Biomedical subjects
C A Finch
Publications and source records attributed to C A Finch.
Effect of induced fever on serum iron and ferritin concentrations in man.
Previous reports have shown that endotoxin decreases serum iron in experimental animals. In this study fever was produced in nine female and nine male normal subjects in order to define the temporal and quantitative changes in serum iron and ferritin concentrations. Six volunteers were randomly given bacterial endotoxin (5 ng/kg) or saline intravenously and received the alternative compound a week later. Serial blood samples were drawn at 4-hr intervals for a 24-hr period, beginning when the compound was administered, for the determination of serum iron and ferritin concentrations. The same study was performed with intramuscular etiocholanolone (0.3 mg/kg) or the vehicle, propylene glycol, as a control, but the first blood sample was obtained 9 hr after the compound was given. In addition, blood samples were obtained at 12-hr intervals in six volunteers for 11 days after an intramuscular injection of etiocholanolone. The results showed a significant increase (p less than 0.005 for etiocholanolone, P less than 0.01 for endotoxin) in serum ferritin and a significant decrease (p less than 0.005 for etiocholanolone, p less than 0.001 for endotoxin) in serum iron for both pyrogenic compounds compared with the control compounds. However, the amount of fever and the changes in the iron parameters were greater with etiocholanolone. One episode of induced fever with etiocholanolone effected changes in serum ferritin and iron concentrations that lasted 10 days. Thus this study demonstrated that a single episode of fever in man produced rapid and prolonged changes in serum iron and ferritin concentrations.
14C cyanate as a tag for red cell survival in normal and uremic man.
14C cyanate was employed as a red cell tag. Incubated cells were washed before reinjection to remove free cyanate. Neither early or late elution was observed, and the mean red cell life span of 10 normal subjects was 115+/-12 days. In nine uremic subjects the mean life span corrected for blood loss was 73 days with a mean red cell turnover of about 0.79 times basal. Survival curves in normal subjects were similar to those observed with DF32P and in uremic subjects to those with 51Cr corrected for elution. These observatios show the reliability of 14C cyanate as a nonelutable red cell tag.
Role of transferrin in determining internal iron distribution.
The behavior in vivo of transferrin in loading and unloading iron from its two sites was examined in rats. Radioiron entering the plasma from the gastrointestinal tract in iron-deficient, normal and iron-loaded rats did not differ in its subsequent tissue distribution between erythroid marrow and liver of normal recipients from a second isotope added to the same plasma in vitro. Loading studies in vitro were then carried out employing a reticulocyte incubation model designed to place one isotope predominantly on one site of transferrin, more available to the erythron, and the second isotope on the other site, more available to the liver. In 15 groups of animals in which 3 different iron salts were employed to load transferrin with iron, the mean isotope ratio in the erythron was 1.03 (+/-0.06 SD) and the mean liver ratio was 0.75 (+/-0.21 SD). It was found that the incubation of plasma with reticulocytes resulted in contamination of the plasma by radioactive hemoglobin. After allowance was made for hepatic uptake of radiohemoglobin in the 13 groups in which proper correction could be made, the isotope ratio in the liver became 0.97 (+/-0.17 SD). It is concluded that iron atoms from the two sites of transferrin have similar tissue distributions in vivo in the experimental situations examined.
Effect of blood donation on iron stores as evaluated by serum ferritin.
Serum ferritin was measured in 2982 blood donors. First-time male donors had a geometric mean of 127 microgram/liter and female donors 46 microgram/liter. While values were essentially constant in the women between the ages of 18 and 45, there was a rapid increase in the men between 18 and 30 years of age consistent with the establishment of iron stores during that time. Blood donation was associated with a decrease in serum ferritin. One unit per year, equivalent to an increased requirement of 0.65 mg/day, halved the serum ferritin level in the male. More frequent donations were associated with further decreases. From the data obtained it would appear that male donors, while depleting their iron stores, were able to donate 2-3 U/yr without an appreciable incidence of iron deficiency. Women could donate only about half that amount, and more frequent donations were associated with a high incidence of iron deficiency and donor dropout. These data have provided information on the effect of graded amounts of iron loss through bleeding on iron balance.
Conditioned EEG desynchronization and seizure occurrence in patients.
Five patients with seizures poorly controlled by standard anticonvulsant medication, underwent EEG operant conditioning. The operant paradigm reinforced the production of low voltage fast activity while decreasing frequencies below 10 c/sec. Seizure frequency decreased in 2 patients, seizure severity was attenuated in 2 others, and one patient who was only given reinforecement for scalp EMG suppression whowed no change in seizure parameters. Pseudoconditioning and control periods ruled out placebo effects. A rationale for this phenomenon is proposed.
Iron deficiency in the rat. Physiological and biochemical studies of muscle dysfunction.
Work performance on a treadmill has been evaluated in normal and iron-deficient rats. Anemia was removed as a variable by adjusting the hemoglobin of all animals to the same concentration. At a hemoglobin compatible with normal work performance, iron-deficient animals showed a marked impairment of running ability as compared to control animals. Iron therapy corrected the disability within 4 days. Concentrations of the cytochrome pigments and myoglobin, and rates of oxidative phosphorylation with pyruvate-malate, succinate, and alpha-glycerophosphate as substrates were all reduced in mitochondrial preparations from skeletal muscle of iron-deficient rats, but only the rate of phosphorylation with alpha-glycerophosphate as substrate increased significantly and in parallel with the recovery in work performance of the iron-deficient rats treated with iron dextran.
Neutrophil kinetics in man.
A method has been developed for measuring neutrophil cellularity in normal human bone marrow, in which the neutrophil-erythroid ratio was determined from marrow sections and marrow normoblasts were estimated by the erythron iron turnover. Neutrophil maturational categories, defined by morphologic criteria, were supported by autoradiographs of marrow flashed-labeled with 3H-thymidine. Correction for multiple counting error was empirically derived by counting serial sections through cells of each maturational category. The normal neutrophil-erythroid ratio in 13 normal human subjects was 1.5 +/- 0.07. The mean number of normoblasts in the same subjects was estimated to be 5.07 +/- 0.84 X 10(9) cells/kg. Total marrow neutrophils (X 10(9) cells/kg) were 7.70 +/- 1.20, the postmitotic pool (metamyelocytes, bands, and segmented forms) was 5.59 +/- 0.90 and the mitotic pool (promyelocytes + myelocytes) was 2.11 +/- 0.36. Marrow neutrophil ("total") production has been determined from the number of neutrophils comprising the postmitotic marrow pool divided by their transit time Transit time was derived from the appearance in circulating neutrophils of injected 3H-thymidine. The postmitotic pool comprised 5.59 +/- 0.90 X 10(9) neutrophils/kg, and the transit time was 6.60 +/- 0.03 days. From these data marrow neutrophil production was calculated to be 0.85 X 10(9) cells/kg per day. Effective production, measured as the turnover of circulating neutrophils labeled with 3H-thymidine, was 0.87 +/- 0.13 X 10(9) cells/kg per day. This value correlated well with the calculation of marrow neutrophil production. A larger turnover of 1.62 +/- 0.46 X 10(9) cells/kg per day was obtained when diisopropylfluorophosphate-32P was used to label circulating neutrophils. Studies using isologous cells doubly labeled with 3H-thymidine and diisopropylfluorophosphate-32P demonstrated a lower recovery and shorter t1/2 of the 32P label.
Striate muscle dysfunction in iron deficiency.
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Extracorporeal treatment with cyanate in sickle cell disease: preliminary observations in four patients.
The effects of extracorporeal carbamylation were determined in four patients with sickle cell anemia. Treatments were carried out in clusters every 4 to 6 weeks over a 6-month period. Mean carbamylation achieved in vivo was 1.3 moles cyanate per mole of hemoglobin. The mean in vitro P50 during treatment was 22.1 mm. Hg as compared to the pretreatment value of 30 mm. Hg. Hemoglobin concentration was increased over the 6 months by 24 per cent. The treatment resulted in the stimulation of erythropoiesis. Treated cells had a prolonged survival of about 40 days, but bilirubin did not fall. Blood volume and heart size remained unchanged. Carbamylation did not appear to alter the degree of sickling at any given O2 saturation. Painful attacks continued through the treatment period with a frequency of 84 per cent and a severity-frequency index of 77 per cent of that in the control period. There was no evidence of cyanate toxicity associated with extracorporeal therapy.
Evaluation of the iron status of a population.
The iron status of a population of 1564 subjects living in the northwestern United States was evaluated by measurements of transferrin saturation, red cell protoporphyrin, and serum ferritin. The frequency distribution of these parameters showed no distinct separation between normal and iron-deficient subjects. When only one of these three parameters was abnormal (transferrin saturation below 15%, red cell protoporphyrin above 100 mug/ml packed red blood cells, serum ferritin below 12 ng/ml), the prevalence of anemia was only slightly greater (10.9%) than in the entire sample (8.3%). The prevalence of anemia was increased to 28% in individuals with two or more abnormal parameters, and to 63% when all three parameters were abnormal. As defined by the presence of at least two abnormal parameters, the prevalence of iron deficiency in various populations separated on the basis of age and sex ranged from 3% in adolescent and adult males to 20% in menstruating women. It is concluded that the accuracy of detecting iron deficiency in population surveys can be substantially improved by employing a battery of laboratory measurements of the iron status.
Why people die or iron poisoning.
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Hemoglobin function, oxygen affinity, and erythropoietin.
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Marrow erythroid and neutrophil cellularity in the dog.
This paper describes a method for determining the number of marrow erythroid and neutrophil cells in which the cellularity of marrow sections was related to that of the total marrow by radioiron dilution. Tissue sections were prepared from methacrylate-embedded dog marrow biopsies, and neutrophils were identified by staining of their primary granules. After correction of direct section counts for multiple counting error, accurate neutrophil-erythroid ratios were established with a coefficient of variation of less than 10 percent when 10-4 cells were examined. An average neutrophil-erythroid ratio of 1.2 was found in six normal dogs. The total number of nucleated red cells in the dog was 5.48 plus or minus 0.78 times 10-9/kg (plus or minus 1 SD), and the corresponding erythron iron turnover was 0.90 plus or minus 0.11 mg Fe/100 ml whole blood/day. The total number of marrow neutrophils, derived from the neutrophil-erythroid ratio, was 6.6 plus or minus 0.59 times 10-9 cells/kg, of which 1.4 were promyelocytes and myelocytes, 2.3 were metamyelocytes and bands, and 3.0 were segmented neutrophils. Leukopheresis studies were carried out in six dogs to confirm the accuracy of these cellular measurements. Marrow counts showed a mean decrease of 22.7 times 10-9 cells or 35 percent of the postmitotic neutrophil pool, and it was calculated that 10.2 times 10-9 additional cells had been taken from already circulating blood. This estimated deficit of 32.9 times 10-9 was almost identical to the 33 times 10-9 cells actually counted in the removed blood.
Neutrophil kinetics in the dog.
The production of neutrophils in dogs has been estimated from the number of postmitotic neutrophils in the marrow and the transit time of a [3H]-thymidine pulse. The number of postmitotic neutrophils was derived from the erythron iron turnover measurement of erythroid number and the neutrophil-erythroid ratio in bone marrow sections. The mean value for marrow postmitotic neutrophils in dogs was 5.61 plus or minus 0.56 times 10-9 cells/kg. The mean transit time of these neutrophils was calculated to be 82.1 h. A marrow production of 1.65 times 10-9 neutrophils/kg/day was calculated from these data. The turnover of circulating neutrophils was measured by [3H]thymidine and [32P]diisopropylphospho-fluoridate (DF32P) labeling of blood neutrophils. [3H]-Thymidine labeling gave a calculated recovery of 65 per cent, a t1/2 disappearance time of 6.7 h, and a calculated turnover of 1.66 times 10-9 cells/kg/day. Corresponding results with DF32P tagging were 51 per cent, 5.4 h, and 2.89 times 10-9 cells/kg/day. The discrepancy between these two tags persisted in doubly tagged cells and was considered to be due to elution of DF32P.
Ferritin in formed blood elements (38539).
The ferritin concentration of the formed elements of the blood has been measured. Nearly equal amounts were found in plasma, red cells, granulocytes, and in the mononuclear (monocyte and lymphocyte) cell fraction. Platelets contained a negligible amount. Concentrations of ferritin were greatest in blood leukocytes, amounting to approximately 24 mug/ml. Changes occurring with iron depletion and iron overload were consistent with those expected in body tissues in general. With infection, increased levels of ferritin were observed in the mononuclear cell fraction, consistent with that which occurs in RE cells.
The absorption of iron as supplements in infant cereal and infant formulas.
The absorption of iron was measured from isotopically tagged salts used in supplementing infant cereals and as the iron supplement in cow's milk and soy-based formulas. Iron as sodium iron pryophosphate and ferric orthophosphate were poorly absorbed from infant cereal (mean, smaller than 1.0%) and thus are not dependable sources of iron to meet the nutritional needs of infants. Reduced iron of very small particle size and ferrous sulfate when added to cereal was absorbed to a greater extent (mean, 4.0% and 2.7% respectively). For technical reasons, these two forms of iron had not been added to commercial cereal products because of discoloration, distribution problems of the iron in the product, and shortened shelf life. Therefore, at the present time, iron supplementation of infant cereals with sodium iron pyrophosphate, ferric orthophosphate, and reduced iron of large particle size does not provide a predictable and available source of iron to meet the needs of infants. Supplemental iron as ferrous sulfate in milk- and soy-based formulas gave a mean absorption of 3.4% and 5.4%. The iron supplements in these formulas can essentially meet the needs for dietary iron of healthy infants.