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In Amputationspraparaten von Patienten mit fortgeschrittener Arteriosklerose und Endangitis obliterans wurde in unmittelbarer Nachbarschaft zu nekrotischen Anteilen der Skeletmuskulatur die Aktivitat der Succino-dehydrogenase, des Succinoxydase- und Cytochromoxydase-Systems, der Hexokinase, ATP-ase und der sauren und alkalischen Phosphomonoesterasen sowie der Gehalt an Glykogen bestimmt. Im Gegensatz zu den schweren klinischen Erscheinungen mit zum Teil ausgedehnten distalen Nekrosen blieb die Aktivitat der Fermente in unmittelbarer Nachbarschaft der Nekrosen unverandert. In den Randzonen von Nekrosen ist dagegen neben starker Verminderung des Glykogenbestandes die Aktivitat dieser Fermente herabgesetzt, die der alkalischen Phosphormonoesterasen gesteigert. Trotz der Tendenz zur Generalisierung weisen die Ergebnisse daraufhin, dass die Folgen der Gefassprozesse durch die Ausbildung von Kollateralen auf eng begrenzte Bezirke beschrankt sind.

Eighty-two patients with Hodgkin's disease (H.D.) and 40 patients with Multiple Myeloma (M.M.) were HL-A typed. The results were compared with those of 255 healthy individuals of the same geographical area. In both diseases W18 (4cr) - belonging to the 4c-complex - was significantly increased.

Let (π,σ) be a pair of cuspidal automorphic representations of GL n × GL n −1 over the adele ring of ℚ having non-vanishing cohomology with constant coefficients. The p-adic distribution interpolating the critical values of the twisted corresponding Rankin–Selberg convolution is shown to be p-adically bounded thus leading to an associated p-adic L-function.

Geographic ignorance is a focus of considerable discussion in the United States. Data on geographic awareness among respondents at four locations in the People's Republic of China are analyzed to provide perspective on the U.S. experience. The general patterns of agreement, degree of accuracy, and possible causes for variations are examined. Comparisons with findings of previous studies indicate a number of similarities and several significant differences in patterns of geographic knowledge.

14 patients (12 men, 2 women, mean age 26.3 [15-47] years) with histologically confirmed Burkitt's lymphoma were subjected between 1984 and 1989 to chemotherapy originally developed for treating lymphomas in children. Treatment consisted of medium doses of methotrexate, cyclophosphamide, teniposide, cytarabine, adriamycin and prednisone, intrathecal administration of methotrexate and if necessary prophylactic or therapeutic irradiation of the cranium. Most of the patients (64%) were in advanced stages of the disease. The rate of complete remissions was 100%. Four patients (29%) had a recurrence. Side effects were leukopenia (WHO grade III and IV) in 71%, grade III anaemia in 43% and grade III-IV thrombopenia in 29% of the patients. Considerable mucositides in 5 of the 14 patients (36%), and in one case a tumour lysis syndrome with transient renal insufficiency were other therapy-induced side effects. These results suggest that this treatment course can be successful also in non-endemic Burkitt's lymphoma in adolescents and adults.

In four patients (a 54-year-old man and three women aged 57, 60 and 65 years, respectively) with colorectal carcinoma and no obvious cardiac abnormality anginal symptoms and ECG changes occurred during chemotherapy with 5-fluorouracil at a dose of 400 and 600 mg/m2. The ECG changes consisted of descending ST depressions with preterminally negative T waves, terminally negative T waves, ventricular extrasystoles and sinus tachycardia with intermittent atrial fibrillation. The signs first appeared between the second and fourth day of treatment; in two patients they improved with glyceryl trinitrate. A few days after 5-fluorouracil had last been administered all ECG changes had disappeared. The causes of cardiotoxicity of the drug remain unknown.

The heterogeneity of cells capable of metastasation has proved to be the greatest obstacle to successful treatment or to prevention of metastatic diseases. This variety appears to be attributable to processes of selection. Cytobiological investigations which are helpful in casting some light at selective mechanisms of metastasation may, perhaps, make substantive contributions to cancer therapy.

The frequency of induced sister chromatid exchange (SCE) is a sensitive tool for the monitoring of DNA damage and has been shown to indicate chemotherapy resistance. Mafosfamide is presently used for the purging of bone marrow in autologous bone marrow transplantation in the treatment of acute leukemia. We studied the SCE-inducing effect of mafosfamide on leukemic cells of Philadelphia (Ph)-positive chronic myeloid leukemia (CML) as a model for leukemic cells. Corresponding data from normal bone marrow were analyzed for comparison. A positive linear correlation (r = 0.99, P = 0.0005) was found between the dose of mafosfamide and induced SCE in Ph-positive CML and normal bone marrow. The concentration of mafosfamide used was 0.1, 0.2, 0.4, and 0.8 micrograms/ml. Additionally, we analyzed five cases of CML and six cases of normal bone marrow. A significant difference in the frequency of induced SCE/metaphase was found between CML and normal bone marrow even after addition of 0.8 micrograms/ml mafosfamide. Also, spontaneous SCE was significantly lower in CML. Our data indicate a lower sensitivity of the leukemic cells to mafosfamide as shown by the induction of a lower frequency of SCE events.

Sister chromatid exchange (SCE) is considered a highly sensitive parameter for the detection of mutagenic and/or cancerogenic effects of drugs. A close correlation between induced SCE frequency and reduction of cell proliferation and cell survival after exposure of cells to alkylating agents was described by Morris et al. [1].

Es werden klinische und eiweischemische Befunde bei 6 Patienten mit μ-Kettenkrankheit mitgeteilt. Bei allen Patienten bestand ein lymphoproliferatives Syndrom, das klinisch am ehesten der Chronischen Lymphatischen Leukamie bzw. einem Non-Hodgkin-Lymphom niedrigen Malignitatsgrades entsprach. Die Ahnlichkeit mit der CLL wird durch den Befund einer eingeschrankten Stimulierbarkeit von PBL dieser Falle mit mitogenen Substanzen wie PHA, PWM und Con A unterstrichen. Freie μ-Ketten im Serum sind keiner einheitlichen, klinisch von anderen lymphoproliferativen Erkrankungen abzugrenzenden Symptomatik zuzuordnen und konnen auch im Rahmen einer gutartigen Lymphadenopathie auftreten. In einem Fall konnte durch eine kombinierte Chemotherapie eine uber 4 Jahre andauernde Remission erzielt werden.

Seit 1975 wurden 140 Patienten mit retroperitoneal-metastasierten nicht-seminomatosen Hodentumoren nach Orchiektomie und retroperitonealer Lymphadenektomie sequentiell alternierend mit den Zytostatika-Kombinationen Velbe/Bleomycin und Adriamycin/Cisplatin plus/minus Radiotherapie behandelt. Davon erhielten 68 Patienten nach totaler retroperitonealer Lymphadenektomie mit postoperativ normalisierten Tumormarkern (Stadium IIA) 6 Chemotherapie-Kurse, woran sich bei 35 Patienten eine Strahlentherapie anschlos. Vierzig Patienten wurden nach subtotaler retroperitonealer Lymphadenektomie oder bei postoperativ erhohten Tumormarkern (Stadium IIB) und 32 Patienten nach palliativer Lymphadenektomie (Stadium IIC) mit mindestens 12 Chemotherapie-Kursen und fakultativer intermittierender Radiotherapie und/oder Relaparotomie behandelt. Der Vergleich der Behandlungsergebnisse bei den Stadien IIA und IIB ergab unabhangig von der zusatzlichen Radiotherapie nach der „Life-table“-Methode Vier-Jahres-Uberlebensraten zwischen 80 und 100%. Diese gunstigen Resultate sind mit den Ergebnissen bei 34 nicht adjuvant behandelten Patienten ohne histologisch nachweisbare retroperitoneale Metastasierung (Stadium I) vergleichbar. Ausdruck einer statistisch signifikant schlechteren Prognose bei fortgeschrittener retroperitonealer Metastasierung ist eine Vier-Jahres-Uberlebensrate von 12% bei den Patienten im Stadium IIC.

Sister chromatid exchange (SCE) frequency has been analyses after short-term culture of leukemic bone marrow cells of eight untreated patients with acute leukemia. Compared to normal bone marrow, results show a statistically significant decrease of SCE (p less than 0.001) in euploid as well as in aneuploid leukemias, ranging from 2.11 to 2.97 SCE per metaphase. The different SCE values were not related to contraction status of chromosomes and could not be explained by the age of patients. Therefore, low SCE may be a typical feature of leukemic cells. An examination of growth rates by the SCE technique revealed a high turnover of normal bone marrow cells. About 80% of the cells did not need more than 50 h to run two or three cell cycles. Leukemic cells, however, apparently divided more slowly, which is in good agreement with data obtained by autoradiographic methods.

Inbred mice were immunized with various cellular and subcellular preparations from a syngeneic, methylcholanthrene-induced sarcoma to induce transplantation immunity against a subsequent challenge of viable cells from the same tumor. Only with conventional immunization procedures using radiation-attenuated tumor cells or viable tumor cells in admixture with bacillus Calmette-Guérin was transplantation immunity obtained. Neither native soluble tumor extracts prepared using several extraction methods, nor cross-linked preparations of these extracts gave rise to transplantation immunity. With few exceptions, however, the immunizing preparations resulted in the production of tumor-specific humoral antibody. The manner in which tumor antigens are presented to the host as well as the experimental system (animal strain; tumor) used appear to play an important role in the development of transplantation immunity against tumors.

Between July 1974 and December 1976 a total of 69 patients were treated for acute nonlymphoblastic leukaemia. The mean age was 42 years. Seven had been previously treated. Induction treatment with daunoblastin and cytarabine was given to 67 patients. It produced complete remission in 37 (55.2%) and partial remission in two. Twelve patients received a minimum of two courses of induction treatment without remission (definite treatment failures). Sixteen patients died during the first 30 days after onset of treatment. Treatment to maintain remission consisted of cytarabine and alternating 6-thioguanine, cyclophosphamide, lomustin and daunoblastin. Treatment could be continued as planned in only a quarter of the patients, because of serious side effects in the others. One year after conclusion of the study (31. 12.77) the median remission period was 42, median survival time for all patients 33 weeks (73.5 weeks for those responding and 8 weeks for those not responding to treatment). Age, fever, and chromosomal status of bone-marrow cells had an effect on prognosis.

Among 334 patients (aged 15-57 years) with malignant non-Hodgkin's lymphoma there were 14 who developed CNS complications, none in 144 with lymphoma of low malignancy. Lymphoblastic lymphoma predominated amoung those with CNS involvement. In adults with this form treatment should therefore be undertaken to prevent such complications. The study confirms the need for histological subclassification in malignant non-Hodgkins's lymphoma.

As an alternative technique to density-gradient separation, we studied the preparation of red blood cell (RBC)-depleted marrow mononuclear cells (MNC) by continuous-flow centrifugation (CFC) using the IBM 2997 cell separator in a dog model. Mean recoveries of nucleated and mononuclear cells obtained by this separation technique were 43.1% and 77.7% , respectively, and the mean residual RBC volume was 1.8 mL (1.2% of the RBC volume prior to separation). A mean of 91.4% of marrow progenitor cells were regained in the RBC-depleted fraction. Transplantation of the separated marrow MNC into seven lethally irradiated beagle littermates resulted in complete and durable hematopoietic chimerism. Our results indicate that separation of marrow MNC using an IBM 2997 cell separator is an effective and technically uncomplicated alternative to gradient medium separation.

In two studies, haematopoietic late effects of prolonged bleomycin treatment were evaluated in mice given serial injections of 21 mg bleomycin/m2 weekly for 31 and 44 weeks, respectively. Femoral bone marrow cellularity measured at 43, 45, and 49 weeks after discontinuation of the drug in the first and after 20 weeks in the second study was found to be significantly (P less than 0.05) lower in the treated mice than in the controls. CFU-S, BFU-E, and CFU-C contents were also reduced in the treated bone marrow, but with the exception of CFU-S in the second study, differences from control values were not significant. Additional long-term bone marrow cultures performed in the second study revealed no marked changes in the marrow proliferative activity and the self-renewal of stem cells to explain the reduced marrow cellularity and stem cell content. These last findings might, therefore, be due to a decrease in femoral size with less marrow content in the treated mice, since measurements of the tibial weights in both groups showed that the bones in the treated animals were significantly (P less than 0.05) lighter than those in the controls.

Es wird uber kritische Punkte in der Methodik der CEA-Bestimmung nach Hansen u.a. (CEA-RIA-Test der Firma Hoffmann-La Roche) berichtet. Bei 82 Patienten mit colorectalem Carcinom konnte die CEA-Bestimmung durchgefuhrt werden. Postoperativ wurden bei 43 Patienten 4 Tage, 8 Tage, 14 Tage, 3 Monate und 6 Monate, vereinzelt auch spater, die CEA-Werte beobachtet. Von 61 praoperativ bestimmten Patienten lagen 52,5% uber der vorgeschlagenen Normgrenze von 2,5 ng/ml. Bei der statistischen Auswertung mit der Multivarianzanalyse ergab sich eine Wechselwirkung der verschiedenen Stadien auf die CEA-Werte. Postoperativ fallen die CEA-Werte unterschiedlich rasch ab. Ein Wiederanstieg des CEA-Wertes zeigt bereits weit vor der klinischen Manifestierung das Rezidiv an. In einem Fall wurde pra- und postoperativ trotz Lebermetastasen kein erhohter CEA-Wert gemessen. Erst 11 Monate postoperativ, nach Generalisierung der Erkrankung, konnte ein erhohter CEA-Wert nachgewiesen werden. Es sollte deshalb auch bei normalen CEA-Werten die Verlaufskontrolle fortgesetzt werden.

The sister chromatid exchange (SCE) frequency was investigated in normal bone marrow and Ph1-positive cells of chronic myelocytic leukemia (CML) patients with and without mitomycin-C (MMC) treatment in vitro. Even though the spontaneous SCE frequency was found to be significantly lower in CML cells, the absolute SCE values after MMC treatment did not differ between leukemic and normal cells, and this seems to indicate an equilization of SCE rates. However, the fact that leukemic cells with lower spontaneous SCE rates need a further increase of SCE to reach values equal to those of normal cells might indicate a somewhat higher susceptibility of leukemic cells to DNA damage by MMC. This interpretation appears to be confirmed by the fact that the inhibition of cellular proliferation at higher MMC doses considerably reduced the number of leukemic cells that was able to divide twice during a given culture time.

Die jungsten molekularbiologischen Untersuchungen an Lymphocyten der chronisch-lymphatischen Leukamie bestatigen den neoplastischen Charakter dieser Zellen. Funktionelle und strukturelle, z.T. qualitative Unterschiede in der Biochemie von DNA, RNA und Proteinen belegen die biologischen Sonderstellung dieser Erkrankung, bei deren Pathogenese Oncornaviren nach den bisher gesicherten Befunden wahrscheinlich keine Bedeutung haben. Zellen der chronisch-lymphatischen Leukamie sind durch verschiedenste makromolekulare Abnormalitaten ausgezeichnet: multiple DNA-Polymerasen nach PHA-Stimulation, vermindertes Aktinomycin-Bindungsvermogen, veranderte Transcription des Chromatins, erhohten DNA-repair, erhohte RNA-Synthese, vermehrte Synthese ribosomaler Vorstufen bei mangelhafter Ribosomenreifung, veranderte32P-Nucleotidkomposition und veranderte Oligonucleotidfrequenzen in nuclearer 45S RNA und ribosomaler 28S RNA, mangelhafte Stimulierung des nucleolaren „processing“ durch PHA, verminderten Lysosomen- und Polysomengehalt, Funktionseinbuse der Ribosomen in zellfreien Systemen, neue Polyribonucleotidsequenzen in der nuclearen heterogenen RNA sowie durch qualitative und quantitative Veranderungen des Kernproteinmusters nach zweidimensionaler Gel-Elektrophorese. Die Interpretation des CLL-Lymphocyten als Bahnliche Zelle erscheint im Zusammenhang mit diesen neuen biochemischen Daten als nicht ausreichend.

74 patients with disseminated non-seminomatous testicular cancer were randomly entered on a prospective sequential combination chemotherapy regimen with mandatory crossover, consisting of either vinblastine/bleomycin or adriamycin/cis-dichlorodiammineplatinum (II) (DDP) as initial therapy. Independent of the randomization the overall remission rate in 71 evaluable patients was 89% including 54% complete remissions. 35% of the patients remained disease-free at 2+ to 28+ months with a median of 12 months. By additional surgical removal of residual pulmonary metastases in two patients the complete remission rate was increased to 40/71 (56%), and the number of patients with no evidence of disease to 27/71 (38%). According to the life-table method the two-years survival rates were 63% for complete responders and 29% for all other patients, which was significantly lower. 53 patients (75%) were alive at 3 to 28 months with a median of 9 months. Additional advanced abdominal disease, initially elevated beta-HCG and LDH and extension of pulmonary disease were of significant negative influence on the prognosis. The evaluation of single chemotherapy courses revealed equal efficacy of both combinations. However, response to adriamycin/DDP occurred in 46% of the courses, when vinblastine/bleomycin had failed, while response to vinblastine/bleomycin occurred only in 21% of the courses when adriamycin/DDP had failed. Thus different patterns of cross-resistance between these alternative regimens may exist.

A report is given of three new cases of acute monocytic leukemia, FAB M5a, with a t(8;16)(p11;p13). Two cases showed a marked erythrophagocytosis, including one with phagocytosis of normoblasts and granulocytes. Phagocytosis was absent in the third case. The t(8;16) was the only abnormality in two cases, whereas one case showed clonal evolution with partial trisomy 1q and a deletion of part of the short arms of chromosomes 1 and 3. Treatment results and survival were poor in all cases. A complete remission was achieved in two patients, which lasted only for 3 and 6 months, respectively. In one of these cases a central nervous system relapse occurred. Survival was short, lasting between 1 and 9 months. One patient succumbed to interstitial pneumonitis, a complication of allogeneic bone marrow transplantation without evidence for relapsing leukemia.

Phenol-soluble chromatin proteins which may be involved in gene control mechanisms have been isolated from citric acid nuclei of normal and leukaemic human leukocytes derived from freshly obtained venous blood. They were compared by one-dimensional gel electrophoresis and by comparative labelling with14C-leucine or32P-orthophosphate. In addition, the influence of intercalating agents such as adriamycin and daunomycin was studied.

Anhand eines Krankenkollektivs, bestehend aus 113 Patienten mit soliden Tumoren und Systemerkrankungen, wird über die transversale Radioisotopen-Tomographie der umschriebenen Lebererkrankung berichtet. Eine Übereinstimmung zwischen konventioneller Szintigraphie und Emissions-Tomographie fand sich in 61% der Fälle. In 39% der Fälle erbrachte die Emissions-Tomographie Zusatzinformationen (44/113). Korrekt positive und korrekt negative Ergebnisse wurden in 86,3% (63,6% bzw. 22,7%) gefunden, während in 13,6% durch die Emissions-Tomographie falsch positive bzw. falsch negative Resultate (6,8 % und 6,8 %) ermittelt wurden. Insgesamt darf, basierend auf den vorliegenden Ergebnissen, eine Verbesserung der Isotopen-Diagnostik angenommen werden.

The malignant granular cell tumor ist a rare soft tissue neoplasia which is chiefly localized in the sceletal muscles. The uncertain histogenesis gave rise to different terms. The clinical course is often protracted but fatal. Diagnosis, differential diagnosis, and treatment are discussed in the light of a case report concerning a malignant granular cell tumor in a 28-year-old man.

Combined treatment with three or five chemotherapeutic drugs was given to 115 women with metastasizing breast cancer. These were unselected cases. Three drugs (cyclophosphamide, methotrexate and prednisone) were given to 49 patients, with remissions occurring in 28, arrest in a further five. Five drugs (additional to the three mentioned ones: vincristine and 5-fluorouracil) were given to 66, with remission in 45 and arrest of the disease in another eight. There was no certain difference between the response to the two forms of treatment. Mean survival time for both forms was 13 months in the remission group and six months in the failure group.

The sister chromatid exchange (SCE) frequency in bone-marrow cells of 12 untreated patients with chronic myelocytic leukemia (CML) was analysed and compared with the SCE frequency in bone-marrow cells of nine healthy persons. In normal persons the SCE ranged from 3.64 to 5.15 per cell. In CML patients the SCE was significantly lower, ranging from 2.32 to 3.44 per cell. The differences found were unrelated to patients' age and contraction state of the chromosomes. It is suggested that the leukemic process could account for the low SCE rate.

Pratherapeutische Sensibilitatsbestimmungen an menschlichen Tumoren auf der Basis von Nukleinsaurevolraufer-Inkorporationsstudien sind von verschiedenen Arbeitsgruppen beschrieben worden. Diese Ubersicht will zeigen, weshalb solche Tests fur eine dringend erforderliche individuelle Chemotherapieplanung vorerst nur von geringem Nutzen zu sein scheinen. Einer der wesentlichsten Grunde ist, das es gegenwartig fur viele Zytostatika noch keinen Nachweis einer Korrelation zwischen biochemischer und klinischer Wirkung gibt. Daruber hinaus wird der Aussagewert von Sensibilitatsbestimmungen beeintrachtigt durch methodische Probleme bei der In-vitro-Dosierung und der Zellaufbereitung, die unterschiedliche Pharmakologie und Toxikologie der einzelnen Zytostatika sowie deren Wechselwirkungen bei der kombinierten Chemotherapie.

Exploratory laparotomy with splenectomy was performed on 275 patients with hisologically confirmed Hodgkin's disease. In 188 patients the laparotomy was a primary one to determine more precisely the state of the disease. A secondary laparotomy was performed in 87 patients 1-12 years after diagnosis and radiotherapy. In 17.5% of patients the state had to be revised after laparotomy with splenectomy. In 38 the disease had further progressed, while in ten it had slighty regressed. In four cases clinical stage I proved to be stage III. Even prognostically more favourable forms may have progressed at first diagnosis. There was no correlation between B-symptoms and histological type, but there was between B-symptoms and spread of the disease. Calculated spleen weight provided no clue as to spleen involvement. There was no clear relationship between spleen involvement and histological subclassification. Risk-effect analysis indicate that laparotomy with splenectomy was useful because it makes optimal treatment possible.

Fifty patients with inoperable bronchial carcinoma were treated with a combined schedule of adriamycin, cyclophosphamide and vincristine. In those cases with locally/regionally confined tumour spread this was followed - after three chemotherapy cycles - by radiotherapy to mediastinum, hilar region and tumour of 3000 rad focal dose. Remission was achieved in 25 of 27 patients with small-cell carcinoma: full clinical remission in 12, part remission in 13. Mean duration of the (in most instances still continuing) remission has so far been 4 + months. Mean survival time is, of course, not yet calculable. Only a few patients had to be admitted to hospital for short periods because of toxic reactions. Four full and 11 part remission (some still continuing) have so far been achieved in the group of larger-cell carcinoma (squamous cell, 4; large cells, 5; anaplastic, medium-large, undifferentiated or polymorph, 14).

Let K be an absolute abelian number field. The conductor of the Hecke characters of K formed by Gaussian sums is investigated. In some cases we obtain formulas for this conductor while in others a bound is given. These enable us to obtain a general upper bound for the conductor in terms of the class field theoretic conductor of K . Our bound is an improvement on existing bounds in the literature.

6 Patienten mit einer Haarzellenleukamie wurden 3–35 Monate nach Splenektomie mit IFN-γ (4 × 106 E/m2/2. Tag sc) behandelt. Wahrend einer Therapiedauer von 9–35 Wochen konnte bei keinem Patienten eine signifikante klinische oder hamatologische Befundbesserung erzielt werden. Nach einem therapiefreien Intervall von 0–13 Wochen erhielten alle Patienten IFN-α-2b (zunachst 4 × 106 E/m2/2. Tag, Erhaltungstherapie 1 × 106 E/2. Tag). Zum Zeitpunkt der Beendigung der jeweiligen IFN-α-2b-Gabe war bei 5 von 6 Patienten (1 Patient mit postthrombotischem Syndrom verstarb an einer Lungenembolie) eine deutliche Befundbesserung eingetreten. Nach einer Beobachtungszeit von jetzt 9–14 Monaten konnten 1 CR, 3 PR und 1 MR induziert werden. Die Nebenwirkungen beider Interferon-Praparationen unterschieden sich nicht signifikant.

The near threshold fatigue crack growth behavior of alloy 718 was studied in air and helium environments at room temperature and at 538°C. Tests were performed at 100 Hz and at load ratios of 0.1 and 0.5. At room temperature and at 538°C, the ΔKth values in helium were lower than in air. The ΔKth values in air decreased with increasing load ratio. These results can be explained with a model that involves the accumulation of oxide in the crack which enhances crack closure. In the air tests, the oxide build-up on the fatigue fracture surfaces at ΔKth was of the order of magnitude as the crack tip opening displacement. In the helium tests, no significant build-up of oxide on the fracture surface at threshold was found.

Seit Juli 1978 wurden 103 Patienten mit inoperablem kleinzelligem Bronchialkarzinom mit der Zytostatikakombination Adriamycin, Cyclophosphamid und Vincristin (ACO) behandelt. Im Stadium „limited disease“ (n=64) erfolgte wahrend des zweiten Chemotherapiekurses eine prophylaktische Schadelbestrahlung, nach dem vierten eine konsolidierende thorakale Bestrahlung. Nach Erreichen einer kompletten Remission erhielten die Patienten prospektiv randomisiert Etoposid oder keine weitere spezifische Therapie. Ein objektives Ansprechen konnte bei 88/100 auswertbaren Patienten erzielt werden. Im Stadium „limited disease“ fanden sich 72%, im Stadium „extensive disease“ nur 33% komplette Remissionen. Im Stadium „limited disease“ betrug die hochgerechnete mediane Uberlebenszeit 15,8, im Stadium „extensive disease“ 9,3 Monate (p

Clinical reports concerning the therapeutic effects of high dose Cytosine arabinoside (HD Ara-C) in meningeal leukemia are relatively rare. Pharmacokinetic studies, however, have indicated potentially effective concentrations of Ara-C in cerebrospinal fluid (CSF) during and after high-dose infusions of the drug given intravenously. In this report, the treatment results of HD Ara-C in 14 patients with refractory or relapsed acute leukemia are presented including those of 2 patients with meningeal leukemia. In these 2 patients as well as in 1 patient without central nervous system (CNS) leukemia, Ara-C and Ara-U concentrations in CSF and plasma were measured during a 6-day therapy with HD Ara-C (3 g/m2 q 12h 12 X). Ara-C and Ara-U levels were determined on Days 3 and 6 of therapy, each at the end of a 3-h i.v. infusion of the drug. In the 14 patients (8 with AML, 6 with ALL) treated, a total number of 17 treatment cycles were given for remission induction with doses of Ara-C ranging from 1-3 g/m2 q 12 h 6-12 X. A complete remission rate of 47% was achieved. The duration of remission ranged from 1 to 6 months. Of the 2 patients with CNS leukemia, 1 patient achieved complete remission both in CSF and in bone marrow, the other patient only in CSF. The mean concentration of Ara-C in CSF was 903 ng/ml with a ratio of 0.38 to that in plasma. Ara-C and Ara-U did not appear to accumulate in CSF or in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)