E. M. Alstead

Safety of azathioprine in pregnancy in inflammatory bowel disease

Although azathioprine has been reported to be safe during pregnancy in renal transplant recipients and patients with systemic lupus erythematosus, opinions vary whether it should be continued in pregnancy in inflammatory bowel disease. A retrospective analysis of the outcome of 16 pregnancies in 14 women receiving azathioprine for inflammatory bowel disease was performed. There was one infective complication of pregnancy (hepatitis B virus infection), but there were no congenital abnormalities or subsequent health problems in the children. This preliminary study suggests that azathioprine is safe in pregnancy in inflammatory bowel disease patients and that termination of pregnancy is not mandatory for those who conceive while taking the drug.

Symptom relief and quality of life after stenting for malignant bile duct obstruction.

Palliative treatment is appropriate for most patients with cancer of the head of pancreas. Insertion of a biliary stent relieves jaundice and pruritus but it is not known if stenting affects other symptoms or changes the quality of life. Nineteen patients have completed a standard questionnaire to assess symptom relief and quality of life after stent insertion. After stenting there was complete relief of jaundice and pruritus. Furthermore, there was also considerable improvement in anorexia and indigestion. All patients had anorexia before stent insertion, this was moderate/severe in 13 (68.4%). Anorexia was significantly better (p < 0.01) a week after stenting and this benefit was maintained at 12 weeks (p < 0.01). Sixteen (84.2%) patients complained of indigestion before stenting, moderate/severe in 11 (57.9%). This was significantly better (p < 0.01) a week after stenting with complete relief in six at eight weeks (p < 0.01). Fifteen (78.9%) felt that their mood was good/very good before stent insertion and this was unchanged even at the 12 week assessment. A similar result was obtained for physical health and level of activity. In conclusion stent insertion not only relieves jaundice and pruritus in these patients but also improves other symptoms and quality of life. The considerable improvement in appetite after stenting was of particular benefit.

Role of interferon α in promoting T helper cell type 1 responses in the small intestine in coeliac disease

Coeliac disease (CD) is caused by a CD4 T helper cell type 1 (Th1) response in the small intestinal mucosa to dietary gluten. As the major Th1 inducing cytokine, interleukin 12, is undetectable in CD gut mucosa, the mechanism by which Th1 effector cells are generated remains unknown. Interferon (IFN) α, a cytokine capable of promoting IFN-γ synthesis, has been implicated in the development of Th1 mediated immune diseases. Here we report a case of CD-like enteropathy in a patient receiving IFN-α for chronic myeloid leukaemia. Morphological assessment of duodenal biopsies taken from the patient showed total villous atrophy, crypt cell hyperplasia, and a high number of CD3+ intraepithelial lymphocytes. Both antigliadin antibodies and antiendomysial antibodies were positive. RNA analysis revealed pronounced expression of IFN-γ. Withdrawal of gluten from the diet resulted in a patchy improvement in intestinal morphology, normalisation of laboratory parameters, and resolution of clinical symptoms. By western blot analysis, IFN-α protein was seen in the duodenal mucosa from untreated CD patients but not in controls. This was associated with marked expression of IFN-γ protein in CD mucosa. Collectively, these results suggest a role for IFN-α in promoting Th1 responses to gluten.

Inflammatory bowel disease in pregnancy

Concerns about sexual health, fertility, and pregnancy are common in patients with inflammatory bowel disease (IBD). Fertility is usually normal, although may be decreased in women with active Crohns disease. Women with active IBD (especially Crohns disease) are at risk of having small and premature babies. In some patients with IBD it may be desirable to continue drug treatment during pregnancy in order to control disease activity. Early engagement in discussion of these issues is important and it should be possible for most patients with IBD to have a normal outcome of pregnancy.

Is intervention necessary after a first episode of acute idiopathic pancreatitis

Acute idiopathic pancreatitis is a term used when no underlying cause has been identified on routine investigation. However, more specialised investigations may identify aetiological factors, biliary sludge and sphincter of Oddi dysfunction for example, in 38-72% of patients with recurrent episodes. Treatment of these abnormalities may prevent further episodes of pancreatitis. The aim of this study was to follow up and determine the outcome in patients with a first episode of idiopathic pancreatitis, and thus determine the need for further investigation and treatment in this group of patients. Thirty one patients with a single episode of idiopathic pancreatitis were studied who had no specialised investigations or specific treatment. During a median follow up of 36 months only one patient has had recurrent pancreatitis. Two patients experienced a single episode of unexplained abdominal pain; serum amylase, liver biochemistry, and abdominal ultrasound were all normal and the pain resolved within 48 hours. In conclusion, in the medium term, the prognosis is good after a first episode of idiopathic pancreatitis and specialised investigation is unnecessary.

Ornithine decarboxylase activity is a marker of premalignancy in longstanding Helicobacter pylori infection.

BACKGROUND: Longstanding Helicobacter pylori infection may increase the risk of developing gastric adenocarcinoma. The sequence of chronic active gastritis leading to gastritis with atrophy and subsequent intestinal metaplasia is thought to be a key step in gastric carcinogenesis. Ornithine decarboxylase (ODC) activity is increased in some pre-malignant gastrointestinal conditions and is essential for malignant transformation in vitro. AIMS: To measure ODC activity in the antrum of H pylori infected and non-infected subjects and to relate this to histological abnormalities associated with recent and longstanding H pylori infection. METHODS: Six antral mucosal biopsy specimens were obtained from 75 patients for detailed histological assessment and measurement of ODC activity. Samples were measured in duplicate and results expressed as median, interquartile range in pmol/mg protein/h. RESULTS: ODC activity was significantly higher in H pylori positive (164, 88-259 pmol/mg/h) than H pylori negative subjects (99.8, 55-158 pmol/mg/h, p = 0.003). However the presence of gastritis, irrespective of the severity of inflammation or activity had no influence on ODC activity. Gastritis with atrophy was associated with increased ODC activity, which was closely related to the severity of the atrophy (p = 0.01). Similarly, ODC activity was significantly increased in subjects with intestinal metaplasia (196, 83-25) compared with those without intestinal metaplasia (111.7, 65-175, p < 0.04). CONCLUSIONS: These results indicate that the histological changes associated with longstanding H pylori infection rather than inflammation alone are associated with increased polyamine biosynthetic activity. This may be relevant to H pylori associated gastric carcinogenesis.

Ornithine decarboxylase as a marker for premalignancy in the stomach.

Assessment of mucosal ornithine decarboxylase (ODC) activity in the human large bowel may be of value as a marker of potential malignant risk. Its value as a marker of premalignancy in the upper gastrointestinal tract is less clear. Using a [14C]-ornithine bioassay, gastric mucosal ODC activity was measured in 32 normal subjects and 22 patients with confirmed gastric cancer. These results were compared with 47 patients at increased risk of upper gastrointestinal malignancy, (32 patients with partial gastric resection, 15 patients with familial adenomatous polyposis). Median ODC activity in normal subjects was 371 pmol/mg protein/h, (interquartile range (IQR), 230-617). There was no variation with age or sex and no relation to Helicobacter pylori status. Normal subjects had significantly lower ODC activity than patients with a gastric resection or confirmed gastric cancer, but similar to patients with familial adenomatous polyposis. Furthermore, no difference in activity was identified between patients with a gastric resection and established gastric cancer. ODC activity was, however, significantly increased in areas of gastric atrophy or intestinal metaplasia, regardless of the clinical group from which the samples were obtained. It is concluded that measurement of mucosal ODC activity does not provide additional predictive information of malignant risk in the stomach and investigation of other potential biomarkers of malignancy is warranted.

Applying your clinical skills to students and trainees in academic difficulty.

Background:  When students and trainees in difficulty present late, there are often signs in their history that suggest that earlier identification and intervention might have been possible. Clinical supervisors may have been reluctant to explore issues with them, perhaps because they felt that it was not their role to do so, or that they may not have the necessary skills or perhaps because of the concern of ‘opening a can of worms’ that they would not be able to address.

Persistent systemic inflammatory response after stent insertion in patients with malignant bile duct obstruction

Background—Surgery in patients with malignant bile duct obstruction is associated with high postoperative morbidity and mortality. Tumour necrosis factor α (TNF-α) plays a key role in the pathogenesis of these complications. Aims—To determine the effect of biliary drainage on plasma concentrations of TNF-α, its soluble circulating receptors (sTNFr), and other proinflammatory cytokines. Methods—Plasma concentrations of TNF-α, sTNFr-P75, interleukin 6 (IL-6), and IL-1α were measured in 25 patients with malignant bile duct obstruction before and after endoscopic stent insertion. Results—Mean serum bilirubin was 157 μmol/l before stent insertion and 35.2 μmol/l one week post stent insertion. There was complete relief of jaundice in 77% of patients by four weeks. Plasma concentrations of TNF-α and IL-1α were below the detection limit of the assays in all samples. Median plasma sTNFr-P75 in the cancer patients was 960 ng/l (range 400–6600) before stent insertion and remained unchanged at one and four weeks after stenting. Plasma sTNFr-P75 in cancer patients was significantly higher (p<0.01) than in healthy controls (250 (200–650) ng/l). Before stent insertion, plasma IL-6 concentrations were detectable (above 5 ng/l) in 17 (68%) patients. After relief of biliary obstruction IL-6 levels fell from a prestent median of 13.2 to less than 5 ng/l at one week after stent insertion. Plasma concentrations of IL-6 were undetectable in 76% of patients at this time. Conclusion—Activation of the TNF/sTNFr complex is unchanged after biliary drainage in patients with malignant bile duct obstruction. This may explain why preoperative drainage does not influence the high morbidity and mortality associated with surgery in these patients.

Phenotypic and genotypic variation in Giardia lamblia isolates during chronic infection.

Two Giardia isolates were axenised in vitro after recovery by duodenal aspiration from a man with hypo-gamma globulinaemia and chronic giardiasis, before and after three unsuccessful courses of metronidazole. In vitro drug sensitivity assays showed that the pretreatment isolate was sensitive to metronidazole with minimum inhibitory concentration (MIC) and dose that inhibited growth by 50% (ED50) values of 0.1 and 0.03 mumol/l, respectively. The post-treatment isolate was 20-fold more resistant (MIC and ED50 4.3 and 0.58 mumol/l, respectively). Differences between these isolates were also found in the surface protein profiles after radioiodination, metabolic labelling patterns with 35S-methionine, malic enzyme isoenzyme patterns, and by DNA fingerprinting with a M-13 bacteriophage probe. The phenotypic and genotypic differences between the pretreatment and post-treatment isolates suggest that we have isolated two different strains from the same patient and that treatment with metronidazole resulted in selection of the more resistant strain.