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Both hydrogen and natural gas engines with an effective power of more than 400 kW can be tested under transient operation with the recently developed test bench. By means of the Road Load Simulation software package the longitudinal vehicle dynamics can be investigated already on the engine test bench. Furthermore, any driving cycles can be defined and redriven afterwards. The hydrogen storage volume allows several hours of full-load operation of heavy-duty truck engines. This paper only concentrates on the hydrogen-specific features and hardware of the test bench.

One hundred twenty-one anemic, transfusion-dependent patients with multiple myeloma (MM) or low-grade non-Hodgkin's lymphoma (NHL) were randomly allocated to receive (a) recombinant human erythropoietin (rhEPO) 10,000 U/d subcutaneously 7 days a week (fixed dose group) (n = 38), or (b) rhEPO 2,000 U/d subcutaneously for 8 weeks followed by step- wise escalation of the rhEPO dose (titration group) (n = 44), or (c) no rhEPO therapy (control group) (n = 39). The total treatment period was 24 weeks. There were no differences between the three groups with regard to baseline clinical, demographic, or health status measures. The cumulative response frequency, defined as elimination of the transfusion need in combination with an increase in the hemoglobin concentration by >20 g/L, was 60% in both rhEPO treatment groups and 24% in the control group (P = .01 and .02, respectively, log rank test). For patients in the titration group the response rate on the first dose level (2,000 U/d) was only 14%. Cox's univariate regression analysis revealed that an inadequately low endogenous erythropoietin concentration in relation to the degree of anemia and a baseline platelet concentration > or = 100 x 10(9)/L were significant predictors for response to rhEPO therapy (P < .01). Multivariate regression analysis showed that relative erythropoietin concentration was the most important factor and the platelet count had no additional influence on response. Treatment with rhEPO was well tolerated. We conclude that treatment with rhEPO may be indicated in anemic MM and NHL patients with a relative erythropoietin deficiency. An initial dose of 5,000 U/d subcutaneously may be recommended.

Previous phase I-II clinical trials have shown that recombinant human erythropoietin (rHuEpo) can ameliorate anemia in a portion of patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). Therefore, we performed a randomized controlled multicenter study to define the optimal initial dosage and to identify predictors of response to rHuEpo. A total of 146 patients who had hemoglobin (Hb) levels < or = 11 g/dL and who had no need for transfusion at the time of enrollment entered this trial. Patients were randomized to receive 1,000 U (n = 31), 2,000 U (n = 29), 5,000 U (n = 31), or 10,000 U (n = 26) of rHuEpo daily subcutaneously for 8 weeks or to receive no therapy (n = 29). Of the patients, 84 suffered from MM and 62 from low- to intermediate- grade NHL, including chronic lymphocytic leukemia; 116 of 146 (79%) received chemotherapy during the study. The mean baseline Hb level was 9.4 +/- 1.0 g/dL. The median serum Epo level was 32 mU/mL, and endogenous Epo production was found to be defective in 77% of the patients, as judged by a value for the ratio of observed-to-predicted serum Epo levels (O/P ratio) of < or = 0.9. An intention-to-treat analysis was performed to evaluate treatment efficacy. The median average increase in Hb levels per week was 0.04 g/dL in the control group and -0.04 (P = .57), 0.22 (P = .05), 0.43 (P = .01), and 0.58 (P = .0001) g/dL in the 1,000 U, 2,000 U, 5,000 U, and 10,000 U groups, respectively (P values versus control). The probability of response (delta Hb > or = 2 g/dL) increased steadily and, after 8 weeks, reached 31% (2,000 U), 61% (5,000 U), and 62% (10,000 U), respectively. Regression analysis using Cox's proportional hazard model and classification and regression tree analysis showed that serum Epo levels and the O/P ratio were the most important factors predicting response in patients receiving 5,000 or 10,000 U. Approximately three quarters of patients presenting with Epo levels inappropriately low for the degree of anemia responded to rHuEpo, whereas only one quarter of those with adequate Epo levels did so. Classification and regression tree analysis also showed that doses of 2,000 U daily were effective in patients with an average platelet count greater than 150 x 10(9)/L. About 50% of these patients are expected to respond to rHuEpo. Thus, rHuEpo was safe and effective in ameliorating the anemia of MM and NHL patients who showed defective endogenous Epo production. From a practical point of view, we conclude that the decision to use rHuEpo in an individual anemic patient with MM or NHL should be based on serum Epo levels, whereas the choice of the initial dosage should be based on residual marrow function.

Background : Anemia in patients with myelodysplastic syndromes (MDS) is usually put down to ineffective erythropoiesis, although the contributory role of other mechanisms has not bee

Background: A clinical phase II study with a topical formulation of hexadecylphosphocholine (Miltefosine solution 6%) was performed in patients with skin-metas-tasized or locally re

Follow-up data of 320 multiple myeloma (MM) patients entering the German Myeloma Treatment Group (GMTG) trial MM01 were analysed for factors predicting overall (OAS) and tumour related survival (TRS). Response to primary induction chemotherapy was relevant for prognosis if a limit of 25% tumour cell mass (TCM) reduction was used to separate responders from non-responders. Furthermore, TCM, histological grading of myeloma cells, degree of bone marrow infiltration, haemoglobin, platelet counts, calcium, creatinine, albumin, beta 2M, and Bence Jones proteinuria correlated to both OAS and TRS. Age was relevant for OAS only. The multivariate analysis revealed histological grading, TCM and platelets as the most reliable prognostic factors. Based on these data the Durie/Salmon classification could be improved by defining poor prognosis patients (50% TRS: 16 months) characterised by pretreatment platelets of < or = 150,000 and/or poorly differentiated myeloma cell morphology. Patients lacking both risk factors displayed 50% survival times of 46 months in stage III and 88 months in stage II.

A clinical phase II trial with an oral formulation of miltefosine (MIL) was performed in patients with non-small cell lung cancer (NSCLC). Eligibility criteria for this phase II study included histolo

Nach heutigem Kenntnisstand mus bei jeder unvollstandigen Verbrennung, die im Beisein halogenierter Verbindungen ablauft, mit der Entstchung von polyhalogenierten Dibenzodioxinen und Dibenzofuranen (PXDD/PXDF) gerechnet werden. Bestechenden Anzeichen, das auch Verbrennungsmotoren diese Substanzen im Spurenbereich emittieren, mus man Bedeutung beimessen. Da es bisher nur stichprobenartige Untersuchungen des Kfz-Verkehrs gab, hat der Bundesminister fur Forschung und Technologie (BMFT) gemeinsam mit der Deutschen Wissenschaftlichen Gesellschaft fur Mineralolwirtschaft und Kohlechemie e.V. (DGMK) sowie der Forschungsvereinigung Verbrennungskraftmaschinen e.V. (FVV) zur Klarung dieser Frage umfangreiche Forschungsarbeiten durchfuhren lassen. Die Ergebnisse des seit Juli 1987 geforderten Verbundforschungsvorhabens “Untersuchungen zur Emission halogenierter Dibenzodioxine und Dibenzofurane aus Verbrennungsmotoren beim Betrieb mit handelsublichen Betriebsstoffen” fuhrten schlieslich zu dem Entwurf einer“Verordnung uber ein Verbor der Scavenger im bleihaltigen Benzin”, der z.Z. auf seine Verabschiedung wartet. Partner der Untersuchung waren das Institut fur Verbrennungsmotoren und Kraftfahrwesen der Universitat Stuttgart fur den motorischen Teil, das Institut fur Organische Chemie der Universitat Tubingen und der Lehrstuhl fur Okologische Chemie und Geochemie der Universitat Bayreuth fur den analytischen Teil sowie die Deutsche Gesellschaft fur Mineralolwirtschaft und Kohlechemie e.V. fur die begleitende Analytik der Mineralolprodukte. Ausgangslage fur die Untersuchungen war, das polychlorierte Dibenzodioxine und Dibenzofurane aus Verbrennungsmotoren nur dann auftreten, wenn uber mindestens einen der drei Wege—Ansaugluft, Motorol, Kraftstoff—chlorhaltige Verbindungen in den Brennraum gelangen. Wahrend uber Ansaugluft und Motorol nur Spuren von Halogenverbindungen in den Brennraum gelangen, ist beim Motorbetrieb mit verbleitem Ottokraftstoff uber die sog. Scavenger ein relativ hoher Eintrag dieser Verbindungen gegeben. Scavenger sind chlor-und bromhaltige Zusatze, deren Aufgabe es ist, Bleiablagerungen im Brennraum durch die Einbindung von Bleihalogeniden zu verhindern. Sie werden als leichte fluchtige Verbindungen schneller aus dem Motorbrennraum mit dem Abgas ausgetragen. (Bleizusatze haben die Aufgabe, den Motor zu schonen und seine “Lebenszeit” zu verlangern.) Unverbleite Ottokraftstoffe und Dieselkraftstoffe enthalten dagegen Halogenverbindungen allenfalls im Spurenbereich. Ziel des bis Ende 1990 gelaufenen Forschungsvorhabens war es, den Halogeneintrag und die Freisetzung bestimmter halogenierter Kohlenwasserstoffe aus den VerbrennungsmotorentypenOttomotor, Personenkraftwagen-Dieselmotor undNutzfahrzeug-Dieselmotor zu untersuchen. Fur diese Untersuchungen werden Motorole sowie Otto- und Dieselkraftstoff handelsublicher Marktqualitaten (Erstraffinate) eingestzt. Die Versuche an den Fahrzeugmotoren erfolgten uberwiegend auf demMotorenprufstand unter reprasentativen Betriebsbedingungen. Erganzend fanden Fahrzeuguntersuchungen auf demRollenprufstand statt. Bei Betrieb desOttomotors mitverbleitem, d.h. Scavenger-haltigen Ottokraftstoff wurden im Abgas uberwiegendgemischthalogenierte undbromierte Dioxine und Furane nachgewiesen. Die Summe dieser Emissionen kann bis zu mehreren 1000 ng/m3 betragen. Es wurden vorwiegend Mono-bis Trichlor-bzw. Mono-bis Tribrom-dibenzodioxine und-dibenzofurane gefunden. Die toxikologisch bedeutsamen Tetra-bis Octachlor-dibenzodioxine und-dibenzofurane machen nur einen untergeordneten Anteil (1/100 bis 1/1000) an der Summe der freigestzten Dioxine und Furane aus. Die Emissionskonzentrationen derchlorierten Dioxine (berechnet als Toxizitatsaquivalente nach den vom Bundesgesundheitsamt vorgeschlagenen Gewichtsfaktoren) liegen im Bereich von 0,1 ng/m3. Im Betrieb mitunverbleitem, d.h. Scavenger-freiem Ottokraftstoff entstehen dagegen bedeutend weniger Dioxine. Die Gesamtemission betragt dabei deutlich weniger als ein Zehntel der Summenemission beim Betrieb mit ver bleitem Kraftstoff. Aufgrund dieser Ergebnisse darf deshalb als gesichert angesehen werden, das die Hauptmenge der Dioxine und Furane beim Motorbetrieb mit verbleitem Ottokraftstoff aus den als Scavenger zugesetzten Chlor-und Bromwverbindungen entsteht. ImKatalysatorbetreib liegen die Gesamtemissionen gegenuber denen mit unverbleitem Ottokraftstoff nochmals um den Faktor 10 niedriger. BeimDieselmotor wurden fur die freigesetzten Dioxine und Furane die gleichen niedrigen Werte wie fur den Ottomotor mit Katalysator gemessen. Der Hauptteil der Dioxinemissionen des Kraftfahrzeugverkehrs wird demnach durch Ottomotoren verursacht, die mit bleihaltigem, d.h. momentan noch Scavenger-haltigem, Kraftsoff betrieben werden.

In einer multizentrischen Studie wird gepruft, ob der Einsatz von Hydroxyurea oder von Interferon alpha anstatt von Bulsulfan die Dauer der chronischen Phase bei Patienten mit Philadelphia-Chromo-som-positiver CML verlangert. Zusatzliche Ziele sind die Prufung, ob sich der Typ der Krankheitsevolution und die terminalen Phasen bei den verschiedenen Therapiegruppen unterscheiden, sowie die pro-, spektive Erkennung von Prognosekriterien fur die Dauer der chronischen Phase. Bis zum 5.9.1990 waren 593 CML-Patienten randomisiert, 221 fur Busulfan, 228 fur Hydroxyurea und 144 fur Interferon alpha. Das Durchschnittsalter aller Patienten liegt bei etwa 51 Jahren. Bis zum Stichtag am 30.4.1990 hatten 106 Patienten das Ende der chronischen Phase erreicht, 126 waren verstorben. Die mediane Uberlebenszeit der Philadelphia-positiven Patienten betrug 3,95 Jahre, die aller Patienten 3,75 Jahre. Die mittlere Beobachtungszeit betrug 1,34 (1,60) Jahre. Erwartungsgemas besteht bisher noch kein signifikanter Unterschied zwischen den drei Studienarmen, wenn auch im Hydroxyurea-Arm weniger Nebenwirkungen beobachtet wurden.

One hundred twenty-one anemic, transfusion-dependent patients with multiple myeloma (MM) or low-grade non-Hodgkin's lymphoma (NHL) were randomly allocated to receive (a) recombinant human erythropoietin (rhEPO) 10,000 U/d subcutaneously 7 days a week (fixed dose group) (n = 38), or (b) rhEPO 2,000 U/d subcutaneously for 8 weeks followed by step-wise escalation of the rhEPO dose (titration group) (n = 44), or (c) no rhEPO therapy (control group) (n = 39). The total treatment period was 24 weeks. There were no differences between the three groups with regard to baseline clinical, demographic, or health status measures. The cumulative response frequency, defined as elimination of the transfusion need in combination with an increase in the hemoglobin concentration by20 g/L, was 60% in both rhEPO treatment groups and 24% in the control group (P = .01 and .02, respectively, log rank test). For patients in the titration group the response rate on the first dose level (2,000 U/d) was only 14%. Cox's univariate regression analysis revealed that an inadequately low endogenous erythropoietin concentration in relation to the degree of anemia and a baseline platelet concentrationor = 100 x 10(9)/L were significant predictors for response to rhEPO therapy (P.01). Multivariate regression analysis showed that relative erythropoietin concentration was the most important factor and the platelet count had no additional influence on response. Treatment with rhEPO was well tolerated. We conclude that treatment with rhEPO may be indicated in anemic MM and NHL patients with a relative erythropoietin deficiency. An initial dose of 5,000 U/d subcutaneously may be recommended.

Previous phase I-II clinical trials have shown that recombinant human erythropoietin (rHuEpo) can ameliorate anemia in a portion of patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). Therefore, we performed a randomized controlled multicenter study to define the optimal initial dosage and to identify predictors of response to rHuEpo. A total of 146 patients who had hemoglobin (Hb) levelsor = 11 g/dL and who had no need for transfusion at the time of enrollment entered this trial. Patients were randomized to receive 1,000 U (n = 31), 2,000 U (n = 29), 5,000 U (n = 31), or 10,000 U (n = 26) of rHuEpo daily subcutaneously for 8 weeks or to receive no therapy (n = 29). Of the patients, 84 suffered from MM and 62 from low- to intermediate-grade NHL, including chronic lymphocytic leukemia; 116 of 146 (79%) received chemotherapy during the study. The mean baseline Hb level was 9.4 +/- 1.0 g/dL. The median serum Epo level was 32 mU/mL, and endogenous Epo production was found to be defective in 77% of the patients, as judged by a value for the ratio of observed-to-predicted serum Epo levels (O/P ratio) ofor = 0.9. An intention-to-treat analysis was performed to evaluate treatment efficacy. The median average increase in Hb levels per week was 0.04 g/dL in the control group and -0.04 (P = .57), 0.22 (P = .05), 0.43 (P = .01), and 0.58 (P = .0001) g/dL in the 1,000 U, 2,000 U, 5,000 U, and 10,000 U groups, respectively (P values versus control). The probability of response (delta Hbor = 2 g/dL) increased steadily and, after 8 weeks, reached 31% (2,000 U), 61% (5,000 U), and 62% (10,000 U), respectively. Regression analysis using Cox's proportional hazard model and classification and regression tree analysis showed that serum Epo levels and the O/P ratio were the most important factors predicting response in patients receiving 5,000 or 10,000 U. Approximately three quarters of patients presenting with Epo levels inappropriately low for the degree of anemia responded to rHuEpo, whereas only one quarter of those with adequate Epo levels did so. Classification and regression tree analysis also showed that doses of 2,000 U daily were effective in patients with an average platelet count greater than 150 x 10(9)/L. About 50% of these patients are expected to respond to rHuEpo. Thus, rHuEpo was safe and effective in ameliorating the anemia of MM and NHL patients who showed defective endogenous Epo production. From a practical point of view, we conclude that the decision to use rHuEpo in an individual anemic patient with MM or NHL should be based on serum Epo levels, whereas the choice of the initial dosage should be based on residual marrow function.

From July 1983 to January 1991 a total of 622 patients were randomized (585 eligible) to compare the effects of hydroxyurea, interferon alpha (IFN), and busulfan on the duration of chronic phase, and survival. Further goals included the determination of prognostic parameters. 598 CML patients were documented and 575 evaluable. The Ph-status was known for 547 patients. 89.4% of the patients were Ph-positive (+). 11% had additional chromosome aberrations. The median survival of Ph+ patients by now is 4.2 years, that of Ph-patients 1.4 years. Ph-negative patients are older, tend to have lower cell counts and, as a group are more ill at diagnosis. A survival difference of about one year is expected between busulfan and hydroxyurea treated patients. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, number of erythroblasts and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined which was superior to Sokal's score in the study population. 164 patients were randomized to receive IFN. In 54 patients (33%) IFN had to be terminated because of adverse effects, therapy resistance or other reasons. Clinically relevant neutralizing antibodies were detected in 9 cases. Most frequent adverse events were flu-like symptoms in 74%, gastrointestinal symptoms in 52%, and neurologic-psychiatric symptoms in 30% of patients. Reduction of the Ph-chromosome was observed in 13% of evaluable patients (10 of 75). In 4 patients complete cytogenetic remissions were observed, in three of these ongoing. Cytogenetic responders have a survival advantage. Interferon treated Philadelphia-negative CML patients have no survival disadvantage. The study is expected to allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers.

Recent developments in CML research are illustrated by the results of one large randomized multicenter study carried out by the German CML Study Group. From July 1983 to January 1991, a total of 703 CML patients were recruited; 624 patients were randomized to compare hydroxyurea and interferon alpha (IFN) with busulfan. The median survival of Ph+ patients by now is 3.95 years, that of Ph- patients 1.1 years. Some difference in survival is recognizable between the treatment arms, but this is not yet significant. Fewer adverse effects are being observed in the hydroxyurea group. Ph-negative patients tend to have lower white blood cell and platelet counts. Patients (164) were randomized to receive IFN. In 50 patients (30%) IFN had to be terminated because of adverse effects, therapy resistance, or other reasons. Reduction of the Ph-chromosome was observed in 20% of evaluable patients. In 3 patients complete cytogenetic remissions were observed. Clinically relevant neutralizing antibodies were detected in 9 cases. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, erythroblasts, and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined and compared to Sokal's score. It is expected that the study results will allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers.

Pirarubicin is a more lipophilic derivative of doxorubicin, with a higher uptake rate of cells, lower cardiotoxicity and better antitumor efficacy in preclinical models. Thirty-four patients with metastatic breast cancer were treated in a multicenter phase II study with pirarubicin (THP) using a dosage of 75 mg/m2/every 3 weeks. The patients had a median age of 56 years (range 41-73) and a performance status of WHO grade 0-2. Patients pretreated with anthracyclines, or who were older than 75 years and without sufficient bone marrow reserve were excluded. The 32 evaluable patients received a median number of 4 cycles (range 2-8). The myelosuppression was dose-limiting and led to infections (grades 1 and 2) in 5 patients. Twenty-eight patients developed leukocytopenia grade 3 and 4 toxicity and 7 patients experienced thrombocytopenia grade 1 and 2. The drug was subjectively well tolerated and nausea, vomiting and alopecia were mild. One complete remission with a duration of 15.4 months (67 weeks) and 7 partial remissions with a median duration of 9.3 months (40 weeks) were achieved, which resulted in an overall response rate of 25%. Twenty-one patients were stable for 17 weeks (median) under the treatment with pirarubicin.

Fur die palliative Therapie wahrend der chronischen Phase der CML hat sich Busulfan als Medikament der Wahl erwiesen. In den letzten Jahren haben Hydroxyurea und auch Interferon-alpha zunehmende Bedeu

Die Injektion von Serum von Patienten mit chronischem myeloproliferativem Syndrom (Polycythaemia vera, Osteomyelofibrose, chronischer Myelose) und Serum von letal bestrahlten Ratten vor Injektion einer einzelnen Dosis Erythropoetin, verstarkt die Wirkung dieser Erythropoetindosis — gemessen mittels der Eiseneinbaurate polyglobuler Mause — nicht.

Zur Frage einer toxischen Wirkung hohermolekularer Urinmetabolite durch Retention bei Uramie wurde der Effekt auf Lymphozytentransformation und Autohamolyse inkubierter Erythrozyten untersucht. Nach viertagiger Dialyse gegen Wasser wurde das lyophilisierte, nicht dialysable Retentat aus dem 24 Std Urin gesunder Personen mit einer Konzentration von 2,22 mg/ml in Medium TC 199 bzw. physiologischer Kochsalzlosung gelost und davon steigende Mengen (0,1 bis 1,0 ml) Lymphozytenkulturen (3 × 106 Zellen in 4 ml Medium) und Erythrozyten (3 ml Vollblut nach Separation der Granulozyten) von 6 gesunden Blutspendern zugesetzt. Die durch Messung des3H-Thymidineinbaus nach funftagiger Inkubation ermittelte spontane Lymphozytentransformation zeigte eine deutliche, dosisabhangige Hemmung bis auf 30,4% des Ausgangswertes, wahrend der Abfall nach Stimulation mit 400 µg PHA nur bis 65,2% nachweisbar war. Die als Parameter des Zelluntergangs im Kulturmedium gemessene LDH-Aktivitat wies in beiden Fallen einen dosisabhangigen Anstieg auf. Die negative Korrelation zu den3H-Thymidinwerten last als Hauptursache der verminderten Transformation einen vermehrten Zelluntergang annehmen. Die Autohamolyse der Erythrozyten zeigte einen dosisabhangigen Abfall bis auf 59,3% des Ausgangswertes. Hohermolekulare Urinmetabolite kommen demnach als Retentionsprodukte lediglich fur die zytotoxische Teilwirkung uramischen Serums auf kultivierte Lymphozyten in Frage, wahrend die gesteigerte Autohamolyse durch Toxine geringerer Molekulgrose ausgelost wird.

Die Ergebnisse eines biologischen Erythropoietinnachweises (mittels der Eiseneinbaurate polyglobuler Mause) und eines kauflichen immunologischen Erythropoietinnachweises (Haemagglutinationshemmtest) wurden miteinander verglichen. Von 19 untersuchten Chargen des immunologischen Tests waren 7 Chargen vollig inaktiv und bei drei weiteren Chargen wurde nur eine Reaktion mit dem mitgelieferten Kontrollserum beobachtet.

Die Haarzelleukamie wurde mit α-2-Interferonen nach zwei aufeinander abgestimmten Therapieprotokollen behandelt. Die Wirksamkeit niedriger Tagesdosen konnte belegt werden und ebenso die geringe Rate an Nebenwirkungen. Die niedrigen Dosen verbesserten bei taglicher Applikation die hamatologischen und klinischen Parameter rasch, erzeugten aber eine erhohte Anfalligkeit fur todliche Infektio-nen bei Splenektomierten. Eine ebenso niedrig dosierte pulsatile Therapie wurde in das 2. Protokoll mit einem klar abgesetzten zeitlichen Verhalten fur die Splenektomierten eingesetzt, um die Bedeu-tung einer rhythmischen Applikation abschatzen zu lernen. Sie hat sich inzwischen und vorlaufig als wirksam und sicher erwiesen. Die weitere Entwicklung sicherer und nebenwirkungsarmer Therapien fur die HCL bleibt das Hauptziel der Studiengruppe. Der Stellenwert des bisher in der Rezidivbehandlung eingesetzten Desoxicoformicins [4, 7] wird noch zu erarbeiten sein.

Zur Frage der spontanen Lymphocytentransformation bei chronischer Niereninsuffizienz wurde der3H-Thymidineinbau in Lymphocytenkulturen regelmasig dialysierter Patienten nach funftagiger Inkubation gemessen, nachdem in Vorversuchen die maximale DNS-Synthese zu diesem Zeitpunkt ermittelt worden war. Die spontane Lymphocytentransformation war bei 12 Patienten mit 1137±1122 c.p.m./Kultur signifikant erniedrigt (Kontrollkollektiv: 9783±7499 c.p.m./Kultur), wahrend die als Parameter des kontinuierlichen Zelluntergangs im Kulturmedium bestimmte LDH-Aktivitat keine Abweichung ergab. Nach Stimulation mit 400µg PHA war die Transformation bei 7 Patienten erniedrigt, bei 5 Patienten mit kurz zuvor uberstandenen Infekten dagegen erhoht. Nach Inkubation mit Seren von insgesamt 11 chronisch dialysierten Patienten lies sich auch im Lymphocytenkulturen von zwei gesunden Personen eine signifikant erniedrigte Spontantransformation nachweisen, deren Ausmas mit dem Hamoglobingehalt und dem Hamatokrit des betreffenden Patientenblutes korrelierte. Die als Folge einer verkurzten cellularen Lebensdauer signifikant erhohte LDH-Aktivitat im Kulturmedium zeigte eine positive Korrelation mit dem3H-Thymidineinbau, so das ein beschleunigter Zelluntergang als alleinige Ursache der herabgesetzten DNS-Synthese auszuschliesen ist. In Analogie zu den roten Blutzellen werden zwei gleichzeitige Wirkungen uramischer Toxine im Serum auf die Lymphocyten angenommen: metabolische Hemmung der DNS-Synthese und cytotoxische Zellschadigung mit verkurtzer Uberlebenszeit.

Ziel der Studie war die Verbesserung der Remissionsqualitat durch Anwendung einer intensivierten Induktionstherapie, welche sich bei der kindlichen ALL bewahrt hat (Westberliner Therapieprotokoll); in

This report deals with a cryopreservation technique and procedure; clinical data concerning the therapy itself are not presented here. A cryopreservation procedure was developed which proved to be effective for large volumes of lymphocytes and stem cells (CFU-c) obtained exclusively from the peripheral blood of man. Viability criteria used for lymphocytes include determination of the number of living cells, absolute recovery and immunologic assays. Stem cell counts and recovery were determined by the semisolid agar colony assay. A specially designed freezing process and a revitalization method using an atomizing system were applied to cell concentrates of patients with different types of cancer. The results indicate that nearly all cell functions of interest are fully preserved and that very high amounts of MNC and CFU-c are obtained after the freeze-thaw cycle. Up to now, units of cryopreserved autologous cells were retransfused to 40 patients.

In eight patients suffering from polycythaemia vera, the proliferation of erythroid colonies in methylcellulose with and without exogenous erythropoietin was studied. After three and five weeks, respectively, no colonies grew. Due to addition of erythropoietin more erythroid colonies proliferated which could be cultivated over nine weeks. The experiments suggest that the erythropoiesis in polycythaemia vera depends on erythropoietin.

Es wird erstmals uber die prospektive kontrollierte deutsche Studie zur Therapie der chronisch myeloischen Leukamie (CML) berichtet. Nach einer Laufzeit von 3 Jahren wurden bisher 188 von 300 vorgeseh

400 ml Erythropoetin-reiches Plasma (entsprechend 500 E Erythropoetin) von Patienten, die an aplastischer Anamie litten, wurden drei mannlichen Normalpersonen infundiert.

Wir fanden im Blut von Patienten mit aplastischer Anamie hohere Erythropoetinaktivitat als im Blut von Patienten mit Blutungsanamie gleichen Schweregrades.

Bei 26 Patienten mit Niereninsuffizienz, davon 22 mit chronischer Glomerulonephritis, 2 mit chronischer Pyelonephritis, einer Patientin mit Phenacetinniere und einem Patienten mit Pyelonephritis bei Hydronephrose wurde mit der59-Fe-Einbaurate an polyglobulen Mausen die erythropoetische Aktivitat des Serums untersucht. Bei einem Patienten mit chronischer Glomerulonephritis fand sich eine leicht erhohte Erythropoetinaktivitat. Die Patientin mit Phenacetinschadigung der Niere wies eine ausgepragte erythropoetische Aktivitat des Plasma und des Acsites auf. Auch der Patient mit Pyelonphritis und Harnabflusstorung hatte erhohte Serumerythropoetinwerte. Eine Hemmung der Wirkung exogen zugefuhrten Erythropoetins an der polyglobulen Maus durch Serum uramischer Patienten wurde nicht beobachtet.

Bei 10 Patienten mit primarer und sekundarer Polycythamie wurden Bestimmungen von Erythropoetin, Renin, Aldosteron, Erythrocyten- und Plasmavolumen durchgefuhrt. Der Erythropoetingehalt im Serum war bei einem Patienten mit Polycythaemia vera, 2 Patienten mit Hypoxamie und einem Patienten mit metastasierendem Lebercarcinom deutlich erhoht.

In eight patients suffering from polycythaemia vera, the proliferation of erythroid colonies in methylcellulose with and without exogenous erythropoietin was studied. After three and five weeks, respectively, no colonies grew. Due to addition of erythropoietin more erythroid colonies proliferated which could be cultivated over nine weeks. The experiments suggest that the erythropoiesis in polycythaemia vera depends on erythropoietin.

For palliative therapy during the chronic phase of CML busulfan has proved to be the drug of choice. During the past years hydroxyurea and also interferon-alpha have gained increasing significance since they might prolong the duration of the chronic phase. In a multicenter study it is being determined, whether the use of hydroxyurea or of interferon-alpha instead of busulfan prolongs the duration of the chronic phase of Philadelphia positive CML. Additional goals are the examination of whether the types of disease evolution and the terminal phases differ between the treatment groups, and the prospective recognition of prognostic criteria for the duration of the chronic phase of CML. By December 31, 1987, 326 CML-patients had been randomized, 150 for busulfan, 150 for hydroxyurea and 26 for interferon-alpha. The average age is 50 years. 59 patients reached the end of the chronic phase, 55 died. The mean observation time of all patients is 1.34 years. At present no significant difference in survival is recognizable between the busulfan and hydroxyurea groups. Fewer adverse effects have been observed in the hydroxyurea group. Philadelphia chromosome negative patients show a higher average age and tend to have lower white blood cell and platelet counts. The number of patients having received interferon-alpha is still too small to allow evaluation. This report intends to document organization and progress of this study which to our knowledge is, at present, the largest ongoing prospective multicenter study on the therapy of CML.

One of the most common and technically interesting handling maneuvers in everyday service is braking in a turn. For this reason the braking performance in a turn is one of the most important points in the vehicle concept, which has to be precisely observed when designing a motor vehicle. The reactions of the vehicle must demonstrate, after the corresponding optimizations on the vehicle have been completed, a most favorable compromise between steerability, directional stability and deceleration (A).

Die Polycythamia vera (PV) stellt eine klinische Ausschlusdiagnose dar, deren Differentialdiagnose vor allem kardiale, pulmonale, renale und endokrine Erkrankungen umfast. Die Diagnose PV kann erschwert sein, wenn eine isolierte Steigerung der Erythropoese besteht. Untersuchungen von Prchal und Axelrad (1974) sowie Zanjani et al. (1977) hatten ergeben, das Knochenmarkkulturen von PV ohne Zusatz von Erythropoietin ein Wachstum von hamoglobinisierten Kolonien aufweisen. Nissen et al. (1978) fanden vergleichbare Befunde im peripheren Blut.

Reverse osmosis (40 bar) using membranes with a nominal cut-off of 500 Dalton is a useful method for the desalting and concentration of hemofiltrates (20-30 L) or even dialysates (120-240 L) from patients with end-stage renal failure. The removal of electrolytes and lower molecular weight solutes from the middle and higher molecular weight fractions can be carried out in one step. The freeze-dried residues show characteristic differences in their molecular weight distributions which are dependent upon their origin (Cuprophane dialysates or RP-6-hemofiltrates). Subfractionation is performed using Sephadex G-15 macrocolumns (2 m x 5 cm), the LKB-Ultrogel AcA 54 and Sephacryl S-200 as well as ion exchange chromatography. The fractions are characterized by their ability to suppress the incorporation of 3H-thymidine into rat bone-marrow as well as HeLa cell cultures. The greatest inhibitory activity originates from those fractions which are not dialysable using Visking tubes in vitro. The results indicate that the middle and higher molecular weight spectra do in fact overlap, suggesting that also higher molecular weight substances are involved in uremic intoxication.

3H-thymidine uptake of lymphocytes cultured from patients with regular dialysis treatment was determined at the time of maximal transformation, which was ascertained in previous investigations to be 5 days after the beginning of incubation. Spontaneous DNS synthesis was found to be significantly depressed: 1137 plus or minus 1122 c.p.m./culture; controls: 9783 plus or minus 7499 c.p.m./culture, whereas LDH activity in the supernatant culture medium measured as a parameter of continuous cell destruction showed no alteration. After stimulation with 400 mug PHA DNS synthesis in 7 patients was also decreased, but elevated in 5 patients with previous infections. After incubation with added serum from 11 chronic uremic patients, spontaneous lymphocyte transformation in cultures sampled from 2 healthy subjects was also found to be depressed with positive correlation to the hemoglobin and hematocrit levels in the corresponding blood. The significantly increased LDH activity values in the medium as the consequence of impaired cll viability showed also positive correlation with 3-H-thymidine uptake levels; therefore depressed DNS synthesis cannot be due alone to accelerated cell destruction. In analogy to the erythrocytes, two stimultaneous effects of uremic toxins in serum are assumed to be exerted on the lymphocytes: metabolic inhibition of DNS synthesis and impaired cell viability.