Search

The classical presentations of necrolytic migratory erythema associated with alpha cell pancreatic tumour have been well documented. In addition, the occurrence of extracutaneous hallmarks of this disease such as weight loss, diabetes, anaemia, stomatitis and diarrhoea have been described in various reports. Here we report three cases with glucagonoma syndrome. Early detection is important in view of the malignant course of the disease. However, diagnosis is sometimes complicated by the fact that some patients may fail to show the characteristic feature of glucagonoma syndrome.

Dietary fibre possibly protects against colonic cancer by effects on bile acid metabolism. We investigated the effect of a natural high-fibre diet on secondary bile acid formation. Twelve healthy subjects on an habitual low-fibre diet (for 4 weeks) consumed a high-fibre menu for 10 weeks (experimental group). A control group of 10 subjects consumed their regular high-fibre diet during this period. Faecal and biliary acid composition, faecal weight, faecal pH and gut transit time were studied before and after 6 and 10 weeks of fibre addition. Changes in the experimental group were compared to changes in the control group. The concentration, but not the excretion, of the secondary faecal bile acids was reduced in the experimental group. Faecal weight increased, faecal pH dropped and gut transit time was not altered. The biliary deoxycholic acid content decreased and the cholic acid content increased after 6 weeks, but returned to baseline values after 10 weeks of fibre addition. This study shows that a natural high-fibre diet lowers secondary faecal bile acid concentration through an increase in stool weight. The 7 alpha-dehydroxylation of primary bile acids is probably not or only transiently inhibited.

In zinc deficiency, the function of leukocytes is impaired. However, the results of studies on the zinc concentration of blood cells in zinc deficiency are conflicting, probably in part because of technical and analytical problems. The aim of this study was to investigate, under standard conditions, the uptake of 65Zn-labeled zinc by blood cells, taken from zinc-deficient rats and from rats in which an inflammation is induced. In both conditions, the serum zinc concentration is reduced. In clinical practice, this makes it difficult to determine whether the decrease in serum zinc is the result of a real or an apparent zinc deficiency. In stress, like an inflammatory disease, the decrease of zinc reflects an apparent zinc deficiency because of redistribution of serum zinc into the liver and because of decrease in serum albumin concentration. Over 70% of the serum zinc is bound to albumin. Blood cells from zinc-deficient and control rats were isolated using a discontinuous Percoll gradient and incubated under nearly physiological conditions in a 65Zn-containing medium. A significant increase in the in vitro uptake of 65Zn-labeled zinc by the blood cells of zinc-deficient rats was seen: erythrocytes 1.3, mononuclear cells 2.0, and polymorphonuclear cells 2.6 times the control values. During inflammation, no change in 65Zn-labeled zinc uptake by erythrocytes and mononuclear cells was demonstrated after 2 d, although the serum zinc and albumin concentrations were decreased, but a small but significant increase in zinc uptake by polymorphonuclear cells was observed. This study of 65Zn uptake in vitro under standard conditions may prove of value for distinguishing in patients real zinc deficiency from apparent zinc deficiency owing to, e.g., stress, although additional experiments should be performed.

The disposition of mesalazine from the azo compounds sulphasalazine and olsalazine (Dipentum) and from the slow-release mesalazine drugs Pentasa, Asacol, and Salofalk was studied in 20 patients with inflammatory bowel disease. Ten of them had diarrhoea, and 10 had normal stools. On the last 2 days of a 7-day maintenance treatment with each of the study drugs urine and faeces were collected for determination of mesalazine, acetyl-mesalazine, and unsplit azo compound. In patients with and without diarrhoea the urinary and the faecal excretion of acetyl-mesalazine was lowest during treatment with olsalazine. The proportion of acetyl-mesalazine in faeces was highest during treatment with Pentasa in both groups. The presence of diarrhoea was associated with a decrease in the proportion of acetyl-mesalazine in faeces during treatment with all drugs, not significant only for Pentasa. The proportion of unsplit azo compound in faeces increased in the case of diarrhoea to almost 50%. It is concluded that in patients with inflammatory bowel disease diarrhoea substantially influences the disposition from all these drugs except Pentasa.

Forty-nine patients with ulcerative colitis in remission were entered into a prospective, double-blind, multicenter trial comparing the relapse-preventing effect and safety of 4 g sulfasalazine and 2 g olsalazine daily during 48 wk. Of the 46 evaluable patients, 23 were assigned to sulfasalazine and 23 to olsalazine. Seven of 23 patients (30.4%) relapsed on sulfasalazine and six of 23 patients (26.1%) on olsalazine (95% confidence interval of the difference -22.0% to 30.3%). The relapse-free survival curves did not differ significantly at any time during the trial period. In both treatment groups, three patients dropped out because of adverse effects. Four patients on sulfasalazine and six patients on olsalazine experienced minor adverse effects. One patient on sulfasalazine had mild leukopenia, and four patients on sulfasalazine and one patient on olsalazine had decreased levels of haptoglobin. Thus, sulfasalazine and olsalazine are equally effective in maintaining remission of ulcerative colitis and are accompanied by a similar incidence of adverse effects.

After oral administration of 5-aminosalicylic acid a substantial proportion of the acetylated form is excreted in the faeces. We have studied the role of the faecal microflora in acetylating 5-aminosalicylic acid. In faeces incubated under both aerobic and anaerobic conditions there was acetylation of 5-aminosalicylic acid. Of the anaerobic bacteria isolated from a 10(8) faecal dilution 44% were able to acetylate 5-aminosalicylic acid. We conclude that the normal faecal microflora contribute to the acetylation of 5-aminosalicylic acid.

Objective: To determine whether sulphasalazine plus prednisone is more effective than sulphasalazine alone in treating active Crohn disease., Design: Randomized, double-blind, placebo-controlled trial., Setting: Multicenter trial in one university hospital and nine general hospitals., Patients: Patients with active Crohn disease and a Van Hees Activity Index of 140 or more. Of 71 patients who were randomly assigned, 60 completed treatment and were analyzed., Interventions: For 16 weeks, 30 patients received sulphasalazine, 6 g/d (or 4 g/d if adverse effects occurred) and prednisone, 30 mg/d initially. Prednisone therapy was tapered in increments of 5 mg/2 wk to 10 mg/d after 8 weeks. Thirty other patients received sulphasalazine and a placebo., Measurements and Main Results: In the first 6 weeks of treatment, the Van Hees Activity Index decreased to a median of 70% (interquartile range, 57% to 81%) of the initial value in patients treated with sulphasalazine and prednisone and to a median of 87% (interquartile range, 70% to 94%) in patients treated with sulphasalazine alone (P = 0.001). In the last 4 weeks of treatment, the corresponding figures were 63% (interquartile range, 40% to 75%) and 70% (interquartile range, 54% to 90%) (P = 0.10). The Crohn's Disease Activity Index decreased in the first 6 weeks to a median of 65% (interquartile range, 57% to 86%) in patients receiving sulphasalazine and prednisone and to a median of 75% (interquartile range, 58% to 101%) in patients receiving sulphasalazine alone (P = 0.13). In the last 4 weeks of treatment, the corresponding figures were 65% (interquartile range, 42% to 90%) and 76% (interquartile range, 49% to 110%) (P = 0.19)., Conclusions: The use of prednisone in addition to sulphasalazine in patients with active Crohn disease results in a significantly faster initial improvement, but not in a significantly better result after 16 weeks of treatment, when disease activity is measured by the Van Hees Activity Index.

Although the risk of vitamin intoxication is well recognised, massive doses of these preparations continue to be prescribed, especially in the so-called 'alternative' medical sector. We describe a patient with hypervitaminosis D due to administration of megadoses of vitamin D in the absence of an obvious indication. Mode of action and symptoms of vitamin D intoxication are discussed. It is emphasized that vitamin preparations should only be used when strictly indicated and that close clinical and biochemical supervision is necessary.

Constrictive pericarditis is a slowly progressive disabling disease. The diagnosis is easily overlooked because of the striking extracardial signs and symptoms such as abdominal discomfort, general fatigue, cachexia, ascites and oedema. We describe 7 patients with these symptoms in whom the diagnosis was missed during 0.5-17 years. The decisive clue for correct diagnosis appeared to be the raised central venous pressure. This proves the importance of an accurate physical examination. Other findings were: ascites (7/7), hepatomegaly (7/7), oedema (6/7), narrow pulse pressure (less than or equal to 35 mmHg) (5/7), ECG abnormalities (7/7) and pericardial calcifications on the chest X-ray (5/7). In addition we found slightly raised liver enzymes and a protein-losing enteropathy leading to low serum protein levels. These abnormalities are all explained by the alterations in haemodynamics and lymph flow. The only curative therapy is surgical decortication of the heart.

The data of 301 ulcerative proctitis/colitis patients, with a mean follow-up of 10 (1/2-26) years were analysed retrospectively. In 84 patients (28%) the diagnosis was made in this hospital (non-selected group), the other 217 patients were referred from other hospitals with an established diagnosis of ulcerative colitis. At any time after the fifth year of illness approximately 55% of the non-selected patients were free of symptoms, for the referred patients this proportion was 30%. In one half of the cases the inflammation started as a proctitis, almost 60% of these progressed to colitis later. Fourteen patients (5%) had a toxic megacolon, and a colon carcinoma developed in 9 patients (3%) on average 13 years after the first symptoms of colitis. We recorded 9 colitis-related deaths. Fifty patients (17%) underwent a colectomy, mostly because of failure of conservative therapy.

Hemoperfusion through charcoal adsorbers has often been proposed for use in exogenous and endogenous intoxication. A serious drawback of this technique is the often encountered loss of platelets and leucocytes. In vitro hemoperfusion studies with heparinized human blood and in vivo hemoperfusion of heparinized Labrador dogs through different types of charcoal adsorbers (Becton-Dickinson [B-D], Gambro, Haemocol) clearly demonstrated that addition of the anticoagulant acid citrate dextrose (ACD) might reduce the loss of platelets. ACD seemed to have no distinct influence on leucocyte retention.

A new analytical technique is described for measuring volatile sulphur compounds in human breath. The sulphur compounds were trapped and concentrated onto Tenax GC and then assayed by gas chromatography, using a specific sulphur detector. The detection limit amounts to about 0.2 ng/l (0.1 ppb). Among the sulphur volatiles, dimethylsulphide and methanethiol were quantitatively analysed in 100 ml of breath of 20 normal subjects and 35 cirrhotic patients. Dimethylsulphide in the breath of cirrhotics (113.4 +/- 31.9 ng/l, mean +/- SEM) was significantly elevated (p less than 0.05) compared with normals (21.1 +/- 1.7 ng/l). The concentration of methanethiol in the breath of normals and of most cirrhotics was less than 1 ng/l. In only five cirrhotics could methanethiol be detected in 100 ml of breath (3-23 ng/l). Dimethyldisulphide and hydrogen sulphide were not present in detectable amounts in the breath of normals. In cirrhotics, dimethyldisulphide was detected in a few cases. Ethanethiol was absent in the breath of both normals and cirrhotics.

Twenty-two duodenal and 16 gastric ulcer patients were treated with 400 mg cimetidine twice daily for one year after their ulcers had healed. No change in gastric acid secretion was observed before and after treatment in 20 duodenal and 13 gastric ulcer patients. Similarly, the inhibitory effect of 200 mg cimetidine on gastric acid secretion was unaltered in 11 duodenal and 6 gastric ulcer patients studied and cimetidine blood concentration were unchanged in 9 duodenal and 4 gastric ulcer patients after one year. In 7 duodenal and 6 gastric ulcer patients the serum gastrin response to a standard test meal before and after treatment was identical.

Methods: The stability of disodium azodisalicylate, 5-aminosalicylic acid and acetyl-5-aminosalicylic acid dissolved in distilled water and in urine or mixed with faeces to which HgCl2 was added, was studied at -20 degrees C, 4 degrees C and room temperature., Results: In water, no marked differences were found between the three storage regimens. In urine, disodium azodisalicylate and acetyl-5-aminosalicylic acid were stable, while the 5-ASA concentration decreased when stored at 4 degrees C and room temperature. In faeces stored during seven days, a marked decrease in 5-aminosalicylic acid concentration to about zero was found when it was kept at 4 degrees C and room temperature. No marked change in the concentration of disodium azodisalicylate and 5-aminosalicylic acid added to the faeces-HgCl2-mixtures appeared.

The response of active Crohn's disease to sulphasalazine (4-6 g per day) has been studied in a placebo-controlled trial. The study was carried out at two hospitals. From August 1977 to August 1979 all patients with established Crohn's disease were examined for their eligibility for the trial. A nine-item index of inflammatory activity was used as the primary measure of response. The variables in this index were serum albumin, ESR, body weight released to height, abdominal mass, temperature, stool consistency, bowel resection, and extraintestinal symptoms related to Crohn's disease. A favourable response to therapy was defined as a decrease of the activity index with 25% or more at the end of the trial period, compared with the initial value. Twenty-six patients (13 in each treatment group) have been followed up for six months. The response of active Crohn's disease to sulphasalazine was significantly better than to placebo.

Cytosolic glutathione S-transferases were purified from the epithelial cells of human small and large intestine. These preparations were characterized with regard to specific activities, subunit and isoenzyme composition. Isoenzyme composition and specific activity showed little variation from proximal to distal small intestine. Specific activities of hepatic and intestinal enzymes from the same patient were comparable. Hepatic enzymes were mainly composed of 25 kDa subunits. Transferases from small intestine contained 24 and 25 kDa subunits, in variable amounts. Colon enzymes were composed of 24 kDa subunits. In most preparations, however, minor amounts of 27 and 27.5 kDa subunits were detectable. Separation into isoforms by isoelectric focusing revealed striking differences: glutathione S-transferases from liver were mainly basic or neutral, enzymes from small intestine were basic, neutral and acidic, whereas large intestine contained acidic isoforms only. The intestinal acidic transferase most probably was identical with glutathione S-transferase Pi, isolated from human placenta. In the hepatic preparation, this isoform was hardly detectable. The specific activity of glutathione S-transferase showed a sharp fall from small to large intestine. In proximal and distal colon, activity seemed to be about equal. In the ascending colon there might be a relationship between specific activity of glutathione S-transferases and age of the patient, activity decreasing with increasing age.

Suppositories of sulphapyridine, 5-aminosalicylic acid, and placebo were used in 45 patients with idiopathic proctitis to determine the active part of sulphasalazine. Each patient used one of the suppositories twice daily for four weeks in a double-blind controlled trial. Complete clinical remission with normal rectal mucosa on sigmoidoscopy occurred in 60% of patients given 5-aminosalicylic acid, but in only 13% and 27% of those given sulphapyridine and placebo respectively. Twelve patients were included twice. In eight of these patients 5-aminosalicylic acid was given one time and sulphapyridine (two patients) or placebo (six patients) another time. Clinical remission occurred in each patient with 5-aminosalicylic acid, but in only one patient during other therapy. The results suggest that 5-aminosalicylic acid is the active therapeutic moiety of sulphasalazine.

The disposition of disodium azodisalicylate and salicylazosulfapyridine was studied in 6 healthy volunteers. After a single oral dose (1.0 g disodium azodisalicylate; 2.3 g salicylazosulfapyridine) maximum serum concentrations of the intact compound ranged between 1.4 and 6.8 mumol/L and 32 and 114 mumol/L, respectively. Mean residence time and serum half-life of disodium azodisalicylate were considerably longer than those of salicylazosulfapyridine, probably because of a higher apparent volume of distribution. Both compounds were largely split by colonic bacteria and comparable amounts of the active moiety, (acetyl-)5-aminosalicylic acid, were recovered in feces. During long-term ingestion of disodium azodisalicylate (1.0 g/day) it took 6-19 days to reach a steady state. Serum concentrations of disodium azodisalicylate at steady state were low: 2.2-8.4 mumol/L. The serum half-life was 6-10 days. It is concluded that the disposition of disodium azodisalicylate is similar, in important respects, to that of salicylazosulfapyridine. Disodium azodisalicylate, therefore, deserves therapeutic trial.

Continuous treatment of three Zollinger-Ellison patients with histamine H2-receptor antagonists for 14, 26 and 31 months resulted in effective relief of complaints and marked reduction in gastric acid secretion. In one of the patients the dose of cimetidine had to be doubled after 15 months of treatment because of a rise in basal gastric acid secretion accompanied by recurrent diarrhea. Fasting and secretin-stimulated serum gastrin levels were not affected by long-term treatment with histamine H2-receptor antagonists. No side-effects were observed in the three patients on long-term treatment.

In order to assess the efficacy of cimetidine in patients with endoscopically anastomotic ulcer after partial gastrectomy, 21 such patients entered a double-blind prospective clinical trial. At endoscopy after 4 wk of treatment, 8 of 12 patients treated with 1 g of cimetidine daily compared with 1 of 9 patients who received a placebo had healed ulcers (P less than 0.05). Evaluation of symptoms relief supported the efficacy of cimetidine compared with placebo. Healing rate after 1 mo of treatment with cimetidine was 67% and increased to 86% after 2 mo. During 1 year of maintenance therapy with 800 mg cimetidine daily, 3 of 19 patients relapsed. No serious side effects were observed. The results of this study demonstrate a beneficial effect of cimetidine on healing and symptoms of anastomotic ulcers.

Plasma responses of the major immunoreactive glucagon (IRG) components have been investigated in a case of glucagonoma syndrome. Fasting plasma IRG was 4155 pg/ml. Gel chromatography of plasma revealed that 66% of immunoreactivity was present as IRG9000, while IRG3500 accounted for an additional 26%. The appearance in peripheral plasma of these two glucagon fractions was examined after administration of a number of compounds. IRG levels were clearly elevated after arginine and tolbutamide. Both calcium and calcitonin induced a biphasic rise of IRG, the increase being slower after calcium administration. Somatostatin suppressed plasma IRG levels. All tests induced changes in both IRG3500 and IRG9000. In general, relative changes were more pronounced in IRG3500 than in IRG9000, while absolute changes were greater in IRG9000. The shape of the response curves of IRG3500 and IRG9000 was quite similar after arginine, calcium and somatostatin. After tolbutamide the IRG9000 response was delayed as compared to the IRG3500 component. During the latter part of the calcitonin infusion, IRG9000 remained elevated while IRG3500 was back at its starting level.

Secondary bile acids have been implicated in colonic carcinogenesis. Transformation of primary into secondary bile acids (7 alpha-dehydroxylation) in the large bowel is a pH-dependent process. Inhibition of this reaction could be achieved by lowering colonic pH. We, therefore, studied the effects of lactulose (a non-absorbable disaccharide), which is capable of acidifying colonic contents, on secondary bile acid metabolism. Because this metabolism is age dependent, lactulose was given (0.3 g kg-1 twice daily for 12 weeks) to nine middle-aged (age 31-54 years; mean 45.7) and ten elderly subjects (age 56-81 years; mean 66.4). Twice before, and after 6 and 12 weeks' lactulose administration, biliary and faecal bile acids, whole gut transit time, faecal weight and dry weight, and faecal pH were recorded. The concentration of (iso)lithocholic and deoxycholic acid in faeces was higher in elderly subjects (P less than 0.05) but the excretion was comparable. After lactulose the concentration and excretion of the major secondary bile acids decreased. The primary bile acid fraction rose from 5% before, to more than 20% after, lactulose (P less than 0.05). Faecal weight increased and faecal dry weight decreased, resulting in a higher faecal water output during lactulose. Whole gut transit time did not change. The faecal pH dropped after 6 (P less than 0.05) and further after 12 weeks' lactulose (P less than 0.05). The percentage deoxycholic acid in bile was higher, and cholic acid lower, in elderly subjects (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

In a middle-aged group of normal subjects achlorhydria after maximal stimulation with pentagastrin was found in 12 out of 366 males (3%) and 2 out of 198 females (1%); 13 of these 14 (93%) had an elevated serum gastrin, of which nine were more than two times normal. In another 11 persons a moderately elevated serum gastrin - less than two times normal - was found in absence of achlorhydria. At least seven of them had hypochlorhydria. Of 540 persons with a normal serum gastrin one had achlorhydria. Determination of the serum gastrin appeared to be fairly reliable as a method of detecting achlorhydria.