Magnesium hydrogen breath test using end-expiratory sampling to assess achlorhydria in pernicious anaemia patients

A modified magnesium hydrogen breath test, using end expiratory breath sampling, is described to investigate achlorhydria. The efficacy of this test in the diagnostic investigation of pernicious anaemia was compared with that of serum pepsinogen I. Twenty one patients with pernicious anaemia--that is, patients with achlorhydria--and 22 with healed duodenal ulcer and normal chlorhydria were studied. Magnesium hydrogen breath test, serum pepsinogen I, serum gastrin, and standard gastric acid secretory tests were performed in all subjects. The mean (SEM) hydrogen peak value was lower in patients with pernicious anaemia than in the duodenal ulcer group (21.7 (1.9) v 71.3 (5.2) ppm; p = 0.00005). The hydrogen peak value had a 95.2% sensitivity and a 100% specificity to detect pentagastrin resistant achlorhydria. Mean serum pepsinogen I concentrations were also significantly lower in patients with pernicious anaemia than in the duodenal ulcer group (10.7 (2.7) v 123.6 (11.8) micrograms/l p = 0.00005). Sensitivity and specificity to detect pernicious anaemia were both 100% for pepsinogen I. It is concluded that this modified magnesium hydrogen breath test is a simple, noninvasive, cost effective, and accurate method to assess achlorhydria and may be useful in the diagnostic investigation of patients with suspected pernicious anaemia.

Dexamethasone inhibition of leucocyte adhesion to rat mesenteric postcapillary venules: role of intercellular adhesion molecule 1 and KC

BACKGROUND A previous study showed that the glucocorticoid dexamethasone, at doses of 100 ¿g/kg and above, inhibited leucocyte adhesion to rat mesenteric postcapillary venules activated with interleukin 1ß (IL-1ß), as assessed by videomicroscopy. AIMS To identify whether the adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), or the chemokine KC could be targeted by the steroid to mediate its antiadhesive effect. METHODS Rat mesenteries were treated with IL-1ß (20 ng intraperitoneally) and the extent of leucocyte adhesion measured at two and four hours using intravital microscopy. Rats were treated with dexamethasone, and passively immunised against ICAM-1 or KC. Endogenous expression of these two mediators was validated by immunohistochemistry, ELISA, and the injection of specific radiolabelled antibodies. RESULTS Dexamethasone greatly reduced IL-1ß induced leucocyte adhesion, endothelial expression of ICAM-1 in the postcapillary venule, and release of the mast cell derived chemokine KC. Injection of specific antibodies to the latter mediators was also extremely effective in downregulating (>80%) IL-1ß induced leucocyte adhesion. CONCLUSIONS Induction by IL-1ß of endogenous ICAM-1 and KC contributes to leucocyte adhesion to inflamed mesenteric vessels. Without excluding other possible mediators, these data clearly show that dexamethasone interferes with ICAM-1 expression and KC release from mast cells, resulting in suppression of leucocyte accumulation in the bowel wall, which is a prominent feature of several gastrointestinal pathologies.

Nadolol plus isosorbide mononitrate alone or associated with band ligation in the prevention of recurrent bleeding: A multicenter randomized controlled trial.

Background and aims: Previous clinical trials suggest that adding non-selective beta-blockers improves the efficacy of endoscopic band ligation (EBL) in the prevention of recurrent bleeding, but no study has evaluated whether EBL improves the efficacy of beta-blockers + isosorbide-5-mononitrate. The present study was aimed at evaluating this issue in a multicentre randomised controlled trial (RCT) and to correlate changes in hepatic venous pressure gradient (HVPG) during treatment with clinical outcomes. Methods: 158 patients with cirrhosis, admitted because of variceal bleeding, were randomised to receive nadolol+isosorbide-5-mononitrate alone (Drug: n=78) or combined with EBL (Drug+EBL; n=80). HVPG measurements were performed at randomisation and after 4¿6 weeks on medical therapy. Results: Median follow-up was 15 months. One-year probability of recurrent bleeding was similar in both groups (33% vs 26%: p=0.3). There were no significant differences in survival or need of rescue shunts. Overall adverse events or those requiring hospital admission were significantly more frequent in the Drug+EBL group. Recurrent bleeding was significantly more frequent in HVPG non-responders than in responders (HVPG reduction ¿20% or ¿12 mm Hg). Among non-responders recurrent bleeding was similar in patients treated with Drugs or Drugs+EBL. Conclusions: Adding EBL to pharmacological treatment did not reduce recurrent bleeding, the need for rescue therapy, or mortality, and was associated with more adverse events. Furthermore, associating EBL to drug therapy did not reduce the high rebleeding risk of HVPG non-responders.

The extent of the collateral circulation influences the postprandial increase in portal pressure in patients with cirrhosis.

Background: In cirrhosis, repeated flares of portal pressure and collateral blood flow provoked by postprandial hyperaemia may contribute to variceal dilation and rupture. Aim: To examine the effect of the extent of the collateral circulation on the postprandial increase in portal pressure observed in cirrhosis. Patients and methods: The hepatic venous pressure gradient (HVPG), hepatic blood flow and azygos blood flow were measured in 64 patients with cirrhosis before and after a standard liquid meal. Results: Peak increases in HVPG (median+14.9%), hepatic blood flow (median+25.4%), and azygos blood flow (median+32.2%) occurred at 30 min after the meal. Compared with patients with marked postprandial increase in HVPG (above the median, n¿=¿32), those showing mild (<15%, n¿=¿32) increase in HVPG had a higher baseline azygos flow (p<0.01) and underwent a greater postprandial increase in azygos flow (p<0.02). Hepatic blood flow increased similarly in both groups. Postprandial increases in HVPG were inversely correlated (p<0.001) with both baseline azygos flow (r¿=¿¿0.69) and its postprandial increase (r¿=¿¿0.72). Food intake increased nitric oxide products in the azygos (p<0.01), but not in the hepatic vein. Large varices (p<0.01) and previous variceal bleeding (p<0.001) were more frequent in patients with mild increase in HVPG. Conclusions: Postprandial hyperaemia simultaneously increases HVPG and collateral flow. The extent of the collateral circulation determines the HVPG response to food intake. Patients with extensive collateralisation show less pronounced postprandial increases in HVPG, but associated with marked flares in collateral flow. Collateral vessels preserve their ability to dilate in response to increased blood flow.

Enteral nutrition as primary therapy in Crohn's disease

The developments in enteral feeding for Crohn's disease in the past decade are critically reviewed. The advent of amino acid based chemically defined elemental diets signalled the end of 'total bowel rest' in the management of these patients. Subsequently, controlled clinical trials showed that elemental diets were as effective as corticosteroids in inducing clinical remission in patients with acute exacerbations of Crohn's disease. The later use of peptide based elemental diets, in Crohn's disease produced somewhat conflicting results. The initial uncontrolled studies suggest that polymeric whole protein diets might also be effective in the management of acute exacerbations of the disease, casting in turn doubts concerning the role of dietary antigens in the pathogenesis of Crohn's disease. Results of controlled studies comparing the use of elemental and polymeric diets as primary therapy in Crohn's disease have, however, also produced conflicting results. The results of one recent controlled trial in which

Changes of the mucosal N3 and N6 fatty acid status occur early in the colorectal adenoma-carcinoma sequence

Despite data favouring a role of dietary fat in colonic carcinogenesis, no study has focused on tissue n3 and n6 fatty acid (FA) status in human colon adenoma-carcinoma sequence. Thus, FA profile was measured in plasma phospholipids of patients with colorectal cancer (n = 22), sporadic adenoma (n = 27), and normal colon (n = 12) (control group). Additionally, mucosal FAs were assessed in both diseased and normal mucosa of cancer (n = 15) and adenoma (n = 21) patients, and from normal mucosa of controls (n = 8). There were no differences in FA profile of both plasma phospholipids and normal mucosa, between adenoma and control patients. There were considerable differences, however, in FAs between diseased and paired normal mucosa of adenoma patients, with increases of linoleic (p = 0.02), dihomogammalinolenic (p = 0.014), and eicosapentaenoic (p = 0.012) acids, and decreases of alpha linolenic (p = 0.001) and arachidonic (p = 0.02) acids in diseased mucosa. A stepwise reduction of eicosapentaenoic acid concentrations in diseased mucosa from benign adenoma to the most advanced colon cancer was seen (p = 0.009). Cancer patients showed lower alpha linolenate (p = 0.002) and higher dihomogammalinolenate (p = 0.003) in diseased than in paired normal mucosa. In conclusion changes in tissue n3 and n6 FA status might participate in the early phases of the human colorectal carcinogenesis.

Spectrum of gluten sensitive enteropathy in first degree relatives of patients with coeliac disease: clinical relevance of lymphocytic enteritis.

Background: Limited data on a short series of patients suggest that lymphocytic enteritis (classically considered as latent coeliac disease) may produce symptoms of malabsorption, although the true prevalence of this situation is unknown. Serological markers of coeliac disease are of little diagnostic value in identifying these patients. Aims: To evaluate the usefulness of human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy for the detection of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease and to assess the clinical relevance of lymphocytic enteritis diagnosed with this screening strategy. Patients and methods: 221 first-degree relatives of 82 DQ2+ patients with coeliac disease were consecutively included. Duodenal biopsy (for histological examination and tissue transglutaminase antibody assay in culture supernatant) was carried out on all DQ2+ relatives. Clinical features, biochemical parameters and bone mineral density were recorded. Results: 130 relatives (58.8%) were DQ2+, showing the following histological stages: 64 (49.2%) Marsh 0; 32 (24.6%) Marsh I; 1 (0.8%) Marsh II; 13 (10.0%) Marsh III; 15.4% refused the biopsy. 49 relatives showed gluten sensitive enteropathy, 46 with histological abnormalities and 3 with Marsh 0 but positive tissue transglutaminase antibody in culture supernatant. Only 17 of 221 relatives had positive serological markers. Differences in the diagnostic yield between the proposed strategy and serology were significant (22.2% v 7.2%, p<0.001). Relatives with Marsh I and Marsh II¿III were more often symptomatic (56.3% and 53.8%, respectively) than relatives with normal mucosa (21.1%; p=0.002). Marsh I relatives had more severe abdominal pain (p=0.006), severe distension (p=0.047) and anaemia (p=0.038) than those with Marsh 0. The prevalence of abnormal bone mineral density was similar in relatives with Marsh I (37%) and Marsh III (44.4%). Conclusions: The high number of symptomatic patients with lymphocytic enteritis (Marsh I) supports the need for a strategy based on human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy in relatives of patients with coeliac disease and modifies the current concept that villous atrophy is required to prescribe a gluten-free diet.

Upper gastrointestinal bleeding in cirrhosis: clinical and endoscopic correlations

The clinical data of 180 episodes of upper gastrointestinal bleeding in 168 patients with cirrhosis of the liver are examined. The source of bleeding had been determined by early endoscopy in all cases. In men under the age of 50 years, and without symptoms of liver failure, bleeding was due to ruptured gastro-oesophageal varices in 84% of cases. Severe liver failure was associated with acute lesions of gastric mucosa in many cases. No presumptive diagnosis of the source of haemorrhage could be based on the examination of other clinical data (presence of ascites, mode of presentation and pattern of bleeding, history of ulcer disease, alcoholism, and previous medication.

Chronic intestinal pseudoobstruction and ophthalmoplegia in a patient with mitochondrial myopathy

A 38 year old woman having chronic intestinal pseudoobstruction associated with mitochondrial myopathy is reported. The clinical and radiographic features suggested the diagnosis of chronic intestinal pseudoobstruction. Muscular atrophy and ophthalmoplegia led to muscle biopsy, which disclosed accumulation of normal and abnormal mitochondria ('ragged red fibres'), characteristic of mitochondrial myopathy.

Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease

Background and aims: Increased pancreatitis associated protein (PAP) mRNA has been reported in active inflammatory bowel disease (IBD). The aims of the current study were to characterise PAP production in IBD and the effects of PAP on inflammation. Patients and methods: Serum PAP levels were determined in healthy controls (n¿=¿29), inflammatory controls (n¿=¿14), and IBD patients (n¿=¿171). Ex vivo PAP secretion in intestinal tissue was measured in 56 IBD patients and 13 healthy controls. Cellular origin of PAP was determined by immunohistochemistry. The effects of exogenous PAP on nuclear factor ¿B (NF¿B) activation, proinflammatory cytokine production, and endothelial adhesion molecule expression were also analysed ex vivo. Results: Patients with active IBD had increased serum PAP levels compared with controls, and these levels correlated with clinical and endoscopic disease severity. Ex vivo intestinal PAP synthesis was increased in active IBD and correlated with endoscopic and histological severity of inflammatory lesions. PAP localised to colonic Paneth cells. Incubation of mucosa from active Crohn¿s disease with PAP dose dependently reduced proinflammatory cytokines secretion. PAP prevented TNF-¿ induced NF¿B activation in monocytic, epithelial, and endothelial cells and reduced proinflammatory cytokine mRNA levels and adhesion molecule expression. Conclusions: PAP is synthesised by Paneth cells and is overexpressed in colonic tissue of active IBD. PAP inhibits NF¿B activation and downregulates cytokine production and adhesion molecule expression in inflamed tissue. It may represent an anti-inflammatory mechanism and new therapeutic strategy in IBD.