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Biomedical subjects

L S Valberg

Publications and source records attributed to L S Valberg.

At least 37 records · Page 2Linked to original sources
PubMed1985

Does the oral zinc tolerance test measure zinc absorption?

Increases in plasma zinc concentration were compared with radiozinc absorption after oral test doses. Ten healthy, fasting subjects were each given 385 mumol zinc chloride (25 mg Zn) labelled with 0.5 muCi 65ZnCl2 and a non-absorbed marker, 51CrCl3, dissolved in 100 ml of water; another 10 persons were given 354 mumol zinc chloride and 125 g of minced turkey containing 31 mumol zinc also labelled with 65Zn and 51Cr. Measurements were made of plasma zinc concentration at hourly intervals for 5 hours, radiozinc absorption by stool counting of unabsorbed radioactivity 12-36 hours later, and radiozinc retention by whole body counting at 7 days. The mean percentage of radiozinc absorbed and retained in the body from the two test meals was found to be identical (42%). In contrast the increased area under the plasma zinc curve up to 5 hours after the turkey meal, 28 +/- 9 mumol/L (mean +/- SD) was significantly less than that for zinc chloride alone, 47 +/- 15 mumol/L, p less than 0.005. Despite this difference, a good correlation was found between the area under the plasma zinc curve and 65Zn absorption in individual subjects after each meal. The discrepancy between the results of zinc absorption derived from the plasma zinc curve and 65Zn absorption for the liquid and solid test meals was most likely explained by binding of zinc to food and delayed gastric emptying of the solid meal. With a test meal of turkey meat at least this dampened the plasma appearance of zinc but did not affect its overall absorption.

Administration, Oral↗
PubMed1985

Dual-isotope method for determination of human zinc absorption: the use of a test meal of turkey meat.

The percentage of 65Zn taken up (absorbed) from extrinsically labeled turkey meat was calculated from the amounts of 65Zn and a nonabsorbed 51Cr marker present in the body or in a single stool specimen after 1-2 d. 51CrCl3 proved to be a suitable marker for unabsorbed 65Zn and so the early determination of 65Zn absorption was possible. With stool counting, 65Zn absorption data from first stool samples after 1-2 d were accurate as judged by correlation with the amount of 65Zn in the body 7-10 d later (retention); results from subsequent stools gave lower absorption values due to the early excretion of some absorbed 65Zn. The dual-isotope method gave reproducible results when four successive tests of zinc absorption were carried out in a group of six subjects. The average (mean +/- SD) 65Zn absorption from turkey meals containing 31 mumol (2 mg) and 46 mumol (3 mg) of zinc was 39 +/- 8% and 29 +/- 6%, respectively, measured by stool counting; 65Zn absorption and retention correlated well in both studies. A series of different beverages was given in place of water with the turkey meal. Orange juice significantly reduced 65Zn absorption and milk also showed this tendency, but tea, whiskey, wine or beer had no significant effect on the absorption of 65Zn from the turkey meal. In groups of subjects the mean ratio of 65Zn absorption from extrinsically labeled turkey meat on two occasions (1.06) was not significantly different from that of the absorption of extrinsic to intrinsic 65Zn labels (1.16). The dual-isotope technique with either stool or body counting is suitable for the rapid determination of 65Zn absorption from extrinsically labeled turkey within 2 d.

Adult↗
PubMed1985

Diagnosis and management of hereditary hemochromatosis.

Hereditary hemochromatosis is inherited in an autosomal recessive manner with partial biochemical expression in heterozygotes. A high percentage of saturation of serum transferrin is the hallmark of the disorder, and serum ferritin concentration gives an approximate estimation of the size of iron stores. Hepatic computed tomography, magnetic susceptometry, and nuclear magnetic resonance provide new noninvasive ways of determining hepatic iron content, but chemical estimation of iron in a percutaneous liver biopsy specimen remains the mainstay of diagnosis. Once a proband is identified, transferrin saturation and serum ferritin are used to screen family members and HLA typing is employed selectively to detect homozygotes at risk. Removal of excess body iron and maintenance of normal iron stores by repeated venesection arrests tissue injury and prolongs survival.

Adolescent↗
PubMed1984

Diagnostic efficacy of screening tests for hereditary hemochromatosis.

Hereditary hemochromatosis is transmitted as an autosomal recessive trait. Analyses of pedigrees suggest that the frequency of disease (proportion of homozygous individuals) in the general population is approximately 0.3% and that approximately 11% of the population are heterozygous. The genotype of 194 persons in 38 pedigrees was determined by HLA-A and HLA-B haplotyping. Likelihood analysis was then used to appraise the transferrin saturation test when used alone and in combination with the serum ferritin test to detect homozygosity and heterozygosity in these pedigrees. A single cut-off point of 55% for transferrin saturation and a cut-off point at the 90th percentile for the serum ferritin level were adequate for the detection of hemochromatosis if homozygosity was considered to be present when the results of one or both tests were positive. To further assess the value of the transferrin saturation test the percentages were stratified into five intervals. A percentage transferrin saturation of 75 or greater and a serum ferritin level above the 90th percentile ruled in homozygosity, whereas a percentage transferrin saturation of less than 55 and a serum ferritin level at or below the 90th percentile ruled it out with confidence. The probability of heterozygosity rose to 90% when the percentage transferrin saturation was between 35 and 55 and the serum ferritin level was at or below the 90th percentile. The use of five cut-off points allowed the probability of homozygosity and heterozygosity in a pedigree to be estimated for all values of transferrin saturation. Although these screening tests are not recommended for use in the general population, they may be worth while in selected groups of patients.

Adult↗
PubMed1984

Effects of iron, tin, and copper on zinc absorption in humans.

Zinc absorption as measured by body retention of [65Zn]zinc chloride or a turkey test meal extrinsically labeled with 65Zn was determined in human subjects by whole body counting after 7 days. Average 65Zn absorption from zinc chloride in persons with a high iron-absorbing capacity was similar to persons with a low capacity to absorb iron. Inorganic iron, 920 mumol (51 mg), or HB iron, 480 mumol (26 mg), inhibited 65Zn absorption from 92 mumol (6 mg) of zinc chloride. When 610 mumol of iron (34 mg) was added to a turkey test meal containing 61 mumol of zinc (4 mg), 65Zn absorption was not inhibited. Tin, 306 mumol (36 mg), given with zinc chloride or turkey test meals (61 mumol, 4 mg, of Zn) significantly reduced 65Zn absorption. Copper, 79 mumol (5 mg), had no significant effect on the 65Zn absorption from 7.9 mumol (0.5 mg) of zinc chloride. In summary, the capacity to absorb iron did not influence 65Zn absorption, but both inorganic iron and heme-iron inhibited 65Zn absorption from zinc chloride. Inorganic iron had no effect, however, on 65Zn absorption from the turkey test meal. Tin in a large dose also inhibited 65Zn absorption from both zinc chloride and the turkey test meal.

Adolescent↗
PubMed1984

Intestinal absorption of zinc: competitive interactions with iron, cobalt, and copper in mice with sex-linked anemia (sla).

Duodenal uptake and transfer of 59Fe and 65Zn and absorptive interactions between iron, zinc, cobalt, and copper were studied in sla mice and in genetically normal Swiss albino control mice. Genetically normal mice with a high iron-absorbing capacity, induced by being fed an iron-deficient diet, showed greater uptake and transfer of 65Zn in duodenum but not ileum, compared with mice with a low iron-absorbing capacity. 59Fe transfer from the duodenal mucosa to the body was lower in sla mice compared with controls and bleeding stimulated the capacity to absorb 59Fe less in sla mice relative to normal controls. In contrast, 65Zn transfer in sla was no different from controls and was not stimulated by bleeding in sla or in control mice. Iron or cobalt in a 10-fold molar excess predominantly lowered 65Zn transfer in both sla and controls, but in a study of the effect of zinc on iron transport only the uptake of 59Fe in sla mice was lowered by excess zinc in the perfusate. The effect of added copper on 65Zn transport was paradoxical; in both sla and control mice copper markedly increased 65Zn uptake relative to perfusates containing 65Zn alone, but transfer in normal mice was lowered whereas it was increased in sla animals. The interaction between zinc and iron does not appear to take place at the site of the genetic defect in sla mice. The lesion in iron transport in these mice is likely due to defective binding and transfer sites in the basolateral membrane; these sites are apparently exclusive for iron and not shared by zinc.

Anemia↗
PubMed1983

Zinc absorption, intraluminal zinc and intestinal metallothionein levels in zinc-deficient and zinc-replete rodents.

Zinc absorption, endogenous luminal zinc and intestinal metallothionein were examined in rats and mice fed zinc-deficient and zinc-replete diets for 5-7 days. Small intestinal luminal washings from undosed rodents fed the replete diet contained 18- to 20-fold more zinc than those from zinc-deficient animals. Isotope dilution by this endogenous zinc could account for apparent differences between the groups in absorption of 65Zn from oral doses of 0.1-0.2 mumol 65Zn. With larger (1-2 mumol) oral doses of 65Zn in mice, no difference between the dietary groups was found, although zinc-deficient rats still absorbed more zinc than zinc-replete controls. In mice, zinc absorption from perfused duodenum, jejunum and ileum also was not increased by zinc deficiency. With oral doses, food generally lowered zinc absorption where endogenous or exogenous zinc was present in the gastrointestinal tract; food in perfusates lowered uptake more than transfer. Polarographically determined metallothionein was highest in duodenum of mice. It was lowered by feeding the deficient diet for 5 days without an increase in zinc absorption. It was concluded that zinc absorption is homeostatically increased by zinc deficiency in rats but not in mice and that intestinal metallothionein levels do not affect zinc absorption in mice.

Administration, Oral↗
PubMed1983

Genetic and phenotypic expression of hemochromatosis in Canadians.

Twenty-three probands with idiopathic hemochromatosis were assigned the status of homozygotes: 132 of their relatives were classified as homozygotes, heterozygotes or normal individuals using the HLA haplotypes of the probands as markers of the hemochromatosis allele. Only half of the probands sought help because of symptoms or signs of iron overload. Clinical manifestations of iron loading were present, however, 95% of the probands and 67% of the discovered homozygotes. The commonest symptom was joint pain and stiffness. None of the heterozygotes had any clinical symptoms of excess body iron. High transferrin saturation and serum ferritin levels were prevalent in homozygotes: only 1 of 38 homozygotes had values for both of these measurements that were within normal limits. The level of transferrin saturation was increased in 6% of heterozygotes but only 1% had serum ferritin concns greater than 350 ng ml-1. The mean radioiron absorption levels of 27 homozygotes and 28 heterozygotes were similar to those in 44 controls. Radioiron absorption in relation to the respective serum ferritin concn was above the 95% confidence interval of controls in 65% of the homozygotes and 7% of the heterozygotes. The inverse relation between radioiron absorption and the respective serum ferritin concn observed in controls was absent in homozygotes but remained strong in the heterozygotes. Absence of the inverse relation indicates a deregulation of the iron absorptive mechanism in homozygotes which results in the size of body iron stores having no effect on the level of iron absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1983

Diagnostic efficacy of hepatic computed tomography in the detection of body iron overload.

To determine whether or not hepatic computed tomography density is an alternative to liver biopsy for the diagnosis of body iron overload, hepatic computed tomography density was determined in healthy controls, patients with idiopathic hemochromatosis, and patients with liver disease. Hepatic computed tomography density was obtained from a single computed tomography slice taken through the liver on a General Electric CT/T 8800 scanner. In 69 controls, hepatic computed tomography density ranged from 11 to 36 units (mean = 30). Given an upper limit of normal of 36 computed tomography units, 4 of 6 untreated patients with idiopathic hemochromatosis had elevated hepatic computed tomography density compared with 0 of 8 patients after venesection (X2 = 7.5, p = 0.01). Hepatic computed tomography density correlated directly with serum ferritin (r = 0.72, p = 0.01). In 58 consecutive patients with clinical or biochemical evidence, or both, of liver disease who underwent liver biopsy for diagnostic purposes, 0 of 52 patients with normal hepatic iron had an elevated hepatic computed tomography density as compared with 4 of 6 patients with excess iron (X2 = 35, p less than 0.001). An elevated hepatic computed tomography density associated with an elevated serum ferritin indicates iron overload; however, a normal hepatic computed tomography density does not exclude iron overload. When computerized tomography is applied to patients with an unexplained elevation of the serum ferritin, it provides a noninvasive alternative to liver biopsy for the detection of excess hepatocellular iron.

Adult↗
PubMed1982

The relationship between iron and lead absorption in humans.

Approximately 60% of an oral dose of 100 micrograms of 203Pb was retained in 85 fasting subjects with no difference noted between males and females. Body retention was proportional to dose up to 400 micrograms of lead. It was not related to the capacity to absorb iron or to the size of body iron stores, nor was it affected by the simultaneous ingestion of a 10-fold molar excess of iron. The effect of several dietary factors was also determined. Lead retention was lowered by eating food, slightly increased by ingestion of fat, but was unaffected by the administration of lactose or a 10-fold molar excess of zinc, cobalt, or calcium. One chelating agent, ascorbic acid, slightly lowered lead retention, whereas another agent ethylenediaminetetraacetic acid, produced a marked reduction. Several of these results suggest that human gastrointestinal lead absorption behaves differently to that of rodents. In particular, human lead retention was found to be unrelated to iron absorption or to body iron stores.

Absorption↗
PubMed1982

Technique for determination of human zinc absorption from measurement of radioactivity in a fecal sample or the body.

The intestinal absorption of an oral dose of zinc chloride was determined from the ratio of 65Zn and a nonabsorbed radioactive marker, 51Cr, present in a single stool specimen or the body 24-72 h later. Chromic chloride had no effect on [65Zn]zinc chloride absorption and 51Cr and 65Zn had similar intestinal transit times. In 17 healthy control subjects given 92 mumol ZnCl2 labeled with 0.5 microCi 65Zn, 52 +/- 14% (SD) of the dose was taken up from the lumen. Intestinal absorption of 65Zn at 24 h correlated closely with 65Zn body retention of zinc measured by whole-body counting 7 days later, r = 0.995. Neither zinc absorption nor zinc retention correlated with blood leukocyte zinc levels. An average of 55% of 65Zn was retained in the body from doses of 18-90 mumol ZnCl2 but a progressively smaller proportion of zinc was absorbed from doses of 180-900 mumol. The average absorption and body retention of 65Zn were significantly reduced in 7 patients with mucosal disease of the proximal intestine but they were not affected by resection of the lower jejunum, ileum, and colon. Thus the absorption of ZnCl2 from a 92-mumol dose predominantly takes place by a rate-limited mechanism in the duodenum and upper jejunum.

Adolescent↗
PubMed1980

Plasma ferritin concentrations: their clinical significance and relevance to patient care.

In healthy persons the plasma ferritin concentration is a sensitive index of the size of body iron stores. It has been successfully applied to large-scale surveys of the iron status of populations. It has also proved useful in the assessment of clinical disorders of iron metabolism. A low plasma ferritin level has a high predictive value for the diagnosis of uncomplicated iron deficiency anemia. It is of less value, however, in anemia associated with infection, chronic inflammatory disorders, liver disease and malignant hematologic diseases, for which a low level indicates iron deficiency and a high level excludes it, but intermediate levels are not diagnostic. Measuring the plasma ferritin concentration is also useful for the detection of excess body iron, particularly in idiopathic hemochromatosis, but again it lacks specificity in the presence of active hepatocellular disease. If iron overload is suspected in these circumstances determination of the iron content of a percutaneous liver biopsy specimen is required. In families with idiopathic hemochromatosis the combined determination of the plasma ferritin concentration and the transferrin saturation is a sufficient screen to identify affected relatives; however, estimation of the hepatic iron concentration is required to establish the diagnosis.

Absorption↗
PubMed1980

Comparative effects of iron deficiency induced by bleeding and a low-iron diet on the intestinal absorptive interactions of iron, cobalt, manganese, zinc, lead and cadmium.

Dietary iron deficiency enhances the absorption of iron, cobalt, manganese, zinc, cadmium and lead, whereas, iron deficiency due to bleeding increases the absorption of iron, cobalt and perhaps manganese. To determine whether the response to bleeding is qualitatively different from that induced by dietary iron deficiency, metal absorption was studied in mice fed either a high-iron diet (120 ppm Fe) and bled (0.5 ml) or fed a low-iron diet (< 3 ppm Fe). Iron absorption from an intragastric dose was increased by the loss of 0.5 ml of blood; smaller losses of blood had no effect. Also, iron absorption was increased more by dietary iron deficiency than by bleeding. In perfusion experiments, bleeding increased the duodenal absorption of only iron and cobalt, whereas dietary iron deficiency enhanced the absorption of all the metals except cadmium. The patterns of absorptive inhibition of the metals by each other were similar in bled mice and in mice with dietary iron deficiency except that interactions among metals with lower affinities for the iron absorption mechanism--manganese, zinc, cadmium and lead--were more obvious in mice fed the low-iron diet. We concluded that bleeding only partially activates the iron absorptive mechanism and that the lack of a bleeding effect on the absorption of manganese, zinc, cadmium and lead results from the weaker interactions of these metals, with a partly-activated absorption process.

Animals↗
PubMed1980

Passage of iron out of the intestinal mucosa of the rat.

To determine the effect of removal of the "lumen-to-mucosa" concentration gradient on the passage of iron (Fe) out of the intestine, duodenal loops of rats with loaded (FeL) or deficient (FeD) iron stores were perfused for 30 min with 5.0 mM solutions containing 59Fe. The test solutions were then removed and in vivo perfusion of the washed mucosa was continued for up to 60 min with saline or unlabelled FE-saline. Despite the greater initial uptake of Fe by FeD than FeL, continued perfusion with saline was associated with the appearance of similar quantities of 59Fe in the perfusate; in contrast, when perfusion was continued with Fe-saline, the loss of 59Fe into the perfusate was increased and was twice as great in FeD as in FeL. Iron transfer to the carcass was higher in FeD than in FeL, but continued perfusion with saline was associated with the appearance of increased amounts of 59Fe in the carcass of FeL but not FeD; the amount of 59Fe appearing in the carcass was greatly increased in both FeD and FeL by continued perfusion with Fe-saline. Thus, the amount of 59Fe available for entry into the intestinal lumen and carcass after removal of the lumen-to-mucosa concentration gradient is influenced by the size of the body iron stores and by the presence of iron in the fluid remaining in the lumen. Therefore, the amount of iron in the fluid remaining in the intestinal lumen after the administration of the Fe test dose must be carefully defined when estimating the kinetics of the intestinal absorption of iron.

Animals↗