, the courses themselves and the final results in terms of working experience. Thirteen participants were selected for each course. Patients were treated in different Lombardy Epilepsy departments, which addressed them to the Epilepsy Center, S. Paolo Hospital, Milan, where the selection took place. Seventy percent of the participants in the formative courses found a job in 1 year, even though most of the positions were temporary. The work integration seemed to be mainly related to the level of intelligence and to verbal memory. We stress the importance of organising similar courses in the future, in the context of wider networks. This will help more patients in acquiring both economic and psychological autonomy from their families.

Adult↗

Italian neuropsychological instruments to assess memory, attention and frontal functions for developmental age.

In this study, a series of tests exploring long-term verbal memory (the Short Story Test), attention (a modified version of Attentional Matrices and the Trail Making Test) and frontal functions (a modified version of the Frontal Assessment Battery) have been standardised on an Italian population of 283 children aged 5-14. Raw scores for each test have been adjusted for a series of variables (child's age, years of parents' education, handedness, gender) and transformed in equivalent scores enabling direct comparison across measures. This study was promoted by LICE (the Italian League Against Epilepsy) in order to provide Italian instruments standardised on the developmental age population and to study some of the most frequently impaired cognitive functions in epilepsy.

Adolescent↗

From psychiatric ward to the streets and shelters.

The issue of discharge from hospital ward to the streets is seldom explored in the literature, but all too commonly experienced by individuals experiencing psychiatric disorders. The Community University Research Alliance on Housing and Mental Health sought to determine how frequently people were discharged from psychiatric wards to shelters or the street in London, Ontario, Canada. A number of data sources were accessed to determine instances of discharges to shelters or the street. Data were analysed to determine the number of moves occurring between hospital and shelter or no fixed address. All datasets revealed the problem of discharge to shelters or the street occurred regularly. All data sources used have the difficulty of likely underestimating the extent of the problem. This type of discharge occurred at least 194 times in 2002 in London, Ontario, Canada. Policies that contribute to this problem include income-support policies, the reduction in psychiatric hospital beds and the lack of community supports. Without recognition, this problem is at risk of remaining invisible with no further improvements to the situation.

Adult↗

Audit on the management of epididymo-orchitis by the Department of Urology in Edinburgh.

Epididymo-orchitis among men younger than 35 years is mainly caused by chlamydial infection. National guidelines for the management of this condition have been published. The aim of this study was to audit the management of epididymo-orchitis in a major teaching hospital. To this end we performed a retrospective study of patients with epididymo-orchitis admitted to the Department of Urology in the Western General Hospital, Edinburgh between 1998 and 2003. Case-notes of 108 cases of epididymo-orchitis were reviewed. The diagnosis was established by ultrasound in 94% of cases. Patients were not tested routinely for chlamydial infection and the majority of men younger than 35 years were treated inappropriately with ciprofloxacin. The management of patients younger than 35 years was not in accordance with the recommendations of national guidelines. Chlamydia trachomatis is sexually transmissible and is not responsive to ciprofloxacin. As a result of this audit, each patient will be tested for chlamydial infection and men younger than 35 years will be treated with ofloxacin. Sexual partners of patients with chlamydial infection will be treated in the department of genitourinary medicine.

Adult↗

Reflex writing seizures in two siblings with juvenile myoclonic epilepsy.

We report on two siblings who presented with juvenile myoclonic epilepsy, and in whom myoclonic jerks of the right arm and hand were also triggered by writing tasks. Both patients underwent intensive video-electroencephalography monitoring, with simultaneous neuropsychological tests. In both patients, reflex epileptic myoclonus was more easily triggered by writing that required a higher degree of concentration. Conversely, other cognitive tasks, such as reading, typing, thinking, or calculation never elicited any seizures or myoclonus. Valproate was effective in controlling both spontaneous and reflex epileptic seizures. The results of this study further support the notion that 'praxis-induced' reflex epilepsy precipitated by specific stimuli occurs in the context of idiopathic generalized epilepsy. Our results also illustrate that writing tasks are more effective in eliciting seizures when they require higher levels of concentration and mental elaboration.

Adolescent↗

The Humber catchment and its coastal area: from UK to European perspectives.

The present water quality of the Humber rivers and coastal zone depends on a complex interplay of factors, including physical ones, such as the underlying geology, which influences soil type, climatic ones, such as the rainfall, which influences runoff, socio-economic ones, which influence present-day human activities in the catchment, and the legacy of former activities, such as contaminated sediments from mining. All of these factors affect the fluxes of nutrients and other contaminants to the rivers and coastal zone. The Water Framework Directive (WFD) requires the production of a river basin management plan intended to lead to the achievement of good chemical and ecological status for all water bodies in the catchment over the next two decades. This paper provides an overview of the current environmental and socio-economic state of the Humber catchment and coastal zone, and broadly examines how socio-economic drivers affect the fluxes of nutrients and contaminants to the coastal zone, using the driver-pressure-state-impact-response (DPSIR) approach. This is followed by an overview of future research, describing the use of scenarios to simulate future fluxes and provide a consistent framework to evaluate potential policies to improve water quality in the estuary. The Humber catchment is one of eight case studies within a European research project, EUROCAT (EVK1-CT-2000-00044), which aims to achieve integrated catchment and coastal zone management by analysing the response of the coastal sea to changes in fluxes of nutrients and contaminants from the catchments. For the Humber case study, the research focuses on the fluxes of two nutrient elements, N and P, and four metal contaminants, As, Cu, Pb and Zn. The project requires the integration of scientific and socio-economic approaches, bringing together quantitative environmental data garnered for individual river catchments and coastal zones in previous research programmes, and local and regional socio-economic data, to aid decision-makers in their search for integrated and sustainable coastal zone management strategies.

Animals↗

Structural characterization of a 2'F-RNA aptamer that binds a HIV-1 SU glycoprotein, gp120.

Here we describe the isolation of specific 2'F-substituted RNA ligands for the SU glycoprotein, gp120, of HIV-1 strain HXB2. These aptamers bind the target protein with an affinity of the order of 10(-7) M. Binding was specific to SU glycoprotein and directed to a non-neutralizing epitope that was not shared with the related strain, HIV-1(BaL). The structure of one aptamer was defined by a combination of deletion analysis and enzymatic probing studies, revealing a 42 nt minimal element comprising a three-helix junction that retained the binding affinity of the parental sequence. Interestingly, binding to SU glycoprotein was accompanied by structural changes in the aptamer that stabilized the weakest of the 3 helices.

Animals↗

A critical review of vascular endothelial growth factor (VEGF) analysis in peripheral blood: is the current literature meaningful?

Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor with a key role in many physiological and pathological processes. Investigation into the implications of circulating levels of this cytokine is progressing at an exponential rate. However, there are important inconsistencies between reports ranging from method of sample collection, processing, software manipulation and data interpretation and controversy as to whether plasma, serum or whole blood will provide the best prognostic information. Different techniques of centrifugation and temperature on sample handling and the impact of in vitro collection of blood on subsequent VEGF results have not been fully appreciated. We provide a critical review of the literature, report the results of our further investigations, suggest a uniform protocol for handling blood samples and highlight previously unsuspected problems in data interpretation.

Blood Specimen Collection↗

Vascular endothelial growth factor-B and vascular endothelial growth factor-C expression in renal cell carcinomas: regulation by the von Hippel-Lindau gene and hypoxia.

Angiogenesis is essential for tumor growth and metastasis. It is regulated by numerous angiogenic factors, one of the most important being vascular endothelial growth factor (VEGF). Recently VEGF-B and VEGF-C, two new VEGF family members, have been identified that bind to the tyrosine kinase receptors flt-1 (VEGFR1), KDR (VEGFR2), and flt-4 (VEGFR3). Although the importance of VEGF-A has been shown in renal carcinomas, the contribution of these new ligands in kidney tumors is not clear. We have, therefore, measured the mRNA level of VEGF-B and VEGF-C together with their receptors by RNase protection assay (RPA) in 26 normal kidney samples and 45 renal cell cancers. We observed a significant up-regulation of VEGF-B (P = 0.002) but not VEGF-C (P = 0.3) in neoplastic kidney compared with normal tissues. In addition, although VEGF receptors were higher in tumors than normal kidney, there was a significant up-regulation of only flt-1 (P = 0.003) but not KDR (P = 0.12) or flt-4 (P = 0.09). There was also a significant correlation between VEGF-C and both of its receptors flt-4 (P = 0.006) and KDR (P = 0.03) but no association between VEGF-B and its receptor flt-1 (P = 0.23). A significant increase was observed in flt-1 (P < 0.001), KDR (P = 0.02), and flt-4 (P = 0.01) but not VEGF-B (P = 0.82) or VEGF-C (P = 0.52) expression in clear cell compared with chromophil (papillary) carcinomas. No significant association was demonstrated between VEGF-B, VEGF-C, flt-1, KDR, and flt-4 with patient sex, patient age, or tumor size (P > 0.05). The effect of von Hippel-Lindau (VHL) gene and hypoxia on VEGF-B and VEGF-C expression in the renal carcinoma cell line 786-0 transfected with wild-type and mutant VHL was determined by growing cells under 21% O2- and 0.1% O2. In wild-type VHL cells, whereas VEGF-A was significantly up-regulated under hypoxic compared with normoxic conditions (P < 0.001), expression of VEGF-C was reduced (P < 0.002). Nevertheless, the repression of VEGF-C was lost in mutant VHL cell lines under hypoxia. In contrast VEGF-B was not regulated by VHL despite clear up-regulation in vivo. These findings strongly support an enhanced role for this pathway in clear cell carcinomas by regulating angiogenesis and/or lymphangiogenesis. The study shows that clear cell tumors are able to up-regulate angiogenic growth factor receptors more efficiently than chromophil (papillary), that clear cell tumors can use pathways independent of VHL to regulate angiogenesis, and that this combined regulation may account for their more aggressive phenotype, which suggests that targeting VEGFR1 (flt-l) may be particularly effective in these tumor types.

Adenocarcinoma, Clear Cell↗

Biosensor based on enzyme-catalysed degradation of thin polymer films.

A biosensor based on the enzyme-catalysed dissolution of biodegradable polymer films has been developed. Three polymer-enzyme systems were investigated for use in the sensor: a poly(ester amide), which is degraded by the proteolytic enzyme alpha-chymotrypsin; a dextran hydrogel, which is degraded by dextranase; and poly(trimethylene) succinate, which is degraded by a lipase. Dissolution of the polymer films was monitored by Surface Plasmon Resonance (SPR). The rate of degradation was directly related to enzyme concentration for each polymer/enzyme couple. The poly(ester amide)/alpha-chymotrypsin couple proved to be the most sensitive over a concentration range from 4 x 10(-11) to 4 x 10(-7) mol l(-1) of enzyme. The rate of degradation was shown to be independent of the thickness of the poly(ester amide) films. The dextran hydrogel/dextranase couple was less sensitive than the poly(ester amide)/alpha-chymotrypsin couple but showed greater degradation rates at low enzyme concentrations. Enzyme concentrations as low as 2 x 10(-11) mol l(-1) were detected in less than 20 min. Potential fields of application of such a sensor system are the detection of enzyme concentrations and the construction of disposable enzyme based immunosensors, which employ the polymer-degrading enzyme as an enzyme label.

Biodegradation, Environmental↗

Late-onset depression: genetic, vascular and clinical contributions.

BACKGROUND: Neuropsychiatric research needs to examine the relationships between aetiological, genotypic and clinical risk factors and behavioural phenotypes. These relationships can now be examined in older patients with depressive disorders. METHODS: Key behavioural features, clinical and vascular risk factors and putative genotypes for late-onset neurodegenerative disorders and/or vascular disease were recorded in 78 older patients with depression (mean age = 549 years, S.D. = 14.1) and 22 healthy control subjects (mean age = 55.5 years, S.D. = 9.6). RESULTS: Two or more vascular risks were more common in older patients (65% v. 26% of control subjects, P < 0.01), and in patients with late-onset disorders (82% v. 57% in patients with early-onset disorders, P < 0.05). Patients with late-onset depression had a higher prevalence of the homozygous or heterozygous forms of the C677T mutation of the methylenetetrahydrofolate reductase enzyme (MTHFR)(74% v. 48% in patients with early-onset disorders, P < 0.05). In a multivariate model, only presence of the MTHFR gene mutation predicted late-onset depression (odds ratio = 3.8, 95% CI = 1.1-12.9). Neither apolipoprotein E epsilon 4 or epsilon 2 was associated with depression, late-onset depression, cognitive impairment, or psychomotor change. Patients with apolipoprotein E epsilon 4 were less likely to have psychotic forms of depression. CONCLUSIONS: Patients with late-onset depression had an increased rate of the C677T MTHFR gene mutation and other vascular risk factors. This suggests that a proportion of these patients may have genetically-determined and/or other vascular aetiologies. Patients at risk of these disorders may be assisted by currently-available preventative strategies.

Adult↗

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↗

Intravenous apomorphine therapy in Parkinson's disease: clinical and pharmacokinetic observations.

Six patients with Parkinson's disease and refractory motor fluctuations, with severe subcutaneous (s.c.) nodule formation as a result of long-term s.c. apomorphine infusions, were switched to intravenous (i.v.) therapy via a long-term in-dwelling venous catheter. Five patients were followed-up for a mean of 7 months (range 0.5-18 months). All patients had plasma apomorphine concentrations measured at baseline during s.c. infusions and three had follow-up measurements when stabilized on i.v. therapy, to test the hypothesis that motor fluctuations in these patients are largely due to impaired absorption of apomorphine. The mean i.v. rate of 9.0 mg/h (range 5-14 mg) and 24-h dose of 256.7 mg (range 90-456 mg) of apomorphine were not significantly reduced compared with the s.c. route (9.24 mg/h and 243.4 mg). However, additional oral anti-parkinsonian medication was reduced by a mean of 59%, and 'off' time was virtually eliminated (mean reduction from 5.4 to 0.5 h per day, P< 0.05). There was also a significant reduction in dyskinesias and markedly improved quality of life. Pharmacokinetic analysis demonstrated more reliable and smoother delivery of apomorphine via the i.v. route, although 'off' periods were not always explained by low plasma apomorphine concentrations. Complication rates were high and included three unforeseen hazardous intravascular thrombotic complications, secondary to apomorphine crystal accumulation, necessitating cardiothoracic surgery. We conclude that i.v. apomorphine therapy holds promise as a more effective way of controlling motor fluctuations than the s.c. route. However, further preclinical research is required before i.v. Britaject apomorphine can be recommended for routine clinical practice. Even when stable plasma apomorphine concentrations were achieved, motor fluctuations could not be totally eradicated, suggesting that postsynaptic receptor changes may also play a role in the refractory 'off' periods in these patients.

Aged↗