SUMMARY BackgroundAminosalicylates are first-choice treatment for mild-to-moderately active ulcerative colitis (UC); however, multi-dosing regimens are inconvenient.

Antibiotics can be omitted in selected patients with mild colonic diverticulitis and should be given on indication only.

Thromb Haemost 2004; 91: 506-13form. No release of MMP-2 from the graft could be detected. In contrast, plasma levels of MMP-9 increased sharply during the anhepatic and postreperfusion periods. Peak MMP-9 levels of about eight times above baseline were found at 30 minutes after reperfusion. Most MMP-9 appeared to be in its active/inhibitorcomplexed form. No significant differences were observed between the three treatment groups. However, in patients with more severe ischemia/reperfusion (I/R) injury the MMP-9 concentration, particularly of the active/inhibitor-complexed form, remained high at 120 minutes postreperfusion compared to patients with no or mild I/R injury. The decrease in plasma levels of MMP-2,TIMP-1 and TIMP-2 during OLT occurred irrespective of the severity of the I/R injury. There was a significant correlation between MMP-9 and t-PA levels, but not with TNF-α. In conclusion, OLT is associated with a sharp increase of MMP-9 during the anhepatic and postreperfusion periods, which coincided with the changes in t-PA. MMP-2, TIMP-1 and TIMP-2 gradually decreased during OLT. The composition of these MMPs was not altered by the use of aprotinin, suggesting that serine-protease/plasmin-independent pathways are responsible for MMP regulation during OLT. In addition, only MMP-9 seems to be involved in I/R injury during human liver transplantation. KeywordsAprotinin, ischemia/reperfusion injury, liver transplantation, matrix metalloproteinases, plasmin Summary Uncontrolled activation of matrix metalloproteinases (MMPs) can result in tissue injury and inflammation, yet little is known about the activation of MMPs during orthotopic liver transplantation (OLT). OLT is associated with increased fibrinolytic activity due to elevated plasmin generation. The serine-protease plasmin not only causes degradation of fibrin clots but is also thought, amongst others, to play a role in the activation of some matrix metalloproteinases.We therefore studied the evolution of MMP-2 and -9 plasma concentrations during OLT and the effect of serine-protease inhibition by aprotinin on the level and activation of these MMPs. In a group of 24 patients who participated in a randomized, double-blind, placebo-controlled study we determined serial MMP-2 and MMP-9 plasma levels during transplantation using ELISA (total MMP), activity assays (activatable MMP) and zymography. In addition, the MMP-inhibitors TIMP-1 and TIMP-2 were assessed by ELISA. The putative regulating factors tumor necrosis factor alpha (TNF-α) and tissue-type plasminogen activator (t-PA) were assessed as well. Patients were administered high-dose aprotinin, regular-dose aprotinin or placebo during surgery. Plasma TIMP-1, TIMP-2 and MMP-2 level gradually decreased during transplantation. Approximately twothirds of total MMP-2 appeared to be in its activatable proMMP Correspondence to:

ObjectiveThe aim of this study was to describe the long-term health outcomes of children born to mothers with inflammatory bowel disease (IBD) and to assess the impact of maternal IBD medication use on these outcomes.DesignWe performed a multicentre retrospective study in The Netherlands. Women with IBD who gave birth between 1999 and 2018 were enrolled from 20 participating hospitals. Information regarding disease characteristics, medication use, lifestyle, pregnancy outcomes and long-term health outcomes of children was retrieved from mothers and medical charts. After consent of both parents, outcomes until 5 years were also collected from general practitioners. Our primary aim was to assess infection rate and our secondary aims were to assess adverse reactions to vaccinations, growth, autoimmune diseases and malignancies.ResultsWe included 1000 children born to 626 mothers (381 (61%) Crohn’s disease, 225 (36%) ulcerative colitis and 20 (3%) IBD unclassified). In total, 196 (20%) had intrauterine exposure to anti-tumour necrosis factor-α (anti-TNF-α) (60 with concomitant thiopurine) and 240 (24%) were exposed to thiopurine monotherapy. The 564 children (56%) not exposed to anti-TNF-α and/or thiopurine served as control group. There was no association between adverse long-term health outcomes and in utero exposure to IBD treatment. We did find an increased rate of intrahepatic cholestasis of pregnancy (ICP) in case thiopurine was used during the pregnancy without affecting birth outcomes and long-term health outcomes of children. All outcomes correspond with the general age-adjusted population.ConclusionIn our study, we found no association between in utero exposure to anti-TNF-α and/or thiopurine and the long-term outcomes antibiotic-treated infections, severe infections needing hospital admission, adverse reactions to vaccinations, growth failure, autoimmune diseases and malignancies.

SummaryMatrix metalloproteinases (MMPs) have the ability to degrade basement membranes and may thus play an important role in extracellular matrix turnover in liver fibrosis and carcinogene-sis. Serum levels of MMPs have been suggested as diagnostic markers in these processes.We measured serum MMP-2 and MMP-9 by ELISA in 91 patients with chronic liver disease, including 25 patients with hepatocellular carcinoma (HCC), and in 60 controls.MMP-2 was significantly higher in patients with chronic liver disease compared to controls, and increased with Child-Pugh class. There was a significant correlation between MMP-2 and liver function (bilirubin, albumin, and prothrombin time), and a strong opposite correlation between MMP-9 and these parameters.MMP-2 levels in patients with HCC were significantly higher than in controls, but comparable to patients with chronic liver disease without this malignancy. MMP-9 yielded no significant differences between patients with or without HCC and controls.Serum MMP-2 and to a lesser extent MMP-9 correlate with the severity of liver disease and may reflect changes in extracellular matrix remodeling. Due to a considerable overlap in patients with chronic liver disease with or without HCC, MMP-2 and MMP-9 can not be used as a diagnostic marker for HCC.Theme paper: Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.