The pancreatic lesions of cystic fibrosis develop in utero and closely resemble those of chronic pancreatitis. Therefore, we hypothesized that mutations of the cystic fibrosis transmembrane ...conductance regulator (CFTR) gene may be more common than expected among patients with chronic pancreatitis.
We studied 134 consecutive patients with chronic pancreatitis (alcohol-related disease in 71, hyperparathyroidism in 2, hypertriglyceridemia in 1, and idiopathic disease in 60). We examined DNA for 22 mutations of the CFTR gene that together account for 95 percent of all mutations in patients with cystic fibrosis in the northwest of England. We also determined the length of the noncoding sequence of thymidines in intron 8, since the shorter the sequence, the lower the proportion of normal CFTR messenger RNA.
The 94 male and 40 female patients ranged in age from 16 to 86 years. None had a mutation on both copies of the CFTR gene. Eighteen patients (13.4 percent), including 12 without alcoholism, had a CFTR mutation on one chromosome, as compared with a frequency of 5.3 percent among 600 local unrelated partners of persons with a family history of cystic fibrosis (P<0.001). A total of 10.4 percent of the patients had the 5T allele in intron 8 (14 of 134), which is twice the expected frequency (P=0.008). Four patients were heterozygous for both a CFTR mutation and the 5T allele. Patients with a CFTR mutation were younger than those with no mutations (P=0.03). None had the combination of sinopulmonary disease, high sweat electrolyte concentrations, and low nasal potential-difference values that are diagnostic of cystic fibrosis.
Mutations of the CFTR gene and the 5T genotype are associated with chronic pancreatitis.
We describe a dramatic response to antioxidant therapy in three
patients with familial lipoprotein lipase deficiency complicated by
frequent severe episodes of pancreatitis who had failed to respond ...to
other dietary and pharmacological measures. Antoxidant therapy may be
an important advance in the management of this type of patient.
To determine the relative incidence and characteristics of endomysial antibody (EMA)-negative coeliac disease in adults.
Retrospective analysis of prospectively collected data on adults with newly ...diagnosed coeliac disease, with determination of EMA status before gluten withdrawal.
District general hospital (secondary care institution).
Sixty consecutive incident cases.
(i) Proportion of cases who were EMA-negative; (ii) comparison of clinical and laboratory variables at diagnosis for EMA-positive and EMA-negative subjects.
Fifteen subjects (25%, 95% CI 15-38%) were EMA negative, of whom only two were IgA deficient. There was clinical evidence in all 15 patients and histological evidence in 13 patients of a response to gluten withdrawal. No significant differences were found between EMA-positive and EMA-negative subjects with respect to histological features, age, gender, clinical manifestations, concurrent autoimmune disorders, family history of coeliac disease, or haemoglobin and albumin concentrations at diagnosis. However, EMA-negative status at diagnosis was associated strongly with current or recent cigarette smoking (OR 7.0, 95% CI 1.7-31.5, P= 0.003).
A substantial minority of patients with otherwise typical coeliac disease are EMA negative, and most of these are IgA replete. The value of EMA as a screening tool is therefore limited. EMA status in untreated coeliac disease correlates strongly with cigarette smoking history: this may be of pathogenic significance, given the previously demonstrated association between smoking and the risk of coeliac disease.
Vitamin C can be used to overcome oxidative stress and ease pain in chronic pancreatitis. But its use is deprecated in conditions of tissue iron overload, because its bioactive form, ascorbate, can ...accelerate free-radical reactions that are driven by transition metals. We measured iron, ascorbate and copper in Sowetan Blacks (RSA) with chronic pancreatitis, obtaining serum/plasma from 14 consecutive patients and 15 controls. Compared with data from corresponding groups in Manchester, African samples had less ascorbate (p < 0.0001), but more caeruloplasmin (p < 0.0001). African and British controls had comparable iron and iron-binding capacity. Plasma from African patients had less ascorbate than that from African controls (p < 0.005) and in six samples, ferritin exceeded 300 micrograms/l (677 pmol/l). Low-molecular-mass iron or copper, capable of participating in free radical reactions, was not detected. British patients, had similar caeruloplasmin levels to African patients but higher ascorbate levels. There is no evidence of iron overload in our African samples. Outwardly healthy controls from Soweto have elevated levels of caeruloplasmin, possibly to compensate for dietary deficiency of ascorbate. Persistent oxidative stress is a unifying feature of chronic pancreatitis, but its degree is higher in African than British patients. Supplements of vitamin C should be safe in Blacks of southern Africa.
To clarify the relationship between childhood environment and the risk of subsequent development of Crohn's disease or ulcerative colitis.
A case-control study, assessing the risk of inflammatory ...bowel disease in relation to a series of historical and serological markers of childhood circumstance, analysed using the maximum likelihood form of conditional logistic regression.
District general hospital (secondary care institution).
Subjects with Crohn's disease (n = 139) or ulcerative colitis (n = 137) aged between 16 and 45 years, each matched for sex and age with an outpatient control.
Helicobacter seroprevalence was substantially reduced in Crohn's disease (OR 0.18; 95% CI, 0.06-0.52) but not in ulcerative colitis (OR 0.91; 95% CI, 0.38-2.16). In ulcerative colitis, a strong negative association with childhood appendectomy was confirmed (OR 0.05; 95% CI, 0.01-0.51). Crohn's disease was associated with childhood eczema (OR 2.81; 95% CI, 1.23-6.42) and the frequent use of a swimming pool (OR 2.90; 95% CI 1.21-6.91). There was no association between hepatitis A seroprevalence and either disease.
The findings are consistent with the hypothesis that improved childhood living conditions are associated with increased risk of Crohn's disease. The study confirms that the negative association between appendectomy and ulcerative colitis relates primarily to events in childhood. Overall, the findings strongly support the assertion that childhood environment is an important determinant of the risk of inflammatory bowel disease in later life, with quite distinct risk factors for ulcerative colitis and Crohn's disease.
Plasma concentrations of methionine, tryptophan, phenylalanine and S-adenosyl methionine (SAM) were measured at the beginning and end of general anaesthesia (for routine surgery) lasting between 25 ...and 217 min which included 60–70% nitrous oxide. Plasma methionine, tryptophan and phenylalanine concentrations in patients prepared for surgery averaged 68 (SD 11.3)% of values in a group of normal control subjects. At the end of administration of nitrous oxide (mean duration 88 min) there were no significant changes in the mean methionine and phenylalanine concentrations, but the mean concentration of tryptophan was reduced by 15% (P = 0.0075). SAM concentrations averaged 40% greater in males than females in all groups, but there were no significant differences between the concentrations in the control subjects and the patients before or after the administration of nitrous oxide.
Hepatic methionine synthase activity has been determined in rats continuously exposed (24h day−1 and 7 day week−1) to concentrations of nitrous oxide ranging from 500 to 50000 p.p.m. for periods ...ranging from 24 h to 28 days. The inactivation of this enzyme was dependent upon both time and concentration of nitrous oxide exposure, but there was no statistical evidence that exposure continuing beyond 48 h increased the effect. However, the dose-response curve for 24 h was significantly different from the curve for pooled data from exposures lasting 2–28 days. These latter data indicated no significant effect with 450 p.p.m. and an ED 50 of 5400 p.p.m. Significant inhibition was detected at 1000 p. p.m. These results suggest that the limit of exposure of 25 p.p.m. recommended by the American National Institute of Occupational Safety & Health may be unduly restrictive.
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