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Biomedical subjects

H Blattmann

Publications and source records attributed to H Blattmann.

At least 19 recordsLinked to original sources

Radiation-induced genetic instability: no association with changes in radiosensitivity or cell cycle checkpoints in C3H 10T1/2 mouse fibroblasts.

We investigated various phenotypic characteristics of radiation-induced morphologically transformed C3H 10T1/2 mouse fibroblasts. The cells were treated with 8 Gy x-rays, and type II/III foci were isolated. Cell lines were developed from these foci, and subsequently clones were established from these focal lines. The clones were examined for DNA content, radiosensitivity and inducible cell cycle arrests. Besides the morphological changes associated with the transformed state, the major difference between the isolated focal lines or derived clones and the parental C3H 10T1/2 line was one of ploidy. The transformed cells often displayed aneuploid and multiple polyploid populations. No change in the radiosensitivity of the transformed cells was observed. Furthermore, the two major radiation- and staurosporine-induced G1 and G2 cell cycle arrests observed in the parental cell line were also observed in the morphological transformants, suggesting that checkpoint function was normal.

Aneuploidy

Potential tumour doubling time: determination of Tpot for various canine and feline tumours.

Spontaneous tumours in dogs and cats are an excellent model for clinical human research, such as in developing proton conformation radiotherapy for humans. The kinetics of tumour cells can be used effectively to predict prognosis and response to therapy in patients with tumours. Knowledge of the kinetic parameters in these tumours is therefore important. In the present study the kinetic parameters evaluated included the labelling index (LI), relative movement (RM), mitotic index (MI), and potential doubling time (Tpot). These parameters were determined using in vivo labelling with bromodeoxyuridine, flow cytometry and histological preparation. Samples were obtained and evaluated from 72 dogs and 20 cats, presenting as patients in our clinic. Within the groups of epithelial and mesenchymal tumours from dogs and cats, the kinetic parameters LI, RM and MI were compared with Tpot. Significant correlations were observed for the comparison Tpot and LI. No correlation was found between Tpot and RM.

Animals

The 200-MeV proton therapy project at the Paul Scherrer Institute: conceptual design and practical realization.

The new proton therapy facility is being assembled at the Paul Scherrer Institute (PSI). The beam delivered by the PSI sector cyclotron can be split and brought into a new hall where it is degraded from 590 MeV down to an energy in the range of 85-270 MeV. A new beam line following the degrader is used to clean the low-energetic beam in phase space and momentum band. The analyzed beam is then injected into a compact isocentric gantry, where it is applied to the patient using a new dynamic treatment modality, the so-called spot-scanning technique. This technique will permit full three-dimensional conformation of the dose to the target volume to be realized in a routine way without the need for individualized patient hardware like collimators and compensators. By combining the scanning of the focused pencil beam within the beam optics of the gantry and by mounting the patient table eccentrically on the gantry, the diameter of the rotating structure has been reduced to only 4 m. In the article the degrees of freedom available on the gantry to apply the beam to the patient (with two rotations for head treatments) are also discussed. The devices for the positioning of the patient on the gantry (x rays and proton radiography) and outside the treatment room (the patient transporter system and the modified mechanics of the computer tomograph unit) are briefly presented. The status of the facility and first experimental results are introduced for later reference.

Cyclotrons

Improved dose concept for radioiodine therapy of multifocal and disseminated functional thyroid autonomy.

The present study analyzes the improvement of the outcome of radioidine therapy in non-immunogenic hyperthyroidism by adapting the target dose to the 99mTc-pertechnetate thyroid uptake under suppression (TcTUs) prior to radioiodine therapy. The TcTUs is a substitute for the non-suppressible iodine turnover. The 89 patients presented with a basal thyrotropin level of < 0.1 mU/l, normal values for free triiodothyronine and thyroxine and with multifocal or disseminated thyroid autonomy. These terms describe the scintigraphic distribution pattern of autonomous iodine turnover. Thirty-two patients had a TcTUs between 1.6 and 3.2% (group A) and 57 had a TcTUs > 3.2% (group B). Fifty-five patients (three of group A and 52 of group B) were treated previously for overt hyperthyroidism with antithyroid drugs. Target doses of 150 and 200 Gy were used in both groups and 300 Gy in group B only. Six months after radioiodine therapy, a basal TSH level of > or = 0.5 mU/l as criterion of therapy success was observed in 94% of group A and in 54% of group B. Further differentiation of group B shows an increasing success rate with the target dose used: 45% after 150 Gy, 50% after 200 Gy and 90% after 300 Gy. In patients with a basal TSH level of < 0.5 mU/l after radioiodine therapy, the TcTUs was evaluated again.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Coincidence of unifocal thyroid autonomy and follicular carcinoma. Case report].

The case is reported of a 53-year-old man with differentiated thyroid carcinoma within a hot nodule and typical scintigraphic findings of a unifocal adenoma. Preoperative cytology revealed no malignancy. The preliminary histological diagnosis after hemithyroidectomy on the right side was follicular adenoma. The final histological evaluation, however, revealed follicular carcinoma of the thyroid gland. As a result, a thyroidectomy was performed with postoperative radioiodine treatment. The combination of thyroid carcinoma and hot nodules is extremely rare. In all cases of rapid growing nodules or other abnormalities of the thyroid cytological and/or histological verification is mandatory.

Adenocarcinoma, Follicular

[Radiotherapy in small animal medicine: fundamentals, indications and significance].

This article describes the general principles of radiation therapy, reviews the indications for this treatment modality and discusses the response of tumors and normal tissue to radiation. Radiation modalities and treatment protocols currently available in Switzerland are presented. Treatments of spontaneous tumors in animals contribute to the development of radiation therapy in human medicine at the same time.

Animals

[Thyrotoxic crisis after exposure to iodine. A case with fatal outcome].

A 78-year-old woman is presented with a multinodular toxic goiter and euthyroidism under continuous low-dose treatment with antithyroid drugs. A period of hyperthyroidism had been documented 3 years previously. In the preoperative management, prior to resection of a benign ovarian tumour, an intravenous urogram was performed. Perchlorate was given for thyroid protection. One day after surgery the clinical signs of thyroid storm were observed. Immediately, high-dose antithyroid drug therapy was started. Nevertheless, the patient died of acute cardiovascular failure 3 days later. This case report focuses on the risk of thyroid storm following iodine excess in the presence of relevant functional thyroid autonomy without adequate thyroid protection.

Aged

The RBE of negative pions in the treatment of tumors with different volumes.

For negative pions, large differences exist between experimental RBE values obtained by in vivo investigations with animals and corresponding data being used in clinical tumor therapy. Therefore, the influence of the treatment volume on the radiation quality and respectively on the RBE is examined. The RBE for euoxic mammalian cells is measured with high precision in different volumes irradiated in the spot-scan mode with the PIOTRON at the Paul Scherrer Institute. It is shown experimentally that the RBE is reduced if the radius of the irradiation volume is increased. Using a simple mathematical approximation for the spot-scan technique this relation can be understood quantitatively. The same approximation is also used to calculate dose mean values for the lineal energy yD present in different irradiated volumes. The good agreement with existing experimental data for yD indicates that the approximation used is adequate and the main physical parameters have been taken into consideration. The above mentioned differences between animal experiments and treatment of patients can be explained by changes in the effective radiation quality due to the scanning procedure used in the clinical treatments.

Animals

Beam delivery systems for charged particles.

Heavy charged particle therapy, started at research institutes three decades ago, is now on the verge of entering a clinical phase. This phase has resulted from the evolution and development of various beam delivery systems and techniques with existing research accelerators and with newly built accelerators. For the first thirty years, heavy charged particle therapy was administered with a fixed horizontal beam line. In 1991, the first treatment with an isocentric gantry was administered. The development of the isocentric gantry, the newest beam delivery system, and clearly a consequence of all the experience gained at the earlier facilities has many advantages. It offers advantageous physical properties of the particles as well as being equal in the flexibility of dose delivery to the modern photon radiotherapy gantries.

Humans

Conformal radiotherapy for unresectable retroperitoneal soft tissue sarcoma.

Local tumor control remains a continuing challenge in the treatment of retroperitoneal soft tissue sarcoma. Though complete resection by means of wide excision or excisional biopsy can be performed in a minority of patients only, aggressive surgical approach remains the treatment of choice. Unresectable sarcoma can rarely be controlled by conventionally applied radiotherapy--only a few percent of patients survive. A superior dose distribution of external radiation is demanded in order to spare healthy tissue. The presumably greatest advantage will occur when radiotherapy is used preoperatively. The possible clinical gain of superior dose distribution is demonstrated by results of the dynamic, 3-D conformal pion radiotherapy at PSI. Between April 1983 and June 1988 a total of 21 patients were treated with high doses (greater than or equal to 30 Gy) for unresectable retroperitoneal soft tissue sarcoma. The follow-up time is 13-74 months, median 24. Fifteen patients were treated with 20 fx, and 19 patients were treated with fraction sizes of 150 or 165 cGy. Except for one patient with thrombocytopenia after chemotherapy, no treatment interruption was necessary. Five patients developed late reactions, caused also by surgery and chemotherapy: two intestinal obstructions, one liver abscess, one leg edema, and one superficial skin necrosis. Nine patients had laparotomy after pion irradiation, five for resection of the previous unresectable tumor; 3/5 sarcoma were completely resected. Morbidity rate after post-pion laparotomy did not increase. Three patients had local tumor progression, 1/3 inside the treatment volume. The actuarial five-year local tumor control rate of these unresectable retroperitoneal sarcoma is 60%, the actuarial five-year survival rate is 33%. Out of the 21 patients, 15 are alive, two have died from local progression, one from peritoneal progression, and three from metastases.

Humans

Effects of respiratory motion on dose uniformity with a charged particle scanning method.

A three-dimensional spot-scanning technique for radiotherapy with protons is being developed at the Paul Scherrer Institute. As part of the effort to optimize the design and ensure clinically useful dose distributions, a computer simulation of the dose deposition in the presence of respiratory motion was performed. Preliminary experiments have characterized the proton beam and the scanning procedure. Using these parameters, the computer program calculated the dose within a uniform volume of water in the presence of respiratory motion. Respiration amplitude, respiration period, respiration direction, number of fractions, size and position of the beamspots and rescanning multiplicity were systematically varied and the effect on the dose distribution determined. The dose uniformity is very dependent on the direction of the respiration relative to the three independent beam scanning directions. The dose uniformity decreases with increasing respiration amplitude, but has little response to changes in respiration frequency. Rescanning the volume, such as with fractionation, improves the dose uniformity roughly as the square root of the number of fractions. Broad, Gaussian beams result in better dose uniformity than narrow, sharply delineated ones, but produce slower dose fall-off at the edges of the scanned volume. Results of this work are being incorporated into the design of the system.

Computer Simulation

[Improving function by decortication. Functional studies with particular evaluation of lung perfusion scintigraphy].

The study presents functional and scintigraphic lung perfusion measurements before and after decortication of 9 patients treated for chronic pleural empyema with special emphasis to changes in perfusion scintigraphy. Preoperatively, the average vital capacity was 60% and the average FEV1 was 65% of the predicted. Perfusion of the affected side showed an average reduction to 22%. After decortication all functional data showed an improvement (average VC 78.5%, average FEV1 79.5%) the percentage of lung perfusion having increased to a mean of 37.8%.

Adolescent

Anaplastic astrocytoma and glioblastoma: pion irradiation with the dynamic conformation technique at the Swiss Institute for Nuclear Research (SIN).

Clinical phase I/II studies have been performed at the Swiss Institute for Nuclear Research (SIN) since February 1982. Fifty-two out of 249 patients accepted for pion treatment by the end of 1986 were treated for malignant glioma with high dose pion irradiation. A substantial influence of their radioresistance was expected from increased radiation quality due to the contribution of high LET particles from pion capture, and by the possibility of target volume shaping and dose distribution related to the dynamic spot-scan conformation technique. The patients' treatment followed a dose escalation program with total doses from 2720-3420 cGy, fraction sizes from 170 to 205 cGy (90% isodose, minimum target dose), and treatment times from 4 to 5 weeks. 12/52 patients received an accelerated treatment with 3280 cGy in 14-22 days. 49/52 patients are eligible: 3 with astrocytoma of clinical aggressive behaviour, 14 with anaplastic astrocytoma (median age 42 years), and 32 patients with glioblastoma (median age 52 years). 8/49 patients had total/subtotal tumour resection, 19 patients a stereotactic biopsy. The patients were divided into three groups according to total dose, and a fourth group which received the accelerated treatment. There was no statistically significant difference in the median survival rate between the four groups, which was 13 months for the non-glioblastoma patients and 9 months for the glioblastoma patients. No radiation necrosis and no demyelination was found in 17 patients (6 recraniotomies, 11 autopsies). In 10/17 patients, clearly identifiable tumour cells were not demonstrated. NMR findings showed the tumour-surrounding oedema mostly stimulated by tumour necrosis and tumour progression. From these findings, further dose escalation programs, together with a shaping of the target volume close to the tumour, are not contraindicated.

Adult

Decortication in chronic pleural empyema. Investigation of lung function based on perfusion scintigraphy.

The study presents measurements in spirometry and scintigraphic lung perfusion, before and after decortication, in 9 patients treated for chronic pleural empyema with special emphasis on measuring changes by perfusion scintigraphy. Preoperatively, the average vital capacity (VC) was 60% and the average FEV1 was 65% of the predicted. Perfusion of the affected side showed an average reduction to 22%. After decortication all functional data showed an improvement (average VC 78.5%, average FEV1 79.5%) the percentage of lung perfusion having increased to a mean of 37.8%.

Adolescent

Spot scanning for 250 MeV protons.

Protons have a long tradition in precision treatment of lesions of limited size at limited depth. Recently interest has developed in hospital based proton therapy accelerators, able to treat deep seated tumors. Heavy charged particles, and especially protons, are particularly suited to treat well localized tumors. Protons can be collimated as precisely as photons, but in addition have a well defined range. Protons are therefore predestinated for conformation radiotherapy also for larger target volumes. At the Swiss Institute for Nuclear Research a computer optimized treatment planning system has been developed for pion radiotherapy. The principle of this dynamic treatment technique can be adapted for proton therapy. It could prove to be a valid alternative to passive scattering for proton treatment especially of large irregularly shaped volumes. Dose calculations have been performed for specific cases using a 250 MeV pencil beam. The dose distributions and dose volume histograms have been compared with pion therapy. A horizontal experimental beam line, using a degraded 590 MeV proton beam of the PSI ring cyclotron, is set up to verify calculations in phantoms.

Humans

Repair inhibition in tumours irradiated with fast protons and negative pions.

Solid Ehrlich mouse tumours were irradiated in the 80 MeV proton beam of the Paul-Scherrer-Institute. The tumour volume was measured as a function of time after irradiation and two experimental endpoints were determined: local tumour control and minimal tumour volume after irradiation. The application of 2-deoxy-D-glucose (2-DG; 2 mg/kg) increased the radiation effect of protons by a factor of 1.4. The same tumour system was used with negative pions. Human tumours are usually irradiated with a mixed radiation produced by the "spot-scan-technique". This radiation quality was simulated in the mouse experiment by two successive irradiations with a spot of densely ionizing peak pions and a spot of sparsely ionizing plateau pions. Application of 2-DG raised the radiation effect due to the sparsely ionizing component again by a factor of 1.4. This indicates that clinical results in radiotherapy might be improved by application of 2-DG during the treatment.

Animals