Ferrioxamine excretion in iron-loaded man.
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Adult↗
Biomedical subjects
C A Finch
Publications and source records attributed to C A Finch.
Clinical studies of a continuous extracorporeal cyanate treatment system for patients with sickle cell disease.
An extracorporeal carbamylation system was evaluated in two patients with sickle cell disease. Access was achieved with existing veins in one patient and an AV fistula in the second. Modifications in the treatment procedure were made as experience indicated. Levels of carbamylation of greater than 1 mol/mol of hemoglobin tetramer were achieved with 4 to 6 hr of treatment every 2 weeks. Cyanate returned to the patient averaged 68.5 mg per treatment. As expected, P50 values decreased and hemoglobin levels increased as the treatment progressed. Patterns of cyanate distribution among the red cell population were those predicted by computer calculations. These observations document the safety and reliability of the treatment system but do not permit conclusions as to efficacy.
Adult↗
Serum ferritin in refractory anemias.
The relationship between the level of erythropoiesis and iron balance was evaluated in 13 subjects with idiopathic refractory anemias. Serum ferritin levels and bone marrow iron stores were increased only in those patients with ring sideroblasts, erythroid hyperplasia and ineffective erythropoiesis. The magnitude of the increase correlated with the duration of anemia and the degree of increase in the erythron iron turnover. Ferritin levels were not related to the severity of the anemia, indicating that increased iron stores did not represent a shift of iron from the erythron or an absorption response to anemia per se. It does suggest that the level of erythroid proliferation directly affects gastrointestinal iron absorption, which in time leads to iron overload.
Adult↗
A rapid assay for evaluation of iron-chelating agents in rats.
The animal assay of potential new iron-chelating agents is at present dependent on cumbersome and imprecise iron balance studies in hypertransfused rodents. We report the development of a radioisotope assay in intact rats based on the transient labeling by ferritin 59Fe of the main source of chelatable iron within hepatocytes. The isotope was maximally available to chelators during the first 6 hr after its injection, nearly all the excretion being in the bile. The bile 59Fe/total iron ratio was independent of both the chelator and its dose. However, in iron-loaded rats, the ratio was reduced, and the isotope excretion was a less sensitive measure of intrahepatic chelation. In the proposed assay, test chelators were given to normal rats 2 hr after an intravenous injection of 59Fe-ferritin. Four hours later, the radioiron in the liver and in the gut gave a sensitive measure of the mobilization of hepatic iron to the bile. In addition, chemical iron determinations identified a small alternative source of urinary chelate with agents known to promote urine excretion in man. The assay gave a rapid and precise screen for chelators given by parenteral and oral routes.
Animals↗
Deleterious effects of iron deficiency.
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Anemia, Hypochromic↗
A patient with polycythemia.
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Blood Volume Determination↗
Transferrin gene expression. Effects of nutritional iron deficiency.
Nutritional iron deficiency was produced experimentally by raising newly hatched chicks on an iron-deficient diet for several weeks. During this time, hematocrit and hemoglobin values declined, iron stores were depleted, and the circulating level of transferrin increased 2- to 4-fold. The increase in serum transferrin was related to a similar increase in the rate of transferrin synthesis in liver. In addition, the level of transferrin mRNA sequences, as determined by hybridization to a specific cDNA, increased 2- to 3-fold, and more than 80% of the transferrin mRNA was associated with polyribosomes in both control and iron-deficient liver. These results demonstrate that the induction of transferrin synthesis in iron-deficient chicks is regulated directly by an increase in transferrin mRNA. The iron-mediated effects on transferrin also appear to be gene-specific since the rate of synthesis of serum albumin, the major secretory product of liver, was unaffected by any of the experimental conditions. Furthermore, when iron stores were rapidly replenished by the administration of iron-saturated ferritin, both the rate of transferrin synthesis and the level of transferrin mRNA returned to control values with 2 to 3 days.
Animals↗
Reproductive studies in the iron-deficient rat.
Severe iron-deficient anemia was produced in the rat by diet. Controls consisted of animals raised on the same diet but injected with iron intraperitoneally. The deficient rats were bred and found to have normal numbers of corpora leutea of pregnancy and implantation sites. Resorptions were very common, and only about 25% of the deficient fetuses were viable on day 20. The peak mortality occurred on about day 12 of gestation. The viable fetuses were smaller than the controls, and a predominance of females was found. More eye defects occurred in the deficient groups, but a significantly increased gross defect rate over controls did not occur. The deficient maternal hemoglobins dropped during pregnancy, and the maternal and fetal hemoglobins on day 20 of gestation averaged 4.5 and 4.7 gm/dl, respectively. Partial treatment of the deficient animals by iron injection on days 0 and 7, or on day 7, prevented embryonic and fetal loss and partially corrected both fetal and maternal hemoglobin concentrations.
Anemia, Hypochromic↗
Idiopathic hemochromatosis, an interim report.
Experience over the last 20 years with 34 patients with idiopathic hemochromatosis is summarized and the literature is reviewed. Methods are now available which are highly effective in the diagnosis of iron overload and virtually all diagnoses are made antemortem. The nature of the disease has changed through the removal of iron by phlebotomy. Early deaths are limited to patients with severe and rapidly progressive heart disease and to those presenting with neoplasm. The major mortality has shifted to a much later period and the incidence of hepatoma is increasing. There is particular interest at the present time in family studies since excessive iron stores are frequently found within the family. The significance of intermediate degrees of iron overload is unclear, but future attention should be given to the recognition of iron overload long before clinical manifestations appear.
Bloodletting↗
Slow-speed EEG for chronic monitoring of clinical seizures in monkey model.
A method for utilizing slow-speed EEG (1/4 mm sec) to detect and quantify gross-motor clinical seizures in a chronic monkey model is described. The technique is particularly useful in the detection of small clinical seizures that may occur in studies of drug efficacy. It estimates the reams of paper generated by standard EEG recording (30 mm/sec) that heretofore precluded easy data collation and thereby essentially prevented continuous monitoring of EEG paroxysms. (This method, however, does not allow the detection of single or non-clumped interictal spikes.) The headplug and recording procedures employed in our laboratory are detailed. The technique can be used alone or, for greater precision, in conjunction with either the recording of motor-activity envelopes or a videotape seizure-confirmation system, or both (Lockard and Barensten, 1967; Lockard et al., 1976c). Unlike our motor-activity and closed-circuit TV method for detecting clinical seizures, the technique of slow-speed EEG could be easily employed in other laboratories already equipped with EEG polygraphs. This method also permits the simultaneous recording of slow-speed and standard-speed EEGs (on separate polygraphs) to facilitate periodically the discrimination between artifacts and clinical seizures.
Animals↗
Assessing iron status of a population.
Reliable methods for assessing the iron status of a population are essential for developing effective public health measures to combat iron deficiency. The hemoglobin concentration, transferrin saturation, free erythrocyte protoporphyrin, and serum ferritin are all useful but they vary widely in their specificity and sensitivity for detecting iron deficiency. In applying these laboratory parameters, the usual approach in nutritional surveys is to determine the percentage of values outside the normal range. As an alternative, a model is presented here that uses these measurements to estimate the distribution of iron stores in a population. This approach may be particularly useful for evaluating the effectiveness of iron supplementation and fortification programs.
Adult↗
Practical considerations in using counterimmunoelectrophoresis to identify the principal causative agents of bacterial meningitis.
Many clinical laboratories are currently using counterimmunoelectrophoresis (CIE) as an aid in the rapid diagnosis of bacterial meningitis. Because cross-reactions among causative agents have been reported, the present study was undertaken to explore the problems that might occur when reference and commercial antisera are used in CIE. Broth cultures of 35 bacterial strains were tested with 76 reference and commercial antisera by CIE. Some of the antisera tested failed to react with their homologous strains. Furthermore, several cross-reactions between genera, as well as within species, were noted. These findings suggest that precautions must be taken to insure that all materials used in CIE tests are of high quality. If properly performed and interpreted, CIE may be a valuable adjunct in the identification of organisms causing bacterial meningitis, but it is, nevertheless, a presumptive test and should not be used to replace the Gram stain and culture techniques.
Antigens, Bacterial↗
Lactic acidosis as a result of iron deficiency.
Iron-deficient rats have an impaired work performance, even when their anemia is corrected by exchange transfusion. Muscle activity is associated with a higher blood lactate concentration than is observed in iron-replete animals. The accumulation of lactate is a result of excessive production as lactate clearance from the blood was shown to be unaffected. By adjusting the work load to a lower level, it was possible to divide iron-deficient animals into two groups, one capable of continued treadmill running and another in which animals stopped before 20 min. In the former, blood lactate concentration reached a plateau at moderate levels, whereas it continued to increase in the latter until the animal stopped running. Levels of alpha-glycerophosphate oxidase in skeletal muscle mitochondria were found to be much lower in the second group (P < 0.001). Lactate infusion into normal animals was shown to interfere with work performance, and maintenance of a normal pH in iron-deficient and iron-replete animals did not prevent the impairment in work associated with high blood lactate concentrations. Additional evidence was obtained that energy substrate (blood glucose and free fatty acids, muscle glycogen) was adequate in irondeficient animals. Oxygen tension in their vena caval blood was higher than in controls. Furthermore, the in situ behavior of electrically stimulated gastroenemius and soleus muscles appeared similar to that of control animals. Because the stimulation of the single muscle in the iron-deficient animal did not result in appreciable elevation of blood lactate and did not show impaired contractility further supported the hypothesis that the elevation of blood lactate caused the decreased work performance. It is concluded that iron deficiency by a depletion in the iron-containing mitochondrial enzyme, alpha-glycerophosphate oxidase, impairs glycolysis, resulting in excess lactate formation, which at high levels leads to cessation of physical activity.
Acidosis↗
Iron deficiency in the rat: effects on phenylalanine metabolism.
Concentrations of phenylalanine in the plasma were markedly elevated in iron-deficient rats and appeared to vary directly with the degree of iron deficiency. Plasma concentrations of phenylalanine returned to control levels within one week after treatment of the iron-deficient rats with iron dextran. The elevated levels of plasma phenylalanine were probably not produced by a deficiency in liver phenylalanine hydroxylase because levels of activity of the enzyme were found to be normal in the livers of the iron-deficient animals.
Animals↗
Effects of oxygen tension and pH on the ultrasonic absorption properties of sickle cells.
The ultrasonic absorption of sickle cells was compared with the morphological changes in these cells are produced by varying oxygen tensions and pH. A decrease in oxygen tension caused increased sickling and an increase in the ultrasonic absorption of the blood. An increase in pH reduced the ultrasonic absorption and decreased sickling. These findings indicate that ultrasonic absorption can detect changes in the aggregation state of sickle cell hemoglobin in situ within the red cell and that the method may be used to monitor the degree of sickling under various environmental conditions.
Adult↗
Neutrophil kinetics in chronic neutropenia.
Quantitative studies of bone marrow neutrophil pool sizes and production rates and of blood neutrophil kinetics were performed in 16 patients with chronic neutropenia without splenomegaly. Marrow netrophil cellularity was determined from a ferrokinetic estimate of marrow normoblasts and from neutrophil-erythroid ratios determined from marrow sections. Postmitotic pool turnover was derived from the postmitotic pool size and transit time, the latter determined from 3H-thymidine neutrophil emergence time. Blood neutrophil kinetics were studied with 32P-diisopropylfluoophosphate-labeled autologous neutrophils. Mitotic pool size was basal or below basal in 12 of the 16 patients. The turnover of the post-mitotic neutrophils was subbasal in 6, basal in 7, and above basal in 3 patients. Blood neutrophil turnover was within the normal range in 8 patients and decreased in 8. The degree of ineffective granulocytopoiesis was assessed by comparing the relative size of the mitotic pool, postmitotic pool turnover, and blood turnover. On this basis, 13 of the 16 patients showed appreciable degrees of ineffective granulocytopoiesis. Ineffective neutrophil production occurred both early and late in neutrophil development. These studies indicate that most patients with chronic neutropenia without splenomegaly lack a proliferative marrow response to the neutropenia and suggest that ineffective granulocytopoiesis is a common feature of this disorder.
Adult↗
Erythrocyte protoporphyrin/heme ratio in the assessment of iron status.
The protoporphyrinemia of iron deficiency is well recognized. Clinically, information on the protoporphyrin/heme molar ratio in whole blood offers certain advantages over protoporphyrin measurement alone. A procedure for determining this ratio is reported. Protoporphyrin is extracted, solubilized, and measured fluorometrically. Heme (as hemin chloride) is precipitated with the blood proteins, the precipitate is dissolved in an alkaline/pyridine solvent, and the resulting bispyridine ferriprotoporphyrin is measured spectrophotometrically. The molar ratio of these two metabolites correlates well with values for plasma ferritin, plasma iron, transferrin saturation, hemoglobin, and hematocrit. In some cases the ratio increases detectably while the other variables, especially hematocrit and hemoglobin, remain normal. Evidently it is a more sensitive index to iron status. For healthy men and women, the mean ratio is 16.0 (SD, 5.3). The mean + 3 SD, or a ratio of 32, is distinctly abnormal, as shown by a confirmatory test. We validated the test by surveying routine blood specimens obtained from several population groups.
Anemia, Hypochromic↗