Low serum cobalamin levels in a population study of 70- and 75-year-old subjects. Gastrointestinal causes and hematological effects.

We examined causes and hematological consequences of low serum cobalamin (vitamin B12) concentration in two representative population samples of 70-year-old (N = 293) and 75-year-old subjects (N = 486). Subjects with values below 130 pmol/liter (4.8% and 5.6%, respectively) were investigated with Schilling test, upper gastrointestinal endoscopy, determination of serum gastrin and group I pepsinogens, and bone marrow examination. Gastrointestinal abnormalities of etiologic significance were found in 26 of the 32 examined subjects: atrophy of the gastric body mucosa (N = 16, with pernicious anemia in six), partial gastrectomy (N = 6), and intestinal malabsorption (N = 4). Megaloblastic hematopoiesis was found in 10 individuals, four of whom had macrocytic anemia. Our results indicate that low serum cobalamin concentration in the elderly is usually a consequence of disease rather than of high age per se and that gastric mucosal atrophy is a major etiologic factor.

Causes of malabsorption after total gastrectomy with Roux-en-Y reconstruction.

Malabsorption after total gastrectomy and Roux-en-Y reconstruction was studied in 11 patients. Absorption of fat, xylose and lactose was tested and the orocaecal transit time was radiologically determined. Bacterial colonization of the small intestine was studied by culturing jejunal juice and indirectly with a hydrogen breath test. Ten patients lost weight postoperatively and six had diarrhoea. All 11 had steatorrhoea with mean faecal fat excretion 289 +/- 55 (SEM) mmol free and esterified fatty acids/72 h (upper reference limit 60 mmol/72 h). Low xylose absorption was found in only one patient and low lactose absorption in none. The median orocaecal transit time was only 110 minutes (less than or equal to 60 min in 4 cases). Postoperative weight loss showed significant inverse correlation with orocaecal transit time. Bacterial overgrowth of the small intestine was found in four patients. The cause of malabsorption was assumed to be rapid intestinal transit in four patients and bacterial overgrowth in four others, leaving three in whom pancreatic understimulation is suggested as the reason for steatorrhoea.

The value of the hydrogen (H2) breath test for the diagnosis of bacterial overgrowth in gastric achlorhydria.

Sixteen healthy volunteers, 23 patients with peptic disease, and 38 patients with achlorhydria were investigated with bacterial cultures from gastric juice and a hydrogen (H2) breath test after a standard meal. In acid-secreting subjects upper respiratory tract bacteria were found in 6/39. In every single achlorhydric patient gastric bacterial concentrations were above log 10 5.7/ml. Fecal flora was found in 22/38. The patient with fecal organisms were significantly older than those without (p less than 0.05). The H2 breath test revealed low postprandial carbohydrate fermentation in acid secretors and in achlorhydrics with no fecal flora. The lowest H2 production was found 90 and 120 min after the meal. In achlorhydrics with fecal organisms the mean H2 concentration at these times of measurement was elevated (p less than 0.05). Assuming that a mean H2 concentration at 90 and 120 min above 19 ppm (mean in healthy volunteers at 90 and 120 min + 2 SD) is pathological, the association of fecal bacteria in gastric juice and a "positive" H2 breath test is highly significant (P less than 0.001). Fecal bacteria in the gastric juice would indicate small-intestinal fermentation with a probability of 81%. A gastric culture negative for fecal organisms would predict a "negative" H2 breath test with a probability of 91%.

Nutrient malassimilation after total gastrectomy and possible intervention.

Malnutrition is common after total gastrectomy. Different pathophysiological reasons have been reported. We have investigated malabsorption in patients after total gastrectomy and Roux-Y esophagojejunostomy, analyzing the orocecal transit time, the bacterial flora of the upper intestine, and the small intestinal carbohydrate fermentation. Furthermore, we studied the benefit of pancreatic enzymes in this condition. The orocecal transit time was found to be short in 5/11 patients. In 4/11 patients upper intestinal bacterial overgrowth was probable. In the remaining 3/11 patients with steatorrhea, pancreatic dysfunction, due to understimulation, was suspected to be the reason for malassimilation. A subsequent double-blind, cross-over trial on supplementary treatment with pancreatic enzymes was performed in 15 patients. This treatment did not significantly reduce the degree of steatorrhea in these patients.

Effect of selective and non-selective antimuscarinics on rectosigmoid motility and gastrointestinal transit.

In 12 healthy volunteers, a rectosigmoid motility index (RSMI) was measured when either placebo, 0.5 mg atropine, or 5 mg pirenzepine was given intravenously as a single dose, double-blind, in random order after a control period of 30 min. Compared with the control period, atropine gave a significant decrease of the RSMI during the entire recorded period of 90 min, whereas pirenzepine inhibited RSMI only during the first two 15-min periods. In another series of experiments, gastrointestinal transit was assessed by means of a radiographic marker method. In healthy volunteers, gastrointestinal transit was estimated (n = 20) and gastric secretion was measured (basally and after modified sham feeding; n = 10) during oral medication with placebo, 50 mg pirenzepine twice daily, or 17.5 mg benzilonium bromide twice daily. In 10 of the volunteers gastrointestinal transit was also estimated with 35 mg benzilonium bromide twice daily, and in the other 10 volunteers with 0.6 mg L-hyoscyamine twice daily. The number of retained markers was significantly lower during pirenzepine than during L-hyoscyamine treatment. Neither dose of benzilonium bromide changed the transit of markers. Compared with non-selective antimuscarinics, the effect of pirenzepine was differential: with equipotently acid-reducing doses the decrease of the RSMI after pirenzepine lasted shorter and gastrointestinal transit was accelerated.

The hydrogen (H2) breath test. Sampling methods and the influence of dietary fibre on fasting level.

Three end-expiratory breath hydrogen (H2) sampling methods were compared in a patient group (n = 12) and a laboratory staff group (n = 12) on two separate occasions. H2 samples obtained with each method showed significantly different concentrations (p less than 0.001) but no significant differences in coefficient of variation when individual triplicate samples were evaluated. There was a high correlation between the breath H2 concentrations obtained by the three methods (r = 0.93-0.96). Fasting breath H2 values after an overnight fast and an unrestricted diet the day before the investigation were compared with values obtained after an overnight fast and a low-fibre diet the day before the test in two patient groups (n = 39 and 39) with a comparable distribution of diagnoses and in one group of healthy volunteers (n = 17). Fasting breath H2 concentrations were significantly lower after a low-fibre diet in the patient groups (p less than 0.005) and in healthy volunteers (p less than 0.02). We conclude that each of the three end-expiratory sampling methods can be chosen for use in H2 breath tests depending on suitability and convenience and that a low-fibre diet the day before the H2 breath test lowers fasting breath H2 concentration.

Hydrogen (H2) breath test and gastric bacteria in acid-secreting subjects and in achlorhydric and postgastrectomy patients before and after antimicrobial treatment.

Sixteen patients with pentagastrin-fast achlorhydria and 12 patients who had undergone Billroth II gastrectomy (at least 3 years previously) were compared with 10 acid-secreting volunteers and 13 patients with endoscopically proven peptic disease. The concentration and type of gastric bacteria were analysed in achlorhydrics, Billroth II patients, and patients with peptic disease. A 6-h hydrogen (H2) breath test after a standardized meal was performed in all subjects. The mean concentration of gastric bacteria was significantly higher in achlorhydrics and Billroth II patients than in patients with peptic disease. End-expiratory H2 excretion was elevated in achlorhydrics and Billroth II patients to levels significantly exceeding those of acid-secreting volunteers and patients with peptic disease. In achlorhydrics, total bacterial concentration in gastric juice was correlated to H2 excretion between 60 and 180 min after the meal. Treatment of achlorhydric and postgastrectomy patients with trimethoprim/sulphamethoxazole lowered H2 breath concentrations in both groups and reduced symptoms in achlorhydrics. Elevated end-expiratory H2 levels after a test meal indicate upper gastrointestinal bacterial overgrowth in achlorhydrics and in postgastrectomy patients.

Bacterial overgrowth as a consequence of reduced gastric acidity.

Reduction in acid secretion in atrophic gastritis allows bacterial colonization of the stomach, most extremely in achlorhydric patients with pernicious anaemia, in whom overgrowth may cause nitrate reduction and formation of potentially carcinogenic N-nitroso compounds. Subsequent bacterial contamination of the upper small intestine can induce mucosal damage and malabsorption. The situation is similar after gastrectomy. In achlorhydria and after gastrectomy, the risk of gastric cancer is increased. There is controversy as to the risks of long-term treatment with H2-receptor antagonists. Increase in nitrate-reducing bacteria, nitrite and N-nitrosamine have been observed in patients by some investigators but not in volunteers and patients by others. Bacterial concentrations after cimetidine are inversely related to pretreatment acid secretory capacity. Demonstration of increased mutagenicity of gastric juice after H2-receptor antagonists gives grounds for caution. Drastic acid reduction may in future be reserved for short-term and intermittent treatment and mild or moderate reduction for long-term treatment of peptic ulcer and ulcer prevention.

Pernicious anaemia, intragastric bacterial overgrowth, and possible consequences.

Intragastric bacterial colonization is well known in pernicious anaemia (PA), but its consequences have rarely been investigated. We have studied the clinical history, blood samples, and endoscopic biopsies from the stomach and duodenum of 80 patients with PA. In a random subgroup of 22 patients gastric juice was collected for aerobic culture and for estimation of nitrate, nitrate-reducing bacteria, nitrite, and N-nitrosamines; duodenal juice was studied in parallel in eight of these subjects. Gastric and duodenal juice had high bacterial counts; faecal organisms were found in 14 patients. The mean count of nitrate-reducing bacteria was significantly higher than in a control group of patients with peptic ulcer disease (p less than 0.001), as was the nitrite concentration (p less than 0.001). Thirty-three of the 80 patients had gastric dysplasias; 1 early gastric carcinoma was also found. Duodenitis was present in 39 out of 80 cases, in 6 associated with partial villous atrophy. A history of malabsorption and/or chronic intermittent diarrhoea was obtained significantly more often from patients with duodenitis. Four patients developed acute gastroenteritis shortly before or during the time of the study, two having a salmonella infection. Bacterial overgrowth in PA may be facilitated by altered immunological conditions, since low serum levels of IgA and IgG were found in this patient group.

Intragastric bacteria and nitrite after short-term treatment with different doses of antimuscarinic drugs.

In 11 volunteers gastric acid secretion was measured under basal conditions and after modified sham-feeding after 4 1/2 days' treatment with placebo tablets twice daily (placebo), pirenzepine, 50 mg twice daily (pirenzepine), benzilonium bromide, 17.5 mg twice daily (benzilonium 35), or benzilonium bromide, 35 mg twice daily (benzilonium 70), respectively. The first basal portion of gastric fluid was cultured aerobically and anaerobically, and its nitrite concentrations were measured by a colorimetric technique. Basal acid output was reduced 40% by pirenzepine, 71% by benzilonium 35, and 84% by benzilonium 70. Reduction of the stimulated acid output was 47%, 57%, and 74%, respectively. Mean bacterial count (in log10/ml gastric juice) after placebo was 3.50 +/- 0.81 (SEM). Only the treatment with benzilonium 70 gave significantly increased bacterial counts (6.41 +/- 0.68; p less than 0.01). Mean nitrite concentrations (in mumol/l) after placebo, pirenzepine, benzilonium 35, and benzilonium 70 were 2.90 +/- 1.26 (SEM), 3.90 +/- 1.17, 11.36 +/- 7.24, and 18.81 +/- 5.71, respectively. The last value was significantly different from that after placebo (p less than 0.025). Bacterial counts were negatively correlated to basal acid output (p less than 0.001) but not to stimulated acid output. Nitrite was directly correlated to bacterial counts and inversely correlated to basal and stimulated acid output. Even a short-lasting but strong inhibition of gastric acid output by antimuscarinics can change the intragastric milieu significantly. No significant changes occur after moderate reduction of gastric acid output.