Responses of human intestinal microvascular endothelial cells to Shiga toxins 1 and 2 and pathogenesis of hemorrhagic colitis.
Endothelial damage is characteristic of infection with Shiga toxin (Stx)-producing Escherichia coli (STEC). Because Stx-mediated endothelial cell damage at the site of infection may lead to the characteristic hemorrhagic colitis of STEC infection, we compared the effects of Stx1 and Stx2 on primary and transformed human intestinal microvascular endothelial cells (HIMEC) to those on macrovascular endothelial cells from human saphenous vein (HSVEC). Adhesion molecule, interleukin-8 (IL-8), and Stx receptor expression, the effects of cytokine activation and Stx toxins on these responses, and Stx1 and Stx2 binding kinetics and bioactivity were measured. Adhesion molecule and IL-8 expression increased in activated HIMEC, but these responses were blunted in the presence of toxin, especially in the presence of Stx1. In contrast to HSVEC, unstimulated HIMEC constitutively expressed Stx receptor at high levels, bound large amounts of toxin, were highly sensitive to toxin, and were not further sensitized by cytokines. Although the binding capacities of HIMEC for Stx1 and Stx2 were comparable, the binding affinity of Stx1 to HIMEC was 50-fold greater than that of Stx2. Nonetheless, Stx2 was more toxic to HIMEC than an equivalent amount of Stx1. The decreased binding affinity and increased toxicity for HIMEC of Stx2 compared to those of Stx1 may be relevant to the preponderance of Stx2-producing STEC involved in the pathogenesis of hemorrhagic colitis and its systemic complications. The differences between primary and transformed HIMEC in these responses were negligible. We conclude that transformed HIMEC lines could represent a simple physiologically relevant model to study the role of Stx in the pathogenesis of hemorrhagic colitis. (+info)
Validation of the Rockall risk scoring system in upper gastrointestinal bleeding.
BACKGROUND: Several scoring systems have been developed to predict the risk of rebleeding or death in patients with upper gastrointestinal bleeding (UGIB). These risk scoring systems have not been validated in a new patient population outside the clinical context of the original study. AIMS: To assess internal and external validity of a simple risk scoring system recently developed by Rockall and coworkers. METHODS: Calibration and discrimination were assessed as measures of validity of the scoring system. Internal validity was assessed using an independent, but similar patient sample studied by Rockall and coworkers, after developing the scoring system (Rockall's validation sample). External validity was assessed using patients admitted to several hospitals in Amsterdam (Vreeburg's validation sample). Calibration was evaluated by a chi2 goodness of fit test, and discrimination was evaluated by calculating the area under the receiver operating characteristic (ROC) curve. RESULTS: Calibration indicated a poor fit in both validation samples for the prediction of rebleeding (p<0.0001, Vreeburg; p=0.007, Rockall), but a better fit for the prediction of mortality in both validation samples (p=0.2, Vreeburg; p=0.3, Rockall). The areas under the ROC curves were rather low in both validation samples for the prediction of rebleeding (0.61, Vreeburg; 0.70, Rockall), but higher for the prediction of mortality (0.73, Vreeburg; 0.81, Rockall). CONCLUSIONS: The risk scoring system developed by Rockall and coworkers is a clinically useful scoring system for stratifying patients with acute UGIB into high and low risk categories for mortality. For the prediction of rebleeding, however, the performance of this scoring system was unsatisfactory. (+info)
Management and outcome of patients undergoing surgery after acute upper gastrointestinal haemorrhage. Steering Group for the National Audit of Acute Upper Gastrointestinal Haemorrhage.
Most patients with acute upper gastrointestinal haemorrhage are managed conservatively or with endoscopic intervention but some ultimately require surgery to arrest the haemorrhage. We have conducted a population-based multicentre prospective observational study of management and outcomes. This paper concerns the subgroup of 307 patients who had an operation because of continued or recurrent haemorrhage or high risk of further bleeding. The principal diagnostic group was those with peptic ulcer. Of 2071 patients with peptic ulcer presenting with acute haemorrhage, 251 (12%) had an operative intervention with a mortality of 24%. In the non-operative group mortality was 10%. The operative intervention rate increased with risk score, ranging from 0% in the lowest risk categories to 38% in the highest. Much of the discrepancy between operative and non-operative mortality was explainable by case mix; however, for high-risk cases mortality was significantly higher in the operated group. In 78% of patients who underwent an operation for bleeding peptic ulcer there had been no previous attempt at endoscopic haemostasis. For patients admitted to surgical units, the operative intervention rate was about four times higher than for those admitted under medical teams. In patients with acute upper gastrointestinal haemorrhage operative intervention is infrequent and largely confined to the highest-risk patients. The continuing high mortality in surgically treated patients is therefore to be expected. The reasons for the low use of endoscopic treatment before surgery are not revealed by this study, but wider use of such treatments might further reduce the operative intervention rate. Physicians and surgeons have not yet reached consensus on who needs surgery and when. (+info)
Hemorrhagic enteritis associated with Clostridium perfringens type A in a dog.
A female Shetland sheep dog died suddenly with hemorrhagic diarrhea and vomitting, and was examined pathologically and microbiologically. Gross pathological change was restricted to the intestinal tract. The intestine contained watery, blood-stained fluid. Histopathologically, the principal intestinal lesion was superficial mucosal hemorrhagic necrosis at the jejunoileum. Many Gram-positive bacilli were found adhering to the necrotic mucosal surface in parts of the intestinal tract. Clostridium perfringens in pure culture were isolated from jejunal contents by anaerobic culture. These results suggested that the typical lesion of this case coincided with canine hemorrhagic enteritis and enterotoxemia due to C. perfringens infection could be the cause of sudden death. (+info)
Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding.
BACKGROUND AND METHODS: We compared propranolol therapy and endoscopic ligation for the primary prevention of bleeding from esophageal varices. This prospective, controlled trial included consecutive eligible patients who had large varices (>5 mm in diameter) that were at high risk for bleeding. The patients were assigned to either propranolol therapy, at a dose sufficient to decrease the base-line heart rate by 25 percent, or variceal ligation, to be performed weekly until the varices were obliterated or so reduced in size that it was not possible to continue treatment. RESULTS: Of the 89 patients, 82 of whom had cirrhosis of the liver, 44 received propranolol and 45 underwent variceal ligation. The mean (+/-SD) duration of follow-up in each group was 14+/-9 and 13+/-10 months, respectively. The mean time required to achieve an adequate reduction in the heart rate was 2.5+/-1.7 days; the mean number of sessions needed to complete variceal ligation was 3.2+/-1.1. After 18 months, the actuarial probability of bleeding was 43 percent in the propranolol group and 15 percent in the ligation group (P=0.04). Twelve patients in the propranolol group and four in the ligation group had bleeding. Three of the four in the ligation group had bleeding before their varices had been obliterated. Nine patients in the ligation group had recurrent varices, a mean of 3.7 months after the initial treatment. Five patients in each group died; bleeding from the varices was the cause of death of four patients in the propranolol group and of three in the ligation group. There were no serious complications of variceal ligation; in the propranolol group, treatment was stopped in two patients because of side effects. CONCLUSIONS: In patients with high-risk esophageal varices, endoscopic ligation of the varices is safe and more effective than propranolol for the primary prevention of variceal bleeding. (+info)
Effect of angiotensin II and telmisartan, an angiotensin1 receptor antagonist, on rat gastric mucosal blood flow.
BACKGROUND: Angiotensin II (ATII) has been suggested to contribute to shock-induced dysfunction of the gastric circulation. AIM: To substantiate this conjecture, the effects on gastric mucosal haemodynamics and the hyperaemic response to acid back-diffusion of ATII and the angiotensin AT1 receptor antagonist, telmisartan, were examined in normal rats and in animals subjected to haemorrhage. METHODS: Gastric mucosal blood flow in phenobarbital-anaesthetized rats was recorded with the hydrogen clearance technique, and acid back-diffusion was induced by perfusing the stomach with ethanol (25%) in HCl (0.05 M). RESULTS: Intravenous infusion of ATII (0.3-10 nmol/min/kg) led to dose-dependent hypertension and a reduction of blood flow and vascular conductance in the gastric mucosa. The gastric hyperaemia caused by acid back-diffusion was attenuated by ATII (1 nmol/min/kg). These effects of ATII were antagonized by intravenous injection of telmisartan (1-10 mg/kg) which per se caused hypotension and dilated the gastric mucosal vasculature, but did not modify the gastric mucosal hyperaemia evoked by acid back-diffusion. Hypotension induced by haemorrhage (1.3 mL blood per 100 g body weight) failed to alter the hyperaemia due to acid back-diffusion, but caused gastric mucosal vasoconstriction, an effect that was left unaffected by telmisartan. CONCLUSIONS: ATII constricts the rat gastric microvasculature via an action involving AT1 receptors. The effects of telmisartan indicate that endogenous ATII contributes to the homeostatic regulation of gastric vascular tone but does not compromise the ability of the gastric microvasculature to react to influxing acid. These results negate the concept that ATII contributes to the gastric vascular perturbances in haemorrhagic shock. (+info)
Thrombelastographic changes and early rebleeding in cirrhotic patients with variceal bleeding.
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 (42 v 24 mm, p < 0.001) and k (48 v 13 mm, p < 0.001) and smaller a (12 v 38 degrees, 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. (+info)
Two way push videoenteroscopy in investigation of small bowel disease.
AIMS: To evaluate the diagnostic yield and safety of a new push type videoenteroscope (PVE) for diagnosis of small bowel disease. METHODS: Three hundred and thirteen patients were referred for one or two way PVE from December 1993 to June 1996. Indications for PVE were: an unexplained iron deficiency anaemia with or without clinically evident gastrointestinal bleeding; or a complementary investigation for suspected small bowel disease, after a small bowel barium follow through (SBBFT) considered as normal or abnormal, but without a definite diagnosis. RESULTS: A jejunoscopy and a retrograde ileoscopy were carried out in 306 and 234 patients, respectively. In patients with isolated anaemia (n = 131) and those with clinically evident gastrointestinal bleeding associated anaemia (n = 72), PVE provided a diagnosis in 26 (19.8%) and 22 (30.5%) cases, respectively. Lesions found were located in the jejunoileum in 30 (14.7%) patients and in the gastroduodenum or the colon in 18 (8.8%) patients--that is, within the reach of the conventional gastroscope/colonoscope. In patients with normal (n = 54) or abnormal (n = 56) SBBFT, PVE provided a diagnosis in 17 (31%) and 27 (48%) cases, respectively. In 25% of cases, the abnormal appearance of SBBFT was not confirmed. The site of the radiological abnormality was not reached in 27% of cases. Lesions were located at the jejunum and the ileum in 59 (64%) and 33 (36%) cases, respectively. CONCLUSIONS: PVE is useful in around 30% of cases of unexplained anaemia or after an SBBFT which failed to provide an accurate aetiological diagnosis. Use of retrograde videoenteroscopy increases diagnostic yield by one third. (+info)