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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

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.

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 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.

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.

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).

257 untreated myeloma patients (stage II and III) were studied in a multicenter trial. The patients were randomized and received MP or VCMP therapy. No differences in remission rate could be found in both therapy arms. After successful remission induction those patients without maintenance therapy relapsed significantly earlier than those patients receiving maintenance therapy. In pilot studies an etoposide therapy was found ineffective and a multidrug therapy (VBAMDex) could induce high remission rates in high risk and pretreated patients.