Pieter Evenepoel

Major Coagulation Disturbances During Fractionated Plasma Separation and Adsorption

Fractionated Plasma Separation and Adsorption (FPSA) is a novel nonbiologic detoxification system for the removal of protein‐bound solutes. FPSA is used to bridge patients during fulminant liver failure, either to functional recovery or to liver transplantation. Besides liver failure associated protein bound solutes, several important uremic retention solutes share important protein binding. We observed repeated occlusive thrombosis of the arterio‐venous conduit during FPSA in hemodialysis (HD) patients, resulting in acute loss of function. A major reduction of several coagulation factors was demonstrated, exceeding 50% for factor II, factor X and protein C. Broad disturbances of the coagulation system were confirmed in FPSA treated liver failure patients. An ex vivo recirculation model demonstrated nonspecific adsorption of coagulation factors protein S and protein C on the anion exchange cartridge. Direct contact between fractionated plasma and the Prometh02 anion exchanger causes significant adsorption of procoagulant and anti‐coagulant factors, associated with clinically relevant adverse events.

The influence of inulin on the absorption of nitrogen and the production of metabolites of protein fermentation in the colon

In the present study, the production and fate of bacterial metabolites in the colon were investigated in a direct way using two substrates labelled with stable isotopes: lactose [(15)N,(15)N]ureide as a source of labelled ammonia and egg proteins intrinsically labelled with [(2)H4]tyrosine as a precursor of [(2)H4]p-cresol. Both ammonia and phenolic compounds are believed to be carcinogenic. Stimulation of carbohydrate fermentation in order to prevent accumulation of these toxic metabolites was induced by inclusion of inulin in a test meal or by addition of inulin to the daily diet, allowing us to distinguish between changes induced by the actual presence of a fermentable carbohydrate and effects caused by a long-term dietary intervention. When a single dose of inulin was administered together with the labelled substrates, a significant increase in faecal (15)N excretion, accompanied by a proportional decrease in urinary (15)N excretion was observed, probably reflecting an enhanced uptake of ammonia for bacterial biosynthesis, since an increased concentration of labelled N in bacterial pellets was found. A statistically significant reduction of urinary [(2)H4]p-cresol excretion was also noted. Upon supplementation of inulin to the daily diet during 4 weeks, however, only a tendency towards decreased urinary excretion of both labelled and unlabelled p-cresol was noted. Further studies are warranted to confirm these results in a larger cohort.

Activity related increase of breath nitric oxide in Crohn's disease and ulcerative colitis: A manifestation of systemic involvement

Nitric oxide (NO) is an important mediator of inflammation in several pathological conditions. Patients with lung diseases, like asthma, have higher levels of exhaled NO (eNO) in active disease in comparison with healthy volunteers. Aspirated colonic gas in patients with ulcerative colitis (UC) showed more than 100 times higher levels of NO in comparison with normal subjects. Crohns disease (CD) and UC are associated with a variety of systemic manifestations, although lung diseases as an extra-intestinal expression of inflammatory bowel disease (IBD) are not well investigated. In some studies, clinical and subclinical pulmonary abnormalities are described in active IBD as well as in the stable situation. The aim of the present study is to evaluate whether eNO is increased in patients with active IBD and to investigate whether there exists a correlation between (1) the eNO levels and the disease activity, and (2) the spirometry and the disease activity in a subgroup of patients. In 31 patients with CD (mean age 36.8 +/- 12.9 years) and 24 patients with UC (mean age 38.0 +/- 14.7 years) the Crohns Disease Activity Index (CDAI) and Colitis Activity Index (CAI) were measured, respectively. Exhaled NO was measured with a chemiluminescence analyzer, according to standardized criteria. In a subgroup of CD patients, spirometry was also performed according to standardized criteria. The mean CDAI in CD patients was 192.4 +/- 94.3 and their mean eNO value was 13.5 +/- 4.6 ppb. For UC the mean CAI was 6.2 +/- 4.8 and the mean eNO value was 15.8 +/- 6.2 ppb. In a matched control group of 27 healthy, non-smoking volunteers (mean age of 33.7 +/- 13.2 years) the eNO was 10.2 +/- 2.5 ppb (P < 0.05 compared to CD and P < 0.01 compared to UC). There was a disease-activity-related increase of the eNO level in patients with IBD. For patients with UC the correlation coefficient (r = 0.63, P < 0.001) was more pronounced than for CD (r = 0.39, P < 0.05). In 17 patients with CD, spirometry was available at the time of the eNO measurement. We found a significant negative correlation between the CDAI and the FEV1 and FVC in these patients (r = -0.559, P = 0.02 and r = -0.634, P = 0.006, respectively). We conclude that eNO is increased in active IBD and correlates with the activity of the disease; furthermore, we found a negative correlation between spirometry and disease activity in patients with CD. These observations strengthen the arguments that IBD is a systemic disease. Further research is needed to try to explain the significance of an increased eNO in IBD.