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Biomedical subjects

Y Beguin

Publications and source records attributed to Y Beguin.

At least 127 records · Page 7Linked to original sources

Serum immunoreactive erythropoietin during pregnancy and in the early postpartum.

We studied 209 women during normal pregnancy, at delivery, or in the early postpartum, to determine whether erythropoietin (EPO) response was appropriate for the degree of anaemia. Serum immunoreactive EPO was measured in 74 nonpregnant women, including 33 normal subjects (16.4 +/- 4.1 mU/ml) and 41 women with hypoplastic, haemolytic, dyserythropoietic, or iron-deficient anaemia. An inverse linear relationship (R = -0.88, P less than 0.0001) between log(EPO) and Hct was observed. Predicted EPO values were derived for each Hct and an O/P ratio of observed/predicted log(EPO) was calculated for each sample (1.00 +/- 0.10, range 0.80-1.20). Serum EPO levels (mU/ml) were significantly higher during pregnancy (30 +/- 16, n = 142), at delivery (31 +/- 16, n = 41), and on day 7 postpartum (37 +/- 35, n = 26) than in normal women (P less than 0.001). EPO levels increased steadily from 18 +/- 6 mU/ml in the first, to 26 +/- 14 mU/ml in the second, and to 35 +/- 18 mU/ml in the third trimester (P less than 0.0001). The O/P ratio was normal on day 7 postpartum (1.01 +/- 0.16), at delivery (1.03 +/- 0.16), and in the third trimester (0.96 +/- 0.15), but was significantly reduced in the first two trimesters (0.88 +/- 0.15, P less than 0.001). A significant negative correlation between log(EPO) and Hct was lacking in the first two trimesters, was present but with a reduced slope during the third trimester and at delivery, and was normal postpartum. We conclude that EPO response to anaemia is impaired in early pregnancy, recovers in late pregnancy, and normalizes rapidly in the postpartum.

Adolescent↗

Model of reticuloendothelial iron metabolism in humans: abnormal behavior in idiopathic hemochromatosis and in inflammation.

Iron transport in the reticuloendothelial (RE) system plays a central role in iron metabolism, but its regulation has not been characterized physiologically in vivo in humans. In particular, why serum iron is elevated and RE cells are much less iron-loaded than parenchymal cells in idiopathic hemochromatosis is not known. The processing of erythrocyte iron by the RE system was studied after intravenous (IV) injection of 59Fe heat-damaged RBCs (HDRBCs) and 55Fe transferrin in normal subjects and in patients with iron deficiency, idiopathic hemochromatosis, inflammation, marrow aplasia, or hyperplastic erythropoiesis. Early release of 59Fe by the RE system was calculated from the plasma iron turnover and the 59Fe plasma reappearance curve. Late release was calculated from the ratio of 59Fe/55Fe RBC utilization in 2 weeks. The partitioning of iron between the early (release from heme catabolism) and late (release from RE stores) phases depended on the size of RE iron stores, as illustrated by the inverse relationship observed between early release and plasma ferritin (P less than .001). There was a strong correlation between early release and the rate of change of serum iron levels during the first three hours in normal subjects (r = .85, P less than .001). Inflammation produced a blockade of the early release phase, whereas in idiopathic hemochromatosis early release was considerably increased as compared with subjects with similar iron stores. Based on these results, we describe a model of RE iron metabolism in humans. We conclude that the RE system appears to determine the diurnal fluctuations in serum iron levels through variations in the immediate output of heme iron. In idiopathic hemochromatosis, a defect of the RE cell in withholding iron freed from hemoglobin could be responsible for the high serum iron levels and low RE iron stores.

Erythrocytes, Abnormal↗

Ferrokinetic study of splenic erythropoiesis: relationships among clinical diagnosis, myelofibrosis, splenomegaly, and extramedullary erythropoiesis.

Splenic erythropoiesis was demonstrated by surface counting of 59Fe in 129 of 1,350 ferrokinetic studies performed over a 15 year period. These 129 studies were carried out in 108 patients, including 40 with chronic myelogenous leukemia (CML), 24 with agnogenic myeloid metaplasia (AMM), 18 with polycythemia vera (PV), six with a myelodysplastic syndrome, five with acute leukemia, three with prostate or breast carcinoma, two each with aplastic anemia or Hodgkin's disease, and one each with idiopathic thrombocythemia, multiple myeloma, chronic renal failure, or treated hypopituitarism. Splenomegaly was present in 83% of the studies and hepatomegaly in 72%. Grade II-III myelofibrosis was demonstrated in 62% of the cases. Hepatic erythropoiesis was present in 77% of the studies (only 38% in PV), and marrow erythropoiesis was undetectable in 33%. Total erythropoiesis was about twice normal (range 0.2 to 8 times normal) but was ineffective to varying degrees in 86% of the studies. Relationships between organomegaly, myelofibrosis, and extramedullary erythropoiesis, as well as differences among clinical disorders, are discussed. Differences observed between CML in chronic or blastic phase suggested that the erythroid cell line was involved in the proliferative process. It is concluded that splenic erythropoiesis 1) is encountered in a variety of clinical conditions; 2) is not necessarily associated with splenomegaly or myelofibrosis, even in the myeloproliferative disorders; 3) is part of a predominantly extramedullary (in the liver as well as in the spleen), expanded, and largely inefficient total erythropoiesis; and 4) can be evaluated in a semiquantitative manner by surface counting.

Erythropoiesis↗

Relationship of serum selenium levels to tumor activity in acute non-lymphocytic leukemia.

Serum selenium (Se) levels were measured before, during and after high-dose induction chemotherapy in 70 patients with acute non-lymphocytic leukemia (ANLL). Pre-treatment serum Se levels were lower in patients than in controls (0.082 +/- 0.033 micrograms/ml versus 0.097 +/- 0.035 micrograms/ml, P less than 0.01). Pretreatment serum Se correlated inversely with the absolute peripheral blast cell count (R = -0.62, P less than 0.001) and other measurements of the tumor burden. Seven days after the initiation of chemotherapy, serum Se increased significantly in proportion to the initial tumor burden (P less than 0.01). Thereafter, serum Se levels remained essentially normal in patients entering a complete remission while decreasing gradually in failures. In conclusion, these data do not lend support to the hypothesis that a low selenium status enhances the risk of developing ANLL, but indicate that serum Se levels in patients with acute leukemia are mostly dependent on tumor activity.

Female↗

[Reutilization of iron in the body and regulation of iron reserves. The value of plasma transferrin receptor levels].

A model for reticulo-endothelial iron metabolism is proposed which characterises diseases of the reutilisation of iron in man. In idiopathic hemochromatosis the RE cell is defective in withholding iron freed from senescent red cells and unable to control the plasma iron level. Transferrin receptor can be measured in plasma, where its concentration is proportionnal to the number of cellular receptors. Plasma levels of transferrin receptor serve as a convenient monitor of total erythropoiesis.

Humans↗

Experience with a totally implantable catheter in adult patients: a single institution retrospective study of 114 cases.

One hundred and fourteen consecutive totally implantable catheters were inserted in 114 patients between April 1984 and April 1987. Catheters were inserted under neuroleptanalgesia, through the jugular vein in 101 cases or the internal saphenous vein in 13 cases. No problem was encountered during the insertion procedure. Infection occurred in 5.2% of the patients but removal of the device was required in only 2.6%. Occlusion of the catheter occurred in 6.1% of the patients but never during the first 2 months. This complication rate is lower than the one observed with external tunnelled catheters. The comfort of the patient is substantially improved and nursing care is greatly facilitated.

Adolescent↗

Hepatocyte iron release in rats.

Hepatocyte iron release was studied in vivo in rats. After the injection of iron 59-labeled ferritin, hemoglobin, or human asialotransferrin, the proportions of the radioactive iron returned to the plasma and incorporated into stores were determined under various conditions. Iron 55-labeled rat transferrin was injected at the same time as the 59Fe-labeled compound, and storage iron release was calculated from the cumulative incorporation of the two isotopes in the red cell mass over 2 weeks. The various 59Fe-labeled compounds were processed differently by the hepatocyte, but the radioactive iron was incorporated in the same iron stores. About 6% of the hepatocyte storage iron was released daily in normal rats, but a pool of iron that is not mobilized spontaneously was clearly identified in iron overload. Iron turnover in the hepatocyte was regulated by the rate of erythropoiesis and iron status of the animal, and inflammation blocked hepatocyte iron release. A strong correlation between hepatocyte iron release and plasma transferrin receptor levels was observed (p less than 0.001), suggesting that plasma transferrin receptors could mediate the regulation of hepatocyte iron mobilization in rats.

Animals↗

Random distribution of iron among the two binding sites of transferrin in patients with various hematologic disorders.

The distribution of iron among the two binding sites of transferrin was studied by isoelectric focusing in 41 patients with a variety of disorders of iron metabolism and erythropoiesis. The proportion of diferric and the two monoferric transferrins were very close to the values predicted from the transferring saturation. It is concluded that iron distribution on transferrin is random or close to random within the experimental error in patients with a variety of clinical disorders.

Hematologic Diseases↗

The behavior of asialotransferrin-iron in the rat.

The effect of desialylation of rat and human transferrins on hepatocyte processing of the protein and its iron was studied in rats. No alteration in early transferrin catabolism was observed. Radioiron disappearance from the plasma and liver iron uptake were more rapid for asialotransferrins than for normal transferrins (P less than .001). Furthermore, radioiron plasma clearance of human tri-sialotransferrin was faster (P less than .05) and liver uptake higher (P less than .002) than for human pentasialotransferrin. When the asialoglycoprotein receptor was blocked by the prior injection of asialofetuin, asialotransferrin behaved like normal transferrin. When the transferrin receptor was blocked by the prior injection of 50 mg human diferric transferrin, iron uptake from all transferrins was delayed to such an extent that uptake through both receptors seemed to be affected. Approximately 90% of the hepatic radioiron from all transferrins was chelated by desferrioxamine and excreted into the bile, indicating its uptake by the hepatocyte rather than the reticuloendothelial (RE) cell. The rate of iron release into the plasma and its subsequent accumulation in the red cell mass over a 2-week period was similar for human asialotransferrin, ferritin, and hemoglobin iron. This study 1) confirmed that asialotransferrin-iron uptake by the hepatocyte is mediated by both transferrin and asialoglycoprotein receptors; 2) demonstrated that not only asialotransferrin but also transferrin of low sialic acid content will increase iron turnover and lead to excessive iron loading of the hepatocyte; 3) and showed that the intrahepatocyte metabolism of asialotransferrin-iron did not differ from that of iron delivered by normal transferrin.

Animals↗

Transferrin receptors in rat plasma.

Antigenic material in rat plasma reacting with rat transferrin receptor antibodies was identified as an intact receptor molecule complexed with transferrin. Plasma transferrin receptors were measured by ELISA in rats of different age and sex, of different iron status, with different degrees of erythropoiesis, and with inflammation. An inverse relationship between iron status and receptor number was found, whereas a direct relationship existed between erythropoiesis and receptors. These changes in receptor number can be explained by assuming that the number of tissue receptors determined the number of plasma receptors and that the erythroid cells possessed most of the body's receptors. Increases in plasma receptors lagged behind the appearance of circulating reticulocytes, suggesting that receptors were released to the plasma during the terminal phase of erythrocyte maturation.

Animals↗

Ferrokinetic measurement of erythropoiesis.

Ferrokinetic measurements have proved useful because of the dominant role of the erythron in tissue iron uptake. Detailed measurements of the plasma iron disappearance curve coupled with in vivo counting have defined the major pathways of iron utilization and early refluxes of iron into plasma. Recent studies have disclosed two separate plasma kinetic pools consisting of mono- and diferric transferrin, and have demonstrated the effect of their relative abundance on tissue iron uptake. Allowance for the amount of each has made possible the calculation of iron-bearing transferrin uptake, which is independent of plasma iron concentration as long as receptors are saturated. This refinement permits the measurement of functional erythron transferrin receptors, and thereby the relative number of immature erythroid cells.

Anemia↗

Observations of serum trace elements in chronic lymphocytic leukemia.

Serum trace elements (STE) were measured in 50 patients with chronic lymphocytic leukemia (CLL) and 100 normal subjects. Copper was higher in patients than in controls (1.50 +/- 0.06 versus 1.10 +/- 0.02 micrograms/ml, P less than 0.001), increased steadily from Stage 0 to Stage 4 (P = 0.002), and correlated with the lymphocyte count and serum lactate dehydrogenase (P less than 0.01) but not with acute phase reactants. Zinc was lower in patients than in controls (0.94 +/- 0.03 versus 1.10 +/- 0.02 micrograms/ml, P less than 0.001). Zinc (NS), selenium (P = 0.039), and calcium (P = 0.033), were decreased in Stages 3-4 as compared to Stages 0-2. The copper-to-zinc ratio (CZR) increased continuously from Stage 0 to Stage 4 (P less than 0.001). Discriminant analysis between two groups, Stage 0-2 and Stage 3-4, based on serum copper, zinc, calcium, and protein levels, allowed for a correct classification of 94% of the patients. Moreover, the clinical staging of the remaining 6% was modified retrospectively according to the results of discriminant analysis. It was concluded that (1) serum copper and CZR are useful indices of the extent of disease, (2) they are independent of a nonspecific acute phase reaction, (3) STE determination could be helpful in the staging of a limited number of CLL patients, and (4) zinc deficiency could contribute to immune dysfunction in CLL.

Aged↗