Biomedical subjects

M Riepl

Publications and source records attributed to M Riepl.

12 recordsLinked to original sources

PubMed2000

[Endoscopic pretherapeutic clipping for gastrointestinal tumors. A method for exact definition of the target volume].

BACKGROUND: In many cases it is not possible to exactly define the extension of carcinoma of the gastrointestinal tract with the help of computertomography scans made for 3-D-radiation treatment planning. Consequently, the planning of external beam radiotherapy is made more difficult for the gross tumor volume as well as, in some cases, also for the clinical target volume. PATIENTS AND METHODS: Eleven patients with macroscopic tumors (rectal cancer n = 5, cardiac cancer n = 6) were included. Just before 3-D planning, the oral and aboral border of the tumor was marked endoscopically with hemoclips. Subsequently, CT scans for radiotherapy planning were made and the clinical target volume was defined. Five to 6 weeks thereafter, new CT scans were done to define the gross tumor volume for boost planning. Two investigators independently assessed the influence of the hemoclips on the different planning volumes, and whether the number of clips was sufficient to define the gross tumor volume. RESULTS: In all patients, the implantation of the clips was done without complications. Start of radiotherapy was not delayed. With the help of the clips it was possible to exactly define the position and the extension of the primary tumor. The clinical target volume was modified according to the position of the clips in 5/11 patients; the gross tumor volume was modified in 7/11 patients. The use of the clips made the documentation and verification of the treatment portals by the simulator easier. Moreover, the clips helped the surgeon to define the primary tumor region following marked regression after neoadjuvant therapy in 3 patients. CONCLUSIONS: Endoscopic clipping of gastrointestinal tumors helps to define the tumor volumes more precisely in radiation therapy. The clips are easily recognized on the portal films and, thus, contribute to quality control.

Endoscopy, Gastrointestinal↗

PubMed2000

Neoadjuvant radio-chemotherapy in advanced primarilynon-resectable carcinomas of the pancreas.

AIM: To investigate the feasibility of neoadjuvant radio-chemotherapy (RCT) in the treatment of primarily non-resectable pancreas carcinoma the parameters tumour regression, possibility of subsequent resection and tolerability were examined. METHOD: Between 1995 and 1997, 27 patients with locally inoperable (assessed by CT criteria) pancreatic carcinoma received radio-chemotherapy for 5 weeks comprising irradiation (55.8 Gy) and chemotherapy with 5-fluorouracil (5-FU, 1000 mg/m(2)/day; 120 h continuous infusion) and mitomycin C (10 mg/m(2)i.v.-bolus, day 2 and day 30) during the first and fifth week of radiotherapy. Two target volumes were irradiated with fractionated doses of 1.8 Gy up to a total of 50.4 Gy. Radiation was applied once a day five times a week and target volume 1 was irradiated with the same fractionated dose, and an additional boost of 5.4 Gy to make an overall total of 55.8 Gy. RESULTS: Sixteen patients underwent explorative laparotomy, 10 of these were resected (eight Whipple's procedures, two distal pancreatic resections), while six could not be resected due to peritoneal carcinosis (n=3), local irresectability (n=2) and liver cirrhosis (n=1). A further nine patients were found to have unresectable tumours on CT and did not undergo surgery after restaging (five of these patients were staged as < >, three patients had distant metastases and one patient refused surgery). In two patients RCT was abandoned because of progression of disease. CONCLUSIONS: The study protocol described is feasible without significant acute toxicity and when used the resectability rate was improved; the survival rate, however, was not improved. Additional intra-arterial or intraportal application of such drugs as mitomycin C or cisplatin may be necessary.

Adenocarcinoma↗

PubMed1998

[Use of G-CSF (Neupogen) in multimodal treatment in radiotherapy].

BACKGROUND: Therapy-induced leukopenias with corresponding consequences repeatedly occur in radiotherapy using combined modalities treatment. In radiotherapy, where G-CSF (granulocyte-colony-stimulating-factor) is not licensed, G-CSF has been used successfully under individual circumstances. These results were confirmed in several studies with small patient groups. The aim of this study was to check former results in a larger patient group, to verify postulated side effects and specially to define a cost-effective schedule in the treatment with G-CSF (Neupogen). PATIENTS AND METHODS: In this surveillance trial 50, partially previously treated patients with different malignant tumors were treated with G-CSF. According to the probability of a leucocytosis lower than 1000/mm3, G-CSF (Neuropogen) was already given at leukocyte values lower than 2500/mm3 (500/mm3 bis 2450/mm3). It administered subcutaneously every other day, based on body weight until reaching normal leucocyte levels. RESULTS: In 92% of the patients the increase of leucocytes occurred in the first 24 hours. On average G-CSF was given 4.9 times per patient. Patients without prior therapies or less complex therapies needed less G-CSF applications (3.5 to 5.8 applications). Due to individually varying leucocyte courses the G-CSF therapy was started with leucocyte values between 500/mm3 and 2450/mm3. Patients who were treated with up to 3 G-CSF applications had higher leucocyte levels than those with 4 or more applications (1620/mm3 to 1250/mm3). Leucopenia related infections, therapy interruptions or break-offs did not occur. Besides light "flu like" symptoms in 14% of the patients, no side effects were observed. CONCLUSIONS: When a decrease of leucocyte values lower than 1000/mm3 is expected, the most cost-effective treatment is given when starting the interventional G-CSF administration already at leucocyte values around 1600/mm3. Leucopenias can be treated effectively, with little side effects and in a cost-effective way when G-CSF is given on time.

Adult↗

PubMed1997

[G-CSF in radiochemotherapy].

BACKGROUND: G-CSF enhances the division, maturation and release of granulocyte precursor cells. The shortening of chemotherapy-induced leukopenia via G-CSF is well documented in literature, with fractionated radiotherapy alone one finds a distinct increase of the granulocyte level. There are only few results for combined simultaneous radiochemotherapy. PATIENTS AND METHODS: In the Department of Radiotherapy of the University of Erlangen 102 patients were treated with G-CSF since 1992. Twenty-eight patients (31 applications) undergoing radiotherapy only (n = 4) or combined simultaneous radiochemotherapy (n = 27) received G-CSF interventional daily. These results are presented and discussed. Indications for the application of G-CSF were severe leukopenia below 1000/mm3 (level IV according to WHO) or rapid decreasing leukocytes during therapy. G-CSF was not applied during chemotherapy and terminated at least 24 h before the next chemotherapy cycle. r-metHuG-CSF (Filgrastim, Neupogen) was used subcutaneously. Documented were the duration until the leukocyte increase, neutrophil granulocytes, thrombocytes, interruption of radiotherapy, febrile episodes and side effects. RESULTS: In case of severe leukopenia (< 1000/mm3 n = 16) the leukocytes increased after 3 days of G-CSF application, the radiotherapy was interrupted in 2 cases, terminated in 1 case. Four patients had lever before during G-CSF 4 additional febrile episodes occurred. If G-CSF application was started between leukocyte levels of 1000 and 1500/mm3 after 1 day the leukocytes increased in 9 of 10 cases beyond the starting level. Interruption of radiotherapy was not necessary. Only 1 febrile episode occurred (1/11). There were no relevant side effects of G-CSF. CONCLUSIONS: Rapidly developing or severe leukopenia during radio(chemo)therapy are indications for an interventional application of G-CSF. The leukocyte level for the start of G-CSF should be chosen so that without G-CSF an interruption of therapy or a level IV leukopenia seems to be unavoidable.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Capacitive monitoring of protein immobilization and antigen-antibody reactions on monomolecular alkylthiol films on gold electrodes.

Self-assembled monolayers of omega-mercaptohexadecanoic acid and omega-mercaptohexadecylamine on gold electrodes are stable at neutral pH and display pure capacitive behavior at frequencies around 20 Hz. Different methods of covalent immobilization of proteins on these monolayers are compared. Various reagents including succinimides, thionylchloride, p-nitrophenol and carbodiimides were used to activate the carboxy groups of the adsorbed monolayer of omega-mercaptohexadecanoic acid. Glutaraldehyde, cyanuric chloride and phenylene diisocyanate were used to activate the amino groups of the monolayer of omega-mercaptohexadecylamine. The immobilization of albumin on the activated surface was studied by capacitive measurements. The N-hydroxysuccinimide and carbodiimide methods were identified as most suitable for protein immobilization in that they did not compromise the insulating properties of the alkylthiol layer and led to maximal increase of its dielectric thickness. These approaches were used for a layer-by-layer preparation of a capacitive immunosensor. Specifically, antibodies to human serum albumin were immobilized on the alkylthiol mono-layer. Binding of the antigen led to a decrease of the electrode capacitance. The detection limit of the immunosensor is as low as 15 nM (1 mg/l).

Alkylation↗

PubMed1997

Supportive use of megestrol acetate in patients with head and neck cancer during radio(chemo)therapy.

To study the supportive effect of megestrol acetate during intensive combined modality treatment, a randomised, double-blind, placebo-controlled study was performed in patients with head and neck cancer. The patients received either 160 mg of megestrol acetate daily or placebo during radio(chemo)therapy and for up to 6 weeks thereafter. The nutritional status as measured by anthropometric and biochemical parameters and the subjective quality of life were assessed prior to therapy, at weeks 1, 4 and 6 of radiotherapy and 12 and 18 weeks from the start of therapy. 61 of 64 patients were evaluable. In the control group (n = 30), the nutritional parameters deteriorated during therapy and were fully restored during follow-up. By contrast, the patients treated with megestrol acetate (n = 31) could maintain their baseline values. The difference between the groups was most pronounced in patients taking food per mouth (weight loss during treatment: control group: 4.1 kg; megestrol acetate group: 0.8 kg, P = 0.0004), but was not significant in patients fed via percutaneous endoscopically guided gastrostomy (PEG). Subjective quality of life remained constant in the megestrol acetate group while it decreased in the control group. However, differences were not statistically significant. Megestrol acetate prevents further deterioration of nutritional status during radio(chemo)therapy and may have an impact on subjective quality of life.

Adult↗

PubMed1996

[Radiochemotherapy and simultaneous hormonal therapy of locally advanced prostatic carcinoma].

PURPOSE: The results of radiotherapy alone in the prostate cancer stage T3-T4 are not satisfactory. We investigated, whether the combination of radio-chemotherapy with hormone therapy, possible most effective therapy in stage III, will be tolerated without serious side effects. PATIENTS AND METHODS: Eight patients with prostate cancer T3/T4 were treated with concurrent radio-chemotherapy and hormone therapy. The mean doses in reference point was 61.7 Gy, the single dose was 1.8 Gy. The patients received epirubicin 20 mg/m2 and 5-fluorouracil 800 mg/m2 on day 1 to 5 and 29 to 33 of radiotherapy. The hormone therapy began before the radio-chemotherapy started. RESULTS: Only the hematological side effects were relevant. Three out of 8 patients had leucopenia grade III and 1 of 8 patients leucopenia grade IV according WHO. Other serious complications could not be observed. CONCLUSION: The concurrent radio-chemotherapy with epirubicin and 5-fluorouracil in the combination with hormone therapy was tolerated well. The effectiveness of this new treatment should be examined prospectively in prostate cancer stage T3-T4.

Adenocarcinoma↗

PubMed1996

[Supportive treatment with megestrol acetate during radio(chemo)therapy in patients with tumors in the head-neck area. A randomized study].

BACKGROUND: The value of megestrol acetate in treating tumor anorexia and cachexia of terminal patients is well known. However, the supportive effect of megestrol acetate during intensive radio-(chemo-)therapy was not investigated up to now. Therefore a randomized trial was performed including patients with advanced tumors in the head and neck region. PATIENTS AND METHODS: From June 1991 to December 1993 a total of 64 patients were admitted to a randomized, double-blind placebo-controlled study. During and up to 6 weeks following radiotherapy patients received 160 mg/d megestrol acetate or placebo. The nutritional status (anthropometric and laboratory parameters) and the quality-of-life index according to Padilla et al. [24] were determined prior to therapy, 1, 4, 6 weeks later during radiotherapy and 12, 18 weeks after completion. RESULTS: Sixty-one out of 64 patients were evaluable (control group: n = 30; megestrol acetate patients: n = 31). One patient refused further participation after randomization. One patient in each arm was excluded due to side effects (impotence, diarrhoea). Further side effects were not observed. In the control group the nutritional parameters (body weight, triceps skinfold) and the subjective feeling of the patients deteriorated during radiotherapy and did not restore following radiotherapy. By contrast, the patients of the megestrol acetate group were able to stabilize these parameters. This difference was most prominent in the orally nourished patients (weight loss during therapy: control group: -4.1 kg; megestrol acetate group: -0.8 kg; p = 0.004); but not in the patients fed by percutaneous endoscopically guided gastrostomy (weight loss control group: -2.4 kg; megestrol acetate group: -0.8 kg; p = 0.14). CONCLUSION: In patients on radiochemotherapy megestrol acetate prevents patients from further deterioration of the nutritional status and quality of life.

Anthropometry↗

PubMed1996

[Reoxygenation in Yoshida sarcoma during different fractionated radiotherapy].

PURPOSE: Tumor reoxygenation is one of the most important factors determining the tumor control probability after radiotherapy. In experimental studies reoxygenation has been measured preferably after single dose irradiation. Only few data exist about changes in the hypoxic tumor fraction during fractionated radiotherapy. MATERIAL AND METHODS: The changes in the pO2 during fractionated radiotherapy were studied in Yoshida sarcoma transplanted to Wistar rats. Tissue oxygenation was assessed using a polarographic electrode system at the beginning, in the middle and at the end of radiation therapy. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy. RESULTS: In the statistical analysis significant changes emerged in the mean, median, 10%-percentile and 0 to 2.5 mm Hg and 0 to 5.0 mm Hg values dependent on time. The tumors were significantly more hypoxic at the end of therapy. This trend became more pronounced with decreasing dose per fraction. CONCLUSIONS: The Yoshida sarcoma has no effective reoxygenation during fractionated radiotherapy.

Animals↗

PubMed1994

[Hypoxia-radiotherapy: the changes in selected physiological parameters of healthy tissue during the breathing of a hypoxic gas mixture].

BACKGROUND: Chronic hypoxia in tumors is generally accepted to be one of the most important factors concerning sensibility to irradiation. The principle of hypoxyradiotherapy is to achieve a limited (maximal 30 min) radioresistance of the healthy (actually euoxic) tissue by acute aerogen hypoxia, without protecting effects in the average chronic hypoxic tissue of the tumor. This study investigates changes in selected physiological parameters in vivo during acute aerogen hypoxia. PATIENTS AND METHODS: In 31 persons (group A) we documented changes in blood-gas-analysis, ECG-parameters, blood pressure and pulse during acute hypoxia lasting 5 minutes. During 30 minutes of acute hypoxia we determined in another 10 persons (group B) the relations between different phosphoryl-metabolites by means of 31-phosphorus magnetic resonance spectroscopy (31P-MRS). The 31P-MRS of the Musculus triceps surae was performed on our 1.5 T imaging system (Magnetom, Siemens) using a 8 cm diameter surface coil. To achieve the hypoxic condition in the persons tested, a gas-mixture with 8.2% O2 was used. RESULTS: In group A the acute hypoxia led to significant changes in O2-pressure, the blood O2-saturation and pulse frequency. The pO2-values drop in the 5th minute to about 50% of the initial value. Concerning group B the relations of the phosphoryl metabolites show no significant changes during acute hypoxia. CONCLUSIONS: The results show an excellent tolerability of breathing of the hypoxic gas-mixture, and confirm that this mixture containing 8.2% of O2 ensures a decrease in the pO2-levels of more than 50%. This is necessary to achieve a dose modifying factor (DMF) of at least 1.15 to 1.2. The changes in relations of phosphoryl metabolites seem to reflect the ability of healthy tissue to adapt to hypoxic conditions starting after 10 minutes and leading to the loss of the radioprotective effect after 30 minutes.

Acute Disease↗

PubMed1994

[Radiochemotherapy in the liver metastases of cystosarcoma phyllodes].

BACKGROUND: Cystosarcoma phyllodes is a rare mesenchymal tumor in the breast with a quite different prognosis depending on its specific dignity. There are almost no data in the literature concerning therapeutic strategies of metastasized cystosarcoma phyllodes. PATIENTS AND METHODS: We report the unique case of a young female patient with advanced multiple liver metastases of a cystosarcoma phyllodes malignum. RESULTS: After irradiation of the total liver combined with simultaneous chemotherapy containing ifosfamide and adriamycin an impressing 12 months lasting remission and control of the liver metastases was achieved. No relevant treatment side effects were observed. CONCLUSION: Combined liver irradiation and simultaneous chemotherapy should be considered as effective treatment strategy for comparable situations in young patients with good physical conditions.

Adult↗

PubMedDate not supplied

A minimal binding domain of the low density lipoprotein receptor family.

As more relatives of the low density lipoprotein receptor (LDLR) are discovered, defining their minimal binding domain(s) becomes a challenge. Here we have chosen the multifunctional chicken oocyte receptor for yolk deposition (termed LR8), and the pan-receptor ligand, receptor associated protein (RAP), as model systems to characterize a minireceptor using the phage display approach. Displayed fragments derived from the entire 819 residue LR8 molecule, followed by selection via panning on RAP, led to the definition of an 80 residue stretch LR8 minireceptor. It contains 12 cysteines, and represents parts of the second, the entire third, and parts of the fourth, of the eight clustered 'ligand binding repeats' in LR8; only two of the eight stretches of negatively charged residues of LR8, i.e., EDGSDE and DSGEDEE, are present. The latter sequence is reminiscent of that in the fifth repeat of the human LDLR, thought to be most critical for interaction with positive charge clusters in ligands. Baculovirus-mediated expression of the soluble minireceptor in insect cells showed it to fold as a monomer, and sulfhydryl-reduction-sensitive interaction with RAP was demonstrated for immobilized as well as soluble minireceptor. Furthermore, the LR8-derived minireceptor provided a RAP-responsive surface when covalently coupled to the surface of a gold electrode. In addition to its use in defining minimal binding domains, the phage display approach provides powerful tools for dissection, and consequently, manipulation, of the function of receptors so as to direct their binding activity toward ligands of diagnostic and/or therapeutic interest.

Amino Acid Sequence↗