A fast method of measuring vitamin B12 absorption using a whole-body counter.

The conventional method of measuring vitamin B12 absorption using a whole-body counter normally involves a delay of fourteen days before complete faecal excretion of unabsorbed B12 tracer can be assumed. A modified technique has been used which reduces the delay to four days. A non-absorbable tracer, 51Cr-chromic chloride, was administered firstly with 58Co-labelled vitamin B12 and then three hours later with 57Co-labelled vitamin B12 and then three hours later with 57Co-labelled vitamin B12 plus 50 mg hog intrinsic factor which normalises B12 malabsorption in patients with pernicious anaemia. Three days later, the residual whole-body activities of the three radionuclides were measured. The retention of 51Cr indicated the efficiency of faecal excretion of unabsorbed B12 tracer and could be used to quantify vitamin B12 absorption before complete excretion of unabsorbed B12 tracer. Vitamin B12 absorption values were measured at four days by this technique and compared with the corresponding values at fourteen days in 38 tests on 33 subjects, 16 of whom had pernicious anaemia. Excellent correlations between the results obtained at four and 14 days were obtained for both B12 tracers.

Clinical evaluation of simultaneously administered 58Co labelled vitamin B12 and 57Co labelled vitamin B12 bound to intrinsic factor in patients with pernicious anaemia.

The clinical and laboratory data from 75 patients with altered vitamin B 12 absorption were reviewed. In 36 cases the diagnosis of pernicious anaemia had been established. Of these, 14 patients showed malabsorption of radiolabelled vitamin B 12, but the absorption of vitamin B 12 bound to the intrinsic factor (IF) was normal (Group A). The other 22 patients with pernicious anaemia showed altered free and IF-bound vitamin B 12 absorption (Group B). Laboratory and clinical data and the absorption tests (xylose and fat excretion) were more abnormal in group B than in group A. Finally, 39 patients (Group C) with general malabsorption showed alternation of the absorption of free and IF-bound vitamin B 12 (Group C). The clinical nd biological data were different in these patients from that found in groups A and B. It is possible that in patients with pernicious anaemia who are untreated an alteration of the intestinal mucosa may produce a malabsorption of vitamin B 12 even in the presence of intrinsic factor.

Determination of 58Co-vitamin B12 absorption in pernicious anemia by use of whole-body counting: Reproducibility and control of gut transit time.

In 15 patients with pernicious anemia, the fractional retention of 58Co-cyanocobalamin (FRB12) without administration of intrinsic factor (IF) averaged 4.9% (range 0-12.7). With administration of IF, FRB12 averaged 32.7% (range 26.6--42.3) in the patients and 65.6% (range 38.8--84.6) in 16 control subjects. The gut transit time for vitamin B12 was evaluated from the excretion of radiopaque pellets given concomitantly with the 58Co-vitamin B12. The retention of the pellets was positively correlated to that of the non-absorbed 58Co-B12. Control of the gut transit time is recommended at each examination of FRB12 in order to avoid falsely high values due to the retention of non-absorbed 58Co-B12. We found a good reproducibility of FRB12 when determined in fasting subjects, and it is therefore unnecessary to give the patients a B12-free meal prior to the examination. As the FRB12 in all probability is only a little lower than the fractional absorption, the present method is applicalble for the determination of B12 absorption.

An augmented Schilling test in the diagnosis of pernicious anaemia.

A patient with otherwise typical addisonian pernicious anaemia and serum anti-intrinsic-factor antibody failed to respond to oral intrinsic factor on repeated testing during three years of therapy with parenteral vitamin B 12. There was no evidence of generalised malaborption. To test the hypothesis that binding of intrinsic factor to gut secretory antibody was responsible, an "augmented" Schilling test was devised using eight times the usual dose of intrinsic factor. This increased dose of intrinsic factor resulted in normal absorption of the test dose of vitamin B 12 confirming the diagnosis. It is suggested that the augmented Schilling test may be useful in the diagnosis of the occasional patient with features of pernicious anaemia who fails to respond to conventional doses of intrinsic factor in the Schilling test.

[Biologic activity of various intrinsic factor preparations in Schilling's test]. / Biologische Aktivität verschiedener Intriniscfaktor-Präparationen im Schillingtest

In 16 patients with pernicious anaemia investigations concerning the biological activity of 7 different Intrinsic-factor praeparations by means of the urinary excretion test were performed. Oral longterm-pretreatment with IF and biologically inactive IF-praeparations may cause false pathologic results.

[Blocking and binding antibodies to intrinsic factor and their behaviour during oral therapy with intrinsic factor-vitamin B 12 complex (author's transl)]. / Uber blockierende und bindende Antikörper gegen Intrinsic-Factor und deren Verhalten unter peroraler Intrinsic-Factor B 12-Therapie

13 patients with pernicious anaemia and 2 patients who had been subjected to total gastrectomy were treated orally with a hog instrinsic factor preparation (IF) for 1 to 4.5 years. During this therapy 11 of the patients with pernicious anaemia and both gastrectomized patients developed blocking and binding antibodies to IF. Antibodies already present before the commencement of therapy showed an increase in titre. All patients remained in complete haematological remission. The conclusion is drawn that circulating antibodies to IF do not play any significant role in the absorption of the hog IF-B 12 complex.

Spurious Schilling test results obtained with intrinsic factor enclosed in capsules.

Three urinary excretion tests of vitamin B12 absorption were done in 12 patients with classic pernicious anemia. The 24-hour urinary excretion of radioactivity was 2.1% +/- 0.7% (mean +/- SEM) of the ingested dose of cyanocobalamin-57 Co. When cyanocobalamin-57 Co was mixed with hog intrinsic factor in water, excretion increased to 15.6% +/- 1.6%. When cyanocobalamin-57 Co and intrinsic factor were given in two separate capsules, which is now a frequent practice, excretion was 9.5% +/- 2.2%. In 6 patients, use of the results obtained with capsules could have led to an incorrect diagnosis. When cyanocobalamin-57 Co and intrinsic factor are given in separate capsules, binding of radioactive vitamin to intrinsic factor may be incomplete due to inadequate mixing in the stomach or to binding of intrinsic factor to blocking antibody in the gastric juice. The classic technique in which intrinsic factor and cyanocobalamin-57 Co are mixed in water before administration should be used.

Effect of vitamin B12 and folic acid deficiency on small intestinal absorption.

Three patients are described, and they provide further evidence that deficiency of folic acid and vitamin B(12) may sometimes affect small intestinal function. Malabsorption of both xylose and vitamin B(12) returned to normal in one patient after treatment of a megaloblastic anaemia due to dietary deficiency of folic acid. Impaired absorption of vitamin B(12) was corrected by vitamin B(12) therapy in the other two patients. The initial cause of the vitamin B(12) deficiency in one patient was not apparent, but she was taking Gynovlar 21, which may have been an aetiological factor. In the third patient the small intestinal defect was secondary to pernicious anaemia, and in a group of 98 other patients with pernicious anaemia intrinsic factor did not improve vitamin B(12) absorption in six, and only partially corrected absorption in 30. The significance of these observations is discussed.