Status on fasting definition for blood sampling in the Nordic countries - time for a harmonized definition.

The preanalytical phase contains a vast number of practices whose variation may influence the results of laboratory testing and should, therefore, be standardized. The Working Group on Preanalytical Phase of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM WG-PA) has suggested a standardization of venous blood specimen collection (VBSC) requirements for fasting samples including 12 h fasting time and water ad lib in the morning prior to specimen collection. The Nordic Scientific Preanalytical Working Group investigated the fasting definitions used in the Nordic countries.

Hypopituitarism 3 and 12 months after traumatic brain injury and subarachnoid haemorrhage.

Objective: High prevalence of hypopituitarism (HP) has been reported after traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH). The aim of the study was to prospectively evaluate the prevalence and progression of HP in patients after TBI and SAH in Icelandic population.

Design: A 12 month prospective single-centre study.

Structure-activity relationship studies leading to the identification of (2E)-3-[l-[(2,4-dichlorophenyl)methyl]-5-fluoro-3-methyl-lH-indol-7-yl]-N-[(4,5-dichloro-2-thienyl)sulfonyl]-2-propenamide (DG-041), a potent and selective prostanoid EP3 receptor antagonist, as a novel antiplatelet agent that does not prolong bleeding.

The EP(3) receptor on the platelet mediates prostaglandin E(2) potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to the identification of diverse peri-substituted heterocycles as potent and selective EP(3) receptor antagonists. A simultaneous chemical optimization and druglike assessment of prioritized molecules converged on a lead compound 50 (DG-041) that displayed favorable in vitro and functional activities as an inhibitor of human platelet aggregation.

Discovery of 4-[(2S)-2-{[4-(4-chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl]butanoic acid (DG-051) as a novel leukotriene A4 hydrolase inhibitor of leukotriene B4 biosynthesis.

Both in-house human genetic and literature data have converged on the identification of leukotriene 4 hydrolase (LTA(4)H) as a key target for the treatment of cardiovascular disease. We combined fragment-based crystallography screening with an iterative medicinal chemistry effort to optimize inhibitors of LTA(4)H. Ligand efficiency was followed throughout our structure-activity studies.

Antagonists of the EP3 receptor for prostaglandin E2 are novel antiplatelet agents that do not prolong bleeding.

Myocardial infarction and stroke are caused by blood clots forming over a ruptured or denuded atherosclerotic plaque (atherothrombosis). Production of prostaglandin E(2) (PGE(2)) by an inflamed plaque exacerbates atherothrombosis and may limit the effectiveness of current therapeutics. Platelets express multiple G-protein coupled receptors, including receptors for ADP and PGE(2).

The effects of AZD3582 [4-(nitroxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate], and naproxen on key pathogenic steps in NSAID-enteropathy in the rat.

Background: The pathogenesis of NSAID-induced enteropathy may involve dual inhibition of the cyclooxygenase (1 and 2) and a topical effect with sequential increased intestinal permeability, development of inflammation and ulcers. It has been suggested that nitric-oxide donating drugs cause significantly less gastrointestinal injury by counteracting for NSAID-induced reductions in blood flow.

Aims: To compare the effects of AZD3582 [4-(nitroxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate], and naproxen on key pathogenic steps in NSAID-enteropathy in the rat.

Role of bile in pathogenesis of indomethacin-induced enteropathy.

Ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) causes an enteropathy. The pathogenesis involves biochemical initiation of intestinal mucosal damage due to NSAID-induced inhibition of cyclooxygenase and the topical effects of these drugs. These effects lead to increased intestinal permeability and inflammation.

[Effect of Pentavac and MMR vaccination on the intestine.].

Objective: The safety of infant vaccination has been questioned in recent years. In particular it has been suggested that the measles, mumps and rubella (MMR) vaccination leads to brain damage manifesting as autism consequent to the development of an "enterocolitis" in the immediate post-vaccination period.

Aim: To assess if MMR vaccination is associated with sub-clinical intestinal inflammation which is central to the autistic "enterocolitis" theory.

Subclinical intestinal inflammation and sacroiliac changes in relatives of patients with ankylosing spondylitis.

Background & Aims: It has been suggested that subclinical intestinal inflammation plays a pathogenic role in the spondylarthropathy of ankylosing spondylitis (AS). We assessed the possible presence and inheritance pattern of subclinical intestinal inflammation in first-degree relatives of patients with AS. The relationship between this inflammation and the subjects' HLA-B27 genotype as well as computerized tomographic sacroiliac abnormalities was also assessed.

Subclinical intestinal inflammation: an inherited abnormality in Crohn's disease relatives?

Background & Aims: One approach to unraveling the genetics of complex inherited disease, such as Crohn's disease, is to search for subclinical disease markers among unaffected family members. We assessed the possible presence, prevalence, and inheritance pattern of subclinical intestinal inflammation in apparently healthy relatives of patients with Crohn's disease.

Methods: A total of 49 patients with Crohn's disease, 16 spouses, and 151 (58%) of 260 available first-degree relatives underwent a test for intestinal inflammation (fecal calprotectin concentration).

Effect of Pentavac and measles-mumps-rubella (MMR) vaccination on the intestine.

Background: The safety of infant vaccination has been questioned in recent years. In particular it has been suggested that the measles, mumps, and rubella (MMR) vaccination leads to brain damage manifesting as autism consequent to the development of an "enterocolitis" in the immediate post-vaccination period.

Aim: To assess if MMR vaccination is associated with subclinical intestinal inflammation, which is central to the autistic "enterocolitis" theory.

Use of surrogate markers of inflammation and Rome criteria to distinguish organic from nonorganic intestinal disease.

Background & Aims: Differentiating symptoms of irritable bowel syndrome (IBS) from those of organic intestinal disease is a familiar problem for physicians. The aim of this study was to assess the sensitivity, specificity, and odds ratios (ORs) of fecal calprotectin, small intestinal permeability, Rome I criteria, and laboratory markers of inflammation (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], blood count) in distinguishing organic from nonorganic intestinal disease.

Methods: A total of 602 new referrals to a gastroenterology clinic who had symptoms suggestive of IBS or organic intestinal disease were studied for these parameters.

COX-1 and 2, intestinal integrity, and pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in mice.

Background & Aims: The pathogenesis of nonsteroidal anti-inflammatory drug-induced enteropathy is controversial, but it is thought that cyclooxygenase-1 (COX-1) inhibition is of pivotal importance. We compared small intestinal function and morphology in untreated wild-type, COX-1- and COX-2-deficient mice and the effect of indomethacin, selective COX-1 (SC-560), and COX-2 (celecoxib) inhibition.

Methods: Intestinal permeability ((51)CrEDTA), inflammation (fecal granulocyte marker protein), prostaglandin E(2) (PGE(2)) levels, and macroscopic and microscopic appearances were assessed at baseline and after the drugs.

Effects of NSAIDs on cryoprobe-induced gastric ulcer healing in rats.

Background: Failure of ulcer healing may be critically important to the development of serious gastrointestinal complications in patients on long-term NSAIDs.

Aim: To determine the effect of indometacin, celecoxib, a cyclooxygenase-2-specific inhibitor, and nabumetone, a pro-drug, on ulcer healing rates in the rat.

Methods: Gastric ulcers were induced using a cryoprobe.

Epidemiology and differential diagnosis of NSAID-induced injury to the mucosa of the small intestine.

Non-steroidal anti-inflammatory drugs cause small-bowel inflammation in about 60% of patients receiving these drugs long-term. The inflammation is associated with small intestinal bleeding, protein loss, ulcers and occasionally strictures. Treatment options for NSAID enteropathy include metronidazole, sulphasalazine and misoprostol, and some patients may require surgery.

Faecal calprotectin and faecal occult blood tests in the diagnosis of colorectal carcinoma and adenoma.

Background And Aims: Testing for faecal occult blood has become an accepted technique of non-invasive screening for colorectal neoplasia but lack of sensitivity remains a problem. The aim of this study was to compare the sensitivity and specificity of faecal calprotectin and faecal occult blood in patients with colorectal cancer and colonic polyps.

Methods: Faecal calprotectin and occult blood were assessed in 62 patients with colorectal carcinoma and 233 patients referred for colonoscopy.

Selective inhibition of COX-2 in humans is associated with less gastrointestinal injury: a comparison of nimesulide and naproxen.

Background: Selective inhibitors of cyclooxygenase (COX)-2 may provoke less gastric damage and platelet inhibition than conventional non-steroidal anti-inflammatory drugs.

Aims: We compared the biochemical and gastrointestinal effects of nimesulide, a potent and selective COX-2 inhibitor, with naproxen which exhibits no selectivity.

Subjects: Thirty six healthy volunteers were randomised to nimesulide 100 mg or naproxen 500 mg twice daily for two weeks in a double blind, crossover study with a washout between treatments.

Gastric acid secretion in cyclooxygenase-1 deficient mice.

Background: Constitutive cyclooxygenase-1 enzyme synthesizes prostaglandins which are thought to play an important role in the functional integrity of the stomach gastric mucosa. Recently, it was shown that cyclooxygenase-1 deficient mutant mice did not develop spontaneous gastric pathology and appear less sensitive to indomethacin-induced gastric damage.

Aim: To investigate gastric acid secretion in cyclooxygenase-1 deficient mutant mice.

Comparison of the intestinal toxicity of celecoxib, a selective COX-2 inhibitor, and indomethacin in the experimental rat.

Background: It is suggested that the gastrointestinal toxicity of conventional non-steroid anti-inflammatory drugs (NSAIDs) is due to a 'topical' effect in addition to inhibition of the mucosal constitutive cyclo-oxygenase-1 (COX-1) enzyme. COX-2 selective inhibitors have been shown to have excellent gastrointestinal tolerability, but it is not known whether this is due to their selectivity and/or a lack of a 'topical' effect. We assessed the effects of celecoxib (a highly selective COX-2 inhibitor) on key pathophysiologic events in NSAID enteropathy.

COX-2 inhibition with rofecoxib does not increase intestinal permeability in healthy subjects: a double blind crossover study comparing rofecoxib with placebo and indomethacin.

Background: Acute and chronic use of non-steroidal anti-inflammatory drugs can increase intestinal permeability. Rofecoxib, which selectively inhibits cyclooxygenase 2 (COX-2), is a novel anti-inflammatory drug with the potential to produce minimal gastrointestinal toxic effects while retaining clinical efficacy.

Aims: To assess the potential for rofecoxib to affect the intestine adversely, in comparison with placebo and indomethacin.

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

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 (111)indium white cells.

The prevalence and severity of intestinal disaccharidase deficiency in human immunodeficiency virus-infected subjects.

Background: Gastrointestinal symptoms are distressing features of human immunodeficiency virus (HIV) infection, and management is often empirical, including withdrawal of dietary lactose. We assessed the prevalence and severity of intestinal disaccharidase deficiency in vitro and in vivo.

Methods: Fifty-four HIV-seropositive patients (19 HIV well +/- mild diarrhoea, 7 acquired immunodeficiency syndrome (AIDS) well, and 28 AIDS with diarrhoea) were studied with a combined non-invasive absorption-permeability-disaccharidase test that enables quantitative assessment of the rate of intestinal hydrolysis of lactose, sucrose, and palatinose.

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

Background & Aims: Prediction of relapse of inflammatory bowel disease has important implications for therapeutic strategies. We assessed whether measurement of intestinal permeability and inflammation could predict relapse of inflammatory bowel disease (IBD).

Methods: Forty-three patients with Crohn's disease (CD) and 37 with ulcerative colitis (UC) in clinical remission provided a stool sample to be assayed for calprotectin (a neutrophil-specific marker), and patients with CD additionally underwent a small intestinal permeability test.

Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat.

Background: The pathogenesis of NSAID-induced gastrointestinal damage is believed to involve a nonprostaglandin dependent effect as well as prostaglandin dependent effects. One suggestion is that the nonprostaglandin mechanism involves uncoupling of mitochondrial oxidative phosphorylation.

Aims: To assess the role of uncoupling of mitochondrial oxidative phosphorylation in the pathogenesis of small intestinal damage in the rat.

Assessment of ileal pouch inflammation by single-stool calprotectin assay.

Purpose: Assessment of inflammation within the ileal pouch to establish a diagnosis of "pouchitis" requires both pouch endoscopy and biopsy because there can be a poor correlation between macroscopic and histologic assessments of inflammation. A simplified diagnostic test would be of clinical advantage. Calprotectin is a stable myelomonocytic protein, measurable in feces.