The response of pig skin to single doses of irradiation from strontium-90 sources of differing surface area.
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Animals↗
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Clinical experience with electron pseudoarc therapy.
Between November 1986 and June 1990, 24 patients were treated with electron pseudoarc therapy at McGill University. There were 21 females and three males aged 27 to 81 years (median 62 years). 17 patients, nine of whom had received previous conventional locoregional irradiation, were treated palliatively for locally extensive breast carcinoma. Eight of these 17 patients achieved a complete, and six a partial, response to treatment; nine subsequently developed evidence of progressive disease within the treatment field after intervals of one to 27 months (median 5 months) following therapy. Eight patients developed moist desquamation of the treated chest wall, which was extensive in four; one of these patients developed chronic ulceration of the skin. The latter and one additional patient developed radiation pneumonitis. Seven patients were treated with radical intent, two following mastectomy for breast carcinoma, and one each for chest wall lymphoma, chest wall sarcoma, scalp angiosarcoma, scalp lymphoma and posterior cervical soft tissue sarcoma. Local control was achieved in six of these seven patients with minimal toxicity. Electron pseudoarc therapy is a treatment option for selected breast carcinoma patients for palliation of extensive chest wall disease, although morbidity may be considerable. The technique may, however, play a more useful role in other situations where the superficial portion of large curved surfaces is to be treated with curative intent.
Adult↗
Single dose irradiation response of pig skin: a comparison of brachytherapy using a single, high dose rate iridium-192 stepping source with 200 kV X-rays.
An experimental brachytherapy model has been developed to study acute and late normal tissue reactions as a tool to examine the effects of clinically relevant multifractionation schedules. Pig skin was used as a model since its morphology, structure, cell kinetics and radiation-induced responses are similar to human skin. Brachytherapy was performed using a microSelectron high dose rate (HDR) afterloading machine with a single stepping source and a custom-made template. In this study the acute epidermal reactions of erythema and moist desquamation and the late dermal reactions of dusky mauve erythema and necrosis were evaluated after single doses of irradiation over a follow-up period of 16 weeks. The major aims of this work were: (a) to compare the effects of iridium-192 (192Ir) irradiation with effects after X-irradiation; (b) to compare the skin reactions in Yorkshire and Large White pigs; and (c) to standardize the methodology. For 192Ir irradiation with 100% isodose at the skin surface, the 95% isodose was estimated at the basal membrane, while the 80% isodose covered the dermal fat layers. After HDR 192Ir irradiation of Yorkshire pig skin the ED50 values (95% isodose) for moderate/severe erythema and moist desquamation were 24.8 Gy and 31.9 Gy, respectively. The associated mean latent period (+/- SD) was 39 +/- 7 days for both skin reactions. Late skin responses of dusky mauve erythema and dermal necrosis were characterized by ED50 values (80% isodose) of 16.3 Gy and 19.5 Gy, with latent periods of 58 +/- 7 days and 76 +/- 12 days, respectively. After X-irradiation, the incidence of the various skin reactions and their latent periods were similar. Acute and late reactions were well separated in time. The occurrence of skin reactions and the incidence of effects were comparable in Yorkshire and Large White pigs for both X-irradiation and HDR 192Ir brachytherapy. This pig skin model is feasible for future studies on clinically relevant multifractionation schedules in a brachytherapy setting.
Animals↗
Evidence for humoral effects on the radiation response of rat foot skin.
The influence of perturbation of the physiologic state of the whole body on the outcome of radiation exposure has been examined in a rat foot model. Irradiation was carried out using 60Co gamma-rays. Moist desquamation was used as an endpoint. Rats were given a priming dose of 2 Gy, 4 Gy or 7 Gy to their whole body except their hind feet (partial body priming dose). After a variable time period both hind feet of these animals were irradiated with graded doses of 60Co gamma-rays. The incidence of moist desquamation in the irradiated feet of these animals was compared with the incidence of moist desquamation in animals that had not received the initial partial body priming dose. It was noticed that the incidence of moist desquamation in the rat foot skin of animals that received 7 Gy partial body priming dose 4 h prior to irradiation of their hind feet was significantly less than moist desquamation in control animals. The ED(50) value of 22.53+/-0.16 Gy for moist desquamation of the foot skin of control animals was significantly lower (p<0.01) than the value of 25.25+/-0.29 Gy obtained for animals that received a partial body priming dose of 7 Gy 4 h prior to irradiation of their hind feet. It was concluded that the response of rat foot skin to radiation was not purely the result of epidermal stem cell kill and that it can be modified by alterations in the overall physiological state of the animal's body brought about by a priming dose to the whole of the animal's body except the hind feet.
Animals↗
Identification of Skin injury-related genes induced by ionizing radiation in human keratinocytes using cDNA microarray.
The skin is an external organ that is most frequently exposed to radiation. High-dose radiation initiates and promotes skin cancer and acute radiation injury. It is important to investigate the influence of high-dose radiation exposure on the skin at the molecular level to understand acute radiation injury. To identify genes that are associated with injury caused by high-dose radiation exposure of the skin, we used microarray technology to examine the effect of irradiation on approximately 1000 genes in normal human epidermal keratinocytes at 3 h postirradiation with a cytotoxic dose of X-ray (5 Gy). We found that 16 and 59 genes were up- and down-regulated respectively in the keratinocytes. Several apoptosis-related genes, for example, BAK and TSC-22, and anti-proliferative genes, for example, BTG-1 and BTG-3, were up-regulated. We focused on ATF3 because ATF3 is induced most strongly by X-irradiation, and its function in keratinocytes is unknown. The induction of the ATF3 mRNA and protein in keratinocytes following X-ray was confirmed by RT-PCR and western blot analysis. ATF3 was also induced and accumulated within the nuclei of keratinocytes after X-ray irradiation in vivo and in vitro. Exogenous EYFP-ATF3 also accumulated within the nuclei of keratinocytes. In the transient expression assay, EYFP-ATF3, but not EYFP, induced apoptosis in keratinocytes. Taken together, these results suggest that ATF3 plays a role in apoptosis in keratinocytes and is associated with skin injury caused by ionizing radiation.
Animals↗
Biological gain of carbon-ion radiotherapy for the early response of tumor growth delay and against early response of skin reaction in mice.
The biological effectiveness of carbon ions relative to gamma rays (RBE) was compared between the tumor growth delay and an early skin reaction of syngeneic mice. The RBE was larger for a tumor than skin when irradiated with large doses of high-LET (linear energy transfer) carbon ions. The intra-track damage (a term of a linear quadratic model) of a tumor and skin increased equally with an increase of the LET, while the inter-track damage (beta term) of skin alone increased with the LET. These data provide evidence that high-LET radiotherapy could achieve therapeutic gain by minimizing the difference in response to fractionated irradiation between the tumor and normal tissue.
Animals↗
Repair of skin damage during fractionated irradiation with gamma rays and low-LET carbon ions.
In clinical use of carbon-ion beams, a deep-seated tumor is irradiated with a Spread-Out Bragg peak (SOBP) with a high-LET feature, whereas surface skin is irradiated with an entrance plateau, the LET of which is lower than that of the peak. The repair kinetics of murine skin damage caused by an entrance plateau of carbon ions was compared with that caused by photons using a scheme of daily fractionated doses followed by a top-up dose. Right hind legs received local irradiations with either 20 keV/microm carbon ions or gamma rays. The skin reaction of the irradiated legs was scored every other day up to Day 35 using a scoring scale that consisted of 10 steps, ranging from 0.5 to 5.0. An isoeffect dose to produce a skin reaction score of 3.0 was used to obtain a total dose and a top-up dose for each fractionation. Dependence on a preceding dose and on the time interval of a top-up dose was examined using gamma rays. For fractionated gamma rays, the total dose linearly increased while the top-up dose linearly decreased with an increase in the number of fractions. The magnitude of damage repair depended on the size of dose per fraction, and was larger for 5.2 Gy than 12.5 Gy. The total dose of carbon ions with 5.2 Gy per fraction did not change till 2 fractions, but abruptly increased at the 3rd fraction. Factors such as rapid repopulation, induced repair and cell cycle synchronization are possible explanations for the abrupt increase. As an abrupt increase/decrease of normal tissue damage could be caused by changing the number of fractions in carbon-ion radiotherapy, we conclude that, unlike photon therapy, skin damage should be carefully studied when the number of fractions is changed in new clinical trials.
Animals↗
Chromosome aberrations in cultured peripheral lymphocytes from persons with elevated skin radiosensitivity.
The purpose of this study was to elucidate whether an enhanced skin radiation reaction correlated with an enhanced chromosome radiation response. Twelve patients with late radiation skin ulcers formed after courses of radiation therapy were chosen as a group of individuals with elevated skin radiosensitivity. Half of the venous blood samples from each donor were irradiated with 2 Gy gamma-rays; the other half remained unexposed. Using standard cytogenetic technique, lymphocyte cultures were prepared with all samples. On the metaphase preparations, all chromosome aberrations detectable without karyotype identification were scored. The frequency of various aberrations in each patient were compared with relevant mean values in healthy unexposed donors. In several patients, the frequency of one aberration type or another exceeded the control value significantly. Comparison of aberration patterns in irradiated and nonirradiated cultures and consideration of elapsed time after therapeutic exposures suggested that the observed increased aberration levels reflected individual features of the patients' radiosensitivity, rather than lesions induced by previous in vivo exposures. Therefore, the question of a correlation between skin and chromosome radiosensitivity can be answered positively. Analysis of the peculiarities of cellular distribution of aberrations and of the relative contribution of different aberration types in patients and healthy donors indicates that the investigation of in vitro-induced aberrations is more suitable for the assessment of individual radiosensitivity than the study of aberrations observed in unexposed cultures.
Cells, Cultured↗
Catrix: an easy-to-use collagen treatment for wound healing.
Collagen plays a major role in wound healing. Its presence is important in all stages of the healing process. Catrix is a new collagen wound-healing powder that has been shown to be effective in the treatment of wounds healing by secondary intent such as pressure ulcers, venous stasis ulcers and diabetic ulcers as well as second-degree burns and post-radiation dermatitis. Catrix has also been shown to be effective in the treatment of wounds unresponsive to conventional treatments. It promotes the growth of fibroblasts and keratinocytes in the wound, prevents loss of fluid from the wound and protects the wound from bacterial infections and other agents. Catrix is biodegradable and therefore does not require removal from the wound bed before re-application.
Administration, Topical↗
Radiation-induced reactions. 1: An examination of the phenomenon.
In this article, the first in a series of three, the author examines the phenomenon of radiation-induced skin reactions. This includes a description of the theoretical aspects of radiation and its effect on the skin, the prevalence and significance of skin reactions seen in clinical practice and a summary of the assessment tools that have been used in their evaluation. From this information, an analysis of the key signs and symptoms of radiation-induced skin reactions is presented. These clinical indicators and descriptors are then available to be used as the basis for the development of a comprehensive yet specific assessment tool. In part two, these descriptions are integrated into an assessment tool to measure radiation-induced skin reactions and the radiation-induced skin reaction assessment scale (RISRAS) is described. In part three the methods and results from the initial evaluation of the RISRAS are reported.
Humans↗
Radiation-induced skin reactions. 2: Development of a measurement tool.
Radiation-induced skin reactions occur commonly in clinical practice and cause various problems for the patient. Assessment and treatment of these reactions is an important part of the healthcare professional's role in the radiotherapy unit. To accomplish this effectively a specific, yet comprehensive, measuring tool is needed. The first article in this three-part series (Vol 8(17): 1134-40) examined the phenomenon of radiation-induced skin reactions, including descriptions of how radiotherapy affects the skin and the prevalence and significance of these skin reactions. Using the literature, the most common signs and symptoms were isolated. This provided the basis for the development of a specific yet holistic assessment tool. In this article, an explanation of the methods used to collect and analyse data for the development of an assessment tool to measure radiation-induced skin reactions is described. The tool is called the Radiation-Induced Skin Reaction Assessment Scale (RISRAS). In the third article in the series, the results of RISRAS's initial evaluation is reported along with its efficacy for clinical practice.
Humans↗
Radiation-induced skin reactions. 3: Evaluating the RISRAS.
This article, the last in a three-part series, reports the methods used to evaluate the Radiation-induced Skin Reaction Assessment Scale (RISRAS), along with the results. For a newly developed tool, the results of the elementary reliability and validity testing were satisfactory. The RISRAS could be used in clinical practice following revision and further development and its introduction into clinical oncology practice is recommended as it will improve the assessment process of radiation-induced skin reactions and lead to better care for those patients undergoing radiotherapy. In the first article in the series (Vol 8(17): 1134-40), the extensive nature of radiotherapy-induced skin reactions were reported, along with their significance for the patient undergoing radiotherapy. Previously described assessment scales were examined in preparation for the development of the RISRAS. In the second article (Vol 8(18): 1208-11), the need for holistic yet specific assessment of these reactions was demonstrated and the methods used to develop the RISRAS were described.
Humans↗
Measurement of breast skin viscoelasticity and a pilot study on the potential radioprotective effect of a zinc-based cream.
Radiation-induced late skin effects were studied in patients with breast cancer in relation to different protocols of fractionated radiotherapy in three different medical centres, in Israel, the UK and the USA. The mechanical properties of skin were evaluated in breasts of healthy volunteers, and non-irradiated and irradiated breasts of patients, using a newly developed viscoelasticity skin analyser (VESA). The increase of the dose of radiation per fraction was found to have more impact on the development of radiation-induced late skin effects than the elevation of the total dose given. In addition, a pilot study on the possible radioprotective effect of external application of a cream containing zinc oxide on radiation-induced early skin changes in patients with breast cancer was initiated. Non-invasive measurement of trace elements and zinc pharmacokinetics in the skin of healthy controls following the application of the zinc oxide cream were performed by unique diagnostic X-ray spectrometry (DXS). Application of the cream, followed by thorough skin cleansing, significantly increased the amount of residual zinc in the skin, but continuous daily treatment did not cause further build-up of the dermal zinc level. The radioprotective effect of the zinc oxide cream on the skin is now being studied.
Administration, Cutaneous↗
Pulmonary edema associated with hyperbaric oxygen therapy.
We report three cases of pulmonary edema associated with hyperbaric oxygen therapy, including one fatality. All three patients had cardiac disease and reduced left ventricular (LV) ejection fractions (EFs). Two patients had diabetes, and one patient had severe aortic stenosis. Hyperbaric oxygen therapy may contribute to pulmonary edema by increasing LV afterload, increasing LV filling pressures, increasing oxidative myocardial stress, decreasing LV compliance by oxygen radical-mediated reduction in nitric oxide, altering cardiac output between the right and left hearts, inducing bradycardia with concomitant LV dysfunction, increasing pulmonary capillary permeability, or by causing pulmonary oxygen toxicity. We advise caution in the use of hyperbaric oxygen therapy in patients with heart failure or in patients with reduced cardiac EFs.
Aged↗
Radiation in dentistry--surgical comments.
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Dentists↗
[Optical radiation and its effect on the skin].
Optical radiation ranges from short wave ultraviolet via visible light to the far infra-red. Both natural and artificial light sources may cause desired and undesired effects, both on the skin and on the organism as a whole. The nature and extent of such effects depend primarily on the energy of the photons, the absorption capacity of the chromophores, the mean depth of penetration, and on the density and dose of the radiation. The present paper discusses the mechanisms of action and desired and undesired effects in the organism, including therapeutic applications, separately for ultraviolet radiation, visible light and infrared radiation.
Dose-Response Relationship, Radiation↗
[Accidental exposure to X-ray from a diffractometer].
The patients's clinical pictures, characterized by an erythema preceding the skin manifestations, their aspect and the occupational histories, made the diagnosis of a radiation accident possible before its dosimetric identification. Doses evaluations using thermoluminescence dosimeters and ionizing chambers correlated well with the clinical estimations. The immediate cause of the accident was poor maintenance of the device that caused its back window to be permanently open, but lack of adequate information on the biological effects of ionizing radiation and on the correct operational procedures were contributory facts. The description of this accident is relevant in virtue of the misconception that such equipment have "virtually no occupational risk". The patients's medical evolutions have had a favorable course, specially because the low energy of the X-ray and its low penetrating capacity. This accident highlights the need for the adequate training of workers on the handling of radiation devices.
Acute Disease↗