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Occult myeloproliferative disorders (MPD) are present in 25% of patients with chronic portal, splenic and mesenteric venous thrombosis (PSMVT). A somatic mutation of JAK2 (JAK2V617F) can be used to identify patients with latent MPD.We evaluated the prevalence and clinical significance of JAK2V617F in patients with chronic PSMVT.Allele-specific polymerase chain reaction was performed to screen for JAK2V617F.Thirty-five patients were tested for JAK2V617F. The underlying pro-coagulant condition was MPD in seven of 35 (20.0%) patients; other aetiologies included hereditary thrombophilia (n = 5), chronic pancreatitis (n = 2), liver abscess (n = 1) and umbilical vein sepsis (n = 3). The remainder were labelled idiopathic, i.e. 17/35 (48.6%) patients. JAK2V617F was detected in 16/35 (45.7%) patients: seven of seven (100%) with MPD, two of 11 (18.1%) with non-MPD acquired conditions and seven of 17 (41.2%) with 'idiopathic' chronic PSMVT. Mean haemoglobin concentration (P = 0.04), haematocrit (P = 0.04), white cell count (P = 0.002) and platelet count (P = 0.05) were significantly higher in patients with JAK2V617F. None of the seven patients with latent MPD have progressed to overt MPD over median follow-up of 85 months.JAK2V617F occurs in 41% of patients with idiopathic chronic portal, splenic and mesenteric venous thrombosis, confirming the presence of latent myeloproliferative disorders, and should form part of the routine pro-coagulant screen.

The management of autoimmune hepatitis (AIH) continues to be refined. However, several issues remain unresolved, primarily as a consequence of the low incidence of the disease. This factor has contributed both to a lack of understanding of and a paucity of large scale clinical trials involving therapeutic agents.To summarize the latest evidence regarding the pathogenesis, diagnosis, therapy and long-term management of AIH with a focus on clinical aspects of the disease.We searched PUBMED for articles pertaining to AIH, its pathogenesis, treatment and clinical outcomes, combined with the authors' own knowledge of the literature.Standard therapy (corticosteroids and azathioprine) is effective in more than 80% of patients which renders study of novel agents difficult. Budesonide appears to show equivalence to prednisolone. Available, but limited, data suggest that mycophenolate mofetil, tacrolimus and ciclosporin are all variably effective second line agents. Patients with AIH and cirrhosis are at risk of hepatocellular carcinoma (HCC) and require screening. Patients with end stage liver disease represent excellent candidates for liver transplantation.Despite ongoing limitations in the understanding of pathogenesis and difficulties in evaluating novel therapies, the management of AIH continues to evolve slowly. Multi-centre collaboration is necessary to obtain sufficient patient numbers to undertake good quality therapeutic studies.

Fas-expressing cytotoxic T lymphocytes (CTLs) are important antitumor immune effector cells in patients with hepatocellular carcinoma (HCC). The role of transforming growth factor beta 1 (TGF-beta1) in modulating the expression of Fas by CTLs is not known in HCC. The objectives of this study were to characterize the expression of Fas by CTLs and natural killer (NK) cells among peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs) in patients with HCC and to correlate the association, if any, with serum TGF-beta1 levels.PBLs from 18 patients with HCC and TILs from 5 HCC liver specimens were isolated, and Fas expression was analyzed by three-color flow cytometry. The results were compared with results from normal control volunteers (n = 19 individuals). Serum TGF-beta1 levels in patients with HCC were measured by enzyme-linked immunosorbent assay.The median percentage of Fas expression by CD3 positive T cells was significantly higher in patients with HCC compared with normal controls (54.37% vs. 32.03%, respectively; P = 0.0036), and this was attributable solely to Fas expression by CD4 positive PBLs (54.46% vs. 34.90%, respectively; P = 0.0234). In contrast, Fas expression was significantly higher in all the subtypes of TILs (CD3 positive, CD4 positive, CD8 positive, NK cells, and natural T cells) compared with controls (all P values were0.001). Tumor size was inversely proportional to the TGF-beta1 levels (correlation coefficient [r] = -0.725; P0.0001), which were correlated inversely with Fas expression by CD4 positive PBLs (r = -0.516; P = 0.01).In patients with HCC, TILs exhibit significantly increased expression of Fas compared with PBLs that may enhance their susceptibility to apoptotic mechanisms. Larger tumors were associated with lower serum TGFbeta1 levels, and this was correlated with greater Fas expression by CD4 positive PBLs.

Editor,—In a recent issue of Gut , Zheng et al reported that peptic ulcer disease was associated with increased expression of Lewis (Le) antigens but not cagA , iceA , or vacA in Chinese patients infected with Helicobacter pylori ( (2000) Gut 47:18–22. [OpenUrl][1][Abstract/FREE Full Text][2] ). These data raise as many questions as they answer and add further controversy to an intriguing area of microbiology and gastroenterology. Lex and/or Ley blood group determinants are commonly found on the lipopolysaccharide (LPS) of H pylori isolates. These determinants have been identified on approximately 80–90% of isolates from all patient series examined to date.1-3 In our own series, 74/84 (88%) isolates expressed either Lex or Ley, with 47/84 (56%) of isolates coexpressing both determinants.4 No difference was identified in the prevalence of Lex or Leyexpression on H pylori strains isolated from ulcer patients and those strains isolated from patients with chronic gastritis, nor was an association demonstrated between host and bacterial Lewis phenotype. Since the report of Zheng et al we have reviewed our raw data regarding the prevalence of strains expressing two or more Lewis antigens. We found that two or more Le determinants were present in 9/12 … [1]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2BClinical%2BMicrobiology%26rft.stitle%253DJ.%2BClin.%2BMicrobiol.%26rft.aulast%253DSimoons-Smit%26rft.auinit1%253DI.%2BM.%26rft.volume%253D34%26rft.issue%253D9%26rft.spage%253D2196%26rft.epage%253D2200%26rft.atitle%253DTyping%2Bof%2BHelicobacter%2Bpylori%2Bwith%2Bmonoclonal%2Bantibodies%2Bagainst%2BLewis%2Bantigens%2Bin%2Blipopolysaccharide%26rft_id%253Dinfo%253Apmid%252F8862584%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=jcm&resid=34/9/2196&atom=%2Fgutjnl%2F48%2F6%2F869.1.atom

Cholestasis is a common finding after liver transplantation and usually signifies graft dysfunction. The most important factor in the evaluation of patients with cholestasis is an awareness of the disorders that commonly arise along a time continuum post-transplant. Therefore, the approach to cholestasis requires a systematic review of biochemical, histological, and radiographic data. This article considers the causes of cholestasis in liver transplant recipients, excluding those associated with biliary anastomotic stricturing. These causes include conditions as diverse as ischemia reperfusion injury, ABO blood group incompatibility, hepatic arterial thrombosis, cytomegalovirus infection, fibrosing cholestatic hepatitis secondary to hepatitis B and C viruses, recurrent primary sclerosing cholangitis, recurrent primary biliary cirrhosis, and chronic rejection. Also examined are management issues pertinent to these conditions and strategies used in preventing or diminishing the effects of cholestasis once established.

Thromboembolic events frequently complicate the clinical course of patients with inflammatory bowel disease (IBD). Hereditary thrombophilia may contribute to this tendency. Resistance to activated protein C is the most recently described thrombophilic state and may account for up to 40% of patients with thrombophilia. Thirty-seven patients with IBD were studied (mean age 44 years, range 18-82 years). Three patients had a history of thrombotic episodes. The 37 controls included 23 men and 17 women (mean age 48 years, range 16-89 years). Disease activity was assessed using the Harvey Bradshaw index for patients with Crohn's disease and the Truelove and Witts grading system for patients with ulcerative colitis. Levels of fibrinogen, antithrombin III (ATIII), protein C, protein S, activated protein C resistance (APCR), and the presence of a lupus anticoagulant (LA) were determined. Median ATIII levels in patients with IBD were significantly lower than controls (98% vs 106%, P = 0.007), while fibrinogen was elevated (4.2 vs 3.3 g/liter, P = 0.026) despite quiescent disease activity. LA was detected in 7/37 patients in the IBD group compared to 0/37 controls. (chi2 = 5.68, P = 0.017). No significant difference was observed in levels of inherited thrombophilic factors and in particular APCR between IBD patients and controls. In conclusion, the presence of inherited thrombophilic defects, in particular APCR, is uncommon in patients with IBD and does not merit routine screening.

The use of 14C-urea breath testing for diagnosis of Helicobacter pylori infection in gastric mucosa has gained widespread acceptance and utilisation. We evaluated a 14C urea breath test (UBT) in 116 patients undergoing endoscopy. Seventy four patients were administered 185 kBq (5 mCi-conventional dose), and 42 patients reduced dose (92.5 IBq, 2.5 mCi) of 14C-urea. All were tested for H. pylori using culture, direct microscopy of gastric biopsies and histological evaluation of paraffin stained sections. Using the mean + three standard deviations as the cut-off value, a sensitivity of 96% and specificity of 100% was found for the conventional dose test. At reduced dose, sensitivity was 100% and specificity 96%. Positive and negative predictive values were 100% and 93% for the conventional dose test, and 96% and 100% for testing at reduced dose. We conclude that the UBT is a simple, non-invasive and useful diagnostic alternative for detection of H. pylori in infected patients. We advocate its use in patients less than 45 years of age without alarm symptoms, and also in cases where the need for endoscopic evaluation is not vital, such as after eradication therapy.

AIMS: To investigate the prevalence of lymphocytic gastritis in patients with coeliac disease. METHODS: Gastric biopsies from 70 patients with coeliac disease were examined by light microscopy for the presence of lymphocytic gastritis, defined as 25 or more intraepithelial lymphocytes/100 gastric columnar epithelial cells. RESULTS: Lymphocytic gastritis was found in seven cases. Positive cases had a mean of 32.1 intraepithelial lymphocytes/100 columnar cells, compared with a mean of 13.9 in negative cases, and 5.15 in noncoeliac controls. No differences were found for age, sex, gastric corpus or antrum, or degree of inflammation in the gastric lamina propria. All intraepithelial lymphocytes were of T cell lineage. Cases not showing lymphocytic gastritis did however show significantly increased gastric intraepithelial lymphocytes compared with non-coeliac controls. Eighteen of 70 cases were positive for Helicobacter pylori, and four of seven cases of lymphocytic gastritis were H pylori positive; no significant difference was observed between H pylori positive and negative patients. Three cases had concomitant ulcerative enteritis, of which none showed lymphocytic gastritis, while five cases had concomitant enteropathy associated T cell lymphoma, of which one showed lymphocytic gastritis. CONCLUSIONS: Lymphocytic gastritis occurred in 10% of patients with coeliac disease. Cases without lymphocytic gastritis nevertheless showed increased gastric intraepithelial lymphocytes. Coeliac disease may on occasion be a diffuse lymphocytic enteropathy occurring in response to gluten. Lymphocytic gastritis outside coeliac disease may involve an immune response to luminal antigens, such as H pylori, not unlike the response to gluten in patients with coeliac disease.

Retrocalcaneal bursitis is a distinct condition causing posterior heel pain in active, healthy children. It appears to result from post-traumatic inflammation of the soft tissues of the posterior heel, and is unrelated to avascular necrosis of the calcaneal apophysis. The diagnosis may be confirmed radiographically by the loss of the lucent retrocalcaneal recess, with a normal Achilles tendon and superficial soft tissue contour, and intact cortex of the underlying os calcis.

Haglund syndrome is a common cause of posterior heel pain, characterized clinically by a painful soft-tissue swelling at the level of the achilles tendon insertion. On the lateral heel radiograph the syndrome is characterized by a prominent calcaneal bursal projection, retrocalcaneal bursitis, thickening of the Achilles tendon, and a convexity of the superficial soft tissues at the level of the Achilles tendon insertion, a "pump-bump." An objective method for evaluating prominence of the bursal projection is measurement using the parallel pitch lines. This measurement helps to identify patients with Haglund syndrome and patients predisposed to develop this condition, and also to differentiate local causes of posterior heel pain from systemic causes. The parallel pitch line measurement was determined in 10 symptomatic feet and 78 control feet and the results were analyzed statistically.