Ursodeoxycholic acid treatment lowers the serum level of antibodies against pyruvate dehydrogenase and influences their inhibitory capacity for the enzyme complex in patients with primary biliary cirrhosis.

A two-year randomized, double-blind, placebo-controlled clinical trial used paired serum samples from 122 patients with primary biliary cirrhosis to compare the effect of ursodeoxycholic acid and colchicine on their immune parameters. IgG antibodies to pyruvate dehydrogenase, the major autoantigen in primary biliary cirrhosis, were determined by enzyme-linked immunosorbent assay and immunoblot; enzyme inhibition assay against pyruvate dehydrogenase was used to test the changes of the functional reactivity of the serum autoantibodies. Treatment with ursodeoxycholic acid decreased both the level of IgG antibodies to pyruvate dehydrogenase (P < 0.01) and the inihibitory titer of the sera for pyruvate dehydrogenase (P < 0.01). Treatment with colchicine or placebo showed no statistically significant changes in either the antibody levels or the inhibitory titers. Ursodeoxycholic acid thus alters the immune parameters of patients with primary biliary cirrhosis. The mechanism of these changes needs further investigation.

Pancreatitis in patients with chronic inflammatory bowel disease.

We describe six patients with acute pancreatitis associated with chronic inflammatory bowel disease (IBD) and no other etiological factor of pancreatic disease in a series of 513 patients with IBD. Five of the 6 patients had Crohn's disease and one indeterminate colitis; four had simultaneous symptoms of active colitis. The pancreatis was not caused by drugs or duodenal involvement of IBD. Our study suggests that pancreatic disease is one of the extra-intestinal manifestations of IBD, in particular of Crohn's disease.

Elevated serum PIIINP and laminin in inflammatory bowel disease indicate hepatobiliary and pancreatic dysfunction.

BACKGROUND/AIMS: Levels of S-PIIINP (serum aminoterminal propeptide of type III procollagen) have been shown to be increased in patients with primary sclerosing cholangitis and inflammatory bowel disease. The aim of the study was to investigate the serum concentrations of PIIINP and laminin in inflammatory bowel disease patients, their relationship with inflammatory bowel disease-associated hepatobiliary and pancreatic dysfunction, and to correlate them with clinical, endoscopic, and histologic variables. METHODOLOGY: S-PIIINP and S-laminin were measured in 222 consecutive inflammatory bowel disease patients, who were screened for abnormal liver and pancreatic enzymes and for pancreatic exocrine hypofunction with the p-aminobenzoic acid test (215 patients). The patients with abnormal screening results were further scheduled for endoscopic retrograde cholangiopancreatography, liver biopsy, secretin test and ultrasound. RESULTS: S-PIIINP and S-laminin were abnormally high in 19% and 40% of all inflammatory bowel disease patients, respectively. The elevated levels of the fibrosis markers were associated with laboratory signs of either hepatobiliary or pancreatic disease. Hepatobiliary disease was found in 37 (17%) of inflammatory bowel disease patients, 15 of whom had primary sclerosing cholangitis. The median levels of S-PIIINP and S-laminin were significantly higher in patients with hepatobiliary disease than in those without (P < 0.0001 and P < 0.001, respectively), being most strikingly elevated in primary sclerosing cholangitis. Abnormal pancreatic screening tests were found in 67 (30%) patients. High levels of S-PIIINP and S-laminin were also significantly associated with low values in p-aminobenzoic acid (P < 0.001 and P < 0.005) and secretin (P < 0.01 and P < 0.05) tests, but not with inflammatory bowel disease category, endoscopic or histological disease extent, frequency of bowel resection or actual clinical activity. CONCLUSIONS: In inflammatory bowel disease, increased S-PIIINP and S-laminin are associated with hepatobiliary and pancreatic disorders.

Relationship of pancreatic function and glucose tolerance to the morphology of the pancreatic ductal system as revealed by ERCP.

A series of 226 patients with suspected pancreatic disease examined with ERCP, included 130 patients with normal ductal morphology (group I), 24 with 1-2 smooth narrowings of the main duct of the pancreas (group II), 20 with ectatic small branches (group III), 22 with an irregular main duct and ectatic small branches (group IV), and 30 patients with other findings in the pancreatogram. Pancreatic exocrine function was measured in 140 patients using the secretin test. The mean value of the maximal bicarbonate concentration was significantly (p less than 0.001) lower in the patients with severe ductal changes than in those with a normal pancreatogram. In addition, the number of patients with impaired exocrine function was significantly higher in group IV than in group I. The other groups did not differ significantly. A two-hour glucose tolerance test was done on 104 patients in addition to which 19 patients had overt diabetes. The number of patients with abnormal glucose tolerance was significantly higher in group IV (60%) than in group I (27.5%). The mean blood sugar value was also higher after one hour in group IV than in group I. The patients in the other groups did not differ significantly with regard to glucose metabolism. An almost significant negative correlation was found between the maximal bicarbonate concentrations and the one-hour blood glucose values (p less than 0.05).

Gastric carcinoids with minimal or no macroscopic lesion in patients with pernicious anemia.

In a series of 44 patients with pernicious anemia examined by gastroscopy, three cases of gastric carcinoids were found. During the same ten-year period about 11,000 gastroscopies were performed on patients not suffering from pernicious anemia, and only one case of gastric carcinoid was detected. In two of the cases no endoscopic lesion was seen and the carcinoid was detectable only at histological examination, while in one case an unusual combination of carcinoid tumor and tubular adenoma in the same polyp was found. Most of the carcinoids arose in atrophic body mucosa, but in one case the mucosa around the carcinoid showed antral properties. One patient had slightly elevated values of pancreatic polypeptide, while no hormonal activity was found in others. No growth or spread of the carcinoid was observed during follow-up. It is suggested that the same pathogenetic factors may operate in the genesis of gastric carcinoid and gastric carcinoma in patients with pernicious anemia.

Helicobacter pylori in dyspeptic patients: quantitative association with severity of gastritis, intragastric pH, and serum gastrin concentration.

The relationship between different features of gastric mucosal inflammation, intragastric pH and serum gastrin concentration and the distribution and quantity of Helicobacter pylori was studied in a series of 107 dyspepsia patients. H. pylori was identified in 62 cases (59%), and its presence was associated with increased amounts of mononuclear inflammatory cells and neutrophilic and eosinophilic leucocytes in both the antrum and the corpus. The number of H. pylori in the antral mucosa was significantly associated with the quantity of mononuclear inflammatory cells. It was also associated with glandular atrophy in antral mucosa, so that slight and moderate glandular atrophy were significantly more common in cases with abundant H. pylori. Intragastric pH and serum gastrin concentration were inversely related to the number of H. pylori in both the antral and corpus mucosa. H. pylori positive patients were also divided into groups according to proportions of H. pylori in the antral and corpus mucosa. In 5 of these patients (8%) the bacteria were present only in the corpus, and this group had a significantly more pronounced degree of glandular atrophy in the corpus mucosa, higher intragastric pH and a higher serum gastrin concentration than the other H. pylori positive patients. The other patients with a higher corpus H. pylori than antral H. pylori score (n = 25; 34%) also had a significantly higher intragastric pH and serum gastrin concentration than those with a corpus H. pylori score lower than or equal to the antral score, while the latter had more severe inflammation in the antral mucosa and a lower intragastric pH and serum gastrin concentration. The results suggest that inflammation in the antrum forms a favourable environment for H. pylori, while atrophy of the corpus glands, being connected with increased pH, leads to a diminished amount of H. pylori. They thus support the view that proliferation of H. pylori is dependent on acid produced by the corpus mucosa.

Structure of liquid linear alcohols.

The properties of linear alcohols in the liquid phase are studied by molecular dynamics simulations. We analyze the effects of the use of bond length constraints on the simulation density, self-diffusion constant, and hydrogen-bonding characteristics of the alcohol series. We find that the densities are well-reproduced in each of the cases but that the constraints have clear effects on the value of the diffusion constant and hydrogen-bonding properties, which is probably caused by the use of a gas-phase reference value in the OH bond length constraint. Although finite size effects are found to be present in the hydrogen bond networks, the networks are determined to be composed of chain-type structures that are well-converged. The results indicate that liquid alcohols consist of hydrogen-bonded chains of molecules. This finding can likely be tested experimentally with inelastic X-ray techniques at modern synchrotron radiation sources.

Universal signature of hydrogen bonding in the oxygen K-edge spectrum of alcohols.

We present a study of the local electronic structure surrounding the OH group in a series of alcohols by X-ray Raman scattering at the oxygen K edge. The samples include the linear alcohols from methanol to butanol as well as the isomers isopropanol, isobutanol, and 2-butanol. For interpretation and computational benchmarks, we combine classical molecular dynamics (MD) simulations and density functional theory (DFT) spectrum calculations. The results indicate that intramolecular structure influences the spectra considerably. Nevertheless, hydrogen bonding produces a clear spectral signature that is nearly identical in all of the alcohols. The spectral calculations using MD structures closely reproduce the experimental results and support the picture provided by the MD simulations.

Clinical significance and outcome of gastric mucosal erosions: a long-term follow-up study.

Our purpose was to evaluate the long-term clinical significance of gastric erosions. A series of 117 patients with gastric erosions without peptic ulcer disease, and matched controls were studied in 1974-1979. All available subjects were reinvestigated 17 years later, including detailed clinical history and laboratory analysis. At follow-up, erosions were still more prevalent (39%; 20/50) in the erosion group than in the controls (11; 7/66). In Helicobacter pylori-positive participants, peptic ulcer or a scar was more common in the erosion group (17%; 9/52) than in controls (5%; 3/66). Overall malignancy rate was higher in controls (15%; 17/117) than in erosion group (5%; 6/117; P = .025), but no other differences were seen between the groups or related with current erosion. We conclude that a significant proportion of gastric erosions are chronic or recurrent but mostly without serious complications. However, H. pylori-positive patients with erosions have significant risk to develop a peptic ulcer.

Effect of indomethacin and phenylbutazone-prednisone combination of gastric mucosa: gastroscopic and histological study.

The effect of a phenylbutazone-prednisone combination and indomethacin on the anatomical state of the gastric mucosa were studied by gastroscopy, gastrophotography, and gastrobiopsy. All four patients examined had redness of the antral mucosa after administration of either drug. Intramucosal gastric haemorrhage was present in two patients after both phenylbutazone-prednisone combination and indomethacin. Mucosal erosions occurred in three cases after the phenylbutazone-prednisone combination, one of them slight, and in two cases after indomethacin. On histological examination, increased intramucosal haemorrhage could be seen in the specimens from all four patients after indomethacin, and in the specimens from three patients after the phenylbutazone-prednisone combination. There was considerable mucosal vasodilatation in one patient on the phenylbutazone-prednisone combination and in two patients on indomethacin. The effects of both drugs on the gastric mucosa were similar. None of the subjects suffered from abdominal symptoms during the drug administration.

Family behaviour of gastric carcinoma.

The etiology of gastric carcinoma was investigated by the family study method. Familial factors had no great significance when gastric carcinoma was treated as a single disease. The role of familial factors could be demonstrated much better when gastric carcinomas were divided into histological subgroups. They appeared to be significant in the aetiology only of diffuse gastric carcinoma. The analysis based on the age and sex of the patient indicated that familial factors were associated with gastric carcinoma only in females, particularly young females.

Absorption, and effect on gastric mucosa, of buffered and non-buffered tablets of acetylsalicylic acid.

The effect of buffered and non-buffered acetylsalicylic acid tablets on gastric mucosa and gastric distress was investigated in healthy volunteers and in patients with rheumatoid arthritis. The absorption of acetylsalicylic and salicylic acids was also measured. The absorption of salicylic acid was not affected in clinically significant amounts by buffering the tablets. Buffered tablets containing aluminum subacetate showed a slightly delayed absorption of salicylic acid. Damage to the gastric mucosa tended to be less after the preparation buffered by magnesium hydroxide. Subjective feelings to gastric distress were not affected by buffering.

A gastroscopic and histological double-blind study of the effects of diclofenac sodium and naproxen on the human gastric mucosa.

The effects of diclofenac sodium and naproxen on the gastric mucosa were studied in a double-blind trial by gastroscopy, gastrophotography and histological examination of the mucosa in six healthy volunteers. Detectable lesions were evident in the mucosa of four subjects after administration of both drugs, and the lesions were more extensive after the ingestion of naproxen than after diclofenac sodium in all of these cases. The most serious lesions verified by both gastroscopy and histology always occurred after exposure to naproxen. The histology of the gastric mucosa of two subjects with severe lesions showed spotty to moderate chronic superficial gastritis, whereas the overall histological appearance of the mucosa was normal in subjects with slight or moderate lesions after drug administration. The maximal acid output was positively correlated with the severity of the lesions. Subjective symptoms occurred in one person during diclofenac sodium and in three during naproxen administration.