Testing for haemochromatosis in the diabetic clinic.

Random serum transferrin saturation (TS) was measured in 1194 patients attending a diabetic clinic. Twenty-one patients had TS > 55% and in three of these patients repeat random TS was < 55%. Seventeen patients were recalled for fasting serum TS and ferritin measurement. Ten patients had fasting TS > 55%. The diagnosis of haemochromatosis was confirmed by liver biopsy in a total of six patients, three of whom were previously unsuspected. Haemochromatosis was the possible diagnosis in a further four patients. Family studies using HLA typing confirmed haemochromatosis in four family members, three of whom were asymptomatic. We conclude that measurement of TS is a simple and effective method of finding cases of haemochromatosis in the diabetic clinic.

Zinc metabolism in celiac disease.

The turnover of a radiolabeled (65Zn) pool of endogenous zinc was monitored by using a whole-body counter in eight patients with celiac disease (CD) and analyzed by using a two-compartment model. The biological half-life of the first compartment (1-3 wk postadministration) was similar in healthy volunteers (122 +/- 34 d, means +/- SD) and untreated patients (97 +/- 21 d). The second compartment in the patients (3-12 wk postadministration) was shorter (159 +/- 22.5 d. p less than 0.001) than were reference values (218 +/- 27 d) but increased (291 +/- 71 d) after the patients started gluten-free diets. The percentage absorption of 65Zn (9.25 kBq) from a test meal containing 31 mumol (2 mg) zinc was similar in untreated patients (30.0 +/- 13%) and healthy volunteers (32.5 +/- 12.4%). These data show that in mild untreated CD increased turnover and loss of endogenous zinc occurs whereas the absorption of zinc from a customary zinc intake may be normal. The pathophysiological basis of this loss was not investigated.

Inorganic zinc and the intestinal absorption of ferrous iron.

The effect of inorganic zinc on the absorption of inorganic iron (Fe+2) from a solution was assessed in two studies on healthy male volunteers. In the first study coadministration of 344 mumol of zinc had no effect (p less than 0.5) on the absorption of 842 mumol of radiolabeled Fe, assessed by the area under plasma Fe increment time curve during the 3 (AUC3) and 6 (AUC6) h postadministration (Fe alone AUC3 = 176.4 +/- 39.3; AUC6 = 387 +/- 101; Fe + Zn AUC3 = 180 +/- 33.1; AUC6 = 396 +/- 73.1 mumol.h-1.L-1), total plasma content of 59Fe, and whole-body retention of 59Fe. In the second study only the plasma appearance of Fe was monitored. After administration of 421 mumol of Fe alone, the AUC3 and AUC6 were 167 +/- 21.2 and 429.4 +/- 57 mumol.h-1.L-1, respectively; these were reduced to 56.4 +/- 17 and 119 +/- 34 (p less than 0.002) by 421 mumol Zn and further reduced by 1048 mumol Zn to 33 +/- 15 and 43.4 +/- 23.8 mumol.h-1.L-1 (p less than 0.001), respectively. It is concluded that Zn can impair the intestinal absorption of Fe.

Zinc absorption in celiac disease and dermatitis herpetiformis: a test of small intestinal function.

The increments in plasma zinc concentrations after an oral dose of elemental zinc (50 mg) as the sulphate were used to assess the intestinal absorption of the metal in 11 patients with dermatitis herpetiformis (DH) before starting a gluten-free diet, 12 patients with newly diagnosed celiac disease (CD), 10 patients known to have CD, and 15 healthy volunteers. The areas under the plasma zinc increment curve plotted against time were determined for 3 (AUC3) and 6 (AUC6) h. The AUC3 in healthy volunteers was 401 +/- 48 mumol 1(-1) 3 h (mean +/- SD); it was reduced in newly diagnosed CD 187 +/- 76 mumol 1(-1) 3 h (p less than 0.001), and in dermatitis herpetiformis 206 +/- 87 mumol 1(-1) 3 h (p less than 0.01); but it was normal in the known CD 396 +/- 204 mumol 1(-1) 3 h, the wide variation reflecting the variable compliance with a previously instituted gluten-free diet. The AUC6 was similarly affected, healthy volunteers 700 +/- 111 mumol 1(-1) 6 h, new CD 380 +/- 169 mumol 1(-1) 6 h (p less than 0.01); dermatitis herpetiformis 471 +/- 107 mumol 1(-1) 6 h (p less than 0.01); known CD 725 +/- 380 mumol 1(-1) 6 h. The AUC3 was more consistently abnormal than conventional tests of small intestinal function. In a prospective study the AUC3 and AUC6 improved and reflected compliance with a gluten-free diet.

Preparation of lymphoid cells from small specimens of human gastrointestinal mucosa.

Several methods for the preparation of cell suspensions from human gastrointestinal mucosa were investigated. Satisfactory suspensions were obtained by incubating tissue fragments in a solution of collagenase and hyaluronidase overnight at 4 degrees C followed by 30 minutes at 37 degrees C. The resulting suspension contained large numbers of intact lymphoid cells; in addition, variable amounts of epithelial cells and cell debris were present. A high proportion of the lymphoid cells were shown by immunofluorescence to contain immunoglobulin (mainly IgA). Viability of these cells was demonstrated by dye exclusion, their ability to survive in short-term culture, and their ability to incorporate radio-labelled amino acid into immunoglobulin in vitro.

The origin, kinetics, and characteristics of the Kupffer cells in the normal steady state.

Enzymatic digestion with pronase and DNAase was used to isolate Kupffer cells from mouse liver. The characteristics of these cells were found to be similar to those of peritoneal macrophages, except that in the initial suspension the percentage of Kupffer cells with Fc receptors was low, C receptors were absent and the ingestion of opsenized bacteria was very poor, because of the effect of pronase on the cell membrane. After 24 h incubation in vitro all these characteristics return. The in vitro and 1 h-pulse [(3)H]thymidine labeling of the Kupffer cells is low (0.8 and 1 percent, respectively) indicating that in essence these cells do not divide. It was also shown that the small percentage of in vitro labeled Kupffer cells was recently derived from the circulation. After an intravenous injection of zymosan the in vitro labeling index of the Kupffer cells increased 16-fold, but it was proven that these dividing cells were immature mononuclear phagocytes very recently recruited from the bone marrow. The labeling of Kupffer cells aider one or four injections of [(3)H]thymidine reached a peak of 10.4 percent at 48 h or 24.1 percent at 60 h, respectively, indicating that these cells are derived from labeled monocytes. Further evidence for this conclusion was obtained by the absence of an increase of labeled Kupffer cells during treatment with hydrocortisone, which causes a monocytopenia during which no circulating monocytes are available to migrate to the tissues. Labeling studies in animals X-irradiated with hind-limb shielding gave a Kupffer cell labeling index of 5-10 percent of the normal values, which confirms their bone marrow origin. A quantitative study on the production of labeled monocytes in the bone marrow and their transit through the circulation showed that in the normal steady state at least 56.4 percent of the monocytes leaving the circulation become Kupffer cells. Considering the Kupffer cells as kinetically homogeneous this gives a mean turnover time of the total population of Kupffer cells of 21 days.