Hypergastrinaemia during long-term omeprazole therapy: influences of vagal nerve function, gastric emptying and Helicobacter pylori infection.

AIM: elucidate the mechanisms that lead to severe hypergastrinaemia during long-term omeprazole therapy for gastro-oesophageal reflux disease (GERD). PATIENTS AND METHODS: A total of 26 GERD patients were studied during omeprazole maintenance therapy. Twelve patients with severe hypergastrinaemia (gastrin > 400 ng/L) were compared with 14 control patients (gastrin < 300 ng/L). Helicobacter pylori serology and a laboratory screen were obtained in all patients. Gastric emptying was scored by the evidence of food remnants upon endoscopy 12 h after a standardized meal. Gastric antrum and corpus biopsies were analysed for histological parameters, as well as somatostatin and gastrin concentrations. All patients underwent a meal-stimulated gastrin test and the hypergastrinaemia patients also underwent a vagal nerve integrity assessment by pancreatic polypeptide testing (PPT). RESULTS: Severe hypergastrinaemia patients had a longer duration of treatment (80 vs. 55 months; P = 0.047) and were characterized by a higher prevalence of H. pylori infection (9/12 vs. 2/14, P = 0.004), corpus mucosal inflammation and atrophic gastritis (P < 0.04). This was reflected in lower serum pepsinogen A concentrations (mean +/- S.E.M. 53.6 +/- 17.9 vs. 137 +/- 16.0 mg/L, P = 0.03), pepsinogen A/C ratio (1.8 +/- 0.3 vs. 4.1 +/- 0.6, P = 0.005) and mucosal somatostatin concentrations (2.75 +/- 0.60 vs. 4.48 +/- 1.08 mg/g protein, P = 0.038). Two patients in the hypergastrinaemia group had signs of delayed gastric emptying, but none in the normogastrinaemia group did (P = N.S.). In addition, both groups had a normal meal-stimulated gastrin response. CONCLUSION: Severe hypergastrinaemia during omeprazole maintenance therapy for GERD is associated with the duration of therapy and H. pylori infection, but not with abnormalities of gastric emptying or vagal nerve integrity.

Atrophic gastritis during long-term omeprazole therapy affects serum vitamin B12 levels.

BACKGROUND: Omeprazole maintenance therapy for gastro-oesophageal reflux disease (GERD) has been associated with an increased incidence of atrophic gastritis in H. pylori-infected patients and with a decreased absorption of protein-bound, but not of unbound cobalamin. AIM: : To test the hypothesis that the combination of decreased cobalamin absorption and atrophic gastritis decreases serum cobalamin levels during omeprazole therapy. METHODS: Forty-nine H. pylori-positive GERD patients were treated with omeprazole for a mean (+/- s.d.) period of 61 (25) months. At the start of omeprazole treatment (T0) and at the latest follow-up visit (T1), serum was obtained for measurement of cobalamin. Corpus biopsy specimens were obtained at entry and follow-up for histopathological scoring according to the updated Sydney classification. RESULTS: At inclusion, none of the 49 patients had signs of atrophic gastritis. During follow-up, 15 patients (33%) developed atrophic gastritis, nine of whom had moderate to severe atrophy. These 15 patients did not differ from the other 34 patients with respect to age, serum cobalamin at T0 or the duration of follow-up. During follow-up, no change was observed in the median serum cobalamin level in the 34 patients without atrophy; (T0) 312 (136-716) vs. (T1) 341 (136-839) pmol/L (P=0.1). In the 15 patients who developed atrophy, a decrease in cobalamin was seen from 340 (171 to 787) at baseline to 285 (156-716) at latest follow-up (P < 0.01). CONCLUSIONS: The development of atrophic gastritis during omeprazole treatment in H. pylori-positive GERD patients is associated with a decrease of serum vitamin B12 levels.

Titres of anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease are not related to disease activity.

In the systemic vasculitides, serial measurement of titres of anti-neutrophil cytoplasmic autoantibodies (ANCA) is useful for follow-up of disease activity and prediction of relapses. ANCA have been detected in patients with inflammatory bowel disease, but their relation to disease activity in these diseases is unclear. We analysed the relation between disease activity and ANCA titres as determined by indirect immunofluorescence in paired samples obtained during active disease and at remission from individual patients with ulcerative colitis (n=60) and Crohn's disease (n=101). In addition, patients were followed prospectively, to study the fluctuations of ANCA with time in relation to disease activity. We did not detect a correlation between disease activity and ANCA titres, either in paired samples from active disease and remission, or in serial samples, either in ulcerative colitis or in Crohn's disease. In contrast to the ANCA-associated systemic vasculitides, serial measurement of ANCA titres is not useful in the monitoring of disease activity in patients with inflammatory bowel disease.

Dyspepsia as initial symptom of splanchnic vascular insufficiency.

A patient is reported with an unusual presentation of splanchnic ischaemia, causing gastritis. Although mesenteric ischaemia is well described in the literature, there is little information on gastric ischaemia resulting in gastritis. There was a considerable delay in diagnosis and treatment, adding to a complicated course of events. After revascularization the patient made a complete recovery.

Does long-term inhibition of gastric acid secretion with omeprazole lead to small intestinal bacterial overgrowth?

OBJECTIVE: Gastric acid secretion and small intestinal motility are the main mechanisms of defense against bacterial overgrowth of the proximal digestive tract. Bacterial colonization of the stomach during gastric acid inhibition has been documented, but is probably without clinical consequence. However, small intestinal bacterial overgrowth can have serious clinical implications with malabsorption and diarrhoea. METHODS: We prospectively investigated small intestinal bacterial overgrowth in 40 patients receiving long-term omeprazole treatment using the [14C]glycocholic breath test. Tests were performed before omeprazole treatment, after 6 weeks treatment with 40 mg o.m. and after 26 weeks treatment with 20 mg; in the test each patient served as his own control. RESULTS: Breath tests, using individual curves, peak values, time at which the peak appeared and the area under the curve, did not differ significantly during treatment from those before treatment. CONCLUSIONS: We conclude that long-term strong inhibition of gastric acid secretion does not lead to small intestinal bacterial overgrowth.

Antineutrophil antibodies in inflammatory bowel disease recognize different antigens.

Anti-neutrophil cytoplasmic antibodies (ANCA) were observed in 31 out of 68 sera (45%) from Ulcerative Colitis (UC) patients and in 13 out of 38 Crohn's Disease (CD) sera (34%). The presence of ANCA was not related to disease activity, nor to the localization of the disease manifestations. By Western Blotting ANCA showed reactivity with either lactoferrin, polypeptides occurring as a doublet of 66/67 kD MW, or polypeptides occurring as a doublet of 63/54 kD MW.

[2 patients with a non-Hodgkin lymphoma located in the pancreas]. / Twee patiënten met non-Hodgkin-lymfomen gelokaliseerd in het pancreas.

A small percentage (around 1.5%) of pancreatic malignancies are well treatable non-Hodgkin's lymphomas. Two patients with this disease are described. One patient was treated with both surgery and chemotherapy, the other with chemotherapy only. The results in both patients were excellent with complete responses being achieved. The literature on pancreatic non-Hodgkin's lymphomas is reviewed.

[Acute disorders of intestinal perfusion; a nonrigid abdomen may still be acute]. / Acute doorbloedingsstoornissen van de darm: een soepele buik kan toch acuut zijn.

Three patients, a man aged 50 years and two women aged 46 and 45 years, with abdominal pains and an undistended abdomen, were found to have acute mesenteric ischaemia. The causes were: unknown, a thrombus in the descending aorta and severe atherosclerosis, respectively. In the male patient, only 30 cm of vital small intestine ultimately remained; in one woman embolectomy sufficed, in the other, resection of a limited portion of the jejunal tract. All three patients fully recovered. Acute mesenteric ischaemia is a potentially lethal disease. Diagnosis in the first reversible phase makes full recovery of the intestine possible. This may be difficult since the clinical signs and symptoms are not specific in this phase and invasive diagnostic procedures (angiography) are required for accurate diagnosis. By making an angiogram of the mesenteric vessels in each patient with severe abdominal pain, no signs of peritonitis and leukocytosis, without another diagnosis, reversible mesenteric ischaemia can be diagnosed and a vascular surgical reconstruction can be planned.

Safety profile of omeprazole. Adverse events with short-term treatment.

Omeprazole is a very potent inhibitor of gastric acid secretion and has proven to be efficacious in the healing of peptic ulcer and reflux oesophagitis. A search for adverse events during short-term treatment with omeprazole has been made, based on data from published comparative trials, data on file at the manufactor's (Hässle Research Laboratories, Mölndal, Sweden) and personal series. Omeprazole does not show more adverse events than drugs currently widely in use for the treatment of acid-related disorders. A change in a wide range of laboratory parameters has not been observed, except for a rise in basal and meal-stimulated serum gastrin which can be ascribed directly to the inhibition of acid secretion. For short-term treatment omeprazole can be considered as a safe drug.

Nitrofurantoin-induced pancreatitis: report of a case.

A patient with nitrofurantoin-induced pancreatitis is described, representing the first patient with this condition to be reported in the literature. The diagnosis of nitrofurantoin-induced pancreatitis was confirmed by rechallenge. The clinical and biochemical picture cleared rapidly after discontinuation of the drug. The conclusion is proffered that nitrofurantoin-induced jaundice is not always due to cholestatic hepatitis, but can result from obstruction of the common bile duct due to edema of the pancreatic head secondary to nitrofurantoin pancreatitis.

Anorexia, weight loss, and diarrhea as presenting symptoms of angiokeratoma corporis diffusum (Fabry-Anderson's disease).

Fabry-Anderson's disease or angiokeratoma corporis diffusum (ACD) is an X-linked sphingolipidosis with a systemic character and occurs in 2-5 per million births (1-3). The basic defect is the absence of a lysosomal enzyme x-galactosidase A. This enzyme is necessary for the metabolization of ceramide trihexoside (globotriglycosyl ceramide), a breakdown product of cell membranes (4, 5). Clinically the disease is characterized by cutaneous angiokeratoma's and severe pain in the limbs from the second decade, followed by progressive renal insufficiency and cardiovascular and cerebrovascular damage in the third or fourth decade (6-8). In patients with established ACD, gastrointestinal symptoms have been described incidentally, mainly mild diarrhea (9, 10). We describe a kindred with ACD showing two extraordinary clinical features: (1) Anorexia, weight loss, and diarrhea were the presenting symptoms and antedated limb pain by many years, which has not been described before. (2) The disease was associated with another rare X-linked disorder: hypoplastic amelogenesis imperfecta.

The effect of oral cimetidine on the basal and stimulated values of prolactin, thyroid stimulating hormone, follicle stimulating hormone and luteinizing hormone.

The effect of cimetidine on the basal values of PRL, TSH, FSH and LH and on the TRH/LHRH-stimulated values of these hormones was investigated in patients with peptic ulcer. No difference was found between the values before, during or after cimetidine maintenance treatment. To evaluate whether a rise in PRL occurs during the early phase of cimetidine treatment, daily estimations were made of basal PRL values during the first week of cimetidine adminstration in volunteers. No significant difference was found. It is concluded that oral cimetidine treatment has no influence on the basal and stimulated values of PRL, TSH, FSH and LH.

Comparative effect of cimetidine and ranitidine on prolactin secretion.

Cimetidine has been shown to stimulate prolactin secretion after a intravenous administration. Cimetidine 200 mg and ranitidine 50 mg was given i.v. in a randomly allocated order to 22 volunteers on consecutive days; these doses can be regarded as equivalent as far as inhibition of gastric acid output is concerned. Plasma prolactin was estimated at regular intervals. The prolactin stimulating effect of cimetidine was confirmed while ranitidine did not influence plasma prolactin levels. Although cimetidine and ranitidine seem to be equally effective in reducing gastric acid output, the effect of the drugs are not the same on their entire spectrum of action since ranitidine does not influence plasma prolactin. It still has to be established in clinical trials which drug is the best choice in clinical medicine.

Role of fructose-sorbitol malabsorption in the irritable bowel syndrome.

Because even after low doses of fructose and sorbitol, fructose-sorbitol malabsorption has been found in a high number of patients with the irritable bowel syndrome, an etiological role of fructose-sorbitol malabsorption in the irritable bowel syndrome has been suggested. However, these studies have been uncontrolled. Therefore, a controlled study of fructose-sorbitol malabsorption in the irritable bowel syndrome compared with healthy controls was performed. Seventy-three patients, 23 men and 50 women with a mean age 43.1 +/- 1.7 years (range, 18-66 years) with the irritable bowel syndrome were compared with 87 age- and sex-matched control subjects. Fructose-sorbitol malabsorption was determined by a breath-hydrogen test (Lactoscreen, Hoek Loos, Schiedam, The Netherlands) following an oral load of 25 g fructose and 5 g sorbitol after a 10-hour fast. Fructose-sorbitol malabsorption, as shown by an H2 peak of 20 ppm over basal values, was found in 22 (30.1%) of the patients and 35 (40.2%) of the control subjects. With a lower peak level of 10 ppm over basal values, these percentages were 45.2% and 57.5%, respectively. Also, the highest H2 peak values (15.2 +/- 2.3 ppm vs. 21.5 +/- 2.6 ppm), time to reach peak levels (110.7 +/- 5.4 min vs. 107.1 +/- 5.9 min), and area under the H2 curve (1310 +/- 219 ppm.min vs. 1812 +/- 255 ppm.min) did not discriminate between patients and controls. During the test, symptoms developed in 31 of 70 patients and in 3 of 85 control subjects (P less than 0.0001). Symptomatic patients did not differ from asymptomatic patients regarding the presence or absence of fructose-sorbitol malabsorption, H2 peak values, and area under the curve. No differences could be identified between male and female patients or controls. In conclusion, fructose-sorbitol malabsorption is frequently seen in patients with irritable bowel syndrome, but this is not different from observations in healthy volunteers. Therefore, fructose-sorbitol malabsorption does not seem to play an important role in the etiology of irritable bowel syndrome.

Influence of RP 40749 on basal and meal-stimulated serum-gastrin, serum-pepsinogen I, and gastrin-content of the antral mucosa in duodenal ulcer patients.

Eighteen patients with active duodenal ulcer were treated with a novel antisecretory drug, RP 40749, either 100 mg or 150 mg as a daily nocturnal dose for 28 days. In these patients we evaluated the clinical course, endoscopic healing rates after 28 days, routine laboratory parameters, basal serum gastrin and pepsinogen I levels, meal-stimulated serum gastrin concentration, and the gastrin content of the antral mucosa. All nine patients receiving 150 mg RP 40749 and eight of nine patients receiving 100 mg RP 40749 healed their ulcers completely within 28 days, becoming rapidly symptom-free after an average of three days. The basal (53.8 +/- 5.2 vs 99.8 +/- 11.4 pg/ml) and meal-stimulated serum gastrin levels (109.2 +/- 12.1 vs 189.2 +/- 16.7 pg/ml) rose significantly after treatment with RP 40749, as did the gastrin content of the antral mucosa (11.3 +/- 2.1 vs 26.0 +/- 5.1 micrograms/g), suggesting increased synthesis and secretion of gastrin. Between the 100 mg and 150 mg groups, no significant differences in response were observed. Serum pepsinogen I levels (64.9 +/- 7.3 vs 147.9 +/- 17.9 ng/ml) increased after treatment; the increase after 150 mg RP 40749 was significantly greater than that after 100 mg RP 40749. The increase of serum pepsinogen levels are probably due to a spillover effect resulting from a blockade in exocrine secretion into the lumen. There were no relevant changes in routine laboratory parameters.