Note: Sample holder with open area for increased deposition rate in plasma immersion ion implantation and deposition.

A sample holder with a large open area offers several benefits when used in the process of plasma immersion ion implantation and deposition in which the plasma is generated by a high voltage applied to the sample holder: The ignition voltage of the plasma is lower, and the deposition rate can be several times higher than in the case of a normal plate-like holder. There is a more pronounced edge effect regarding the film thickness. Other film properties are also affected; for diamond-like carbon films, the film structure exhibits more disorder. The hardness of the samples is similar, with the surfaces of the samples being very smooth.

Chemical interactions in the layered system BCxNy/Ni(Cu)/Si, produced by CVD at high temperature.

Layered samples Si(100)/C/Ni/BC(x)N(y) and Si(100)/C/Cu/BC(x)N(y) were produced by physical vapor deposition of a metal (Ni, Cu, resp.) and low-pressure chemical vapor deposition of the boron carbonitride on a Si(100) substrate. Between the Si and the Ni (Cu) and on the surface of the Ni (Cu) layer, thin carbon layers were deposited, as a diffusion barrier or as a protection against oxidation, respectively. Afterwards, the surface carbon layer was removed. As precursor, trimethylamine borane and, as an auxiliary gas, H(2) and NH(3) were used, respectively. The chemical compositions of the layers and of the interfaces in between were characterized by total-reflection X-ray fluorescence spectrometry combined with near-edge X-ray absorption fine-structure spectroscopy, X-ray photoelectron spectroscopy, and secondary ion mass spectrometry. The application of H(2) yielded the BC(x)N(y) compound whereas the use of NH(3) led to a mixture of h-BN and graphitic carbon. At the BC(x)N(y)/metal interface, metal borides could be identified. At the relatively high synthesis temperature of 700 °C, broad regions of Cu or Ni and Si were observed between the metal layer and the substrate Si.

[Goal and results of the COSS study]. / Ziele und Ergebnisse der COSS-Studien.

Osteosarcoma is the most common primary malignant tumor of bone (annual incidence: 2 - 3/Mio). Ever since 25 years ago, affected children, adolescents, and adults from Germany, Austria, and Switzerland receive their therapy within trials of the Cooperative Osteosarcoma Study Group (COSS). Approximately 60 % of all patients ever entered into COSS-trials could be cured with an interdisciplinary treatment approach consisting of complete surgical removal of the primary tumor plus intensive pre- and postoperative chemotherapy. The COSS-group's database now includes information on more than 3,000 osteosarcoma patients treated with such a multimodal approach, the largest series worldwide. The present paper is intended to detail the experience gathered from this cohort.

[Surgery of primary malignant bone tumors]. / Operative Therapie primär maligner Knochentumoren.

The term primary malignant bone tumors covers a diversity of entities. Tumor resection is preferable in most. In some, surgery alone is sufficient, in others therapy will be based on a combined modality concept. Resection plays the essential role in those tumors treated by surgery alone, e.g., primary osseous fibrosarcoma. The combined modality approach in osteosarcomas or Ewing's tumors provides for additional elements of local therapy (radiotherapy) or systemic treatment (chemotherapy). The relevance of surgery for local control varies in these latter diagnoses. In highly malignant osteosarcoma, where wide margin surgery is of utmost importance, only 10-20% of patients will survive longer than 5 years without aggressive systemic chemotherapy. Radiotherapy in these patients is only indicated when "marginal" or "less than marginal" surgery is expected. In terms of efficacy, radiotherapy is inferior to surgery. In disseminated osteosarcoma, a curative treatment approach will also provide for surgical removal of all metastases. Treatment of primary malignant fibrous histiocytoma (MFH) of bone is identical to osteosarcoma therapy. Since radiotherapy appears to be marginally more effective than in osteosarcoma, both modalities of local therapy are used. Systemic chemotherapy adds an additional benefit for improved survival. Therapy for Ewing's tumor also follows a combined modality approach. The introduction of systemic chemotherapy has raised 5-year survival rates from less than 10% to above 60%. The role of surgery is currently subject to debate. At present, the use of surgery or irradiation for local control is tailored to the individual patient's needs.

Quantification of daunorubicin and daunorubicinol in plasma by capillary electrophoresis.

Capillary electrophoresis (CE) with laser-induced fluorescence detection was applied to quantify daunorubicin and daunorubicinol in plasma. Separation was carried out in a 47 cm x 50 microm I.D. fused-silica capillary, with a running buffer. pH 5 containing 60 microM spermine and 70% acetonitrile. Sample preparation was done either by protein precipitation with acetonitrile or by liquid-liquid extraction. The assay can be applied in a concentration range from 40 mg/l down to 2 microg/l for daunorubicin and from 1 mg/l to 2 microg/l for daunorubicinol. Precision and accuracy were between 2.9 and 14.5% (n=6) on 1 day and between 1.0 and 14.7% from day to day (n=6) for both analytes. Thus, the CE method enables precise and accurate quantification of daunorubicin and daunorubicinol in small sample volumes over a wide concentration range.

High-activity samarium-153-EDTMP therapy followed by autologous peripheral blood stem cell support in unresectable osteosarcoma.

PURPOSE: Despite highly efficacious chemotherapy, patients with osteosarcomas still have a poor prognosis if adequate surgical control cannot be obtained. These patients may benefit from therapy with radiolabeled phosphonates. PATIENTS AND METHODS: Six patients (three male, three female; seven to 41 years) with unresectable primary osteosarcoma (n = 3) or unresectable recurrent sites of osteosarcomas (n = 3) were treated with high-activity of Sm-153-EDTMP (150 MBq/kg BW). In all patients autologous peripheral blood stem cells had been collected before Sm-153-EDTMP therapy. RESULTS: No immediate adverse reactions were observed in the patients. In one patient bone pain increased during the first 48 hrs after therapy. Three patients received pain relief. Autologous peripheral blood stem cell reinfusion was performed on day +12 to +27 in all patients to overcome potentially irreversible damage to the hematopoietic stem cells. In three patient external radiotherapy of the primary tumor site was performed after Sm-153-EDTMP therapy and in two of them polychemotherapy was continued. Thirty-six months later one of these patients is still free of progression. Two further patients are still alive. However, they have developed new metastases. The three patients who had no accompanying external radiotherapy, all died of disease progression five to 20 months after therapy. CONCLUSION: These preliminary results show that high-dose Sm-153-EDTMP therapy is feasible and warrants further evaluation of efficacy. The combination with external radiation and polychemotherapy seems to be most promising. Although osteosarcoma is believed to be relatively radioresistant, the total focal dose achieved may delay local progression or even achieve permanent local tumor control in patients with surgically inaccessible primary or relapsing tumors.

Therapeutic drug monitoring of doxorubicin in paediatric oncology using capillary electrophoresis.

A method for the determination of doxorubicin and its main metabolite doxorubicinol in human plasma is described. Two different sample preparation procedures are applied depending on the expected concentration: To monitor the peak plasma levels, 10 microL of plasma are deproteinated with acetonitrile. After centrifugation, the supernatant is directly applied to the capillary by hydrodynamic injection. For the determination of lower amounts of doxorubicin and its main metabolite doxorubicinol 100 microL of plasma is extracted by liquid-/liquid extraction with chloroform. After evaporation of the organic phase, the sample is reconstituted in acetonitrile/water (95/5 v/v) and injected into the capillary by electrokinetic injection. Idarubicin serves as the internal standard. Laser-induced fluorescence detection with an Ar-ion laser emitting at 488 nm and a 520 nm cut-off filter is used for detection. The accuracy of the method was calculated to be 3.0% at higher concentrations and 15.0% at the limit of quantification. Reproducibility data are in accordance to the generally accepted criteria for bioanalytical methods. The limit of quantification is 2 microg/L, enabling us to monitor doxorubicin plasma levels for several days after application. Noninvasive blood sampling (from the fingertip) using heparinized capillaries was found to be a simple and convenient procedure and provides reproducible data. Initial results show high interindividual variability in doxorubicin peak plasma levels.