A detailed study of the kinetics and magnitude of thermotolerance has been made using the endpoint of loss of vertebrae in the baby rat tail. A range of different priming treatments was used and for analysis each priming treatment (PT) was given in terms of the heat sensitivity of the tissue as defined by the single treatment (Ds) required for a given effect, i.e. fractional priming treatment PT/Ds. A considerable degree of thermotolerance could be induced so that at maximum the tissue sensitivity was reduced by a factor of more than four in heating time to produce a given effect, or by more than the equivalent of 2 degrees C. The main results of the study were: (a) that the time to reach maximum thermotolerance depends primarily on PT/Ds, independent of the particular conditions used in the priming treatment; (b) that the extent of the maximum also depends primarily on PT/Ds, but the precise form of the relationship depends on the method used to define thermotolerance; and (c) that the rate of decay of thermotolerance is independent of the priming treatment. The implications of these results for clinical hyperthermia are briefly discussed.

Age Factors↗

PubMedDate not supplied

Thermotolerance after fractionated hyperthermia: assessment of cell survival by response to X-rays.

A previous study of the mouse ear showed that daily treatment at 43.5 degrees C, either 10 X 20 min or 20 min + 9 X 70 min, induced the same resistance to further heating as was induced by a single treatment of 20 min. The results could be explained in at least two ways: (a) no cells are killed by the heat treatments but thermotolerance is induced; and (b) a proportion of cells is killed by each fraction and the degree of thermotolerance induced in survivors increases as the number of fractions is increased. These two possibilities were tested by measuring the response to X-rays at 24 h after various regimes of fractionated hyperthermia. At this time interval the enhancing effect of a single heat treatment would have decayed, so that radiosensitivity should then be related to the number of surviving cells. Up to 49 daily treatments of 20 min had little effect on radiosensitivity, suggesting that these heating regimes did not cause a significant reduction in the number of basal epidermal cells. A regime of 20 min + 4 X 70 min daily also had little effect but a treatment of 20 min + 9 X 70 min daily increased the radiation response, suggesting that the more severe heat treatment had reduced cell survival to approximately 4 per cent.

Animals↗

PubMedDate not supplied

An assessment of local hyperthermia in clinical practice.

A total of 116 small superficial tumours have been treated by radiation alone, hyperthermia alone, or radiation and hyperthermia combined in a Phase I/II study. Most tumours were metastases or local recurrences of adenocarcinoma of breast but other histologies were involved including melanoma. Hyperthermia was delivered predominantly by microwaves, but radiofrequency and ultrasound methods were also used. Rigorous thermal dosimetry, based on measurements from invasive multipoint thermocouple arrays, has shown that 58 per cent of hyperthermal treatments reached a minimum dose within tumour equivalent to 20 min at 43 degrees C (minEq43); 24 per cent reached at least 60 minEq43. Minima of 20 minEq43 were achieved successfully on every intended occasion in a quarter of the 75 tumours heated, and on one/two occasions in 39; unfortunately, this minimum threshold was not reached at any point monitored at any hyperthermia session in 17(23 per cent) tumours. Tumours that received radiation and effective hyperthermia were more likely to disappear completely (CR rate 86 per cent) than those that were irradiated but inadequately heated (CR rate 35 per cent) (P less than 0.001) or were treated by the same doses of radiation alone (CR rate 35 per cent) (P less than 0.05). This improvement with hyperthermia became more apparent with suboptimal radiation doses. A small but measurable growth delay was imposed by heat alone with a poor complete response rate (11 per cent). The real-time use of a thermal dose unit in clinical practice facilitates hyperthermal treatment comparisons and provides an important parameter for checking the technical performance of a heat delivery system. The results of this study emphasizes the need for improvements in intratumour temperature distribution, in order to establish minimum threshold temperatures to enhance tumour response rates.

Adenocarcinoma↗

PubMedDate not supplied

Studies relevant to a means of quantifying the effects of hyperthermia.

There is as yet no fully satisfactory method of defining 'thermal dose'. However, in order to relate different hyperthermal treatments it has been suggested that the relationship between heating time and temperature be used to derive an isoeffect parameter which might be useful in this context. The equation t2/t1 = RT1-T2, where t is the treatment time, T the temperature, R = 2 for T greater than 42.5 degrees C and R = approximately 6 for T less than 42.5 degrees C, has been shown to fit the isoeffect data from many studies both in vivo and in vitro. Whether or not this relationship is applicable when the temperature is varying has been tested using an animal model system, i.e. the response of the baby rat tail. It has shown that the relationship between time and temperature is indeed characterized by the above equation, and the phenomena of thermotolerance and step-down sensitization were clearly demonstrated. Tails were then alternated between waterbaths at different temperatures in order to simulate varying temperature. The measured effects were, in general, in good agreement with those derived from the formula. The maximum difference between the observed and predicted effect, obtained under rather extreme conditions unlikely to be experienced clinically, amounted to an under-estimate of the effective temperature by approximately 0.3 degrees C, i.e. a net small effect of thermotolerance. It is therefore suggested that the above formula for 'heat dose' provides a reasonable interim method for comparing clinical hyperthermic treatments. The formula does not, however, account for differing absolute sensitivities between tissues nor for effects of fractionating heat treatments.

Animals↗

PubMedDate not supplied

Thermal dose and thermal isoeffect dose.

Explore the source record for details and available documents.

Animals↗

PubMedDate not supplied

Treatment of menorrhagia by radiofrequency heating.

A new technique is described for the treatment of menorrhagia by heating the whole of the endometrial cavity of the uterus. A capacitively coupled probe at 27.12 MHz is inserted into the uterine cavity, which causes the basilis layer to be raised to approximately 50-55 degrees C whilst the rest of the pelvic contents remain at approximately normal (body) temperature. A major advantage of the method is that no special hysteroscopic skills are required, unlike the two other techniques currently used for endometrial ablation: the Nd-Yag laser or the hysteroresectoscopic loop. Also no toxic flushing/distension fluids are necessary, as are required for all hysteroscopic surgery. The method, however, does require the application of a large amount of RF power to the probe and so care must be taken to position the probe correctly in order to prevent any serious complications. Of 32 patients given a single treatment at a power level of 550 W for 20 min, the 'success rate' was 84% with 31% becoming amenhorrhoiec and 53% showing significant reduction in menstrual bleeding. However, retreatment is possible and by this means, combined with improved treatment techniques, an even higher success rate could be achieved. In two of the earlier patients treated at 550 W a fistula was produced at the anterior vaginal wall which had to be surgically repaired. The probe was subsequently modified, since when this problem has not recurred. This new treatment approach offers an alternative to hysterectomy in the treatment of menorrhagia and may offer a number of significant advantages over methods currently used for endometrial ablation.

Adult↗

PubMedDate not supplied

From hydralazine to CGRP to man?

Attempts to selectively reduce tumour blood flow have, in the past, concentrated on the use of hydralazine. However, although this vasodilator can be highly effective in experimental animals, it is only at such high concentration as to result in a severe and clinically unacceptable reduction in systemic blood pressure. At clinically acceptable levels, the drug appears to produce a small increase in tumour blood flow. We have used the techniques of magnetic resonance spectroscopy as indicators of metabolism and blood flow in a search for vasoactive drugs that would produce an effective reduction in tumour blood flow without causing severe hypotension or other serious side effects. Single injections of either prazosin or CGRP are shown to be substantially more effective than hydralazine in causing a reduction in tumour blood flow without massive reduction in blood pressure. Even more effective was CGRP given by continuous infusion. In this case a three-fold reduction in tumour blood flow could be obtained with a reduction of only 15-20% in systemic blood pressure. All these studies, however, have been made with transplanted animal tumours. Using high-dose hydralazine and primary tumours that were either radiation or chemically induced, we obtained a success rate of only about a 35% in causing selective reduction in blood flow. In contrast, in a transplanted tumour line derived from one of the non-responding radiation-induced primary lesions, the success rate was about 95%, consistent with the majority of animal studies using transplanted tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗