An alternating pressure trolley mattress in A&E.
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Beds↗
Biomedical subjects
D Gray
Publications and source records attributed to D Gray.
Epidurals and fever: association or cause?
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Analgesia, Epidural↗
Determination of HLA-A*02 antigen status in Hodgkin's disease and analysis of an HLA-A*02-restricted epitope of the Epstein-Barr virus LMP-2 protein.
There is good evidence for an association between Epstein-Barr virus (EBV) and Hodgkin's disease (HD). In approximately one-third of cases, the EBV genome is detectable in Reed-Sternberg (RS) cells and there is expression of the viral nuclear antigen EBNA-1 and the latent membrane protein LMP-1. Expression of LMP-2 has been demonstrated at the mRNA level, and it is presumed that the protein is expressed alongside LMP-1. The LMP-2 protein is known to contain an epitope presented to cytotoxic T-cells which is restricted through the HLA class I antigen A*0201 in healthy seropositive individuals. Since most HLA-A*02-positive Caucasians are HLA-A*0201-positive, it was hypothesized that HLA-A*02-positive individuals would be under-represented among Caucasians with EBV-associated HD. HLA-A*02 status was determined, using flow cytometry and/or the polymerase chain reaction, for 276 individuals including 176 cases of HD. There was no significant difference between the frequency of HLA-A*02 positivity in HD cases and controls, and between EBV-associated and non-associated cases of HD. The A*02 alleles of 14 cases of EBV-associated HD were further subtyped using nested PCR; all except one case were found to be A*0201-positive. We therefore investigated whether there was any evidence for mutation of the epitope representing amino acids 426-434 of LMP-2a which is restricted through HLA-A*0201. In 10/11 cases the nucleotide sequence encoding this epitope was identical to the published sequence; in the remaining case there was a mutation which would not be expected to alter the conformation of the epitope. Overall, our data suggest that other mechanisms of immune escape must be operative in EBV-associated HD.
Adolescent↗
Inpatient deaths from acute myocardial infarction, 1982-92: analysis of data in the Nottingham heart attack register.
OBJECTIVE: To assess longitudinal trends in admissions, management, and inpatient mortality from acute myocardial infarction over 10 years. DESIGN: Retrospective analysis based on the Nottingham heart attack register. SETTING: Two district general hospitals serving a defined urban and rural population. SUBJECTS: All patients admitted with a confirmed acute myocardial infarction during 1982-4 and 1989-92 (excluding 1991, when data were not collected). MAIN OUTCOME MEASURES: Numbers of patients, background characteristics, time from onset of symptoms to admission, ward of admission, treatment, and inpatient mortality. RESULTS: Admissions with acute myocardial infarction increased from 719 cases in 1982 to 960 in 1992. The mean age increased from 62.1 years to 66.6 years (P < 0.001), the duration of stay fell from 8.7 days to 7.2 days (P < 0.001), and the proportion of patients aged 75 years and over admitted to a coronary care unit increased significantly from 29.1% to 61.2%. A higher proportion of patients were admitted to hospital within 6 hours of onset of their symptoms in 1989-92 than in 1982-4, but 15% were still admitted after the time window for thrombolysis. Use of beta blockers increased threefold between 1982 and 1992, aspirin was used in over 70% of patients after 1989, and thrombolytic use increased 1.3-fold between 1989 and 1992. Age and sex adjusted odds ratios for inpatient mortality remained unchanged over the study period. CONCLUSIONS: Despite an increasing uptake of the "proved" treatments, inpatient mortality from myocardial infarction did not change between 1982 and 1992.
Age Factors↗
Observations on memory B-cell development.
We dissect in this article the roles of CD40 and its ligand in memory B-cell formation. Our data indicate that CD40 ligation does not directly lead to GC formation but it plays an indirect role related to maturation of helper T cells; signalling is bidirectional, to B cells, via CD40, upregulating cytokine receptor expression and to T cells, via CD40L, causing secretion of cytokines necessary for GC initiation. Later in the GC, CD40 selects mutated B cells for entry into the memory pool. This second T-cell-mediated CD40 ligation has consequences distinct from the first (rescue versus proliferation) that arise from rewiring of CD40 signal transduction pathways.
Animals↗
Healthy or druggy? Self-image, ideal image and smoking behaviour among young people.
Recent research indicates that there is an important, though complex, relationship between the social image of smoking and young people's self- and aspirational images. This study explored how young people see themselves (self-image), how they would like to be (ideal image), and whether these differ according to age, gender and smoking status. Focus groups were used to elicit attributes which young people use to describe smoking and non-smoking images taken from fashion pages in youth magazines. These attributes were incorporated into a self-completion questionnaire which was administered to 897 young people from three age groups (12-13 years, 15-16 years and 18-19 years). The respondents rated their self- and ideal images on each of these attributes. Overall, there were few differences between the rank order of attributes by age, sex or smoking status. However, there were differences in the trait scores, with males and smokers tending to rate themselves more positively. The two traits which most clearly differentiated smokers and non-smokers were druggy/takes drugs (self- and ideal image) and healthy (self-image). It appears that smokers in general, and male smokers in particular, embraced certain dimensions of self- and aspirational image of which druggy, tough and tarty are signifiers. In contrast, the differences between female smokers and non-smokers were less consistent and differed with age. The implications for health promotion are discussed.
Adolescent↗
The use of tobacco, alcohol and other drugs by young Aboriginal people in Albany, Western Australia.
This paper describes patterns of tobacco, alcohol and other drug use among Aboriginal people aged 8 to 17 years in the town of Albany, Western Australia. Of a total of 110 young Aboriginal people residing in the town at the time of the study, 105 were interviewed by two trained Aboriginal research assistants using interview schedules that included questions based on the national guidelines for the comparability of studies of drug use among young people. The most commonly used drugs were tobacco, alcohol and cannabis. Use of other substances was usually experimental, The majority (57 per cent) of this population had not used any drugs, 13 per cent made some use of alcohol and/or tobacco, 15 percent were polydrug users, and 15 per cent were frequent polydrug users. Use of drugs increased with age: 48 per cent of those aged 15 to 17 were frequent polydrug users. Tobacco consumption was greater and alcohol use less than that reported among Western Australian secondary school children of comparable age.
Adolescent↗
Viral immunity: interferons jog old T-cell memories.
The mechanism by which life-long immunity to viruses persists is a matter of some controversy. Interferons induced by subsequent unrelated viral infections may propagate existing memory T cells non-specifically.
Animals↗
Immunological memory and protective immunity: understanding their relation.
The immune system can remember, sometimes for a lifetime, the identity of a pathogen. Understanding how this is accomplished has fascinated immunologists and microbiologists for many years, but there is still considerable debate regarding the mechanisms by which long-term immunity is maintained. Some of the controversy stems from a failure to distinguish between effector and memory cells and to define their roles in conferring protection against disease. Here the current understanding of the cellular basis of immune memory is reviewed and the relative contributions made to protective immunity by memory and effector T and B cells are examined.
Animals↗
B cells solicit their own help from T cells.
We have made use of T cell receptor (TCR)-transgenic mice with CD4+ T cells expressing a receptor specific for the self-antigen C5 (fifth component of complement) to study the role of different antigen-presenting cells in the determination of CD4+ T cell effector type. Contact of T cells from C5 TCR-transgenic mice with C5 protein or C5 peptide in vivo or in vitro induces biased T helper cell (Th) 1 type responses resulting in exclusive production of high levels of interferon gamma and interleukin (IL) 2. Transgenic mice, in contrast to nontransgenic littermates, do not generate an antibody response to C5. We show in this paper that B cell presentation in vitro induces a switch to the Th2 subset indicated by production of IL-4, and targetting C5 to B cells in vivo results in the generation of C5-specific antibodies.
Animals↗
Somatic mutation of immunoglobulin V genes in vitro.
The molecular mechanism behind affinity maturation is the introduction of point mutations in immunoglobulin (Ig) V genes, followed by the selective proliferation of B cells expressing mutants with increased affinity for antigen. An in vitro culture system was developed in which somatic hypermutation of Ig V genes was sustained in primed B cells. Cognate T cell help and cross-linking of the surface Ig were required, whereas the addition of lipopolysaccharide or a CD40 ligand to drive proliferation was insufficient. This system should facilitate understanding of the molecular and cellular mechanisms that regulate somatic mutation and B cell selection.
Amino Acid Sequence↗
CD40-mediated regulation of interleukin-4 signaling pathways in B lymphocytes.
The importance of cytokines in controlling immunoglobulin isotype switching is well known. Given the defect in switching to IgG, IgA and IgE isotypes in mice and humans that carry mutations in the CD40 and CD40 ligand genes, we have investigated the role of CD40 ligation in controlling B cell responses to interleukin (IL)-4. We have found that CD40-mediated signals cause a fivefold upregulation of IL-4 receptor (IL-4R) on the B cell surface and that this is associated with a 100-1000-fold increase in the cells' responsiveness to the cytokine. While we found no evidence of increased affinity or structural change of the receptor, we do find that prestimulation of B cells with anti-CD40 antibodies brings about several changes in the IL-4 signaling pathways. Subsequent delivery of IL-4 to CD40-prestimulated cells provokes intracellular signals distinct from those induced in resting B cells in response to IL-4. While resting B cells phosphorylate Jak3 kinase shortly after IL-4 activation, cells pre-incubated with anti-CD40 exhibit active dephosphorylation of this molecule and phosphorylation of proteins of around 45 kDa upon addition of IL-4. The common gamma chain, Jak3 and Jak1 can all be immunoprecipitated in normal amounts with the IL-4R chain after CD40 prestimulation. We show that the observed dephosphorylation of Jak3 may be due to a stable association with the src-homology protein tyrosine phosphatase SH-PTP2. In contrast, the enzyme appears to be inactive and to dissociate very quickly from the signaling complex in cells that are stimulated with IL-4 alone.
Animals↗
Regulation of B cell growth and differentiation via CD21 and CD40.
Stimulation in vitro of murine splenic B cells by lipopolysaccharide, anti-kappa Sepharose, anti-CD40 or allo-reactive T helper cells all up-regulated CD21 and CD23 surface expression. Neither anti-CD21 nor anti-CD23 antibodies induced B cell growth or differentiation when added in soluble form or coupled to Sepharose. However, anti-CD40-stimulated B cells showed increased proliferation in the presence of anti-CD21 antibodies coupled to Sepharose; co-stimulation via CD21 also induced differentiation to immunoglobulin secretion in a fraction of anti-CD40-stimulated B cells. Furthermore, anti-CD40 antibodies inhibited differentiation to immunoglobulin secretion induced by lipopolysaccharide and, hence, appears to be a dominant negative signal for B cell differentiation.
Animals↗
Commentaries on Landau's "The prospects of a harm reduction approach among indigenous people in Canada".
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Comment↗
In vitro immunization of naive mouse B cells: establishment of IgM secreting hybridomas specific for souble protein or hapten from B cells cultured on CD40 ligand transfected mouse fibroblasts.
CD40 has been shown to play an important role in the regulation of B cell survival, proliferation and Ig class switching. The natural partner for CD40 is CD40 ligand, gp 39, which is transiently expressed on activated T cells. In vitro, CD40 ligation leads to polyclonal B cell proliferation and, in the presence of appropriate cytokines, to the secretion of Ig of various isotypes. In the present study we show that naive B cells cultured in vitro on CD40L-transfected mouse fibroblasts in the presence of two different soluble antigens (beta-galactosidase and phenyloxazolone coupled to ovalbumin) can be specifically immunized as shown by direct single cell Elispot assays or after establishment of B cell hybridomas. However, under the conditions of in vitro immunization used, all hybridomas analysed produced specific IgM antibodies only and we failed to detect cells that had switched to other isotypes. The data suggests that CD40 ligation can be used for efficient in vitro immunization against soluble antigens for IgM production but that CD40 signals even in conjunction with cytokines are insufficient to induce high rate switching.
Animals↗
B-T lymphocyte interactions in the generation and survival of memory cells.
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Animals↗
Disaster plan education: how we made and tested a video.
OBJECTIVE: To describe the making and testing of a 40 minute video to educate staff about a hospitals disaster plan. METHODS: A disaster scene was created and 30 staff volunteers took part in the simulation of a major accident. The simulation was used to explain and demonstrate disaster triage. A multiple choice questionnaire was used to compare information recall in a group who had seen the video and a group who had read the written plan. RESULTS: Large numbers of hospital staff voluntarily watched the video. The video group scored significantly higher than the reading group (P < 0.01), with mean scores of 72% and 45% respectively. CONCLUSIONS: Videos have an impact lacking in written disaster plans and improve recall of emergency procedures.
Disaster Planning↗
Laparoscopic versus open appendectomy: a prospective randomized trial of 81 patients.
OBJECTIVE: To compare the efficacy of laparoscopic appendectomy (LA) and open appendectomy (OA) in the treatment of acute appendicitis. DESIGN: A prospective randomized trial. SETTING: A university teaching hospital. PATIENTS: Eighty-one patients with a diagnosis of acute appendicitis were prospectively randomized to undergo either LA or OA. The two groups were matched for age and sex. INTERVENTIONS: LA or OA. MAIN OUTCOME MEASURES: Number of days in hospital and time to full recovery. RESULTS: The mean hospital stay for LA was 3.23 days compared with 3.03 days for OA (p < 0.001). The mean number of narcotic injections required for patients in the LA group was 4.05 compared with 5.58 for patients in the OA group (p < 0.001). The mean time to complete recovery for patients in the LA group was 9.0 days compared with 16.2 days for patients in the OA group (p < 0.001). The mean operative time for LA was 73.8 minutes compared with 45.0 minutes for OA (p < 0.001). Three patients in the LA group had intra-abdominal abscesses (p > 0.25). No significant difference in wound infection rates was demonstrated (p > 0.05). Similarly, pain scores at 7 and 28 days showed no significant difference (p > 0.05). CONCLUSIONS: With LA significantly fewer narcotic injections are required and there is a more rapid return to normal activities. LA takes longer to perform and was associated with three intra-abdominal abscesses. In cases of simple acute appendicitis the hospital stay for LA is significantly shorter.
Adult↗