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Biomedical subjects

S Dische

Publications and source records attributed to S Dische.

At least 91 records · Page 5Linked to original sources
PubMed1978

Hyperbaric oxygen: the Medical Research Council trials and their clinical significance.

The clinical trials of the use of hyperbaric oxygen in radiotherapy conducted by the Medical Research Council's working party have shown that local cure and survival can be improved in head and neck and cervical cancer. Evidence for benefit has been presented in carcinoma of bronchus, but none has so far been found in carcinoma of the bladder. Although hyperbaric oxygen has produced increased effect upon normal tissues as well as upon tumour, a real improvement in therapeutic ratio appears to be present. The future use of hyperbaric oxygen in radiotherapy will depend upon a comparison of effectiveness with other methods now being tested to improve radiotherapy. The trials have yielded much fundamental and clinical data of general relevance in the radiotherapy of malignant disease.

Bronchial Neoplasms↗
PubMed1978

The neurotoxicity of misonidazole and its relationship to dose, half-life and concentration in the serum.

Misonidazole has been given to a total of 87 patients. Neurotoxicity has occurred--convulsions with the higher doses and peripheral neuropathy with the lowern ones. The data from 34 patients receiving 4--7 doses has been analysed. Peripheral neuropathy is related to the total tissue exposure. By monitoring serum levels and controlling the total dose given, convulsions are avoidable and peripheral neuropathy restricted to a low and acceptable level.

Drug Administration Schedule↗
PubMed1978

The optimum regime for the administration of misonidazole and the establishment of multi-centre clinical trials.

The amount of misonidazole which may be given to one patient is limited because of the risk of neurotoxicity. The drug may be given with every treatment of a multi-fraction course of radiotherapy or only with some of the treatments. The number of radiotherapy treatments can be reduced or multiple treatments given after each dose of the drug. Experience in 19 patients given daily doses of misonidazole is reported. This is practical regime to be considered for clinical trials of this hypoxic cell sensitizer.

Drug Administration Schedule↗
PubMed1978

Clinical experience with misonidazole.

A total of 62 patients with advanced tumours have now been treated by a fractionated course of radiotherapy, with misonidazole. The prime purpose of the administration of the drug to these patients was to determine safe dosage and suitable regimes for use in clinical radiotherapy. The reaction of normal tissues did not seem enhanced but there was an impression of increased tumour response.

Digestive System↗
PubMed1977

Clinical testing of the radiosensitizer Ro 07-0582: experience with multiple doses.

The hypoxic cell radiosensitizer, Ro 07-0582, has now been given in multiple doses to 16 patients. They have received a total of 15-51 g in 3-20 doses. Immediate tolerance was good, and satisfactory plasma levels of the drug were consistently obtained. Neurotoxicity was, however, troublesome: convulsions occurred in the patient given the highest dose, and there was peripheral neuropathy in 11 cases. Tumour concentrations similar to those in plasma were obtained in human tumours, in contrast to the findings in mouse tumours where concentrations are usually below 40% of plasma levels. In the treatment of human tumours, a lower dose of Ro 07-0582 should give useful hypoxic cell sensitization. Although the total dose of Ro 07-0582 must be limited, there is a real prospect that it will give benefit in clinical radiotherapy.

Adult↗
PubMed1976

Hypoxic cell sensitisers in radiotherapy.

Solid tumours contain poorly oxygenated cells, and these are disproportionately resistant to therapeutic radiation. Several methods of overcoming this problem have been used clinically, including the administration of hyperbaric oxygen during irradiation, radiotherapy with heavy nuclear particles such as neutrons from cyclotrons, optimum size and spacing of multiple doses of conventional radiation, and, most recently, chemical radiosensitisers. These radiosensitisers mimic the sensitising effect of oxygen and are active only against hypoxic cells. They do not, therefore, increase radiation response in well-oxygenated normal tissues. They are not rapidly metabollised and so can penetrate further than oxygen from the vascular capillaries and effectively reach the hypoxic cells in the tumour. Some of these drugs are of considerable clinical promise. The results of in vitro and in vivo studies with radiosensitisers are summarised and preliminary clinical work is described.

Animals↗
PubMed1976

Skin reaction. A quantitative system for measurement of radiosensitisation in man.

Areas of skin have been irradiated using a radio-strontium plaque giving 800 to 1100 rad. Visual ranking of the reactions produced proved to be the best method of measuring the response. Erythema was poorly related to dose but in most cases the amount of pigmentation produced was directly related to it. This system, for use in the testing of radiosensitisers, allows a quantitative estimate of enhancement of response to be made.

Abdominal Neoplasms↗
PubMed1976

Clinical testing of the radiosensitiser Ro-07-0582. I. Dose tolerance, serum and tumour concentrations.

Patients have been given single oral doses of the radiosensitiser Ro-07-0582 and serum concentrations have been attained in the range expected to be of value in radiosensitisation. Immediate gastrointestinal side effects appear to limit the dose to below 140 mg/kg but radiosensitising serum levels of approximately 200 mug/ml can be attained. Tolerance may be improved by giving anti-emetics and a more palatable preparation. Estimates of the concentration of Ro-07-0582 in tumour have ranged from 12 to 92% of the serum concentration at the time of determination.

Adult↗
PubMed1976

Clinical testing of the radiosensitiser Ro-07-0582. II. Radiosensitisation of normal and hypoxic skin.

The effectiveness of the radiosensitiser Ro-07-0582 has been tested in man by observing the skin reaction after irradiation using a radio-strontium source with and without administration of the drug. The skin reaction technique has been extended so that skin was irradiated when at low oxygen tension (hypoxic) as well as when fully oxygenated (oxic). Limbs have been made hypoxic by occlusion of the circulation using a sphygmomanometer cuff. To this has been added the prior use of an Esmarch's bandage to reduce the volume of blood in the skin and the enclosing of the limb in a bag of nitrogen. The Oxygen Enhancement Ratios obtained without the sensitiser in nine studies using this system ranged from 1-64 to 2-46. Using Ro-07-0582 skin reactions after oxic exposures were not enhanced but those after hypoxic exposures were markedly increased. The Relative Sensitising Efficiency expresses, as a percentage, the restoration of the sensitivity of cells protected by hypoxia. In six cases where Ro-07-0582 was given in doses ranging from 81 to 165 mg/kg, efficiencies ranged from 27 to 71%. These results can be compared with three studies using metronidazole where efficiencies ranged from 11 to 15%. Using comparable dosage Ro-07-0582 seems approximately three times more effective than metronidazole. In this first study in man, Ro-07-0582 appears to be a highly effective radiosensitiser of hypoxic cells.

Constriction↗
PubMed1976

Clinical testing of the radiosensitiser Ro-07-0582. III. Response of tumours.

The nitro-imidazole Ro-07-0582, a known radiosensitiser of hypoxic cells in animals, was administered orally to seven patients with metastatic tumour, before irradiation. The delay imposed on the growth of tumour treated in this way was compared to that of tumour in the same patient treated with radiation alone. Two patients died before any assessment of response could be made. Qualitative evidence from a further three patients suggested some enhancement of radiation effect in two patients but not in the third. Quantitative evidence was obtained from the remaining two patients. In one, a patient with multiple pulmonary metastases from a carcinoma of the breast, no enhancement was shown. In the other, a patient in whom 21 subcutaneous metastases from a carcinoms of the cervix of the uterus were measured, an enhancement ratio of 1-2 was found. This agrees with the value from the same patient's skin when rendered artificially hypoxic, as reported previously. The conditions under which quantitative information may best be obtained in this type of trial are described and various factors affecting the interpretation of results are discussed. Ro-07-0582 has thus been shown to have a radiosensitising effect in man and may therefore prove of value in radiotherapy.

Adult↗
PubMed1976

Bowel gas--a cause of elevated dose in radiotherapy.

The presence of gas in bowel could lead to higher than expected doses being given in the radiotherapy of abdominal and pelvic tumors. Radiation detectors were placed in the uterus and vagina of ten patients with caricnoma of cervix, and the actual dose compared with that expected when anterior fields of treatment were employed. Elvations greater than 10% were obtained in six, and severe postradiation morbidity subsequently occured in two of the three showing the highest readings.

Female↗