Börje Larsson

Lesions in the Depth of the Brain Produced by a Beam of High Energy Protons

Restricted lesions were produced in the depth of the goats brain by means of cross-fire irradiation with a narrow beam of high-energy protons. The radiosurgical technique and the histopathology of the lesions are described. It was possible to produce circumscribed cerebral lesions of a type well suited for physiologic experimentation without damaging surrounding nervous tissue. The method may also be applied to neurosurgery in man. (auth)

Irradiation of Small Structures Through the Intact Skull

The physical conditions for producing minute disc-shaped lesions for functional radiation surgery by means of narrow beam irradiation are discussed. The intention was a treatment procedure for routine clinical use and with high physical and mechanical reproducibility. The possibilities of using high energy electrons, supervoltage roentgen radiation, gamma emitting nuclides or fast neutrons in a technique for routine clinical use were investigated. The radiation of choice taking physical properties, radiation biologic factors and practical circumstances into account was considered to be 60-Co gamma radiation. A treatment apparatus containing 179 60-Co sources within a spherical sector of 70 degrees latitude and 160 degrees longitude was constructed.

Pilot Study on Proton Irradiation of Human Carcinoma

Seven cases of carcinoma were irradiated by a synchrocyclotron with a beam of high energy protons. Large volumes of tissue were in some of the cases uniformly covered by a continuous variation of the range of the protons during irradiation. Microscopic changes similar to those described being due to other forms of ionizing radiation were found in the carcinomas and could be corroborated with changes previously observed in rabbits sfter irradiation with protons. A single proton dose of 3,000 rad caused obvious regressive changes without producing any severe damage to the skin or urinary bladder, even in those cases in which almost the entire pelvis was irradiated. (auth)

Chromosome aberrations following irradiation with high-energy protons and their secondary radiation: a study of dose distribution and biological efficiency using root-tips of Vicia faba and Allium cepa.

SummarySome radiological properties of a 185 mev proton beam were stuided with root-tips of bean and onion seedlings.The relationship between dose and number of abnormal metaphases was investigated at different depths of penetration in Lucite. The effect, found in the final part of the range of penetration, was higher than expected when the physical depth-dose to surface-dose ratio is considered. The difference is partly attributed to a variation of the relative biological efficiency.The enhancing effect of oxygen was studied at high and low energies. It was found to be nearly constant.The relative biological efficiency of 170 mev protons as compared with 180 kv roentgen rays for producing chromosome aberrations was found to be 0·7.The chromosome-breaking efficiencies of the secondary radiations from proton-irradiated tissue and brass were studied. The results indicate that the effects of secondary radiation may be neglected in therapeutic procedures.

Melanin Capacity to Accumulate Drugs in the Internal Ear: A Study on Lidocaine, Bupivacaine and Chlorpromazine

The distribution and retention of labelled lidocaine, bupivacaine, and chlorpromazine to melanin in the internal ear after intravenous and intraperitoneal injection were examined by whole-body autoradiography. Both young pigmented hooded rats and albino rats were studied. In the pigmented rats chlorpromazine showed the greatest accumulation, which was more pronounced in the cochlea than in the vestibular portion. The other two substances were evenly distributed in the internal ear. After a single injection of chlorpromazine and of bupivacaine these substances were still bound to the melanin of the internal ear after 14 days, which was the longest survival time. Lidocaine, on the other hand, had disappeared after only 4 days. Strong uptake and retention of the three substances were observed in the eyes of pigmented animals. In albino animals there was very weak, transient uptake in the internal ear of chlorpromazine and bupivacaine, but not of lidocaine. In studies in vitro on isolated bovine eye melanin there was considerably greater adsorption of chlorpromazine than of lidocaine and bupivacaine. An uptake was noted in the human eye in experiments in vitro. Clinical tests revealed no acute or late damage to hearing or sight after large doses of lidocaine. The participation of melanin in different basal labyrinthine functions such as the energy transfer mechanism and the sound protective mechanism is discussed in the light of the results obtained. Further, the theory is put forward that the melanin affinity of certain substances can be of both therapeutic and ototoxic importance.

Accumulation of 14C-Lidocaine in the Inner Ear Preliminary Clinical Experience utilizing Intravenous Lidocaine in the Treatment of Severe Tinnitus

Clinical experience has demonstrated that intravenously administered local anaesthetics have a mitigating effect on severe tinnitus. In an attempt to gain some insight into the mechanism of this effect, autoradiography of the inner ear of young pigmented rats was performed after intravenous injection of 14C-lidocaine. Some accumulation of lidocaine was found in the modiolus, but almost none in the stria vascularis. A large accumulation was observed in other melanincontaining tissues, such as the hair follicles and uvea. The in vitro accumulation of 14C-labelled lidocaine adsorbed on melanin granules was low (12%) as compared with that of other drugs, such as kanamycin (89%) and chloroquine (85%). These autoradiographic results indicate that lidocaine has an effect upon the inner ear, in addition to its previously demonstrated effect on the CNS.

Zur Morphogenese der akuten Strahlenschdigung in Rattenspinalganglien nach Bestrahlung mit 185 MeV-Protonen

Zusammenfassung1.Spinalganglien der Ratte werden lokal mit energiereichen Protonen mit einer Dosis von 20 krad bestrahlt. Die akuten Strahlenschäden, die in den ersten 18 Tagen p. irr. auftreten, werden nach Fixierung in Osmiumtetroxyd und Einbettung in Methacrylat mit dem Phasenkontrast- und Elektronenmikroskop ausgewertet.2.Der histopathologische, mit phasenkontrastmikroskopischen Übersichten erfaßte Ablauf der akuten Strahlenreaktion läßt sich in drei Stadien einteilen. Das initiale Stadium zeichnet sich durch solitäre Strukturumwandlungen aus, die in erster Linie die Perikarya und das Gefäßendothel betreffen. In einem intermediären Stadium beherrschen chromatolytische Veränderungen der Perikarya und Permeabilitätsstörungen der Gefäßendothelien das Erscheinungsbild. Das degenerative Stadium zeigt eine allgemeine Ganglienerkrankung, die durch Nervenzell-Degenerationen und Nekrolysen, „segmentale Erkrankung“ der ganglionären Nervenfasern und eine in- und transsudative, fibrinöse Vasculopathie gekennzeichnet ist.3.Die Beteiligung der einzelnen Perikarya an den zytopathologischen Reaktionen ist sehr unterschiedlich. Im Vergleich mit den A-Zellen scheinen die Perikarya vom Typ B etwas strahlenresistenter zu sein. Aber auch innerhalb einer Typengruppe zeigen die Ganglienzellen ein sehr individuelles Verhalten.4.Abgesehen von zirkumskripten Plasmaaufhellungen und „Ringkörpern“ im Zellkern der Ganglienzellen treten die strahleninduzierten Strukturschäden erst nach einer Latenz von 1–3 Tagen in Erscheinung. Es läßt sich belegen, daß in Spinalganglien sowohl neuroektodermale als auch mesenchymale Gewebsanteile direkt geschädigt werden. Die elektronenmikroskopischen Befunde am Zellkern und am Ergastoplasma machen wahrscheinlich, daß in den Nervenzellen besonders die nukleoproteidbildenden Systeme von der Strahlenschädigung betroffen werden.5.Im ausgeprägten Stadium der akuten Strahlenreaktion treten durch nachfolgende und wechselseitige Wirkungen der primär geschädigten Gewebsanteile weitere pathogenetische Faktoren auf, die das Erscheinungsbild der Strahlenschädigung zusätzlich verwandeln. Hierbei kann das Ausmaß der Vaskulopathie eine entscheidende Rolle spielen.

Changes in MR of Malignant Melanomas Induced by Glucose and Fructose: A clinical and experimental investigation

MR imaging has been performed on malignant melanomas in vitro and in vivo. Changes of the water content in an enucleated malignant melanoma in vitro were followed by significant changes of the T1 and T2 values. In mice with implanted subcutaneous melanoma similar changes could be obtained after injection of glucose and fructose intraperitoneally. Malignant melanoma of the eye could be influenced in the same way in 10 consecutive patients after oral intake of glucose and fructose. The present study shows that the MR images may be significantly changed after a few hours by altered metabolism induced by glucose and fructose. It is anticipated that this is due to changes within the tumor leading to different water distribution. The finding may be of importance as a further help for diagnosing malignant melanoma of the eye.

Neutron Capture Therapy in Support of Other Radiation Treatment

Neutron capture therapy (NCT) appears potentially useful, not only as a treatment modality per se, but also as an adjuvant in the context of established clinical measures to control pathological growth. Since the probability of local control is a steep function of absorbed dose, even a modest specific exposure of neoplasms by such techniques would significantly increase the chances of cure. Such a prospect seems most natural in fast neutron therapy 1,2,3 where slow neutrons are automatically available in the target area. As a promising alternative, it would be possible to combine the use of protons or heavier ions with a booster therapy based on boron compounds and intermediate-energy neutrons.4 Such a situation would be particularly relevant when there are needs both for the precision of heavy charged-particle beams--permitting tailored 3-dimensional dose plans for the treatment of structures visible by computerized imaging methods--and for the particular features of NCT that also aim at eradication of invisible but suspected microsopic growth in larger anatomical regions.

Concomitant changes in MR image and morphology induced by glucose and fructose in B16 mouse melanomas

The short proton relaxation times in the MR images of malignant melanomas make them different from most other tumors. We have previously shown that the T1 and T2 signals may be significantly influenced when the water distribution of the tumor is changed in vivo and in vitro. In the present work T1 and T2 were estimated and compared with the electron microscopy picture in subcutaneously implanted B16 melanomas in mice. Two hours after the mice were given an i.p. injection of 0.9% NaCl containing 10% glucose and 10% fructose (9 mice) both the T2 components were markedly and the T1 slightly prolonged. At the same time the electron microscopy picture displayed swelling of the melanocytes together with a marked decrease in number and size of their mitochondriae. There were no changes in the MR image or the melanocyte structure in control mice injected with 0.9% NaCl (9 mice) or 0.9% NaCl containing 10% fructose. It is concluded that the changed MR image may be coupled to the metabolism in melanoma.