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L Plasswilm

Publications and source records attributed to L Plasswilm.

At least 19 recordsLinked to original sources
PubMed2000

Activity of extracranial metastases as a prognostic factor influencing survival after radiosurgery of brain metastases.

Information about prognostic factors influencing survival have been only occasionally reported in studies on the use of radiosurgery in the treatment of patients with brain metastasis. To answer the question of whether activity of extracranial metastases is an independent prognostic factor influencing survival in radiosurgery of brain metastases, a review of the literature was performed. Fourteen studies were identified in the English language literature that dealt with this topic. Only three studies showed borderline insignificance of the influence of activity of extracranial metastases when analysed by univariate methods. When multivariate analysis was used to test for the independent influence of this factor on survival, of nine studies that used that statistical approach eight showed that it is an independent prognosticator influencing survival, most often being the strongest one. This review of literature supports the view that the "activity of extracranial metastases" is an independent prognostic factor influencing survival of these patients as documented in published reports. However, prospective randomised trials are necessary to definitely establish the independent influence of this prognostic factor.

Analysis of Variance↗
PubMed2000

Time- and dose-limiting erysipeloid rash confined to areas of lymphedema following treatment with gemcitabine--a report of three cases.

Gemcitabine is a deoxycytidine analog with broad antitumor activity. Its main toxicities include myelosuppression, flu-like symptoms, bronchospasms and mild skin rash. We report three cases, in which the patients developed time- and dose-limiting erysipeloid skin reactions confined to areas of impaired lymphatic drainage after application of gemcitabine. Three patients with metastatic tumors (breast cancer, endometrial cancer and non-small cell lung cancer) received weekly infusions of gemcitabine (1000 mg/m2). All patients suffered from lymphedema of different origin and developed an erysipeloid erythema 40-48 h after chemotherapy within their preexisting lymphedema. Genuine erysipela was ruled out by laboratory tests and clinical observation. The skin reaction was repeatedly observed and faded after 14 days without specific treatment. Although the pathogenesis of the observed reaction is unclear, it is suspected that the skin symptoms were caused by gemcitabine or its metabolites. Gemcitabine is usually metabolized fast and excreted renally. In areas with impaired lymphatic drainage pharmakocinetics might be altered: inactivation happens slower and the drug might accumulate in the s.c. and cutaneous tissue, thus increasing local toxicity. Clinical judgement and biochemical parameters can help to tell apart genuine erysipela and the erysipeloid reaction.

Aged↗
PubMed1999

Interaction of paclitaxel (Taxol) and irradiation. In-vitro differences between tumor and fibroblastic cells.

AIM: Optimal dose and schedule of paclitaxel in combined drug-irradiation treatment could not be determined for most of tumors yet. The aim of this study was to compare in vitro cytotoxicity and radiosensitizing abilities as a function of single paclitaxel (Taxol) exposure in tumor and fibroblastic cells using different drug incubation irradiation intervals. MATERIAL AND METHOD: A lung-carcinoma (SK-LU-1), glioblastoma (U-138 MG) and rodent fibroblast cell line (HyB14FAF28) were used. The clonogenic assay was applied for survival investigation. alpha beta-values were calculated using the linear-quadratic model (log S = -alpha D - beta D2). Cytotoxicity of Taxol was examined at 0 to 50 microM. Combined Taxol-radiotherapy exposure was accomplished with 10 microM Taxol plus 10 Gy irradiation (RT) following after a 1-hour and 9-hour interval. For controls cells were exposed to Cremophor EL/ethanol (CEL/eth) and a phosphate buffered saline (PBS). RESULTS: Single Taxol exposure (10 microM) resulted in 0.54/0.50/0.84 (3-hours incubation) and 0.094/0.48/0.82 (15-hours incubation) survival of SK-LU-1, U-138 MG and HyB14FAF28 cells, respectively. Taxol concentrations from 2 to 50 microM only had cytotoxic effect in tumor cells. Single dose RT (10 Gy) led to cell survival of 0.0006/0.006/0.03. The diluent CEL/eth also showed cytotoxic activity. Taxol plus RT led to cell survival of 0.00025/0.0014/0.042 (1 hour) and 0.0004/0.0019/0.04 (9 hours) without significant difference between chosen time intervals. alpha beta-values showed great variation lacking evidence for definite radiosensitization. alpha increase after Taxol and alpha decrease after CEL/eth exposure were detected. CONCLUSIONS: The data presented demonstrate a potential beneficial effect, described as co-operation, by combining Taxol and RT in human tumor cells and rodent fibroblasts. High intrinsic alpha components of the tumor cells as well as CEL/eth's antagonizing actions could be likely to disturb and influence paclitaxel's abilities leading to radiosensitization.

Adenocarcinoma↗
PubMed1999

Effect of amifostine (Ethyol) on the development of extraembryonic blood vessels in chick embryos.

AIM: Systemic and local side effects can limit radio- as well as chemotherapy in patients suffering from neoplastic diseases. One possibility to reduce the therapy-dependent side effects is to attenuate radical induced alterations of normal healthy tissue by application of antioxidants. Preclinical and clinical studies demonstrated the ability of amifostine to protect normal, but not neoplastic, tissues from cytotoxic effects of chemotherapy or irradiation. The purpose of the present study was to establish whether amifostine (Ethyol) can affect microvessel density in vivo. MATERIAL AND METHODS: For this study fertilized crossbred "White-Plymouth-Rocks x Sussex" eggs were used. After 48 hours of incubation 0.05 ml solution containing 25.7 micrograms (approximately 120 microM) amifostine were injected next to the germ disc. Taking into account the mean surface area of the are vasculosa and the embryo, this corresponds to a dose of 26 micrograms/cm2. As controls, the area vasculosa of eggs treated with 0.05 ml NaCl 0.9% were used. Twenty-four and 48 hours after injection of amifostine or NaCl photographs and video microscopic pictures from treated areas and controls were taken and evaluated for vascular density. Results of vascular density are given as vascular intersections per mm2 (VIS/mm2). RESULTS: There was a significant (p < 0.001) difference in vascular density with a mean microvessel count of 30.40 (+/- 12.84 SD) VIS/mm2 in the NaCl control and 53.69 (+/- 24.56 SD) VIS/mm2 in the amifostine-treated area vasculosa. CONCLUSION: The results show that amifostine induced an increase in vascular density in the rapidly proliferating area vasculosa of the early chick embryo.

Amifostine↗
PubMed1999

Investigation of microvessel density after irradiation.

It is believed that malignant cell populations need the development of microvessels to grow and metastasize. The aim of our investigation was to find out whether gamma irradiation can affect proliferation of endothelial cells and thus can affect microvessel density in vivo. We used fertilized chicken eggs. The vascularized part of the yolk sac membrane (area vasculosa) of the eggs received single doses of 2 to 10 Gy. Forty-eight hours after irradiation, the area vasculosa was photographed in vivo, and prints of known magnification were evaluated to determine the density of the blood vessels. Microvessel count is the well-established marker used to determine vascular density. In addition, the proliferative activity of endothelial cells in the yolk sac membrane was determined by estimating the expression of proliferating cell nuclear antigen (PCNA). PCNA immunostaining was assessed immunohistochemically. After a single dose of 10 Gy, a statistically significant increase in vascular density was found compared to values determined at 0, 2, 4 and 8 Gy (P < 0.05). Twenty-four hours after 10 Gy irradiation, 44.8% (mean) of the endothelial cells were PCNA-positive. This was significantly higher (P < 0.05) compared to the results 24 h after 4.0 Gy (22.7%) and compared to control (19.4%). Twenty-four hours later, i.e. 48 h after irradiation with 10 Gy, the endothelial cells also showed a significantly (P < 0.05) higher PCNA positivity with a mean of 34.1% compared to the nonirradiated area vasculosa (18.1%) and compared to the results after 4.0 Gy irradiation (12.0%). The prerequisite for blood vessel formation is the proliferation of endothelial cells. Thus a single-dose irradiation with 10 Gy induces endothelial cell proliferation and subsequent neovascularization in the area vasculosa of the fertilized egg.

Animals↗
PubMed1998

Schedule-dependent interaction of paclitaxel (Taxol) and irradiation in vitro.

The optimal dose and schedule of paclitaxel in combination with irradiation have not been determined yet. The aim of this study was to compare the in vitro cytotoxicity and enhancement of radiation sensitization as a function of single vs. fractionated paclitaxel exposure. A fibroblast cell line (B14) in exponential growth phase was used. The clonogenic assay was applied to determine cell survival. Flow cytometric measurements were performed to study cell cycle DNA distribution. Cytotoxicity of Taxol was examined at concentrations varying from 2 to 50 microM. Single (1 x 0 microM) vs. fractionated (2 microM/day, days 1-5) exposure of Taxol was investigated. The combination of Taxol plus irradiation as single and fractionated treatment was accomplished with 10 microM Taxol on day 1 plus 10 Gy irradiation on day 1 vs. Taxol 2 microM/day, days 1-5, plus irradiation 2 Gy/day, days 1-5. One-, 9-, and 24-hr intervals between end of incubation and irradiation were defined. Control populations demonstrated an average plating efficiency of 93%. Single Taxol exposure showed an average clonogenic survival of 84%. No significant difference between concentrations varying from 2 to 50 microM was observed. Single dose irradiation (1 x 10 Gy) led to clonogenic survival of 3%. Single exposure of Taxol plus single dose irradiation led to clonogenic survival of 4%. Fractionated radiation showed an average clonogenic survival of 41%. Fractionated Taxol treatment led to an average clonogenic survival of 63%. The combination of fractionated Taxol treatment (2 microM/day, days 1-5) plus fractionated irradiation (2 Gy/day, days 1-5) showed an average clonogenic survival of 15%. No significant difference between the chosen intervals was demonstrated. Flow cytometric measurements did not indicate any significant alterations in cell cycle DNA distribution. In conclusion, the data demonstrate a potential beneficial effect by combining fractionated Taxol exposure with fractionated irradiation without evidence for G2/M arrest in DNA analysis.

Animals↗
PubMed1998

Cytotoxicity of fractionated paclitaxel (Taxol) administration in vitro.

PURPOSE: Paclitaxel (Taxol) is a new anticancer agent with a novel mechanism of action. It has demonstrated broad clinical activity in a variety of malignancies. Several aspects of paclitaxel's usage remain to be clarified, including the optimal treatment schedule. Furthermore, the diluent of paclitaxel, Cremophor EL/ethanol, alone has shown to be markedly active in tumor samples. MATERIAL AND METHODS: The in-vitro cytotoxicity of paclitaxel (Taxol) due to single dose (1 x 10 microM/day, day 1 incubation time: 3 h and 15 h) and fractionated exposure (5 x 2 microM/day, day 1 to 5 incubation time: 3 h/day) was evaluated, measuring surviving fraction (clonogenic assay) and DNA distribution (flow cytometric analysis). In the control population, the diluent Cremophor EL/ethanol or a phosphate buffered salt solution (PBS) were applied using identical doses and schedules. A mammalian fibroblast cell line (HyB14FAF28) was used. RESULTS: Fractionated application of paclitaxel (Taxol) produced a significant lower clonogenic survival (0.63) in comparison with single dose exposure for 3 h (0.84) and 15 h (0.82). DNA analysis showed no evidence for a significant difference in DNA distribution of the paclitaxel-specific G2/M phase over a 10-day period. Controls with the diluent Cremophor EL/ethanol showed a clonogenic survival of 0.87 (3 h exposure) and 0.88 (15 h exposure) versus 0.65 after fractionated drug administration (5 x 2 microM/day, day 1 to 5, incubation time: 3 h/day). PBS controls and untreated controls did not show any significant effect. CONCLUSIONS: It seems that clonogenic survival after Taxol exposure of this mammalian fibroblast cell line varies with treatment schedule through a yet unknown process that does not involve G2/M arrest. The results indicate the treatment effects to be mainly based on the diluent combination without any further benefit induced by paclitaxel.

Animals↗
PubMed1998

The phantom.

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Adult↗
PubMed1997

In vivo investigations of vascular density and local mitochondrial metabolism after irradiation.

It is obvious that irradiation increases local oxygen uptake. Because the oxygen supply is not altered, a decrease in local oxygen partial pressure may develop. This state may be called relative hypoxia. If the metabolism is altered for a period of at least 24 hrs an increase in angiogenic mitogens, inducing angiogenesis will occur. Presumably this is the mechanism underlying the therapeutic effect of radiotherapy in benign disease.

Animals↗
PubMed1996

Simultaneous radiochemotherapy for recurrent and metastatic breast carcinoma: evaluation of two treatment concepts.

Patients with locally recurrent and metastatic breast carcinoma require effective palliation of pain and complicating cutaneous, soft tissue, and lymph node metastases. Since October 1989, 48 consecutive patients with recurrent breast carcinoma after mastectomy and no further surgical option were entered in a phase I-II study comparing two radiochemotherapy (RCT) regimens. Treatment-related toxicity was analyzed in 48 patients together with short- and long-term efficacy in 44 patients who had a minimum follow-up of at least 1 year. Since October 1989, group A (28 patients) received 60 Gy "split-course" radiotherapy (RT) over 10 weeks with two breaks of 2 weeks each after the second and fourth week of RT. Simultaneous 5-fluorouracil, methotrexate, and cyclophosphamide (CMF) was given during RT. From October 1991 to April 1993, group B (20 patients) received 54-60 Gy "conventional" RT over 6 weeks. Simultaneous 5-fluorouracil/mitomycin C was applied in the first and fifth week. Overall response [complete response (CR) + partial response (PR)] was 82% in group A (CR, 21%). Five of 28 patients developed grade 3-4 toxicity (EORTC/RTOG/WHO). Overall response rate in group B was 87% (CR, 19%). In this group, 6 of 20 patients experienced grade 3-4 toxicities. In both groups, the rate of local response was remarkably lower in patients with distant metastases and a short relapse interval < 2 years. Although both regimens achieved a similar local response rate, group B patients experienced a higher toxicity rate than did group A patients, but the treatment duration was considerably shorter. The local tumor response was greatly influenced by the extent of systemic disease.

Antibiotics, Antineoplastic↗
PubMed1996

[Radiobiologic in-vivo investigation of angiogenesis in the yolk sac vascular system of chicken embryos].

PURPOSE: The aim of this study was to investigate whether the yolk sac blood vessel system of chick embryos represents a useful model of in-vivo measurements of angiogenesis in radiobiology. MATERIAL AND METHODS: The fertilized eggs of the crossbreeding White Plymouth Rox X Sussex were used for the study of the extraembryonic vascularisation after irradiation with different fractionation and dosage. On day 3 of incubation an oval window was cut into the shell and then the area vasculosa was irradiated with 1.0 cm in diameter. Forty-eight hours after irradiation in-vivo photographs were taken for quantitative evaluation of blood vessel density. RESULTS: Irradiation from 2.0 to 8.0 Gy in a single fraction leads to a slight decrease in vascular density. After a single fraction of 10.0 Gy a distinct increase in vascular density occurs. Fractionated irradiation leads to a considerable clear increasing of vascular density in comparison with the single fraction and same total dose. CONCLUSION: Our model of the fertilized egg enables in-vivo measurements of angiogenesis in radiobiology.

Animals↗
PubMed1996

Concurrent Taxol and split-course accelerated radiotherapy for advanced head and neck cancer.

AIM: The aim of this study was to investigate feasibility and toxicity of fractionated paclitaxel administration concurrently with accelerated radiotherapy in the treatment of advanced head and neck cancer. PATIENTS AND METHODS: Patients with a proven histology of inoperable head and neck carcinoma were eligible for this study. Between July 1994 and August 1995, 12 patients with stage IV (UICC) tumors were treated. Patients were required to have normal end-organ function. Exclusion criteria included: age > 70 years, metastatic disease, performance status (Karnofsky < 70), major intercurrent medical disorders, and previous chemotherapy. External radiation was delivered twice a day at 1.5 Gy per fraction, specified to the reference point (ICRU 50), with a minimum interfraction interval of 6 hours. The accelerated scheme was split into 2 courses by a rest period of 9 days (including weekends) after administration of 30 Gy within 2 weeks. After 39 days a total dose of 72 Gy was reached. Paclitaxel (30 mg/m2/d) was administered as a continuous intravenous infusion over a period of 3 hours on days 1 to 5 and 29 to 33 of radiation therapy. All patients received premedication to avoid allergic reactions and circulatory monitoring was used routinely. RESULTS: Radiochemotherapy was completed in 10 patients with 8 complete and 2 partial remissions. Most important toxicity was a short period of neutropenia, which occurred 3 to 6 days after chemotherapy and was associated with fever in 9 cases. During paclitaxel infusion there was a significant but clinically not relevant increase in blood pressure and a decrease in heart rate. No acute cardiac effects occurred and no hypersensitivity reaction was seen. CONCLUSIONS: This regimen demonstrates a high activity in locally advanced head and neck cancer. Neutropenia associated with fever was the major dose limiting toxicity.

Aged↗
PubMed1995

[Simultaneous radiochemotherapy in recurrent and metastatic breast neoplasm. Clinical experience].

BACKGROUND: To improve the quality of life for patients with recurrent and metastatic breast cancer, palliation of pain, skin and soft tissue metastases and complicating lymph node relapses are mandatory. Toxicity and efficacy of 2 simultaneous radiochemotherapy regimens was tested in this study. PATIENTS AND METHODS: From October 1989 to March 1993, 48 patients with locoregional relapse of breast carcinoma after primary mastectomy and no option for curative resection were entered in the study. Seventeen patients had additional distant metastases. Two different radiochemotherapy regimens were applied: Group A (28 patients) received a "split course" radiotherapy within 10 weeks (1.8 to 2 Gy single dose) on day 1 to 12, 29 to 40 and 57 to 68 up to a total dose of 54 Gy. Chemotherapy with 5-FU, methotrexate and cyclophosphamide was applied simultaneously with radiation. After the second and fourth week the treatment was interrupted for 2 weeks. Group B (20 patients) received "conventional" radiotherapy over 6 weeks with 1.8 to 2 Gy single and 54 Gy total dose. 5-FU and mitomycin C was applied in the first and fifth week of radiotherapy. Treatment toxicity was analyzed in 48 patients, while treatment efficacy was assessed in 44 patients with a minimum follow-up of at least 1 year. RESULTS: Overall treatment response (CR+PR) was 82% in group A (CR 21%). Five of 28 patients developed toxicities of grade 3 to 4 (EORTC/RTOG/WHO). The overall response rate in group B was 87% (CR 19%). In this group 6 of 20 patients experienced toxicities of grade 3 to 4. In both groups, the local response rate was remarkably reduced in patients with additional visceral metastases. CONCLUSIONS: Both treatment concepts achieved similar response rates. Group B patients experienced a higher toxicity rate, but treatment duration was considerably shorter. The local response rate correlated well with the extent of systemic metastatic disease.

Antibiotics, Antineoplastic↗
PubMed1994

[Supportive therapy during radiochemotherapy--prevention and therapy of infections].

BACKGROUND: In current radiooncology the consistent use of best supportive care during aggressive combined treatment protocols is indispensible. Presently the optimal management of fever in granulocytopenic patients is controversially discussed. MATERIAL AND METHODS: Based on own clinical experiences and a literature review we report about empiric antibiotic and antifungal therapy in febrile patients with granulocytopenia. Particular consideration is given to the new antifungal agent fluconazole (compared to amphotericin B) and the beta-lactamase inhibitor sulbactam. We also discuss the use of hematopoietic growth factors and selective gastrointestinal decontamination. RESULTS: In fever of unknown origin the use of a two drug antibiotic combination containing an ureidopenicillin (acyl-penicillin) and an aminoglycoside is recommended. After five days of persisting fever additional antimycotic therapy is initiated. Fluconazole shows a high response rate with only few side effects in the treatment of infections with candida albicans and cryptococcus neoformans. In the early empiric antifungal therapy it is more and more replacing amphotericin B. With encouraging results sulbactam can be combined with piperacillin or mezlocillin during radiochemotherapy. Concerning G-CSF there are no general recommendations allowed. We prefer a calculated prophylaxis for patients who receive a myelotoxic chemotherapy and have a high individual risk for severe neutropenia. During the second day of reverse isolation we start a selective decontamination of the digestive tract until white-blood-cell-count increases to more than 1000 to 1500 granulocytes/mm3. CONCLUSION: The radiooncologist should be able to completely manage prevention and treatment of infectious diseases to provide an optimal use of all new options in combined modality treatment in radiooncology.

Anti-Infective Agents↗
PubMed1992

Use of an oxygen multiwire surface electrode for the direct measurement of the distribution of alveolar PO2 at different inspired oxygen concentrations.

Experiments were performed in six anaesthetised, mechanically ventilated rabbits. After thoracotomy, a multiwire surface PO2 electrode was placed at the pleural surface by means of a special holder. The local distribution of PO2 was investigated at different values of inspired oxygen concentration (FIO2). The data were analysed in order to establish (a) whether the PO2 values measured at the lung surface reflect intra-alveolar PO2 and (b) that the distribution of these values represent real physiological differences between alveoli. The mean PO2 values were related to the calculated mean alveolar PO2 (PAO2) values (r = 0.97) indicating that it is possible to study PAO2 by local measurements. It can therefore be concluded that the technique used allows the study of the influence of different FIO2 values on the distribution of PAO2. Each local PAO2 value is the result of the corresponding local ventilation/perfusion ratio (VA/Q) therefore the distribution of PAO2 values represents the distribution of VA/Q. An increasing FIO2 causes an increasing heterogeneity of PAO2 and thus VA/Q leading to a concomitant increase in the alveolo-arterial oxygen difference. At the moment it is not possible to decide if this heterogeneity is primarily caused by heterogeneities in perfusion or ventilation. The results could throw fresh light on the effect of different ventilation procedures.

Animals↗