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Biomedical subjects

K R Trott

Publications and source records attributed to K R Trott.

At least 91 records · Page 5Linked to original sources

Effect of X-irradiation on the stomach of the rat.

A model for localized 300 kV X-irradiation of the rat stomach was developed. After irradiation with single doses, three distinct gastric disorders were observed which occurred at different latency times. Acute death 2-3 weeks after irradiation was caused by an erosive and ulcerative gastritis and occurred in all animals given 28.5 Gy without diet, in 17% of the animals given 28.5 Gy plus diet, and in 13% of the animals given 23 Gy. Subacute to chronic fatal disorders 4 weeks to 7 months after irradiation were seen as stomach dilatation and gastroparesis, associated with the replacement of the normal gastric mucosa by a hyperkeratinized multilayered squamous epithelium. These disorders occurred in 40-100% of the animals after doses between 16 Gy and 28.5 Gy (+diet). An ED 50 value of 19.2 Gy (16.5-21.2 Gy, 95% confidence interval) was calculated for this gastroparesis. Late gastric obstruction exceeding 7 months after irradiation was seen in the rats because of profound changes in the gastric wall in 13-18% of the animals after doses between 23 Gy and 14 Gy. In animals surviving these three periods, an atrophic mucosa and intestinal metaplasia developed. From functional and morphohistological studies, it can be concluded that there are differences in the pathogenesis of the fatal radiation damage for each of these periods after irradiation.

Animals↗

Simultaneous chemo-radiotherapy with 5-FU/folinic acid/cis-platinum and accelerated split-course radiation in advanced head and neck cancer.

In a clinical phase-II trial, 62 previously untreated patients suffering from unresectable stage III (4 patients) and IV (56 patients) squamous cell carcinoma of the head and neck were treated with a simultaneous chemoradiotherapy consisting of a 5-fluorouracil/folinic acid/cis-platinum combination and of an accelerated split-course radiotherapy. As results, 3 patients died from tumor arrosion bleeding during the treatment. The median follow-up time of the surviving patients is 27+ months (range 18-44 months). Forty-eight out of 62 patients (77%) achieved complete remission, and 11/62 patients (18%) partial remission. Presently, 32 patients (52%) are without evidence of disease. The actuarial 3-year overall survival rate (Kaplan-Meier method) out of 62 patients is 53%. The actuarial disease-free survival and local tumor control rates at 3 years are 58% and 72%. Toxicity on oral mucosa was severe but tolerable, bone marrow depression was marked but not life-threatening. In conclusion, this combined simultaneous modality approach is highly effective in locally advanced head and neck cancer. It appears to provide superior survival and local control rates as compared to conventional radiotherapy or sequential chemo-radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

First experiences with fission neutrons in the radiation therapy of cancer patients.

16 patients have been treated until October 1987 at the mixed reactor beam of the RENT-facility in Munich-Garching. All of them received a single dose of 200 to 250 cGy after complete conventional radiotherapy and in same cases also surgery because of the lack of complete tumor resection or local tumor control after radiation control. The ages ranged from 40 to 84 years. The follow-up amounted between two and 28 months, 8.5 months on the average. The tumors selected appeared to be particularly suitable because of their growth in poorly perfused tissues, after the previous surgery and/or radiotherapy. All cases are briefly reported. The general experience from the very limited study is promising. The local effects to the tumor tissue so far are impressive. No severe side effects which could be related to the RENT-session were observed until now.

Adult↗

Morphological and functional changes in the rat heart after X irradiation: strain differences.

The hearts of mature male rats of the Wistar and Sprague-Dawley strains were locally irradiated with single doses of 17.5 and 20.0 Gy of X rays, respectively. These two dose levels had previously been shown to result in a comparable latent period between irradiation and the death of rats of these two strains from cardiac failure. Morphological changes in the myocardium and modifications in cardiac function were assessed in the animals at 28, 70, and 100 days after irradiation. The first radiation-induced change which was observed in the myocardium was a rapid decline in capillary density and a loss of alkaline phosphatase activity by the capillary endothelial cells. The capillary density was reduced to approximately 50% of that of unirradiated control values at 28 days and to approximately 40% of the control values between 70 and 100 days after irradiation. The loss of enzyme activity was also detected at 28 days. Examination of histological sections showed an increase by 70 days in the areas with negative enzyme activity up to approximately 70% of the myocardium. The reduction in capillary density and the loss of enzyme activity occurred before any marked pathological changes were seen in the myocardium. The pathological lesions seen in the myocardium at 100 days after irradiation were qualitatively and quantitatively the same in the two strains of rat. Measurements of cardiac output in Sprague-Dawley rats showed a gradual decline in output after irradiation; however, measurements in Wistar rats showed a progressive increase in cardiac output over the same period of time. It was shown by rubidium extraction that there was an increase in the percentage of the total cardiac output distributed to the ventricular muscle of Sprague-Dawley rats, while similar measurements in Wistar rats showed no significant change. In spite of the marked strain differences observed in cardiac output and rubidium extraction, blood perfusion per gram of ventricular muscle was apparently not modified in both strains of rat after irradiation. These findings indicated that the correlation between morphological effects after irradiation and the functional expression of damage is highly complex.

Alkaline Phosphatase↗

Radiation induced heart disease in hypertensive rats.

Spontaneously hypertensive Wistar rats were given single doses of X rays to their heart. Irradiation decreased the blood pressure before any myocardial radiation damage was apparent. Male rats, which were more hypertensive than female rats, had a shorter survival time after local heart irradiation than female rats. Antihypertensive treatment with hydralazine did not increase the survival time. It is considered that myocardial hypertrophy is the cause of the increased susceptibility of spontaneously hypertensive rats to local heart irradiation.

Animals↗

Clonogenicity of the progeny of surviving cells after irradiation.

The clonogenic potential of the progeny of irradiated cells was tested in vitro by replating irradiated cultures after various times, allowing between five and over 25 subsequent divisions to take place after irradiation. Whereas the plating efficiency of surviving Chinese hamster cells was not decreased, in C3H10T1/2 cells a dose-dependent but slight decrease in plating efficiency was observed even after the longest follow-up period. These data do not contradict the prevalent hypothesis in radiobiology that the proliferation potential of a clonogenic cell surviving after irradiation is not significantly different from that of a non-irradiated cell.

Animals↗

Possible dose rate dependence of recovery kinetics as deduced from a preliminary analysis of the effects of fractionated irradiations at varying dose rates.

Data relating to jejunal crypt survival following fractionated total body irradiation of C3H mice have been subjected to a preliminary analysis using the linear-quadratic formalism. Because the regimes considered involved fairly closely-spaced fractions, delivered at dose rates in the range 1.2-72 Gy h-1, it was necessary to further develop previously established forms of the model in order to carry out the evaluation. The magnitude of the recovery half-life has been deduced for each of the regimes and found to be in the approximate range 0.1-0.6 h. For any given fraction number, the half-life appears to be markedly dependent on dose rate, increasing with dose rate up to approximately 25 Gy h-1, falling off thereafter. Tentative reasons for this behaviour are given, together with an assessment of the possible shortcomings of the analytical method.

Animals↗

[Endoscopic control of the course and its histological correlation in chronic radiation injury of the rat rectum].

On the basis of endoscopic investigations, the reaction to X-radiation of the hindgut of the rat could be divided into four phases. Their courses after different radiation doses as well as after dietary influence are described. This enabled us-besides the acute (diarrhoea) and chronic (diarrhoea followed by intestinal occlusion) phases shown by clinical examination - to demonstrate the early vascular reaction (first week after irradiation) as well as the asymptomatic interval between the acute and chronic phases. The interval phase was found to be of importance for prognosis and therapy, because all animals who died later on of intestinal occlusion developed already during this phase circular ulcerations which could be demonstrated by endoscopy.

Animals↗

Accelerated split-course radiotherapy and simultaneous cis-dichlorodiammine-platinum and 5-fluorouracil chemotherapy with folinic acid enhancement for unresectable carcinoma of the head and neck.

Thirty-four (6 stage III, 28 stage IV) patients with advanced squamous cell carcinoma of the head and neck were treated by simultaneous radio-chemotherapy. Treatment was divided into three cycles. Chemotherapy consisted of cis-diamminedichloroplatinum(II) (cis-DDP) 60 mg/sqm i.v., 5-fluorouracil (5-FU) 350 mg/sqm i.v. and folinic acid (FA)-50 mg/sqm i.v. on day 2 and 5-FU 350 mg/sqm per 24 h and FA 100 mg/sqm/24 h on days 2-5. Radiotherapy consisted of 23.4 Gy/9 days divided in 13 fractions of 1.8 Gy delivered twice a day from day 3 through day 11. This regimen was repeated on days 22 and 44. Total radiation dose amounted to 70.2 Gy/51 days. Mean follow-up of surviving patients was 21 (14-34) months. 28/32 patients achieved complete response, 4/32 partial response. Actuarial one and two years survival were 88 and 58% including two early deaths from tumour bleeding. Local control rates at one and two years were 87 and 81%, respectively. This protocol produces excellent palliation and the chance of improved long term tumour control. Two patients developed distant metastases. Overall toxicity was tolerable. Since the treatment breaks were inserted after low radiation doses, acute mucositis healed rapidly and was not a limiting factor.

Adult↗

The effect of combined treatment of HeLa cells with actinomycin D and radiation upon survival and recovery from radiation damage.

The presence of actinomycin D during irradiation of HeLa cells leads to radiosensitization under aerobic but not under hypoxic conditions. Depending on the time interval between incubation with the drug and irradiation, pre- or post-treatment with actinomycin D also increases the radiosensitivity of HeLa cells irradiation in air. Pretreatment with actinomycin D does not inhibit recovery from potentially lethal radiation damage. In split-dose experiments, recovery from sublethal radiation damage was not impaired by the drug if present during the entire fractionation interval or if it was given as a short exposure after the first radiation dose.

Cell Survival↗

Experimental irradiation of the rat ureter: the effects of field size and the presence of contrast medium on incidence and latency of hydronephrosis.

Following X-irradiation of a 1.5 cm length of rat ureter, hydronephrosis developed after doses down to 10 Gy. The estimated ED50 was 11.8 Gy. In the dose range 37.4 Gy to 17.5 Gy there was a significant increase in latency with decreasing dose, but at lower doses the latency did not increase further. Reducing the length of ureter irradiated to 0.5 cm or 0.8 cm caused a decrease in incidence of hydronephrosis and longer latency periods. The ED50 for rats irradiated to 0.5 cm of ureter was 29.6 Gy. The possibility that secondary radiation produced as a result of interaction between X-radiation and iodinated contrast medium might affect the radiation induction of hydronephrosis was investigated. No difference was found between groups of rats irradiated with or without injection of contrast media.

Animals↗

The effects of dose-fractionation on radiation-induced heart disease in rats.

The hearts of Wistar rats were irradiated locally with a range of total doses given in 1, 3, 5 or 10 fractions in 4 weeks. As even after the lowest single dose of 17.5 Gy all animals died within 18 months after irradiation from heart failure, no ED50 could be determined. Therefore, the mean survival time following irradiation was chosen as isoeffect for the comparison of different treatment groups. Fractionation has a marked sparing effect on the radiation-induced heart disease. For an isoeffect of a mean survival time of 42 weeks an alpha/beta of 1 Gy was found.

Animals↗

Survival and quality of life after continuous accelerated radiotherapy of glioblastomas.

One hundred and thirty three patients were given radiotherapy after subtotal resection of glioblastoma with different total doses and fractionation schedules including 38 patients receiving continuous accelerated fractionation with 3 fractions of 1.6 Gy per day up to 60 Gy in 2 weeks. Tolerance of the accelerated schedule was as good as of the conventional schedules but overall survival was not improved.

Adult↗

Jejunal crypt stem-cell survival after fractionated gamma-irradiation performed at different dose rates.

Jejunal crypt survival after fractionated total body irradiation of C3H mice given at dose rates between 1.2 and 0.08 Gy/min was studied and the results analysed according to the linear quadratic model. Whereas alpha was independent of dose rate beta decreased with dose rate to approach zero at about 0.01 Gy/min. During the period of recovery, sublethal damage from doses given at high dose rate interact with low dose rate irradiation given immediately after, and increases its effectiveness.

Animals↗