Images of interest. Gastrointestinal: diffuse osephageal spasm.
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Biomedical subjects
Publications and source records attributed to I C Roberts-Thomson.
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BACKGROUND: Endoscopic sphincterotomy for biliary-type pain after cholecystectomy remains controversial despite evidence of efficacy in some patients with a high sphincter of Oddi (SO) basal pressure (SO stenosis). AIM: To evaluate the effects of sphincterotomy in patients randomised on the basis of results from endoscopic biliary manometry. METHODS: Endoscopic biliary manometry was performed in 81 patients with biliary-type pain after cholecystectomy who had a dilated bile duct on retrograde cholangiography, transient increases in liver enzymes after episodes of pain, or positive responses to challenge with morphine/neostigmine. The manometric record was categorised as SO stenosis, SO dyskinesia, or normal, after which the patient was randomised in each category to sphincterotomy or to a sham procedure in a prospective double blind study. Symptoms were assessed at intervals of three months for 24 months by an independent observer, and the effects of sphincterotomy on sphincter function were monitored by repeat manometry after three and 24 months. RESULTS: In the SO stenosis group, symptoms improved in 11 of 13 patients treated by sphincterotomy and in five of 13 subjected to a sham procedure (p = 0.041). When manometric records were categorised as dyskinesia or normal, results from sphincterotomy and sham procedures did not differ. Complications were rare, but included mild pancreatitis in seven patients (14 episodes) and a collection in the right upper quadrant, presumably related to a minor perforation. At three months, the endoscopic incision was extended in 19 patients because of manometric evidence of incomplete division of the sphincter. CONCLUSION: In patients with presumed SO dysfunction, endoscopic sphincterotomy is helpful in those with manometric features of SO stenosis.
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Persuasive data exist as to the importance of environmental factors in the pathogenesis of sporadic colorectal cancer. One possibility is that the effect of environmental factors varies between individuals, perhaps on the basis of inherited variation (polymorphism) in genes which influence the activation or inactivation of dietary carcinogens. Thus far, the focus has been on acetylator genes (NAT1, NAT2) and the activation of heterocyclic amines, carcinogens generated by cooking meat for prolonged periods at high temperature. Three case-control studies and one prospective study have shown a consistent trend towards higher risks for cancer with higher intakes of meat in rapid acetylators for NAT1, NAT2 or both genotypes. Other links between meat, cooking methods, metabolic genotypes and risk for cancer might include enhanced activation of polycyclic aromatic hydrocarbons and N-nitroso compounds by variant genotypes of CYP1A1 and CYP2E1, respectively, and modulation by meat of the protective effect of the E4 allele of apolipoprotein E on risk for cancer of the proximal colon.
BACKGROUND: The observation that only a minority of alcoholics develops clinical pancreatic disease has led to a search for a predisposing factor to the disease. One possible predisposing factor is mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene as cystic fibrosis leads to pancreatic injury. We have recently demonstrated that 15 common CFTR mutations are not found in patients with alcoholic pancreatitis. Another common polymorphism of the CFTR gene has recently been implicated in the pathogenesis of idiopathic chronic pancreatitis, the 5T variant of the variable length polythymidine tract in intron 8 (the normal genotypes are 7T and 9T). The 5T variant inhibits transcription of exon 9 resulting in a CFTR protein lacking chloride channel activity. The aim of this study was to determine whether the 5T variant is associated with alcoholic pancreatitis. METHODS: Fifty-two patients with alcoholic pancreatitis were identified using standardized diagnostic criteria. Fifty alcoholics without pancreatitis were also studied as controls. Genomic DNA was extracted from peripheral blood leukocytes and the polythymidine tract of intron 8 was amplified by nested polymerase chain reaction using established primers. The polymerase chain reaction products were digested with MseI, separated by electrophoresis on 15% polyacrylamide gels and genotypes assigned by comparison with known positive controls. RESULTS: The 5T allele we found in only two patients with alcoholic pancreatitis (3.9% of th index group; 95% confidence intervals 0-10%) and in seven alco holic controls. Allele frequencies for 5T, 7T, and 9T in patients with alcoholic pancreatitis were 1.9%, 85.6%, and 12.5%, respectively These did not differ from the allele frequencies in alcoholic controls (7%, 79%, and 14% for 5T, 7T, and 9T, respectively). CONCLUSION: The 5T allele was not associated with alcoholic pancreatitis. Individual susceptibility to this disease remains unexplained.
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