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Notes: Zusammenfassung Die auch beim Neugeborenen und Säugling zuverlässigste, empfindlichste und schonendste Methode zur exakten Bestimmung der intestinalen59Fe-Resorption ist die Messung der Gesamtkörperretention des resorbierten59Fe in einem 4π-Großraum-Radioaktivitätsdetektor mit organischem Szintillator. Mit dieser Methode bei 42 Reifgeborenen und 35 Frühgeborenen im ersten Trimenon (4.–80. Lebenstag) durchgeführte Messungen ergaben einen bei etwa 5–35% der oralen 10µMol (≙ 0,558mg)59Fe++-Testdosis liegenden Normalbereich der intestinalen Eisenresorption. Ähnlich wie beim Erwachsenen so führt auch beim Säugling die Erschöpfung der utilisierbaren Eisenreserven zu einem starken, diagnostisch verwertbaren Anstieg der intestinalen59Fe-Resorption auf 40–81%. Solange eine diätetische Eisen-Prophylaxe bzw. Therapie der vom 6.–24. Lebensmonat ubiquitären prälatenten, latenten bzw. manifesten Eisenmangelzustände wegen der schlechten Resorbierbarkeit des Nahrungseisens nicht realisiert werden kann, ist die orale Prophylaxe und Therapie mit dem auch beim Säugling sehr gut und beim Vorliegen eines Eisenmangels sogar stark vermehrt resorbierbaren Fe++ die Methode der Wahl.

Notes: Zusammenfassung Es wird über die diagnostischen Möglichkeiten einer neuen cytochemischen Methode (der Sulfid-Silber-Reaktion) zum Nachweis des Nichthämoglobineisens in Blutzellen berichtet. In vergleichenden cyto- und mikrochemischen Eisenstoffwechsel-untersuchungen konnte nachgewiesen werden, daß die Methode bei nachfolgend aufgeführten hämatologischen Erkrankungen des Kindesalters eine diagnostische Bedeutung hat. 1. Der Nachweis des Nichthämoglobineisens in den einzelnen Zellformen der Erythropoese ist entscheidend für die Differentialdiagnose der hyposiderämischen Anämien. Ein negativer Ausfall der Reaktion in nur einem Teil der basophilen Erythroblasten ist beweisend für eine echte Eisenmangelanämie. Ein positiver Befund in nur ganz vereinzelten Erythrocyten spricht für eine Pseudoeisenmangelanämie. 2. Cytochemisch nachweisbares Nichthämoglobineisen in den Lymphocyten ist eines der ersten Zeichen einer Hämosiderose und kann daher bei der Diagnose der Eisenüberladung eine entscheidende Hilfe sein. Das Ausmaß der Hämosiderose und ihre Behandlungsmöglichkeit ist mit Hilfe des Desferaltestes abzuschätzen. 3. Neben den Zeichen der Eisenüberladung läßt sich die Eisenverwertungsstörung durch den Nachweis von feinstkörnig verteiltem Eisen in den Erythrocyten nachweisen.

Notes: Summary In 23 children with mild iron-deficiency anemia, 22 children with latent iron-deficiency, and in 46 healthy controls the3H-thymidine incorporation in blood lymphocytes after stimulation with phytohemagglutinin, concanavalin A, pokeweed mitogen, and serum against thymocytic cells was measured. In 11 of the children with iron-deficiency anemia, in 13 of the children with latent iron-deficiency, and in 20 controls the lymphotoxin secretion after phytohemagglutinin stimulation was also performed. All patients studied were without intercurrent infections and were well nourished. No alteration of the lymphocyte function in the patients was found. The concentrations of immunoglobulins and the components C3 and C4 of complement system were also found to be normal. It is suggested that lymphocyte functions are eventually only altered in more severe states of iron-deficiency anemia.

Notes: Zusammenfassung Es wird gezeigt, daß mit neuen Mikromethoden Eisen mit einer Genauigkeit von 0,002–0,005γ und Kupfer mit einer Genauigkeit von 0,004 bis 0,010γ in biologischem Material bestimmt werden kann. Es lassen sich daher notfalls in 0,05 ml, besser in 0,10 ml, Serum Eisen und in 0,10 ml Serum Kupfer mit einer Fehlerbreite von 5–10γ/100 ml bestimmen. Die Methode gestattet erstmalig, fortlaufende Eisen- und Kupferanalysen bei sehr jungen Kindern (selbst Frühgeborenen) und bei kleinen Versuchstieren im Serum durchzuführen. Durch die Anwendung der Mikromethode zur Eisen- und Kupferbestimmung im Urin und Gewebe ist die Aufarbeitung des Materials auf Grund der geringen benötigten Mengen wesentlich erleichtert.

Notes: Zusammenfassung Es wird über Untersuchungen mit verschiedenen Methoden zur Bestimmung der latenten und totalen Serumeisenbindungskapazität berichtet. Die Methoden vonRamsay und vonRath undFinch können mikrochemisch mit 0,100–0,200 ml Serum durchgeführt werden. Die Methode vonRamsay arbeitet sicherer, es lassen sich bei diesen Serummengen Fehlerbreiten unter 20γ/100 ml einhalten. Bei der Methode vonRath undFinch muß man mit einer Fehlerbreite von über 50γ/100 ml rechnen. Der Bilirubingehalt beeinflußt bei diesen Methoden die Bestimmung der Eisenbindungskapazität nicht.

Notes: Abstract  Glial cell-line-derived neurotrophic factor (GDNF), a member of the transforming growth-factor- (TGF-) β-family, is an essential factor for the development of the enteric nervous system (ENS) during embryogenesis. In the present study, the effects of GDNF on postnatal ENS development were investigated using cultures of myenteric plexus from the small intestine of newborn albino rats of different developmental phases (P1, P7, P14). Myenteric plexus was dissociated and cultivated as mixed cultures of enteric neurons and glial cells. After seeding, the cultures were kept for 24 h or 7 days in serum-free medium containing various doses (1, 10, 100 ng/ml) of GDNF. The effect of the neurotrophic factor was evaluated using parameters such as cell size, neuronal survival, or neurite elongation. While neither glial-cell nor neuronal size was influenced by GDNF, there was an observable effect upon neuronal survival and neurite elongation. The cultures treated with GDNF displayed increased neurite outgrowth. The promoting effect was dose- and age-dependent, decreasing clearly during the early postnatal period. Already after 24 h, neuronal survival was increased in P1 and P7, but not in P14 cultures. In long-term cultures, a marked tendency to form cell aggregates and dense fiber networks was observed when treated with GDNF. These observations suggest that GDNF plays an important role not only in pre-, but also in postnatal development of the enteric nervous system.

Notes: Abstract Since 1966 we treated 22 patients with ulcerative colitis, 15 of which with severe diseases were selected for immunosuppressive therapy according to strictly defined criteria. Difficulties were observed in 2 cases. In 13 cases immunosuppressive therapy promptly resulted in clinical and rectoscopic remissions. Roentgenologic findings of colon were normalized in 2 cases, improved in 3 cases and not yet controlled in the other cases. Side effects were noted in 2 patients, they included cholestatic jaundice and vomiting. Alopecia and decreased linear growth were not observed. In summary our experience with the immunosuppressive therapy of childhood ulcerative colitis so far has been encouraging.

Notes: Abstract A high negative correlation (coefficient ∼ 0.9) between increased 59Fe absorption from a diagnostic 0.56 mg 59Fe2+ dose and the depletion of available storage iron was observed in menstruating and pregnant women, fullterm and premature infants, blood donors, patients with infections, inflammations, tumors, hepatic cirrhosis, gastric surgery, increased urogenital or gastrointestinal blood loss. The increased diagnostic 59Fe2+ absorption is a reliable and sensitive indicator of at least depleted iron stores or prelatent iron deficiency as caused by iron malnutrition or maldigestion, increased iron requirement in pregnancy, infancy, urogenital or gastrointestinal blood loss. Although the messenger system which signalyzes the depletion of iron stores to the iron absorbing enterocytes of the duodenal and jejunal mucosa is not yet known available storage iron seems to control intestinal iron absorption under normal and the great majority of pathological conditions in humans. Anemia per se or high erythropoietin levels in blood do not influence iron absorption since patients with even severe erythroblastic hypoplasia, aplastic anemia and megaloblastic anemia due to vitamin B12 deficiency absorb iron according to their iron stores. An only mild hyperplasia of the erythropoietic system in the bone marrow does also not effect iron absorption which was still under the control of available storage iron in patients with hereditary spherocytosis, nonspherocytic congenital hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency, acquired hemolytic anemia and vitamin B12 deficiency induced megaloblastic anemia. An exception from the general rule that depleted iron stores do cause increased iron absorption, which can be used therefore for the reliable diagnosis of depleted iron stores or prelatent iron deficiency, was observed only in anemic children with hereditary nonspherocytic enzymopenic hemolytic anemia due to pyruvate kinase deficiency. In these cases a strong normoblastic hyperplasia correlated well with the increased iron absorption in the presence of normal amounts of available storage iron. Blood transfusions which suppress the normoblastic hyperplasia do also reduce the increased iron absorption to normal levels. A similar iron absorption increasing effect of hyperplastic ineffective erythrocytopoiesis was also observed in adults with sideroblastic anemia and children with severe homozygous β-thalassemia although the iron stores of these patients were normal or increased. The messenger system which is used by the body for signalyzing severe normoblastic hyperplasia to the iron absorbing intestinal mucosa and induces a useless and even dangerous augmented iron absorption is not yet known. Since the diseases with severe normoblastic hyperplasia are extremely rare and easily to diagnose the increased intestinal iron absorption from the diagnostic 0.56 mg 59Fe2+ dose is a very useful, reliable and sensitive indicator of already the earliest stage of iron deficiency.

Notes: Abstract The intestinal absorption of 59Fe from a diagnostic 10 μmole (0.56 mg) 59Fe2+ test dose and 5 mg Fe equivalents of 59Fe-labeled pork, hog liver and hemoglobin was measured with a 4 π geometry whole-body radioactivity detector with liquid organic scintillator and the results compared with the stainable amounts of diffuse cytoplasmatic (non-heme) storage iron in the bone marrow macrophages, serum iron concentrations and total iron-binding capacity, erythropoietic activity and other hematological parameters. Children with mild hypochromic, microcytic anemia due to heterozygous β-thalassemia absorbed normal amounts of 59Fe from the diagnostic dose of 59Fe2+ if their bone marrow macrophages contained normal or mildly increased amounts of diffuse cytoplasmatic storage iron. Depleted iron stores also caused increased absorption of diagnostic 59Fe in children with heterozygous β-thalassemia, so that prelatent iron deficiency can be diagnosed by measurement of increased iron absorption. The diagnostic 59Fe2+ absorption was increased to 70–100% in children with homozygous β-thalassemia when it was measured 64–300 days after the last blood transfusion. Since all these children contained normal to increased amounts of diffuse cytoplasmatic storage iron in the bone marrow macrophages, the high intestinal iron absorption was not caused, as is usual, by depleted iron stores but coincided with considerable hyperplasia of ineffective erythropoiesis demonstrated by the increased numbers of normoblasts in the bone marrow and peripheral blood during a period of severe anemia. Blood transfusions which elevate the hemoglobin levels from 4–5 g/100 ml to 8.5–9.9 g/100 ml and suppress the erythroblastic hyperplasia in the bone marrow also reduce the increased absorption of inorganic and food iron to normal values. Interruption of blood transfusions always results in the next erythroblastic hyperplasia and a simultaneous increase of intestinal iron absorption. Mild hyperplasia of the erythropoietic system such as is observed in megaloblastic anemia due to vitamin-B12 deficiency or in hereditary spherocytosis is not sufficient to increase iron absorption. Anemia per se does not increase iron absorption, as is borne out by the observation that patients with severe aregenerative anemia or megaloblastic anemia absorb 59Fe2+ according to their normal iron stores within the normal range. The messenger which signalizes depleted iron stores or erythropoietic hyperplasia to the duodenal and jejunal mucosa so that intestinal iron absorption is increased is not yet known. The food iron absorption from 59Fe-labeled pork and hog liver was increased to 2–4 times the normal average when measured in homozygous β-thalassemia with severe anemia and erythroblastic hyperplasia 28–42 days after the last blood transfusion. This increased food iron absorption was normalized by blood transfusion which suppressed the erythropoietic hyperplasia and raised the hemoglobin levels to 9.7–10.4 g/100 ml. The development of hemosiderosis either from blood transfusions or from increased food-iron absorption seems to be unavoidable in patients with homozygous β-thalassemia. Regular transfusion of 2–8 l blood per year is necessary to keep the hemoglobin at a level of at least 9 g/100 ml, which does not induce erythrocytopoietic hyperplasia and increased food-iron absorption. After 18 years on such a transfusion schedule, between 18 and 73 g iron have been incorporated into the body and produced transfusion hemosiderosis. Patients with homozygous β-thalassemia who survive without blood transfusions and have low hemoglobin levels (〈8 g/100 ml) absorb 3 times more iron from a mixed diet and after 18 years have accumulated about 19 g iron from increased food-iron absorption, which is also enough to produce hemosiderosis.