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Biomedical subjects

C H Håkansson

Publications and source records attributed to C H Håkansson.

At least 19 recordsLinked to original sources

Tumour vessel damage resulting from laser-induced hyperthermia alone and in combination with photodynamic therapy.

This study examined tumour vessel injury resulting from laser-induced hyperthermia alone and in combination with photodynamic therapy (PDT) in the treatment of rat liver tumours by means of scanning electron microscopy. A total of 18 Wistar rats were divided into three groups. Group I (six animals) underwent hyperthermia for 15 min (15-min hyperthermia). Group II (six animals) underwent hyperthermia for 30 min (30-min hyperthermia). Group III (six animals) received the combined treatment of PDT and 30-min hyperthermia. For PDT, delta-amino laevulinic acid at a dose of 60 mg/kg of body weight was intravenously administered 60 min before irradiation at 635 nm. The morphological results indicated that 15-min hyperthermia gave rise to an increase in permeability of the vessels in the treated tumour. Thirty-min hyperthermia caused extreme oedema of vascular endothelial cells and restrictive openings of tumour branch vessels. The combined therapy of PDT and hyperthermia destroyed tumour vasculature. Large breaks of the inner wall of the treated tumour vessels were deeply involved in the basement membrane of the vessel. The results indicate that there may be a close link between inhibition of tumour growth and degree of damage to tumour vessels.

Animals↗

The effect of ionizing irradiation on type I collagen of the tail in growing mice: a histology and electron microscopy study.

In order to examine the effect of radiation on growing tissue, especially the fibroblasts and their end-product, the collagen fibres, tails from 24 mice were irradiated at an age of 8 days with 20 Gy and 30 Gy (60Co). Tails from 18 animals served as controls. Six mice from each group were sacrificed on day 8, 20 and 30. Transmission electron microscopy was used to examine the fibroblasts and the collagen fibrils. Non-irradiated fibroblasts had a nucleus rich in chromatin and an abundant endoplasmic reticulum with cisternae and condensing vacuoles. On day 20, approximately 50%, and on day 30, 25% of the fibroblasts irradiated with 30 Gy had a sparse endoplasmic reticulum pointing to a reduction of protein synthesis. While, on day 20, the fibrils irradiated with 20 Gy and with 30 Gy had significantly larger diameters compared to the controls, on day 30, the irradiated fibrils had a notably smaller diameter compared to the controls; 30 Gy-fibrils were larger than the 20 Gy-fibrils on both days. On day 20, the binding mean value of the 30 Gy-fibrils exceeded that of the controls and was significantly higher than that of the 20 Gy-fibrils, which was lower, though not significantly, than the controls. On day 30, the banding mean value of the 30 Gy-fibrils was notably lower than the control; and the value of the 20 Gy-fibrils was significantly lower than that of the 30 Gy-fibrils. The results are explained as an edema together with an inhibitory effect on the protein synthesis of the fibroblasts caused by the irradiation. This deduction is further supported by light microscopy of the tails.

Animals↗

Intra-operative laser-induced photodynamic therapy in the treatment of experimental hepatic tumours.

OBJECTIVE: To examine the effect of photodynamic therapy (PDT) on experimental liver tumours in rats. DESIGN: An experimental liver tumour model was used. Each of a group of rats had two tumours simultaneously inoculated into its liver. The tumour located in the left hepatic lobe was used for PDT, and the other one, in the median lobe, as a control. The haem precursor delta-amino laevulinic acid (ALA), at a dose of 30 mg/kg body weight, was injected 60 min before laser irradiation. Rats in group I received ALA through a femoral vein. Those in group II received ALA through the portal vein. Group III had an injection of ALA solution through the portal vein plus hepatic inflow occlusion. Three and 6 days after the treatment, the rats were killed, and the tumours were measured, and ultrastructural changes were examined using scanning electron microscopy. SETTING: Lund University Medical Laser Centre, Lund, Sweden. RESULTS: The mean tumour volume of the treated tumours increased by factors of 1.9, 1.5 and 1.7 in groups I, II and III, respectively, compared with the pretreatment baseline value. However, the mean tumour volume in the control tumours increased by factors of 9.5, 4.3 and 4.8 in the respective groups. Under the light microscope, marked necrosis of the treated tumour and the surrounding liver tissue was observed. Scanning electron microscopy revealed heavy damage to the cells and vessels in the treated tumour. CONCLUSION: PDT with ALA is an effective treatment modality for rat liver tumours.

Aminolevulinic Acid↗

Immunotherapy in liver tumors: II. Intratumoral injection with activated tumor-infiltrating lymphocytes, intrasplenic administration of recombinant interleukin-2 and interferon alpha causes tumor regression and lysis.

This study tested the effect of intratumoral injection with activated tumor-infiltrating lymphocytes (TIL), and simultaneous administration of recombinant interleukin-2 (rIL-2) and interferon alpha (IFN-alpha) (LII protocol), on mouse liver tumor. Group I (n = 10) served as the controls. Group II (n = 17) received rIL-2 + IFN-alpha schedule. Group III (n = 20) received the LII protocol. A total of 5 x 10(6) of TIL were injected into 4 sites of a tumor in a single treatment. rIL-2 (1 x 10(6) IU) on the first day and IFN-alpha (1 x 10(5) IU) on the second day were alternately given with a total of 10 treatment doses that were completed in 20 days. Tumor remission or regression rates of 29% and 40% were obtained in groups II and III, respectively, but no remission was obtained in the controls. A large number of TIL were also observed in the tumors treated with the LII protocol. Making comparisons between the control group and IL-2 + IFN-alpha schedule, and the control group and LII protocol, the ratios of cytolytic activity of TIL in vitro were 0:32 and 0:57, respectively. We conclude that the LII protocol appears to be more effective in the treatment of mouse liver tumor than the IL-2 + IFN-alpha schedule, and that it may be a new promise for the treatment of patients with liver malignancies.

Animals↗

Scanning electron microscopy of human esophageal mucosa in patients with carcinoma of the esophagus.

Specimens taken at surgery from 15 patients with carcinoma of the esophagus were examined with scanning electron microscopy. Nine patients were treated with chemotherapy (cisplatin + 5-fluorouracil), surgery and radiotherapy; one received preoperative radiotherapy only; and the remaining five primary surgery only. Scanning electron microscopy was performed on specimens of both tumor tissue and the mucosa at least 5 cm from the tumor. In adjacent non-tumor tissue, damage due to treatment was observed in the form of changes in microridges and increased cell loss. In tumor tissue, the degree of damage was correlated to tumor response to treatment. For patients with no residual tumor after treatment, the ultrastructure was normalized with a low tumor score, while for patients with residual tumor, the score was high.

Adenocarcinoma↗

Response of the esophageal epithelium to concomitant cis-dichlorodiammineplatinum(II) and radiation treatment. An electron microscopic study in rabbits.

The rabbit esophageal mucosa was irradiated with daily fractions of 2 Gy up to an accumulated dose of 20 Gy (total dose 2, 6, 10. 16 or 20 Gy). Fifteen to forty-five minutes before the start of each irradiation 0.3 mg Cis-dichlorodiammineplatinum (cis-DDP, cisplatinum) was given by intraperitoneal injection to each rabbit. Examinations were carried out 1-10 days after each fractionation schedule, when specimens were taken for morphological investigations. Scanning electron microscope (SEM) examination showed a gradual development of damage with cell loss and structural disarrangement of the microridges and whorls on the surface. However, with further treatment the esophageal mucosa exposed to cis-DDP and radiation normalized faster and more complete compared to the esophageal part exposed to cis-DDP alone. The difference may depend on an accelerated proliferation in the part of the trachea that is exposed to a combined treatment.

Animals↗

The response of the tracheal epithelium to concomitant cis-diamminedichloroplatinum (II) and radiation. An electron microscopic study in rabbits.

The ciliated epithelium of the rabbit trachea was irradiated with daily fractions of 2 Gy up to an accumulated dose of 20 Gy (total dose: 2, 6, 10, 16, or 20 Gy). Fifteen to forty-five minutes before the start of each irradiation 0.3 mg Cis-diamminedichloroplatinum (cis-DDP) was given by intraperitoneal injection to each rabbit. Examinations were carried out 1-10 days after each fractionation schedule, when specimens were taken for morphological investigations. Scanning electron microscope (SEM) examination showed a gradual development of ciliary damage, from blebs on the cilia to swollen tips, broken and bent cilia and finally an epithelial injury with areas free from cilia, and a surface covered with microvilli-like structures. SEM also showed cell loss, and remnants of dead cells on the surface together with detritus. By transmission electron microscopy (TEM), ciliary damage, cell death and cell loss of the ciliated cell layer, as well as exfoliation of portions of goblet-like cells on the surface, could be confirmed. Scoring of SEM and TEM micrographs showed that for the tracheal part treated with cis-DDP and radiation, the maximal damage was expressed in the dose group 10 Gy, and above this no further increase in the average reaction occurred. For the part of the trachea only exposed to cis-DDP, the damage increased with the dose. The difference observed speaks for an accelerated proliferation exerted by the radiation.

Animals↗

Scanning electron microscopy and transmission electron microscopy of the ciliated cells of the trachea of the rabbit treated with misonidazole alone and in combination with ionizing radiation.

The trachea is often located in the treatment volume when irradiating malignant tumours in the thorax. In order to evaluate possible synergism between misonidazole and irradiation on this tissue, the following studies were made. Fifty rabbits were treated with daily injections of 100 mg misonidazole given i.p. on consecutive days from 1 to 10 days. Morphological investigations of the trachea were made with scanning electron microscopy (SEM), transmission electron microscopy (TEM) and light microscopy (LM). Physiological examinations were performed with recording of the ciliary beat frequency. The results were compared with those from a group of 100 rabbits given misonidazole in a similar manner and exposed to irradiation (2 Gy) 15-30 min after each injection. Ten rabbits were used as controls. The results are compared to the effect of fractionated irradiation alone with 2 Gy/day. Fractionated irradiation of the ciliary epithelium in the trachea of the rabbit has shown dose-dependent physiological and morphological effects. Misonidazole potentiates these effects of radiation with a more pronounced change of the ciliary beat frequency and an increased metabolic activity as could be visualized on TEM. The combination of drug and irradiation also induced a hyperplasia of the ciliary epithelium. Misonidazole itself had no effect on the ciliary beat frequency, but caused a hypoplasia of the ciliary epithelium.

Animals↗

Reaction of the vascular system in the trachea of the rabbit exposed to fractionated irradiation with and without the addition of misonidazole.

As the radiation field used in the radiation therapy of malignancies in the thoracic cavity often exposes the trachea to ionizing irradiation, it is important to ascertain the effects of radiation on this tissue either as a single therapy or in combination with radiosensitizers. In the study reported here the vascular area in the subepithelial layer of the trachea has been calculated in 160 rabbits treated in four ways: (1) 10 rabbits received no treatment and served as controls; (2) 50 rabbits were given 100 mg misonidazole daily on consecutive days, with the individual total dose ranging from 100 to 1000 mg; (3) 50 rabbits were treated with misonidazole in the same way, but were also exposed to radiation (2 Gy/F) at 15-30 min later; (4) 50 rabbits received only fractionated radiation (2 Gy/F). The total radiation dose in the irradiated animals ranged from 2 to 20 Gy. In the treated groups, an oedema was observed in both the ciliary cell layer and in the subepithelial area. In the group given only irradiation, this oedema was dose-dependent, but no such dose-dependency was observed in the two groups treated with misonidazole. The vascular area in the groups treated with misonidazole was significantly increased as compared with the group given only irradiation and the control group; this was valid both with and without correction for the oedema. There was a significant correlation between the oedema and the vascular area in the groups treated with misonidazole, which was not found in the group irradiated without the drug.

Animals↗

Intracellular recording of potential oscillations in ciliated cells exposed to ionizing radiation.

Intracellular potential oscillations of the ciliated cells of the rabbit's trachea have been measured by means of glass capillary microelectrodes during exposure of the cells to ionizing radiation. The electrophysiologic activity was fairly stable during the entire exposure at a total administered dose of 10.0 Gy. This finding is contradictory to the change in mucociliary activity obtained under the same conditions when measured with a light beam reflex method, but is in agreement with the findings regarding the influence of radiation on the membrane potentials as far as nerves and muscles are concerned.

Action Potentials↗

The effects of 10 Gy single-dose irradiation on the ciliated epithelium measured during and one-to-ten days following irradiation. A comparative physiological and morphological study.

Experiments recently done in this laboratory have shown that ionizing irradiation can result in an increase in the ciliary beat frequency of the trachea in vitro even during ongoing irradiation, implying an immediate stimulation of the physiological activity of the cells. This phenomenon is not fully understood and is by itself contradictory to general radio-biological concepts. Ultrastructural investigations on specimens taken immediately after irradiation (10 Gy) have, so far, not shown any changes. It has therefore seemed useful to extend the investigations by examining the effects of in vivo- irradiation (10 Gy) on rabbit trachea during the first 10 days after treatment. The following results have been obtained: Phase I: On days 1-3 after irradiation the beat frequency showed a slight increase (10%) within the irradiated part in comparison with a non-irradiated area of the trachea. No pronounced ultrastructural changes were found these days. Phase II: On days 4-7 after irradiation the mucociliary activity was reduced in those places where it could be measured. The surface of the cilia assumed a generally destructed appearance with elongated cilia and disorganisation. TEM-pictures showed an increased amount of goblet cells and signs of membrane damage such as cytoplasmic extrusions at the apical end of the cells. Phase III: On days 8-10 after irradiation a normalization of the tissue gradually took place with a beat frequency returning to normal. The ciliary surface showed a recovery process which also could be observed in the TEM-pictures.

Animals↗

Scanning electron microscopy and recording of the physiological activity of tracheal ciliated cells treated by fractionated irradiation.

The ciliated epithelium of the rabbit's trachea was irradiated with daily fractions of 2 Gy to an accumulated dose of 20 Gy. The beat frequency of the cilia was recorded and specimens were taken for SEM-, TEM- and LM-investigations. Examination was made 1-10 days after each fractionation schedule. An increased ciliary beat frequency was recorded at 2 Gy and 4 Gy. With increasing dose, there was an inverted relationship to the frequency. Light-microscopy showed edema and an increased amount of goblet cells in relation to the increasing dose. With SEM an increased number of ciliary blebs could be seen. These could be classified according to size and number, and showed a positive correlation to the dose. TEM-investigations showed signs of increased intracellular activity at higher doses in the form of multilobulated nuclei and an increasing number of nuclear pores. At lower doses, an increased amount of mitochondria appeared in the apical part of the cell. It is at present difficult to evaluate any correlation between the physiological activity and the morphology. More biological data are needed to explain the early irradiation effects.

Animals↗

The effects of ionizing irradiation on the ciliated cells of the central nervous system (CNS) in man--a scanning electron microscopy study.

In order to investigate the effects of radiotherapy on the ciliated ependymal lining of the CNS, samples were taken at autopsy from the lateral ventricles down to the IVth ventricles in patients irradiated for Glioblastoma multiforme in one hemisphere. Doses higher than 20 Gy affected the cilia and the lesions were more pronounced the heavier the dose. No regeneration of cilia were found in those regions which had received more than 20 Gy. In the areas irradiated with 20 - 15 Gy the cilia had a more normal form and cilia irradiated with less than 15 Gy were considered to be normal.

Adult↗

Cytological and cytogenetical analysis of thoracic duct lymph in patients with pulmonary carcinomas.

Seven patients with squamous cell carcinomas of the lung and nodular metastases underwent Daniels' biopsy and cannulation of the thoracic duct. Lymph specimens obtained by aspiration the day after catheter insertion were examined by cytologic and cytogenetical techniques, including chromosome banding methods. In five of the seven cases maligant cells could be detected by karyotype analysis, whereas standard cytologic examinations yielded no positive diagnoses. This indicates that chromosome analysis is applicable as a diagnostic tool in lymph fluid.

Carcinoma, Squamous Cell↗

The computer leucocyte. Analysis of the random movement of leucocytes in a visual field by means of computer simulation.

In vital preparations moving polymorphonuclear leucocytes (PMNs) disappear from the visual field. The present study provides evidence by means of geometrical analysis and computer simulation, that this disappearance is due to a heterogeneous distribution of the PMNs at the beginning of observation. The path of random-moving computer leucocytes is more tortuous than the path of comparable vital PMNs without obvious attractant, i.e. vital PMNs supposed to be random-moving. This finding is in agreement with the Allan-Wilkinson observation of 'persistent random walk' of vital cells.

Cell Movement↗