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Biomedical subjects

K R Trott

Publications and source records attributed to K R Trott.

At least 73 records · Page 4Linked to original sources
PubMed1994

Therapeutic effects of low radiation doses.

PURPOSE: This editorial explores the scientific basis of radiotherapy with doses of < 1 Gy for various non-malignant conditions, in particular dose-effect relationships, risk-benefit considerations and biological mechanisms. METHODS: A review of the literature, particularly clinical and experimental reports published more than 50 years ago was conducted to clarify the following problems. 1. The dose-response relationships for the therapeutic effects on three groups of conditions: non-malignant skin disease, arthrosis and other painful degenerative joint disorders and anti-inflammatory radiotherapy; 2. risks after radiotherapy and after the best alternative treatments; 3. the biological mechanisms of the different therapeutic effects. RESULTS: Radiotherapy is very effective in all three groups of disease. Few dose-finding studies have been performed, all demonstrating that the optimal doses are considerable lower than the generally recommended doses, yet few of these studies meet the required standard. In different conditions, risk-benefit analysis of radiotherapy versus the best alternative treatment yields very different results: whereas radiotherapy for acute postpartum mastitis may not be justified any more, the risk-benefit ratio of radiotherapy of other conditions and particularly so in dermatology and some anti-inflammatory radiotherapy appears to be more favourable than the risk-benefit ratio of the best alternative treatments. CONCLUSIONS: Radiotherapy can be very effective treatment for various non-malignant conditions such as eczema, psoriasis, periarthritis humeroscapularis, epicondylitis, knee arthrosis, hydradenitis, parotitis and panaritium and probably be associated with less acute and long-term side effects than similarly effective other treatments. Randomized clinical studies are required to find the optimal dosage which, at present, may be unnecessarily high. Since no adequate experimental studies have been performed nothing is known about the mechanisms of these therapeutic radiation effects. Good experimental models are now available which should be used to investigate the cellular and molecular mechanisms involved.

Humans↗
PubMed1993

Post-irradiation bladder dysfunction: development of a rat model.

The aim of this research was to establish a small animal model for the functional and morphological study of post-irradiation bladder dysfunction. Young adult female Wistar rats were X-irradiated with single doses of 10, 15, 20 or 25 Gy. Filling cystometry was performed to assess changes in reservoir function: the volume infused to produce a rise in intravesical pressure of 5 cmH2O was calculated as an index of compliance. A biphasic reduction in this index was noted in animals receiving 15-25 Gy; the first reduction developed at about 4 weeks, and the second started at 3-4 months and persisted at 6 months. Bladder tissue was taken at this time (6 months post-irradiation) for morphological study. Histological examination demonstrated an increased mast cell density in the irradiated bladders, but was otherwise non-specific; fibrosis was discernible in only half of the 18 animals studied. Electron microscopy showed focal degeneration of smooth muscle cells, and in some areas there was selective degeneration of unmyelinated axon profiles. The biphasic reduction in the compliance index is consistent with the timing of the symptoms of the acute and late irradiation reactions reported by radiotherapy patients. Changes in axon profiles and mast cell density may be of functional significance.

Animals↗
PubMed1993

Clonal heterogeneity in delayed decrease of plating efficiency of irradiated HeLa cells.

The clonogenic potential of progeny of irradiated HeLa cells was studied at different times after single doses of 4-12 Gy. The dose-dependent decrease in plating efficiency that was observed resembled the effect termed "delayed lethal mutation" by Seymour et al. (1986). The effect decreased with time after irradiation. Individual clones of irradiated and non-irradiated cells were isolated, expanded and replated 5 weeks after irradiation, i.e., after between 200,000 and 1,000,000 progeny had formed from the individual parent cell. The plating efficiency of progeny of unirradiated cells did not vary much, whereas clonal progeny of irradiated cells had plating efficiencies ranging from 3% to 76%. The plating efficiency was not related to the cell number in the original clone.

Cell Survival↗
PubMed1993

The effect of dose fractionation on radiation injury in the rat stomach.

Localized 300 kV X-irradiation of the rat stomach with single and fractionated (two and five fractions given daily and in 4 weeks) doses was performed. In the second and third week after irradiation acute radiation gastritis developed which resulted in a dose-dependent drop in body weight. The alpha/beta value for a 10% drop in body weight was calculated to be 9.6 Gy (95% confidence interval 2.1-25.9 Gy). Between 4 and 40 weeks after irradiation subchronic radiation damage was observed which presented itself as atonic dilatation of the stomach. For this effect, the alpha/beta value is 4.8 Gy (graphical estimation) and 5.3 Gy (95% confidence interval 0.4-13.1 Gy; direct Poisson model). In the five-fraction (5F) experiment a significant increase in tolerance amounting to 0.8 Gy/day for the acute effect and 0.4 Gy/day for the subchronic effect was observed when intervals were increased from 1 day to 1 week. In a separate experiment animals were pre-irradiated with subtoxic and toxic radiation doses. One hundred days later acute tolerance to a second irradiation was completely restored. However, no recovery of subchronic damage was observed.

Acute Disease↗
PubMed1992

[The differences between interstitial pneumonia following whole-body irradiation and radiation-induced pneumonitis].

Clinical observations and experimental results suggest that radiation pneumonitis occurring after localised lung irradiation and interstitial pneumonia occurring after localised lung irradiation and interstitial pneumonia occurring after total body irradiation and bone marrow transplantation (no matter whether or not associated with cytomegalovirus infection) are two different pathological entities. They differ with regard to latency, pathogenesis, dose dependence, and probably dose distribution. Based on these considerations some recommendations on the planning of total body irradiation are made.

Animals↗
PubMed1992

[Acute and chronic disorders in gastric emptying after the x-ray irradiation of the rat stomach and their therapeutic modification].

After localized 300 kV X-irradiation of the rat stomach the stomach emptying time of a liquid and a solid test meal was examined with a non-invasive radiological method. In the acute period one to three weeks after irradiation with single doses between 10.7 and 21.3 Gy we observed a faster emptying of the liquid and a delayed emptying of the solid test meal. The faster emptying of the liquid test meal was treated successfully with atropine. In the chronic period we observed a delayed emptying of the liquid and of the solid test meal. These emptying disorders were treated partially successfully with the parasympathomimeticum carbachol and they were treated completely successfully with the dopamine antagonist metoclopramide.

Animals↗
PubMed1992

Radiographic and function changes after partial lung irradiation in the rat.

The early and late changes in the right rat lung following single dose X-irradiation were studied using computerised axial tomography (CT) and noninvasive lung function tests. The biphasic response of the lung, i.e., the early pneumonitis phase, from six to ten weeks and later fibrosis starting at 18 weeks after irradiation, were both detectable by increased lung density. Whereas functional changes were prominent during the pneumonitis phase, these were only minor in the late phase.

Animals↗
PubMed1991

Rapid repopulation in radiotherapy: a debate on mechanism. Accelerated repopulation in tumours and normal tissues.

Accelerated repopulation is a well established response pattern of normal epithelial to fractionated irradiation. It is delayed until the tissue recognises functional injury. It is well regulated to maintain a steady state and continues until integrity of the tissue is restored. We assume that some of these features of the parental normal tissue are preserved and still operate in squamous cell carcinoma, although probably in a less well controlled and organised manner.

Carcinoma, Squamous Cell↗
PubMed1991

[Effects of tetrachlorodecaoxide (TCDO) in chronic radiation lesions of the rat colon].

The influence of tetrachlorodecaoxide (TCDO) on the chronic radiation damage after local irradiation of the rat colon was examined when given at different times and at different doses. A tetrachlorodecaoxide treatment before the acute period resulted in an extension of the latency period. When tetrachlorodecaoxide was given by the highest dose of 0.8 ml WF 10 at the onset of the chronic phase we observed an increase in the survival rate. Endoscopically and histologically we did find demonstrable signs of an improved healing of the mucosa.

Animals↗
PubMed1990

Cell repopulation and overall treatment time.

Prolongation of the overall treatment time in radiotherapy, especially of squamous cell carcinomas of the head and neck, decreases the chances of cure. This is most likely because of the proliferation of surviving clonogenic tumor cells between dose fractions. Between the 3rd and 7th week of conventional radiotherapy of head and neck cancers, on average 0.5 to 0.7 Gy are lost per day by repopulation. As this represents an average value, repopulation may be even more efficient in subgroups of faster tumors. There is little information on repopulation rates during the first 2 weeks of radiotherapy. Prolongation of the overall treatment time in radiotherapy helps to avoid severe side effects from acutely responding tissues, especially oral mucosa. This sparing effect of increasing overall treatment time is mainly caused by the regeneration of mucosal stem cells and transit cells. This repopulation is slow in the first 2 weeks and accelerates dramatically thereafter. The nature of the trigger for acceleration is not known but seems to be related to a critical threshold of acute tissue hypoplasia and the development of the inflammatory reaction of the connective tissue. It is not known whether accelerated tumor repopulation is stimulated by the same or a similar mechanism as the normal epithelium. During accelerated repopulation the oral mucosa is able to compensate a considerably higher proportion of the daily dose fraction than the tumor. These factors have to be taken into account when treatment strategies are designed to cope with the problem of accelerated repopulation.

Cell Division↗
PubMed1990

Physiologic consequences of local heart irradiation in rats.

Noninvasive methods have been used to study the long-term cardiovascular and pulmonary functional changes at rest and after exercise in adult rats following local heart irradiation with single x-ray doses of 15, 17.5 or 20 Gy, and in non-irradiated control animals. Rats that had undergone a chronic exercise program were compared with untrained cohorts. The earliest dysfunction detected was an increased respiratory rate (f) at 10 weeks after irradiation in the highest dose group. In contrast, both telemetric heart-rate (HR) and rhythm and indirect systolic blood pressure measurements performed at rest only revealed changes starting at 43 weeks after irradiation with 20 Gy, up to which point the rats showed no clinical signs of heart failure. However, the number of minutes required for the recovery of the HR to pre-exercise levels following the implementation of a standardized exercise challenge was elevated in untrained rats compared with their trained cohorts at 18 weeks after irradiation with 20 Gy. Increases in recovery times were required in the two lowest dose groups, starting at 26 weeks after irradiation. It was concluded that the reserve capacity of the cardiopulmonary system masks functional decrements at rest for many months following local heart irradiation, necessitating the use of techniques which reveal reductions in reserve capacities. Further, the influence of local irradiation to the heart and lungs deserves closer scrutiny due to mutual interactions.

Animals↗
PubMed1990

Endothelial cell proliferation in the rat heart following local heart irradiation.

Radiation-induced myocardial degeneration in the rat is preceded by changes in capillary structure and function, which may be a major factor in the pathogenesis of radiation-induced heart disease. In order to investigate the mechanism of capillary damage we studied endothelial cell proliferation in untreated control rats and in rats at different times following local heart irradiation with 20 Gy using [3H]thymidine autoradiography. Since the latency times of myocardial degeneration as well as capillary damage are about twice as long in Sprague-Dawley rats as in Wistar rats, endothelial cell proliferation was studied in both strains. The percentage of labelled nuclei (LI) after repeated labelling over a period of 12 h was 0.32 +/- 0.06 in control animals of both strains. Therefore the turnover time of endothelial cells was estimated to be between 115 and 400 days. Following irradiation the LI increased above control levels. In both strains this was concurrent with the time of onset of capillary depletion and alkaline phosphatase loss, which occurred at around 23 days post-irradiation in Wistar rats and 58-74 days in Sprague-Dawley rats. In both strains the increase in LI was confined to alkaline-phosphatase-negative areas. In phosphatase-positive areas endothelial cell proliferation was unchanged in spite of the reduction in capillary density. Since, in general, the latency to post-irradiation death of a cell is closely related to its normal turnover time, the decrease in capillary density is not due to mitotic death of proliferating cells as is commonly seen in other tissues.

Animals↗
PubMed1990

[Radiogenic effects on liver tissue].

In a review of literature the presented studies on radiogenic liver injuries are summarized. Whereas in the past the liver tissue was supposed to be radioresistant nearly completely, to newer knowledge this organ has to be classed with most radiosensitive tissues at all. The early picture of a liver injury in man is characterized by the veno-occlusive syndrome. Like in Budd-Chiari-Syndrome a congestion begins in the central veins and the centrolobular sinusoids, that has severest threatening consequences for the patients with extensive liver irradiation. The clinic picture is demonstrated. At present no suitable animal model exists for this disease yet. The presented pathological and electron microscopical findings do not allow any final estimation of the pathogenesis in this disease. The radiogenic late-effects are manifested in the liver in a centrolobular fibrosis, also starting from the Glisson's triangles, with cirrhotic reconstruction of liver architecture. The great compensatory power of the organ does not cause clinical pictures to be effected in radiotherapeutic practice with only partial liver irradiation in most cases. The dose-time-relation of the radiogenic hepatitis shows a very little alpha-/beta-value. With this the liver renders as typical late-effect tissue and should be spared effectively by choice of small single doses.

Animals↗
PubMed1989

The effect of actinomycin D on split-dose recovery and repopulation in jejunal crypt cells in vivo.

The effect of actinomycin D in combination with radiation on the survival of mouse jejunal crypt cells was measured using the microcolony technique. When administered 30 min before irradiation the drug was seen to enhance the cell killing of single doses of radiation. No significant changes in the rate or amount of repair in split-dose irradiation were found. Protracted split-dose intervals revealed cell repopulation commenced within 12 h after the first radiation dose. When given 6 h post-conditioning dose actinomycin D did not inhibit cell repopulation.

Animals↗