Low-dose oral iron absorption test in anaemic patients with and without iron deficiency determined by bone marrow iron content.

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 (micromol/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 micromol/l always indicated absent bone marrow iron stores.

Low-dose oral iron absorption test: establishment of a reference interval.

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.

Trisomy 10 survival: a literature review and presentation of seven new cases.

Trisomy 10 as the only chromosome aberration is a rare phenomenon in malignant and premalignant hemopoietic disorders. We describe 7 new cases and have found another 12 in the literature. It appears that, whereas adult patients have myeloid disorders (acute myeloid leukemia, myeloproliferative, or myelodysplastic syndromes), in children the diagnosis is lymphocytic leukemia or lymphoma. The median survival was 122 months in the total material. Age above 60 years proved to be a significant adverse factor (median survival only 5 months; p = 0.003). None of the other clinical, cytogenetic, or hematological variables were of demonstrable prognostic importance. In contrast with the larger trisomy 10 clones, those of limited size were associated with nonleukemic diagnoses, normal or slightly elevated leukocyte counts, and few or no circulating blasts. This may suggest that expansion of the trisomy 10 clone is associated with clinical and hematological progression.

Lack of correlation between methotrexate concentrations in serum, saliva and sweat after 24 h methotrexate infusions.

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.

Association of pernicious anemia and intrinsic factor antibody with HLA-D.

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.

The role of serum gastrin in the secretion of calcitonin: studies in patients with pernicious anaemia and in healthy subjects.

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.

Abnormal duodenal loop demonstrated by X-ray. Relation to gastric emptying time.

Gastric emptying time of a solid meal was estimated on X-ray in 7 patients with a normal duodenal loop, 7 patients with a proximal duodenal anomaly, and 12 patients with a distal duodenal anomaly. A determination coefficient between gastric emptying time and duration of serum gastrin increase was calculated. The food-stimulated serum gastrin secretory pattern was studied in 9 patients with a normal duodenal loop, 6 with a proximal duodenal anomaly, and 13 with a distal duodenal anomaly. The various groups presented significantly different gastric emptying times; thus patients with normal duodenal loop had a mean gastric emptying time of 6 h, patients with proximal duodenal anomalies ahd a mean gastric emptying time of 4.5 h, and patients with distal duodenal anomalies had a mean gastric emptying time of 9 h. Gastric emptying time and duration of increased serum gastrin secretion was positively correlated (R2 = 0.89). The food-stimulated serum gastric secretory pattern was equal in patients with proximal duodenal anomalies and those with distal duodenal anomalies and furthermore, reached significantly higher serum gastrin concentrations than in patients with a normal duodenal loop.

The effect of renal transplantation on basal serum gastrin concentration.

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.

Serum gastrin and serum calcitonin in patients with chronic renal failure.

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.

The effect of vagotomy on human gastroesophageal sphincter pressure in the resting state and following increases in intra-abdominal 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.

Inhibition of gastrin secretion by hypertonic solutions in patients with pernicious anaemia and duodenal ulcer.

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.

The influence of cimetidine on basal gastro-oesophageal sphincter pressure, intargastric pH, and serum gastrin concentration in normal 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.

Increased sensitivity of gastrin release to adrenaline in duodenal ulcer.

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.