Complications of coeliac disease: are all patients at risk?

Coeliac disease is a common condition that is increasingly being recognised as a result of the development of sensitive and specific serology. The diagnosis of coeliac disease and its subsequent treatment with a gluten-free diet have implications for the patient, not just for symptom control but also for the possible effect on quality of life and risk of complications. Whether the mode of presentation of coeliac disease has an effect on survival or risk of complication is yet unclear. This article reviews the available evidence regarding these issues.

Predicting the outcome of severe ulcerative colitis: development of a novel risk score to aid early selection of patients for second-line medical therapy or surgery.

BACKGROUND: The failure rate of medical therapy in severe ulcerative colitis is high. A risk index, to aid the identification of patients of not responding at an early stage to intravenous corticosteroid therapy, would be useful to facilitate second-line treatment or surgery. METHODS: We recruited 167 consecutive patients with severe ulcerative colitis between January 1995 and March 2002; and employed multiple logistic regression to analyse parameters within the first 3 days of medical therapy. We applied statistical modelling to formulate a risk score according to the likelihood of medical failure. RESULTS: Sixty-seven (40%) patients failed to respond to medical therapy. Multiple logistic regression analysis identified mean stool frequency and colonic dilatation within the first 3 days and hypoalbuminaemia as independent predictors of outcome (P < 0.001, 0.001 and 0.002 respectively). A numerical risk score was formulated based on these variables. Patients with scores of 0-1, 2-3 and > or =4 had a medical therapy failure rate of 11%, 43% and 85% respectively. Receiver-operator characteristic analysis of this score yielded area under curve of 0.88, with a sensitivity of 85% and specificity of 75% using score > or =4 in predicting non-response. CONCLUSION: This risk score allows the early identification of patients with severe ulcerative colitis who would be suitable for second-line medical therapy or surgery.

Localisation and semiquantitative assessment of hepatic procollagen mRNA in primary biliary cirrhosis.

BACKGROUND: Chronic liver disease is characterised by excessive deposition of collagen and other extracellular matrix proteins, produced mainly, but not exclusively, by activated hepatic stellate cells in the perisinusoidal space. In primary biliary cirrhosis (PBC) fibrosis is concentrated mainly around the portal tracts. AIMS: To examine the hypothesis that, in addition to hepatic stellate cells, portal tract fibroblasts might play a significant role in the deposition of collagen in PBC. METHODS: Fifty liver biopsy specimens from patients with PBC were studied. An in situ hybridisation technique was adapted to localise and measure semiquantitatively type I procollagen mRNA in formalin fixed, paraffin wax embedded sections, using an 35S labelled cRNA probe specific for the alpha 1 chain of rat type I procollagen. Hepatic fibrogenic activity was also assessed using serum type III procollagen peptide (PIIINP). RESULTS: In PBC, type I procollagen gene expression was significantly increased. Signal was localised mainly in and around inflamed portal tracts, to cells which had the appearances of portal fibroblasts. Signal activity in these cells correlated with the degree of portal fibrosis and inflammation and also with serum PIIINP concentrations. CONCLUSIONS: Results are consistent with the hypothesis that the excessive extracellular matrix, deposited within the liver in PBC, is synthesised not only by hepatic stellate cells but also by portal tract fibroblasts. The semiquantitative assessment of procollagen mRNA in liver biopsy specimens may provide a useful method of evaluating the rate of synthesis of collagen and therefore disease activity in patients with PBC.

Raised liver enzymes in asymptomatic patients: investigation and outcome.

Asymptomatic patients with raised liver enzymes are frequently encountered in clinical practice. The commonest lesion in such patients appears to be fatty liver, which may be found in those only modestly overweight. Proven treatments other than abstention from alcohol and weight loss are available for approximately 20% of asymptomatic people with abnormal liver enzymes. However, if experimental therapies are taken into account this would rise to over 50%, making an early accurate diagnosis important. Most conditions can be diagnosed non-invasively, especially in those people with markedly abnormal transaminases. The recent introduction of new non-invasive tests decreases the need for liver biopsy for diagnostic purposes, however liver biopsy retains an important role in establishing patient prognosis and response to treatment.

CP-66,948: an antisecretory histamine H2-receptor antagonist with mucosal protective properties.

CP-66,948 is a histamine H2-receptor antagonist with gastric antisecretory activity and mucosal protective properties. The affinity of CP-66,948 for the guinea pig atria histamine H2-receptor is 15 times greater than that of cimetidine and seven times greater than that of ranitidine. In vivo, the ED50 value for inhibition of gastric acid secretion in pylorus-ligated rats is 2 mg/kg intraduodenally, and in histamine or pentagastrin-stimulated Heidenhain pouch dogs the antisecretory ED50 values are 0.3 mg/kg per os and 1.0 mg/kg per os, respectively. CP-66,948 also inhibits ethanol-induced gastric hemorrhagic lesions in rats following either oral or systemic administration (ED50 values of 12 mg/kg per os and 6 mg/kg subcutaneously). In addition, the mucosal protective activity is independent of prostaglandin synthesis. CP-66,948 inhibits gastric acid secretion in man, and its mucosal protective activity may provide additional benefits in peptic ulcer therapy.

Amiodarone overdose and its management.

A patient taking an overdose of 3.4 g of amiodarone is described. Consciousness and physical examination remained normal throughout. Continuous electrocardiographic monitoring for 48 hours after admission revealed only a self-limiting episode of ventricular tachycardia, despite high serum levels of the drug (serum desethylamiodarone levels 4.4 mg/l). The pharmacokinetic properties of amiodarone and treatment strategies for the overdose situation are discussed. It is suggested that there may be a role for the use of cholestyramine in the treatment of both acute and chronic amiodarone toxicity.

Alopecia totalis in a patient with Crohn's disease and its treatment with azathioprine.

A patient with Crohn's disease and alopecia totalis is described. Despite relative inactivity of the Crohn's disease, treatment with azathioprine was commenced. This led to complete regrowth of hair which was lost when the drug was discontinued. Re-institution of azathioprine restored hair to normal again and the patient has since declined to try stopping the drug despite the knowledge of potential side effects.