Vitamin K prophylaxis in the newborn.
Explore the source record for details and available documents.
Hemorrhage↗
Biomedical subjects
G Landbeck
Publications and source records attributed to G Landbeck.
Platinum disposition after intraarterial and intravenous infusion of cisplatin for osteosarcoma. Cooperative Osteosarcoma Study Group COSS.
Preoperative chemotherapy according to the COSS 86 protocol, including two courses of cisplatin, was used for high-risk osteosarcoma. Patients were randomised to receive either intraarterial (i.a.) or intravenous (i.v.) cisplatin infusions. As measured by flameless atomic absorption spectroscopy (FAAS), platinum (Pt) levels in serum, ultrafiltrate, and urine did not show a decrease in systemic drug availability with i.a. administration. Tumors were surgically removed 3 weeks after the last cisplatin dose and analysed for Pt content and response to chemotherapy. A correlation could not be demonstrated between Pt levels in tumor tissue samples and the mode of CDDP application or extent of tumor cell destruction.
Bone Neoplasms↗
Doxorubicin: effect of different schedules on toxicity and anti-tumor efficacy.
The risk of congestive heart failure restricts the clinical use of doxorubicin to cumulative doses of 450-550 mg/m2, when it is given using high-dose rapid intravenous application. As the high peak serum levels which follow rapid administration seem to be correlated with cardiotoxicity, application schedules leading to lower peak serum concentrations have been developed. This paper reviews the influence of those schedules on cardiotoxicity, non-cardiac toxicities, pharmacokinetic data and antineoplastic efficacy. While the reduction of cardiotoxicity by long-term application schedules is well documented, much less can be said about the antitumor effect of those schedules. Controlled studies dealing with this problem are needed. This review provides a base for that purpose.
Doxorubicin↗
Pharmacokinetics of doxorubicin in man: dose and schedule dependence.
Doxorubicin serum elimination kinetics were measured by HPLC in three different patient groups. A dose of (a) 30 mg/m2; (b) 50 mg/m2, and (c) 4 x 15 mg/m2 every 10 h was administered by bolus injection to (a) 10, (b) 6, and (c) 8 patients. The results obtained provided strong evidence for a nonlinear dependence of doxorubicin serum elimination on the dose and administration schedule used. Comparing the 15 and 30 mg/m2 dose there was no significant increase in early drug levels but a marked increase in terminal half-life. At doses higher than 30 mg/m2, however, there was a steep increase in early drug levels, too. Moreover a marked cumulation of the anthracycline in the central compartment following short-term (4 x 15 mg/m2 every 10 h) consecutive administration was found. To obtain an optimal concentration x time product by single bolus injection a dose equal or higher than 30 mg/m2 should be used. However, in this dose range a steep dose-dependent rise in early drug levels is to be expected. As early high serum levels correlate with congestive heart failure, administration schedules reaching effective concentration x time products without high peak levels such as continuous infusion or consecutive administration of low doses seem to be necessary.
Adolescent↗
Long term doxorubicin cardiotoxicity in childhood: non-invasive evaluation of the contractile state and diastolic filling.
Cardiac performance was evaluated at least two years after doxorubicin treatment in childhood in 55 patients without overt congestive cardiomyopathy. None of the patients had received mediastinal irradiation. Computer-assisted analysis of digitised echocardiograms showed impaired rapid diastolic filling and an increased change of dimension between minimal cavity dimension and mitral valve opening. This impairment of diastolic function was related to the cumulative dose of doxorubicin. In contrast when angiotensin II was infused to increase the afterload the end systolic pressure-length and stress-shortening relation indicated normal left ventricular systolic function. But during baseline conditions the end systolic wall stress was significantly increased in patients in whom the cumulative dose of doxorubicin exceeded 360 mg/m2.
Adolescent↗
[Detection of neuroblastoma cells in bone marrow by Southern blot and in situ hybridization using a NMYC DNA probe].
Recently an amplification of NMYC oncogene was discovered in stage III and stage IV as well as in stage II neuroblastoma cells. The extent of NMYC amplification is of prognostic value. A high expression of NMYC on mRNA level is correlated to the NMYC gene-amplification. We utilized the in situ-hybridization technique for the detection of NMYC-mRNA expression on cellular level, and the Southern Blot method for analysing the total genomic DNA. In three stage IV patients with overt neuroblastoma in bone marrow cells, NMYC gene-amplification as well as NMYC-mRNA were detected. Seven control bone marrows of patients with different heamatological diseases in different stages did not contain positive cells in our in situ-hybridization assay.
Base Sequence↗
A rapid chromatographic procedure for the determination of adriamycin, daunomycin and their 13-OH metabolites adriamycinol and daunomycinol.
A rapid chromatographic procedure for the quantitative determination of the anthracycline antibiotics adriamycin and daunorubicin and their chief metabolites adriamycinol and daunorubicinol in plasma and urine is described. The extraction is performed using SEP-PAK silica cartridges. After filtration the eluate is chromatographed on a reversed-phase column.
Adult↗
Determination of 7-hydroxymethotrexate in human plasma by reversed phase high-performance liquid chromatography.
A rapid and sensitive reversed phase HPLC method was developed for the detection of 7-hydroxymethotrexate (7-OHMTX) which is the main metabolite in human plasma after high-dose methotrexate (MTX) therapy. The simple clean-up procedure of plasma samples described allows the measurement of 7-OHMTX during clinical management of MTX infusions. Elimination kinetics of 7-OHMTX are given from 53 drug cycles of 6 patients.
Child↗
Translocation (9;11)(p21;q23) in a child with acute monoblastic leukemia following 2 1/2 years after successful chemotherapy for neuroblastoma.
This is a case report of a 4 1/2-year-old boy who developed acute monoblastic leukemia 2 1/2 years after he had been treated successfully with combined chemotherapy for neuroblastoma. All analyzable bone marrow-derived metaphases had the karyotype 47,XY, + 8,t(9;11)(p21;q23). The rare occurrence of specific chromosomal translocations in leukemias following prior chemotherapy and/or radiotherapy and their possible clinical implications in such cases are discussed.
Acute Disease↗
Kinetics of 7-hydroxy-methotrexate after high-dose methotrexate therapy.
Kinetics of 7-hydroxy-methotrexate (7-OH-MTX) excretion after high-dose methotrexate (MTX) (12 g/m2) therapy were monitored in 93 consecutive drug cycles of 19 adolescent patients with osteosarcoma. A reversed-phase HPLC method was used. Serum elimination was found to be monophasic with a mean half-life of 5.5 h. Shortly after the 4-h MTX infusion period 7-OH-MTX levels exceeded those of the parent compound. By 12 h after MTX infusion 7-OH-MTX levels were 16.5 times higher than those of MTX itself. Autostimulation of MTX metabolism leading to enhanced 7-OH-MTX production after repeated drug cycles was not observed. The production of 7-OH-MTX decreased significantly from the first to the last high-dose MTX cycle of the adjuvant chemotherapy protocol.
Adolescent↗
Effect of oral cholestyramine on the elimination of high-dose methotrexate.
The anion exchange resin cholestyramine binds methotrexate (MTX) effectively in vitro. The binding capacity exceeds that of activated charcoal by a factor of 5.4. On two patients undergoing high-dose MTX therapy it is also shown that cholestyramine binds MTX in vivo. This leads to an enhanced non-renal excretion of MTX. Therefore, cholestyramine may be of clinical value in patients who develop renal function impairment whilst undergoing MTX therapy.
Administration, Oral↗
7-Hydroxy-methotrexate and clinical toxicity following high-dose methotrexate therapy.
7-Hydroxy-MTX production after consecutive high-dose MTX therapy (12 g/m2) was measured in 7 patients with osteosarcoma by HPLC. 7-Hydroxy-MTX serum values in the last cycle were found to be significantly lower compared with the first high-dose MTX treatment of the adjuvant chemotherapy protocol (COSS 80). Moreover, in another patient highly reduced 7-hydroxy-MTX production was correlated with severe clinical toxicity. As 7-hydroxy-MTX is a 200 fold less potent dihydrofolic acid reductase inhibitor compared with MTX decreased production of the metabolite may lead to enhanced clinical toxicity which may not be predictable monitoring MTX serum levels alone.
Chromatography, High Pressure Liquid↗
[Acyclovir therapy in varicella/zoster diseases in immunocompromised children with cancer].
21 patients, aged 1 to 15 years, who developed manifest varicella/zoster-virus infection while on chemotherapy for malignant disease were treated with acyclovir. Drug dosage was 10 mg/kg every eight hours for 5 days as a one hour infusion. The clinical course of the infection in all patients was mild. 1 to 4 (median 2,2) days after beginning of acyclovir therapy the formation of new lesions stopped. Within 4 to 8 (median 5,9) days all vesicles were scabbed . In 13 patients with fever in the beginning the temperature fell within 2 to 6 (median 2,6) days of treatment. The development of visceral involvement was not observed during or after acyclovir therapy. Acyclovir was well tolerated. Tests of the hematopoietic, liver and renal functions before and after acyclovir therapy revealed no adverse effects of the drug. Also the immunologic response seemed not to be impaired. With one exception, all patients investigated had antibodies against varicella/zoster-virus after recovery. In order to prevent varicella infection after household exposure two immunocompetent patients were treated prophylactically with acyclovir tablets (400 mg 5 times a day for 5 days). Both children did not exhibit manifest varicella/zoster infection, but five weeks later they had antibodies against varicella/zoster-virus (KBR 1:10, resp. KBR 1:20).
Acyclovir↗
Adjuvant chemotherapy in osteosarcoma - effects of cisplatinum, BCD, and fibroblast interferon in sequential combination with HD-MTX and adriamycin. Preliminary results of the COSS 80 study.
In a cooperative adjuvant chemotherapy study of osteosarcoma (COSS-80), 192 patients were registered from December 1979 to March 1982. Forty-one patients have been excluded from study because of their nonadjuvant situation, therapy-limiting clinical conditions, or inadequate diagnosis. One hundred and fifty-one patients have been randomized to receive either the drug combination bleomycin + cyclophosphamide + dactinomycin (BCD) or cisplatinum (CPL) within a course of sequential multidrug chemotherapy including adriamycin (ADR) and high dose methotrexate (HDMTX). After exclusion of 51 patients with some deviation in history and/or management 100 selected patients were randomized once more to receive in addition or not fibroblast interferon after preoperative chemotherapy and surgical removal of the primary tumor. Patients were stratified for age and sex and for site and extension of tumor as well in both randomizations. Median follow up is now 12 (1-16) months. The expected 2-year disease free survival (DFS) rate of the total doubly randomized group is 78% and of the single randomized group 76%. No difference could be discerned between recombined groups receiving BCD vs CPL or interferon vs no interferon. The effect of preoperative chemotherapy on the tumor was evaluated clinically and by histopathologic grading; 66/85 (78%) patients were judged clinically as responders with pathohistologic verification of this finding in 71% of these cases. No adverse effect arose from delaying definite surgery for preoperative chemotherapy, but initial application of chemotherapy as well as planning, preparing, and performing of the surgical procedure have been facilitated. The majority of patients received some kind of limb-salvage treatment without local recurrences so far. A statistically insignificant but intriguing tendency for a slightly higher incidence of pulmonary metastases after resection as opposed to amputation could be detected. Similar to observations in the previous study COSS-77.
Adult↗
Problems of cooperative studies.
Explore the source record for details and available documents.
Clinical Trials as Topic↗
Pancreatic sonography in thalassemia major.
Four patients with thalassemia major and well documented transfusional anamnesis were investigated sonographically. Beside the fibrous reaction of iron overload in the liver the outstanding finding was the grossly increased echogenicity of the normal sized fibrotic pancreas in transfusional hemosiderosis. Upper abdominal sonography may be an useful - noninvasive - method for the assessment of iron load in regularly transfused patients. Moreover, pancreatic sonography may be helpful as follow-up method of chelation therapy.
Adolescent↗
[Intracranial metastasis in neuroblastoma].
Computed tomography is the most useful diagnostic method to demonstrate the pathophysiological consequences of secondary craniocerebral neuroblastoma. Hyperostotic metastases with subperiostal epidural tumour plaques as well as tumour deposits displacing and compressing adjacent venous sinuses show up well. Moreover, post-contrast computed tomography is a sensitive method for controlling patients under cytostatic or radiation therapy. In general, cranial computed tomography should be a part of basic diagnostics in neuroblastoma.
Abdominal Neoplasms↗
[Therapy of acute lymphoblastic leukemia in childhood. Multicenter prospective therapy study COALL-80].
Since 1979 in a cooperative study (COALL-80) 110 children with acute lymphoblastic leukemia (ALL) and 13 children with high grade malignant non Hodgkin's lymphoma (NHL) have been treated with a less aggressive modification of the Westberlin Study Program BFM 76/79. Asparaginase has been delayed from the initial 4 drugs regimen and interposed in between induction therapy and treatment of central nervous system (CNS). Induction therapy that way was well tolerated and realized mostly on an outpatient basis. The expected 2 1/2 years disease free survival rate for ALL is 86% and no worse than the results of the original BFM study. We were able to define by age (greater than 2, less than 7 years), initial blast count (less than 25000/mm3) and immunological typing (cALL Ag+) a great group of patients (52%) which has remained in continuous remission as a whole. For this group further reduction of therapy intensity is planned (omission of cyclophosphamide during CNS-phase and use of intermediate dose methotrexate (MTX-mHD) instead of CNS-irradiation).
Age Factors↗