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The skin microbiome exists in dynamic equilibrium with the host, but when the skin is compromised, bacteria can colonize the wound and impair wound healing. Thus, the interplay between normal skin microbial interactions versus pathogenic microbial interactions in wound repair is important. Bacteria are recognized by innate host pattern recognition receptors, and we previously showed an important role for the pattern recognition receptor NOD2 in skin wound repair. NOD2 is implicated in changes in the composition of the intestinal microbiota in Crohn's disease, but its role on skin microbiota is unknown. Nod2-deficient (Nod2-/-) mice had an inherently altered skin microbiome compared with wild-type controls. Furthermore, we found that Nod2-/- skin microbiome dominated and caused impaired healing, shown in cross-fostering experiments of wild-type pups with Nod2-/- pups, which then acquired altered cutaneous bacteria and delayed healing. High-throughput sequencing and quantitative real-time PCR showed a significant compositional shift, specifically in the genus Pseudomonas in Nod2-/- mice. To confirm whether Pseudomonas species directly impair wound healing, wild-type mice were infected with Pseudomonas aeruginosa biofilms and, akin to Nod2-/- mice, were found to exhibit a significant delay in wound repair. Collectively, these studies show the importance of the microbial communities in skin wound healing outcome.
This retrospective study reviews the complications which occurred in 257 patients who had supraduodenal exploration of the common bile duct in one hospital during a 15-year period. One hundred and eighteen patients (46 per cent) developed complications: septic and cardiorespiratory complications were most common, occurring in 19.5 per cent and 16.7 per cent of patients respectively. Postoperative retained stones were detected in 37 patients (14 per cent), causing complications in 54 per cent. Peroperative postexploratory cholangiography did not significantly reduce the incidence of this problem. None of the 12 patients who had postexploratory choledochoscopy had retained stones. Five patients (1.9 per cent) died, three of whom had duct procedures in addition to supraduodenal exploration and two of whom had retained stones. It is concluded that common bile duct exploration has a high associated morbidity, particularly due to sepsis and retained stones.
Abstract Background and objectives Arginase1 (ARG1) is an enzyme expressed by keratinocytes that drives several functions linked to skin barrier function. However, the mechanisms underpinning keratinocyte ARG1 function in barrier homeostasis is not fully elucidated. Atopic dermatitis (AD) is linked to impaired skin barrier via altered keratinocyte differentiation and susceptibility to infection. Therefore, we investigated the role of ARG1 in keratinocyte differentiation and anti-microbial responses. Methods In vitro 2D differentiation assays using ARG knockdown or ARG inhibited keratinocytes were used to explore the function of ARG1 in keratinocyte differentiation and barrier formation. ARG1 was also assessed in an ex vivo model of AD. Results ARG1 was strongly expressed in the apical layers of human skin, corresponding with high ARG1 expression in late differentiated keratinocytes. ARG was downregulated in an ex vivo AD model relative to controls, suggesting altered ARG1 is clinically relevant. ARG1 inhibition in keratinocytes led to a significant decrease in late differentiation markers Filaggrin (FLG), Involucrin (IVL), and Loricrin (LOR) and significant downregulation of the Anti-microbial Peptides (AMPs), Lipocalin 2 (LCN2), Kallikreins (KLKs) and Small Proline Rich Proteins (SPRRs). ARG forms part of the urea cycle and the action of ARG on L- arginine causes the production of L-ornithine and urea. L-ornithine, in turn, is catabolised for putrescine (Put) production. Supplementation with ARG products, Put and urea, could rescue late keratinocyte differentiation and AMP expression in ARG deficient cells. Conclusions ARG1 activity plays a major role in keratinocyte differentiation and AMP production. ARG1 is downregulated in AD, but in cell systems is amenable to rescue by ARG1 downstream products Put and urea. Manipulation of the ARG1 pathway may, therefore, have potential to be used for the management of skin conditions such as AD.
To compare the success rates of external dacryocystorhinostomy (EXT-DCR) with 5-fluorouracil (5-FU) augmented endonasal laser dacryocystorhinostomy (ENL-DCR) and to record the complications associated with 5-FU augmented ENL-DCR MATERIALS AND METHODS: This was a retrospective non-randomised study. Forty-one patients with primary acquired nasolacrimal duct obstruction underwent an EXT-DCR (19 patients) or an ENL-DCR (22 patients) over a 3-year period. A Holmium YAG laser (Ho:YAG) was used in the latter group of patients. Silicone tubes intubated in all patients were removed at three months. 5-FU was applied intraoperatively at the site of the ostium in the ENL-DCR patients. The median follow-up was 12 months (range 3-24 months) for the ENL-DCR group and 22 months (range 6-28 months) for the EXT-DCR group. The patency of the lacrimal system and the severity of epiphora were assessed at a final-review.The median age of the EXT-DCR group was 77 years (range 53-87) and that of the ENL-DCR group was 71 years (range 23 to 84). There were 12 female patients in the former group and 19 in the latter. The percentage of success in the EXT-DCR group was 94.7% (95% confidence interval (CI) = 75.4-99.1) = ), and 63.6% in the ENL-DCR group (95% CI= 43.0-80.3). The confidence interval for the difference of 31.1% was 5.6-52.2. There was a statistically significant difference between the two groups, p=0.024 (Fisher exact test).These data suggest that EXT-DCR provides better results than 5-FU augmented ENL-DCR. However, ENL-DCR is the procedure of choice in certain circumstances such as in elderly, frail or medically unfit patients. Our results of 5-FU augmented ENL-DCR compare favourably with other published series.
Infectious mononucleosis causing upper airway obstruction due to tonsillar disease and associated lymphadenopathy in adolescents is well recognized. However, infection with Epstein-Barr virus (EBV) in a young child of six months is rare. The authors present such a case, with massive swelling of the retropharyngeal lymph nodes, that has not been published previously. The patient presented to this department with a short history of an upper respiratory tract infection and mild upper airway obstruction. On examination there was a massive enlargement of the retropharyngeal space with a compromised airway. This was confirmed on X-ray. She made an uneventful recovery following incision and drainage and a short period of endotracheal intubation. Because of the presence of retropharyngeal lymphoid tissue in infancy an alternative site of upper airway obstruction may occur here in this age group.
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