Mental health. Eye off the ball?
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Biomedical subjects
Publications and source records attributed to D Richards.
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A polymorphism in the Myeloperoxidase gene (MPO) has previously been demonstrated to be associated with gender-specific risk in an Alzheimer's Disease (AD) autopsy sample. We have investigated this polymorphism in our own samples of 226 Caucasian cases and 166 controls and 59 Hispanic cases and 75 controls. In Caucasians we find a significant association between MPO genotype and AD (P = 0.03), although we do not observe any effects of gender or any interaction with the APOE gene. Specifically, the MPO GG genotype contributes a 1.57-fold increased risk for AD. In Hispanics there was no effect of MPO genotype, or of MPO genotype in interaction with age or gender, on diagnosis of AD.
The enhancement in electric field strength in the vicinity of a metal tip, through the excitation of plasma modes in the tip, is investigated using the finite difference time domain method; such tip enhancement has significant potential for application in scanning near-field Raman microscopy. To represent an experimentally realistic geometry the near-field probe is described by a conical metal tip with a spherical apex, with radii 20 nm and 200 nm considered, in close proximity to a glass substrate. Illumination through the substrate is considered, both at normal incidence and close to the critical angle, with the polarization in the plane of incidence. By modelling the frequency dependent dielectric response of the metal tip we are able to highlight the dependence on the scattering geometry of the nature of the electromagnetic excitations in the tip. In particular, the strongest electric field enhancement with the greatest confinement occurs for the excitation of modes localized at the tip apex, excited only for off-normal incidence. Bulk modes excited in the tip also produce enhancement, although over a larger area and with significantly less enhancement than that of the localized modes; however, the excitation of bulk modes is independent of the angle of incidence.
Fluorescence scanning near-field optical microscopy (SNOM) is used to investigate binary polyfluorene-based composites of varying composition. The samples investigated contain blends of the polymer poly(9,9'-dioctylfluorene-cobenzothiadiazole), F8BT, with similar polyfluorenes of wider band gap. Images acquired from a film containing 50% by weight F8BT exhibit a high degree of correlation between the topography and fluorescence, with an F8BT-rich phase which protrudes from the surface of the film forming isolated regions with sizes from hundreds of nanometres to several micrometres. A film containing 10% by weight F8BT also has micrometre-size F8BT-rich regions, but also present are small and locally varying proportions of F8BT in the other polyfluorene component phase, indicating a hierarchy of phases within this sample. The fluorescence and topographic images of a third sample studied, containing 90% by weight F8BT, display no correlation, demonstrating that it is not always appropriate to use topographic information to determine the phase structure within polymer blends. The fluorescence SNOM images acquired from these samples are able to assist our understanding of the photovoltaic efficiency of devices fabricated from these films, which are governed by the extent of the interfacial area between these two constituent polymers.
Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP), which stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO). NESP has been shown to be safe and efficacious in patients with chronic renal failure. NESP is biochemically distinct from rHuEPO, due to its increased sialic acid content. NESP has an approximately 3-fold greater half-life. rHuEPO has been shown to be safe and effective for the treatment of chemotherapy-induced anaemia. This study assessed the safety and efficacy of NESP administered once per week, under the supervision of a physician, to patients with solid tumours who were receiving multicycle chemotherapy for up to 12 weeks. Three dose cohorts are presented in this sequential, unblinded and dose-escalating study. Thirteen to 59 patients received NESP (0.5, 1.5 or 2.25 mcg kg(-1)wk(-1)) in each cohort. Patients were monitored for adverse events, including antibody formation to NESP and for effects on haemoglobin. NESP appeared to be well tolerated. Adverse events were similar across all cohorts and were consistent with the population being studied. No antibody formation was detected over the 16-week study period and follow-up. A dose-response relationship was evident for NESP and multiple measures of efficacy, including proportion of patients responding to NESP and the mean change in haemoglobin by week 4 and end of treatment for NESP 0.5, 1.5 and 2.25 mcg kg(-1)wk(-1)cohorts (mean change in haemoglobin at end of treatment was 1.24, 1.73 and 2.15 g dl(-1)respectively). Controlled studies of this agent at higher doses and less frequent schedules of administration are ongoing.
Historically, there have been many attempts to develop interventions to support the carers of people with dementia. To date the evidence of effectiveness has been limited. However, the success of psychosocial interventions for carers of people with schizophrenia has suggested the possibility of utilizing this approach. A systematic review was undertaken to assess the evidence of effectiveness for psychosocial interventions with carers of people with dementia. Thirty controlled trials that evaluated a psychosocial approach were identified. The overall methodological quality of these studies was poor, particularly with regard to sample size, and methods of random allocation. Individualized interventions that utilized problem solving and behaviour management demonstrated the best evidence of effectiveness. This approach is also closest to the effective model of psychosocial interventions currently in use with other severe and enduring illnesses. This suggests that there is scope for developing interventions, based more specifically on this model, for supporting the carers of people with dementia.
Unilateral cleft of the soft palate occurs sporadically in dogs, and there are few reports in the veterinary literature regarding its aetiology and management. This report describes six dogs with the condition. The dogs' primary presenting problem was rhinitis. The defects were successfully repaired using a two-layer closure technique with absorbable suture in five of the cases. Surgical correction was not performed in the remaining case.
This study integrates social value orientation (Messick & McClintock, 1968) and the consideration of future consequences (CFC; Strathman, Gleicher, Boninger, & Edwards, 1994) within the extended norm activation model of proenvironmental behaviour (Stern, Dietz, & Kalof, 1993). A survey of college students (N = 161) revealed some preliminary support for the proposed model, using past and intended involvement in proenvironmental political behaviour as the primary outcome variables. Relative to proselfs, prosocials expressed stronger proenvironmental intentions and a stronger belief in the social consequences of environmental conditions. Relative to low CFCs, high CFCs expressed stronger proenvironmental intentions, greater involvement in proenvironmental behaviour, and a stronger belief in the personal, social and biospheric consequences of environmental conditions. Perceived consequences mediated the relationship between CFC and proenvironmental intentions and behaviour, and high CFCs evidence a stronger positive relationship between perceived social consequences and proenvironmental intentions.
Variation in health care, and more particularly in dental care, was recently chronicled in a Readers Digest investigative report. The conclusions of this report are consistent with sound scientific studies conducted in various areas of health care, including dental care, which demonstrate substantial variation in the care provided to patients. This variation in care parallels the certainty with which clinicians and faculty members often articulate strongly held, but very different opinions. Using a case-based dental scenario, we present systematic evidence-based methods for accessing dental health care information, evaluating this information for validity and importance, and using this information to make informed curricular and clinical decisions. We also discuss barriers inhibiting these systematic approaches to evidence-based clinical decision making and methods for effectively promoting behavior change in health care professionals.
OBJECTIVE: To describe methods and procedures for the assembly of very large scale microscopic image arrays. STUDY DESIGN: Microscopic imagery was recorded on different video microphotometers, equipped either with a three-chip CCD Sony MD 760 (Park-ridge, New Jersey, U.S.A.), a COHU vidicon (San Diego, California, U.S.A.) or a PROGRES camera (JenOptik, Jena, Germany), yielding image tiles of 512 x 470, 512 x 470 or 1,496 x 1,120 pixels, respectively. The slide was moved while mounted on a Maerzheuser scanning stage with 0.1-micron precision, under computer control. The MERGE software. (Optical Sciences Center, University of Arizona, Tucson, Arizona, U.S.A.) was written in C and currently implemented on a Sun. Ultra Sparc 2 computer (Sun Microsystems, Palo Alto, California, U.S.A.). RESULTS: The MERGE program allows the assembly of very large scale digitized image arrays preserving exact tile alignment such that even within a single nucleus, highly precise registration is maintained. Images up to 150 megapixels have been assembled, although most practical applications required assembly of only 60-300 tiles. CONCLUSION: The single limiting effect of assembling very large image arrays is the problem of angular misalignment between CCD scan line orientation and scanning stage travel direction. For misalignment of even less than 1 degree, very large arrays need substantial tile overlap. For object areas extending over only 5-10 mm, the effects can be controlled.
Anxiety and depression are prevalent in primary care; however, current treatments differ in their availability, cost-effectiveness, and acceptability to patients. Self-help treatments (such as manual-based bibliotherapy) may be an appropriate intervention for some patients. The aim of this research was to determine the clinical and cost-effectiveness of self-help treatments for anxiety and depression in primary care by conducting a systematic review of randomised and non-randomised trials of self-help interventions for patients with anxiety and depression in primary care, from electronic database searches, correspondence with authors, and limited handsearching. Eight studies were identified, examining written interventions based mostly on behavioural principles. Although the majority of trials reported some significant advantages in outcome associated with self-help treatments, the number of included studies was limited and a number of methodological limitations were identified. There were no data concerning long-term clinical benefits or cost-effectiveness. In conclusion, self-help treatments may have the potential to improve the overall cost-effectiveness of mental health service provision. However, the available evidence is limited in quantity and quality and more rigorous trials are required to provide more reliable estimates of the clinical and cost-effectiveness of these treatments.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
OBJECTIVE: To investigate whether or not a coding polymorphism in the cystatin C gene (CST3) contributes risk for AD. DESIGN: A case-control genetic association study of a Caucasian dataset of 309 clinic- and community-based cases and 134 community-based controls. RESULTS: The authors find a signficant interaction between the GG genotype of CST3 and age/age of onset on risk for AD, such that in the over-80 age group the GG genotype contributes two-fold increased risk for the disease. The authors also see a trend toward interaction between APOE epsilon4-carrying genotype and age/age of onset in this dataset, but in the case of APOE the risk decreases with age. Analysis of only the community-based cases versus controls reveals a significant three-way interaction between APOE, CST3 and age/age of onset. CONCLUSION: The reduced or absent risk for AD conferred by APOE in older populations has been well reported in the literature, prompting the suggestion that additional genetic risk factors confer risk for later-onset AD. In the author's dataset the opposite effects of APOE and CST3 genotype on risk for AD with increasing age suggest that CST3 is one of the risk factors for later-onset AD. Although the functional significance of this coding polymorphism has not yet been reported, several hypotheses can be proposed as to how variation in an amyloidogenic cysteine protease inhibitor may have pathologic consequences for AD.
The aspartyl protease Cathepsin D has previously been suggested to play a role in the Alzheimer's disease (AD) process because of its ability to cleave the beta-amyloid precursor protein and the possibility that it may be one of the 'secretase' enzymes. A functional C-->T polymorphism in the Cathepsin D gene (CATD) has been reported to be associated with increased risk for AD in Caucasian case-control studies; specifically, the T-carrying genotypes confer increased risk. We have examined this association in our own Caucasian dataset of 210 AD cases and 120 controls, and in an additional Hispanic dataset comprising 79 AD cases and 112 controls. In Hispanics we find a modest interaction between CATD genotype and age of onset on risk for AD, such that the non-T-carrying genotype confers increased risk. In our Caucasian dataset we find no evidence for association between the CATD polymorphism and AD, although we do observe a small tendency towards an increase in the T-carrying genotypes in the case group, consistent with previous studies. We conducted an aggregate analysis of the published Caucasian datasets and found evidence that this CATD polymorphism (or another locus in linkage disequilibrium) does contribute significant, but small (<2%) risk for AD.
A characteristic feature of allergic asthma is the overexpression of the T helper type 2 (Th2) cytokines interleukin-4 (IL-4), IL-5 and IL-13 by T lymphocytes. Of these cytokines, IL-5 is critical for the growth, survival and recruitment of eosinophils which are thought to be responsible for the tissue damage observed in asthmatic airways. The expression of human IL-5 is primarily regulated at the transcriptional level; however, little is known about the mechanisms that control its transcription. Using nuclear extracts from allergen-specific human T-cell clones we have performed DNase I footprinting of the human IL-5 promoter in order to establish sites occupied by transcription factors. We show footprints covering the conserved lymphokine element 0 ¿(CLE0) -60 to -44 base pairs (bp) and GATA (-73 to -62 bp) elements, which have previously been identified to be important in the regulation of the murine IL-5 promoter. We also describe a footprint covering a considerably extended Octamer binding site (-249 to -217 bp), which encompasses two hitherto unidentified CCAAT/enhancer binding protein consensus binding sites. We have also identified a previously unknown Ets binding site (-274 to -264 bp). These novel data on the regions of the human IL-5 promoter that are bound by transcription factors should allow dissection of the regulatory mechanisms involved in the transcription of IL-5 in the T-helper lymphocytes of asthmatics.
The purpose of this study is to determine immune recovery and function after treatment with docetaxel or paclitaxel. Peripheral blood mononuclear cells were harvested before chemotherapy and at weekly times afterwards for cycle 1. Leukocyte subsets ICD45hiCD14lo polymorphonuclear neutrophils, CD45hiCD14hi monocytes, CD45hiCD14- lymphocytes, CD3+CD4/CD8+ T cells, CD3-CD19+ B cells, CD3-CD16/CD56+ natural killer (NK) cells], and circulating cytokine levels [tumor necrosis factor-alpha, gamma-interferon (gamma-IFN), and interleukins (IL-2, IL-10, IL-12)] were followed. In addition, T-cell mitogenic function, NK function, and lymphokine activated killer (LAK) function was assessed. Ten patients were entered in the trial. T-cell frequency, B-cell frequency, and CD4/CD8 ratio did not change. IL-10 serum levels significantly decreased in paclitaxel-treated patients (4.4+/-1.3 pg/ml at week 4 versus 7.8+/-2.1 pg/ml at baseline; p < 0.05). IL-2, IL-12, and gamma-IFN levels were not detectable. NK cytotoxic activity decreased in docetaxel-treated patients. LAK cell activity was not altered. Four patients achieved a partial or complete response. They demonstrated higher than normal CD4:CD8 T-cell ratios and an improved phytohemagglutinin stimulation index (SI = 2.5). In conclusion, our findings suggest that immune function was affected more significantly after docetaxel treatment. Investigational approaches, which enhance cellular immunity, may be of greater relevance after treatment with docetaxel. Additional studies monitoring NK function after chemotherapy are recommended.