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Biomedical subjects

D Allen

Publications and source records attributed to D Allen.

At least 73 records · Page 4Linked to original sources

Opportunity and the promotion of activity among adults with severe intellectual disability living in community residences: the impact of training staff in active support.

Active support, a package of procedures which includes activity planning, support planning and training on providing effective assistance, was introduced in five community residences serving 19 adults with severe intellectual disability following a multiple baseline design. The residents were directly observed to ascertain the level of assistance they received from staff and their engagement in activity. The introduction of active support increased the levels of assistance residents received, their engagement in domestic activities and their total engagement in activity. The intervention did not affect the level of social engagement. Across individuals, increases in assistance and engagement in activity were significantly and positively correlated. Both were significantly inversely related to resident adaptive behaviour. At baseline, staff gave more attention and assistance to people who were behaviourally more able. After the introduction of active support, receipt of attention was unrelated to adaptive behaviour and the behaviourally less able received more assistance. The disparity in activity between the more and less able was reduced. Gains were maintained in the majority of houses.

Activities of Daily Living↗

Mediator analysis: an overview of recent research on carers supporting people with intellectual disability and challenging behavior.

Families and front-line care staff are often key agents in helping deliver behavioural interventions to people with intellectual disability and challenging behaviour. The present paper reviews factors which may impact on the effectiveness of such interventions. Both PsychLit and MedLine were used to conduct an automated literature search which included the terms 'learning disability', 'mental handicap', 'mental retardation', 'intellectual disability', 'challenging behaviour', 'families' and 'staff. This search was substantially augmented by additional citations obtained from books and journal articles. The impact of attitudes, beliefs and emotional states as setting conditions for interventions was highlighted. A variety of more general setting conditions related to intervention effectiveness were also identified. Implications for both clinical practice and future research were discussed.

Adaptation, Psychological↗

Effect of tropisetron on vomiting during patient-controlled analgesia in children.

Patient-controlled analgesia (PCA) is associated with a high incidence of vomiting which is distressing and interferes with postoperative recovery. Tropisetron, a long-acting selective 5-HT3 receptor antagonist, has been shown to be effective in preventing nausea and vomiting associated with PCA use in adults and chemotherapy in children. We assessed the efficacy of prophylactic intraoperative administration of tropisetron on the incidence of vomiting in children using morphine PCA. We studied 58 patients, allocated randomly to receive tropisetron 0.1 mg kg-1 to a maximum of 5 mg, or normal saline. Children who received tropisetron had an incidence of vomiting during the first 24 h after operation of 22% compared with 66% in the control group (P = 0.001). In addition, the severity of vomiting was less in the tropisetron group with only one child (4%) vomiting more than twice compared with nine (31%) in the control group (P = 0.01). We conclude that tropisetron is efficacious in reducing the incidence and severity of postoperative vomiting in children using PCA.

Adolescent↗

Disruption of anthrax toxin binding with the use of human antibodies and competitive inhibitors.

The protective antigen (PA83) of Bacillus anthracis is integral to the mechanism of anthrax toxicity. We have isolated a human single-chain Fv antibody fragment (scFv) that blocks binding of a fluorescently tagged protective antigen (PA) moiety to cell surface receptors. Several phage-displayed scFv were isolated from a naive library biopanned against PA83. Soluble, monomeric scFv were characterized for affinity and screened for their capacity to disrupt receptor-mediated binding of PA. Four unique scFv bound to PA83, as determined by surface plasmon resonance, the tightest binder exhibiting a Kd of 50 nM. Two scFv had similar affinities for natural PA83 and a novel, recombinant, 32-kDa carboxy-terminal PA fragment (PA32). Binding of scFv to green fluorescent protein fused to the amino-terminal 32-kDa fragment of B. anthracis edema factor, EGFP-EF32, was used to confirm specificity. Fusion of EGFP to PA32 facilitated development of a novel flow cytometric assay that showed that one of the scFv disrupted PA receptor binding. This method can now be used as a rapid assay for small molecule inhibitors of PA binding to cell receptors. The combined data presented suggest the potential utility of human scFv as prophylactics against anthrax poisoning. Moreover, recombinant PA32 may also be useful as a therapeutic agent to compete with anthrax toxins for cellular receptors during active infection.

Animals↗

Measuring visual symptoms in British cataract patients: the cataract symptom scale.

AIMS: To develop and validate a scale for the measurement of visual symptoms and functional disability due to cataract in older UK residents. METHODS: In depth semistructured interviews were undertaken with 44 consecutive patients awaiting cataract surgery. Patients were asked to describe visual symptoms and problems with social functioning which were then incorporated into a questionnaire, the cataract symptom scale (CSS). The CSS was further examined in a cohort of 118 consecutive cataract patients awaiting surgery. Further assessments in these patients included visual acuity, visual function using an existing scale (the VF-14), activities of daily living, perceived health status, anxiety and depression, and a global assessment of how much patients felt their visual symptoms affected their daily life. RESULTS: A 15 item scale was derived which was simple to administer to older patients and had a high internal consistency. The test-retest correlation coefficient for the total instrument score was r = 0.91 (p<0.0001). The CSS correlated well with the VF-14 and to a lesser extent with visual acuity in the better eye, activities of daily living, perceived health status, anxiety and depression, and the patients' global assessment of visual symptoms. CONCLUSION: The CSS provides information regarding the symptomatic and functional status of older cataract patients resident in the UK which cannot be obtained by measurement of visual acuity alone.

Activities of Daily Living↗

Essential and partially overlapping role of CD3gamma and CD3delta for development of alphabeta and gammadelta T lymphocytes.

CD3gamma and CD3delta are two highly related components of the T cell receptor (TCR)-CD3 complex which is essential for the assembly and signal transduction of the T cell receptor on mature T cells. In gene knockout mice deficient in either CD3delta or CD3gamma, early thymic development mediated by pre-TCR was either undisturbed or severely blocked, respectively, and small numbers of TCR-alphabeta+ T cells were detected in the periphery of both mice. gammadelta T cell development was either normal in CD3delta-/- mice or partially blocked in CD3gamma-/- mice. To examine the collective role of CD3gamma and CD3delta in the assembly and function of pre-TCR and in the development of gammadelta T cells, we generated a mouse strain with a disruption in both CD3gamma and CD3delta genes (CD3gammadelta-/-). In contrast to mice deficient in either CD3gamma or CD3delta chains, early thymic development mediated by pre-TCR is completely blocked, and TCR-alphabeta+ or TCR-gammadelta+ T cells were absent in the CD3gammadelta-/- mice. Taken together, these studies demonstrated that CD3gamma and CD3delta play an essential, yet partially overlapping, role in the development of both alphabeta and gammadelta T cell lineages.

Animals↗

The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM.

In addition to triggering the activation of B- or T-cell antigen receptors, the binding of a ligand to its receptor at the cell surface can sometimes determine the physiological outcome of interactions between antigen-presenting cells, T and B lymphocytes. The protein SLAM (also known as CDw150), which is present on the surface of B and T cells, forms such a receptor-ligand pair as it is a self-ligand. We now show that a T-cell-specific, SLAM-associated protein (SAP), which contains an SH2 domain and a short tall, acts as an inhibitor by blocking recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region. The gene encoding SAP maps to the same area of the X chromosome as the locus for X-linked lymphoproliferative disease (XLP) and we found mutations in the SAP gene in three XLP patients. Absence of the inhibitor SAP in XLP patients affects T/B-cell interactions induced by SLAM, leading to an inability to control B-cell proliferation caused by Epstein-Barr virus infections.

Amino Acid Sequence↗

Cortical metastatic lesions of the appendicular skeleton from tumors of known primary origin.

BACKGROUND AND OBJECTIVES: Metastatic disease represents the most common neoplastic process involving bone. Recently, a small subset of cortical based metastatic lesions has been identified. We attempted to delineate the incidence, origin, location, and possible significance of these lesions within an orthopaedic patient population. METHODS: A chart and radiographic review of patients treated for metastatic disease to bone over a 17-year period was performed. Inclusion criteria for lesions were as follows: 1) an appendicular skeletal site, 2) histopathologic confirmation of origin, and 3) presence within a patient diagnosed with a single, known neoplastic process. The lesions were classified as either cortical or medullary based. RESULTS: Eighty-three lesions (70 patients) satisfied inclusion criteria. Most lesions were of pulmonary (26), breast (22), renal (16), or prostatic (8) tumor origin. Eighteen lesions (22%) from 15 patients were identified as cortical and represented initial presentation in 7 patients. These lesions were of pulmonary (11), renal (5), and breast (2) tumor origin. CONCLUSIONS: Cortical based metastases within the appendicular skeleton may occur more frequently than previously expected. While tumors of pulmonary and renal origin accounted for 42 of the 83 (51%) appendicular lesions, they were responsible for 16 of the 18 (89%) cortical metastases. This preponderance of pulmonary and renal metastases to the cortex is consistent with previously published reports. Our findings may be of value when diagnosing and treating patients whose initial presentation is a cortically based lesion.

Adenocarcinoma↗

Is the rod visual field temporally homogeneous?

Cone vision has been shown to be temporally inhomogeneous across the visual field. In the periphery, contrast sensitivity is lower for low temporal frequencies and higher for high temporal frequencies. Here we ask a similar question for rod vision at mesopic luminances. Isolation is obtained by testing a well documented rod monochromat. We show that the rod visual field exhibits only a modest degree of temporal inhomogeneity.

Color Vision Defects↗

Boston HAPPENS Program: a model of health care for HIV-positive, homeless, and at-risk youth. Human immunodeficiency virus (HIV) Adolescent Provider and Peer Education Network for Services.

The Boston HAPPENS [Human immunodeficiency virus (HIV) Adolescent Provider and Peer Education Network for Services] Program is a project supported by Special Projects of National Significance (SPNS) Program, HIV/AIDS Bureau, Health Resources and Services Administration, which provides a network of care for homeless, at-risk, and HIV-positive youth (ages 12-24 years), involving eight agencies. The program has provided services to 1301 youth, including 46 who are HIV-positive. Boston HAPPENS provides a citywide network of culturally and developmentally appropriate adolescent-specific care, including: (a) outreach and risk-reduction counseling through professional and adult-supervised peer staff, (b) access to appropriate HIV counseling and testing support services, (c) life management counseling (mental health intake and visits as part of health care and at times of crisis), (d) health status screening and services needs assessment, (e) client-focused, comprehensive, multidisciplinary care and support, (f) follow-up and outreach to ensure continuing care, and (g) integrated care and communication among providers in the metropolitan Boston area. This innovative network of youth-specific care offers a continuum from street outreach to referral and HIV specialty care that crosses institutional barriers.

Acquired Immunodeficiency Syndrome↗

The responses of autistic children to the distress of others.

The behavior of preschool children from five groups (developmental language disordered, high-functioning autistic, low-functioning autistic, mentally retarded, and normally developing) were coded in three situations: presentation of a nonsocial orienting stimulus (an unfamiliar noise) and two social situations involving simulated distress on the part of an adult with whom they were playing. Cognitive level was correlated with level of responsiveness to stimuli only for the two retarded groups (mentally retarded and low-functioning autistic). Girls showed more prosocial behavior than boys in both social situations, independent of diagnosis. The language-disordered children showed only mild and subtle social deficits. The low-functioning autistic children showed pronounced deficits in responding in all situations. The mentally retarded and high-functioning autistic children showed good awareness of all situations, but were moderately impaired in their ability to respond prosocially; they rarely initiated prosocial behavior, but did respond to specific prompts. The behavioral feature that marked both autistic groups, in contrast to all other groups, was a lack of social referencing; they did not tend to look toward an adult in the presence of an ambiguous and unfamiliar stimulus. Results are discussed in terms of variability between and among high- and low-functioning autistic children, and implications for the core deficits in autism.

Affect↗

Antigen specificity and tumour targeting efficiency of a human carcinoembryonic antigen-specific scFv and affinity-matured derivatives.

We have examined the biological properties of CEA6, a human carcinoembryonic antigen (CEA)-specific single-chain Fv (scFv) isolated by phage display, and five related clones derived by affinity maturation and selected for improved off-rate (Koff). All clones bind strongly and specifically to CEA-positive human tumours by immunocytochemistry and show negligible cross-reactivity with normal colon. Flow cytometry of scFv on human liver cells indicates a shift in fine epitope specificity resulting from mutagenesis. All monomeric scFv have been radioiodinated, retaining effectively full binding activity. A single intravenous injection into nude mice bearing human colon tumour xenografts confirms tumour targeting in all cases. As reported in other studies, the kidney is the main route of elimination of scFv at early time points. Tumour binding of the parental antibody CEA6 consistently gives the highest tumour-blood ratios at 24 h (mean 16:1). Clone TO6D11, which has a sevenfold reduced Koff relative to CEA6, showed no difference in tumour uptake at 24 h but persisted at the tumour site for longer than CEA6. This study demonstrates a possible correlation between binding affinity and tumour residence time when examined in this model.

Animals↗

Ki67 expression in lichen sclerosus of vulva in patients with and without associated squamous cell carcinoma.

AIMS: To investigate the malignant potential of lichen sclerosus, a study using the cell proliferation marker Ki67 comparing lichen sclerosus with and without associated squamous cell carcinoma was performed. METHODS AND RESULTS: Formalin-fixed, paraffin-embedded slides of 13 cases of lichen sclerosus with associated carcinoma, and 31 cases without associated carcinoma, including 16 random cases, seven with epidermal thickening and eight with epidermal thinning, were examined by the immunoperoxidase technique for Ki67, a cell proliferation marker. Ki67 reactivity was mostly seen in the basal and parabasal cells in both groups of lichen sclerosus and this pattern was similar to normal skin, squamous cell hyperplasia and analogous to that of one form of squamous cell carcinoma. There was a mean of 50 Ki67 positive cells per 100 basal cells in lichen sclerosus with associated squamous cell carcinoma; however, in squamous cell hyperplasia adjacent to carcinoma this rose to 90 Ki67 positive cells per 100 basal cells. In lichen sclerosus without associated carcinoma, the random cases had a count of 53 per 100 basal cells, those with epidermal thickening 53 and those with thinning 42. Non-genital normal skin had a count of 71 per 100 basal cells. CONCLUSION: The lack of qualitative differences of Ki67 expression in normal skin, in lichen sclerosus with and without carcinoma, in squamous cell hyperplasia and in one form of squamous cell carcinoma indicates that these conditions share a common localized pattern of cell proliferation and does not support or deny the malignant potential of lichen sclerosus. The higher Ki67 count in squamous cell hyperplasia adjacent to carcinoma could indicate premalignancy or a reaction to the carcinoma. In patients without carcinoma, the higher Ki67 count in thickened lichen sclerosus compared to thinned suggests that some or all of the cases of thickened lichen sclerosus were lichen sclerosus with squamous cell hyperplasia or that lichen simplex chronicus superimposed on lichen sclerosus has a higher Ki67 expression or that the distinction between squamous cell hyperplasia and lichen simplex chronicus is only one of terminology.

Basal Cell Carcinoma↗

Record-keeping and routine nursing practice: the view from the wards.

This paper examines general nurses' views of the nursing record and its routine usage in contemporary hospital practice. It draws on ethnographic data generated on a surgical ward and a medical ward in a single District General Hospital in the United Kingdom (UK). A key research finding was ward nurses' equivocal attitudes to the nursing record. On the one hand, because of its links with the nursing process, the nursing record was highly valued as a symbol of professionalism and ward staff were loathe to criticise it directly. On the other hand, however, the nurses in this study clearly found it difficult to reconcile their professional ideals with the ways in which the nursing record was routinely employed on the wards. In this paper it is suggested that at one level, nurses' ambivalence towards the nursing record reflected the distortion of its founding philosophy by the new managerialism in the contemporary UK health care context. At another level, however, there are also difficulties which arise from the tension between the assumptions about the nature of nursing work which underpin the nursing record and the workplace reality on hospital wards.

Anthropology, Cultural↗

16-Epiestriol, a novel anti-inflammatory nonglycogenic steroid, does not inhibit IFN-gamma production by murine splenocytes.

All the steroidal anti-inflammatory drugs currently available are glucocorticoids. The desired anti-inflammatory activities of glucocorticoids frequently are accompanied by adverse side effects, notably glycogenic activities and profound immunosuppression, that can limit clinical use. We recently identified 16-epiestriol, a naturally occurring steroid, as exhibiting significant anti-inflammatory activity without glycogenic activity. In the present study, we compared the effects of 16-epiestriol and hydrocortisone on the capacity of murine splenocytes to produce interferon-y (IFN-y). We injected young adult male BDF1 mice once with 20 mg/kg hydrocortisone or 20, 5, or 1 mg/kg 16-epiestriol and 4 h later harvested the splenocytes. Flow cytometric analysis confirmed that 16-epiestriol did not alter the number of CD3+ T cells in the spleen. In contrast to the suppressive effects of hydrocortisone, none of the 16-epiestriol concentrations inhibited concanavalin A-stimulated IFN-gamma production by spleen cells, as determined by ELISA. Incubating spleen cells from untreated mice in concentrations of 16-epiestriol ranging from 1 mg/ml to 100 pg/ml did not alter profiles of IFN-gamma production, in contrast to the suppressive dose-response effects of hydrocortisone. Collectively, these results support the contention that 16-epiestriol may be a clinically useful safe anti-inflammatory steroid without profound immunosuppressive activities.

Adjuvants, Immunologic↗