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Bei 27 Patienten mit Haarzell-Leukamie konnte der Krankheitsverlauf uber maximal 97 Monate beobachtet werden. Eine Splenektomie war bei 17 Patienten durchgefuhrt worden; sie besserte den hamatologischen Status zumeist eindrucksvoll. Von den splenektomierten Patienten leben zehn inzwischen 8 bis 88 Monate nach der Operation. Bei funf von ihnen konnte ein Krankheitsprogres, der sich entweder als isolierte Leukozytose, als Verschlechterung des gesamten hamatologischen Status oder als intraabdominelles Lymphomwachstum auserte, durch Leukapherese, niedrig dosierte Langzeitbehandlung mit Chlorambucil, Gabe von Doxorubicin (Adriamycin) bzw. einer Doxorubicin enthaltenden Zytostatikakombination sowie abdominelle Lokal- oder Ganzbestrahlung erfolgreich behandelt werden. The course of hairy cell leukaemia was observed in 27 patients for a maximum of 97 months. Splenectomy had been performed in 17 patients and improved the haematological situation impressively in most cases. Amongst patients with splenectomy ten are alive with 8 to 88 months postoperatively. In five of them disease manifesting as isolated leucocytosis, deterioration of the overall haematological situation or as intraabdominal lymphomatous growth could be treated successfully. Treatment consisted of leucapheresis, low-dose long-term therapy with chlorambucil, administration of doxorubicin (adriamycin) or a combination of cytostatics containing doxorubicin as well as abdominal localized or overall irradiation.

Hereditary (idiopathic, genetic) haemochromatosis is a genetic disease in which food iron absorption is inadequately increased and not balanced to the body iron stores. As a consequence, untreated patients have a risk to develop iron overload which can give rise to various iron-induced organ damages, leading in some cases to multi-organ dysfunction (liver cirrhosis, diabetes, cardiomyopathy). Diagnosis in this iron loading disease was formerly based on highly increased transferrin saturations, elevated serum ferritin concentrations and on excessive iron deposits in biopsy material from liver. After the identification of the HFE gene and its most common mutations, a genetic diagnosis independent from iron stores has become available. Because of individual variations in the loading process, diagnostic criteria are still necessary to characterise the risks of a given patient to develop iron-induced lesions and clinical symptoms. This review describes the current knowledge of the molecular pathology and discusses criteria for diagnosis and screening of hereditary haemochromatosis. Non-invasive liver iron quantification could represent the optimal complement to the HFE gene testing. Data on our experience with SQUID biosusceptometry, which makes liver biopsy unnecessary in most cases, are presented.

The physiological site of iron storage in the human bone marrow is the macrophage (orthotopic iron store). Iron-storing plasma cells, as bone marrow indicators of iron overload, and/or chronic alcoholism represent a pathological (heterotopic) iron store. They were demonstrated by light and electron microscopy in 23 iron-overloaded patients: transfusional siderosis (n = 8), genetic haemochromatosis (GH; n = 11), iron-loading anaemias (n = 4) and in patients with bone marow impairment due to chronic alcoholism (n = 6). The pattern of iron storage in bone marrow plasma cells was monitored during iron loading in patients receiving continuous transfusional therapy (n = 7) and also upon reversal of iron overload by repeated phlebotomies in GH (n = 9) and in iron-loading anaemias (n = 4). The first ultrastructural evidence of iron storage in plasma cells was the appearance of free ferritin molecules in the cytosol, thus indicating endogenous ferritin synthesis. Accumulation of iron proceeded with the additional formation of ferritin- and haemosiderin-containing lysosomes (siderosomes) in these cells. Lysosomal ferritin partially showed a paracrystalline arrray. The siderosomes originated from autophagocytosis of cytoplasmic areas containing free ferritin molecules. In addition, the formation of ferritin-containing vesicles in the proximity of the Golgi apparatus was observed. The heterotopic iron store of bone marrow plasma cells was less readily mobilizable by blood-letting than the orthotopic store of macrophages.

Iron-deficient female Wistar rats were fed a diet which contained 0.5% 3,5,5-trimethylhexanoyl (TMH)-ferrocene over a 57-week period. The state of iron deficiency was characterized by means of the absence of stainable iron in the bone marrow. After the first days on the iron-enriched diet, ferritin-containing siderosomes were found, in numerous erythroblasts up to orthochromatic nor-moblasts and in reticulocytes, i.e. the dispensed iron was used for haemoglobin synthesis. After 1 week the first macrophages showed a positive Perls’ Prussian blue reaction. In the cytoplasm they stored the iron in the form of free ferritin molecules and lysosomally as aggregated ferritin and/or haemosiderin. The iron loading of the macrophages increased in both of the storage qualities proportionally with duration of the feeding period and reached a maximum after 38 weeks. Final stages showed extremely iron-loaded macrophages with high concentrations of free ferritin molecules and large siderosomes, partially flowing together to still greater units. Iron deposits within endothelial cells of bone marrow sinusoids can be observed for the first time after 4 weeks. In these cells the iron is stored as ferritin in siderosomes of relatively small and uniform size; free ferritin molecules in the cytosol were of only slight concentration. The TMH-ferrocene model of iron overload shows in the bone marrow: (1) an unimpeded utilization of the iron component for erythropoiesis, (2) development of excessive iron overload of the bone marrow in macrophages and endothelial cells of sinusoids and (3) a pattern of distribution of iron as seen in secondary haemochromatosis.

Iron-deficient female Wistar rats were fed a diet, which contained 0.5% trimethylhexanoylferrocene, over a 56-week period. This dietary iron loading resulted in a progressive siderosis and enlargement of the liver with a maximum iron content of 947.0 ± 148.0 mg (vs. 0.07 ± 0.04 mg in iron deficiency) and a maximum organ weight of 39.4 ± 6.6 g (vs. 6.9 ± 1.4 g in iron-deficient control rats). Up to 43 weeks, whole liver iron rose by increase in iron concentration (max. 28.0 ± 6.1 mg/g wet weight, w.w.) as well as by enlargement of the organ. Afterwards whole liver iron increased solely by ongoing hepatomegaly. At the commencement of iron loading, stainable iron was almost exclusively stored by hepatocytes equally throughout all areas of the liver lobule. Later, the distribution of iron-loaded hepatocytes became strikingly periportal, and, in addition, Kupffer cells as well as sinus-lining endothelia began to store iron. Animals with a liver iron concentration of more than 10.4 ± 0.75 mg/g w.w. showed no further increase in ferritin and haemosiderin within hepatocytes. Iron-burdened Kupffer cells/macrophages, however, accumulated permanently, hereby forming intrasinusoidal and portal siderotic nodules and areas. First signs of liver damage such as necrosis of single hepatocytes and mild fibrosis began at a liver iron concentration of 14.7 ± 1.4 mg/g w.w. With advancement of iron loading, focal necrosis of hepatocytes and iron-burdened macrophages took place, and significant perisinusoidal as well as portal fibrosis developed. Cirrhosis, however, the final stage of impairment in iron overload of the liver in humans, could not be induced in this animal model up to now.

In the HFE-gene era, precise diagnostic parameters remain important to characterize individual iron stores, because the indication for therapy and prognosis are mainly related to the extent of iron loading. The frequently used serum ferritin interferes with non-iron related factors such as inflammation and may produce falsely positive values. We used a SQUID-biosusceptometer in a large series of patients (n = 679) to measure liver iron concentration in the differential diagnosis and therapy control of hereditary hemochromatosis (SQUID = superconducting quantum interference device). This truly non-invasive technique is sensitive, reliable, fast (online results), and also cost-effective when compared to invasive liver biopsy. Recently, ferritin iron content was propagated as a better parameter than ferritin protein. However, we found a poor correlation between ferritin iron and individual liver iron concentrations in patients with iron overload. Ferritin iron saturation varied in a range between 3 and 10%, independent from liver iron concentration. No differences were found between patients with hemochromatosis and secondary iron overload disease. Only patients with liver cell damage had increased ferritin iron saturations. In conclusion the diagnostic values of serum ferritin protein and iron to assess iron overload are limited.

The iron content of serum ferritin has been determined in groups of patients with normal or increased iron stores by using a technique of ferritin immunoprecipitation followed by iron quantitation with atomic absorption spectroscopy. The results were correlated to individual liver iron concentrations, measured non-invasively by superconducting quantum interference device (SQUID) biomagnetometry. A close correlation between serum concentrations of ferritin protein and ferritin iron was found (r = 0.92) in all groups of patients. However, the correlation between ferritin iron concentration and individual liver iron concentration was poor in patients with hemochromatosis (r = 0.63) and patients with beta-thalassemia major (r = 0.57). The degree of ferritin iron saturation was about 5% in iron-loaded patients, which contrasts with results in two recent studies but confirms older observations. In patients with liver cell damage, the ferritin iron saturation in serum was significantly higher than that found in groups with iron overload disease, probably indicating the release of intracellular iron-rich ferritin into the blood. The monitoring of patients undergoing bone marrow transplantation indicated that the release of iron-rich and iron-poor ferritin occurred during phases of hepatocellular damage and inflammation, respectively. We find the benefits of serum ferritin iron measurement to be marginal in patients with iron overload disease.

Die Leber ist als zentrales Stoffwechselorgan zwischen Pfortader und unterer Hohlvene in den Blutkreislauf eingeschaltet. Auf diese Weise erhalt sie den grosten Teil ihres Blutes direkt vom Gastrointestinaltrakt, so das die meisten der dort resorbierten Nahrungsstoffe, Vitamine, Medikamente und Xenobiotika ihrer Kontrolle oder Verarbeitung unmittelbar unterliegen. Auserdem erfullt sie durch ihren hohen Gehalt an Makrophagen in der terminalen Strombahn der Sinusoide eine wichtige Filterfunktion fur Endotoxine und Keime aus dem Darm.

Seit der 1. Auflage dieses Bandes hat die Hepatologie eine gewaltige Entwicklung auf vielen Gebieten erfahren. Der enorme Aufschwung der Laparoskopie und Endoskopie, die Forschungsergebnisse der Virologie und Immunologie sowie die neuen Methoden der Molekularbiologie und Genetik haben fur die Klassifikation, Therapie und Prognose der Krankheiten der Leber- und Gallenwege neue Akzente gesetzt. Insgesamt liegt ein aktueller, mit modernen Methoden durchgefuhrter, durch instruktives Bildmaterial dokumentierter Band vor, der eine prazise informative Zusammenschau fur den Kliniker und Pathologen uber die vielfaltigen Erkrankungen der Leber und Gallenwege vermittelt."

Because of their oxygen binding capacity, cell-free hemoglobin solutions are promising blood substitutes. However, their clinical use has so far been limited by toxic side effects on liver and kidney until ultrapurification and chemical modifications have been established in the production process of hemoglobin-based oxygen carriers. The present study has been designed to examine structural changes of liver and kidney by light and electron microscopy after complete isovolemic blood exchange with a new ultrapurified bovine hemoglobin solution (UPBH-2) in eight beagle dogs. The results have been compared with a sham-operated control and eight animals having undergone blood exchange with hydroxyethyl starch (HES), a clinically used colloidal volume substitute. In the kidney, no changes were observed after blood exchange with UPBH-2 as compared with the sham control. These findings indicate sufficient tissue oxygenation and lack of renal toxicity. In contrast, histological signs of severe proximal tubular damage, eg, wide lumina, cytoplasmic protrusions, brush-border defects, and tubular necroses, were seen after blood exchange with HES. These changes are consistent with hypoxic tissue damage. In the liver, a slight increase in the number of single cell necroses was observed after UPBH-2 treatment as well as after blood exchange with HES. At the ultrastructural level, partial loss of microvilli and cytoplasmic protrusions of hepatocytes as well as swelling of endothelial cells were present in both groups, but slightly more pronounced in the UPBH-2 group. In all UPBH-2-treated animals, a marked diminution of glycogen-granula in hepatocytes was observed indicating an influence of UPBH-2 upon glycogen metabolism. Whereas the alterations of hepatocytes after nearly complete blood exchange with HES can be interpreted as a consequence of tissue hypoxia, the ultrastructural changes after UPBH-2 treatment cannot be attributed to hypoxic conditions, because improved tissue oxygenation has been demonstrated during treatment with UPBH-2. Hepatocyte damage was very discrete and comparable with the alterations observed after HES treatment. Hence, major hepatotoxicity can be excluded. The absence of significant adverse effects on the ultrastructural integrity of the kidney indicates that UPBH-2, owing to ultrapurification and polymerization, is an oxygen-carrying hemoglobin without acute renal toxicity.

Female Wistar rats with slight iron deficiency anemia were kept on a diet containing 0.5% trimethylhexanoyl (TMH)-ferrocene for up to 79 weeks. In the state of iron deficiency, the heart was free of light-microscopically detectable iron. After 7 weeks of the TMH-ferrocene diet, the first iron-positive granules appeared in perivascular macrophages. Further oral administration caused a progression of iron deposition in these cells, visible in the form of a granular staining but also as a diffuse iron staining of the cytoplasm. Accordingly, at the electron-microscopical level, the iron was stored partly as free ferritin molecules in the cytosol, and partly in lysosomes in the form of ferritin and/or hemosiderin. After 11 weeks, further iron-positive cells with relatively small dark-blue granules were found in the vicinity of capillaries, which could be identified as fibrocytes by means of electron microscopy. In addition, slight iron deposition occurred in the endothelial cells of the cardiac capillaries, likewise mainly in the form of small, uniform siderosomes. The myocytes showed no product of Perls’ Prussian blue reaction during the whole period of investigation. From the 11th week onwards, discrete ferritin molecules were detected electron microscopically within lysosomes of these cells. Their amount increased slowly with progression of the TMH-ferrocene feeding period. Free ferritin molecules could be observed in the cytosol of fibrocytes, endothelial cells and myocytes in only very slight concentrations, whilst they were more plentiful in macrophages. In hereditary hemochromatosis and posttransfusional siderosis, the iron is found predominantly in myocytes and appears to cause cell damage, whilst this is not the case in experimental iron overload in rats.

1. The use of carbonyl-iron and (3,5,5-trimethylhexanoyl)-ferrocene (TMH-ferrocene) as a dietary iron-overload model was studied in rats using 59 Fe-labelled compounds. 2. The intestinal absorption of carbonyl-iron but not from the TMH-ferrocene-iron was dependent upon the dosage and downregulated in iron-loaded rats. 3. In both models, and similar to hereditary haemochromatosis in humans, the storage of excess iron in the liver started in hepatocytes, whereas the range of iron-loading was strikingly different. 4. Because of the fast and progressive iron-loading, the TMH-ferrocene-model is the most encouraging animal model for experimental haemochromatosis.

The light and electronmicroscopic representation of non-haemiron in the bone-marrow provides the unique opportunity of extensively evaluating the iron metabolism. In the bone-marrow, macrophages represent the physiological place of iron storage. The iron in the cytoplasma is stored in them in the form of free ferritin molecules and lysomally as aggregated ferritin and/or haemosiderin in siderosomes. In an equal iron balance and unimpaired internal iron exchange only erythroblasts (sideroblasts) and erythrocytes (siderocytes) of the bone-marrow besides macrophages possess siderosomes. In addition to this physiological or orthotopic iron storage a heterotopic iron storage can be observed under pathological conditions, particularly with iron overloading of the organism, in the endothelial cells of sinusoids and plasma cells. In detail, the patterns of iron storage in the bone-marrow are described in the different stages of iron deficiency, disturbance of iron utilization in chronically inflammatory processes or tumour diseases, condition after intravenous iron administration, transfusion siderosis, hereditary haemochromatosis and sideroblastic anaemia.

In secondary haemochromatosis up to fourfold higher amounts of iron are tolerated in the organism than in primary (hereditary) haemochromatosis. This is connected with the marked iron storage of macrophages in secondary iron overloading, which is relatively without any dangers. In primary haemochromatosis, however, a relative insufficiency of storage of extrahepatic macrophages can be observed for iron, a fact which favours a premature parenchymatous iron storage leading to organ lesions. Because of the discrepant behaviour of macrophages characteristic, diagnostically relevant differences will occur in the pattern of iron storage in the bone-marrow, spleen and small intestine between primary and secondary haemochromatosis.

Das Knochenmark der Ratte wurde impulscytophotometrisch, histologisch und cytologisch nach Daunomycinapplikation untersucht. 24 Std p.i. zeigt sich impulscytophotometrisch eine Ansammlung von Zellen in der G2-Phase (29% Zellen in G2 + M gegenuber 12% bei den Kontrollen) und eine Abnahme der G1-Zellen auf 53% gegenuber 65% bei den Kontrollen. Die Verminderung des Anteils der Zellen in G1 hat als morphologisches Substrat eine auffallende Reduzierung kernhaltiger Vorstufen der Erythropoese. Der G2-Block wird morphologisch nicht erkannt. Im weiteren Verlauf (48–120 Std p.i.) sieht man impulscytophotometrisch eine Vermehrung des Anteils von Zellen in der S-Phase. Dieser Befund wird als Regenerationsphanomen nach Cytostaticawirkung gedeutet und geht morphologisch mit einem promyelocytaren Knochenmarksbefund einher.

Untersucht wurde die markhaltige periphere Nervenfaser mit Hilfe der sog. Semidunnschnittechnik. Die Untersuchungen wurden am N. ischiadicus der Ratte durchgefuhrt und durch elektronenmikroskopische Befunde erganzt. Besondere Aufmerksamkeit galt der paranodalen Region und den Schmidt-Lantermannschen Einkerbungen.

Am N. ischiadicus von Rhesusaffen und Frosch wurden Verteilung und Vorkommen der Schmidt-Lantermanschen Einkerbungen in Abhangigkeit von der Markscheidendicke mit einem Teilchengrosenanalysator bestimmt. Dazu wurden die Markscheiden in Klassen mit exponentiell zunehmendem Durchmesser eingeteilt. Die Anzahl der Einkerbungen pro Langeneinheit nimmt mit wachsender Markscheidendicke zu. Diese Berechnungen aufgrund der Zahlungen an Querschnittsbildern wurden moglich, da sich der Winkel unter dem die Einkerbungen die Markscheide durchziehen, bei allen Markscheidendurchmessern als konstant erwies. Diese Tatsache ermoglichte die Berechnung der Hohe der Einkerbungen und ihrer durchschnittlichen Abstande in der jeweiligen Durchmesserklasse der Markscheide. Die Durchmesser der Markscheiden des N. ischiadicus von Rhesusaffen und Frosch weisen eine dreigipflige Verteilung auf, die beim Frosch starker ausgepragt ist. Der Frosch besitzt insgesamt geringere Markscheidendurchmesser als der Rhesusaffe. Bei beiden ist die Haufigkeit der Schmidt-Lantermanschen Einkerbungen aber ausschlieslich von der Dicke der Markscheiden abhangig; in den einzelnen Dickenklassen ergeben sich kaum Unterschiede. Damit erweisen sich die Einkerbungen als spezifische Strukturen der Markscheide, die weder von der unterschiedlichen phylogenetischen Stellung der Arten noch von deren physiologischen Besonderheiten abhangen.

69 patients (median age 53 years, 19-79 years old) with untreated acute non-lymphoblastic leukemia (ANLL) were randomized to receive either a regimen of amsacrine, cytarabine, thioguanine (AAT) or daunorubicin, cytarabine, thioguanine (DAT). AAT consisted of amsacrine 200 mg/m2/day x 5, thioguanine 100 mg/m2/12 h p.o. x 10; DAT was daunorubicin 50 mg/m2/day x 3, cytarabine 200 mg/m2/day x 5, thioguanine 100 mg/m2/12 h p.o. x 10. After one or two induction courses the patients subsequently received 2 consolidation courses. 17 patients were not assessable for response to therapy due to exitus during induction treatment. Complete remission could be obtained in 14/24 (58%) of DAT patients respectively. Patients less than 60 years of age achieved CR in 63% (AAT) vs 65% (DAT), whereas patients greater than or equal to 60 years obtained a CR in 50% (AAT) vs 13% (DAT). Toxicity appears not to be increased significantly with amsacrine. These data indicate that amsacrine could replace daunorubicin in remission induction regimens of ANLL containing cytosin arabinoside and thioguanine without decreasing the response rate.

69 patients (median age 53 years, 19-79 years old) with untreated acute non-lymphoblastic leukemia (ANLL) were randomized to receive either a regimen of amsacrine, cytarabine, thioguanine (AAT) or daunorubicin, cytarabine, thioguanine (DAT). AAT consisted of amsacrine 200 mg/m2/day x 5, thioguanine 100 mg/m2/12 h p.o. x 10; DAT was daunorubicin 50 mg/m2/day x 3, cytarabine 200 mg/m2/day x 5, thioguanine 100 mg/m2/12 h p.o. x 10. After one or two induction courses the patients subsequently received 2 consolidation courses. 17 patients were not assessable for response to therapy due to exitus during induction treatment. Complete remission could be obtained in 14/24 (58%) of DAT patients respectively. Patients less than 60 years of age achieved CR in 63% (AAT) vs 65% (DAT), whereas patients greater than or equal to 60 years obtained a CR in 50% (AAT) vs 13% (DAT). Toxicity appears not to be increased significantly with amsacrine. These data indicate that amsacrine could replace daunorubicin in remission induction regimens of ANLL containing cytosin arabinoside and thioguanine without decreasing the response rate.

Radioimmunologische Serumferritinbestimmungen erleichtern den Nachweis erschopfter Eisenreserven in der Diagnostik des Eisenmangels und seiner Abgrenzung gegenuber Infekt- und Tumoranamien. Die Ergebnisse verschiedener Untersucher lassen sich jedoch nur grob vergleichen, da die Methoden nicht standardisiert und die Normbereiche uneinheitlich definiert sind. Wenn in den Kontrollgruppen Personen mit pralatentem (Speicher-) Eisenmangel ausgeschlossen werden, wird man die hierdurch bereinigte untere Normgrenze zwischen 20 und 40 μg/1 und die obere Grenze nach Berucksichtigung zunehmender Werte im Alter zwischen 300 und 500 μg/1 Serumferritin ansetzen konnen. Fur Manner werden Mittelwerte zwischen 50 und 208 μg/1, fur Frauen zwischen 26 und 166 μg/1 angegeben.

In the bone marrow of two patients with acute leukemia 46% and 55% of atypical eosinophilic cells were found, respectively. Blood eosinophilia was absent. The N-AS-D-Cl-Esterase reaction of the granules was positive in the first case in 58%, and in the second case in 3% of the eosinophils, as well as the PAS-reaction in all cells of this series. The ultrastructure of the eosinophils reveals nuclear maturation up to hypersegmentation. The maturation of the granules, in part of abnormal size, is arrested at the primary stage. Typical secondary granules with cristalloid cores are lacking. Only in the first case a few, small, semicircular or circular profiles of lamellar substructure are seen in the granules. The cytoplasm of hypersegmentated eosinophils shows an abnormally high glycogen content. Besides the eosinophils, monocytic cells and their precursors proliferate in the bone marrow of the first patient. In the second patient myeloblasts, promyelocytes with Auer rods, and monocytic cells characterize further neoplastic cell population. The elements of the monocytic series can be identified by their ultrastructural features, such as irregular configuration of the nuclei, bundles of cytoplasmatic microfilaments, and numerous small electron-dense lysosomal granules. In both cases the Alpha-Naphthyl-Acetase-Esterase reaction is weakly positive. The findings presented are summarized under the terms "eosinophil-monocytic leukemia" and "eosinophil-myelomonocytic leukemia" (collective term).

The course of hairy cell leukaemia was observed in 27 patients for a maximum of 97 months. Splenectomy had been performed in 17 patients and improved the haematological situation impressively in most cases. Amongst patients with splenectomy ten are alive with 8 to 88 months postoperatively. In five of them disease manifesting as isolated leucocytosis, deterioration of the overall haematological situation or as intraabdominal lymphomatous growth could be treated successfully. Treatment consisted of leucapheresis, low-dose long-term therapy with chlorambucil, administration of doxorubicin (adriamycin) or a combination of cytostatics containing doxorubicin as well as abdominal localized or overall irradiation.

Die Ergebnisse zahlreicher Untersucher stimmen darin uberein, das das Serumferritin bei definierten Krankheitsbildern mit Eisenuberladung die Grosenordnungen des Speichereisens widerspiegelt. Die Relationszahlen von Serumferritin in μg/1 zu Speichereisen in mg werden von einigen Autoren mit 1:8 oder 1:10 angegeben. Diese Angabe ist zu erweitern auf einen Streubereich von 1:2 bis 1:20 mit Mittelwerten von 1:5 bis 1:10. Dieser grose Streubereich ist nur zum Teil auf methodische Unterschiede zuruckzufuhren. Eine wesentliche Rolle spielt der Zeitpunkt der Messung zur jeweiligen klinischen Situation (vorangegangene Transfusionen, Aderlasse, hamolytische Aktivitat), denn Eisenumverteilungen konnen zu kurzfristigen Hyper- und Hypoferritinanamien fuhren.

Seit Einfuhrung der immunoradiometrischen Ferritinbestimmung im Serum haben zahlreiche Untersucher [4, 7] eine enge Korrelation zwischen dem Serumferritinspiegel und dem Speichereisen gefunden. Die Serumferritinbestimmung gewinnt deswegen zunehmend an Bedeutung als ein zusatzliches diagnostisches Kriterium des Eisenstoffwechsels. Nach Jacobs [7] entspricht 1 μg Serumferritin 8 mg Speichereisen. Wieweit diese Relation auch uber einen groseren Krankheitsbereich mit anderen Kriterien des Eisenstatus — insbesondere dem cytochemischen Nicht-Hamoglobineisen des Knochenmarks und den histochemischen Befunden von Leber und Milz — vergleichbar ist, erscheint bisher nicht eindeutig geklart.

Die Anwendung der zytostatisch wirksamen Alkaloide der Vinca rosea, insbesondere des Vincristinsulfat, ist mit neurologischen Komplikationen in Form von Polyneuropathien belastet. Distal betonte Paraesthesien werden in fast jedem Fall beobachtet. Starkere sensible und motorische Ausfalle zwingen haufig zum Abbruch einer Behandlung.