Background: Primary hyperparathyroidism (PH) is a common endocrine condition, with an estimated prevalence of 7 in 1,000 in the general population. In most patients, a single, benign adenoma is responsible for the disease, but in a very small percentage of patients multiple gland adenoma (two gland mostly but very rarely three gland) is evident.
Background: Oesophageal carcinoma accounts for approximately 7000 deaths p.a. in the UK.The majority of cases present with advanced disease with overall 5 year survival less than 12%; in those receiving palliative treatment the median survival is 3-6 months.Aims: To establish the immediate complication rate associated with all methods of palliation used in the management of malignant dysphagia.Whilst these techniques do not affect survival, avoidance of iatrogenic morbidity and mortality is highly desirable.Methods: Data were retrospectively gathered from the West Midlands oesophageal database (1992)(1993)(1994)(1995)(1996).All cases that received palliative therapy were included.
Abstract β1 integrins play a crucial role in supporting tumor cell attachment to and invasion into the extracellular matrix. Endotoxin/LPS introduced by surgery has been shown to enhance tumor metastasis in a murine model. Here we show the direct effect of LPS on tumor cell adhesion and invasion in extracellular matrix proteins through a β1 integrin-dependent pathway. The human colorectal tumor cell lines SW480 and SW620 constitutively expressed high levels of the β1 subunit, whereas various low levels of α1, α2, α4, and α6 expression were detected. SW480 and SW620 did not express membrane-bound CD14; however, LPS in the presence of soluble CD14 (sCD14) significantly up-regulated β1 integrin expression; enhanced tumor cell attachment to fibronectin, collagen I, and laminin; and strongly promoted tumor cell invasion through the Matrigel. Anti-β1 blocking mAbs (4B4 and 6S6) abrogated LPS- plus sCD14-induced tumor cell adhesion and invasion. Furthermore, LPS, when combined with sCD14, resulted in NF-κB activation in both SW480 and SW620 cells. Inhibition of the NF-κB pathway significantly attenuated LPS-induced up-regulation of β1 integrin expression and prevented tumor cell adhesion and invasion. These results provide direct evidence that although SW480 and SW620 cells do not express membrane-bound CD14, LPS in the presence of sCD14 can activate NF-κB, up-regulate β1 integrin expression, and subsequently promote tumor cell adhesion and invasion. Moreover, LPS-induced tumor cell attachment to and invasion through extracellular matrix proteins is β1 subunit-dependent.
Background: Prophylactic negative pressure wound therapy (NPWT) is a promising technology for preventing wound complications in closed surgical incisions. We aimed to evaluate the association of prophylactic NPWT with rates of wound complications for closed incisions in breast surgery and compare them with those of conventional dressings. Methods: This meta-analysis was conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A systematic search of Medline, Embase, CINAHL and Cochrane Library was undertaken for articles in which prophylactic application of a single use NPWT device was compared with standard dressings for total wound complications, surgical site infection (SSI), seroma, haematoma, wound dehiscence and necrosis. Results: Seven studies met the inclusion criteria for analysis, reporting on 1,500 breast incisions in 904 patients. On random effects analysis, NPWT was associated with a significantly lower rate of total wound complications [pooled odds ratio (OR), 0.36; 95% CI, 0.19–069; P=0.002], SSI (pooled OR, 0.45; 95% CI, 0.24–0.86; P=0.015), seroma (pooled OR, 0.28; 95% CI, 0.13–0.59; P=0.001), wound dehiscence (pooled OR, 0.49; 95% CI, 0.32–0.72; P=0.000) and wound necrosis (pooled OR, 0.38; 95% CI, 0.19–0.78; P=0.008). There was no significant difference in rates of haematoma (pooled OR, 0.8; 95% CI, 0.19–3.2; P=0.75). Significant heterogeneity existed amongst included studies for rates of total wound complications but not for the other endpoints. Conclusions: Compared with standard dressings, prophylactic application of NPWT significantly reduced the rate of total wound complications, SSI, seroma, wound dehiscence and wound necrosis when applied to closed incisions on the breast.
Candida albicans infection is common in immunocompromised patients. The role of fixed tissue macrophages (M phi), including Kupffer cells (KC) and peritoneal macrophages (PM phi), in host defense against C. albicans is unclear. This study examined murine M phi candidacidal mechanisms and evaluated the in vitro role of the macrophage-activating factor IFN-gamma in augmenting these mechanisms. The effect of in vivo administration of IFN-gamma on survival after lethal C. albicans challenge in the murine system was also assessed. Percent PM phi and KC ingestion of C. albicans were similar. Prior opsonization of Candida increased the percentage of M phi ingestion of this pathogen. PM phi and KC phagocytic function was similar for both nonopsonized and opsonized C. albicans, but KC demonstrated markedly decreased ability to kill this pathogen (O2-, Candida killing). IFN-gamma enhanced KC and PM phi candidacidal activity. PM phi and KC Ag presentation was increased in early Candida infection, but diminished in established infection, when the majority of animals died. C. albicans failed to elicit significant amounts of either IL-1 or TNF compared with LPS stimulation of PM phi and KC in vitro. IFN-gamma treatment in vivo was associated with significantly improved survival (p < 0.01).
ST2, a member of the Toll/IL-1R superfamily, negatively regulates both TLR2 and TLR4 signaling. In this study, we report that ST2-deficient mice were more susceptible to polymicrobial sepsis than their wild-type littermates, with increased production of proinflammatory cytokines. Bacterial clearance from the circulation and visceral organs following polymicrobial infection was markedly impaired in ST2-deficient mice. This was associated with substantially reduced uptake, phagocytosis, and intracellular killing of both Gram-positive and Gram-negative bacteria by ST2-deficient phagocytes. Consistent with a reduced antimicrobial response, phagocytes lacking ST2 displayed a defect in bactericidal activity in response to bacterial challenges with severely impaired phagosome maturation and NOX2 function. Thus, ST2-deficient mice exhibit an increased susceptibility to polymicrobial infection with impaired bacterial clearance, which is associated with defects in phagosome maturation and NOX2-derived production of reactive oxygen species characterized in ST2-deficient phagocytes.
The toll-like receptor (TLR) system constitutes a pylogenetically ancient, evolutionary conserved, archetypal pattern recognition system, which underpins pathogen recognition by and activation of the immune system. Toll-like receptor agonists have long been used as immunoadjuvants in anti cancer immunotherapy. However, TLRs are increasingly implicated in human disease pathogenesis and an expanding body of both clinical and experimental evidence suggests that the neoplastic process may subvert TLR signalling pathways to advance cancer progression. Recent discoveries in the TLR system open a multitude of potential therapeutic avenues. Extrapolation of such TLR system manipulations to a clinical oncological setting demands care to prevent potentially deleterious activation of TLR-mediated survival pathways. Thus, the TLR system is a double-edge sword, which needs to be carefully wielded in the setting of neoplastic disease.
Thyroid drains following thyroid surgery are routinely used despite minimal supportive evidence. Our aim in this study is to determine the impact of routine open drainage of the thyroid bed postoperatively on ultrasound-determined fluid accumulation at 24 hours. We conducted a prospective randomised clinical trial on patients undergoing thyroid surgery. Patients were randomly assigned to a drain group (n = 49) or a no-drain group (n = 44) immediately prior to wound closure. Patients underwent a neck ultrasound on day 1 and day 2 postoperatively. After surgery, we evaluated visual analogue scale pain scores, postoperative analgesic requirements, self-reported scar satisfaction at 6 weeks and complications. There was significantly less mean fluid accumulated in the drain group on both day 1, 16.4 versus 25.1 ml (P-value = 0.005), and day 2, 18.4 versus 25.7 ml (P-value = 0.026), following surgery. We found no significant differences between the groups with regard to length of stay, scar satisfaction, visual analogue scale pain score and analgesic requirements. There were four versus one wound infections in the drain versus no-drain groups. This finding was not statistically significant (P = 0.154). No life-threatening bleeds occurred in either group. Fluid accumulation after thyroid surgery was significantly lessened by drainage. However, this study did not show any clinical benefit associated with this finding in the nonemergent setting. Drains themselves showed a trend indicating that they may augment infection rates. The results of this study suggest that the frequency of acute life-threatening bleeds remains extremely low following abandoning drains. We advocate abandoning routine use of thyroid drains. ISRCTN94715414
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