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Biomedical subjects

M Albertsson

Publications and source records attributed to M Albertsson.

50 records · Page 3Linked to original sources

Adverse cardiac effects during induction chemotherapy treatment with cis-platin and 5-fluorouracil.

Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.

Adult↗

Discoid lateral menisci: a report of 29 cases.

Of 7,056 knee arthroscopies performed during the period September 1979-November 1986, 30 patients had discoid menisci, one medially and 29 laterally. The frequency of discoid lateral menisci appears to be lower in Sweden than in North America, Scotland, and Japan. Our policy, to do a meniscectomy only when the discoid meniscus is thought to play a role in the symptoms, but leave it intact when an incidental finding, seems to give good results. Nine of the 29 patients studied had trauma as an initiating factor, but of those 10 patients whose discoid lateral menisci were thought to cause the symptoms, only one had trauma as an initiating factor. Theories of the cause of discoid menisci are discussed, as well as recommended treatment.

Adult↗

Changes in the tracheal ciliated cells in rabbits treated by cis-diamminedichloroplatinum (II) as studied by electron microscopy.

The ciliated epithelium of the rabbit's trachea was investigated after a single 5 mg dose of cis-diamminedichloroplatinum (cis-DDP). Specimens were taken for scanning electron microscopy, transmission electron microscopy and light microscopy. Examination was performed daily for 20 consecutive days. A cytotoxic effect of the drug on the ciliated epithelium was observed with bent ciliary tips, swollen tips and broken cilia. Finally the cilia were lost and large areas of the surface were covered with microvilli. However, 20 days after the drug injection, the restitution of the ciliary carpet was almost complete.

Animals↗

Effects of fractionated irradiation on the esophageal mucosa: a scanning and transmission electron microscopic study.

The mucosa of rabbit esophagus was irradiated with daily fractions of 2 Gy to an accumulated dose of 20 Gy. Specimens were taken for scanning electron microscopy, transmission electron microscopy and light microscopy investigations. Examination was made 1-10 days after each fractionation schedule. Light microscopy showed dose-dependent edema of the irradiated mucosa which also could be seen and scored from SEM pictures. SEM investigations showed that this was accompanied by loosening of microridges and a slightly increased cell loss. By SEM, a varying amount of bacteria could be seen which did not make intimate contact with the surface cells. During the first five days there was a steady decrease of the number of bacteria in relation to the absorbed dose. In the later period of examination, the amount of bacteria increased up to a given dose of 10 Gy. Thereafter, the number faded off to about zero when 20 Gy had been administered.

Animals↗

Effects of cis-dichlorodiammineplatinum alone and in combination with ionizing radiation of the esophageal mucosa: a scanning and transmission electron microscopic study.

Cis-dichlorodiammineplatinum (cis-DDP) has for more than 20 years been part of the therapeutic arsenal of oncology. Most of the knowledge about its biological action is based on clinical investigations and therefore an examination of the influence of cis-DDP at the cellular and sub-cellular level is necessary. Five mg of cis-DDP was given intraperitoneally (i.p.) to ten rabbits. Ultrastructural examinations were performed on the upper and lower parts of the esophagus each day after the injection on the following ten days. Another 50 rabbits were given 5 mg cis-DDP and were irradiated in an area just beneath the hypopharynx. They were given 2 Gy at each irradiation and were maximally treated with up to 20 Gy. Examinations were carried out from the first day after the final treatment and each day during ten consecutive days. Five animals were used as controls. Cis-DDP proved to have a deleterious effect on the epithelial layer of the esophageal mucosa with cell loss and structural disarrangement of the microridges and whorls on the surface. This finding was an early phenomenon and lasted for all ten examination days. The changes were not more exaggerated when irradiation was added to the experiments. Repopulation of new cells from the matrix was noticed about five days after the administration of cis-DDP alone.

Animals↗

Ciliated cells of the trachea of the rabbit, treated with cis-diamminedichloroplatinum (II) alone, or in combination with ionizing radiation.

The ciliated epithelium of the rabbit trachea was irradiated with daily fractions of 2 Gy to an accumulated dose of 20 Gy (TD: 2, 6, 10, 16, or 20 Gy). Fifteen to forty-five minutes before start of the first irradiation (treatment day 1), 5 mg cis-DDP was given by intraperitoneal injection to each rabbit. Examination was made 1 - 10 days after each fractionation schedule, when specimens were taken for investigations. Scanning electron microscope investigations showed a gradual development of ciliary damage from blebs on the cilia to swollen tips, broken and bent cilia and finally an epithelial lining with areas free from cilia with 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 microscope 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. The irradiated ciliated epithelium and the untreated control epithelium in each animal showed no difference in this respect. Thus no enhancement of the effects of radiation could be observed. The development of ultrastructural damage may be due to a cytotoxic effect of the drug on the ciliated epithelium. However, 19 days after the start of cis - DDP injection, a hyperplasia of the basal cell layer was observed, which indicates that the observed cytotoxicity of the drug is reversible and a normalisation occurs during the last days of observation in this study.

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↗

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↗

Electron microscopy of squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck carries a bad prognosis. In order to achieve cure, the most important thing to attain is local tumour control. The main therapy available is external radiotherapy, which can be supplemented when necessary, with interstitial radiotherapy, chemotherapy and surgery. In this paper we have evaluated specimens, taken before therapy, from 35 patients with squamous cell carcinoma of the head and neck. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses were made. With SEM, the parameters analysed were the amount and appearance of microvilli, filaments, and blood vessels. From TEM, scoring was made of the filaments, desmosomes, nuclei, nucleoli, mitochondria, and blood vessels. Scoring of the samples showed a difference between the group with recurrent disease (n = 10, Group 1) and the group with local tumor control (n = 25, Group 2) in regard to both blood vessels and intracellular filaments. No differences of the nuclei, nucleoli, or the mitochondria were observed.

Blood Vessels↗

Antithrombotic treatment in protection against thrombogenic effects of 5-fluorouracil on vascular endothelium: a scanning microscopy evaluation.

Cardiotoxicity is a serious side effect of treatment of malignant diseases with 5-fluorouracil (5-FU). The underlying pathophysiologic mechanism remains unclear but clinical data suggest that the endothelium of coronary arteries may be involved. Experimental studies indicate that the endothelium is especially susceptible to 5-FU and support the hypothesis that a thrombogenic effect of 5-FU, secondary to its direct toxic effect on the endothelium, is one of the pathophysiologic mechanisms behind 5-FU-induced cardiotoxicity. In the present study we evaluate the role of antithrombotic treatment with dalteparin as protection against the thrombogenic effect of 5-FU on the vascular endothelium in a rabbit model. The effects on the vascular endothelium of 5-FU, dalteparin, and the combination of these two substances were evaluated with scanning electron microscopy 1, 3, 7, 14, and 30 days after treatment and compared with a control group. Very severe damage to the endothelium was seen in 5-FU-treated animals, often leading to intima disruption and denudation of underlying structures, with accompanying platelet accumulation and fibrin formation. The most extensive damage was observed on Day 3 after treatment. The cytotoxic effect of 5-FU was partly reversible. The combination of 5-FU and dalteparin gave lower scores on Day 3 because of less evidence of thrombotic events. However, the reversibility of the endothelial damage was poorer in this group, as well as in the group that received dalteparin alone. The findings support the hypothesis that antithrombotic treatment with dalteparin can protect against the thrombogenic effect of 5-FU, secondary to its direct toxic effect on the vascular endothelium. However, the study indicates that dalteparin per se has a toxic effect on the endothelium that is different from that of 5-FU.

Animals↗

Body protein as a prognostic instrument for cancer patients?

Many cancer patients are affected by loss of appetite, weight loss and fatigue in the course of disease. These symptoms reduce the patients' quality of life, increase morbidity, and lessen tolerance to anti-tumor treatment. In some cases the symptoms are partly caused by various treatment modalities. The aim of this study was to investigate if radiotherapy affects the body weight and body protein of patients, and if changes in body protein have any clinical significance.

Appetite↗

Dose-response studies of single dose ionizing radiation on the ciliated epithelium of the trachea of the rabbit. A physiologic and ultrastructural investigation.

The effects of ionizing radiation on the ciliated epithelium of the rabbit's trachea were studied by ultrastructural and physiologic examinations during 10 days after single doses of 2 to 30 Gy. Low doses (2 and 2.5 Gy) caused during the first days after irradiation increased ciliary activity which during the following days returned to normal. Ultrastructurally blebs were observed on the cilia. Five and 10 Gy caused slight increment of the ciliary activity, also more marked structural effects with swollen ciliary tips, bent tips and some cilia broken and adhering to each other. Larger single doses (15-30 Gy) caused reduced and irregular ciliary activity; ultrastructurally, most cilia were broken and adhered to each other, but some cilia seemed to be unaffected. The goblet cells increased in number already after 2 and 2.5 Gy. Mucinous granula could be observed on the ciliary surface and after 30 Gy there was an explosive emptying of the goblet cells.

Animals↗