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Biomedical subjects

J Marshall

Publications and source records attributed to J Marshall.

At least 19 recordsLinked to original sources
PubMed2006

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↗
PubMed2006

Alcohol intake and ovarian cancer risk: a pooled analysis of 10 cohort studies.

Alcohol has been hypothesized to promote ovarian carcinogenesis by its potential to increase circulating levels of estrogen and other hormones; through its oxidation byproduct, acetaldehyde, which may act as a cocarcinogen; and by depletion of folate and other nutrients. Case-control and cohort studies have reported conflicting results relating alcohol intake to ovarian cancer risk. We conducted a pooled analysis of the primary data from ten prospective cohort studies. The analysis included 529 638 women among whom 2001 incident epithelial ovarian cases were documented. After study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then were pooled using a random effects model; no associations were observed for intakes of total alcohol (pooled multivariate RR=1.12, 95% CI 0.86-1.44 comparing > or =30 to 0 g day(-1) of alcohol) or alcohol from wine, beer or spirits and ovarian cancer risk. The association with alcohol consumption was not modified by oral contraceptive use, hormone replacement therapy, parity, menopausal status, folate intake, body mass index, or smoking. Associations for endometrioid, mucinous, and serous ovarian cancer were similar to the overall findings. This pooled analysis does not support an association between moderate alcohol intake and ovarian cancer risk.

Adult↗
PubMed2006

Predictors of success and failure in pulmonary rehabilitation.

The purpose of the present study was to identify prognostic features of chronic obstructive pulmonary disease (COPD) associated with success or failure in pulmonary rehabilitation. Patients were stratified according to the Medical Research Council (MRC) dyspnoea score. A total of 74 stable COPD patients (mean+/-sd age 68+/-10 yrs), 21 MRC dyspnoea score grade 1/2, 29 grade 3/4 and 24 grade 5, with a mean forced expiratory volume in one second of 1.1+/-0.6 L, attended for rehabilitation. Assessments consisted of the following: quadriceps torque, 6-minute walking distance (6MWD), Brief Assessment Depression Cards and St George's Respiratory Questionnaire (SGRQ). Predictors of drop-out and of response (a change in SGRQ of four points or 6MWD of 54 m) were tested using binary logistic regression. In total, 51 patients completed the study. Of these, 39 (77%) showed a clinically significant benefit in either 6MWD or SGRQ. Baseline variables were poor predictors of response in each case. Significant differences were seen between MRC dyspnoea score groups for change in 6MWD and SGRQ Score. Only grade 1/2 and 3/4 patients improved. Depression was a risk factor for subject drop-out compared with nondepressed patients. Baseline state is a poor predictor of response to rehabilitation, although Medical Research Council dyspnoea score grade 5 patients showed smaller magnitudes of improvement than patients with less severe Medical Research Council dyspnoea score grades. Risk of drop-out is significantly greater in depressed compared with nondepressed patients.

Aged↗
PubMed2006

Influence of colostrum deprivation and concurrent Cryptosporidium parvum infection on the colonization and persistence of Escherichia coli O157 : H7 in young lambs.

Escherichia coli O157 : H7 and Cryptosporidium parvum infections of man have been associated with direct contact with small ruminants. Colostrum protects neonates against gastrointestinal pathogens, and orphan lambs, which are common on petting farms, may be deprived of this protection. In a recent study, it was demonstrated that high shedding of E. coli O157 : H7 by an 8-week-old goat kid was associated with coincidental C. parvum infection. Furthermore, both pathogens were co-located in the distal gastrointestinal tract. It was hypothesized that colostrum deprivation and pre-infection with C. parvum predisposed young ruminants to colonization and increased shedding of E. coli O157 : H7. To test this, 21 lambs 5 weeks of age were divided into four groups as follows: (A) colostrum-deprived and inoculated with E. coli O157 : H7, (B) colostrum-deprived and inoculated with C. parvum and then E. coli O157 : H7, (C) conventionally reared and inoculated with E. coli O157 : H7, (D) conventionally reared and inoculated with C. parvum and then E. coli O157 : H7. C. parvum was detected between 8 and 12 days post-inoculation in most of the infected lambs. At 24 h post-inoculation with E. coli O157 : H7, all lambs were shedding between 5 x 10(4) and 5 x 10(7) c.f.u. E. coli O157 : H7 per gram of faeces. E. coli O157 : H7 was shed in higher numbers in the groups pre-inoculated with C. parvum, whether conventionally reared or colostrum-deprived. Interestingly, for the colostrum-deprived lambs on day 3, a significant difference in shedding of E. coli O157 : H7 was observed (P = 0.038), with the lambs inoculated with E. coli alone yielding higher counts than those pre-inoculated with C. parvum. From day 15 onwards, shedding of E. coli O157 : H7 was highest from the colostrum-deprived C. parvum-infected lambs, then (in descending order of shedding) the colostrum-deprived lambs, the conventionally reared lambs infected with C. parvum, and the conventionally reared animals. In total, four animals were euthanized, two at 24 h and two at 96 h post inoculation with E. coli O157 : H7 (two conventionally reared and two colostrum-deprived). All animals euthanized were from groups pre-inoculated with C. parvum prior to challenge with E. coli O157 : H7. On examination of tissues, in three of the four animals examined, multifocal attaching and effacing lesions were observed in the caecum, colon, rectum and at the recto-anal junction, and were confirmed by immunohistochemistry to be associated with E. coli O157 : H7.

Animals↗
PubMed2006

An experimental study of the elastic properties of the human Bruch's membrane-choroid complex: relevance to ageing.

AIM: To investigate the mechanical properties (stress-strain relation, elasticity, hysteresis, response to stress spikes and drops) of isolated human Bruch's membrane-choroid, as well as the effect of ageing and aged related macular degeneration (AMD). METHODS: 13 Bruch's membrane-choroid complexes were obtained from human donors (21-97 years). Two samples (aged 85 and 95) showed signs of AMD including large, soft drusen, choroidal neovascularisation, and/or disciform scars. Various hydrostatic pressures (stress) were applied to the choroidal surface of mid-peripheral samples mounted in a modified open Ussing chamber. Linear scans of the tissue were recorded by optical coherence tomography (OCT) and the pressure induced deformation (strain), elasticity, hysteresis, and response to pressure spikes and drops measured. RESULTS: The elasticity of human Bruch's membrane-choroid complex decreased linearly with ageing (p<0.001) after the age of 21 with an approximate reduction of 1% per year. The decrease was not exaggerated in AMD. The recoil capacity of Bruch's membrane-choroid was not affected by ageing. The response to pressure spikes/drops was similar in age matched normal and AMD eyes. The results suggest that although the aged induced decrease in Bruch's membrane elasticity may contribute to breaks in this membrane in AMD leading to neovascularisation this is not sufficient. The presence of other factors is required for its development. CONCLUSION: The elasticity of Bruch's membrane-choroid complex decreases with age while recoil capacity does not. The decrease was not exaggerated in AMD.

Adult↗
PubMed2006

CpG-C ISS-ODN activation of blood-derived B cells from healthy and chronic immunodeficiency virus-infected macaques.

Cytosine-phosphate-guanine class C (CpG-C) immunostimulatory sequence oligodeoxynucleotides (ISS-ODNs) activate human B cells and dendritic cells (DCs), properties that suggest potential use as a novel adjuvant to enhance vaccine efficacy. After demonstrating that the CpG-C ISS-ODN C274 activates macaque DCs, we examined in vitro activation of macaque B cells by C274 as a prelude to evaluation of this molecule as an adjuvant in the testing of candidate human immunodeficiency virus vaccines in the rhesus macaque-simian immunodeficiency virus (SIV) model. C274 induced macaque CD20(+) B cells to proliferate more strongly than CD40 ligand or CpG-B ISS-ODN. C274 enhanced B cell survival; increased viability was most evident after 3-7 days of culture. Increased expression of CD40, CD80, and CD86 by B cells was apparent within 24 h of exposure to C274 and persisted for up to 1 week. C274-stimulated, B cell-enriched and peripheral blood mononuclear cell suspensions from naïve and immunodeficiency virus-infected monkeys secreted several cytokines [e.g., interleukin (IL)-3, IL-6, IL-12, interferon-alpha] and chemokines [e.g., monocyte chemoattractant protein-1/CC chemokine ligand 2 (CCL2), macrophage-inflammatory protein-1alpha/CCL3, IL-8/CXC chemokine ligand 8]. In comparison, exposure of macaque B cells to SIV had minimal impact on surface phenotype, despite inducing cytokine and chemokine production in cells from infected and uninfected animals. These observations emphasize the need to identify strategies to optimally boost immune function, as immunodeficiency viruses themselves only partially activate B cells and DCs. The ability of C274 to stimulate B cells and DCs in healthy and infected monkeys suggests its possible use as a broad-acting adjuvant to be applied in the rhesus macaque model for the development of preventative and therapeutic vaccines.

AIDS Vaccines↗
PubMed2005

Sgbeta1, a novel locust (Schistocerca gregaria) non-alpha nicotinic acetylcholine receptor-like subunit with homology to the Drosophila melanogaster Dbeta1 subunit.

The cloning, sequencing and functional expression of Sgbeta1, a novel locust (Schistocerca gregaria) non-alpha nicotinic acetylcholine receptor (nAChR) subunit is described. This subunit shows 80% identity with the Drosophila melanogaster Dbeta1 and 92% identity with the Locusta migratoria beta1, non-alpha subunits but only 38% identity to Sgalpha1 (also referred to as alphaL1), a previously cloned S. gregaria nAChR alpha-subunit. When expressed in Xenopus laevis oocytes, Sgbeta1 does not respond to nicotine. Responses to nicotine are observed, however, in oocytes co-expressing Sgalpha1 and Sgbeta1, but the pharmacology is indistinguishable from that of currents produced by expressing Sgalpha1 alone. We conclude that either Sgbeta1 does not co-assemble with Sgalpha1, or that it is unable to contribute to the functional properties of the receptor, in the Xenopus oocyte expression system.

Amino Acid Sequence↗
PubMed2005

Topical fusidic acid/betamethasone-containing gel compared to systemic therapy in the treatment of canine acute moist dermatitis.

The efficacy of a topical preparation containing 0.5% fusidic acid and 0.1% betamethasone-17-valerate was compared to a systemic therapy (comprising a combination of parenteral dexamethasone and oral clavulanate-potentiated amoxycillin) in the treatment of 104 dogs with acute moist dermatitis. Significant improvement was evident after seven days in both treatment groups in all clinical parameters assessed and there was no significant difference in the overall response between the two treatment groups. Staphylococcus intermedius was the most frequently isolated organism from swabs at the first visit (Day 0). No resistance to fusidic acid or clavulanate-potentiated amoxycillin was encountered. The study demonstrates no difference in the clinical improvement achieved in canine acute moist dermatitis following topical or systemic therapy and that both treatment regimes represent effective treatment options for the condition.

Administration, Cutaneous↗
PubMed2005

A randomised, prospective study comparing selective laser trabeculoplasty with latanoprost for the control of intraocular pressure in ocular hypertension and open angle glaucoma.

AIM: To compare 90 degrees , 180 degrees , and 360 degrees selective laser trabeculoplasty (SLT, 532 nm Nd:YAG laser) with latanoprost 0.005% for the control of intraocular pressure (IOP) in ocular hypertension (OHT) and open angle glaucoma (OAG). METHODS: A prospective, randomised clinical trial in the Department of Ophthalmology, St Thomas's Hospital, London, and Clayton Eye Centre, Wakefield, West Yorkshire. 167 patients (167 eyes) with either OHT or OAG were randomised to receive 90 degrees , 180 degrees , and 360 degrees SLT or latanoprost 0.005% at night and were evaluated at 1 hour, 1 day, 1 week and 1, 3, 6, and 12 months. RESULTS: The mean follow up was 10.3 months (range 1--12 months). Early, transient, complications such as postoperative ocular pain, uveitis, and 1 hour IOP spike occurred in a number of eyes after SLT, with pain being reported more frequently after 360 degrees than 90 degrees treatments (p>0.001). Success rates defined in terms of both a 20% or more and a 30% or more IOP reduction from baseline measurements with no additional antiglaucomatous interventions were better with latanoprost than 90 degrees (p<0.001) and 180 degrees SLT (p<0.02) treatments. Differences in success rates between latanoprost and 360 degrees SLT did not reach statistical significance (p<0.5). Success rates were greater with 180 degrees and 360 degrees compared to 90 degrees SLT (p<0.05). With 360 degrees SLT, 82% of eyes achieved a >20% IOP reduction and 59% a >30% reduction from baseline. Although success rates were better with 360 degrees than 180 degrees SLT treatments, differences did not reach statistical significance. There were no differences with regard to age, sex, race, pretreatment IOP, OHT versus OAG, laser power settings, and total laser energy delivered between eyes which responded, in terms of a >20% and a >30% IOP reduction, and those that did not respond with 180 degrees and 360 degrees SLT treatments. CONCLUSIONS: Success rates were higher with latanoprost 0.005% at night than with 90 degrees and 180 degrees SLT treatments. 90 degrees SLT is generally not effective. 360 degrees SLT appears to be an effective treatment with approximately 60% of eyes achieving an IOP reduction of 30% or more. Transient anterior uveitis with associated ocular discomfort is not unusual in the first few days after SLT. Late complications causing ocular morbidity after SLT were not encountered.

Adult↗
PubMed2005

Improving hospital doctors' working lives: online questionnaire survey of all grades.

BACKGROUND: In 2001, the Department of Health produced the Improving Working Lives (IWL) for Doctors document. This is the first national survey which asks hospital doctors what changes are needed to improve their working lives. METHODS: An online questionnaire was run over a period of six weeks and was open to all doctors of all grades. Doctors were asked to choose their top five factors from a list of 35 diverse choices or to provide alternatives in free text. Demographic data were also collected. RESULTS: 1603 hospital doctors working in the UK completed the online questionnaire. Improved secretarial or managerial support was the first IWL choice for consultants, with different aspects of clinical and non-clinical support representing their top four choices. Junior hospital doctors and staff and associate specialist grades (staff grades, associate specialists, and clinical assistants) identified improved support for education and training as their first choice, while among the female specialist registrars, it was improved support for childcare. Greater opportunities to develop new skills was an important issue for doctors in the surgical specialties and improved access to mentoring was important for all junior doctors, staff and associate specialist grades, and doctors from black and ethnic minority groups. CONCLUSIONS: Hospital doctors in the UK need more support to improve their working lives. The principle needs are better secretarial and managerial support for consultants; education, training, and mentoring for junior doctors and staff and associate specialist grades; and improved opportunities to develop new skills for those in surgical specialties. Support with childcare is an important issue for female specialist registrars. The Department of Health, NHS trusts, deaneries, and Royal Colleges need to endorse policies that promote a training and working environment that will improve working lives for all hospital doctors, ensuring that appropriate and continuing support is available from the time doctors enter the new foundation programmes and proposed run-through grades, to their time spent as consultants in today's NHS.

Attitude of Health Personnel↗
PubMed2004

Speech and language therapy to improve the communication skills of children with cerebral palsy.

BACKGROUND: The production of speech, language and gesture for communication is often affected by cerebral palsy. Communication difficulties associated with cerebral palsy can be multifactorial, arising from motor, intellectual and / or sensory impairments, and children with this diagnosis can experience mild to severe difficulties in expressing themselves. They are often referred to speech and language therapy (SLT) services, to maximise their communication skills and help them to take an independent a role as possible in interaction. This can include introducing augmentative and alternative communication (AAC) systems, such as symbol charts or speech synthesizers, as well treating children's natural forms of communication. Various strategies have been used to treat the communication disorders associated with cerebral palsy but evidence of their effectiveness is limited. OBJECTIVES: To determine the effectiveness of SLT that focuses on the child or their familiar communication partners, as measured by change in interaction patterns. To determine if individual types of SLT intervention are more effective than others in changing interaction patterns. SEARCH STRATEGY: Searches were conducted of MEDLINE, CINAHL, EMBASE, PSYCH INFO, LLBA, ERIC, WEB of SCIENCE, NRR, BEI, SIGLE up to December 2002. References from identified studies were examined and relevant journals and conference reports were hand-searched. SELECTION CRITERIA: Any experimental study containing an element of control was included in this review. This includes non-randomised group studies and single case experimental designs in which two interventions were compared or two communication processes were examined. DATA COLLECTION AND ANALYSIS: L Pennington searched for and selected studies for inclusion. J Goldbart and J Marshall independently assessed separate random samples each comprising 25% of all identified studies. Two reviewers independently abstracted data from each selected study. Disagreements were settled by discussion between the three reviewers. MAIN RESULTS: Eleven studies were included in the review. Seven studies evaluated treatment given directly to children, four investigated the effects of training for communication partners. Subjects in the studies varied widely in age, type and severity of cerebral palsy, cognitive and linguistic skills. Studies focusing directly on children suggest that this model of therapy delivery has been associated with increases in treated communication skills by individual children. However, methodological flaws prevent firm conclusions being made about the effectiveness of therapy. In addition, maintenance of these skills was not investigated thoroughly. The studies targeting communication partners describe small exploratory group projects which contain insufficient detail to allow replication, have very low power and cannot provide evidence of effectiveness of this type of treatment. REVIEWERS' CONCLUSIONS: Firm evidence of the positive effects of SLT for children with cerebral palsy has not been demonstrated by this review. However, positive trends in communication change were shown. No change in practice is recommended from this review. Further research is needed to describe this client group, and its possible clinical subgroups, and the methods of treatment currently used in SLT. Research is also needed to investigate the effectiveness of new and established interventions and their acceptability to families. Rigour in research practice needs to be extended to enable firm associations between therapy and communication change to be made.

Adolescent↗
PubMed2004

Strategies for consulting with the community: the cases of four large-scale genetic databases.

Large-scale genetic databases are being developed in several countries around the world. However, these databases depend on public participation and acquiescence. In the past, information campaigns have been waged and little attention has been paid to dialogue. Nowadays, it is important to include the public in the development of scientific research and to encourage a free, open and useful dialogue among those involved. This paper is a review of community consultation strategies as part of four proposed large-scale genetic databases in Iceland, Estonia, United Kingdom and Quebec. The Iceland Health Sector Database and Estonian Genome Project have followed a "communication approach" in order to address public concerns, whereas, UK Biobank and Quebec CARTaGENE have chosen a "partnership approach" to involve the public in decision-making processes. Following a comparison of community consultation strategies, the main concerns of the public are examined as well as the challenges of involving communities. Importantly, reported across all groups is the concern for confidentiality, respect of the individual, transparency, and the donor's right to access to their own result. However, even if researchers demonstrate a willingness to respect values such as fair representation, transparency and accountability, there is still a risk that the public will mistrust researchers and simply will not participate in sufficient numbers. Complications may arise when individual and community interests conflicts. The implementation of a partnership approach is definitely involving and costly; however, if used properly, this method can improve both participation and so database development.

Community Participation↗
PubMed2004

Do blue light filters confer protection against age-related macular degeneration?

Age-related macular degeneration (AMD) is a major health problem in the developed world accounting for approximately half of all blind registrations. Current treatment options are unsuitable for the majority of patients and therefore the identification of modifiable risk factors that may inform disease prevention programmes is a priority. This review evaluates the long-held belief that blue light exposure has a role in the pathogenesis of AMD. Laboratory evidence has demonstrated that photochemical reactions in the oxygen-rich environment of the outer retina lead to the liberation of cytotoxic reactive oxygen species (ROS). These ROS cause oxidative stress which is known to contribute to the development of AMD. The precise chromopore that may be involved in the pathogenesis of AMD is unclear but the age pigment lipofuscin is a likely candidate. Its aerobic photoreactivity and adverse effects on antioxidant activity combined with its gradual accumulation over time suggests that its in vivo phototoxicity increases with age despite changes in the absorption characteristics of the crystalline lens. Evidence from animal studies confirms blue light's damaging potential but the results are not directly applicable to macular degeneration in humans. Studies of human macular pigment density and the risk of AMD progression following cataract surgery lend further weight to the hypothesis that blue light exposure has a role in the pathogenesis of AMD but the epidemiological evidence is equivocal. On balance the evidences suggests but does not yet confirm that blue light is a risk factor for AMD. Given the socio-economic impact of this disease and urgent need to identify modifiable risk factors, future work should include a large-scale clinical trial to evaluate the effect of blue blocking filters on AMD progression rates.

Animals↗
PubMed2004

Chronic physical exercise reduces anxiety-like behavior in rats.

While many individuals with anxiety disorders receive drug therapy, many do not respond or adversely respond to drugs. An alternative treatment, exercise, has been shown to relieve negative feelings and induce positive shifts in mood. The purpose of this study was to establish an animal model to specifically test the effects of chronic physical exercise on anxiety-related behaviors. Thirty-two male Sprague Dawley rats were divided into two groups: runners (R) and nonrunners (NR). Runners ran on a treadmill for 45 minutes a day, five days a week, for ten weeks at a moderate intensity. Nonrunners remained in their cages in the treadmill room during the running period and were handled for an equal amount of time. After ten weeks of training, two behavioral tests were administered including the elevated plus maze and open field tests. Results comparing R and NR showed higher responses by R in percent open arm time and center square time during the elevated plus maze test, as well as in number of entries into the center, number of rears, and lower fecal boli count during the open field test, p < 0.05. In addition, there were no differences in total activity levels between groups as indicated by similar closed arm entries in the elevated plus maze test and total lines crossed in the open field test. These results indicate that treadmill training reduces anxiety-like behaviors in two animal tests of anxiety, without a significant change in total activity levels. These data are in support of treadmill training as a model to test the anxiolytic effects of exercise.

Animals↗
PubMed2004

The relationship between a urinary cachectic factor and weight loss in advanced cancer patients.

A 24K glycoprotein, the proteolysis-inducing factor (PIF), has been identified in mice and humans with cancer cachexia. Clinical cross-sectional studies found an association between the presence of PIF in urine and tumors of patients and weight loss. For the first time, we report results from a longitudinal study establishing the relationship between a urinary PIF pattern and persistent weight loss. Over time, cancer patients positive for the PIF pattern experienced weight loss, whereas those with a negative test gained weight.

Adult↗