bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased serum trypsinogen 2 and trypsin 2-α1antitrypsin complex values identify endoscopic retrograde cholangiopancreatography induced pancreatitis with high accuracy
Authors: Kemppainen E , Hedström J , Puolakkainen P , Halttunen J , Sainio V , Haapiainen R , Kivilaakso E , Stenman U-H
Published: June 2010

Aims—To evaluate the clinical utility of two new tests for serum trypsinogen 2 and trypsin 2-α1antitrypsin complex (trypsin 2-AAT) in diagnosing and assessing the severity of acute pancreatitis (AP) induced by endoscopic retrograde cholangiopancreatography (ERCP).

Patients—Three hundred and eight consecutive patients undergoing ERCP at Helsinki University Central Hospital in 1994 and 1995.

Methods—Patients were followed prospectively for pancreatitis and clinical outcome. They were tested for serum trypsinogen 2, trypsin 2-AAT, and amylase in samples obtained before and one, six, and 24 hours after ERCP.

Results—Pancreatitis developed in 31 patients (10%). Their median serum trypsinogen 2 increased 26-fold to 1401 μg/l at six hours after the procedure and trypsin 2-AAT showed an 11-fold increase to 88 μg/l at 24 hours. The increase in both markers was stronger in severe than in mild pancreatitis, and in patients without pancreatitis there was no significant increase. Baseline trypsinogen 2 and trypsin 2-AAT concentrations were elevated in 29% and 32% of patients, respectively. The diagnostic accuracy of a threefold elevation over the baseline value was therefore analysed. The sensitivity and specificity of these parameters in the diagnosis of post-ERCP pancreatitis was 93% and 91%, respectively, for serum trypsinogen 2 at six hours after the examination, and 93% and 90%, for trypsin 2-AAT at 24 hours.

Conclusions—Serum trypsinogen 2 and trypsin 2-AAT reflect pancreatic injury after ERCP. High concentrations are associated with severe pancreatic damage. The delayed increase in trypsin 2-AAT compared with trypsinogen 2 appears to reflect the pathophysiology of AP. A greater than threefold increase in trypsinogen 2 six hours after ERCP is an accurate indicator of pancreatitis.
Hepatitis G virus infection in fulminant hepatic failure
Authors: Sáiz J C , Sans M , Mas A , Olmedo E , Forns X , López-Labrador F X , Restrepo J C , Costa J , Salmerón J M , Guilera M , Ampurdanés S , Sánchez-Tapias J M , de Anta M T Jiménez , Rodés J
Published: June 2010

Background—RNA sequences of the recently identified hepatitis GB virus C (HGBV-C), also named hepatitis G virus (HGV), have been detected in patients with idiopathic fulminant hepatic failure (FHF) but the role of this agent in the disease remains controversial.

Aims—To investigate the presence and implications of HGV infection in a large series of Spanish patients with FHF.

Patients—Sixty eight patients with FHF, including 19 with idiopathic disease, were studied. In 28 cases, studies were performed before and after liver transplantation. For comparison 200 volunteer blood donors and 22 patients transplanted for chronic liver disease were also studied.

Methods—HGV RNA was measured in serum by reverse transcriptase polymerase chain reaction of the 5′ non-coding region.

Results—Evidence of HGV infection was found in 3% (6/200) of blood donors and in 19% (13/68) of patients with FHF. HGV infection was more frequent in patients with hepatitis B (24%, 6/25) or hepatitis D (42%, 5/12), than in patients with idiopathic disease (11%, 2/19). Half of the patients with HGV infection used illicit intravenous drugs. Specific clinical features associated with HGV infection were not identified. A very high rate of infection with HGV was observed in patients who underwent liver transplantation, either for FHF (60%, 15/24) or chronic liver disease (45%, 9/20).

Conclusions—In our geographical area, HGV infection is relatively frequent in FHF, but it does not seem to play a major role in idiopathic cases.
Impaired absorption of cholesterol and bile acids in patients with an ileoanal anastomosis
Authors: Hakala K , Vuoristo M , Luukkonen P , Järvinen H J , Miettinen T A
Published: June 2010

Background—No data exist on cholesterol absorption in patients with an ileoanal anastomosis (IAA).

Aims—To study cholesterol absorption and its effects on cholesterol and bile acid metabolism in patients with an IAA.

Patients and methods—Cholesterol absorption, and serum, biliary, and faecal lipids were studied in 24 patients with an IAA and 20 controls.

Results—Fractional cholesterol absorption was significantly lower in the patients (36% versus 47% in controls). Surprisingly, the calculated intestinal influx of endogenous cholesterol was reduced so that the absolute absorption of cholesterol was decreased; elimination of cholesterol as faecal neutral steroids remained normal. Thus, the slightly increased cholesterol synthesis was mainly due to increased faecal bile acid excretion, which, in turn, was associated with reduced absorption and biliary secretion of bile acids. Serum total and low density lipoprotein (LDL) cholesterol and LDL triglycerides were lower in the patients. Molar percentage and saturation index of biliary cholesterol were slightly higher in patients with an IAA. Proportions of secondary bile acids in bile and faeces were diminished, and faecal unidentified bile acids were higher in patients.

Conclusions—Cholesterol absorption is significantly impaired in patients with an IAA, and is closely related to changes in serum and biliary lipids observed in these patients.
Prospective evaluation of the treatment of solitary rectal ulcer syndrome with biofeedback
Authors: Vaizey C J , Roy A J , Kamm M A
Published: June 2010

Background—Solitary rectal ulcer syndrome (SRUS) is often resistant to medical and surgical treatment.

Aim—To determine whether biofeedback retraining is a useful treatment for this condition.

Patients—Thirteen consecutive patients with SRUS (three men, median age 34 years, median duration of symptoms three years) underwent treatment. Previous surgical treatment had failed in five.

Methods—Patients were evaluated prospectively. Anorectal physiological studies were performed in 11 patients before treatment. A standardised questionnaire was used before and after treatment, and all but two patients were examined after treatment.

Results—Median follow up was nine months (range 3–22 months). After treatment four patients were asymptomatic, and four felt improved. Symptom improvement or elimination occurred in: need to strain (7/13 patients), digitation (7/11), laxative use (5/9). Time in the toilet (median 30 v 10 minutes, beforev after treatment) and number of visits to toilet (6v 3/day) were also improved. Three patients were able to maintain employment before treatment compared with eight after treatment. The solitary ulcer did not heal completely in any of the nine patients examined after treatment, but improved in four. Previous surgery, the macroscopic appearance of the ulcer, the presence of pelvic floor paradox, and other physiological parameters did not predict outcome.

Conclusion—Biofeedback retraining is a useful treatment for this condition. Long term studies are now required.
Chronic obstructive pancreatitis due to a pancreatic cyst in a patient with autosomal dominant polycystic kidney disease
Authors: Malka D , Hammel P , Vilgrain V , Fléjou J-F , Belghiti J , Bernades P
Published: June 2010

Background—Autosomal dominant polycystic kidney disease, the most frequent inherited polycystic disease, is a systemic disorder characterised by the development of numerous and bilateral kidney cysts leading to chronic renal failure. Extrarenal cysts are located mainly in the liver but also in various organs including the pancreas. To our knowledge, complications of pancreatic cysts in this disease have never been reported.

Patient—The first case of painful chronic obstructive pancreatitis due to a true pancreatic cyst in a patient with autosomal dominant polycystic kidney disease is reported. Abdominal transparietal and endoscopic ultrasonography, computed tomography, and endoscopic retrograde cholangiopancreatography showed a cystic lesion in the body of the pancreas associated with upstream dilatation of the main pancreatic duct. Intraoperative ultrasonography before and after cyst fluid aspiration, and pancreatography and pathological examination of the resected distal pancreas confirmed that both main pancreatic duct enlargement and chronic pancreatitis were caused by a benign cyst.

Conclusion—Chronic obstructive pancreatitis should be added to the extrarenal complications of autosomal dominant polycystic kidney disease.
Reducing risks in gastroenterological practice
Authors: NEALE G
Published: June 2010

Summary

Eightly five malpractice claims against gastroenterologists have been analysed. Thirty seven (44%) arose from adverse events as a result of endoscopy and 48 (56%) from clinical practice. In 31 (84%) of the endoscopy cases (including all 13 endoscopic retrograde cholangiopancreatographies) there seemed to be significant fault. In nine cases the procedure was not clearly indicated and in 10 recognition and treatment of the adverse event was delayed. In no case had the patient given adequate informed consent. Diagnostic error was responsible for most of the claims related to clinical practice (31 of 48) of which 13 were indefensible. Failure to obtain an adequate history (17 cases) and insufficient awareness of disorders of the small intestine (12 cases) were major factors. In 26 cases a key investigation was not performed. Seventeen claims were related to management or treatment but only one of these cases was difficult to defend.

 Overall, there was evidence of serious fault in 50% of claims. Greater care in selecting patients for endoscopic procedures and in providing postprocedural care would have eliminated the basis of more than half the claims arising from endoscopy. There would have been few claims if properly informed consent had been obtained. Over-ready acceptance of the diagnosis of a functional disorder (for example, irritable bowel, dyspepsia) was the usual cause of delays in diagnosis.
Expression of a marker for colonic crypt base cells is correlated with poor prognosis in human colorectal cancer
Authors: van der Wurff A A M , ten Kate J , Marx P T J , van der Linden E P M , Beek C C L , Bovelander F-J , Dekker J , Dinjens W N M , von Meyenfeldt M F , Arends J-W , Bosman F T
Published: June 2010

Background—There is a need for markers in colorectal cancer which will allow subclassification of stage groups into subgroups with high versus low risk of recurrent disease.

Aims—To develop monoclonal antibodies that recognise antigens on immature crypt base cells, on the assumption that in a neoplasm undifferentiated but not the terminally differentiated cells will be responsible for tumour progression.

Methods—Colon crypt cells which were isolated from human colonic mucosa by EDTA/EGTA incubation were studied. By stepwise harvesting, crypt base cell enriched fractions were obtained, and after incubation with antibodies against dominant antigens, used as immunogens.

Results—Of one crypt base cell specific antibody (5E9), the reactive epitope appeared to be a non-terminal carbohydrate in the mucin O-glycans of the colon. The epitope did not seem to be colon specific, but was expressed in a variety of other tissues. In colorectal carcinomas, 5E9 immunoreactivity identified a subgroup of patients with a tendency for worse prognosis.

Conclusion—A mucin associated maturation epitope was identified in colonic crypt base cells, the expression of which in Dukes’ stage B3 colorectal carcinoma may be associated with poor prognosis.
General and cancer specific mortality of a population based cohort of patients with inflammatory bowel disease: the Florence study
Authors: Palli D , Trallori G , Saieva C , Tarantino O , Edili E , D’Albasio G , Pacini F , Masala G
Published: June 2010

Background—A population based epidemiological study identified all the patients diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) resident in the Florence area in the period 1978–1992.

Aims—To assess the mortality of unselected patients with inflammatory bowel disease (IBD) in a Mediterranean country.

Methods—Overall, 920 patients (689 UC and 231 CD) were followed until death or end of follow up (31 December 1996). Information on vital status was available for all except eight patients (0.9%); 70 deaths were identified (23 in patients with CD and 47 in patients with UC). Expected deaths were estimated on the basis of five year age group, gender, and calendar year national mortality rates. Standardised mortality ratios (SMR) and 95% confidence intervals were calculated.

Results—General mortality was significantly lower than expected in UC (SMR 0.6; 95% confidence interval 0.4 to 0.8), due to a reduced number of cardiovascular and, possibly, smoking related deaths. Cancers of the respiratory tract were significantly reduced in UC but tended to be increased in patients with CD. These latter patients had not only an increased cancer mortality but also a 40% increased risk of dying for all causes already evident in the first five year follow up period and persisting thereafter. In contrast, in patients with UC, SMRs were initially very low but tended to increase steadily over the follow up period. Gastrointestinal deaths were particularly increased in patients with CD, but only moderately in those with UC. Overall, there was some evidence of a twofold increased mortality for colorectal cancer, the risk being highest for rectal cancers in patients with UC. A non-significant excess of deaths due to haemolymphopoietic malignancies and suicides was also observed.

Conclusions—This study, the first in a Mediterranean country, supports the existence of two divergent mortality patterns for patients with UC and CD, possibly explained by differences in smoking habits and by a greater severity of CD.
Bone mineral density and nutritional status in children with chronic inflammatory bowel disease
Authors: Boot A M , Bouquet J , Krenning E P , de Muinck Keizer-Schrama S M P F
Published: June 2010

Background—Osteoporosis has been reported in adult patients with inflammatory bowel disease.

Aims—To evaluate bone mineral density (BMD), nutritional status, and determinants of BMD in children with inflammatory bowel disease.

Patients—Fifty five patients (34 boys and 21 girls, age range 4–18) were studied; 22 had Crohn’s disease and 33 ulcerative colitis.

Methods—Lumbar spine and total body BMD, and body composition were assessed by dual energy x ray absorptiometry (DXA). Results were expressed as standard deviation scores (SDS). Lean body mass was also assessed by bioelectrical impedance analysis (BIA). Yearly measurements during two years were performed in 21 patients.

Results—The mean SDS of lumbar spine BMD and total body BMD were significantly lower than normal (−0.75 and −0.95, both p<0.001). Height SDS and body mass index SDS were also decreased. The decrease in BMD SDS could not be explained by delay in bone maturation. The cumulative dose of prednisolone correlated negatively with lumbar spine BMD SDS (r=−0.32, p<0.02). Body mass index SDS correlated positively with total body BMD SDS (r=0.36, p<0.02). Patients with Crohn’s disease had significantly lower lumbar spine and total body BMD SDS than patients with ulcerative colitis, even after adjustment for cumulative dose of prednisolone. In the longitudinal data cumulative dose of prednisolone between the measurements correlated negatively with the change in lumbar spine and total body BMD SDS. Lean tissue mass measured by DXA had a strong correlation with lean body mass measured by BIA (r=0.98).

Conclusions—Children with inflammatory bowel disease have a decreased BMD. Children with Crohn’s disease have a higher risk of developing osteopaenia than children with ulcerative colitis. Corticosteroid therapy and nutritional status are important determinants of BMD in these patients.
Ambulatory gastrojejunal manometry in severe motility-like dyspepsia: lack of correlation between dysmotility, symptoms, and gastric emptying
Authors: Wilmer A , Van Cutsem E , Andrioli A , Tack J , Coremans G , Janssens J
Published: June 2010

Background—Previous studies have failed to identify manometric patterns of gastrointestinal motor activity that can distinguish dyspepsia from health.

Aims—To test the hypothesis that the combined use of prolonged, ambulatory, antrojejunal manometry and computer aided analysis in patients selected for the severity of their symptoms could reveal new insights into gastrointestinal motor activity in patients with severe motility-like dyspesia

Methods—Twenty four hour antrojejunal ambulatory manometry was performed in 14 patients and 10 healthy volunteers. Parameters characterising digestive and fasted motility were obtained by a validated computer program and visual analysis. Scoring systems quantified the degree of dysmotility as well as the severity of symptoms. Gastric emptying times were measured in each patient.

Results—There was a high prevalence of antral and jejunal dysmotility both during the interdigestive period (71% of patients) and in the postprandial period (78%). During the interdigestive period there was a reduced incidence of antral and jejunal phases, a larger contribution of phase 2 during migrating motor complex cycles, and aberrant configuration of jejunal phase 3 in 29% of patients. Postprandially, the most frequent finding was antral (29% of patients) or jejunal (29%) hypomotility or hypermotility. Minute rhythm was present both during the postprandial (29% of patients) and the interdigestive period (21%). There was no positive correlation between symptom scores, gastric half emptying times, or motility scores.

Conclusion—Even with the use of prolonged recordings and advanced computer aided analysis, it is not possible to identify a specific motor pattern which can discriminate patients with severe motility-like dyspepsia from those with other diseases or even healthy individuals. Clinical symptoms or gastric half emptying times are poor predictors of gastrointestinal dysmotility in patients with functional dyspepsia.
The relationship between intrahepatic portal systemic shunts and microsphere induced portal hypertension in the rat liver
Authors: Li X , Benjamin I S , Alexander B
Published: June 2010

Background—Portal hypertension is associated with gross haemodynamic disturbances characterised by high cardiac output, low peripheral vascular resistance, increased splanchnic blood flow, and portal systemic shunting.

Aims—To study the relationship between intrahepatic portal systemic shunts and microsphere induced portal hypertension in the rat liver.

Methods—Different sized microspheres were sequentially injected into the portal vein of male Wistar rats.

Results—Steady state portal venous pressure was increased by 102.2 (35.6)% (14.9 (3.6) mm Hg) and 272.3 (78.0)% (24.0 (2.2) mm Hg) above the basal pressure following sequential injections of 15 and 80 μm diameter microspheres, respectively. Sequential injection of 15, 40, and 80 μm diameter microspheres in either ascending or descending order of size did not generate further increases in portal venous pressure. A single injection of 1.8 × 105 80 μm microspheres consistently produced a steady state portal venous pressure of 19.0 (1.3) mm Hg but did not approach the much higher value of 36.6 (43.2) mm Hg measured during clamping of the portal vein. These data indicate that the opening of patent intrahepatic shunts was responsible for the reduced pressures observed during microsphere injections and further evidence for this was provided by the location of microspheres in the pulmonary vascular bed. The elevation in portal venous pressure achieved by microsphere injections was not significantly different to that produced in rats subjected to partial portal vein ligation (20.7 (0.5) mm Hg, p>0.05). Wedged hepatic venous pressure decreased from 6.7 (0.7) to 3.0 (0.6) mm Hg following injection of 80 μm microspheres, suggesting a decrease in total hepatic blood flow. Conversely, injection of 15 μm microspheres induced an increase in wedged hepatic venous pressure from 7.0 (1.0) mm Hg to 12.4 (1.8) mm Hg, indicating a localised redistribution of blood flow at the presinusoidal level of the portal venous vascular network and increased intrahepatic shunt flow.

Conclusion—It is suggested that there may be a protective pathophysiological role for these shunts when the liver is subjected to changes which induce acute portal hypertension.
A prospective study of oesophageal function in patients with normal coronary angiograms and controls with angina
Authors: Cooke R A , Anggiansah A , Chambers J B , Owen W J
Published: June 2010

Aims—To compare the incidence of oesophageal abnormalities and their correlation with chest pain in patients with normal coronary angiograms, and in controls with angina.

Patients—Sixty one patients with normal coronary angiograms (NCA group) referred to a single cardiac centre between March 1990 and April 1991; 25 matched controls with confirmed coronary artery disease (CAD group).

Setting—Cardiac referral centre and oesophageal function testing laboratory.

Main outcome measures—Oesophageal manometry, provocation tests, and 24 hour ambulatory pH monitoring.

Results—Simultaneous contractions were more common (6.7% versus 0.8%, p<0.01), and the duration of peristaltic contractions was longer (2.9 versus 2.4 seconds, p<0.01) in the NCA group than in the CAD group. There were no group differences in the amplitude of peristaltic contractions, and none had nutcracker oesophagus. Ten (16%) patients with NCA and no patients with CAD had diffuse spasm (p=0.03). Twenty one (34%) patients with NCA, and five (20%) patients with CAD had abnormal gastro-oesophageal reflux (p>0.05). There was no significant difference between the groups in the number of patients whose pain was temporally related to pH events. Particular chest pain characteristics, or the presence of additional oesophageal symptoms, were not predictive of an oesophageal abnormality.

Conclusion—Oesophageal function tests commonly implicate the oesophagus as a source of pain in patients with normal coronary angiograms. With the exception of simultaneous contractions during manometry however, the incidence of abnormalities and in particular the correlation of pH events with chest pain are as common in patients with normal coronary angiograms as in controls with angina. The oesophagus may often be an unrecognised source of pain in both groups of patients.
Spontaneous secretion of interferon γ and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes
Authors: Carol M , Lambrechts A , Van Gossum A , Libin M , Goldman M , Mascart-Lemone F
Published: June 2010

Background—Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses.

Aims—To quantify interferon γ (IFN-γ) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation.

Patients—Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa.

Methods—Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-γ and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT).

Results—The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-γ (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-γ SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-γ and IL-4 were mainly produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-γ in the basal state, and 0.1% secreted IL-4.

Conclusions—Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-γ and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases.
The endothelin receptor antagonist bosentan restores gut oxygen delivery and reverses intestinal mucosal acidosis in porcine endotoxin shock
Authors: Oldner A , Wanecek M , Goiny M , Weitzberg E , Rudehill A , Alving K , Sollevi A
Published: June 2010

Background—Endothelin-1, the most potent vasoconstrictor known, is produced in septic states and may be involved in the pathophysiology of the deteriorated splanchnic circulation seen in septic shock.

Aims—To elucidate the capability of bosentan, a non-peptide mixed endothelin receptor antagonist, to attenuate splanchnic blood flow disturbances and counteract intestinal mucosal acidosis in endotoxic shock.

Methods—In 16 anaesthetised pigs, central and regional haemodynamics were monitored by thermodilution and ultrasonic flow probes, respectively. A tonometer in the ileum was used for measurement of mucosal pH. Onset of endotoxin challenge was followed by bosentan administration (to eight pigs) two hours later.

Results—Endotoxin infusion reduced cardiac index and systemic oxygen delivery; bosentan restored these parameters. The reduced mean arterial blood pressure and renal blood flow remained unaffected by bosentan. The profound reduction in gut oxygen delivery in response to endotoxin was completely abolished by bosentan. Bosentan significantly improved the notably deteriorated intestinal mucosal pH and mucosal-arterial Pco2 gap. The mucosal-portal vein Pco2 gap, used to monitor the mucosa in relation to the gut as a whole (including the spleen and pancreas), was also greatly increased by endotoxaemia and significantly reversed by bosentan.

Conclusion—Bosentan completely restored the profound endotoxin induced reductions in systemic and gut oxygen delivery with a concomitant reversal of intestinal mucosal acidosis. Results suggest that endothelin is involved in the pronounced perfusion disturbances seen in the gut in endotoxic shock. Bosentan may prove useful in reducing gut ischaemia in septic shock.
Oxidative stress: an important phenomenon with pathogenetic significance in the progression of acute pancreatitis
Authors: Tsai K , Wang S-S , Chen T-S , Kong C-W , Chang F-Y , Lee S-D , Lu F-J
Published: June 2010

Background—Reactive oxygen species and related oxidative damage have been implicated in the initiation of acute pancreatitis. Changes in these parameters during disease progression merit further investigation.

Aims—To evaluate changes and the clinical relevance of superoxide radicals, endogenous antioxidants, and lipid peroxidation during the course of acute pancreatitis.

Patients and methods—Superoxide radicals (measured as lucigenin amplified chemiluminescence), ascorbic acid, dehydroascorbic acid, α tocopherol, and lipid peroxidation (measured as thiobarbiturate reactive substances) were analysed in blood samples from 56 healthy subjects, 30 patients with mild acute pancreatitis, and 23 patients with severe acute pancreatitis. The association with grades of disease severity was analysed. Measurements were repeated one and two weeks after onset of pancreatitis.

Results—In the blood from patients with acute pancreatitis, there were increased levels of the superoxide radical as well as lipid peroxides. There was notable depletion of ascorbic acid and an increased fraction of dehydroascorbic acid. Changes in α tocopherol were not great except in one case with poor prognosis. Differences between severe and mild acute pancreatitis were significant (p<0.01). Variable but significant correlations with disease severity scores were found for most of these markers. The normalisation of these indexes postdated clinical recovery one or two weeks after onset of disease.

Conclusions—Heightened oxidative stress appears early in the course of acute pancreatitis and lasts longer than the clinical manifestations. The dependence of disease severity on the imbalance between oxidants and natural defences suggests that oxidative stress may have a pivotal role in the progression of pancreatitis and may provide a target for treatment.
Acute pancreatitis: the substantial human and financial costs
Authors: NEOPTOLEMOS J P , RARATY M , FINCH M , SUTTON R
Published: June 2010

A greater understanding of the natural history of acute pancreatitis combined with greatly improved radiological imaging has led to improvement in the hospital mortality from acute pancreatitis, from around 25–30% to 6–10% in the past 30 years. Moreover, it is now recognised that the first phase of severe acute phase pancreatitis is a systemic inflammatory response syndrome (SIRS), during which multiple organ failure and death often supervene. Survival into the second phase may be accompanied by local complications, such as infected pancreatic necrosis, which may be prevented by prophylactic antibiotics and treated by judicious surgery. Intensive care unit costs can be substantial, but might be justified because of the excellent quality of life of survivors. Reduction in multiple organ failure by agents such as lexipafant, an antagonist of platelet activating factor (PAF) (which plays a critical role in generating the SIRS), may contribute to intensive care unit cost containment, as well as reducing the incidence of local complications and deaths from acute pancreatitis. A further improvement in the human and financial costs also requires the centralisation of the management of patients with severe acute pancreatitis, to single hospital units whose concentrated expertise equips them to intervene most effectively in what is still recognised as a highly complex disease.
Transcatheter coil embolotherapy: a safe and effective option for major colonic haemorrhage
Authors: Nicholson A A , Ettles D F , Hartley J E , Curzon I , Lee P W R , Duthie G S , Monson J RT
Published: June 2010

Background—The management of major colonic bleeding is problematic. A proportion of patients require emergency surgery which is associated with high morbidity and mortality. Percutaneous embolotherapy, previously considered a high risk procedure in the colon, may provide an alternative treatment in this group of patients.

Aims—To assess the safety and efficacy of embolotherapy in the treatment of life threatening colonic haemorrhage.

Patients and methods—Thirty eight patients with fresh haemorrhage per rectum were referred for surgery because of failed conservative treatment. All underwent angiography; in 14 a bleeding site or vascular abnormality was detected. A coaxial catheter was directed to the most distal bleeding artery and this was embolised with platinum coils.

Results—Detection of a bleeding site correlated with haemodynamic stability at the time of angiography (r=1 for a systolic blood pressure less than 100 mm Hg). Bleeding sites or vascular abnormalities were detected and embolised in 14 patients (37%). In 12/14 there was immediate and sustained haemodynamic improvement; two continued to bleed and required emergency hemicolectomy (14%). Three developed ischaemic complications (21.4%); these were managed conservatively and required no intervention. The 30 day mortality was 7.1% in the embolotherapy group and 10.5% in the overall group of 38 patients.

Conclusion—Colonic embolotherapy for life threatening haemorrhage is an effective, relatively safe procedure with a low incidence of major complications. Its use depends on the identification of a focal bleeding point or vascular abnormality, which in turn depends on the haemodynamic stability of the patient at the time of angiography.
The kappa opioid receptor is associated with the perception of visceral pain
Authors: BLACK D , TREVETHICK M
Published: June 2010

μ-, δ- and κ-opioid receptors are widely expressed in the central nervous system where they mediate the strong analgesic and mood-altering actions of opioids, and modulate numerous endogenous functions. To investigate the contribution of the κ-opioid receptor (KOR) to opioid function in vivo, we have generated KOR-deficient mice by gene targeting. We show that absence of KOR does not modify expression of the other components of the opioid system, and behavioural tests indicate that spontaneous activity is not altered in mutant mice. The analysis of responses to various nociceptive stimuli suggests that theKOR gene product is implicated in the perception of visceral chemical pain. We further demonstrate that KOR is critical to mediate the hypolocomotor, analgesic and aversive actions of the prototypic κ-agonist U-50,488H. Finally, our results indicate that this receptor does not contribute to morphine analgesia and reward, but participates in the expression of morphine abstinence. Together, our data demonstrate that theKOR-encoded receptor plays a modulatory role in specific aspects of opioid function.
Loss of Bcl-2 expression correlates with tumour recurrence in colorectal cancer
Authors: Ilyas M , Hao X-P , Wilkinson K , Tomlinson I P M , Abbasi A M , Forbes A , Bodmer W F , Talbot I C
Published: June 2010

Aims—To investigate the association between immunohistochemical expression of Bcl-2 and p53 in colorectal cancer and tumour recurrence following surgery.

Methods—Sixty six cases of Dukes’ B colorectal carcinoma were studied. All tumours were moderately differentiated and were shown to be histologically clear of the resection margins. Immunohistochemistry was performed on formalin fixed paraffin wax embedded tissue using monoclonal antibodies for p53 and Bcl-2. The Bcl-2 staining was assessed separately for relative intensity of staining and percentage of positive tumour cells and given a final score which combined the two factors. The p53 staining was assessed on number of positive tumour cells only. The patterns of immunostaining of those cases in which there had been tumour recurrence were compared with those cases in which there was no tumour recurrence (controls).

Results—A statistically significant inverse association was found between Bcl-2 score and tumour recurrence (median Bcl-2 score of 6 (interquartile range (IQR) 2–9) in patients with recurrent disease; median Bcl-2 score of 8 (IQR 6–10) in those without recurrence; p=0.03). When examined separately, both the intensity of expression and percentage of positive tumour cells were significantly associated with tumour recurrence (p=0.04 in each case). There was no association between p53 staining and tumour recurrence.

Conclusion—Results suggest that, when controlled for differentiation, Bcl-2 expression is a prognostic marker and may be useful as an adjunctive test in clinical decision making.
Prognostic factors in patients with endocrine tumours of the duodenopancreatic area
Authors: Madeira I , Terris B , Voss M , Denys A , Sauvanet A , Flejou J-F , Vilgrain V , Belghiti J , Bernades P , Ruszniewski P
Published: June 2010

Background—The development of endocrine tumours of the duodenopancreatic area (ETDP) is thought to be slow, but their natural history is not well known. The aim of this study was to determine the factors that influence survival of patients with ETDP.

Patients/Methods—Eighty two patients with ETDP (44 non-functioning tumours, 23 gastrinomas, seven calcitonin-secreting tumours, four glucagonomas, three insulinomas, one somatostatinoma) followed from October 1991 to June 1997 were included in the study. The following factors were investigated: primary tumour size, hormonal clinical syndrome, liver metastases, lymph node metastases, extranodular/extrahepatic metastases, progression of liver metastases, local invasion, complete resection of the primary tumour, and degree of tumoral differentiation. The prognostic significance of these factors was investigated by uni- and multi-variate analysis.

Results—Twenty eight patients (34%) died within a median of 17 months (range 1–110) from diagnosis. Liver metastases (p = 0.001), lymph node metastases (p = 0.001), progression of liver metastases (p<0.00001), lack of complete resection of the primary tumour (p = 0.001), extranodular/extrahepatic metastases (p = 0.001), local invasion (p = 0.001), primary tumour size ⩾3 cm (p = 0.001), non-functioning tumours (p = 0.02), and poor tumoral differentiation (p = 0.006) were associated with an unfavourable outcome by univariate analysis. Multivariate analysis identified only liver metastases (risk ratio (RR) = 8.3; p<0.0001), poor tumoral cell differentiation (RR = 8.1; p = 0.0001), and lack of complete resection of the primary tumour (RR = 4.8; p = 0.0007) as independent risk factors. Five year survival rates were 40 and 100% in patients with and without liver metastases, 85 and 42% in patients with and without complete resection of primary tumour, and 17 and 71% in patients with poor and good tumour cell differentiation respectively.

Conclusion—Liver metastases are a major prognostic factor in patients with ETDP. Progression of liver metastases is also an important factor which must be taken into account when deciding on the therapeutic approach. The only other independent prognostic factors are tumoral cell differentiation and complete resection of the primary tumour.
Microprocessor controlled movement of liquid gastric content using sequential neural electrical stimulation
Authors: Mintchev M P , Sanmiguel C P , Otto S J , Bowes K L
Published: June 2010

Background—Gastric electrical stimulation has been attempted for several years with little success.

Aims—To determine whether movement of liquid gastric content could be achieved using microprocessor controlled sequential electrical stimulation.

Methods—Eight anaesthetised dogs underwent laparotomy and implantation of four sets of bipolar stainless steel wire electrodes. Each set consisted of two to six electrodes (10×0.25 mm, 3 cm apart) implanted circumferentially. The stomach was filled with water and the process of gastric emptying was monitored. Artificial contractions were produced using microprocessor controlled phase locked bipolar four second trains of 50 Hz, 14 V (peak to peak) rectangular voltage. In four of the dogs four force transducers were implanted close to each circumferential electrode set. In one gastroparetic patient the effect of direct electrical stimulation was determined at laparotomy.

Results—Using the above stimulating parameters circumferential gastric contractions were produced which were artificially propagated distally by phase locking the stimulating voltage. Averaged stimulated gastric emptying times were significantly shorter than spontaneus emptying times (t1/2 6.7 (3.0) versus 25.3 (12.9) minutes, p<0.01). Gastric electrical stimulation of the gastroparetic patient at operation produced circumferential contractions.

Conclusions—Microprocessor controlled electrical stimulation produced artificial peristalsis and notably accelerated the movement of liquid gastric content.
Phenotypic differences in familial adenomatous polyposis based on APC gene mutation status
Authors: Heinimann K , Müllhaupt B , Weber W , Attenhofer M , Scott R J , Fried M , Martinoli S , Müller Hj , Dobbie Z
Published: June 2010

Background—Familial adenomatous polyposis (FAP) is a clinically well defined hereditary disease caused by germline mutations within the adenomatous polyposis coli (APC) gene. Although several techniques are applied in the mutation analysis of FAP kindreds about 20–50% of cases remain unclear, with no APC mutation identified (APC negative).

Aims—To delineate phenotypic differences between APC positive and APC negative patients with respect to colonic and extracolonic disease in order to determine whether additional mechanisms are involved in the pathogenesis of FAP.

Methods—The entire coding region of the APC gene was analysed using single stranded conformation polymorphism and protein truncation tests in 50 Swiss FAP families with a total of 161 affected individuals. Differences in phenotypic manifestation were statistically evaluated by Student’s t test, Fisher’s exact test, and χ2 test.

Results—Thirty six families (72%) were APC positive. Statistically significant differences between APC positive and APC negative groups were found for the mean age at diagnosis of colonic polyposis (35.2 versus 45.3 years, respectively) and for the occurrence of stomach polyps (14 patients, all APC positive). Additionally, APC negative patients displayed lower polyp numbers at diagnosis and less extracolonic manifestations.

Conclusions—FAP kindreds without detected APC gene mutations present with a notably milder disease phenotype compared with APC positive families, suggesting that different genetic factors might be involved.
Clinical outcome after infection with Helicobacter pylori does not appear to be reliably predicted by the presence of any of the genes of the cag pathogenicity island
Authors: Jenks P J , Mégraud F , Labigne A
Published: June 2010

Background—The development of clinical disease after infection with Helicobacter pylori has been reported to be associated with expression of the cagA gene. Recently, it has been shown that cagA is part of a multigene locus, described as the cag pathogenicity island (PAI). The role of this region in determining clinical outcome remains to be established.

Aims—To investigate whether the presence ofcagA is always associated with the presence of the complete cag PAI and to evaluate the distribution of selected cag genes in 73 H pylori strains isolated from patients in France.

Methods—Clinical strains of H pyloriwere screened for selected genes of the cag PAI by polymerase chain reaction and colony hybridisation.

Results—Of 64 strains that harboured thecagA gene, 57 (89%) also contained the entirecag PAI. The entire cag PAI was found in 85% (48/56) and 53% (9/17) of duodenal ulcer and non-ulcer dyspepsia isolates, respectively. Eight strains had deletions within thecag PAI, including deletion of the cagA gene in one isolate; the deletions were not associated with the insertion sequence IS605. Of eight strains lacking the cag PAI, four were isolated from patients with duodenal ulcer.

Conclusion—The cag PAI is not a uniform, conserved entity. Although the presence of thecag PAI is highly associated with duodenal ulcer, the clinical outcome of infection with H pylori is not reliably predicted by any gene of the cag PAI.
Impaired splenic function and tuftsin deficiency in patients with intestinal failure on long term intravenous nutrition
Authors: Zoli G , Corazza G R , Wood S , Bartoli R , Gasbarrini G , Farthing M J G
Published: June 2010

Background—Reticuloendothelial system function is impaired in humans receiving lipid regimens.

Aims—To evaluate the effects of long term administration of long chain triglyceride emulsions on reticuloendothelial system function.

Methods—Splenic function and tuftsin activity were measured in 20 patients on intravenous nutrition for intestinal failure, 20 patients with Crohn’s disease who were not receiving intravenous nutrition, and 50 healthy controls.

Results—Pitted red cells counts in patients on intravenous nutrition (8.0%) were significantly higher (p<0.001) than in healthy controls (0.6%) and in patients with Crohn’s disease (0.9%). No difference was found between healthy controls and patients with Crohn’s disease. There was a correlation (r=0.50; p<0.03) between percentage of pitted red cells and duration of intravenous nutrition. Tuftsin activity was significantly reduced in the intravenous nutrition patient group (6%) compared with both disease controls (16.5%, p<0.01) and healthy volunteers (17.8%, p<0.001) . An inverse correlation between tuftsin activity and pitted red cell percentage was found in the patients on intravenous nutrition (rs =−0.44, p<0.05). No relation was found in the patients on intravenous nutrition between pitted red cell percentage or tuftsin activity and type of disease, percentage of ideal body weight, residual length of small intestine, or administration (quantity and frequency) of lipid emulsion. Eight patients on intravenous nutrition had serious infections within the previous 12 months.

Conclusions—Patients with a short bowel treated with long term intravenous nutrition have impaired splenic function, reduced tuftsin activity, and an increased risk of infection.
Scintigraphic validation of a magnetic resonance imaging method to study gastric emptying of a solid meal in humans
Authors: Feinle C , Kunz P , Boesiger P , Fried M , Schwizer W
Published: June 2010

Background

We have previously used a magnetic resonance imaging (MRI) method to study gastric emptying of liquids. So far, however, it has not possible to assess solid gastric emptying with this technique.

Aims

To validate scintigraphically MRI as a method for measuring emptying of a mixed solid/liquid meal.

Methods

In eight healthy subjects, gastric emptying of a solid/liquid (SM) and a liquid meal (LM) of identical energy content and macronutrient composition was studied by scintigraphy and MRI for 120 minutes.

Results

MRI and scintigraphy agreed with respect to emptying profiles (intraclass correlation coefficient (RI) SM: 0.988, RI, LM: 0.917), t1/2 (SMMRI: 129 (9), SMScinti: 123 (11) minutes, NS; LMMRI: 100 (7), LMScinti: 110 (8) minutes, NS) and AUC (SMMRI: 8999 (232), SMScinti: 8788 (277) min%, NS; LMMRI: 8819 (368), LMScinti: 8891 (321) min%, NS).

Conclusions

MRI can be used to measure reliably gastric emptying not only of liquid but also of mixed solid/liquid meals in humans.
Inhibitory effect of oestradiol on activation of rat hepatic stellate cells in vivo and in vitro
Authors: Shimizu I , Mizobuchi Y , Yasuda M , Shiba M , Ma Y-R , Horie T , Liu F , Ito S
Published: June 2010

Background

Hepatic stellate cells play a key role in the pathogenesis of hepatic fibrosis.

Aims

To examine the inhibitory effect of oestradiol on stellate cell activation.

Methods

In vivo, hepatic fibrosis was induced in rats by dimethylnitrosamine or pig serum. In vitro, rat stellate cells were activated by contact with plastic dishes resulting in their transformation into myofibroblast-like cells.

Results

In the dimethylnitrosamine and pig serum models, treatment with oestradiol at gestation related doses resulted in a dose dependent suppression of hepatic fibrosis with restored content of hepatic retinyl palmitate, reduced collagen content, lower areas of stellate cells which express α smooth muscle actin (α-SMA) and desmin, and lower procollagen type I and III mRNA levels in the liver. In cultured stellate cells, oestradiol inhibited type I collagen production, α-SMA expression, and cell proliferation. These findings suggest that oestradiol is a potent inhibitor of stellate cell transformation.

Conclusion

The antifibrogenic role of oestradiol in the liver may contribute to the sex associated differences in the progression from hepatic fibrosis to cirrhosis.