Abstract: The low‐dose oral iron absorption test (OIAT) was performed in 85 consecutive anaemic patients referred for bone marrow examination in order to investigate the ability of the test to predict bone marrow iron stores and to differentiate between different categories of anaemia. Eight patients were excluded for technical reasons. Test results from 77 patients are presented as Cmax (μmol/l): the maximum increase in S‐iron measured during a 3 h period after administration of 10 mg oral iron sulfate. Iron deficiency was defined as the absence of stainable iron in bone marrow aspirates. Cmax was higher in 46 iron deficient patients [3 (median); 0 and 13 (1st and 3rd quartiles); 0–40 (range)] than in 31 non‐iron‐deficient patients (0; 0 and 2; 0–4) (p <0.01). 27 patients had primary bone marrow disease, 25 patients had absent bone marrow iron stores accompanied by inflammation, 17 patients had anaemia of chronic disease (ACD) and 8 patients had uncomplicated iron deficiency anaemia (IDA). Patients with IDA had higher Cmax (15; 13 and 28; 6–40) than patients with ACD (1; 0 and 2; 0–3), and than the 69 non‐IDA patients (1; 0 and 3; 0–19) (p<0.001). Cmax values above 5 μmol/l always indicated absent bone marrow iron stores.

The low-dose oral iron absorption test (OIAT), a possible test for iron deficiency, is based on the fact that intestinal iron absorption is higher in iron-deficient subjects than in those with normal or increased iron stores. The aims of this study were to establish a reference interval for the OIAT, to evaluate five different ways of presenting the results, and to advocate for the use of one of these methods. OIAT was performed in 122 healthy volunteers, 3 of whom were excluded as a result of technical difficulties. The volunteers were given 10 mg of oral iron sulphate at 0900 h on an empty stomach. S-iron was measured just before iron consumption, and after 1, 2 and 3 h. The maximum increase in S-iron during the test, presented as Cmax (micromol l(-1)), was higher in females (5 [median]; 3 and 7 [1st and 3rd quartiles]; 0-34 [range]) than in males (3; 1 and 5; 0-13) (p<0.001 Mann Whitney U-test). Furthermore, Cmax was significantly higher in females aged 22 44 years than in all other age groups (males and females), but did not fluctuate significantly with age in males. Cmax was higher in premenopausal than in postmenopausal females (6; 5 and 10; 0-34 and 4; 2 and 5; 0-12, respectively) (p <0.01 Mann Whitney U-test). In conclusion, iron absorption assessed by the OIAT was higher in premenopausal females than in postmenopausal females and males. We suggest reference intervals of 0-34 micromol l(-1) in premenopausal females, and 0-11 micromol l(-1) in all other persons, i.e. males and postmenopausal females.

1 Methotrexate (MTX) concentrations were studied in serum, mixed saliva and sweat during and after 24 h continuous MTX infusions (0.5-6 g m-2) in 14 patients with various malignant diseases. 2 The serum-MTX concentrations declined in a biphasic manner, but the MTX elimination in saliva and sweat varied to a much greater extent. 3 Saliva/serum and sweat/serum ratios during the MTX infusion were 2.3% and 0.55% respectively. The ratios had increased significantly 20 and 44 h postinfusion. 4 No correlations were demonstrated between salivary- and serum-MTX concentrations during the MTX infusion or 20 and 44 h later. 5 Markedly delayed renal MTX excretions were demonstrated in two patients. In one of them the salivary MTX elimination was also retarded, whereas this was not seen in the other one. 6 We conclude that measurements of MTX concentrations in mixed saliva cannot substitute for serum-MTX determinations in the monitoring of patients after 24 h MTX infusions.

One-hundred-and-six patients with pernicious anemia were HLA-A, B, C typed by serological technique and HLA-D typed by mixed lymphocyte culture technique for the specificities HLA-Dw1 - 8 and the locally defined D "H". In 13 cases, the D-typing was unsuccessful due to technical difficulties. HLA-A, B, C antigen frequencies did not show any significant deviation from expected values, while D typing showed increased frequencies of Dw2 and Dw5 and a possibly decreased frequency of Dw3. The typing was compared with clinical data such as the presence of organ specific autoimmune disease in first degree relatives, presence of anemia or myelopathy at time of diagnosis and presence of antibodies towards parietal cells or intrinsic factor. The presence of intrinsic factor antibody was associated with the presence of Dw2 and a decrease of Dw5 and possibly also with a decrease of Dw4. No associations were found for the other investigated parameters. If intrinsic factor antibodies have a pathogenetic role, our findings might reflect a heterogeneity of pernicious anemia. These findings and the recently reported association between HLA-DR5 and Hashimoto's disease link these two thyrogastric diseases together to form a special subgroup within the group of organspecific autoimmune diseases; the other diseases in the group have as a common denominator the frequent presence of D/DR3.

Basal serum gastrin concentration was measured before and every week during the initial 5 weeks after renal transplantation in 9 of 20 patients with chronic renal failure who obtained a well functioning renal transplant. Furthermore, calcium and phosphorus metabolism in relation to serum gastrin was investigated in all 20 patients 5 weeks after transplantation. Before renal transplantation, serum gastrin was markedly elevated as compared with the levels in normal controls. During the first 3-5 weeks after renal transplantation, serum gastrin decreased towards normal values. A slight but significant increase in serum gastrin persisted 5 weeks after transplantation. No significant relation between changes in serum gastrin concentration and in calcium and phosphorus metabolism was observed.

Basal concentrations of serum gastrin and serum calcitonin were measured in 38 patients with pernicious anaemia and in 32 healthy control subjects. The fasting level of serum gastrin was greatly elevated in 32 patients and was within normal range in 6 patients, the difference between pernicious anaemia patients and controls being highly significant (P less than 0.001). No significant difference between fasting serum calcitonin concentrations in patients and healthy subjects was found. Furthermore, these hormones were studied before and after a beef meal in eight of the patients with hypergastrinaemia and in six healthy control subjects. After the meal serum gastrin concentrations increased significantly from basal values in both patients and controls, the peak values being reached 60 and 30 min after the meal, respectively. No significant changes in serum calcitonin concentrations were observed after the meal in either group. In five patients a transient rise in serum calcitonin occurred 5-10 min after ingestion, beginning, however, before any rise in serum gastrin was observed. Our results indicate that serum gastrin is without influence on calcitonin release, either in hypergastrinaemic patients with pernicious anaemia or in healthy subjects.

A pressure and pH-sensitive probe has been constructed for simultaneous measurement of gastro-oesophageal sphincter pressure and intragastric pH. The coefficient of variation for measurements of the gastro-oesophageal sphincter was 0.24, and for the intragastric pH, 0.09. After peroral ingestion of 400 mg of cimetidine or placebo, simultaneous measurements of gastro-oesophageal sphincter pressure and intragastric pH were made at fixed time intervals, and at the same time blood samples were taken for determination of serum gastrin and serum cimetidine concentrations. No demonstrable difference was found in the time-course of the gastro-oesophageal sphincter pressure after ingestion of cimetidine or placebo. After ingestion of cimetidine a significant rise in intragastric pH (p less than 0.05) occurred after 40 min, and this increased pH was maintained for the remainder of the experimental period, corresponding to a serum cimetidine concentration of over 1.00 mg/l. Similarly, there was a significant rise (p less than 0.05) in serum gastrin concentration after 150 min. There was a significant direct correlation between corresponding measurements of intragastric pH and serum gastrin (p less than 0.001), between intragastric pH and serum cimetidine (p less than 0.001), and between serum gastrin and serum cimetidine (p less than 0.05). Ingestion of cimetidine results in an increase in the serum gastrin concentration in healthy subjects, presumably as a result of reduced secretion of acid in the stomach. Neither the endogenous increase in serum gastrin concentration nor the increase in intragastric pH causes alteration in the gastro-oesophageal sphincter pressure.

The effect of surgical isolation and extrinsic denervation of the distal 5 to 7 cm of the human esophagus on resting gastroesophageal sphincter pressure and its response to graded increases of external abdominal compression was determined in 89 patients with duodenal ulcer. Fasting serum gastrin concentration also was measured. No significant changes in resting sphincter pressure were obtained before and after vagotomy of various types: parietal cell vagotomy, selective gastric vagotomy plus drainage, and selective gastric vagotomy plus precise antrectomy. No correlation between resting sphincter pressure and fasting serum gastrin concentration was found in any of the groups studied. The increase in gastroesophageal sphincter pressure was similar to the increase in intragastric pressure after 10, 20, and 30 mm Hg of external abdominal compression and was unchanged after all types of vagotomies. These results suggest that (1) extrinsic innervation of the lower esophageal sphincter in humans does not regulate the resting tone of the sphincter; (2) extrinsic "mechanical" influence does not play any role in the maintenance of resting pressure; (3) the effect of increased abdominal pressure is a pure mechanical effect, is unchanged after vagotomy, and therefore is not regulated by external neural reflex.

The interrelationship between serum gastrin and serum calcitonin concentrations was studied in 73 patients with chronic renal failure. In both haemodialyzed and non-dialyzed patients increased serum concentrations of these hormones were found compared with normal controls. In non-dialyzed patients with creatinine clearance above 10 ml/min a highly significant correlation between serum gastrin and creatinine clearance was found, whereas no correlation was found in patients with creatinine clearance below 10 ml/min. Between serum gastrin and serum calcitonin, a significant positive correlation was found in non-dialyzed patients. These findings may be explained by a relationship between the two hormones or be secondary to a decreased elimination due to the reduced renal function.

Plasma noradrenaline, heart rate, and serum gastrin were significantly greater in 12 patients with duodenal ulcer compared to 12 normal subjects. Arterial blood pressure was the same in patients and controls. Intravenous infusion of adrenaline resulted in a greater rise in serum gastrin in duodenal ulcer patients, while the rise in plasma adrenaline was very similar in both groups of subjects. This suggests that the clearance of catecholamines from plasma is not retarded in duodenal ulcer patients. The abnormally high plasma noradrenaline concentrations were unchanged after vagotomy, indicating that the elevated plasma noradrenaline in duodenal ulcer patients is not related to epigastric pain. The elevated plasma noradrenaline levels in patients with duodenal ulcer are not explained by a general difference in plasma noradrenaline and sympathetic nervous activity between patients and controls because plasma noradrenaline is not elevated in other groups of patients, viz. patients with essential arterial hypertension and diabetics without ketosis and neuropathy. It may be that patients with duodenal ulcers are subject to more stress than normal subjects, provided that chronic stress does not result in arterial hypertension. It is also possible that the elevated plasma noradrenaline concentrations in these patients are compensatory to other cardiovascular changes or derived from outside the cardiovascular system, e.g. from the gastrointestinal tract. {J Clin Endocrinol Metab49: 331, 1979)

In 36 patients with recurrent peptic ulcer after surgery (11 partial gastrectomy, 25 vagotomy with or without drainage), 12 had a gastric and 24 an intestinal recurrence. Gastric recurrence after partial gastrectomy was characterized by retained antral tissue and a marked serum gastrin response to feeding. Fasting serum gastrin concentration and gastric acid secretion were not correlated with the location of the recurrent ulcer. Gastric recurrences in patients treated by vagotomy correlated mainly with prolonged gastric emptying, and basal acid secretion was significantly lower than in patients with intestinal recurrence. Following complete vagotomy, the recurrence was usually gastric, but it was intestinal after incomplete vagotomy. In the vagotomy group, no correlations between location of ulcer and pentagastrin-stimulated acid secretion, or fasting and foodstimulated serum gastrin concentrations were found.

Serum gastrin increased in patients with pernicious anaemia after a beef-meal, but decreased after an oral load of glucose, xylose or sodium chloride. 50 g of glucose and 25 or 75 g of xylose suppressed serum gastrin to approximately 40% of basal values at 60 min and were slightly more effective than 10 g of sodium chloride. There was no rise in beef-meal stimulated serum gastrin concentration in vagotomized patients and only a slight rise in two patients with duodenal ulcer when an oral dose of 10 g of sodium chloride was given together with the beef-meal. 25 g of xylose suppressed basal serum gastrin concentration significantly in six vagotomized patients. Nasal administration of small amounts of vasopressin decreased basal serum gastrin significantly in six vagotomized patients. Nasal administration of small amounts of vasopressin decreased basal serum gastrin significantly in all subjects examined. Further studies indicated, however, that vasopressin was only effective when pharmacological plasma concenten orally and intraduodenally were compared in six patients with pernicious anaemia. Serum gastrin concentration decreased approximately to the same extent in both experiments. It is concluded that the inhibitory effect of glucose on gastrin secretion most likely is mediated hormonally via osmo-receptors located in the small intestine.

Serum gastrin concentrations were measured in patients with duodenal ulcer and controls before, during, and after one-hour intravenous infusion of various doses of adrenaline (0.12 microgram to 6 microgram/min). Gastrin concentrations in the basal state were significantly increased in duodenal ulcer patients compared to controls. The maximal rise in serum gastrin concentrations was obtained at a dose of 4 microgram/min adrenaline in both groups of subjects, and the increase was significantly higher in duodenal ulcer patients than in controls. Adrenaline increased predominantly the gastrin III component (gastrin-17 like) in both duodenal ulcer patients and controls. The threshold level of adrenaline-induced gastrin release was significantly lower in duodenal ulcer patients: intravenous infusion of adrenaline in a dose of 0.12 microgram and 0.25 microgram/min increased serum gastrin concentrations 23 and 43%, respectively, but had no effect in controls. Rises in plasma adrenaline concentrations were similar in both groups of subjects in response to the various doses of adrenaline employed. Only the smallest dose of adrenaline (0.12 microgram/min) resulted in clearly physiological variations in plasma adrenaline concentrations. The results indicate that endogenous adrenaline may stimulate the secretion of gastrin during physiological conditions in patients with duodenal ulcer.

Gastroesophageal sphincter pressure (GESP) and serum gastrin concentration (SGC) were determined in the basal state and after a protein meal in six patients with duodenal ulcer (DU), six patients after parietal cell vagotomy (PCV), six patients after selective gastric vagotomy plus drainage (SGV + D), and six patients after selective gastric vagotomy plus precise antrectomy (SGV + A). No correlation in the resting state between GESP and SGC was observed. After food ingestion, DU patients showed a sustained rise in GESP which lasted up to the end of the experiment. The vagotomized patients, however, showed no rise in sphincter pressure after food intake--rather a tendency to a decrease in pressure occurred. On the contrary, SGC rose significantly after food ingestion in patients with SGV + D or PCV, while in DU patients this rise was less significant. Patients with vagotomy and antrectomy showed no rise in SGC. These results do not suggest that SGC and extrinsic vagal innervation in the resting state play a significant role in the maintenance of the tone of GES. After food ingestion an interaction may occur between intact vagal innervation and rise in SGC in order to obtain an adequate rise in GESP.

Gastroesophageal sphincter pressure and serum gastrin concentration were determined in the fasting state and after the intake of a protein food in 6 normal subjects, 6 patients with gastric ulcer, and in 6 patients with duodenal ulcer. No significant differences in the fasting state were found. After the food intake, gastroesophageal sphincter pressure increased significantly over basal values in normals and in patients with duodenal ulcer, but in patients with gastric ulcer a decrease in pressure was noted. Serum gastrin rose in all subjects studied after the food stimulation, but it was significant only in the gastric and duodenal ulcer group. In two normals and two patients with duodenal ulcer the ingestion of a potato meal of similar weight to that of the protein meal showed no change either in serum gastrin or in sphincter pressure. In one additional normal subject and one duodenal ulcer patient the constant intravenous infusion of Aminosol for 2 h produced no change in serum gastrin or sphincter pressure. These results indicate that the effect of protein food on sphincter pressure is different for gastric or duodenal ulcers, and, furthermore, that this effect is mediated by proteins in the gastrointestinal tract.