A pilot study to investigate the use of oxpentifylline (pentoxifylline) and thalidomide in portal hypertension secondary to alcoholic cirrhosis.

BACKGROUND: Tumour necrosis factor-alpha is thought to be important in the pathogenesis of portal hypertension. Oxpentifylline (pentoxifylline) and thalidomide inhibit endotoxin-induced tumour necrosis factor-alpha production in vitro. AIMS: To assess the toxicity of oxpentifylline (pentoxifylline) and thalidomide in cirrhosis and their effect on the hepatic venous pressure gradient and tumour necrosis factor-alpha production. METHODS: In an open-label pilot study, 20 abstinent patients with stable alcoholic cirrhosis and oesophageal varices were recruited; 12 patients completed haemodynamic measurements before and after treatment with oxpentifylline (pentoxifylline) 1800 mg (n=6) or thalidomide 200 mg (n=6) daily for 2 weeks. Tumour necrosis factor-alpha production was assessed in ex vivo monocyte cultures stimulated with endotoxin. RESULTS: Thalidomide reduced the hepatic venous pressure gradient from 19.7 mmHg (9.3-23.5 mmHg) to 12.2 mmHg (4.7-19.5 mmHg) (P=0.03) without reducing the hepatic blood flow or altering systemic haemodynamic parameters. Thalidomide reduced ex vivo tumour necrosis factor-alpha production by approximately 50%. Oxpentifylline (pentoxifylline) had no significant effect on any of the parameters measured. Side-effects led to dose reduction or treatment withdrawal in 40% of patients. CONCLUSION: Thalidomide, but not oxpentifylline (pentoxifylline), reduces the hepatic venous pressure gradient in stable alcoholic cirrhotics, an effect that may be mediated by the inhibition of tumour necrosis factor-alpha production. The role of tumour necrosis factor-alpha inhibitory drugs in the therapy of portal hypertension should be investigated in a randomized controlled trial.

Inflammatory bowel disease, azathioprine and skin cancer: case report and literature review.

A 42-year-old blond Caucasian woman taking azathioprine for 8 years developed an intra-epidermal carcinoma of the shin. She regularly used a sun bed to maintain a tan. Although the increased risk of non-melanoma skin cancer in immunosuppressed transplant recipients is well recognized, patients with Crohn's disease are not currently warned of the risk of exposure to ultraviolet light. Individuals with inflammatory bowel disease who take azathioprine, especially those with a fair complexion, should be informed of the potential dangers of sun bathing and should be advised to limit sun exposure.

Intra-hepatic false aneurysm: a rare complication of ERCP.

We report a rare case in which an intra-hepatic false aneurysm formed following endoscopic retrograde cholangiopancreatography and presented with life-threatening gastrointestinal bleeding. The aetiology, investigation and management of intra-hepatic false aneurysm is discussed.

Cholestasis and biliary dilatation associated with chronic ketamine abuse: a case series.

Ketamine is a dissociative anaesthetic agent that is still widely used in veterinary and human medicine. It is increasingly being used as a recreational hallucinogenic drug. Chronic ketamine abuse is known to account for lower urinary tract symptoms and urinary bladder dysfunction. There is now emerging evidence that ketamine misuse is also associated with abnormal liver function tests and biliary tract abnormality. We report three cases of chronic ketamine misuse in three young men who all presented with obstructive jaundice and biliary tract abnormality. We also describe the clinical features, radiological findings and potential underlying mechanisms for this new entity.

Autoimmune pancreatitis presenting as a pancreatic mass mimicking malignancy.

Autoimmune pancreatitis is a rare cause of chronic pancreatitis and pancreatic mass. We describe a case of focal autoimmune pancreatitis in a 51-year-old man presenting with obstructive jaundice and pancreatic mass, mimicking malignancy. The immunological test was suggestive of autoimmune pancreatitis, and the patient responded well to a course of steroids, with complete resolution of the pancreatic mass. Autoimmune pancreatitis, therefore, must be kept in mind as a differential diagnosis of pancreatic mass. Recognition of this disease by its typical radiological and serological findings may help to avoid unnecessary surgical resection.

Responses to free lipopolysaccharide and Escherichia coli by normal human intestinal macrophages, following their migration out of the lamina propria.

Intestinal macrophage responses to luminal bacteria and their constituents are important in mucosal inflammatory responses. We investigated the responses of intestinal macrophages to free lipopolysaccharide (LPS) and Escherichia coli. Macrophages were isolated from normal terminal ileum and colon by allowing them to migrate out of the lamina propria of mucosal samples denuded of epithelial cells. Following exposure to free LPS or fluorescein-labelled E. coli, responsiveness was studied by intracellular expression of tumour necrosis factor-alpha (TNF-alpha). CD14, CD33, CD68, TLR2 and TLR4 expression was studied by fluorescence-activated cell sorter (FACS). TLR and NOD2 expression was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). CD14 was expressed by 36.5 +/- 4.0% of the macrophages obtained following migration out of the lamina propria. These cells also expressed TLR2, TLR4 and NOD2. Of cells exposed to free LPS or those that had taken up E. coli, a greater proportion of CD14(+) than CD14(-) macrophages expressed intracellular TNF-alpha. Moreover, a greater proportion of macrophages (CD14(+) and CD14(-)) demonstrated responses to E. coli than free LPS. In conclusion, a proportion of macrophages obtained following migration out of the lamina propria of normal terminal ileal and colonic mucosal samples express CD14, TLR2 and TLR4. These cells respond to free LPS and E. coli, as demonstrated by the expression of TNF-alpha.

Cigarette smoking and adult coeliac disease.

BACKGROUND: While coeliac disease is clearly induced by dietary gluten ingestion in genetically susceptible individuals, other environmental factors may influence the onset of disease. Two studies have suggested that cigarette smoking has a protective role, but a third has not. METHODS: We examined the relationship between cigarette smoking and coeliac disease in individuals with coeliac disease diagnosed in adulthood from two large population-based disease registers and age and sex-matched controls from local general practitioner lists. Participants were mailed a three-page lifestyle and general health questionnaire. Smoking habits of coeliacs were compared with controls and with habits reported in the Health Survey for England 1995. RESULTS: An inverse association between current smoking and adult coeliac disease was identified (odds ratio: 0.77 (95% CI 0.56-1.06)) and remained when comparing ever smoked versus never smoked (odds ratio: 0.83 (0.68-1.00)). When the smoking habits of the coeliacs were compared with the national figures, the number of coeliacs who currently smoked was 40% lower than expected (smoking ratio 0.60, 0.46-0.78). This inverse association was accounted for by the behaviour of the 35-54-year age group (odds ratio for ever smoked 0.67 (0.51-0.89)). There was no association with having ever smoked in the younger age group (odds ratio: 1.44 (0.75-2.78)) or the older group (odds ratio: 0.92 (0.67-1.26)). CONCLUSIONS: There was an inverse association between adult coeliac disease and cigarette smoking which was accounted for by middle-aged coeliacs having never smoked. These results are consistent with an age-dependent interaction between cigarette smoking and the other environmental factors implicated in coeliac disease, including gluten.

Placement of esophageal self-expanding metallic stents without fluoroscopy.

BACKGROUND: Fluoroscopy is routinely used to guide the placement of self-expanding metallic stents for the palliative treatment of patients with esophageal malignancy. This is a description of a novel method of stent placement without fluoroscopy. METHODS: This technique relies on a clear endoscopic view of the proximal radiopaque marker on the stent. This was achieved by the application of an external white marker at this level. A gastroscope was passed, allowing guidewire deployment and measurement of stricture length. The endoscope was reinserted and placed alongside the guidewire giving direct visualization of the proximal margin of the stricture. The stent delivery device was positioned, keeping the white mark visible proximal to the stricture, and the stent was deployed. RESULTS: Thirty consecutive patients with inoperable esophageal malignancy underwent endoscopic placement of self-expanding metal stents. Deployment in satisfactory position without fluoroscopy was successful in 23 of 30 (77%); there were no complications. CONCLUSIONS: The majority of esophageal stents can be accurately positioned without fluoroscopy.