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  • 1
    Electronic Resource
    Electronic Resource
    Renale Osteodystrophie bei Kindern Therapieversuch mit 1,25-Dihydroxy-Cholecalciferol (1980)
    Springer
    Journal of molecular medicine 58 (1980), S. 511-519 
    Details
    ISSN: 1432-1440
    Keywords: Renal osteodystrophy ; Child ; Metabolites of vitamin D ; Secondary hyperparathyroidism ; Renale Osteodystrophie ; Kind ; Vitamin-D-Metaboliten ; Sekundärer Hyperparathyreoidismus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 1. Durch die Behandlung mit 1,25-DHCC gelingt es nach unseren Untersuchungsergebnissen einen Anstieg des Serumkalziumspiegels zu erhalten, die PTH-Synthese zu blockieren und die intestinale Kalziumresorption zu verbessern. 2. Die Fibroosteoclasie und die aktuellen Zeichen der Knochenresorption können unter der Therapie vollständig behoben bzw. verbessert werden. 3. Bei der Behandlung dialysierter Kinder mit 1,25-DHCC konnten wir eine Verbesserung der Osteoidose in Fällen mit erheblicher Mineralisationsstörung beobachten. 4. Die Zahl der Osteoblasten wird unter der Therapie erheblich reduziert, in den meisten Fällen beobachteten wir Werte im Bereich der unteren Norm oder niedriger. Dies bedeutet in Bezug auf eine Langzeittherapie die Reduktion der Knochenformation mit Gefahr der Osteopenie. 5. Die Entwicklung einer gefährlichen Hyperkalzämie bei gleichzeitiger Imbalance im Serumphosphathaushalt muß streng beachtet werden. Wir beobachteten aufgrund dieser Kalzium- und Phosphatstoffwechselstörungen erhebliche Kalzifikationen im Limbusbereich der Augen. 6. Aufgrund dieser Befunde sollte 1,25-DHCC individuell in niedriger Dosierung nur bei Kindern mit histologisch nachgewiesener schwerer renaler Osteodystrophie verwandt werden, sofern eine engmaschige kontinuierliche Überwachung sämtlicher Stoffwechselparameter möglich ist. 7. Eine Verbesserung des Körperwachstums konnte unter 1,25-DHCC-Behandlung nicht beobachtet werden.
    Notes: Summary Growth arrest and renal osteodystrophy are major problems in renal insufficiency of children. The present report describes our experiences in managing renal osteodystrophy in 14 dialyzed children using 1,25-DHCC for 12 months. Values in plasma of Ca, P, Mg, alkaline phosphatase, iPTH, 25-OH-D, and 1,25-DHCC were determined regulary. Skeletal X-rays and analysis of iliac crest biopsies were obtained in each child. In treatment with 1,25-DHCC episodes of severe but reversible hypercalcemia occurred. Alkaline phosphatase and iPTH normalized completely. Radiographic examinations revealed marked improvement. Histological signs of fibro-osteoclasia and resorptive defects disappeared but there was no recovery of osteomalacia. A reduction of osteoblast population and of bone transformation was obvious. 1,25-DHCC failed to normalize growth in uremic children. In short, neither vitamin D nor 1,25-DHCC can guarantee complete recovery of renal osteodystrophy and growth arrest in uremic children.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01477068
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  • 2
    Electronic Resource
    Electronic Resource
    Levels of parathyroid hormone-related protein in hypercalcemia of malignancy: comparison of midregional radioimmunoassay and two-site immunoradiometric assay (1993)
    Springer
    Journal of molecular medicine 71 (1993), S. 31-36 
    Details
    ISSN: 1432-1440
    Keywords: Hypercalcemia of malignancy ; Parathyroid hormone-related protein ; Serum calcium ; Parathyroid hormones ; Immunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Overproduction of parathyroid hormone-related protein (PTHrP) is a major cause of hypercalcemia of malignancy in patients with solid tumors. We measured plasma levels of the protein by a radioimmunoassay (RIA) against PTHrP(5384) and by an immunoradiometric assay (IRMA) against PTHrP(1–86). Of 16 affected patients 7 had elevated PTHrP levels in both assays and 4 had elevated levels in the RIA only. Median levels were about tenfold higher in these patients when measured by RIA (median of 34 versus 2.2 pmol/1). Measurements from both assays were, however, highly correlated with each other in this patient group (P〈0.01). PTHrP was not elevated in 10 normocalcemic patients with lung carcinoma. During long-term follow-up of a patient with a mesothelioma of the pleura, PTHrP levels measured with both assays decreased during chemotherapy in parallel with a normalization of serum calcium. In another hypercalcemic patient suffering from renal carcinoma, PTHrP measured by IRMA decreased by 40% within 12 h after nephrectomy, whereas PTHrP measured by RIA did not show a significant decline. Direct comparison of the assay results thus pointed to the existence of heterogeneity of circulating forms of PTHrP in plasma. In conclusion, both immunoassays detected elevated levels of PTHrP in a fraction of patients with hypercalcemia of malignancy and thus may be a tumor marker during treatment of malignancies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00210960
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  • 3
    Electronic Resource
    Electronic Resource
    Immunhistochemischer Nachweis von Tumoreinzelzellen im Knochenmarkspunktat beim operablen Mammakarzinom (1987)
    Springer
    Archives of gynecology and obstetrics 242 (1987), S. 347-349 
    Details
    ISSN: 1432-0711
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01783151
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  • 4
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and pharmacodynamics of the new podophyllotoxin derivative NK 611 A study by the AIO groups PHASE-I and APOH (1996)
    Springer
    Cancer chemotherapy and pharmacology 38 (1996), S. 217-224 
    Details
    ISSN: 1432-0843
    Keywords: Key words Podophyllotoxin derivative ; Pharmacokinetics ; Pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  NK 611 is a new podophyllotoxin derivative in which a dimethyl amino group replaces a hydroxyl group at the sugar moiety of etoposide. This results in profound physico-chemical differences: NK 611 is much less hydrophobic than etoposide. Preclinical studies have shown that NK 611 is advantageous in terms of bioavailability and of the potency of its anticancer activity. A clinical phase I study was performed in cancer patients within the framework of the AIO. Additionally, its pharmacokinetics and pharmacodynamics were investigated. NK 611 was given to 26 patients at doses ranging from 60 to 140 mg/m2 [maximum tolerated dose (MTD) 120 mg/m2] in a 30-min infusion. Plasma and urine samples were collected from 25 patients and analyzed using a validated high-performance liquid chromatography (HPLC) assay procedure. The concentration versus time curve of total NK 611 in plasma samples was best described by a three-compartment model. The overall median pharmacokinetic values were as follows (ranges are given in parantheses): mean residence time (MRT) 16.5 (5.4– 42.3)h, terminal half-life 14.0 (8.2–30.5)h, volume of distribution at steady state (Vss) 11.4 (7.9–18.1) l/m2, and plasma clearance (Clp) 15.1 (3.6–36.4) ml min-1 m -2. The total systemic drug exposure, represented by the area under the curve (AUC), varied between 53.4 and 532.0 μg ml-1 h. The mean AUC (±SD) increased with the dose from 78.7±3.7 μg ml-1 h at 60 mg/m2 up to 202.8±157.2 μg ml-1 h at 120 mg/m2. The mean urinary excretion (UE) fraction of unchanged drug at 48 h after the end of the infusion varied between 3.0% and 25.8% of the total dose delivered. Analysis of ultrafiltrate samples showed a protein binding of approx. 99%. The percentage reduction in white blood cells (WBC) and neutrophils (ANC) correlated with the dose, AUC, and AUCfree. The best relationship between the percentage of reduction in ANC and a pharmacokinetic parameter (AUC) took a nonlinear Hill-type form. The laboratory parameter for kidney or liver function did not correlate with the AUC. The variation of pharmacokinetic parameters within each dose level was profound. The reason for this pharmacological behavior remains unclear and should be investigated in further studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050474
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  • 5
    Electronic Resource
    Electronic Resource
    Skeletal homeostasis and ageing. Studies in human femora (1976)
    Springer
    Calcified tissue international 22 (1976), S. 389-392 
    Details
    ISSN: 1432-0827
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02064109
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  • 6
    Electronic Resource
    Electronic Resource
    Peritoneal dialysis in maple-syrup-urine disease: Studies on branched-chain amino and keto acids (1980)
    Springer
    European journal of pediatrics 134 (1980), S. 57-63 
    Details
    ISSN: 1432-1076
    Keywords: Maple syrup urine disease ; Peritoneal dialysis ; Peritoneal clearances ; Branched-chain α-amino acids ; Branched-chain α-keto acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report biochemical data on a child with MSUD who underwent peritoneal dialysis for severe metabolic imbalance. In confirmation of earlier data, the BCKA/BCAA ratios in blood had been found to be fairly stable in this patient during long-term dietary therapy. The child became comatose at comparatively low levels of leucine and KICA (ca. 2 mM each). At this time the blood/cerebrospinal fluid ratio for BCAA's and BCKA's was markedly diminished. During peritoneal dialysis, peritoneal clearance was highest for KIVA, but less for MEVA and BCAA's (40–50% or urea clearance), and least for the allegedly most toxic metabolite, KICA. The differences for BCKA's may be due to their differential protein binding. Given these individual differences, 1.8 to 8.7 initial plasma volumes were cleared in 14h with 24.21 of dialysis fluid. In the same time, urinary excretion of BCAA's and BCKA's was much less efficient. The data are discussed with regard to the pathobiochemical significance of high tissue levels of branched chain acids. A quantitative comparison between peritoneal dialysis and exchange transfusion is not yet possible.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00442404
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  • 7
    Electronic Resource
    Electronic Resource
    Single-agent gemcitabine versus cisplatin–etoposide: Early results of a randomised phase II study in locally advanced or metastatic non-small-cell lung cancer (1997)
    Springer
    Annals of oncology 8 (1997), S. 525-529 
    Details
    ISSN: 1569-8041
    Keywords: cisplatin ; etoposide ; gemcitabine ; non-small-cell lung cancer ; randomised phase II study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: This randomised study was designed to determine the responserate, survival and toxicity of single-agent gemcitabine andcisplatin–etoposide in chemo-naïve patients with locally advancedor metastatic non-small-cell lung cancer. Patients and methods: Gemcitabine 1,000 mg/m2 was given asa 30 min intravenous infusion on days 1, 8, 15 of a 28-day cycle, cisplatin100 mg/m2 on day 1, and etoposide 100 mg/m2on days 1 (following cisplatin), 2 and 3. Major eligibility criteria includedhistologically confirmed non-small-cell lung cancer, measurable disease,Zubrod PS 0–2; no prior chemotherapy, no prior radiation of the measuredlesion, and no CNS metastases. Results: 146 patients were enrolled, 71 patients on gemcitabine and 75patients on cisplatin–etoposide. Patient characteristics were wellmatched across both arms. Sixty-six gemcitabine patients and 72cisplatin–etoposidepatients were evaluable. Partial responses were seen in 12 gemcitabinepatients (18.2%; 95% CI: 9.8–30) and 11cisplatin–etoposide patients (15.3%; 95% CI:7.9–25.7).Early indications show no statistical differences between the two treatmentswith respect to time to disease progression or survival. Haematological andlaboratory toxicity were moderate and manageable. However, hospitalisationbecause of neutropenic fever was required for 6 (8%)cisplatin–etoposide patients but not for any gemcitabine patients.Non-haematological toxicity was more pronounced with significant differencesin nausea and vomiting (grade 3 and 4: 11% gemcitabine vs. 29%cisplatin–etoposide; despite the allowance for 5-HT-3antiemetics during the first cycle of cisplatin–etoposide), and alopecia(grade 3 and 4: 3% gemcitabine vs. 62%cisplatin–etoposide). Conclusions: In this randomised study, single-agent gemcitabine was atleast as active but better tolerated than the combinationcisplatin–etoposide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008207731111
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  • 8
    Electronic Resource
    Electronic Resource
    Front-line treatment of advanced non-small-cell lung cancer with MTA (LY231514, Pemetrexed disodium, ALIMTATM) and cisplatin: A multicenter phase II trial (2000)
    Springer
    Annals of oncology 11 (2000), S. 435-440 
    Details
    ISSN: 1569-8041
    Keywords: cisplatin ; MTA ; non-small-cell lung cancer (NSCLC) ; phase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:To evaluate the activity of MTA plus cisplatin inchemotherapy-naïve patients with non-small cell lung cancer (NSCLC). Patients and methods:Thirty-six chemotherapy-naïve patientswith NSCLC received 500 mg/m2 MTA plus 75 mg/m2cisplatin every 21 days, with 4 mg dexamethasone orally twice daily on the daybefore, of, and after MTA administration. Results:Median age was 58 years. WHO performance status was0–2. Eighteen patients each had stage IIIB and IV disease. Seventeenpatients each had squamous-cell and adenocarcinoma; two had undifferentiateddisease. Fourteen patients (39%; 95% confidence interval:23%–57%) showed partial response; seventeen (47%)had stable disease. Median survival was 10.9 months. Twenty-one patients(59%) experienced grade 3 or 4 granulocytopenia without fever orinfection. Five (14%) and six (17%) patients experienced grade3 anemia and grade 3 or 4 thrombocytopenia, respectively. Nonhematologicaltoxicities included grade 3 nausea in two patients (6%), and grade 3and 4 diarrhea in one patient (3%) each. One patient each experiencedgrade 4 ALT and grade 3 bilirubin and AST elevations. Conclusions:MTA plus cisplatin is well tolerated and activeagainst NSCLC. Further studies of this combination are warranted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008336931378
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  • 9
    Electronic Resource
    Electronic Resource
    Cisplatin/etoposide/ifosfamide stepwise dose escalation with concomitant granulocyte/macrophage-colony-stimulating factor for patients with far-advanced testicular carcinoma (1991)
    Springer
    Journal of cancer research and clinical oncology 117 (1991), S. S198 
    Details
    ISSN: 1432-1335
    Keywords: Testicular cancer ; GM-CSF ; Cisplatin ; Etoposide ; Ifosfamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to develop a more dose-intensive induction regimen for the treatment of far-advanced testicular tumours, the German Cooperative Group for Testicular Tumours started a dose-escalation trial of cisplatin, etoposide and ifosfamide. At the first dose level 18 patients with advanced testicular cancer (Indiana University classification) received cisplatin 25 mg/m2, etoposide 120–150 mg/m2 and ifosfamide 1.2 g/m2 for 5 days every 3 weeks. Of these, 13 patients (72%) became tumour-free, 2 achieved a stable, marker-negative partial remission, 2 had progressive disease and 1 patient died ofClostridium sepsis. The main toxicity was myelosuppression with a white blood cell nadir of 900/μl and a thrombocyte nadir of 47000/μl. Granulocytopenic fever occurred in 43% of all cycles. At the second dose level 15 patients received cisplatin 30 mg/m2, etoposide 150 mg/m2 and ifosfamide 1.6 g/m2 five times every 3 weeks together with s.c. recombinant granulocyte/macrophage-colony-stimulating factor (GM-CSF) 10 μg/kg on days 6–15. Acute toxicity was severe with a white blood cell nadir of 300/μl and thrombocyte nadir of 11 000/μl. The duration of the thrombocytopenia increased with cycle number; 63% of all cycles were associated with granulocytopenic fever and in 83% platelet transfusions were required. One patient died from acute renal failure andAspergillus sepsis; 3 patients experienced adverse reactions to GM-CSF, requiring omission of this drugs in 2; 33% had grade 3 or 4 mucositis. At this dose level 8 patients (53%) became tumour-free, 4 patients (26%) had marker normalization with irresectable residual disease and 2 patients were treatment failures. Though acute toxicity was severe at this dose level, there was no unexpected or unmanageable organ toxicity and thus patients are now entered at dose level 3, which consists of cisplatin 30 mg/m2, etoposide 200 mg/m2 and ifosfamide 1.6 g/m2 for 5 days and GMCSF 10 μg kg−1 day−1 on days 6–15 s.c.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01613227
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  • 10
    Electronic Resource
    Electronic Resource
    The value of bone marrow examination for tumor staging in breast cancer (1988)
    Springer
    Journal of cancer research and clinical oncology 114 (1988), S. 425-428 
    Details
    ISSN: 1432-1335
    Keywords: Bone marrow examination ; Cytokeratin antibodies ; Breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of our study was to investigate the value of cytokeratin antibodies for identifying bone marrow involvement in breast cancer patients who showed no evidence of distant metastases using noninvasive tumor staging procedures. Bone marrow for histological (biopsy) and immunocytochemical (aspiration) evaluation was obtained from the anterior iliac crest from 50 unselected consecutive women during surgical treatment of the primary tumor. The histological examination was done on nondecalcifed bone sections. The immunocytochemical studies were carried out on interface smears of the bone marrow aspirates. For staining, cytokeratin antibodies (PKK 1) and the immune alkaline phosphatase method was used. Cytokeratin-positive cells were found in 4 of the 50 cases (8%). Of those 4 patients, however, 2 also showed evidence of neoplastic bone marrow infiltration histologically. We thus were able to prove that immunocytochemistry on aspirates is superior to conventional histology in identifying tumor in bone marrow. Nonetheless, our results clearly fell below the rate found in previous studies where epithelial membrane antigen antibodies were used.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02128190
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