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Biomedical subjects

A Reid

Publications and source records attributed to A Reid.

At least 19 recordsLinked to original sources

Immunohistochemical detection of CD30 remains negative in nodular lymphocyte-predominant Hodgkin's disease using enhanced antigen retrieval.

AIMS: The aims of this study were to confirm that CD30 is reproducibly negative in cases of nodular lymphocyte-predominant Hodgkin's disease (nLPHD), and its relationship to further antibody targets for the distinction of L&H cells from classical Hodgkin's and Reed-Sternberg cells. METHODS AND RESULTS: We examined 16 cases of nLPHD from two centres in the UK to characterize immunohistochemically L&H cells for CD30, EMA, J-chain and Oct2, using different methods of antigen retrieval, antigen amplification and antigen detection systems. Two cases could not be stained with J-chain and Oct2. All cases were negative for CD30 following manual and automated staining. Only one case became positive for EMA after manual staining using tyramide amplification. J-chain and Oct2 were negative in all cases following manual staining. J-chain showed a positive result of variable degree in all but one case using automated Dako ChemMate amplification system staining. Oct2 demonstrated a positive, albeit variable, staining pattern in all cases following automated staining. CONCLUSIONS: CD30 remains negative in L&H cells of nLPHD using enhanced antigen retrieval and can therefore reliably be used to distinguish nLPHD from classical Hodgkin's disease. The value of EMA in the diagnosis of nLPHD remains uncertain, as it does not reproducibly mark L&H cells, even after the use of enhanced antigen retrieval. J-chain and Oct2 appear to be useful markers in the diagnosis of nLPHD using enhanced immunostaining and should therefore be included in lymphoma panels. Automated enhanced staining, using standardized protocols, precoated slides and the full system of prepared reagents, further diminishes the occurrence of errors associated with manual staining, and thereby improves confidence and reliability in diagnosing nLPHD.

Adult↗

Variant Philadelphia translocations in chronic myeloid leukaemia can mimic typical blast crisis chromosome abnormalities or classic t(9;22): a report of two cases.

A range of fluorescent in situ hybridization techniques have been used to reveal hidden variant Philadelphia translocations in two cases of Ph-positive chronic-phase chronic myeloid leukaemia. In one patient, a highly complex variant Ph translocation affecting four chromosomes had resulted in the formation of structures with the appearance of i(17q) and +8. Misinterpretation of these karyotypes has direct clinical relevance. Our findings illustrate that even established cytogenetic abnormalities may contain cryptic abnormalities beyond the resolution of conventional cytogenetic methods.

Aged↗

Community based medical education in a rural area: a new direction in undergraduate training.

The Greater Murray Clinical School provides a community based medical education programme for the clinical years at the University of New South Wales. Being a new clinica school in rural Australia allowed the development of a patient-centred longitudinal curriculum. Students follow patients through the health care system, with each exposure stimulating the learning about different aspects of a patient problem. The paper outlines the conceptual approach towards the development and implementation of this novel approach to community based medical education.

Clinical Clerkship↗

Neonatal mortality and stillbirths in early twentieth century Derbyshire, England.

Neonatal mortality and stillbirths are recognised to be subject to similar influences, but survival after a successful live birth is usually considered in isolation of foetal wastage. Moreover, individual-level data on age-specific influences and causes of death in a historical context are rare. This paper uses an unusual data set to compare the influences on neonatal mortality and stillbirths in early twentieth century Derbyshire, England. Multivariate hazard and logistic analyses are performed to examine the relative roles of various social, environmental, and demographic factors. The influences on and causal structures of neonatal mortality and stillbirths emerge as broadly similar, with previous reproductive history linked to a considerable amount of variation. The clustering of endogenous deaths was much greater than the clustering of exogenous and post-neonatal deaths, probably reflecting the cause-of-death structure and the relatively healthy social and environmental position of early twentieth century Derbyshire.

England↗

Involvement of mast cells, sensory afferents and sympathetic mechanisms in paw oedema induced by adenosine A(1) and A(2B/3) receptor agonists.

Both the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine and the adenosine A(2B/3) receptor agonist N(6)-benzyl-5'-N-ethylcarboxamido adenosine (N(6)-B-NECA) produce an acute paw oedema response following local s.c. injection into the rat hindpaw. This study characterized aspects of the mechanisms by which these responses occur by determining the effect of compound 48/80 (mast cell depleting agent), capsaicin (sensory neurotoxin) and 6-hydroxydopamine (sympathetic nervous system neurotoxin) on the paw oedema response produced by these agents. Compound 48/80 markedly reduced the increase in paw volume produced by both N(6)-cyclopentyladenosine and N(6)-B-NECA. Capsaicin significantly reduced paw oedema induced by N(6)-cyclopentyladenosine but not N(6)-B-NECA. In contrast, 6-hydroxydopamine reduced paw oedema induced by N(6)-B-NECA but not N(6)-cyclopentyladenosine. These results indicate an involvement of mast cells in paw oedema produced by both adenosine A(1) and A(2B/3) receptor agonists. For N(6)-cyclopentyladenosine, this involvement may be a secondary involvement due to activation of a neurogenic mechanism, but for N(6)-B-NECA, it may be a direct effect on mast cells. The nature of the involvement of the sympathetic nervous system in the action of N(6)-B-NECA is not entirely clear.

Adenosine↗

Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia.

The hallmark of chronic myeloid leukemia (CML) is the BCR-ABL fusion gene, which is usually formed as a result of the t(9;22) translocation. Patients with CML show considerable heterogeneity both in their presenting clinical features and in the time taken for evolution to blast crisis. In this study, metaphase fluorescence in situ hybridization showed that a substantial minority of patients with CML had large deletions adjacent to the translocation breakpoint on the derivative 9 chromosome, on the additional partner chromosome in variant translocations, or on both. The deletions spanned up to several megabases, had variable breakpoints, and could be detected by microsatellite polymerase chain reaction in unfractionated bone marrow and purified peripheral blood granulocytes. The deletions were likely to occur early and possibly at the time of the Philadelphia (Ph) chromosome translocation: deletions were detected at diagnosis in 11 patients, were found in all Ph-positive metaphases, and were more prevalent in patients with variant Ph chromosomes. Kaplan-Meier analysis showed a median survival time of 36 months in patients with a deletion; patients without a detectable deletion survived > 90 months. The survival-time difference was significant on log-rank analysis (P =. 006). Multivariate analysis demonstrated that the prognostic importance of deletion status was independent of age, sex, percentage of peripheral blood blasts, and platelet count. Our data therefore suggest that an apparently simple, balanced translocation may result not only in the generation of a dominantly acting fusion oncogene but also in the loss of one or more genes that influence disease progression. (Blood. 2000;95:738-743)

Adolescent↗

Contrast-enhanced 3D MRA using SENSE.

Sensitivity encoding (SENSE) was used to improve the performance of three-dimensional contrast-enhanced magnetic resonance angiography (3D CE-MRA). Utilizing an array of receiver coils for sensitivity encoding, the encoding efficiency of gradient-echo imaging was increased by factors of up to three. The feasibility of the approach was demonstrated for imaging of the abdominal vasculature. On the one hand, using a SENSE reduction factor of two, the spatial resolution of a breath-hold scan of 17 seconds was improved to 1.0 x 2.0 x 2.0 mm(3). On the other hand, using threefold reduction, time-resolved 3D CE-MRA was performed with a true temporal resolution of 4 seconds, at a spatial resolution of 1.6 x 2.1 x 4.0 mm(3). CE-MRA with SENSE was performed in healthy volunteers and patients and compared with a standard protocol. Throughout, diagnostic quality images were obtained, showing the ability of sensitivity encoding to enhance spatial and/or temporal resolution considerably in clinical angiographic examinations.

Aged↗

Is dosage of physiotherapy a critical factor in deciding patterns of recovery from stroke: a pragmatic randomized controlled trial.

BACKGROUND AND PURPOSE: The best treatment and management of stroke patients has been shown to be in stroke units by multidisciplinary rehabilitation teams. Since the composition of stroke units differs it is important to know the extent to which the different components contribute to this results. Physiotherapy is one component of most rehabilitation teams and recent systematic reviews have shown that patients with stroke receiving more physiotherapy achieve more recovery from disability. However, information about the actual amounts of physiotherapy needed to achieve this result is not known. METHOD: A pragmatic, randomized, single-blind, controlled trial comparing recovery from disability in subjects receiving the current standard amount of 30 minutes' physiotherapy with those receiving double that amount (60 minutes). The study included measures of physical performance and function, psychological aspects of anxiety and depression, and perceived control over recovery. RESULTS: Some 114 subjects were recruited to the study; full six-week data are available for 104 subjects and six-month data for 93 subjects. Comparison of initial to six-week difference scores in the control and intervention groups of the whole sample did not show a significant difference. Scrutiny of the recovery curves of the whole sample showed that, in half the sample, three distinct patterns of recovery were demonstrated. CONCLUSION: These results suggest that doubling the physiotherapy time available for patients in a stroke unit will not provide a measurable benefit for all patients. The subgroup analysis of patterns of recovery must be regarded as speculative, but provides the basis for hypotheses about those likely to respond well to more intensive therapy.

Activities of Daily Living↗

Quantitative assays for the chick chorioallantoic membrane.

Focal application of angiogenic substances to the chick chorioallantoic membrane is quick and easy as a rapid screening test, but is susceptible to artefactual stimulation induced by carriers, hyperosmolarity, proteolytic activity, and indeed any cause of damage to the CAM. This can be deceptive and unanticipated. Focal application methods can be used for subsequent measurement by morphometry of the increased vascularity forming the typical spokewheel pattern of supply vessels. If test and control substances are applied in liquid form to the whole dropped CAM surface, then a much wider variety of quantitative morphometric, histological and biochemical techniques can be applied. Assessment of arterial vascularity, terminal arterial branching, supply vessels in cross-sections, and CAM haemoglobin content are direct measures of angiogenic effects, but are time-consuming. Biochemical assays of collagen, protein and DNA synthesis parallel the other assays, and these parameters can be estimated more quickly within the working week. There is inherent variability in the outbred strains of hen eggs currently commercially available. This means that all assays require substantial group numbers to achieve statistical validity, generally not less than 10 eggs per group. The biochemical assays yield interesting time-course patterns that distinguish between different types of angiogenic stimulants.

Animals↗

Locating the active site for angiogenesis and cell proliferation due to fibrin fragment E with a phage epitope display library.

The plasmin-mediated lysis of fibrin present in a wound, or in chronic inflammatory disease, results in the release of fibrin degradation products. One of the two major products is fibrin fragment E, which has been shown to stimulate cell proliferation in many cell types including endothelium, fibroblasts, and smooth muscle cells, and to be angiogenic in the chick chorioallantoic membrane (CAM) system. The activity of fibrin fragment E is dependent on N-terminus thrombin action. Antibodies against fibrin E, which block the cell proliferative activity, were used to locate the active site. Phage epitope display libraries were used to identify the sequence of a peptide, which resembles a region of the N terminus structure. The equivalent synthetic peptide (WTM110) has optimal stimulatory properties at equimolar concentrations to the parent molecule. Such peptide information has therapeutic potential for both stimulating and suppressing angiogenesis and cell proliferation.

Amino Acid Sequence↗

An economic evaluation of occupational health.

There is an increasing need to evaluate the costs and benefits of an occupational health service (OHS). However, measuring benefits from an OHS is inherently difficult. Instead, an economic model can be constructed to present the minimum threshold benefits required for OHSs to be cost-effective, given what is known about costs. This model assumes that the benefits of an OHS are to maximize health and morale of employees; maximize performance and increase productivity; minimize medico-legal costs; enhance workplace safety; and reduce sickness absence. A certain distribution across these benefits can be assumed for each OHS. The overall required value of all benefits brought about by use of an OHS is in the range 158-199 Pounds per year. The plausibility of results can be assessed using known data and judgement. Despite many uncertainties it is likely that the minimum benefit thresholds will be achieved overall.

Cost-Benefit Analysis↗

Program directors' perspectives on federally funded fellowship training in primary care research.

PURPOSE: To describe the organization, models of training, and institutional impact of National Research Service Award fellowship programs in primary care research. METHOD: Survey of 25 directors of currently-funded and former training sites. RESULTS: Twenty-four program directors (96%) completed the survey. Programs allocated 39% of fellows' time to course work leading to an advanced degree or other didactic instruction, and 40% of time to the conduct of research. Collaborations with other training programs within the institution occurred at 83% of sites. Programs commonly (54%) or exclusively (42%) relied on a research model of "early research independence" in which the fellow defined an area of research interest, rather than an "apprenticeship" model in which the fellow worked in a senior investigator's research area. These programs enriched the local academic environment, but required extensive financial subsidies. The high costs of training often had adverse impacts on recruitment and other components of the training process. CONCLUSION: Research training programs in primary care often substitute acquisition of advanced degrees for early immersion in research. The "early independence" model of research differs from fellowships in the medical specialties, and requires further study to assess its effectiveness. The need to subsidize training costs poses substantial problems for the institutions that host these fellowship programs.

Attitude of Health Personnel↗

Psychiatric symptomatology in borderline and other personality disorders: dissociation and fragmentation as mediators.

This study considered the role of dissociation and personality fragmentation as psychological factors that might distinguish borderline and personality disorder (BPD) patients, and that might explain why BPD patients have higher levels of other psychiatric symptomatology than those with other personality disorders. Two groups of personality-disordered patients (personality disorders including BPD; personality disorders other than BPD) completed measures of dissociation, personality fragmentation, and psychiatric disturbance. The BPD group had higher levels of a number of aspects of psychiatric symptomatology. Those differences were mediated by aspects of dissociation. Personality fragmentation differentiated the two groups but was not related to the higher levels of other aspects of psychiatric disturbance. Treating the syndrome of BPD may depend on addressing both dissociation and personality fragmentation. In contrast, reducing the level of comorbid psychiatric disturbance in BPD is likely to be more strongly dependent on reducing levels of different aspects of dissociation. Psychotherapeutic techniques and targets for achieving such change are discussed.

Adult↗