SummaryThe North American Immune Tolerance Registry was initiated to study of immune tolerance (ITT) in Canada and the United States with respect to: 1) therapeutic regimens in use for haemophilia A (HA) and B (HB) inhibitor patients; 2) therapeutic outcomes; 3) potential predictors of successful outcome and 4) complications of therapy. Data on 188 ITT courses was collected by questionnaire from 60 haemophilia centers from 1993-99. Among the completed courses, the overall ITT success rate was 70% (115/164) for all HA and 31% (5/16) for all HB. Outcome parameters noted to be predictive of ITT success for all HA were 1) pre-ITT induction (p = 0.003), 2) ITT peak (p = 0.007) and 3) historical pre ITT peak (p = 0.04) inhibitor titres. An inverse correlation between total daily dose (units/kg/day) and success: (80% with under 50; 71% with 50-99; 73% with 100-199; and 41% with ≥ 200, p = 0.01) was found. Outcome predictors were not evaluable for HB, although adverse reactions to therapy, including nephrotic syndrome, and access complications were more common among failed courses. Infection most often complicated the use of access catheters. These results are discussed within the context of the international ITT registry and upcoming prospective ITT study.

Several studies performed in alcoholics with advanced liver disease have demonstrated a positive correlation between the serum-ascites albumin gradient (SAAG) and measured portal venous pressure. A single study performed in 15 patients with exudative malignant ascites and 29 patients with alcoholic liver disease demonstrated that a SAAG of less than 1.1 was essentially diagnostic of a malignant origin of the ascites. In an effort to confirm and extend these observations to individuals with nonalcoholic liver disease, 24 patients with nonalcoholic liver disease and 11 with alcoholic liver disease undergoing orthotopic liver transplantation (OTLx) were studied. At the time of liver transplantation, each had their serum and ascitic fluid albumin levels determined, the gradient calculated, and their portal venous pressure (PVP) as well as the corrected portal venous pressure (PPc) measured directly. A significant correlation (r = 0.624) between the PPc and the SAAG was found in the 11 alcoholics (P less than 0.05). No such correlation existed for those with nonalcoholic liver disease (r = 0.398). Moreover, a SAAG less than 1.1 was found in three of nonalcoholics with cirrhosis in the absence of an abdominal malignancy. We conclude that (1) the SAAG and PPc are statistically related to each other in individuals with alcoholic liver disease but not in those with a nonalcoholic cause for cirrhosis, and (2) SAAG less than 1.1 is not diagnostic of abdominal malignancy but can occur in those with advanced nonmalignant hepatic disease.

Spontaneous bacterial peritonitis (SBP) is a common complication of advanced liver disease, which has a reported prevalence of between 4 and 27%. Frequent bacteremias due to inadequate host defense mechanisms, particularly the reticuloendothelial system (RES), with seeding of an ascitic fluid that lacks a normal opsonic activity, is believed to be the principal cause of SBP. Little data exist as to the role of serum levels of complement and immunoglobulins as well as the cell-mediated immune system in the pathogenesis of SBP. The aim of this study was to determine the serum levels of the third and fourth components of complement (C3, C4), total hemolytic complement activity (CH100), and properdin factor B (PFB) and immunoglobulins G, A, and M and various T-cell parameters in individuals admitted to hospital with ascites and advanced liver disease and to determine whether one or more of these factors could be used to predict the development of SBP in patients with advanced liver disease. Fourteen consecutive patients (nine male and five female; age 47.5 +/- 3.1 years, mean +/- SEM) with end-stage liver disease and ascites, who were evaluated for possible liver transplant at the University of Pittsburgh and who developed SBP, comprised the study group. The diagnosis of SBP was determined by positive ascitic fluid culture (three patients) and/or ascitic fluid neutrophil count of greater than 250 cells/mm3 (all patients). The control group consisted of 14 patients, matched for type of liver disease, age, and sex, who did not develop SBP.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the effect of portal hypertension and diminished portal venous blood flow to the liver on hepatic regeneration, male rats were subjected to partial portal vein ligation and subsequently to a two-thirds partial hepatectomy. The levels of ornithine decarboxylase activity at 6 h after partial hepatectomy were greater (p < 0.001) in the rats with prior partial portal vein ligation than in those without portal hypertension. The rats with prior partial portal vein ligation also had greater (p < 0.005) levels of thymidine kinase activity at 48 h after partial hepatectomy than did those without portal hypertension. Hepatic sex hormone receptor activity was not affected by prior partial portal vein ligation either before or after partial hepatectomy. The reductions in both estrogen and androgen receptor activity observed in the hepatic cytosol after partial hepatectomy were similar to those observed in control animals. These data indicate that animals with portal hypertension having a diminished hepatic portal blood flow have a normal capacity to regenerate hepatic mass following a hepatic resection. Keywords hepatic regeneration; portal hypertension; cirrhosis; liver growth; protal blood flow The origin and nature of the factors that control hepatic regeneration remain unresolved. Portal blood has been shown to be hepatotrophic as compared to peripheral blood. 1 However, controversy continues to surround the relative importance of the qualitative changes (hormonal factors) and the quantitative changes (blood flow parameters) in portal blood that occur after partial hepatectomy as they relate to the hepatic regeneration that occurs after a partial hepatic resection. 1-8 The pancreatic hormones, insulin and glucagon, have been shown to modulate, at least in part, the regenerative response that occurs after partial hepatectomy. 1-5 These data, however, do not negate an important role for hepatic blood flow, particularly portal venous blood flow, in the regulation of hepatic regeneration following partial hepatectomy. [6][7][8] The role of hepatic blood flow in modulating liver regeneration was first suggested by the observation that hepatic atrophy occurs after an Eck fistula (end-to-side portal caval shunt). 6 This hepatic atrophy was thought to be the result of a reduced hepatic blood flow,

This study compares the effects of two different benzodiazepines used for conscious sedation during combined upper gastrointestinal endoscopy (EGD) and colonoscopy. Subjects were assessed for their degree of analgesia and amnesia for the procedure, prior experience with endoscopy, and willingness to undergo another similar procedure should such be necessary. The patients were randomized single blind to receive either midazolam or diazepam for their preprocedure sedation. The amount of preprocedure sedation utilized was determined by titration of the dose to achieve slurring of speech. Prior to receiving either agent, the subjects were shown a standard card containing pictures of 10 common objects, were asked to name and remember them, and were told they would be "quizzed" (at 30 min and 24 hr) after being sedated for their recollection as to the objects pictured on the card. Each subject filled out a questionnaire addressing their perceived discomfort during the endoscopic procedure and their memory of the procedure 24 hr after the procedure. Sixty-three percent of the midazolam-sedated subjects reported total amnesia for their colonoscopy vs 20% of diazepam-sedated patients (P less than 0.001). Fifty-three percent of midazolam-sedated patients reported total amnesia of their upper gastrointestinal endoscopy vs only 23% of diazepam-sedated subjects (P less than 0.05). The midazolam-sedated subjects reported experiencing less pain with both upper gastrointestinal endoscopy (P less than 0.05) and colonoscopy (P less than 0.001) than did the diazepam-sedated group. Most importantly, the midazolam group was more willing to undergo another similar endoscopic procedure should they be asked to do so by their physician (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)