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Objective: Immunoglobulin light-chain (AL) amyloidosis is a rare disease that can affect several organs. The aim of this study was to characterize patients with gastrointestinal manifestations of AL amyloidosis, in terms of symptoms, biochemistry, and outcome., Material and Methods: Retrospectively, patients with AL amyloidosis admitted for evaluation of malabsorption in a Department of Gastroenterology between January 2000 and December 2006 were identified., Results: A total of 11 patients (4 F, age 60 years, median (range) 50-69) were included in the study. Gastrointestinal amyloidosis was histologically verified in all patients. All patients had gastrointestinal symptoms, 8 of them prior to establishment of diagnosis. Median (range) delay from initial symptoms to diagnosis was 7 (0-24) months. The most prominent symptom was weight loss (n=10) averaging 7 (0-25) kg, followed by diarrhea (n=5). Steatorrhea (2 mild, 1 moderate, 1 severe) was found in 4 of 7 patients examined. At presentation, 9 patients had hypoalbuminemia and 6 patients had anemia. Three patients were treated with home parenteral nutrition. Five patients received conventional chemotherapy (oral melphalan and prednisone) and 5 patients underwent high-dose melphalan and autologous stem-cell transplantation. Five patients died within the observation period, at a median of 10 (3-36) months after the diagnosis was established. Non-survivors tended to have lower albumin levels on admission and more involvement of other organs compared to survivors., Conclusions: Most patients with gastrointestinal AL amyloidosis experience weight loss and all have signs of malabsorption. Despite treatment the prognosis is grave.

The vitamin B12 (cobalamin) binding proteins, transcobalamin and haptocorrin, were measured in serum and synovial fluid of 12 patients with rheumatoid arthritis (RA) and 11 patients with traumatic synovitis (TS). Levels of both the cobalamin-binding proteins of synovial fluid were markedly elevated in RA compared with TS. In serum, the haptocorrin concentrations were significantly increased in RA vis-à-vis TS. In synovial fluid of RA patients, the transcobalamin and haptocorrin concentrations were positively correlated to the concentrations of macrophages and polymorphonuclear granulocytes, respectively. The demonstration of increased synovial fluid transcobalamin/total protein and haptocorrin/total protein ratios in RA vis-à-vis TS provides further evidence of a local production or liberation of the cobalamin-binding proteins in synovial fluid of patients with RA.

Cobalamin-binding proteins in saliva and in serum were determined in 28 patients with primary Sjögren's syndrome (primary SS), 8 patients with secondary SS and 20 matched healthy controls. The unsaturated transcobalamin II level in serum was significantly increased in patients with secondary SS. The unsaturated cobalamin binding capacity in saliva was increased in patients with primary SS. Considerable interindividual variations were found between patients and in the control group. The local production of cobalamin-binding proteins in SS was sufficient to achieve concentrations in saliva comparable to the control group. The cobalamin-binding capacity in saliva was significantly correlated to the albumin concentration in both primary and secondary SS patients, suggesting a defect in the aqueous phase.

Purified transcobalamin I labeled with radioactive iodine and cobalamin was used for turnover studies in 17 humans. Mean fractional catabolic rate was 0.15 d-1 and mean distribution ratio was 0.57. No difference was observed between the turnover in a control group and in patients with vitiligo or pernicious anemia. The plasma curves of the iodine and the cobalamin label were identical, indicating that cobalamin was liberated from transcobalamin I only when this protein was degraded. It was further concluded that transcobalamin I was of minor importance for the transport of cobalamin from the gut to the tissues. The turnover of transcobalamin I was correlated to the turnover of albumin in 9 patients studied with both proteins.

Of 37 patients with histologically verified hepatocellular carcinoma (HCC) from Bangkok, Thailand, 34 had raised values of plasma cobalamin, and 1 presented with a markedly increased value of plasma transcobalamin I (TC I). One patient with clinical malignancy of the liver, not proven histologically to be HCC, had a raised plasma cobalamin value and a markedly increased value of TC I. From our own studies and from studies in the literature we find circumstantial evidence that TC I occasionally is produced by the malignant liver cells in HCC.

A cobalamin absorption test, the stool spot test (SST), which makes use of radioactive cobalamin and a nonabsorbable isotope, 51Cr-trichloride, has been shown to produce reliable results in patients with pernicious anemia and in healthy controls. The reliability of the SST in patients with bowel disorders and in patients with decreased renal function was investigated by comparing with both whole-body counting and the Schilling test. Fourteen patients with bowel disorders and eight patients with uremia joined the trial. The SST correlated highly significantly with the whole-body counting method. However, the precision of the SST was poor in patients with decreased bowel transit time and inferior to that in the uremic patients. In one of two patients with decreased bowel transit time the two isotopes were shown to have different transit times, thus invalidating the test. In patients with uremia the SST was significantly more reliable than the Schilling test. It is concluded that the SST is reliable also in patients with uremia but may not be reliable in patients with intestinal disorders and decreased bowel transit time. In these patients collection of larger stool samples is recommended.

The use of insolubilized pure human intrinsic factor as binding protein in an isotope dilution assay for quantitation of serum cobalamins is described. The reference interval was 200-600 pmol/l. The coefficients of variation were 0.05 to 0.13 and the equilibrium constant for association to cyanocobalamin was 2 x 10(11) 1/mol. The major advantage of the presented method is that intrinsic factor is kept saturated with cobalamin and is thereby stable until just prior to use.

Transcobalamin I not saturated with cobalamin was purified. After iodine-labelling, a fraction of approximately 0.6 retained its cobalamin-binding capacity. Iodinated protein was used for turnover studies in three healthy subjects. The plasma curves obtained were identical to those of iodinated transcobalamin I saturated with cyanocobalamin. The cobalamin-binding capacity of the iodinated protein was determined on microcolumns containing insolubilized cobalamin. The binding capacity decreased rapidly, only 50% of the initial unsaturated cobalamin-binding capacity remaining after 0.2 to 0.3 days. It is concluded that the turnover of transcobalamin I not saturated with cobalamin does not differ from the turnover of transcobalamin I saturated with cyanocobalamin, and that transcobalamin I saturated with cobalamin in vivo is metabolized at the same rate as is transcobalamin I saturated with cyanocobalamin in vitro.