bluuebunny/crossref_metadata_2025 huggingface dataset:
Search for Mycobacterium paratuberculosis DNA in orofacial granulomatosis and oral Crohn’s disease tissue by polymerase chain reaction
Authors: Riggio M P , Gibson J , Lennon A , Wray D , MacDonald D G
Published: June 2010

Background—Although intestinal Crohn’s disease has long been suspected to have a mycobacterial cause, possible mycobacterial involvement in orofacial granulomatosis (OFG) and oral lesions of Crohn’s disease has not yet been investigated.

Aims—As the slow growingMycobacterium paratuberculosis has been implicated in the aetiology of intestinal Crohn’s disease, the potential involvement of this mycobacterial species in OFG and oral lesions of Crohn’s disease was investigated.

Patients—To attempt detection of the organism in OFG and oral Crohn’s disease tissue samples, a polymerase chain reaction (PCR) assay was used on archival formalin fixed, paraffin wax embedded oral tissue sections from 30 patients with OFG, seven with Crohn’s disease, and 12 normal controls.

Methods—The PCR assay used was based on primers targeting the 5′ region of the multicopy IS900 DNA insertion element of the M paratuberculosis genome. In order to achieve maximum sensitivity, two rounds of PCR were carried out and amplicons confirmed by Southern blot hybridisation to a digoxigenin labelled IS900 DNA probe.

Results—None of the OFG and oral lesions of Crohn’s disease samples were positive forMparatuberculosis and all normal controls were also negative.

Conclusions—These results suggest that M paratuberculosis may not be a major aetiological agent in OFG or oral Crohn’s disease lesions, although the use of paraffin wax embedded tissue as opposed to fresh tissue as a sample source could underestimate the true prevalence of the organism.
One week triple therapy for Helicobacter pylori: a multicentre comparative study
Authors: Misiewicz J J , Harris A W , Bardhan K D , Levi S , O’Morain C , Cooper B T , Kerr G D , Dixon M F , Langworthy H , Piper D ,   Lansoprazole Helicobacter Study Group
Published: June 2010

Background—Eradication ofHelicobacter pylori cures and prevents the relapse of duodenal ulceration and also results in histological resolution of chronic active gastritis.

Aim—To compare four treatment regimens lasting seven days of a proton pump inhibitor and two antibiotics in the eradication of H pylori.

Patients—Men or women with H pylori positive duodenal ulceration or gastritis, or both.

Methods—A single blind, prospectively randomised, parallel group, comparative, multicentre study. After a positive CLO test, patients underwent histology, H pylori culture, and a 13C urea breath test to confirm H pyloristatus. Treatment with one of four regimens: LAC, LAM, LCM, or OAM, where L is 30 mg of lansoprazole twice daily, A is 1 g of amoxycillin twice daily, M is 400 mg of metronidazole twice daily, C is 250 mg of clarithromycin twice daily, and O is 20 mg of omeprazole twice daily, was assigned randomly. A follow up breath test was done at least 28 days after completing treatment.

Results—H pylori eradication (intention to treat) was 104/121 (86.0%) with LAC, 87/131 (66.4%) with LAM, 103/118 (87.3%) with LCM, and 94/126 (74.6%) with OAM. There was a significant difference (p < 0.001) in the proportion of patients in whom eradication was successful between LAC and LCM when compared with LAM, but no significant difference (p = 0.15) between LAM and OAM. Metronidazole resistance before treatment was identified as a significant prognostic factor with regard to eradication of H pylori. The regimens which contained metronidazole were significantly less effective than those without metronidazole in the presence of pretreatment resistant H pylori. There was no difference among the treatment groups with regard to the incidence and severity of adverse events reported.

Conclusions—All four treatment regimens were safe and effective in eradicating H pylori in the patient population studied. LAC was the most efficacious treatment in patients with pretreatment metronidazole resistant H pylori, and was significantly better than LAM and OAM in this group of patients.
Alkyl halides, super hydrogen production and the pathogenesis of pneumatosis cystoides coli
Authors: Florin T H J
Published: June 2010

Background and aims—The colons of patients with pneumatosis cystoides coli produce excessive H2. Exposure to alkyl halides could explain this. Six consecutive patients who had pneumatosis cystoides coli while taking chloral hydrate (1–5+ g/day) are reported. Patients 2 and 3 were investigated after they had ceased chloral hydrate treatment. One produced methane, the other did not. (Pneumatosis cystoides coli patients are non-methanogenic according to the literature.) Both had overnight fasting breath H2 of less than 10 ppm. A literature review disclosed just one patient who was using chloral at the time of diagnosed pneumatosis cystoides coli, but an epidemic of the disease in workers exposed to trichloroethylene.

Methods—(i) In vitro experiments with human faeces: chloral or closely related alkyl halides were added to anaerobic faecal cultures derived from four methane-producing and three non-methanogenic human subjects. H2 and CH4gases were measured. (ii) In vivo animal experiment: chloral hydrate was added to drinking water of four Wistar rats, and faecal H2 compared with control rats.

Results—Alkyl halides increased H2 up to 900 times in methanogenic and 10 times in non-methanogenic faecal cultures. The Ki of chloral was 0.2 mM. Methanogenesis was inhibited in concert with the increase in net H2. In the rat experiment, chloral hydrate increased H2 10 times, but did not cause pneumatosis.

Conclusions—Chloral and trichloroethylene are alkyl halides chemically similar to chloroform, a potent inhibitor of H2 consumption by methanogens and acetogens. These bacteria are the most important H2-consuming species in the colon. It is postulated that exposure to these alkyl halides increases net H2 production, which sets the scene for “counterperfusion supersaturation” and the formation of gas cysts. In recent times, very low prescribing rates for chloral have caused primary pneumatosis cystoides to become extremely rare. As with primary pneumatosis, secondary pneumatosis cystoides, which occurs if there is small bowel bacterial overgrowth distal to a proximally located gut obstruction, is predicted by counterperfusion supersaturation. “Inherent unsaturation” due to metabolism of O2 is a safety factor, which could explain why gas bubbles do not form more often in tissue with high H2 tension.
Enteropathy in Zambians with HIV related diarrhoea: regression modelling of potential determinants of mucosal damage
Authors: Kelly P , Davies S E , Mandanda B , Veitch A , McPhail G , Zulu I , Drobniewski F , Fuchs D , Summerbell C , Luo N P , Pobee J O M , Farthing M J G
Published: June 2010

Background—AIDS is characterised by small intestinal mucosal damage, but its aetiopathogenesis is poorly understood. Enteric infections in Africa differ from those in northern countries, where protozoan infections have been associated with severe enteropathy in AIDS patients.

Aims—To characterise enteropathy in Zambian AIDS patients compared with local controls, and to assess relative contributions of enteric infection, nutritional impairment, and immune dysfunction.

Methods—Computer aided mucosal morphometry of small intestinal biopsy specimens from 56 HIV infected Zambians with persistent diarrhoea and 26 diarrhoea free controls, followed by regression modelling.

Results—Patients with HIV related diarrhoea had reduced villous height and increased crypt depth compared with controls. There was no difference between HIV positive and negative controls. In regression models applied to AIDS mucosal measurements, villous height and crypt depth were related to nutritional parameters and to serum soluble tumour necrosis factor receptor p55 concentration. Crypt depth was also related to lamina propria plasma cell count. Intestinal infection was found in 79%, which consisted predominantly of microsporidia in 34%, Isospora belli in 24%, andCryptosporidium parvum in 21%, but detection of these enteropathogens was not related to severity of enteropathy.

Conclusions—Nutritional and immune disturbances were associated with enteropathy, accounting for over one third of the variation in mucosal morphometric parameters.
Beta human chorionic gonadotropin concentrations in serum of patients with pancreatic adenocarcinoma
Authors: Syrigos K N , Fyssas I , Konstandoulakis M M , Harrington K J , Papadopoulos S , Milingos N , Peveretos P , Golematis B C
Published: June 2010

Background—Human chorionic gonadotropin (hCG) is normally produced and secreted by trophoblastic cells during pregnancy and from gestational trophoblastic neoplasms. It is also detected in ovarian, stomach, and colon adenocarcinomas, as well as in squamous cell carcinoma of the oesophagus. Recently, interest in its role in the pathogenesis of tumours has been enlivened after the presence of βhCG in the cell membrane of several malignant cells was shown in vitro.

Aims—To investigate the circulating concentrations of βhCG in patients with exocrine pancreatic adenocarcinoma and to examine its potential prognostic value.

Patients—Thirty six patients with exocrine pancreatic adenocarcinoma, 12 patients with chronic pancreatitis, and 21 healthy volunteers were studied.

Methods—βhCG serum concentrations were detected by the application of a radioimmunoassay technique.

Results—Fifteen of 36 patients with pancreatic adenocarcinoma and only one patient with chronic pancreatitis had detectable plasma concentrations of βhCG (p<0.01). The patients with circulating serum titres of βhCG had a worse outcome compared with the group of βhCG negative patients: the difference was statistically significant (p=0.01).

Conclusion—More than 40% of pancreatic exocrine tumours produce βhCG and its production is correlated with an adverse effect on outcome.
Mucosal subepithelial binding sites for the bacterial chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP)
Authors: Anton P , O’Connell J , O’Connell D , Whitaker L , O’Sullivan G C , Collins J K , Shanahan F
Published: June 2010

Background—The bacterial chemotactic peptideN-formyl-methionine-leucine-phenylalanine (FMLP) is produced by enteric flora and is one of the factors implicated in contributing to inflammatory bowel disease. Expression of receptors for FMLP on human phagocytes (polymorphs and monocytes) is well established, but there is conflicting evidence regarding the potential expression of FMLP receptors on other cells within the mucosa, particularly the epithelial cells.

Aims—To map FMLP receptors within intestinal mucosa using several different experimental approaches.

Methods and results—Radioligand binding assays with 3H-FMLP revealed no specific binding to primary cultured colonic enterocytes or to the cell line HT29, whereas neutrophils, as expected, exhibited specific binding with a Kd of 19 nM and approximately 2 × 104 receptors per cell. FITC labelled FMLP exhibited specific, displaceable binding on flow cytometry to neutrophils and monocytes but not to 10 gastrointestinal epithelial cell lines. Isolated lamina propria lymphocytes and peripheral blood lymphocytes exhibited no binding. To confirm the absence of receptors on epithelia, reverse transcription polymerase chain reaction for mRNA for the classic FMLP receptor was performed. While the presence of message was detected in activated peripheral blood phagocytes, it was not detected in epithelial cell lines. To exclude the possibility of FMLP binding to other receptors such as tachykinin receptors on epithelia, FITC labelled FMLP binding in tissue sections confirmed that the binding is subepithelial—that is, in the lamina propria.

Conclusion—Receptors for FMLP are subepithelial and map to the lamina propria of the gastrointestinal mucosa.
Peripheral arthropathies in inflammatory bowel disease: their articular distribution and natural history
Authors: Orchard T R , Wordsworth B P , Jewell D P
Published: June 2010

Background—Peripheral arthropathy is a well-recognised complication of inflammatory bowel disease (IBD). Little is known of its natural history, but a variety of joint involvement has been described, from large joint pauciarticular arthropathy to a rheumatoid pattern polyarthropathy.

Aims—To classify the peripheral arthropathies according to pattern of articular involvement, and study their natural history and clinical associations.

Methods—The case notes of all patients attending the Oxford IBD clinic were reviewed, and information on general disease characteristics, extraintestinal features, and arthropathy extracted. This was confirmed by direct patient interview using questionnaires at routine follow up. Patients with recorded joint swelling or effusion were classified as type 1 (pauciarticular) if less than five joints were involved and type 2 (polyarticular) if five or more were involved. Patients without evidence of swelling were classified as arthralgia.

Results—In total, 976 patients with ulcerative colitis (UC) and 483 with Crohn’s disease (CD) were reviewed. Type 1 occurred in 3.6% of patients with UC (83% acute and self-limiting) and in 6.0% of those with CD (79% self-limiting); 83% and 76%, respectively, were associated with relapsing IBD. Type 2 occurred in 2.5% of patients with UC and 4.0% of those with CD; 87% and 89%, respectively, caused persistent symptoms whereas only 29% and 42%, respectively, were associated with relapsing IBD.

Conclusion—Enteropathic peripheral arthropathy without axial involvement can be subdivided into a pauciarticular, large joint arthropathy, and a bilateral symmetrical polyarthropathy, each being distinguished by its articular distribution and natural history.
Chemokines in the gastric mucosa in Helicobacter pylori infection
Authors: Yamaoka Y , Kita M , Kodama T , Sawai N , Tanahashi T , Kashima K , Imanishi J
Published: June 2010

Background—Although chemokines have been suggested to play an important role in Helicobacter pyloriassociated gastritis, few studies have investigated the role of chemokines other than interleukin 8 (IL-8) in gastric mucosa.

Aims—To investigate the expression and production patterns of various chemokines using gastric biopsy specimens.

Methods—In 192 patients, expression patterns of C-X-C chemokines (IL-8 and growth regulated α (GROα)) and C-C chemokines (regulated on activation, normal T cell expressed and presumably secreted (RANTES), monocyte chemotactic and activating factor (MCAF), macrophage inflammatory protein 1α (MIP-1α), and MIP-1β) were examined using reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA).cagA gene was identified using PCR.

Results—H pylori infection was associated with increased rates of expression of mRNA for IL-8, GROα, RANTES, and MIP-1α and with increased levels of mucosal IL-8 and GROα. IL-8 and GROα levels correlated with the density of H pylori in both the antrum and corpus. The levels of these chemokines correlated with cellular infiltration in the antrum but not the corpus. cagA gene positive H pyloriinfection was associated with increased rates of expression of mRNA for IL-8 and GROα and with increased levels of these chemokines.

Conclusion—H pylori infection is associated with increased expression rates and production of C-X-C chemokines (IL-8 and GROα), but not with increased production of C-C chemokines. Although H pylori infection is associated with increased C-X-C chemokines in the antrum and corpus, there is a difference in the inflammatory response between these two areas of the stomach.
Somatic mutations, acetylator status, and prognosis in colorectal cancer
Authors: Hardingham J E , Butler W J , Roder D , Dobrovic A , Dymock R B , Sage R E , Roberts-Thomson I C
Published: June 2010

Background—Somatic mutations in K-ras and TP53 may be associated with both acetylator status and prognosis in colorectal cancer.

Aims—To determine whether cancers with somatic mutations are more frequent in fast acetylators and whether mutations or acetylator status influence prognosis after colorectal surgery.

Patients—One hundred consecutive subjects undergoing elective surgery for colorectal cancer.

Methods—Acetylator status was determined by polymerase chain reaction (PCR) genotyping for polymorphism in the N-acetyltransferase 2 (NAT2) gene. Mutations in K-ras(codon 12) and TP53 were determined by PCR analysis using restriction enzyme digestion and single strand conformation polymorphism respectively. Survival from colorectal cancer for up to five years after diagnosis was analysed using the Kaplan-Meier product limit estimator. Cox proportional hazards regression was used to compare survival rates after adjusting for tumour stage.

Results—Mutations in K-ras andTP53 were independent of acetylator status. By log rank test, survival was significantly reduced in subjects with TP53mutations (p=0.003) but was not significantly related to acetylator status or the presence of K-ras mutations. After adjustment for tumour stage, subjects with both TP53 and K-ras mutations had a 4.2-fold case fatality (95% confidence interval 1.5 to 11.6) when compared with that of aTP53 negative reference group.

Conclusion—The presence of both TP53and K-ras mutations in colorectal tumours is an adverse prognostic marker which is independent of tumour stage.
Arterial hypoxaemia in cirrhosis: fact or fiction?
Authors: Møller S , Hillingsø J , Christensen E , Henriksen J H
Published: June 2010

Background—Although low arterial oxygen tension (Po2) has been claimed to occur in one to two thirds of patients with cirrhosis, hypoxaemia appears to be rare in clinical practice.

Aims—To assess the frequency of arterial hypoxaemia in cirrhosis in relation to clinical and haemodynamic characteristics.

Patients—One hundred and forty two patients with cirrhosis without significant hepatic encephalopathy (grades 0–I) (41 patients in Child class A, 57 in class B, and 44 in class C) and 21 patients with hepatic encephalopathy.

Results—Mean Po2 in kPa was 11.3 in Child class A, 10.8 in class B, 10.6 in class C, and 10.6 in patients with encephalopathy (p<0.05). The fraction of patients with Po2 below the lower normal limit of 9.6 kPa was 10%, 28%, 25%, and 43%, respectively in class A, B, C, and in patients with encephalopathy (p<0.05). Oxygen saturation (So2) in these groups was respectively: 96%, 96%, 96%, and 93% (NS). So2 was below the lower limit of 92% in 0%, 9%, 7%, and 24% (p<0.05). In patients without hepatic encephalopathy, a multivariate regression analysis revealed that independent determinants of a low Po2 were a high arterial carbon dioxide tension, a low systemic vascular resistance, and a low indocyanine green clearance (p<0.0001).

Conclusion—The prevalence of arterial hypoxaemia in cirrhosis is about 22% in patients without encephalopathy, but it varies from 10–40% depending on the degree of hepatic dysfunction. Arterial hypoxaemia in patients with cirrhosis of differing severity seems lower than previously reported, and patients with severe arterial hypoxaemia are rare.
Analysis of Helicobacter pylori vacA andcagA genotypes and serum antibody profile in benign and malignant gastroduodenal diseases
Authors: Basso D , Navaglia F , Brigato L , Piva M G , Toma A , Greco E , Di Mario F , Galeotti F , Roveroni G , Corsini A , Plebani M
Published: June 2010

Background—Helicobacter pylori species comprise different strains, cytotoxic and non-cytotoxic, which can be identified on the basis of their genomic pattern.

Aims—(1) To evaluate the polymorphism of the vacA gene and to ascertain whether thecagA gene is present in patients with gastric adenocarcinoma. (2) To study the anti-H pylori antibody profile using western blotting.

Patients—Twenty one patients with gastric adenocarcinoma and 71 with H pyloriassociated benign disease (nine gastric ulcer, 29 duodenal ulcer, 25 antral gastritis, and eight duodenitis).

Methods—The polymerase chain reaction was used to verify the presence or absence ofcagA and to study the polymorphism of vacA in gastric mucosal samples obtained during endoscopy for patients with benign diseases and at surgery for patients with gastric adenocarcinoma. Fasting sera were used to assess anti-H pylori antibodies against different H pyloriantigens by western blotting.

Results—cagAgene and the allele s1 of vacAwere significantly less frequent in patients with antral gastritis (60% and 60%) compared with patients with gastric adenocarcinoma (94% and 100%) and with other non-malignant gastroduodenal diseases (93% and 87%) (χ2=16.01, p<0.001; and χ2=13.97, p<0.01). In patients with gastric adenocarcinoma, antibodies against a 74 kDa H pylori antigen were less frequently found than in patients with benign diseases.

Conclusions—H pylori infection caused bycagApositive/vacA s1 strains is a frequent finding in patients with gastric adenocarcinoma. Prospective studies are needed to confirm whether the low incidence of positive serological response to the 74 kDa H pyloriantigen in patients with gastric adenocarcinoma is important.
Flat adenomas exist in asymptomatic people: important implications for colorectal cancer screening programmes
Authors: Hart A R , Kudo S , Mackay E H , Mayberry J F , Atkin W S
Published: June 2010

Background—Flat adenomas are non-exophytic with a flat top or central depression and histologically the depth of dysplastic tissue is never more than twice the mucosal thickness. Flat adenomas frequently contain severely dysplastic tissue, and may progress rapidly through the adenoma-carcinoma sequence. Flat lesions have never been described in a British asymptomatic population.

Aims—To determine whether flat adenomas exist in an asymptomatic population participating in a large randomised controlled trial of flexible sigmoidoscopy screening.

Patients—A total of 3000 subjects (aged 55–64 years) underwent screening by flexible sigmoidoscopy.

Methods—All polyps were removed and sent for histology. The number of polyps with endoscopic and histological features of flat adenomas was recorded.

Results—Three subjects had a total of four flat lesions—that is, one per 1000 people screened. Three contained severely dysplastic tissue, one a focus of adenocarcinoma. Three of the four lesions were less than 5 mm in size and the fourth was 15 mm in diameter.

Conclusions—Flat lesions with severe dysplasia exist in the asymptomatic population. This has major implications for gastroenterologists who should be trained to identify them. Their existence is of importance to molecular biologists and epidemiologists investigating the aetiology of colorectal cancer.
Thrombelastographic changes and early rebleeding in cirrhotic patients with variceal bleeding
Authors: Chau T N , Chan Y W , Patch D , Tokunaga S , Greenslade L , Burroughs A K
Published: June 2010

Background—Routine coagulation tests do not necessarily reflect haemostasis in vivo in cirrhotic patients, particularly those who have bleeding varices. Thrombelastography (TEG) can provide a global assessment of haemostatic function from initial clot formation to clot dissolution.

Aim—To evaluate TEG changes in cirrhotic patients with variceal bleeding and their association with early rebleeding.

Patients/Methods—Twenty cirrhotic patients with active variceal bleeding had serial TEG and routine coagulation tests daily for seven days. The TEG variables before the day of rebleeding (n = 6) were compared with those of patients without rebleeding (n = 14).

Results—Baseline characteristics of the rebleeding and non-rebleeding groups were comparable apart from a higher incidence of uncontrolled infection on the day of rebleeding in the rebleeding group (p = 0.007). The patients in the rebleeding group were more hypocoagulable before the day of rebleeding as shown by longer r (42v 24 mm, p<0.001) and k(48 v 13 mm, p<0.001) and smallera (12 v 38°, p<0.001) compared with the mean of daily results of the non-rebleeding group. Routine coagulation tests, however, showed no significant differences between the two groups.

Conclusion—The results of serial TEG measurements suggest that hypocoagulability may be associated with early rebleeding in cirrhotic patients.
Pentagastrin gastroprotection against acid is related to H2 receptor activation but not acid secretion
Authors: Tanaka S , Akiba Y , Kaunitz J D
Published: June 2010

Background—Pentagastrin enhances gastric mucosal defence mechanisms against acid and protects the gastric mucosa from experimental injury.

Aims—To investigate whether this gastroprotection is mediated by histamine receptors or occurs as a secondary effect of acid secretion stimulation.

Methods—The effects of omeprazole (100 μmol/kg), ranitidine (20 mg/kg), and pyrilamine (10 mg/kg) on pentagastrin (80 μg/kg/h) induced gastroprotection against acidified aspirin injury were examined in a luminal pH controlled model. The effects of these compounds on pentagastrin enhanced gastroprotective mechanisms were investigated using intravital microscopy, in which intracellular pH of gastric surface cells (pHi), mucus gel thickness, gastric mucosal blood flow, and acid output were measured simultaneously.

Results—Pentagastrin protected rat gastric mucosa from acidified aspirin injury. This gastroprotection was abolished by ranitidine, but not omeprazole or pyrilamine. Pentagastrin induced a hyperaemic response to luminal acid challenge, increased mucus gel thickness, and elevated pHi during acid challenge. Ranitidine reversed these enhanced defence mechanisms, whereas omeprazole and pyrilamine preserved these effects.

Conclusions—These data indicate that pentagastrin associated gastroprotection and enhanced defence mechanisms against acid result mainly from activation of histamine H2 receptors, and not as an effect of the stimulation of acid secretion.
Photodynamic ablation of early cancers of the stomach by means of mTHPC and laser irradiation: preliminary clinical experience
Authors: Ell C , Gossner L , May A , Schneider H T , Hahn E G , Stolte M , Sroka R
Published: June 2010

Background—Radical surgical treatment has been the first choice for early gastric cancer, but high resolution endosonography allows in situ diagnosis with a high sensitivity and specifity and in consequence the option of local endoscopic treatment.

Aims—To evaluate photodynamic therapy (PDT) usingmeso-tetrahydroxyphenylchlorin (mTHPC) as the photosensitiser in superficial gastric cancer.

Methods—Twenty two patients with superficial early gastric cancer received mTHPC (0.075 mg/kg intravenously) and were treated 96 hours later with red light at 652 nm (20 J/cm2). Tumour response was assessed by endoscopy and extensive biopsy.

Results—Endoscopies performed two to three days after PDT showed a haemorrhagic fibrinoid necrosis of the mucosal layer. Complete remission was achieved in 16/22 (73%) patients: 13/16 (80%) with intestinal type cancer and 3/6 (50%) with a diffuse Lauren’s carcinoma. The mean follow up period was 12 months and 20 months, respectively. An average of 1.8 treatment sessions was required. Severe side effects were not observed. Seven patients had mild to moderate skin photosensivity reactions; 12 had local pain after PDT for 1–10 days.

Conclusion—PDT using mTHPC as the photosensitiser represents a safe and efficient method for topical treatment of early gastric cancer, especially of Lauren’s intestinal carcinoma. If the preliminary results can be verified in larger patient series and during long term follow up, local treatment of early cancers of the stomach by PDT could be considered as a therapeutic option for selected patients.
Multisystemic production of interleukin 10 limits the severity of acute pancreatitis in mice
Authors: Van Laethem J-L , Eskinazi R , Louis H , Rickaert F , Robberecht P , Devière J
Published: June 2010

Background—Interleukin 10 (IL-10) decreases the severity of experimental acute pancreatitis. The role of endogenous IL-10 in modulating the course of pancreatitis is currently unknown.

Aims—To examine the systemic release of IL-10 and its messenger RNA production in the pancreas, liver, and lungs and analyse the effects of IL-10 neutralisation in caerulein induced acute pancreatitis in mice.

Methods—Acute necrotising pancreatitis was induced by intraperitoneal caerulein. Serum levels of IL-10 and tumour necrosis factor (TNF), and tissue IL-10 and TNF-α gene expression were assessed. After injecting control antibody or after blocking the activity of endogenous IL-10 by a specific monoclonal antibody, the severity of acute pancreatitis was assessed in terms of serum enzyme release, histological changes, and systemic and tissue TNF production.

Results—In control conditions, serum IL-10 levels increased and correlated with the course of pancreatitis, with a maximal value eight hours after induction. Both IL-10 and TNF-α messengers showed a similar course, and were identified in the pancreas, liver, and lungs. Neutralisation of endogenous IL-10 significantly increased the severity of pancreatitis and associated lung injury as well as serum TNF protein levels (+75%) and pancreatic, pulmonary, and hepatic TNF messenger expression (+33%, +29%, +43%, respectively).

Conclusions—In this non-lethal model, systemic release of IL-10 correlates with the course of acute pancreatitis. This anti-inflammatory response parallels the release of TNF and both cytokines are produced multisystemically. Endogenous IL-10 controls TNF-α production and plays a protective role in the local and systemic consequences of the disease.
Risk factor assessment of endoscopically removed malignant colorectal polyps
Authors: Netzer P , Forster C , Biral R , Ruchti C , Neuweiler J , Stauffer E , Schönegg R , Maurer C , Hüsler J , Halter F , Schmassmann A
Published: June 2010

Background—Malignant colorectal polyps are defined as endoscopically removed polyps with cancerous tissue which has invaded the submucosa. Various histological criteria exist for managing these patients.

Aims—To determine the significance of histological findings of patients with malignant polyps.

Methods—Five pathologists reviewed the specimens of 85 patients initially diagnosed with malignant polyps. High risk malignant polyps were defined as having one of the following: incomplete polypectomy, a margin not clearly cancer-free, lymphatic or venous invasion, or grade III carcinoma. Adverse outcome was defined as residual cancer in a resection specimen and local or metastatic recurrence in the follow up period (mean 67 months).

Results—Malignant polyps were confirmed in 70 cases. In the 32 low risk malignant polyps, no adverse outcomes occurred; 16 (42%) of the 38 patients with high risk polyps had adverse outcomes (p<0.001). Independent adverse risk factors were incomplete polypectomy and a resected margin not clearly cancer-free; all other risk factors were only associated with adverse outcome when in combination.

Conclusion—As no patients with low risk malignant polyps had adverse outcomes, polypectomy alone seems sufficient for these cases. In the high risk group, surgery is recommended when either of the two independent risk factors, incomplete polypectomy or a resection margin not clearly cancer-free, is present or if there is a combination of other risk factors. As lymphatic or venous invasion or grade III cancer did not have an adverse outcome when the sole risk factor, operations in such cases should be individually assessed on the basis of surgical risk.
Bovine immunoglobulin concentrate-Clostridium difficile retains C difficile toxin neutralising activity after passage through the human stomach and small intestine
Authors: Warny M , Fatimi A , Bostwick E F , Laine D C , Lebel F , LaMont J T , Pothoulakis C , Kelly C P
Published: June 2010

Background

Bovine immunoglobulin concentrate (BIC)-Clostridium difficile is prepared from the colostrum of cows immunised againstC difficile toxins and contains high concentrations of neutralising IgG antitoxin.

Aims

To determine the proportion of BIC-C difficile which survives passage through the human stomach and small intestine.

Methods

Six volunteers with an end ileostomy took 5 g of BIC-C difficilecontaining 2.1 g of bovine IgG on four occasions: alone, with an antacid, during treatment with omeprazole, and within enteric coated capsules.

Results

When BIC-C difficile was taken alone, a mean (SEM) of 1033 (232) mg of bovine IgG was recovered in the ileal fluid representing 49% of the total ingested dose. Bovine IgG recovery was not significantly increased by antacid (636 (129) mg) or omeprazole (1052 (268) mg). The enteric capsules frequently remained intact or only partially opened in the ileal effluent and free bovine IgG levels were low in this treatment group (89 (101) mg). Bovine IgG recovery was higher in volunteers with shorter (less than two hours) mouth to ileum transit times (68% versus 36%, p<0.05). Specific bovine IgG againstC difficile toxin A was detected in ileal fluid following oral BIC. Toxin neutralising activity was also present and correlated closely with bovine IgG levels (r=0.95, p<0.001).

Conclusion

BIC-C difficile resists digestion in the human upper gastrointestinal tract and specific anti-C difficile toxin A binding and neutralising activity was retained. Passive oral immunotherapy with anti-C difficile BIC may be a useful non-antibiotic approach to the prevention and treatment ofC difficile antibiotic associated diarrhoea and colitis.
Expression of endothelin 3 by mesenchymal cells of embryonic mouse caecum
Authors: Leibl M A , Ota T , Woodward M N , Kenny S E , Lloyd D A , Vaillant C R , Edgar D H
Published: June 2010

Background

Mutations in endothelin 3 (EDN3) and endothelin B receptor (EDNRB) genes cause terminal colonic aganglionosis in mice, and mutations in these genes have also been linked to the terminal aganglionosis seen in human Hirschsprung’s disease. However, details of EDN3 expression during embryogenesis are lacking, and consequently the cellular mechanism by which EDN3 regulates innervation of the terminal gut is unclear.

Aims

To localise the expression of EDN3 and EDNRB in the embryonic mouse gut.

Methods

Expression of EDN3 and EDNRB mRNA was analysed by reverse transcription polymerase chain reaction and in situ hybridisation.

Results

High levels of EDN3 mRNA expression were restricted to mesenchymal cells of the caecum before and after the arrival of neural crest cells. In contrast, EDNRB expression along the gut displayed a time dependent pattern similar to those of the protein tyrosine kinase ret and the neural crest cell marker PGP9.5.

Conclusions

Mesenchymal cells of the caecum express high levels of EDN3 mRNA during embryogenesis and hence the production of EDN3 at the caecum is likely to act on neural crest cells as a paracrine factor necessary for subsequent innervation of the terminal gut.
Preservation of postural control of transient lower oesophageal sphincter relaxations in patients with reflux oesophagitis
Authors: Ireland A C , Dent J , Holloway R H
Published: June 2010

INTRODUCTION

In normal subjects, transient lower oesophageal sphincter relaxations (TLOSRs) and gas reflux during belching are suppressed in the supine position. Supine reflux, however, is a feature of reflux disease.

AIMS

To investigate whether postural suppression of TLOSRs and gas reflux is impaired in patients with reflux disease.

PATIENTS

Ten patients with erosive oesophagitis.

METHODS

Oesophageal manometry was performed during gastric distension with 750 ml carbon dioxide. Measurements were made for 10 minutes before and after distension in both sitting and supine positions.

RESULTS

In the sitting position gastric distension substantially increased the rate of gas reflux (median (interquartile range)), as evidenced by increases in oesophageal common cavities from 1 (0–1)/10 min to 7 (5–10)/10 min and TLOSRs from 1 (1–1.5)/10 min to 6 (2.5–8)/10 min. However, this effect was suppressed in the supine position in all but one patient (TLOSRs 0 (0)/10 min to 1 (0–4.5)/10 min, common cavities 0 (0)/10 min to 0.5 (0–2)/10 min).

CONCLUSIONS

Postural suppression of TLOSRs and gas reflux is generally preserved in reflux disease.
Hepatitis C virus (HCV) specific immune responses in anti-HCV positive patients without hepatitis C viraemia
Authors: Cramp M E , Carucci P , Rossol S , Chokshi S , Maertens G , Williams R , Naoumov N V
Published: June 2010

BACKGROUND/AIMS

Most patients infected with hepatitis C virus (HCV) develop chronic infection and persistent viraemia. The immune mechanisms responsible for resolution of viraemia remain poorly understood. HCV specific humoral and cellular immune responses in patients with and without viraemia were investigated.

METHODS

In vitro T helper (TH) lymphocyte responses to structural and non-structural HCV proteins were determined by means of proliferative response and cytokine production in 35 anti-HCV positive/HCV RNA negative patients and in 31 patients with chronic HCV infection and persistent viraemia. Humoral responses were determined by measuring HCV specific antibody quantity and specificity.

RESULTS

A TH response to two or more HCV proteins was present in 18 of 35 patients with serological viral clearance compared with just one of 31 viraemic patients (p = 0.00001). HCV specific interferon-γ production was increased only in the former group. In contrast, the antibody levels were significantly lower and directed at fewer HCV antigens in patients with undetectable HCV RNA.

CONCLUSIONS

Patients without viraemia after HCV infection frequently have strong TH lymphocyte responses of the TH1 type to multiple HCV antigens many years after the onset of infection, whereas antibody responses are less marked. These results suggest that control of HCV replication may depend on effective TH lymphocyte activation.
Prolonged large bowel transit increases serum deoxycholic acid: a risk factor for octreotide induced gallstones
Authors: Veysey M J , Thomas L A , Mallet A I , Jenkins P J , Besser G M , Wass J A H , Murphy G M , Dowling R H
Published: June 2010

BACKGROUND

Treatment of acromegaly with octreotide increases the proportion of deoxycholic acid in, and the cholesterol saturation of, bile and induces the formation of gallstones. Prolongation of intestinal transit has been proposed as the mechanism for the increase in the proportion of deoxycholic acid in bile.

AIMS

To study the effects of octreotide on intestinal transit in acromegalic patients during octreotide treatment, and to examine the relation between intestinal transit and bile acid composition in fasting serum.

METHODS

Mouth to caecum and large bowel transit times, and the proportion of deoxycholic acid in fasting serum were measured in non-acromegalic controls, acromegalic patients untreated with octreotide, acromegalics on long term octreotide, and patients with simple constipation. Intestinal transit and the proportion of deoxycholic acid were compared in acromegalic patients before and during octreotide.

RESULTS

Acromegalics untreated with octreotide had longer mouth to caecum and large bowel transit times than controls. Intestinal transit was further prolonged by chronic octreotide treatment. There were significant linear relations between large bowel transit time and the proportion of deoxycholic acid in the total, conjugated, and unconjugated fractions of fasting serum.

CONCLUSIONS

These data support the hypothesis that, by prolonging large bowel transit, octreotide increases the proportion of deoxycholic acid in fasting serum (and, by implication, in bile) and thereby the risk of gallstone formation.
Perception of and adaptation to rectal isobaric distension in patients with faecal incontinence
Authors: Siproudhis L , Bellissant E , Juguet F , Allain H , Bretagne J-F , Gosselin M
Published: June 2010

BACKGROUND

Perception of, and adaptation of the rectum to, distension probably play an important role in the maintenance of continence, but perception studies in faecal incontinence provide controversial conclusions possibly related to methodological biases. In order to better understand perception disorders, the aim of this study was to analyse anorectal adaptation to rectal isobaric distension in subjects with incontinence.

PATIENTS/METHODS

Between June 95 and December 97, 97 consecutive patients (nine men and 88 women, mean (SEM) age 55 (1) years) suffering from incontinence were evaluated and compared with 15 healthy volunteers (four men and 11 women, mean age 48 (3) years). The patients were classified into three groups according to their perception status to rectal isobaric distensions (impaired, 22; normal, 61; enhanced, 14). Anal and rectal adaptations to increasing rectal pressure were analysed using a model of rectal isobaric distension.

RESULTS

The four groups did not differ with respect to age, parity, or sex ratio. Magnitude of incontinence, prevalence of pelvic disorders, and sphincter defects were similar in the incontinent groups. When compared with healthy controls, anal pressure and rectal adaptation to distension were decreased in incontinent patients. When compared with incontinent patients with normal perception, patients with enhanced perception experienced similar rectal adaptation but had reduced anal pressure. In contrast, patients with impaired perception showed considerably decreased rectal adaptation but had similar anal pressure.

CONCLUSION

Abnormal sensations during rectal distension are observed in one third of subjects suffering from incontinence. These abnormalities may reflect hyperreactivity or neuropathological damage of the rectal wall.
Why children with inflammatory bowel disease are diagnosed at a younger age than their affected parent
Authors: Lee J C W , Bridger S , McGregor C , Macpherson A J S , Jones J E Lennard
Published: June 2010

BACKGROUND

Genetic anticipation has been proposed to explain observed age differences at diagnosis of Crohn’s disease in affected parents and offspring.

AIMS

To compare affected parent-child pairs with Crohn’s disease and ulcerative colitis with a control group of non-familial patients with inflammatory bowel disease (IBD) in order to quantify whether ascertainment bias could account for this effect.

METHODS

137 affected parent-child pairs from 96 families and 214 patients with sporadic IBD were studied. Age at onset of symptoms and diagnosis were ascertained by interview and disease confirmed from clinical records.

RESULTS

Of the 137 affected parent-child pairs, 50 had Crohn’s disease only, 51 had ulcerative colitis only, and in 36, one had Crohn’s disease and the other ulcerative colitis. The median age of parents at diagnosis was 17.5 years older, 16 years older, and 18 years older in the Crohn’s disease, ulcerative colitis, and mixed disease families respectively (p<0.001 in each case). These observed age differences were compatible with those predicted from the regression lines of years of birth against age at diagnosis for the non-familial IBD patients. No evidence was found for an effect of parental sex on age at diagnosis or disease extent in offspring.

CONCLUSIONS

There was no evidence of genetic anticipation or genomic imprinting of age at diagnosis in this sample of IBD families. Ascertainment bias is responsible for the age differences at diagnosis between affected parents and children.
Factors influencing hip protector use among community-dwelling older adults
Authors: Blalock Susan J , Demby Karen B , McCulloch Karen L , Stevens Judy A
Published: June 2010

Purpose

To obtain a better understanding of the issues that influence hip protector use among community-dwelling older adults.

Methods

The study used a longitudinal, crossover design. A convenience sample of 32 participants used four different brands of hip protectors, each for a 1-week period. Data were collected by weekly telephone interviews and a mailed questionnaire administered at baseline and follow-up. Participant perceptions regarding hip protectors were assessed using both open-ended questions and Likert-type items.

Results

The most common concerns about hip protectors mentioned in response to open-ended questions involved: discomfort, poor fit, inconvenience and unfavourable effects on appearance. Participants spontaneously mentioned at least one of these barriers in over 70% of the interviews. In contrast, participants spontaneously mentioned the protective benefits offered by hip protectors in only 16% of the interviews. The intention to continue using a particular hip protector after the study ended was associated with the number of hours the hip protector was worn during the study (p<0.01). After controlling for other variables, beliefs concerning the amount of protection that a hip protector provided was positively associated with the number of hours the hip protector was worn during the study (p<0.05) and the intention to continue using the hip protector after the study (p<0.01).

Conclusion

Study findings suggest that the use of hip protectors by community-dwelling older adults is influenced by beliefs about both barriers to use and the amount of protection provided.
The inclusion of adult vehicle occupants in matched cohort studies of child restraint effectiveness: a study of potential bias
Authors: Rice Thomas M , Anderson Craig L
Published: June 2010

Objective

To determine whether either the inclusion of adults in matched cohort studies of passenger vehicle occupants or modification of age effects by collision severity biases child restraint risk ratios biases estimate of child restraint effectiveness.

Methods

Monte Carlo data simulations were conducted to represent 10 000 collision-involved vehicles carrying a mix of children and adults. The effects of age category, adult seat belt use, child seat belt use, and child safety seat use were set to known values. Age was a modifier of the adult and child seat belt risk ratios and of the safety seat RR, and crash severity was a modifier of the age RRs. We also created an association between restraint use and collision severity to confound the restraint-death risk associations. RRs were estimated using conditional Poisson regression and compared with the true values.

Results

Estimated RRs for death were identical to the simulated values. The average child safety seat RR was 0.42 (true value 0.42), and the average seat belt RRs for children were 0.54 (true value 0.54) for those aged 0–3 years and 0.61 (true value 0.61) for those aged 4–17. Age effects were also correctly estimated, 1.69 (true value 1.69) for those aged 0–3 and 1.35 (true value 1.35) for those aged 4–17.

Conclusions

Neither the use of matched sets of adults and children nor the modification of age effects by collision severity biases estimates of child restraint effectiveness in matched cohort studies.
Incontinentia pigmenti with ultrastructurally disordered leucocytes
Authors: Minić S , Trpinac D , Obradović M , Novotny G E K , Gabriel H D , Kuhn M
Published: June 2010

Incontinentia pigmenti (IP) is a rare X-linked genodermatosis in which skin changes are combined with anomalies of other tissues, mainly of ectodermal origin. Mutations of the IKBKG gene are responsible for IP. Haematological disorders among IP patients are rare. Four female patients from a single family, with typical clinical characteristics of IP, are reported. In addition, all affected family members show a distinct haematological phenotype: hypogranular granulocytes, leucocytes with pseudoplatelets, and different anomalies of nuclei. Pseudoplatelets are a typical finding in patients with leukaemia. As there is dysfunction of the IKBKG gene in leukaemia, it is hypothesised that mis-regulation of the NEMO pathway may cause the appearance of pseudoplatelets in acute leukaemias as well as in IP. These observations suggest that IP may not be only linked to skin and organs of the ectodermal origin.