https://www.journal-of-hepatology.eu/article/S0168-8278(05)00684-7/pdf

Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies.

S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles.

Irritable bowel syndrome

Crohn's disease is a lifelong disease arising from an interaction between genetic and environmental factors, but observed predominantly in developed countries of the world. The precise aetiology is unknown and therefore a causal therapy is not yet available. Within Europe there is a distinct North–South gradient, but the incidence appears to have increased in Southern countries in recent years.1 Many patients live with a considerable symptom burden despite medical treatment in the hope that the aetiology of the disease will shortly be revealed and curative therapies emerge. Since it is uncertain that the precise pathogenesis of Crohn's disease will be revealed anytime soon, clinicians have to advise patients on the basis of information available today rather than an unknown future. Despite a multiplicity of randomised trials there will always be many questions that can only be answered by the exercise of judgement and opinion. This leads to differences in practice between clinicians, which may be brought into sharp relief by differences in emphasis between countries.

The Consensus endeavours to address these differences. The Consensus is not meant to supersede the guidelines of different countries (such as those from the UK,2 Germany,3 or France), which reach broadly the same conclusions since they are, after all, based on the same evidence. Rather, the aim of the Consensus is to promote a European perspective on the management of Crohn's disease and its dilemmas. Since the development of guidelines is an expensive and time-consuming process, it may help to avoid duplication of effort in the future. A Consensus is also considered important because an increasing number of therapeutic trials are based in Europe, especially in eastern European countries where practice guidelines have yet to be published.

This document is based on the European consensus on the diagnosis and management of Crohn's …

https://gut.bmj.com/content/gutjnl/55/suppl_1/i1.full.pdf

The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Definitions and diagnosis

Aims Carotid–femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population. Methods and results We gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors. Conclusion The present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.

Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors

https://www.gastrojournal.org/article/S0016-5085(00)64458-X/pdf

Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease

This study describes methods for extraction and quantification of calprotectin (L1 protein) in feces by enzyme immunoassay. This protein is a prominent antimicrobial component of neutrophils, monocytes, macrophages, and squamous epithelia. Calprotectin was stable in feces during storage for 7 days at room temperature. Small fecal samples taken from a 24-h feces collection gave a reliable estimate of calprotectin. Within-assay precision was 1.9%, and between-assay precision 14.8%. In healthy subjects (n = 33) median fecal calprotectin was 2025 micrograms/l and in hospital controls (n = 40) 10,500 micrograms/l. Median values in patients with Crohn's disease (n = 21) was 43,000 micrograms/l and in ulcerative colitis (n = 17) 40,000 micrograms/l. Fecal calprotectin was significantly correlated to fecal alpha 1-antitrypsin in the patients with Crohn's disease. Ten of 11 patients with gastrointestinal carcinomas had calprotectin level above the suggested reference limit of 6740 micrograms/l.

Assessment of the neutrophil dominating protein calprotectin in feces : a methodologic study

Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin.

BACKGROUND AND AIMS—Assessing the presence and degree of intestinal inflammation objectively, simply, and reliably is a significant problem in gastroenterology. We assessed faecal excretion of calprotectin, a stable neutrophil specific marker, as an index of intestinal inflammation and its potential use as a screening test to discriminate between patients with Crohn's disease and those with irritable bowel syndrome.
METHODS—The validity of faecal calprotectin as a marker of intestinal inflammation was assessed in 22 patients with Crohn's disease (35 studies) by comparing faecal excretions and concentrations using four day faecal excretion of 111indium white cells. A cross sectional study assessed the sensitivity of faecal calprotectin concentration for the detection of established Crohn's disease (n=116). A prospective study assessed the value of faecal calprotectin in discriminating between patients with Crohn's disease and irritable bowel syndrome in 220 patients referred to a gastroenterology clinic.
RESULTS—Four day faecal excretion of 111indium (median 8.7%; 95% confidence interval (CI) 7-17%; normal <1.0%) correlated significantly (p<0.0001) with daily (median ranged from 39 to 47 mg; normal <3 mg; r=0.76-0.82) and four day faecal calprotectin excretion (median 101 mg; 95% CI 45-168 mg; normal <11 mg; r=0.80) and single stool calprotectin concentrations (median 118 mg/l; 95% CI 36-175 mg/l; normal <10 mg/l; r=0.70) in patients with Crohn's disease. The cross sectional study showed a sensitivity of 96% for calprotectin in discriminating between normal subjects (2 mg/l; 95% CI 2-3 mg/l) and those with Crohn's disease (91 mg/l; 95% CI 59-105 mg/l). With a cut off point of 30 mg/l faecal calprotectin has 100% sensitivity and 97% specificity in discriminating between active Crohn's disease and irritable bowel syndrome.
CONCLUSION—The calprotectin method may be a useful adjuvant for discriminating between patients with Crohn's disease and irritable bowel syndrome.


Keywords: inflammatory bowel disease; Crohn's disease; intestinal inflammation; irritable bowel syndrome

https://gut.bmj.com/content/gutjnl/47/4/506.full.pdf

A simple method for assessing intestinal inflammation in Crohn's disease

Background: Several studies have suggested that clinical indices of disease activity in inflammatory bowel disease (IBD) do not adequately reflect the degree of inflammation in most such patients. Faecal excretion of indium-111-labelled neutrophilic granulocytes has been suggested as the gold standard of disease activity, but its complexity and high cost and the exposure of patients to ionizing irradiation have limited the use of this technique. The aim of this study was to investigate the correlation between the faecal excretion of the granulocyte marker protein calprotectin and that of 111In-labelled granulocytes. Methods: Calprotectin in stool extracts from 19 patients with Crohn's disease (CD), 10 with ulcerative colitis (UC), and 9 presumably healthy controls was assessed with a simple enzyme-linked immunosorbent assay. Simultaneously, the faecal excretion of autologous 111In-labelled granulocytes was measured. Results: There was a strong correlation between the average daily excretion of calprotecti...

Correlation between Faecal Excretion of Indium-111-Labelled Granulocytes and Calprotectin, a Granulocyte Marker Protein, in Patients with Inflammatory Bowel Disease

Magne K. Fagerhol

Papers

Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease

Assessment of the neutrophil dominating protein calprotectin in feces : a methodologic study

Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin.

A simple method for assessing intestinal inflammation in Crohn's disease

Correlation between Faecal Excretion of Indium-111-Labelled Granulocytes and Calprotectin, a Granulocyte Marker Protein, in Patients with Inflammatory Bowel Disease