Disability discrimination.
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Dental Care for Persons with Disabilities↗
Biomedical subjects
S Read
Publications and source records attributed to S Read.
Statistical parametric mapping of hypoxic tissue identified by [(18)F]fluoromisonidazole and positron emission tomography following acute ischemic stroke.
Positron emission tomography (PET) and the ligand [(18)F]fluoromisonidazole ((18)F-FMISO) have been used to image hypoxic tissue in the brain following acute stroke. Existing region of interest (ROI)-based methods of analysis are time consuming and operator-dependent. We describe and validate a method of statistical parametric mapping to identify regions of increased (18)F-FMISO uptake. The (18)F-FMISO PET images were transformed into a standardized coordinate space and intensity normalized. Then t statistic maps were created using a pooled estimate of variance. Statistical inference was based on the theory of Gaussian Random Fields. We examined the homogeneity of variance in normal subjects and the influence of normalization by mean whole brain activity versus mean activity in the contralateral hemisphere. Validity of the distributional assumptions inherent in parametric analysis was tested by comparison with a non-parametric method. The results of parametric analysis were also compared with those obtained with the existing ROI-based method. Variance in uptake at each voxel in normal subjects was homogeneous and not affected by mean voxel activity or distance from the centre of the image. The method of normalization influenced results significantly. Normalization by whole brain mean activity resulted in a smaller volume of tissue being classified as hypoxic compared to normalisation by mean activity in the contralateral hemisphere. The ROI-based method was subject to interobserver variability with a coefficient of variability of 16%. The volumes of hypoxic tissue identified by parametric and nonparametric methods were highly correlated (r = 0.99). These findings suggest that using a pooled variance and contralateral hemisphere normalisation, statistical parametric mapping can be used to objectively identify regions of increased (18)F-FMISO uptake following acute stroke in individual subjects.
Acute Disease↗
Escherichia coli O157:H7 infection in cows and calves in a beef cattle herd in Alberta, Canada.
Escherichia coli O157:H7 infection of cows and calves in a naturally-infected beef cattle herd in Alberta, Canada, was investigated over 2 years, encompassing two calf production cycles. In both years of the study, E. coli O157:H7 was isolated from the faeces of cows shortly after but not before parturition in late winter: 6/38 (16%) in 1996 and 13/50 (26%) in 1997. At < 1 week post-partum, 13/52 (25%) calves born in 1997 were shedding the organism. Faecal shedding of E. coli O157:H7 by cows and calves continued over the 7 weeks that they were in the calving pens, with the organism being isolated from the faeces of 2-18% of cows and 23-26% of calves during this period. Five weeks after they were moved onto a native grass pasture, all the calves and all but one cow in 1997 had ceased shedding the organism. When the calves were weaned in the fall, E. coli O157:H7 was isolated from the faeces of 0-1.5% of the calves 1 week prior to weaning and from 6-14% of the calves within 2 weeks after weaning. Parturition, calving pens and weaning appear to be important factors in maintaining E. coli O157:H7 infections in this beef cattle herd. Isolates from cows and calves during the immediate post-partum period were mostly of the same pulsed-field gel electrophoresis (PFGE) type of E. coli O157:H7. Similarly, at weaning a common PFGE type of E. coli O157:H7, which differed slightly from the post-partum PFGE type, was isolated from the calves. These typing data suggest a common source of infection for the animals as well as demonstrate clonal turnover of resident populations of this pathogen.
Animals↗
Baseline blood pressure but not early computed tomography changes predicts major hemorrhage after streptokinase in acute ischemic stroke.
BACKGROUND AND PURPOSE: Intracerebral hemorrhage is the most serious complication of thrombolytic therapy for stroke. We explored factors associated with this complication in the Australian Streptokinase Trial. METHODS: The initial CT scans (< or =4 hours after stroke) of 270 patients were reviewed retrospectively by an expert panel for early signs of ischemia and classified into the following 3 categories: no signs or < or =1/3 or >1/3 of the vascular territory. Hemorrhage on late CT scans was categorized as major or minor on the basis of location and mass effect. Stepwise, backward elimination, multivariate logistic regression analysis was used to identify risk factors for each hemorrhage category. RESULTS: Major hemorrhage occurred in 21% of streptokinase (SK) and 4% of placebo patients. Predictors of major hemorrhage were SK treatment (odds ratio [OR], 6.40; 95% CI, 2.50 to 16.36) and elevated systolic blood pressure before therapy (OR, 1.03; 95% CI, 1.01 to 1.05). Baseline systolic blood pressure >165 mm Hg in SK-treated patients resulted in a >25% risk of major secondary hemorrhage. Early ischemic CT changes, either < or =1/3 or >1/3, were not associated with major hemorrhage (OR, 1.58; 95% CI, 0.65 to 3.83; and OR, 1.11; 95% CI, 0.45 to 2.76, respectively). Minor hemorrhage occurred in 30% of the SK and 26% of the placebo group. Predictors of minor hemorrhage were male sex, severe stroke, early CT changes, and SK treatment. Ninety-one percent of patients with major hemorrhage deteriorated clinically compared with 23% with minor hemorrhage. CONCLUSIONS: SK increased the risk of both minor and major hemorrhage. Major hemorrhage was also more likely in patients with elevated baseline systolic blood pressure. However, early CT changes did not predict major hemorrhage. Results from this study highlight the importance of baseline systolic blood pressure as a potential cause of hemorrhage in patients undergoing thrombolysis.
Acute Disease↗
Selective increases in cytokine expression in the rat brain in response to striatal injection of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and interleukin-1.
A number of cytokines contribute to acute experimental neurodegeneration. The cytokine response can have detrimental or beneficial effects depending on the temporal profile and balance between pro- and anti-inflammatory molecules. Our recent data suggest that the pro-inflammatory cytokine interleukin-1beta (IL-1beta) acts at specific sites (e.g., the striatum) in the rat brain to cause distant cortical injury, when co-administered with the potent excitotoxin alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (S-AMPA). The objective of the present study was to investigate changes in the expression of several cytokines simultaneously in the rat striatum and cortex after intrastriatal administration of vehicle, S-AMPA or human recombinant (hr) IL-1beta alone or S-AMPA co-injected with hrIL-1beta using reverse transcription-polymerase chain reaction (RT-PCR; Taqman fluorogenic probes) and enzyme-linked immunosorbent assay (ELISA). Injection of S-AMPA alone increased IL-6 mRNA expression in the ipsilateral striatum after 8 h, whilst striatal injection of IL-1beta alone increased local IL-1beta and IL-1ra mRNAs. The levels of mRNA encoding IL-1alpha, IL-1beta, IL-1ra, IL-6, IL-10 and TNFalpha were markedly elevated in the ipsilateral cortex 8 h after co-injection of S-AMPA and hrIL-1beta. Cortical mRNA levels for IL-4, IL-18, TGFbeta and IFNgamma were not significantly different between treatment groups after 2 h or 8 h. A similar pattern of change in the levels of IL-1alpha and IL-6 protein was observed 8 h after treatment. These data demonstrate selective increases in the expression of cytokines in areas of remote cell death in response to administration of hrIL-1beta and S-AMPA. Such cytokines may be involved in the ensuing damage, and further clarification of their actions could aid future therapeutic strategies for several acute neurodegenerative disorders.
Animals↗
IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo.
We present evidence that donor-reactive CD4(+) T cells present in mice tolerant to donor alloantigens are phenotypically and functionally heterogeneous. CD4(+) T cells contained within the CD45RB(high) fraction remained capable of mediating graft rejection when transferred to donor alloantigen-grafted T cell-depleted mice. In contrast, the CD45RB(low) CD4(+) and CD25(+)CD4(+) populations failed to induce rejection, but rather, were able to inhibit rejection initiated by naive CD45RB(high) CD4(+) T cells. Analysis of the mechanism of immunoregulation transferred by CD45RB(low) CD4(+) T cells in vivo revealed that it was donor Ag specific and could be inhibited by neutralizing Abs reactive with IL-10, but not IL-4. CD45RB(low) CD4(+) T cells from tolerant mice were also immune suppressive in vitro, as coculture of these cells with naive CD45RB(high) CD4(+) T cells inhibited proliferation and Th1 cytokine production in response to donor alloantigens presented via the indirect pathway. These results demonstrate that alloantigen-specific regulatory T cells contained within the CD45RB(low) CD4(+) T cell population are responsible for the maintenance of tolerance to donor alloantigens in vivo and require IL-10 for functional activity.
Adoptive Transfer↗
CD4(+) regulatory T cells.
There is now compelling evidence that CD4(+) T cells that specialize in the suppression of immune responses play a key role in the control of immune pathology. Recently, there have been a number of reports that have provided information on the generation of CD4(+) regulatory T cells in the thymus and in the periphery. These cells have also been identified in humans, paving the way for analysis of the function of CD4(+) regulatory T cells in immune-mediated disease.
Animals↗
Control of intestinal inflammation by regulatory T cells.
Transfer of CD4+ T cells to immune-deficient mice in the absence of the CD25+ subset leads to the development of colitis, indicating that regulatory cells capable of controlling a bacteria-driven inflammatory response are present in normal mice. Cells with this function are present in the thymus as well as in the periphery of germ-free mice, suggesting they may be reactive with self-antigen. These cells resemble CD4+CD25+ cells that inhibit organ-specific autoimmunity, suggesting that a similar subset of regulatory T cells may control responses to self and foreign antigens. Development of colitis is dependent on accumulation of activated CD134L+ dendritic cells (DC) in the mesenteric lymph nodes, which is inhibited by CD4+CD25+ cells, indicating that regulatory T cells may control DC activation in vivo. Whilst inhibition of T-cell activation in vitro by CD4+CD25+ cells does not involve interleukin-10 and transforming growth factor-beta, these cytokines are required for the suppression of colitis. It may be that control of responses that activate the innate immune system requires multiple mechanisms of immune suppression. Recently, we identified CD4+CD25+ cells with immune suppressive activity in the thymus and peripheral blood of humans, raising the possibility that dysfunction in this mechanism of immune regulation may be involved in the development of autoimmune and inflammatory diseases.
ADP-ribosyl Cyclase↗
Tonabersat (SB-220453) a novel benzopyran with anticonvulsant properties attenuates trigeminal nerve-induced neurovascular reflexes.
1. The effects of tonabersat (SB-220453) were evaluated on trigeminal nerve ganglion stimulation-induced sensory-autonomic neurovascular reflexes in the anaesthetized cat. Comparisons were made to intravenous administration of carabersat (SB-204269), and to valproate, gabapentin and lamotrigine following intraduodenal administration. 2. There were no effects on resting blood pressure, heart rate, carotid blood flow or carotid vascular resistance for any compound evaluated. 3. Trigeminal nerve ganglion stimulation increased carotid blood flow by 65% and reduced vascular resistance by 41% with minimal effect on blood pressure (< 10%) and no effect on heart rate. Intravenous infusion of tonabersat or carabersat (both 3.4 micromol h(-1)) produced time related reductions in stimulation-induced responses with a maximal inhibition (relative to control) of 30 +/- 7% (n=4), at 240 min for tonabersat and 33+/-4% (n=3) at 180 min for carabersat. Tonabersat (11.5 micromol h(-1)) produced a similar inhibitory effect (32 +/- 9%, n=4) after 120 min of infusion. 4. Following intraduodenal administration of tonabersat, the maximal inhibition of nerve stimulation-induced responses was 55 +/- 4% at 120 min (n=4) for tonabersat 10 mg kg(-1), and 24+/-2% after 180 min for 1 mg kg(-1) (n=4). 5. Intraduodenal administration of sodium valproate (10 or 100 mg kg(-1) n=4/group) had no effect on neurovascular reflexes. Maximal inhibition of nerve ganglion-stimulated reductions in carotid vascular resistance were observed at 150 min for lamotrigine (50 mg kg(-1), 52+/-12%, n=4) and gabapentin (100 mg kg(-1), 17+/-13%, n=3). Lamotrigine 10 mg kg(-1) produced 22+/-11% (n=3) inhibition after 180 min. 6. These data demonstrate blockade of trigeminal parasympathetic reflexes with tonabersat, carabersat and other anticonvulsants. These agents may therefore have therapeutic benefit in conditions where this type of reflex is evident.
Anesthesia↗
Clinical role clarification: using the Delphi method to establish similarities and differences between nurse practitioners and clinical nurse specialists.
This article is based on the Department of Health's (England) funded pluralistic evaluation of Nurse Practitioner preparation, 'Realizing Specialist & Advanced Nursing Practice: establishing the parameters of and identifying competencies for "Nurse Practitioner" roles and evaluating programmes of preparation' (RSANP). During this 27-month project, which began in 1996, one of the research methods used, the Delphi study, was aimed at reaching a consensus of views amongst nurses in clinical practice, educators, purchasers, providers and representatives of statutory and professional bodies on the parameters and competencies desirable for the Nurse Practitioner role. The agreed competencies were then used as one measure of the appropriateness of various programmes used to prepare Nurse Practitioners. Of the competencies required for the role, the majority are 'nursing' competencies and are the same as those required for the Clinical Nurse Specialist role. However, for both Clinical Nurse Specialists and Nurse Practitioners, these are practised at a 'higher level'. Other competencies needed for the Nurse Practitioner role relate to the knowledge and skills required to assess, diagnose and determine nursing and medical management of a patient and to evaluate that management. Data indicated, however, that even these competencies were being used by some Clinical Nurse Specialists. Final analysis enabled the identification of the two roles with the use of a 'Typology of Named Clinical Nursing Roles'.
Attitude of Health Personnel↗
Nitric oxide potentiates response of trigeminal neurones to dural or facial stimulation in the rat.
Infusing glyceryl trinitrate as a donor molecule, we have used electrophysiological and c-fos immunostaining techniques to study the effects of nitric oxide on neurones in the nucleus trigeminalis caudalis. Following infusion of glyceryl trinitrate, responses of neurones to electrical stimulation of periorbital cutaneous afferents were potentiated and threshold for activation of neurones by stimulation of dural afferents was reduced. Expression of c-fos was unchanged by glyceryl trinitrate compared to saline controls. Intradermal injection of capsaicin in the periorbital area increased c-fos expression in nucleus trigeminalis caudalis; this was significantly potentiated by glyceryl trinitrate. These results suggest that, in the anaesthetized rat, glyceryl trinitrate alone may not acutely activate the trigeminovascular system to a significant degree at doses that cause headache and later trigger migraine headache in migraineurs. Nevertheless, it is susceptible to exogenous nitric oxide in that activation of trigeminal neurones through cutaneous or dural pathways is potentiated. This may in some measure underlie the pathogenesis of migraine headache.
Afferent Pathways↗
Metaphor: exploring its origins and therapeutic use in death, dying and bereavement.
Metaphor is a commonly used and powerful language device for expressing complex thoughts or feelings. This exploratory qualitative study examined the sources and function of metaphor in relation to death, dying and bereavement. The study involved focus group discussions and follow-up questionnaires with professionals from three different contexts (nursing, hospice and bereavement counselling), and gave rise to a number of interesting observations. The results have implications for professional carers, particularly those working in dying and bereavement contexts, in relation to facilitating the use of metaphor to enhance the quality of communication. Suggestions are made for further research.
Bereavement↗
Extended scope of nursing practice: a multicentre randomised controlled trial of appropriately trained nurses and pre-registration house officers in pre-operative assessment in elective general surgery.
OBJECTIVES: (1) To determine whether pre-operative assessment carried out by an appropriately trained nurse (ATN) is equivalent in quality to that carried out by a pre-registration house officer (PRHO). (2) To assess whether pre-assessments carried out by ATNs and PRHOs are equivalent in terms of cost. (3) To determine whether assessments carried out by ATNs are acceptable to patients. (4) To investigate the quality of communication between senior medical staff and ATNs. DESIGN: The study design was principally a prospective randomised equivalence trial but was accompanied by additional qualitative assessment of patient and staff perceptions, and an economic evaluation. SETTING: The study was carried out at four NHS hospitals, three of which were teaching hospitals, in three NHS Trusts in Southampton, Sheffield and Doncaster. SUBJECTS: All patients attending at one site for assessment prior to general anaesthetic for elective general, vascular, urological or breast surgery were potentially included in the study. Of 1907 patients who were randomised, 1874 completed the study with a full evaluation. INTERVENTIONS: The intervention consisted of a pre-operative assessment carried out by either an ATN or a PRHO. Of the patients who completed the study with a full evaluation, 926 patients were randomised to the PRHO arm of the trial and 948 to the ATN arm. Three ATNs took part in the study, one from each centre, together with a total of 87 PRHOs. MAIN OUTCOME MEASURES: Immediately following the initial assessment of a patient by a PRHO or an ATN, one of a number of clinical research fellows, all specialist registrars in anaesthetics, repeated the assessment and recorded it on a study form, together with a list of investigations required. The clinical research fellow then evaluated the competency of the initial assessor by comparing the quality of their assessment with their own. Any deficiencies in ordering of investigations and referral to other specialities were met in order to maximise patient care. Three areas of ATN and PRHO performance were judged separately, history taking, examination and ordering of tests, and each was graded into one of four categories, the most important of which was under-assessment, which would possibly have affected peri-operative management. In the case of ordering of tests, it was possible to have both over- and under-assessed a patient on different tests. RESULTS: The pre-operative assessments carried out by the ATNs were essentially equivalent to those performed by the PRHOs in terms of under-assessment that might possibly have affected peri-operative management, although there was variation between the ATNs in terms of the quality of history taking. This may be related to the low number of patients seen at one study site. PRHOs ordered significantly more unnecessary tests than the ATNs. The substitution of ATNs for PRHOs was calculated to be cost neutral. The results of the qualitative assessment showed that the use of ATNs for pre-operative assessment was acceptable to patients; however, there was no evidence that communication between senior medical staff and those carrying out pre-operative assessments was improved by their introduction. CONCLUSIONS: This study demonstrated no reason to inhibit the development of fully nurse-led pre-operative assessment, provided that the nurses are appropriately trained and maintain sufficient workload to retain skills. CONCLUSIONS--IMPLICATIONS FOR THE HEALTH SERVICE: ATNs provide an acceptable and efficient alternative to PRHOs for the purposes of routine pre-operative assessment. Consideration will have to be given, however, to the positions of these nurses within the surgical team, and also to their career structure. CONCLUSIONS--RECOMMENDATIONS FOR FUTURE RESEARCH: Further research is needed in the following areas: (1) the extent and type of training needed for nurses undertaking the pre-operative assessment role; (2) the use, costs and benefits of routine pre-operative testing.
Clinical Competence↗
High prevalence of genotypic zidovudine resistance among HIV-infected Canadian children.
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Adolescent↗
Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation.
It is now clear that functionally specialized regulatory T (Treg) cells exist as part of the normal immune repertoire, preventing the development of pathogenic responses to both self- and intestinal antigens. Here, we report that the Treg cells that control intestinal inflammation express the same phenotype (CD25(+)CD45RB(low)CD4(+)) as those that control autoimmunity. Previous studies have failed to identify how CD25(+) Treg cells function in vivo. Our studies reveal that the immune-suppressive function of these cells in vivo is dependent on signaling via the negative regulator of T cell activation cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), as well as secretion of the immune-suppressive cytokine transforming growth factor beta. Strikingly, constitutive expression of CTLA-4 among CD4(+) cells was restricted primarily to Treg cells, suggesting that CTLA-4 expression by these cells is involved in their immune-suppressive function. These findings raise the possibility that Treg cell function contributes to the immune suppression characteristic of CTLA-4 signaling. Identification of costimulatory molecules involved in the function of Treg cells may facilitate further characterization of these cells and development of new therapeutic strategies for the treatment of inflammatory diseases.
Abatacept↗
Predictive validity of the New Zealand MacArthur Communicative Development Inventory: Words and Sentences.
This study assessed the long-term predictive validity of the MacArthur Communicative Development Inventories: Words and Sentences (CDI:WS; Fenson, Dale, Reznick, Thal, Bates, Hartung, Pethick & Reilly, 1993) for children's expressive and receptive vocabulary development. Sixty-one New Zealand children (31 females) were assessed with a New Zealand version of the CDI: WS at 1;7 and 2;1 and with the Expressive Vocabulary Test (Williams, 1997) and the Peabody Picture Vocabulary Test-III (Dunn & Dunn, 1997) at 2;8 and 3;4. Excellent reliability and good predictive validity was obtained for the NZ CDI:WS even over a 21-month delay. Predictive validity of the NZ CDI:WS for the PPVT-III was higher for children of mothers with less education. We discuss the implications of these results for use of the CDI:WS with children from a broad range of cultural and educational backgrounds.
Child Language↗
Practical considerations in case study research: the relationship between methodology and process.
This paper explores the extent to which the design of a research study is influenced by pragmatic as well as theoretical considerations by describing the authors' experience of conducting multiple case studies in the context of a policy-orientated research project. The case studies in question formed part of a collaborative project exploring the development of innovative roles in nursing and the professions allied to medicine. The researchers adopted Yin's approach to the conduct of multiple case studies to explore issues relating to the effectiveness of new roles, their resource implications and educational issues surrounding their development. They address the fact that methodological decisions have practical implications and also explore the effects of practical and ethical issues on research design. Three purposively selected acute National Health Service Trust hospitals in England formed the case study sites for the work recorded in this paper. In each Trust, three nursing roles were selected, making nine cases for study. A variety of data collection strategies were used including semi-structured interviews with post-holders and other stakeholders (n = 51), non-participant observation of meetings, collection of audit, financial and statistical data and review of relevant documentation. This paper describes some of the dilemmas which arose during the course of the study, the rationale for methodological decisions taken to resolve these dilemmas and the steps taken to enhance rigour. In particular, the authors discuss the problems associated with obtaining informed consent in the context of qualitative research and with member validation of transcripts in a context where confidentiality was crucial. The decision to present findings thematically rather than as individual cases is justified both in terms of the nature and purpose of the research and in relation to the particular importance of anonymity and confidentiality in this study. Finally, the degree of reciprocity between researcher and researched is discussed.
Attitude of Health Personnel↗
Palliative care for people who have a learning disability: exploring the professional needs of qualified district nurses.
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Journal Article↗