ObjectiveColonic mucosa-associated Escherichia coli are increased in Crohn's disease (CD) and colorectal cancer (CRC). They variously haemagglutinate, invade epithelial cell lines, replicate within macrophages, translocate across M (microfold) cells and damage DNA. We investigated genes responsible for these effects and their co-association in colonic mucosal isolates.DesignA fosmid library yielding 968 clones was prepared in E coli EPI300-T1 using DNA from a haemagglutinating CRC isolate, and resulting haemagglutinating clones were 454-pyrosequenced. PCR screening was performed on 281 colonic E coli isolates from inflammatory bowel disease (IBD) (35 patients), CRC (21) and controls (24; sporadic polyps or irritable bowel syndrome).Results454-Pyrosequencing of fosmids from the haemagglutinating clones (n=8) identified the afimbrial adhesin afa-1 operon. Transfection of afa-1 into E coli K-12 predictably conferred diffuse adherence plus invasion of HEp-2 and I-407 epithelial cells, and upregulation of vascular endothelial growth factor. E coli expressing afaC were common in CRC (14/21, p=0.0009) and CD (9/14, p=0.005) but not ulcerative colitis (UC; 8/21) compared with controls (4/24). E coli expressing both afaC and lpfA (relevant to M-cell translocation) were common in CD (8/14, p=0.0019) and CRC (14/21, p=0.0001), but not UC (6/21) compared with controls (2/24). E coli expressing both afaC and pks (genotoxic) were common in CRC (11/21, p=0.0015) and UC (8/21, p=0.022), but not CD (4/14) compared with controls (2/24). All isolates expressed dsbA and htrA relevant to intra-macrophage replication, and 242/281 expressed fimH encoding type-1 fimbrial adhesin.ConclusionsIBD and CRC commonly have colonic mucosal E coli that express genes that confer properties relevant to pathogenesis including M-cell translocation, angiogenesis and genotoxicity.

Ca2+- and voltage-activated K+ channels are found in many electrically excitable cells and have an important role in regulating electrical activity. Recently, the large K+ channel has been found in the baso-lateral plasma membranes of salivary gland acinar cells, where it may be important in the regulation of salt transport. Using patch-clamp methods to record single-channel currents from excised fragments of baso-lateral acinar cell membranes in combination with current recordings from isolated single acinar cells and two- and three-cell clusters, we have now for the first time characterized the K+ channels quantitatively. In pig pancreatic acini there are 25-60 K+ channels per cell with a maximal single channel conductance of about 200 pS. We have quantified the relationship between internal ionized Ca2+ concentration [( Ca2+]i) membrane potential and open-state probability (p) of the K+ channel. By comparing curves obtained from excised patches relating membrane potential to p, at different levels of [Ca2+]i, with similar curves obtained from intact cells, [Ca2+]i in resting acinar cells was found to be between 10(-8) and 10(-7) M. In microelectrode experiments acetylcholine (ACh), gastrin-cholecystokinin (CCK) as well as bombesin peptides evoked Ca2+-dependent opening of the K+ conductance pathway, resulting in membrane hyperpolarization. The large K+ channel, which is under strict dual control by internal Ca2+ and voltage, may provide a crucial link between hormone-evoked increase in internal Ca2+ concentration and the resulting NaCl-rich fluid secretion.

Summary Background Anti‐tumour necrosis factor (TNF) agents are effective in Crohn's disease but some patients lose response and require alternative biologic therapy. There are few data on comparative effectiveness of vedolizumab and ustekinumab in this setting. Aim To compare the effectiveness of ustekinumab and vedolizumab in anti‐TNF‐refractory Crohn's disease over 12 months. Methods Patients commencing ustekinumab or vedolizumab for anti‐TNF‐refractory Crohn's disease with minimum follow‐up of 12 months were included. The primary outcome measure was the difference in steroid‐free remission rates at end of induction (2 months) and at 12 months. We also assessed rates of clinical response and remission, treatment persistence, surgery and adverse events in both groups. We performed logistic regression analysis to assess factors associated with steroid‐free remission and clinical response and remission. Results We included 85 patients commencing vedolizumab and 45 commencing ustekinumab. In an unadjusted model, rates of steroid‐free and clinical remission were significantly higher among ustekinumab‐treated patients. After adjusting for confounders, steroid‐free remission was higher among ustekinumab‐treated patients at 2 months (odds ratio, OR 2.79, 95% confidence interval, CI 1.06‐7.39, P = 0.038) and 12 months (OR 2.01, 95% CI 0.89‐4.56, P = 0.095). More patients treated with ustekinumab remained on therapy at the end of 12 months (84.4% vs 61.5%, P = 0.007). Conclusions Ustekinumab appeared more effective in treating anti‐TNF‐refractory Crohn's disease and more patients persisted with therapy.

For many years it has been recognized that seemingly benign neck cysts may contain carcinoma. The true incidence is unknown. This paper investigated nine out of 270 patients presenting with a neck mass — which proved to contain a squamous carcinoma. Records (from a 30-year period) of over 3400 patients with squamous carcinoma of the head and neck, were examined. The histology slides were reviewed, the number of cystic lesions was noted and also the clinical outcome. Out of the 270 patients nine presented with a cystic lesion and these were studied. Six cystic lesions were originally diagnosed as branchial cysts although the youngest age was 39 years. All patients underwent a simple excision.In six cases the tonsil was the primary site, in one the primary was in the base of tongue and in two the primary remained occult. One-third of the patients had died of their disease by the time this report was written and the maximum follow-up time for the remaining patients was 18 months. Therefore 16 per cent of branchial cysts in this series represented metastases from squamous cell carcinoma.At the Royal Liverpool University Hospital only 25 patients had branchial cysts excised between 1988 and 1993: out of these only four contained squamous carcinoma.In patients over 40 years of age panendoscopy and ipsilateral tonsillectomy is mandatory prior to cyst excision.

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