Non-Hodgkin's lymphoma, coeliac disease, and Epstein-Barr virus: a study of 13 cases of enteropathy-associated T- and B-cell lymphoma.

A group of 166 patients with coeliac disease was followed for a period of up to 25 years. During this time, 17 patients developed intestinal tumours that were diagnosed as lymphoma, of which 15 cases were available for review. Eleven of the lymphomas were of T-cell type (enteropathy-associated T-cell lymphoma, EATL) and two were of B-cell type. Two cases were reclassified as undifferentiated carcinoma. The interval between the diagnosis of enteropathy and the onset of lymphoma varied from less than 2 months in four patients to more than 5 years in seven. Seven of the T-cell and both B-cell lymphomas were investigated for the presence of Epstein-Barr virus (EBV) by in situ hybridization (ISH) using probes against Epstein-Barr virus-encoded RNAs (EBERs) and by immunohistochemistry with EBV-specific monoclonal antibodies. All EATL cases were negative, suggesting that EBV is not an important factor in these cases. In one of the B-cell cases, EBV was detectable by ISH and immunohistochemistry in most tumour cells in the mesenteric lymph nodes, but not in any of the tumour cells in the primary ileal tumour, indicating that in this case EBV infection was a late event in the neoplastic process. These results show that lymphoma may develop any time after the onset of coeliac disease and that in our cases of EATL, EBV was not an important factor. In some cases of EBV-related neoplasia, virus infection may be a late event.

Postprandial mesenteric blood flow in humans: relationship to endogenous gastrointestinal hormone secretion and energy content of food.

OBJECTIVE: To examine the relationship between postprandial superior mesenteric arterial blood flow (SMABF) and endogenous gastrointestinal hormone secretion after liquid meals of varying energy content. METHODS: Six healthy volunteers received four isovolumetric meals of differing energy content. SMABF was measured before and for 120 min after feeding using duplex ultrasound; plasma levels of gastrointestinal hormones and noradrenaline were measured. RESULTS: Results are given as means +/- SEM. Postprandial SMABF increased after each meal; the peak mean percentage increment occurred at 28 +/- 8 min, varying from 106 +/- 26% (P < 0.05) with the 800 kj meal to 240 +/- 62% (P < 0.05) with the 4800 kj meal. The rise was sustained and correlated with energy content (r = 0.969; P = 0.031). The subjects' pulse rate increased after each meal and the increment appeared to be related to meal size (r = 0.990; P = 0.008). Blood pressure did not change. The postprandial concentration of N-terminal neurotensin peaked between 30 and 120 min. The mean peak concentration increased from a baseline value of 30.9 +/- 3.5 ng/l by 19.3 ng/l after 800 kj, 31 ng/l after 1600 kj, 38 ng/l after 2400 kj and 64.3 ng/l after the 4800 kj meal (all differences P < 0.05). The rise was sustained and correlated with energy content (r = 0.967; P = 0.033). Plasma noradrenaline concentration also increased significantly after each meal and was related to energy content (r = 0.90; P = 0.036). Plasma insulin concentration showed a similar postprandial response but had no relationship to energy content. Gastrin concentration increased transiently but changes in the concentration of glucagon, vasoactive intestinal polypeptide and neurokinin A were not significant. CONCLUSIONS: The results indicate a relationship between meal energy content, postprandial SMABF and pulse rate increments. Postprandial increases in N-terminal neurotensin and noradrenaline concentration were also related to energy content and may indicate a role for these hormones in the control of SMABF after feeding.

Intracranial pressure monitoring and liver transplantation for fulminant hepatic failure.

Cerebral edema and intracranial hypertension, commonly present in fulminant hepatic failure, may lead to brainstem herniation and limit the survival of comatose patients awaiting liver transplantation before a donor organ becomes available. Also, they are likely responsible for postoperative neurological morbidity and mortality. Although intracranial pressure monitoring has been proposed to aid clinical decision making in this setting, its use in the prevention of brainstem herniation preoperatively, in the selection of patients for liver transplantation who have the potential for neurological recovery and in the maintenance of cerebral perfusion during liver transplantation has not been examined in detail. To address these issues, we established a protocol for intracranial pressure monitoring in comatose patients with fulminant hepatic failure as part of their preoperative and intraoperative management. Twenty adults and three children underwent intracranial pressure monitoring. Ten patients required preoperative medical therapy with mannitol, barbiturates or both for a rise in intracranial pressure above 25 mm Hg. Four patients had a sustained lowering of intracranial pressure, three of whom survived hospitalization. Six patients had intracranial hypertension refractory to medical management, were removed from a waiting list for a donor organ and died with brainstem herniation. Of the remaining 17 patients, 3 died of other causes while awaiting a donor organ, 2 recovered spontaneously without neurological sequelae and 12 underwent liver transplantation. All but one patient undergoing liver transplantation had transient intraoperative intracranial hypertension develop, requiring medical treatment. The 12 patients who had transplants recovered neurologically and were discharged from the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Using transjugular intrahepatic portosystemic shunts to control variceal bleeding before liver transplantation.

OBJECTIVE: To determine the safety and efficacy of transjugular intrahepatic portosystemic shunts (TIPS) in controlling bleeding from esophageal varices in patients awaiting liver transplantation. DESIGN: Prospective, uncontrolled trial. SETTING: University medical center with an active liver transplant program. PATIENTS: Thirteen patients referred for liver transplantation with either active variceal hemorrhage or recurrent variceal hemorrhage despite sclerotherapy; four patients had been previously treated with surgical portosystemic shunts. INTERVENTION: An intrahepatic portosystemic shunt created via a transjugular approach to the hepatic veins using expandable, flexible metallic stents. MEASUREMENTS: Portal pressures before and after the creation of the shunt, the direction of portal blood flow at differing diameters of the shunts, procedure-related complications, and outcome in terms of survival, liver transplantation, and recurrent variceal bleeding. MAIN RESULTS: The transjugular intrahepatic portosystemic shunt was placed successfully in 13 patients, and bleeding was controlled acutely in all 13. After the procedure, the mean portal pressure decreased from 34 +/- 8.9 cm H2O to 22.4 +/- 5.4 cm H2O (P less than 0.001). No complications were associated with the procedure; however, two patients died of causes unrelated to the procedure. Seven patients subsequently underwent liver transplantation and are doing well, and three patients are being managed conservatively. Bleeding recurred in one patient 102 days after the procedure secondary to shunt occlusion caused by neointimal proliferation. CONCLUSION: Placement of a transjugular intrahepatic portosystemic shunt is apparently safe and effective therapy for variceal hemorrhage in patients referred for liver transplantation.

Estimation of total hepatic blood flow by duplex ultrasound.

The volume flow rate of blood in the portal vein and the hepatic artery was measured using a duplex ultrasound system. Two sections of the hepatic artery were studied; the common hepatic artery where measurements were made just after the bifurcation of the coeliac axis to splenic and hepatic arteries and the hepatic artery itself, where measurements were made just proximal to the porta hepatis in a straight stretch of artery overlying the portal vein. Total hepatic blood flow was taken as the sum of hepatic artery and portal vein flows. A group of 10 normal healthy volunteers in the fasting state was studied. The mean (SD) volume blood flow in the vessels was measured to be: hepatic artery 3.5 (45%) ml/min/kg, common hepatic artery 6.9 (30%) ml/min+/kg, portal vein 13.5 (21%) ml/min/kg, total hepatic flow 17.0 (16%) ml/min/kg.

Effect of octreotide on refractory AIDS-associated diarrhea. A prospective, multicenter clinical trial.

OBJECTIVE: To determine the efficacy and safety of octreotide for treatment of refractory, profuse diarrhea in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A prospective, open-label study. SETTING: Inpatient metabolic units of four university medical centers. PATIENTS: Fifty-one patients infected with human immunodeficiency virus (HIV) who had uncontrolled diarrhea (greater than or equal to 500-mL liquid stool per day) despite treatment with maximally tolerable doses of antidiarrheal medications. INTERVENTION: After initial baseline studies, patients received octreotide, 50 micrograms every 8 hours for 48 hours. If stool volume was not reduced to less than 250 mL/d, the dose of octreotide was increased stepwise to 100, 250, and 500 micrograms. MAIN RESULTS: Fifty men and one woman (mean age, 36.3 +/- 1.1 years) entered and completed the 28-day protocol (14 days of inpatient therapy and 14 days of outpatient therapy). Stool frequency and volume decreased significantly (6.5 +/- 0.5 stools per day on day 0 compared with 3.8 +/- 0.3 stools per day on day 21 [P less than 0.001] and 1604 +/- 180 mL/d on day 0 compared with 1084 +/- 162 mL/d on day 14 [P less than 0.001], respectively). Twenty-one patients (41.2%) were considered to be partial or complete responders (reduction in daily stool volume by greater than or equal to 50% of initial collections or reduction to less than or equal to 250 mL/d). Of the 21 responders, 14 (67%) had no identifiable pathogens at initial screening compared with 9 of 30 (30%) nonresponders (P less than 0.01). CONCLUSION: Patients with AIDS-associated refractory watery diarrhea, especially those without identifiable pathogens, may respond favorably to subcutaneously administered octreotide. This drug deserves further study in a randomized, placebo-controlled trial.

Splanchnic haemodynamic changes during acute hypoglycaemia in man.

1. Splanchnic haemodynamic changes were studied in seven healthy subjects during hypoglycaemia induced by the intravenous infusion of insulin. Superior mesenteric artery blood flow and cardiac output were examined noninvasively by a Doppler ultrasound technique. 2. Blood glucose concentration fell from 4.5 (0.14) mmol/l basally to 1.5 (0.09) mmol/l [mean (SEM), P less than 0.003] at the hypoglycaemic reaction ('R') and recovered to baseline by 'R' + 60 min. There was an associated rise in plasma glucagon, adrenaline and noradrenaline levels. 3. Superior mesenteric artery blood flow rose at 'R' from a basal value of 532 (38) ml/min to a peak of 803 (73) ml/min at 'R' + 10 min [mean (SEM), P less than 0.005] and remained significantly elevated until 'R' + 40 min. Resistance in this vessel fell by 33% at 'R' + 10 min (P less than 0.005) and remained significantly low until 'R' + 40 min. 4. Cardiac output rose by 33% at 'R' (P less than 0.004) and returned to normal by 'R' + 20 min. This was associated with a 24% rise in pulse rate (P less than 0.03), but no change in stroke volume or mean arterial pressure. Total peripheral resistance fell by 21% at 'R' (P less than 0.005) and had returned to normal by 'R' + 20 min. 5. The sustained rise in splanchnic blood flow during hypoglycaemic recovery may be of homoeostatic importance by providing metabolic fuel to the liver for gluconeogenesis.

Fasting and post-prandial splanchnic blood flow is reduced by a somatostatin analogue (octreotide) in man.

1. The effects of the subcutaneous administration of a long-acting somatostatin analogue (octreotide) or of placebo on the splanchnic blood flow response to a mixed solid meal has been examined in eight normal subjects by using a transcutaneous Doppler ultrasound technique. Each subject was studied on two occasions more than 1 week apart. 2. On the control day, feeding had a pronounced effect on both superior mesenteric artery and portal venous blood flows, causing a peak rise of 82% in superior mesenteric artery blood flow at 15 min and of 75% in portal venous blood flow at 30 min post-prandially (P less than 0.001). Blood flows remained elevated 2 h after the meal. Pulse and blood pressure showed no significant changes from baseline. 3. Octreotide reduced fasting superior mesenteric artery blood flow by 59% (P less than 0.05) and portal venous blood flow by 49% (P less than 0.01) and blunted the normal post-prandial rise. Pulse and blood pressure did not change in response to either the injection or the ingestion of the meal. 4. Octreotide suppressed the release of insulin, glucagon and pancreatic polypeptide in response to feeding and resulted in post-prandial hyperglycaemia. 5. The mechanism of action of octreotide on splanchnic blood flow is uncertain. It may be mediated via a direct vascular effect or it may act via suppression of vasoactive intestinal hormones.

Hepatitis C in patients undergoing liver transplantation.

OBJECTIVE: To determine the prevalence of antibodies to hepatitis C virus (anti-HCV) among patients undergoing liver transplantation and the relation between anti-HCV and post-transplant hepatitis. DESIGN: Retrospective cohort. PATIENTS: Serum samples from 128 patients who underwent liver transplantation. Sixty-six patients who had 6 months of follow-up and for whom both pretransplant and post-transplant serum samples were available were included in a study to asses the relation between anti-HCV and post-transplant hepatitis. MEASUREMENTS: Sera were tested for anti-HCV using an enzyme-linked immunosorbent assay (ELISA) and, if positive, two confirmatory tests were done. Patients had a biopsy every week until two specimens showed no abnormal findings. MAIN RESULTS: Only patients with chronic non-A, non-B hepatitis (15 of 30; 50%), alcoholic cirrhosis (7 of 19; 37%), and chronic hepatitis B infection (3 of 11; 27%) were anti-HCV positive. No patient with another form of chronic liver disease or with acute liver failure due to non-A, non-B hepatitis was anti-HCV positive. After transplantation, loss of anti-HCV was frequent and acquisition rare. Hepatitis developed in the graft in 17% of patients, but the incidence was similar among anti-HCV negative and anti-HCV-positive patients. CONCLUSIONS: Hepatitis C virus is a common cause of chronic liver disease in patients requiring liver transplantation, but anti-HCV is rarely found in patients with acute liver failure. Previous HCV infection, based on detection of anti-HCV, is not an independent risk factor for post-transplant hepatitis.

Hepatitis C in liver transplant recipients.

HCV infection is commonly found in patients with chronic liver disease undergoing liver transplantation. However, the presence of antibody to HCV does not appear to be associated with the development of hepatitis posttransplant. No other risk factors were identified that appear to predispose patients to development of hepatitis in the posttransplant period, including amount of blood product exposure. The role of immunosuppression in the acquisition and expression of liver disease caused by HCV remains to be determined.

Coeliac disease and malignancy of the duodenum: diagnosis by endoscopy, successful treatment of the malignancy, and response to a gluten free diet.

A patient presented with subtotal villous atrophy and a malignant duodenal tumour of uncertain histogenesis. He was successfully treated by resection and chemotherapy and the small bowel mucosa recovered on a gluten free diet. The tumour was diagnosed at upper gastrointestinal endoscopy when barium studies and abdominal computed tomography were normal, thus making this one of the earliest coeliac malignancies diagnosed.

Measurement of normal portal venous blood flow by Doppler ultrasound.

The volume flow rate of blood in the portal vein was measured using a duplex ultrasound system. The many errors inherent in the duplex method were assessed with particular reference to the portal vein and appropriate correction factors were obtained by in vitro calibration. The effect of posture on flow was investigated by examining 45 healthy volunteers in three different positions; standing, supine and tilted head down at 20 degrees from the horizontal. The mean volume blood flow in the supine position was 864 (188)ml/min (mean 1SD). When standing, the mean volume blood flow was significantly reduced by 26% to 662 (169)ml/min. There was, however, no significant difference between flow when supine and when tilted head down at 20 degrees from the horizontal.

Chronic liver disease. A case control study of the effect of previous blood transfusion.

A means of assessing hepatitis NANB virus infection, via blood transfusion, as a cause of chronic liver disease was investigated in a hospital in each of two cities in England. Patients with chronic liver disease were matched for age and sex with other patients in the same hospital and histories taken included details of previous operations and blood transfusions; if these were within ten years of the study enquiries were made of hospital records officers. All positive histories were found correct, but about one third of previous transfusions had been omitted by both case and control patients. Sixty-seven male and 35 female patients with chronic liver disease and their controls were included in analyses. The only clear difference which emerged related to residence for more than a year in the Middle or Far East by male case- (40%) or control- (21%) patients (P less than 0.05). The exclusion of patients with this history left only 34 pairs in which five (15%) of the case patients and one (3%) of the control patients had a transfusion history: this difference was not statistically significant. Although the study results have shown no clear evidence of blood transfusion as a major cause of chronic liver disease in Britain, the study method, with sufficient numbers to allow analyses of newly diagnosed patients with confirmed transfusion histories, could be used to provide an ongoing assessment of the risk.

Effects of ingestion of carbohydrate, fat, protein, and water on the mesenteric blood flow in man.

Transcutaneous Doppler ultrasound was used to measure superior mesenteric artery blood flow in 12 healthy volunteers in the fasting state and serially for 1 h after the ingestion of isocaloric and isovolaemic carbohydrate, fat, and protein liquid meals. The superior mesenteric artery blood flow increased significantly within 5 min of the end of each meal. The maximal responses were not significantly different but were reached at different times: carbohydrate, 64% at 15 min; fat, 60% at 30 min; and protein, 57% at 45 min. The response to the fat meal was significantly slower than the response to the carbohydrate, and the response to protein was slowest of all. In a further group of 20 fasted normal subjects no significant change in superior mesenteric artery blood flow occurred after drinking 400 ml of distilled water at room temperature. In seven of these subjects, drinking 400 ml of distilled water at 4 degrees C also did not affect mesenteric blood flow. These results indicate that the chemical nature of the meal and not the volume per se is a significant factor determining postprandial mesenteric hyperaemia.

Effects of exercise on mesenteric blood flow in man.

Transcutaneous Doppler ultrasound was used to assess the effects of exercise on both fasting and postprandial superior mesenteric artery blood flow. After treadmill exercise (speed 5 km/h, gradient 20%, duration 15 min) in 16 subjects, superior mesenteric artery blood flow decreased by 43% immediately after the end of the exercise and by 29% at five minutes and 24% at 10 minutes postexercise. The superior mesenteric artery blood flow response to a combination of a treadmill exercise and a liquid meal in 15 volunteers was significantly smaller at five minutes from the end of the stimuli, than the response to the meal alone (15 controls) (635 +/- 51 ml/min v 846 +/- 72 ml/min) (p less than 0.025), but not different at any other time. Thus exercise reduces mesenteric blood flow in both the fasting and postprandial state in normal subjects.