Tracheo-oesophageal fistula caused by electrolysis of a button battery impacted in the oesophagus.
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Biomedical subjects
Publications and source records attributed to R Wall.
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The spatial distribution of blowflies of the genus Lucilia within fields in south west England was examined in 1999 and 2000. Blowflies are economically important agents of sheep myiasis in the UK and understanding local aggregation is an essential step in the development of appropriate sampling and fly control regimes. Fifty, 20 x 20 cm, non-odour-baited, sticky traps were used to catch flies, at randomized, 10 x 10 m grid co-ordinates in fields of permanent pasture. Clear aggregations were evident in all Lucilia distributions. All values of the sigma2:mean ratio were greater than 1. The catches were shown to be highly aggregated using Morisita's index of aggregation. Generalized linear modelling of binary presence/absence catch data was used to relate aggregation to microclimate and habitat. Deletion testing was used to identify significant terms in the models. In general, Lucilia blowflies were predominantly caught around the edges, in warmer and more humid areas of the field. The relationship between microhabitat and the distribution of Lucilia collected in 1999 was used as predictive model to explain the catches made in two fields in 2000. This gave a highly significant fit in one field (P = 0.001) and a relationship which approached significance in the second (P = 0.08). However, these regressions suggest that the relationships between abundance and microhabitat are complex and that 'hot spots' of blowfly catches were not necessarily found in the most extreme microclimate conditions. Nevertheless, microhabitat features do give a relatively good guide to presence or absence of Lucilia in the trap catches, thereby providing important information about the most appropriate location of traps to maximize and standardize sampling and control regimes.
This double-blind randomised study compared the tolerability of ibuprofen (up to 1.2 g daily), aspirin and paracetamol (both up to 3 g daily) for up to seven days, in patients with mild to moderate pain resulting from cold/flu symptoms or sore throat (CF/ST) (n = 2,815). The main outcome was the rate of significant adverse events (SGAE). Rates of SGAE for ibuprofen, aspirin and paracetamol were respectively 12.0%, 15.7% and 12.3%. Ibuprofen was significantly better tolerated than aspirin (p = 0.02) and had comparable tolerability with paracetamol. The latter was also true for total digestive system events and for abdominal pain and dyspepsia. In conclusion, in patients with CF/ST, ibuprofen used at over-the-counter doses is as well tolerated as paracetamol and much better tolerated than aspirin.
Phylogenetic relationships among blowfly (Calliphoridae) species of forensic importance are explored using DNA sequence data from the large sub-unit (lsu, 28S) ribosomal RNA (rRNA) gene, the study includes representatives of a range of calliphorid species commonly encountered in forensic analysis in Britain and Europe. The data presented provide a basis to define molecular markers, including the identification of highly informative intra-sequence regions, which may be of use in the identification of larvae for forensic entomology. Phylogenetic analysis of the sequences also provides new insights into the different evolutionary patterns apparent within the family Calliphoridae which, additionally, can provide a measure of the degree of genetic variation likely to be encountered within taxonomic groups of differing forensic utility.
DNA methylation has been linked to gene silencing in cancer. Primary effusion lymphoma (PEL) and myeloma are lymphoid malignancies that arise from terminally differentiated B cells. Interestingly, PEL do not express immunoglobulins or most B lineage-specific genes. The B cell-specific B29 (Igbeta/CD79b) gene is silenced in PEL and some myelomas but is expressed in other normal and malignant B cells. B29 expression was reactivated in PEL by demethylating and histone deacetylase inhibiting treatments. Bisulfite sequencing revealed two types of DNA methylation in silenced B29 promoters: at conventional CpG and at CC(A/T)GG B29 promoter sites. The pattern of methylated CpG ((m)CpG) and C(m)C(A/T)GG B29 promoter methylation observed was similar to that recently reported for epigenetic silencing of an integrated retrovirus. Methylation of C(m)C(A/T)GG sites in the B29 promoter significantly repressed in vivo transcriptional activity. Also, methylation of a central conserved C(m)CTGG B29 promoter site blocked the binding of early B cell factor. This methylated motif formed DNA-protein complexes with nuclear extracts from all cell types examined. Therefore, C(m)C(A/T)GG methylation may represent an important type of epigenetic marker on mammalian DNA that impacts transcription by altering DNA-protein complex formation.
pp52 (LSP1) is a leukocyte-specific phosphoprotein that binds the cytoskeleton and has been implicated in affecting cytoskeletal remodeling in a variety of leukocyte functions, including cell motility and chemotaxis. The expression of pp52 is restricted to leukocytes by a 549 bp tissue-specific promoter. Here, we show that promoter fragments smaller than the 549 bp pp52 promoter have activity in fibroblasts where pp52 is not normally expressed. Specifically, a truncated construct (+1 to -99) functioned as a basal promoter active in leukocytes and fibroblasts. We identified two upstream regions within the 549 bp pp52 promoter responsible for restricting pp52 promoter activity in fibroblasts. These two regions contained a silencer (pp52 NRE) and an anti-silencer (pp52 anti-NRE) with opposing activities controlling pp52 gene expression. The pp52 NRE was active in both leukocytes and fibroblasts while the pp52 anti-NRE was only active in leukocytes, thereby allowing pp52 gene transcription in leukocytes but not in fibroblasts. The pp52 NRE was localized to an 89 bp DNA segment between -324 and -235 in the 549 bp pp52 promoter and functioned as an active silencer element in a position and orientation independent manner. The pp52 anti-NRE was localized to a 33 bp segment between -383 and -350 of the 549 bp pp52 promoter and acted as an anti-silencer element against the pp52 NRE, but lacked any intrinsic enhancing activity on its own. These findings indicate that the tissue specificity of the pp52 promoter is determined by the pp52 anti-NRE anti-silencer which over-rides the general inhibitory activity of the pp52 NRE silencer.
The relationship between Psoroptes ovis infestation and the nocturnal rubbing and lying behaviour of sheep was examined as part of a longitudinal study of sheep scab. A total of 40 non-infested, scab-naïve sheep were divided into six groups of between 6 and 20 individuals and each group was subsequently penned with a single infested index case. Multilevel statistical models showed that 75% of the variation in rubbing behaviour could be explained by a combination of three variables: the age of the lesion, the size of the affected area and the time since the introduction of the index case. There were significant differences between sheep in both the baseline level of rubbing activity and the rate at which this behaviour increased over time. Increased rubbing behaviour was associated with reduced total lying times and more interrupted lying behaviour. This work has contributed to our understanding of the role of parasite-induced behavioural changes on welfare and disease transmission.
Non-retractable cell surface projections and cytoskeleton-mediated functional defects are distinguishing features of both hairy cell leukemia (HCL) and neutrophil actin dysfunction (NAD). These defects in NAD neutrophils are attributed to moderate over-expression of pp52 (LSP1), the F-actin-binding, leukocyte-specific phosphoprotein. Here we report that pp52 is similarly elevated in HCL patient PBMCs. Established HCL cell lines exhibited characteristic morphological features like those of fresh HCL cells and showed elevated pp52 levels. The excess pp52 in these HCL cell lines was selectively associated with the F-actin-rich cytoskeletal arrays in surface projections. Treatments producing radical changes in HCL cell shape also altered pp52 expression and intracellular distribution. Alpha interferon (IFNalpha, used to treat HCL) reduced pp52 levels, normalized intracellular pp52 distribution and reverted HCL cells to rounded B cell morphology. Phorbol ester stimulation rapidly generated hyper-phosphorylated pp52 isoforms which translocated from the cytoskeleton to the cytosol prior to the further elongation of surface spikes. This indicates a direct role for phosphorylation in controlling pp52 interactions with the cytoskeleton. Overall, these findings strongly suggest that elevated pp52 expression and/or selective cytoskeletal association contributes to the distinctive morphology of HCL cells.
The astigmatid mite, Psoroptes ovis (Hering) (Acari: Psoroptidae), is an obligatory ectoparasite that causes psoroptic mange in a range of domesticated animals, particularly sheep, where the clinical disease is known as sheep scab. A series of laboratory assays were used to assess the use of the fungus, Metarhizium anisopliae (Metchnikoff) (Deuteromycotina: Hyphomycetes) as a biocontrol agent for P. ovis derived from rabbits (syn. P. cuniculi). The immersion of mites in a suspension of conidia of M. anisopliae resulted in the acquisition of fatal infections. The number of mites which developed infections increased significantly with the increasing concentration of the conidial suspension to which they were exposed; 77% of mites developed infections when exposed to the highest concentration used (1 x 10(8) conidia ml(-1)). Controls developed no fungal infections. Mites allowed simply to walk across a surface which had been treated with a suspension of conidia also acquired fungal infections; the number infected was again related to the concentration of conidia present. After contact for 24 h with a surface treated with 1 x 10(8) conidia ml(-1), 73% of the mites became infected. To determine whether dead infected mites could act as sources of infection, infected cadavers were placed in chambers with live uninfected mites. The uninfected mites acquired fatal infections from the cadavers; a higher ratio of infected cadavers to uninfected mites resulted in greater transmission of infection. The time after death of the infected cadaver was also an important factor influencing the number infected, 5-day-old cadavers were the most infective and 18-day-old cadavers the least infective. The results indicate that M. anisopliae is a good candidate control agent for Psoroptes mites.
Activation of the TCL1 oncogene has been implicated in T cell leukemias/lymphomas and recently was associated with AIDS diffuse large B cell lymphomas (AIDS-DLBCL). Also, in nonmalignant lymphoid tissues, antibody staining has shown that mantle zone B cells expressed abundant Tcl1 protein, whereas germinal center (GC; centrocytes and centroblasts) B cells showed markedly reduced expression. Here, we analyze isolated B cell subsets from hyperplastic tonsil to determine a more precise pattern of Tcl1 expression with development. We also examine multiple B cell lines and B lymphoma patient samples to determine whether different tumor classes retain or alter the developmental pattern of expression. We show that TCL1 expression is not affected by Epstein-Barr virus (EBV) infection and is high in naïve B cells, reduced in GC B cells, and absent in memory B cells and plasma cells. Human herpesvirus-8 infected primary effusion lymphomas (PEL) and multiple myelomas are uniformly TCL1 negative, whereas all other transformed B cell lines tested express moderate to abundant TCL1. This observation supports the hypothesis that PEL, like myeloma, usually arise from post-GC stages of B cell development. Tcl1 protein is also detected in most naïve/GC-derived B lymphoma patient samples (23 of 27 [85%] positive), whereas most post-GC-derived B lymphomas lack expression (10 of 41 [24%] positive). These data indicate that the pattern of Tcl1 expression is distinct between naïve/GC and post-GC-derived B lymphomas (P < 0.001) and that the developmental pattern of expression is largely retained. However, post-GC-derived AIDS-DLBCL express TCL1 at a frequency equivalent to naïve/GC-derived B lymphomas in immune-competent individuals (7 of 9 [78%] positive), suggesting that TCL1 down-regulation is adversely affected by severe immune system dysfunction. These findings demonstrate that TCL1 expression in B cell lymphoma usually reflects the stage of B cell development from which they derive, except in AIDS-related lymphomas.
Populations of the blowfly, Lucilia sericata (Meigen) (Diptera: Calliphoridae), have a considerable potential for rapid increase; the lifetime reproductive output of each adult female has been estimated to be between 130 and 172 eggs. Nevertheless, in the field, absolute population densities of this species are relatively low. To account for this difference, the levels of mortality affecting the eggs, feeding and wandering larvae and pupae of L. sericata were assessed in the field and laboratory. Percentage egg hatch was dependent on relative humidity with no egg eclosion at humidities below 50%; there was no significant effect of temperature on egg hatch. On infested sheep, the mean mortality of feeding larvae was 53%, but this ranged widely from 0% to 96%. There was no effect of atmospheric temperature or humidity on the mortality of feeding larvae in vivo. In the laboratory, only 10% of wandering larvae pupariated at 10 degrees C. At above 20 degrees C pupariation was consistently almost 100%. Percentage emergence increased from 0% at 10 degrees C to about 80% between 20 and 30 degrees C. The upper lethal temperature for pupae was approached at 35 degrees C. Analysis of the predation of pupae in the field revealed a weak, but significant curvilinear relationship between temperature and proportionate mortality and a median mortality of 0.49% per 24 h exposure (interquartile range = 5.2%). There was no evidence of density dependence in pupal predation. Overall, it is estimated that pre-adult mortality accounts for losses of approximately 97% of each generation, but this figure is subject to considerable variation depending on factors such as climate, time of year and host susceptibility.
The charts of 1869 patients were reviewed for the occurrence of deep venous thrombosis (DVT) and pulmonary embolism after total hip or knee arthroplasty. Prophylaxis consisted of 3 (group 1; n=1235) or 6 (group 2; n=634) weeks low-dose warfarin, pneumatic compression boots worn by patients in the hospital, mobilization on the first postoperative day, and a clinical surveillance protocol. Venous ultrasound or ventilation/perfusion lung scintigraphy (V/Q) was performed only if patients became symptomatic. patients. Twenty-three (1.8%) patients were positive for DVT. Ventilation/perfusion lung scintigraphy was performed on 25 patients, and 5 (0.4%) patients were positive for pulmonary embolism. In group 2, 117 patients were evaluated for DVT, and 19 (3%) patients had positive results determined by ultrasound. Twenty-five patients were evaluated with V/Q and only 1 (0.16%) patient was positive for pulmonary embolism. No patient developed a fatal pulmonary embolism or postphlebitic syndrome. This prophylaxis protocol is an efficient and cost-effective method for the prevention of significant events after surgery.
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A temporary articulating antibiotic-impregnated cement spacer for use during the first stage of a two-stage revision of a total knee replacement that had failed because of infection was developed by one of us (W.M.G.). It is simply a knee prosthesis made of methylmethacrylate and antibiotics that is manufactured intraoperatively with use of instruments, medications, and supplies that are already available at most hospitals. This construct allows for motion of the knee during treatment of the infection, thereby reducing the risk of loss of motion after subsequent revision. The technique has been successfully utilized in five patients since 1999 and has now become our standard treatment method.
In vitro trials were carried out to evaluate the potential of fungal pathogens as biological control agents of parasitic mites, Psoroptes ovis (Hering) (Acari: Psoroptidae) from rabbit hosts (synonym: Psoroptes cuniculi). The fungus Hirsutella thompsonii Fisher showed no pathogenicity. Metarhizium anisopoliae (Metschinkoff), however, showed a high level of pathogenicity; 3 days after exposure to fungal conidia all mites were dead and 6 days after exposure 60% of the dead adult females, 10% of the dead adult males and 30% of the dead female nymphs had fungal hyphae protruding from their cuticular surface. There was a significant effect of conidial concentration on the number of mite cadavers that displayed fungal infection. Exposure to between 1x10(4) and 1x10(6) conidiaml(-1) resulted in 2-25% of the mites being infected. Mean infection levels were highest, 71%, when the mites were exposed to 1x10(7) conidiaml(-1). Similarly, there was a significant effect of conidial concentration on the time taken for the mites to reach 50% levels of mortality (LT(50)) The mean LT(50) value was approximately 2.7 days, when the mites were exposed to a solution of 1x10(7) and 1x10(8) conidiaml(-1) which was significantly shorter than controls exposed to 0.03% Tween-80 solution only. There was no significant effect of passaging the fungus, either once or twice, through the host on the subsequent infectivity of M. anisopliae. The potential for use of entornopathogenic fungi for the control of parasitic mites, particularly in relation to sheep, is discussed.
Chronic lymphocytic leukemia (CLL) B cells characteristically exhibit low or undetectable surface B cell receptor (BCR) and diminished responses to BCR-mediated signaling. These features suggest that CLL cells may have sustained mutations affecting one or more of the BCR proteins required for receptor surface assembly and signal transduction. Loss of expression and mutations in the critical BCR protein B29 (Igbeta, CD79b), are prevalent in CLL and could produce the hallmark features of these leukemic B cells. Because patient CLL cells are intractable to manipulation, we developed a model system to analyze B29 mutations. Jurkat T cells stably expressing micro, kappa, and mb1 efficiently assembled a functional BCR when infected with recombinant vaccinia virus bearing wild-type B29. In contrast, a B29 CLL mutant protein truncated in the transmembrane domain did not associate with mu or mb1 at the cell surface. Another B29 CLL mutant lacking the C-terminal immunoreceptor tyrosine activation motif tyrosine and distal residues brought the receptor to the surface as well as wild-type B29 but showed significant impairment in anti-IgM-stimulated signaling events including mitogen-activated protein kinase activation. These findings demonstrate that B29 mutations previously identified in CLL patients can affect BCR-dependent signaling and may contribute to the unresponsive B cell phenotype in CLL. Finally, the features of the B29 mutations in CLL predict that they may be generated by somatic hypermutation.
The insecticidal effects of the phenylpyrazole, fipronil, and a pyrethroid, beta-cyfluthrin, on larvae of the blowfly Lucilia sericata were determined in laboratory assays. When first stage larvae of L. sericata were reared on homogenized pig liver which had been treated with known amounts of test compounds, both fipronil and beta-cyfluthrin induced significant levels of mortality compared to acetone and water controls. However, fipronil was approximately 10 times more toxic than beta-cyfluthrin to L. sericata larvae following ingestion. Beta-cyfluthrin had little effect on mortality until concentrations of approximately 0.5 ppm were reached. In contrast, fipronil effected L. sericata mortality at a concentration of 0.05 ppm and 100% mortality was reached by 0.5 ppm. The lethal concentration (LC50) value for beta-cyfluthrin was 1.56 ppm as compared to 0.14 ppm for fipronil. Following contact of first and third stage larvae with cloth impregnated with known amounts of test compound, the mortality profiles of fipronil and beta-cyfluthrin were similar. At short contact times, the LC50 values for fipronil were lower than those for beta-cyfluthrin. However, at the highest contact time evaluated for the first stage larvae, 300 s, there was a reversal in this trend. The results suggest that the phenylpyrazole fipronil may represent a new potential insecticide for development against blowfly strike of sheep.