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Biomedical subjects

R G Müller

Publications and source records attributed to R G Müller.

At least 19 recordsLinked to original sources
PubMed2002

Fractionated stereotactically guided radiotherapy of pharmacoresistant temporal lobe epilepsy.

PURPOSE: This prospective study evaluated the efficacy of fractionated stereotactically guided radiotherapy (SRT) as a treatment of pharmacoresistant temporal lobe epilepsy. PATIENTS AND METHODS: Inclusion criteria were patients aged between 17 and 65 years with unilateral temporal focus, without sufficient epilepsy control by antiepileptic drugs or neurosurgery. Two groups of 6 patients each were treated with 21 Gy (7 times 3 Gy) and 30 Gy (15 times 2 Gy). Study end points were change in seizure frequency, intensity, seizure length and neuropsychological parameters. RESULTS: All patients experienced a marked reduction in seizure frequency. The mean reduction of seizures was 37% (range 9-77%, i.e. seizures reduced from a monthly mean number of 11.75 to 7.52) at 18 months following radiation treatment and 46% (23-94%, i.e. 0.2-23 seizures per month) during the whole follow-up time. Seizure length was reduced in 5 out of 11 patients and intensity of seizures in 7 out of 11 patients. CONCLUSION: Radiotherapy was identified as a safe and effective treatment for pharmacoresistant epilepsy since a good reduction of seizure frequency during longer follow-up was observed. SRT means an appropriate alternative for patients with contraindication against neurosurgery or insufficient seizure reduction after neurosurgery.

Adolescent↗
PubMed2001

Interstitial brachytherapy with Ir-192 low-dose-rate in the treatment of primary and recurrent cancer of the oral cavity and oropharynx. Review of 318 patients treated between 1985 and 1997.

AIM: To evaluate the impact of postoperative interstitial brachytherapy with and without external radiotherapy in the treatment of primary and recurrent squamous cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Between 1985 and 1997, a total of 318 patients were treated by interstitial Ir-192 low-dose-rate brachytherapy as part of their primary (n = 236) or recurrent treatment (n = 82). There were 263 male (83%) and 55 (17%) female patients. The distribution of UICC (1997) stages was as follows: I (61 patients, 19%), II (71 patients, 22%), III (58 patients, 18%), IV (128 patients, 40%). The primary tumor site was located in the oral cavity in 201 patients (63%), in the oropharynx in 86 patients (27%), lower lip in 19 patients (6%) and other regions in twelve cases (4%). Treatment concepts did not vary over the time and were dictated by the initial tumor extension: a total of 175 patients (55%) received a combination of surgery, interstitial brachytherapy (23-25 Gy) and external radiotherapy (50-60 Gy), 60 patients (19%) surgery and interstitial brachytherapy (45-55 Gy) alone. Advanced disease not amenable to primary surgery was either treated by radiochemotherapy and interstitial brachytherapy in 39 patients (12%) or a combination of interstitial brachytherapy, external radiotherapy and interstitial hyperthermia in 44 patients (14%). RESULTS: Overall survival rates following primary and recurrent treatment were 50 +/- 4% and 29 +/- 5%, respectively, at 5 years (p < 0.0001). A significant impact on overall survival rate was noted for UICC stage: patients in stage I/II had survival rates of 64 +/- 5% and 57 +/- 10%, respectively, while patients in stage III/IV had survival rates of 39 +/- 5% and 15 +/- 5%, respectively, at 5 years (p < 0.0001). In addition, grading (p = 0.01) and hemoglobin levels (p = 0.05) had a significant influence on overall survival. Local tumor control rates for all patients were 74 +/- 3% and 57 +/- 7% at 5 years following primary and recurrent treatment (p = 0.01), respectively. The 145 patients treated for primary disease by a uniform concept of surgery, interstitial brachytherapy and external radiotherapy achieved excellent local control rates with 92 +/- 4% (stage I/II) and 65 +/- 6% (stage III/IV) at 5 years. Late treatment-related toxicity with soft tissue necrosis and/or osteonecrosis requiring mandibular resection was 7.5%. CONCLUSION: Local tumor excision followed by postoperative interstitial brachytherapy with and without external radiotherapy is associated with excellent locoregional control, a low risk of chronic sequelae and may therefore considered as a new approach avoiding mutilating radical surgery.

Brachytherapy↗
PubMed1994

[Radiation burden in diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP)].

UNLABELLED: The increasing expansion of diagnostic and, in particular, of therapeutic ERCP calls for greater consideration of the radiation dose to which the investigator and assistant personal are exposed and emphasizes the question of additional radiation protection measures such as leadshielded glasses and thyroid protection. MATERIALS AND METHODS: Local radiation doses were measured in 19 ERCP sessions at head level of the endoscopist, assistant staff and the radiologist, respectively. The fluoroscopic time, the area dose product (ADP) and the measuring height were recorded. A quotient based on the measured local dose and the ADP was formed which includes all variables having an effect on the scattered radiation. Using this quotient and the known ADP-values radiation exposure levels were mapped over a period of three months and then extrapolated to obtain the annual dose. RESULTS: Not only the FT, but also the ADP, the measuring height, and the source-image-distance (SID) are found to influence the magnitude of the radiation dose to which the investigator and his assistants are exposed at head level. For an assumed rate of 1200 ERCPs per year a median radiation at head level of 16.5 mSv/a is calculated for the investigator, and a corresponding head-level dose of 5.5 mSv/a for the assistants. This shows that the eye dose to which the investigator (and his assistants) are exposed amounts to 10% (5%) and the thyroid dose to 5% (1.5%) of the legally prescribed limit dose. If fewer ERCPs are performed, or if the investigations are divided up among several doctors and assistants, radiation exposure is reduced accordingly. CONCLUSIONS: Under the prevailing investigation conditions additional radiation protection measures such as leadshielded safety glasses or thyroid protection do not appear necessary.

Body Burden↗
PubMed1991

Somatic generation of diversity in a mammalian primary lymphoid organ: the sheep ileal Peyer's patches.

Ileal Peyer's patches (IPPs) in the sheep are composed of tightly packed follicles in which surface IgM-positive B cells proliferate and can be exported to the periphery. We report that the light chain rearrangement pattern in a single IPP follicle is much more restricted than in the entire tissue, which indicates that, as in the chicken bursa, ongoing rearrangement does not take place in this organ. Moreover, we show that B cells extensively diversify their antigen receptor while proliferating in IPP follicles. Sequencing of part of the V lambda locus indicates that this diversification is not achieved by gene conversion, but rather by untemplated somatic mutation and intense selective pressure. These results strongly imply that sheep IPPs behave as a bursa-equivalent, primary lymphoid organ of diversification and that somatic point hypermutation, which is known to proceed during secondary immune responses, can also generate an antibody repertoire.

Amino Acid Sequence↗
PubMed1991

[Interstitial and percutaneous radiotherapy after limited surgery in carcinoma of the oral cavity].

From 1.1. 1986 to 31.12. 1990 50 patients with epidermoid carcinoma of the floor of the mouth and the mobile tongue (stage T1 18, stage T2 20, stage T3 eight and stage T4 four patients) were treated by surgery, 192-iridium implantation using the plastic tube technique and percutaneous irradiation. Surgery was performed as enoral resection (35 patients) or en bloc tumour resection with part of the mandible and flap reconstruction (15 patients). Interstitial therapy was considered as a boost to primary tumour region, the dose given ranged between 16 and 33 Gy. 50 to 60 Gy were applied with external beam radiotherapy. Management of the neck consisted of elective or radical neck dissection followed by external beam radiotherapy (50 to 60 Gy). At 2/1991 median follow-up was 17 (three to 53) months. 35 patients are alive and tumour-free, one patient lives with tumour. 14 patients died, eight patients tumour-related, four patients of intercurrent disease and two patients because of a second primary. Primary local control was 18/18 patients for stage T1, 19/20 patients for stage T2, 7/8 patients T3, 3/4 patients for stage T4. Three patients suffered from nodal recurrences, four patients from distant metastases. Complication rate was acceptable. Soft tissue necrosis occurred in 4/18 patients (T1); 5/20 patients (T2); 3/8 patients (T3) and 1/4 patients (T4). Three patients developed osteoradionecrosis. Our results show that combined modality treatment for tumours of the oral cavity yields high local control with acceptable complication rate.

Adult↗
PubMed1991

[Ovariopexy and the treatment of Hodgkin's disease].

Between 1979 and 1989 a total of 113 women underwent treatment for Hodgkin's disease at the Department of Radiation Oncology of the University of Erlangen-Nürnberg. Only 17 female patients of child bearing age received total lymphoid irradiation including pelvic and inguinal nodes. 15/17 patients underwent prophylactic bilateral oophoropexy during staging laparotomy: ten had lateral, five had midline ovarian transposition. Reproductive and ovarian function was investigated in 13 patients--all in complete remission after a minimum follow-up of three years--by menstrual history and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), testosterone, dehydroepiandrosteronsulfate (DHEAS), androstendion, estradiol, progesterone, 17-OH progesterone, sexual hormone binding globulin (SHBG), free androgen index (FAI). Thyroid function was assessed by measuring thyroxine (T4), triiodothyronine (T3), thyroxine stimulating hormone (TSH) and thyroxine binding globulin (TBG). Normal cyclic ovarian activity was found in seven out of nine patients following lateral oophoropexy (including one pregnancy), but only in one out of four cases after midline fixation. Median calculated dose was 325 cGy (range 260 to 500 cGy) to the laterally fixed ovaries and 490 cGy (range 390 to 500 cGy) for midline transposition. We conclude, if ovarian protection is required prior to pelvic radiation, lateral oophoropexy should be preferred.

Adolescent↗
PubMed1990

Oncogenic activation of the human trk proto-oncogene by recombination with the ribosomal large subunit protein L7a.

The trk-2h oncogene, isolated from the human breast carcinoma cell line MDA-MB 231 by genomic DNA-transfection into NIH3T3 cells, consists of the trk proto-oncogene receptor kinase domain fused to a N-terminal 41 amino acid activating sequence (Kozma, S.C., Redmond, S.M.S., Xiao-Chang, F., Saurer, S.M., Groner, B. and Hynes, N.E. (1988) EMBO J., 7, 147-154). Antibodies raised against a bacterially produced beta gal-trk receptor kinase fusion protein recognized a 44 kd phosphoprotein phosphorylated on serine, threonine and tyrosine in extracts of trk-2h transformed NIH3T3 cells. In vitro, in the presence of Mn2+/gamma ATP, this protein became phosphorylated extensively on tyrosine. Cells transformed by trk-2h did not, however, show an elevation in total phosphotyrosine. We have cloned and sequenced the cDNA encoding the amino terminal activating sequences of trk-2h (Kozma et al., 1988). The encoded protein has a high basic amino acid content and the gene is expressed as an abundant 1.2 kb mRNA in human, rat and mouse cells. Antipeptide antibodies raised against a C-terminal peptide recognized specifically a 30 kd protein on Western blots of human, rat and mouse cell extracts. Immunofluorescence revealed, in addition to granular cytoplasmic fluorescence, intense nucleolar staining. The high basic amino acid content and nucleolar staining prompted us to investigate whether the 30 kd protein could be a ribosomal protein. Western immunoblotting analysis of 2D-electrophoretically resolved ribosomal proteins indicated that the 30 kd protein is the ribosomal large subunit protein L7a.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1989

[Results of temporary interstitial iridium 192 implantation in head and neck tumors].

In order to improve local tumor control in advanced head and neck tumors, a temporary interstitial iridium-192 implantation (40 to 50 cGy/h) was performed as a boost therapy (20 to 30 Gy at the surface of the target volume). This treatment was part of a multimodal therapy conception for primary tumors (N = 55) as well as for recurrences (N = 22). Local control was achieved in 89% (49/55) of patients treated for primary tumors. Complications appeared in the form of soft tissue necroses in 55% (30/55) and in the form of osteoradionecrosis of the mandible in 7% (4/55) of the patients. The authors discuss as possible reasons for this high complication rate: implantation volume too large or total activity too high, activities of the individual iridium-192 seeds to high, setting of radiation sources too close together, total dose too high, disturbed reparation capacity of sound tissues due to preceding operation and chemotherapy, premature test biopsies in the area of implantation, lacking oral hygiene and dental care by uncooperative patients. A local control rate of 50% was achieved by the treatment of recurrences, but this has no importance for the course of this tumor disease which is fatefully determined by the formation of remote metastases.

Adult↗
PubMed1989

The TP1 isolate of feline sarcoma virus encodes a fgr-related oncogene lacking gamma actin sequences.

We have isolated a new feline sarcoma virus, TP1-FeSV. The virus encodes a myristilated 83 kD gag-onc fusion protein displaying tyrosine kinase activity. We have established nonproducer cell lines lacking the TP1-FeSV associated helper virus (FeLV) and TP1-FeSV transfected NIH cell lines. Southern Blot analysis of genomic DNA and Northern Blot analysis of RNA isolated from these cell lines revealed that the oncogene of the TP1-FeSV isolate is related to the fgr oncogene of the GR-FeSV, but shows no hybridization to the gamma actin homologous sequences of the GR-FeSV. We have isolated TP1-FeSV specific clones from a genomic library. Restriction enzyme and sequence analysis showed that the TP1-FeSV genome consists of the first 1651 nucleotides of the gag gene, followed directly by fgr sequences. The TP1-FeSV fgr sequence starts 43 nucleotides after the beginning of the GR-FeSV fgr sequence. In contrast to the GR-FeSV fgr which has lost 13 amino acids of the c-fgr carboxy terminus, the TP1-FeSV fgr contains the complete carboxy terminus of the cellular fgr gene. The TP1-FeSV fgr sequence is followed by a unique 328 nucleotide long sequence of unknown origin. The 3' recombination site occurs within the pol gene, 460 nucleotides from the start of the env leader sequence. Comparison of the subcellular localization of the transforming proteins of TP1-FeSV and GR-FeSV show no striking difference; both molecules are in part associated with subcellular membrane/cytoskeletal fractions and form complexes with the cellular pp90 and pp50.

Actins↗
PubMed1989

[A new multi-channel LDR/MDR-afterloading-system (Inter-Pal-C38)].

The methods of temporary interstitial implantation of iridium-192 seed chains have been applied in Erlangen for two years in many cases of squamous cell carcinoma in the head and neck area, the cervix uteri or the anal duct. The afterloading procedure which at the beginning had to be performed manually involved partially considerable radiation-exposures of medical and nursing staff. Therefore we have developed a 38-canal machine for remote control afterloading with iridium-192 seed chains in LDR and MDR therapy which is working in a similar way as the already established methods of remote control afterloading in HDR therapy. Special technical features are the automatic afterloading procedure, the disconnecting of patient and machine for any length of time, the possibility to use the machine for several succeeding patients, and the modern computer control by an IBM PC with color monitor and alpha-numerical keyboard. The new machine is fast and easy to handle, protects the staff completely against radiation and, due to the possibility of disconnection and free mobility, makes it easier and more comfortable for the patient to stay within the radioprotection room.

Anus Neoplasms↗
PubMed1988

The transformation of primary and established mouse mammary epithelial cells by p21-ras is concentration dependent.

We constructed a retroviral vector (pZSR) which is capable of simultaneously expressing the neomycin resistance gene and the viral ras oncogene. Primary mammary gland epithelial cells were prepared from mid-pregnant mice and infected with this virus. Cell lines with epithelial cell characteristics could be established with a low frequency. High expression of p21 v-ras was observed in these cells. They are tumorigenic and form soft agar colonies dependent on the presence of EGF and insulin in the growth medium but progress to hormone independent growth at higher passage numbers. A cloned cell line of non-tumorigenic, established mammary epithelial cells (NOG8) was also infected with the v-ras expressing virus. Individual cell clones expressing increasing amounts of p21 v-ras were selected. The level of p21 v-ras expression directly influences the morphology of the epithelial cells in culture, determines their cloning efficiency in soft agar and their tumorigenicity.

Animals↗
PubMed1988

[Individual collimators as an aid in improving the accuracy of positioning, the reproducibility of irradiation and the sparing of critical organs].

Despite the technical progress regarding radiotherapeutic facilities, the positioning and fixation of the patient and the reproduction of the daily irradiation geometry is still the critical point in planning and performance of radiotherapy treatments. Besides the use of irradiation masks, an improved adjustment precision and reproducibility as well as an individualization of the target volume is achieved above all by individual collimators. The use of individual absorbers offers a precise and fast adjustment of irradiation fields at the therapy unit, an optimum adaptation of the irradiation volumes to the anatomical features of the patient and the loco-regional tumor extent as well as a selective protection of radiosensitive structures. The historical method of field-shaping by standard absorbers should be abandoned.

Humans↗
PubMed1987

The multi-factorial pathogenesis of autoimmune disease.

Development of organ-specific autoimmune diseases depends on both an abnormal immune regulation and a genetically determined primary susceptibility of the target organ to the autoimmune attack. In addition to the essential genetically determined prerequisites there are also facultative, modulating factors that influence the outcome of an autoimmune disease. This concept is exemplified in the Obese strain (OS) chicken model which develops a spontaneous autoimmune thyroiditis closely resembling human Hashimoto disease. Three modulating factors are specifically addressed, viz. (a) the lower threshold of OS thyroid epithelial cells for the gamma-interferon-induced MHC class II antigen expression as compared to normal controls, (b) the decreased glucocorticoid tonus of the OS and (c) the presence of a new endogenous virus (ev 22) locus in the OS that has so far not been found in any normal strain and which seems to influence the glucocorticoid-mediated immunoregulatory process.

Animals↗
PubMed1984

[Whole-skin electrotherapy: a therapeutic concept for mycosis fungoides and Sézary syndrome. I. Irradiation technic and dosimetry].

A simple, but efficient radiotherapeutic method is presented for the irradiation of the whole body surface. Dosimetric measurement shows that the largest part of the skin receives between 80 and 100% of the dose. Only the concave surfaces receive a lower dose. They are saturated by boost irradiation. The total body exposure due to Bremsstrahlung is less than 1% of the target dose.

Electrons↗
PubMed1984

[Dosimetry of lower segment irradiation in Hodgkin disease. II. Radiation burden of risk organs].

The radiation exposure of the risk organs kidneys, spinal marrow, gonads, liver, and pancreas was determined for three different photon energies (Co-60, continuous radiation with 6 MV and 10 MV) at the inverted Y field, as it is applied generally for the infradiaphragmatic segment irradiation of malignant lymphomas. For this purpose, the authors made use of the thermoluminescence dosimetry and film dosimetry in the Alderson phantom. The most important results are: More than half of the left kidney receives more than 50% of the applied focal dose, about 20% receive more than 90% of the focal dose. The participation of the right kidney is minimal. If the dose exceeds 20 Gy, the lumbar spinal marrow is sufficiently protected by a satellite in the dv field. A displacement of the ovaries in caudomedial direction behind the vesical absorber does not protect the ovarian function in a satisfactory manner; the ovaries should be displaced in craniolateral direction on the alae ossis ilii. We recommend the use of a testicular lead protection even if the inguinal lymph nodes are only irradiated with the vd field.

Abdominal Neoplasms↗
PubMed1984

[Dosimetry in radiotherapy of the lower portion of the body in Hodgkin's disease. Dose distribution within the target volume dependent on radiotherapy].

The dose distribution of three radiations (Co-60, Co-6, and 10 MV continuous radiation) within the target volume was evaluated. It is shown that a much more constant reference dose can be achieved with cobalt, whereas continuous radiation causes a more homogeneous dose distribution in the target volume. With the irregular field developed by us, the therapy success could be endangered by too low dosages within the target volume.

Cobalt Radioisotopes↗