[Primary manifestation of Chrohn's disease with toxic megacolon in a patient with long-time primary sclerosing cholangitis]. / Debut af morbus Crohn med toksisk megacolon hos en patient med mangeårig primær skleroserende kolangitis.

A 38-year-old man with a ten year long history of primary sclerosing cholangitis without previous symptoms of inflammatory bowel disease was admitted to hospital after a few weeks with abdominal pain, diarrhoea and fever. A computed tomography revealed that the colon was dilated to a diameter of 17 cm. Based on a diagnosis of toxic megacolon, a subtotal colectomy and an ileostomy were carried out. Gross and histological examination showed changes compatible with Crohn's disease. Ten years' history of primary sclerosing cholangitis before onset of inflammatory bowel disease is very unusual, and toxic colon as the initial symptom of Crohn's disease is rare.

Cyclooxygenase-2, multidrug resistance 1, and breast cancer resistance protein gene polymorphisms and inflammatory bowel disease in the Danish population.

OBJECTIVE: Crohn's disease (CD) and ulcerative colitis (UC) are characterized by an impaired mucosal defence to normal constituents of the intestinal flora and a dysregulated inflammatory response. The purpose of the study was to investigate whether single nucleotide polymorphisms (SNPs) in genes involved in these processes were associated with CD and UC. MATERIAL AND METHODS: Allele frequencies of the cyclooxygenase 2 (COX-2/PTGS2/PGHS2) G-765C and breast cancer resistance protein (BCRP/ABCG2) C421A as well as allele and haplotype frequencies of multidrug resistance 1 (MDR1, ABCB1) SNPs G2677T/A, C3435T and G-rs3789243-A (intron 3) were assessed in a Danish case-control study comprising 373 CD and 541 UC patients and 796 healthy controls. RESULTS: Carriers of the homozygous COX-2 and MDR1 intron 3 variant had a relatively high risk of CD, odds ratio (95% CI) (OR (95% CI))=2.86 ((1.34-5.88) p=0.006) and 1.39 ((0.99-1.92) p=0.054), respectively, and for UC of 2.63 ((1.33-5.26) p=0.005) and 1.28 ((0.96-1.51) p=0.093), respectively, assuming complete dominance. No association was found for BCRP or other MDR1 SNPs, or for selected MDR1 haplotypes. No effect-modification of smoking habit at the time of diagnosis was found. CONCLUSIONS: An effect of the COX-2 polymorphism on both CD and UC was shown which is compatible with the presence of a recessive allele in linkage equilibrium with the SNP marker in the COX-2 gene. The polymorphism located in intron 3 of the MDR1 gene showed a weak association with CD, and a marginally suggestive association with UC.

[Liver biopsy in liver patients with coagulopathy]. / Leverbiopsi hos leverpatienter med koagulopati.

The risk of severe bleeding after liver biopsy is estimated to be 1:12,000 in patients with near normal coagulation (INR < 1,5 and platelet count > 60 billion /l). Beyond these limits, the risk is higher, but still uncertain. The Danish guidelines require INR > 1.5, platelet count < 40 billion /l and normal APTT. In some instances the risk of not knowing the histology is so high that a biopsy is considered even with a more disturbed coagulation. Vitamin K, freshly frozen plasma and recombinant activated factor VII may reduce the risk of bleeding in specific situations, but no firm recommendations can be given.

Liver cirrhosis, other liver diseases, and risk of hospitalisation for intracerebral haemorrhage: a Danish population-based case-control study.

BACKGROUND: Liver diseases are suspected risk factors for intracerebral haemorrhage (ICH). We conducted a population-based case-control study to examine risk of ICH among hospitalised patients with liver cirrhosis and other liver diseases. METHODS: We used data from the hospital discharge registries (1991-2003) and the Civil Registration System in Denmark, to identify 3,522 cases of first-time hospitalisation for ICH and 35,173 sex- and age-matched population controls. Among cases and controls we identified patients with a discharge diagnosis of liver cirrhosis or other liver diseases before the date of ICH. We computed odds ratios for ICH by conditional logistic regressions, adjusting for a number of confounding factors. RESULTS: There was an increased risk of ICH for patients with alcoholic liver cirrhosis (adjusted OR = 4.8, 95% CI: 2.7-8.3), non-alcoholic liver cirrhosis (adjusted OR = 7.7, 95% CI: 2.0-28.9) and non-cirrhotic alcoholic liver disease (adjusted OR = 5.4, 95%CI:3.1-9.5) but not for patients with non-cirrhotic non-alcoholic liver diseases (adjusted OR = 0.9, 95%CI:0.5-1.6). The highest risk was found among women with liver cirrhosis (OR = 8.9, 95%CI:2.9-26.7) and for patients younger than 70 years (OR = 6.1, 95%CI:3.4-10.9). There were no sex- or age-related differences in the association between other liver diseases (alcoholic or non-alcoholic) and hospitalisation with ICH. CONCLUSION: Patients with liver cirrhosis and non-cirrhotic alcoholic liver disease have a clearly increased risk for ICH.

[Acute mesenteric ischaemia in a patient with Crohn's disease]. / Akut mesenteriel iskaemi hos en patient med Crohns sygdom.

A 48-year-old patient known to have Crohn's disease (diagnosis verified by clinical findings, histology and colonoscopy) was admitted to the hospital with acute abdominal pain. Additional examination did not suggest another pathology. Acute mesenteric ischaemia was suspected late and diagnosed only during laparotomy. CT scan and MR were normal, but abdominal angiography confirmed total occlusion of the superior mesenteric artery. In this case the outcome was death.

Hypoalgesia to experimental visceral and somatic stimulation in painful chronic pancreatitis.

OBJECTIVES: To gain more information of the pain mechanisms in chronic pancreatitis we applied standardized experimental pain stimulation of the duodenum, oesophagus and the skin in 12 healthy controls and 13 patients with chronic pancreatitis and typical pain attacks. METHODS: Using endoscopy a guide wire was positioned into the horizontal part of the duodenum, and a probe with a distal balloon was introduced over the guide wire. Mechanical stimuli were given as tonic (38 ml/min) or phasic (increasing volume steps of 5 ml delivered for 60 s) distensions of the balloon. After stimulation of the duodenum, the distal oesophagus was stimulated with the same protocol. Finally, the skin was stimulated with 'single and repeated burst' electrical stimuli reflecting activation of peripheral and central pain mechanisms. RESULTS: The stimuli reliably evoked both painful and non-painful local and referred sensations. The patients had hyposensitivity to both tonic and phasic mechanical stimuli of the duodenum and the oesophagus (P=0.001). Hypoalgesia was also observed to single and repeated electrical skin stimuli in the patients, most evident for repeated stimuli (P=0.001). The evoked referred pain did not differ between the groups, but the patients used on average more words from the McGill Pain Questionnaire to describe the pain evoked in the duodenum (P=0.02). CONCLUSIONS: Generalized hypoalgesia to experimental visceral and somatic stimulations was found in chronic pancreatitis. The findings suggest that the activation and modulation of central mechanisms is fundamental in pancreatic pain, and future studies should address the effect of analgesics with central effects in the treatment of these patients.

Gut pain reactions in man: an experimental investigation using short and long duration transmucosal electrical stimulation.

Visceral pain is a substantial, clinical problem but unfortunately few experimental models are available to study this phenomenon in man. In the present study we inserted a stimulation catheter 5-10 cm into the ileo-sigmoidostomy of nine patients. The catheter contained six small, flexible electrodes separated by 4 mm. The gut was stimulated by single burst, repeated burst (five stimuli delivered at 2 Hz), or continuous burst stimuli (4 Hz for 30, 60, 90, and 120 s). The sensation (ST), pain detection (PDT), and pain tolerance (PTT) thresholds to single/repeated burst stimuli were determined. The location/size/sensitivity of referred pain after repeated/continuous stimulation were characterized. The brain potentials to single burst stimuli and to increasing stimulus intensity were measured. ST to single burst stimuli was easy to determine (8 mA) and to reproduce. The patients found it difficult to determine the PDT and PTT to single burst stimuli, however both thresholds were easily determined for repeated burst stimuli. The pain thresholds to single burst stimuli were twice as high as the thresholds to repeated burst stimuli, indicating the importance of central temporal summation for visceral pain. Minor changes in the stimulus location resulted in changes of the referred pain projection site. The words most frequently selected (78%) from the McGill Pain Questionnaire to describe repeated burst stimulations were shooting, pricking, flashing, and boring. The amplitude of the brain potentials increased at increasing stimulus intensity. A stimulus intensity giving an initial pain rating of around 5 on a 0-10 visual analog scale (VAS) was used for continuous stimulation. A general increase of the pain intensity and the area of referred pain was found during this stimulation. It was concluded that electrical stimulation of the human gut provokes pain and especially long sequences of visceral stimuli are adequate to evoke referred pain mimicking pain profiles of pathologic origin.