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Biomedical subjects

S B Field

Publications and source records attributed to S B Field.

At least 19 recordsLinked to original sources
PubMed2002

Vortex configurations, matching, and domain structure in large arrays of artificial pinning centers.

High-resolution scanning Hall probe microscopy has been used to image vortex configurations in very large periodic arrays of artificial pinning sites. Strong matching effects are seen at fields where either one or two vortices can sit at a site; with three vortices per site, however, no clear matching is observed. Matching effects have also been observed at several fractional multiples of the matching field, including 1/5, 1/4, 1/3, 1/2, and 3/4. These fractional values are characterized by striking domain structure and grain boundaries.

Journal Article↗
PubMed1996

Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials. International Collaborative Hyperthermia Group.

PURPOSE: Claims for the value of hyperthermia as an adjunct to radiotherapy in the treatment of cancer have mostly been based on small Phase I or II trials. To test the benefit of this form of treatment, randomized Phase III trials were needed. METHODS AND MATERIALS: Five randomized trials addressing this question were started between 1988 and 1991. In these trials, patients were eligible if they had advanced primary or recurrent breast cancer, and local radiotherapy was indicated in preference to surgery. In addition, heating of the lesions and treatment with a prescribed (re)irradiation schedule had to be feasible and informed consent was obtained. The primary endpoint of all trials was local complete response. Slow recruitment led to a decision to collaborate and combine the trial results in one analysis, and report them simultaneously in one publication. Interim analyses were carried out and the trials were closed to recruitment when a previously agreed statistically significant difference in complete response rate was observed in the two larger trials. RESULTS: We report on pretreatment characteristics, the treatments received, the local response observed, duration of response, time to local failure, distant progression and survival, and treatment toxicity of the 306 patients randomized. The overall CR rate for RT alone was 41% and for the combined treatment arm was 59%, giving, after stratification by trial, an odds ratio of 2.3. Not all trials demonstrated an advantage for the combined treatment, although the 95% confidence intervals of the different trials all contain the pooled odds ratio. The greatest effect was observed in patients with recurrent lesions in previously irradiated areas, where further irradiation was limited to low doses. CONCLUSION: The combined result of the five trials has demonstrated the efficacy of hyperthermia as an adjunct to radiotherapy for treatment of recurrent breast cancer. The implication of these encouraging results is that hyperthermia appears to have an important role in the clinical management of this disease, and there should be no doubt that further studies of the use of hyperthermia are warranted.

Breast Neoplasms↗
PubMed1995

Effect of vasoactive drugs on tumour blood flow as determined by 2H nuclear magnetic resonance spectroscopy.

A selective reduction in tumour blood flow (TBF) could enhance the effects of hyperthermia treatment and of drugs toxic to hypoxic cells. Vasodilator-induced changes in TBF were monitored in transplanted rat fibrosarcomas by non-invasively measuring the uptake of D2O using 2H nuclear magnetic resonance spectroscopy. Hydralazine (1 or 5 mg kg-1) caused a large (45%) reduction in mean arterial blood pressure (MABP) and a 40-60% reduction in TBF. Low-dose hydralazine (0.1 mg kg-1) caused a 20% reduction in MABP but no significant change in TBF. The doses of prazosin (1 mg kg-1) and calcitonin-gene related peptide (CGRP, 1 nmol kg-1) which caused a 20% reduction in MABP led to a 50-60% reduction in TBF. These results demonstrate the advantage of prazosin and CGRP over hydralazine for the reduction of TBF despite a small hypotensive effect. CGRP may be the most suitable of these agents for clinical use because of its short physiological half-life.

Animals↗
PubMed1991

Differences in vascular response between primary and transplanted tumours.

The vast majority of studies on tumour vasculature are performed on transplanted tumours in rodents. However, it is known that there may be differences between primary and transplanted lesions. The purpose of this study is to test whether a specific vascular response is similar in primary tumours and in transplanted tumours derived from them. The technique used was to give an intraperitoneal injection of 5 mg kg-1 hydralazine, which is known to result in hypoxia in transplanted tumours. Changes in perfusion were indicated by changes in metabolism, monitored using 31P Magnetic Resonance Spectroscopy. The primary tumours were induced by local irradiation many months previously and only 4/11 (36%) of these responded to hydralazine. One of the non responders was subsequently transplanted into isogeneic mice to produce a tumour line which was histologically very similar to the primary. Of these 16/17 (94%) responded. The difference is statistically significant (P = 0.001). The reasons for this difference are not known. A number of possibilities are discussed and in the authors' opinion, the most likely cause is that it results from an artefact of transplantation.

Animals↗
PubMed1991

The potential for prazosin and calcitonin gene-related peptide (CGRP) in causing hypoxia in tumours.

Using 31P NMR spectroscopy, changes in tumour metabolic status were studied in a transplanted rat fibrosarcoma following the administration of vasodilators. Mean Arterial Blood Pressure (MABP) was monitored simultaneously. Two vasodilators were studied, prazosin and CGRP, which altered the NMR parameters Pi/sigma P, beta NTP,Pi, PCr/Pi and PME/Pi in a dose dependent manner. There was a good correlation between the various NMR parameters; for analysis, Pi/sigma P was used for convenience. With increasing doses of vasodilator, Pi/sigma P increased and the MABP decreased. Reduction in pHNMR showed a correlation with decreasing MABP following the administration of prazosin but not after CGRP. Both prazosin and CGRP produced changes in 31P NMR spectra consistent with a reduction in tumour blood flow. The results for prazosin and CGRP were comparable and showed a 15-20% increase in Pi/sigma P for a 20% reduction in MABP. These results were compared with those from hydralazine. With hydralazine an acceptable reduction in blood pressure (up to approximately 25%) has little effect and may even alter NMR parameters consistent with an increase in blood flow, a reduction of approximately 40% is required for a significant decrease in flow. Both prazosin and CGRP are shown to be far more effective than hydralazine in causing tumour hypoxia at a clinically acceptable reduction in blood pressure. CGRP may be the more suitable for clinical use because of its short half life, its capability to achieve controlled hypotension and the relatively few side effects associated with its use.

Animals↗
PubMed1990

Treatment of functional menorrhagia by radiofrequency-induced thermal endometrial ablation.

42 patients were enrolled in a trial of radiofrequency-induced thermal endometrial ablation for the treatment of functional menorrhagia. The radiofrequency electromagnetic energy was delivered via a probe placed within the endometrial cavity. 10 patients received 330 kJ of energy, 10 received 445 kJ, and the other 22 received 660 kJ. 19 (87%) of those receiving the highest dose became amenorrheic or had a considerable reduction in menstrual flow. The procedure is simple and the heat induced in the endometrium does not penetrate much beyond the inner layers of the myometrium. There is no need for distension of the uterine cavity with flushing media.

Adult↗
PubMed1990

The combined measurement of blood flow and metabolism in RIF-1 tumours in vivo. A study using H2 flow and 31P NMR spectroscopy.

Blood flow and phosphorus metabolites have been measured simultaneously in the murine RIF-1 tumour in vivo. Blood flow was measured using the H2 washout technique and 31P NMR spectroscopy was used to measure high energy phosphates, inorganic phosphate and intracellular pH within the tumour. Following NMR and flow measurements, hydralazine was administered and the measurements repeated. There was always a decrease in blood flow, and a fall in nucleoside triphosphate detected by NMR, after administration of hydralazine. At blood flows in excess of 15 mL 100 g-1 min-1, the nucleoside triphosphate/inorganic phosphate ratio was 1.0 or greater, whereas at flows in the range of 5-12 mL 100 g-1 min-1 the ratio fell to below 0.5, and at flows below 5 mL 100 g-1 min-1 there was no detectable resonance from nucleoside triphosphate.

Animals↗
PubMed1990

Expression of dose in neutron therapy.

A pragmatic approach in neutron dosimetry is to consider the energy spectrum to consist of a neutron and a gamma component. The relationship between the two components of dose in neutron radiotherapy has been investigated for energies currently in clinical use. Changes in the neutron component itself are not dealt with. Because the two components are given simultaneously there is some interaction between them so that the gamma fraction is more effective than if the neutron and gamma doses were separated in time. This interaction has been accounted for using a well-proven extension of the linear-quadratic (LQ) equation. Using values of the LQ parameters alpha and beta measured recently in vivo, we have modelled the total effect from the neutron and gamma dose-contributions in terms of an equivalent neutron dose. This allows a comparison of different methods of expressing the measured physical dose with the biologically effective dose. The current practice in neutron therapy is to give the total (neutron plus gamma) dose, quoting also the gamma contamination. In all cases within the range of energies used for therapy, the total dose will give an overestimate of the biologically effective dose by approximately 4% for each 5% of gamma contamination. Expression of the neutron dose only (ignoring the gamma component) will give an underestimate of the biologically effective dose by approximately 1.5% for each 5% of gamma contamination, i.e. the error is approximately three times less for neutron dose than for total dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Gamma Rays↗
PubMed1990

The energy metabolism of RIF-1 tumours following hydralazine.

Phosphorus-31 Magnetic Resonance Spectroscopy (MRS) was used to observe the effect of two doses of the vasodilator hydralazine on the energy status of RIF-1 tumours. An intravenous dose of 5 mg/kg hydralazine reduced the high energy phosphate metabolites PCr and ATP, lowered pHMRS and raised the levels of inorganic phosphate of tumours within 20 min of administering the drug. The levels of high energy metabolites continued to decrease for at least 24 h. Normal muscle spectra obtained up to 1 h after drug administration remained unchanged. An intravenous dose of 0.5 mg/kg hydralazine also reduced NTP/Pi and PCr/Pi levels of tumours up to at least 5 h after drug administration, but the effect was smaller than for the higher dose. Blood flow measurements and measurements of systemic blood pressure demonstrated that 5 mg/kg of hydralazine produced a reduction in both systemic blood pressure and tumour blood flow relative to most normal tissues investigated. It is concluded that the changes in the P-31 MRS spectra of tumours were due to a reduction in tumour vascular perfusion following administration of hydralazine.

Animals↗
PubMed1988

The concept of thermal dose.

1. In the ideal but theoretical situation, where hyperthermia is defined to be at a specific, constant temperature, duration of heating is a perfectly acceptable and satisfactory method of describing thermal dose. 2. In the real situation, the dose is far from constant. Time will be required to reach the desired temperature and to cool afterwards. During hyperthermia the temperature is variable. We are thus obliged to use a biologically equivalent thermal dose to account for these variations. 3. Various attempts have been made to solve this problem, but at present, the most feasible approach appears to be the integration of the biological isoeffect relationship (Dewey formula) over the whole treatment. 4. This method provides a practical and reasonable method of comparing hyperthermal treatments under conditions likely to be met in practice, i.e. moderate variation about a fairly steady temperature. However, the formula would certainly be inaccurate if there were a sudden reduction in temperature resulting in a significant effect of step-down sensitisation or a long treatment resulting in the development of thermotolerance. Also, it must be emphasised that the formula does not account for absolute differences in sensitivity among tissues. Nor does it address the problem of varying sensitivity throughout a course of fractionated heat treatments. 5. Less is known about the applicability of such a formula to the combination of heat and ionizing radiation when the two treatment modalities interact. The parameters are fairly similar to those for heat alone, although the transition appears to be lowered to 41.5 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperthermia, Induced↗
PubMed1988

The response of mouse skin to irradiation with neutrons from the 62 MV cyclotron at Clatterbridge, U.K.

Acute skin reactions on mouse feet were used to measure the effect of 62 MeV p-Be neutrons from the cyclotron at Clatterbridge, U.K. The results were compared with the response to 16 MeV d-Be neutrons from the cyclotron at Hammersmith, 4 MeV d-Be neutrons from the van de Graaff accelerator at the Gray Laboratory, and 250 kVp X-rays. Up to 16 equal radiation fractions were given alone, or 16 fractions followed by "top-up" doses of 4 MeV d-Be neutrons to study the effect of neutron doses less than 1 Gy per fraction. For equivalent skin reactions, 9-16% more dose (total neutron + gamma) was needed with p(62)-Be neutrons compared with d(16)-Be neutrons. This did not vary significantly between 1 and 16 fractions. The top-up studies indicated that this figure might rise to approximately 14-32% at very low doses of neutrons, the value depending on the method of analysis of the data. The data indicate that the "standard" clinical protocol of 1.47 Gy per fraction (N + gamma dose) in 12 fractions given at Hammersmith with d(16)-Be neutrons would correspond to a dose of 1.64 Gy per fraction (N + gamma) at Clatterbridge using a similar regime of p(62)-Be neutrons. d(4)-Be neutrons were more effective than d(16)-Be neutrons by a factor of 1.6 over the whole range of dose per fraction studied (0.05-14.5 Gy per fraction of d(4)-Be neutrons). Relative to X-rays, the RBE for p(62)-Be neutrons was 1.6 +/- 0.02 for a single X-ray dose of 30 Gy, rising to 2.9 +/- 0.04 for an X-ray dose per fraction of 4.6 Gy given 16 times. The full-course fractionation data and the top-up data together indicate an extrapolated limiting RBE at vanishingly small doses per fraction of 4.2-4.8 depending on the method of analysis. The X-ray data were well-fitted by a linear-quadratic (LQ) model of dose-fractionation, with alpha/beta = 8.6 +/- 1.5 Gy. The LQ model also provides a fairly good description of the neutron responses, alpha/beta being large (greater than 24) reflecting predominantly linear underlying dose-responses for all the neutron beams. This in turn reflects the small variation observed in the relative effectiveness between the 3 neutron beams with changes in dose per fraction.

Animals↗
PubMed1987

1985 Douglas Lea memorial lecture. Hyperthermia in the treatment of cancer.

There are sound biological reasons for using hyperthermia in the treatment of malignant disease. This review includes a discussion of this rationale and describes effects of hyperthermia either given alone or in combination with ionising radiation to cells in vitro, tumours or normal tissues. Topics discussed include thermotolerance, step-down sensitisation, fractionation, re-treatment of previously irradiated sites, thermal enhancement ratio and thermal dose. Problems of heat delivery and temperature measurement are considered and the current status of clinical studies is stated briefly.

Cell Survival↗
PubMed1985

The relationship between heating time and temperature for rat tail necrosis with and without occlusion of the blood supply.

The relationship between time of heating and temperature has been investigated for necrosis resulting in the loss of distal vertebrae in the rat tail. The study was made in both normal conditions and with the blood supply to the tail occluded. In normal conditions there was a transition in the isoeffect relationship close to 42.5 degrees C. Above this temperature a 1 degree C change was equivalent to a change in heating time by a factor of 1.95 +/- 0.01; below 42.5 degrees C the factor increased to 8.1 +/- 0.3. When the tail blood supply was occluded by a clamp the factor was 1.86 +/- 0.01 at temperatures above 42 degrees C and the tissue was considerably more sensitive to hyperthermia. The factor decreased to 1.3 +/- 0.01 at lower temperatures so that the difference in sensitivity between normal and clamped tissue markedly increased with increasing heating time. The results are interpreted in terms of decreased pH resulting from occlusion of the blood supply which renders the tissue more sensitive. The transition in the isoeffect relationship for normal tails is thought to result from the induction of thermal tolerance and is eliminated when the blood supply is occluded. The result is clearly relevant to the heat treatment of regions of tumours with poor blood supply.

Animals↗
PubMed1985

Non-stochastic effects: compatibility with present ICRP recommendations.

The present recommendations of the ICRP (International Commission on Radiological Protection) are almost entirely based on 'stochastic effects' of ionizing radiation, i.e. cancer induction and heritable effects. In a recent report the compatibility of present recommendations with non-stochastic effects has been considered. The present paper is a summary of these findings.

Animals↗
PubMed1984

The induction of thermotolerance in the ear of the mouse by fractionated hyperthermia.

The development of thermotolerance in ears of mice was investigated after fractionated hyperthermia. Ears were heated at 43.5 degrees C by immersion in a water bath and the response was measured in terms of the heating time required to cause thermal necrosis in 50% of the ears (NT50). Three types of treatment were given: (1) single treatments, for which the NT50 was 42 minutes; (2) priming treatments, which caused little visible effect but induced thermotolerance. These treatments were given as 1-10 daily fractions, the total heating time ranging from 20-630 minutes; (3) test treatments which were given at various times after priming and were varied to estimate the NT50. Thermotolerance was defined as an increase in the test NT50 for preheated ears relative to the single treatment NT50. It has been suggested that thermotolerance induced by a single priming treatment may be increased by giving additional heat treatments which would not be tolerated by normal cells. In the mouse ear, the maximum thermotolerance induced by a single priming treatment of 20 min at 43.5 degrees C was seen after 24 hr when the test NT50 was about 2.5 times the single NT50. The effect of giving up to nine additional daily treatments of 70 min, each of which would cause necrosis in ears that had not received prior hyperthermia, was measured. The maximum thermotolerance observed was equal to that after a single 20 minute priming treatment but thermotolerance decreased as the number of 70 min treatments was increased from four to nine. The effects of repeating a treatment (20 min or 5 min) which was tolerated by normal ears and induced maximal or less than maximal resistance were compared. The interval between each fraction (24 hr or 12 hr respectively) was equal to the time at which maximal thermotolerance was observed after one treatment. For each regimen, the degree of resistance seen after 2 to 10 exposures was similar to that after the appropriate single treatment. This resistance was maintained throughout the course of priming treatment and decayed after the last fraction. Thus for this regimen, thermotolerance depended on the duration of each treatment rather than on the number of treatments given.

Animals↗