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Biomedical subjects

S Dische

Publications and source records attributed to S Dische.

At least 127 records · Page 7Linked to original sources

The pharmacokinetics of a new radiosensitiser, Ro 03-8799 in humans.

A new hypoxic cell radiosensitiser, Ro 03-8799 has been administered intravenously to human volunteers and its kinetic parameters derived from plasma and urine data. Good penetration of drug into tumour tissue is found, consistent with its large volume of distribution. The plasma clearance of this compound is rapid due to high metabolic and renal clearances. These parameters combine to produce an elimination half-life of 5.6 h, approximately half that of misonidazole, a well studied radiosensitiser. It is hoped that this decrease in total body exposure will also reduce the cumulative toxicity seen when misonidazole is administered repeatedly.

Adult↗

Primary tumor control after radiotherapy for carcinoma of the bronchus.

The primary tumor control and the appearance of distant metastasis was observed closely in 62 patients entered into a randomized controlled trial of the radiosensitizing drug, misonidazole, in carcinoma of the bronchus. Sixty-one of the 62 patients are now dead; an autopsy examination was carried out in 42 (69%). Although survival was comparable to that observed in similar studies, tumor persisted or recurred at the primary site in 95% (58/61) while 39% (24/61) showed no evidence for distant metastasis. In these patients, improvement in the primary tumor control would be important in extending survival.

Bronchial Neoplasms↗

The relationship between tumor response and survival following radiotherapy for carcinoma of the bronchus.

Tumor response was closely observed in a randomized controlled trial of a radiosensitizing drug in the radiotherapy of carcinoma of the bronchus. The persistence of tumor cells in the sputum after treatment and the degree of regression measured radiologically at two months did not correlate with the subsequent course. However, total regression of tumor and time to regrowth both assessed radiologically showed a highly significant correlation with survival (P less than 0.0005).

Bronchial Neoplasms↗

Quality assurance in radiation therapy: European experience--present and future clinical efforts.

A high standard of radiotherapeutic practice must be sought in all phases of management of a patient with malignant disease. Radiation therapy must be appropriately chosen and integrated with surgery, cytotoxic chemotherapy and all other modes of treatment. The most suitable technique with a dose, fractionation and time regime must be devised and executed with technical and personal care. Follow-up to truly assess tumor control and morbidity is essential so as to guide the management of future patients. To achieve this in Europe great reliance is placed upon the training and qualification of the therapist and staff. In England a Fellowship of the Royal College of Radiologists in radiation therapy is regarded as essential for appointment as a permanent consultant within the Health Service. A high examination standard is set with pass rates ranging from 10 to 30%. High standards are applied to the professional qualifications for radiation physicists, nurses and technical staff. Most radiotherapy centers and departments have been visited by the Royal College in order to determine if the standard of staffing and equipment justifies inclusion in the list of training departments. There is, unfortunately, no control of continuing education of the consultant once appointed. In the countries belonging to the European economic union, a new Diploma in Radiation Therapy has been established to be a standard for consultant practice through all the countries included. In a few multi-center trials in the United Kingdom members of the central organization visit centers to look at the case notes and compare them with the material submitted from the trial center. This effort at monitoring clinical trials is only just beginning in the United Kingdom. The European Organization for Research and Treatment of Cancer has recently initiated a quality control study in some of the centers included in the Radiotherapy Group. A preliminary report has just appeared on the results of the clinical and dosimetric studies in 8 centers placed in 5 European countries. This first European effort appears to have been successful and further details will become available. These initiatives through research may well lead to wider studies of quality assurance in radiation therapy within Europe.

Accreditation↗

The clinical testing of Ro 03-8799--pharmacokinetics, toxicology, tissue and tumor concentrations.

Ro 03-8799, a lipophilic nitroimidazole with a basic side chain, has now been administered intravenously to 69 patients. The elimination half-life in plasma was 5.1 hr and the plasma concentration at 30 min was 14.8 micrograms/ml standardized to a dose of 1 g per square meter of surface area. Immediate symptoms of malaise, heat, sweating and disorientation limit the amount of the drug which may be given on any one occasion. However, a dose of 750 mg per square meter of surface area may be given combined with daily radiotherapy. Our data suggest that when given with a 20 fraction course of radiotherapy, sensitization of hypoxic cells may be achieved equal to a 10-fold increase in the dose of misonidazole above that presently permitted.

Drug Evaluation↗

Childhood nocturnal enuresis: factors associated with outcome of treatment with an enuresis alarm.

A study was carried out to assess the factors that may affect the outcome of a single course of treatment for childhood nocturnal enuresis by use of an enuresis alarm. 113 children were treated and followed up; those showing failure of initial arrest of wetting, relapse and longterm successful outcome were analysed separately. Emphasis is placed on the need for the adoption of clear criteria regarding the definition of these three groups, and for an adequate follow-up of treated cases. Unsatisfactory housing conditions and circumstances giving rise to family difficulties were significantly associated with a less favourable rate of initial arrest. In the long term, family difficulties again were found to be significantly related to poor outcome. Behavioural deviance, as revealed by a teacher's behavioural questionnaire also adversely affected long-term success, although less significantly so. Family difficulties emerged as the most important predictor for outcome of treatment and adversely influenced the rate of initial arrest of wetting, the relapse rate and the long-term success rate.

Adolescent↗

Carcinoma of the cervix--anaemia, radiotherapy and hyperbaric oxygen.

Further analyses of the material contained in trials of the hyperbaric oxygen chamber in the radiotherapy of carcinoma of the cervix have shown that patients who were severely anaemic prior to radiotherapy, and who required blood transfusion, showed very poor local tumour control when conventionally treated after transfusion, but very good local tumour control when treated in hyperbaric oxygen. The finding of a special sub-group where hypoxia would seem to be an important cause of radiation failure, and where hyperbaric oxygen was successful in overcoming it, may have importance in the evaluation of other methods for overcoming the hypoxia, including the use of chemical sensitising agents.

Anemia↗

The radiosensitizer Ro 03-8799 and the concentrations which may be achieved in human tumours: a preliminary study.

A new hypoxic cell radiosensitizer, Ro 03-8799, has been administered i.v. to 2 normal and 6 patient volunteers. Generally in non-necrotic tumours the concentrations obtained were 3 times greater than in plasma sampled at the same time. These observations added to the reports concerning toxicology in monkeys and rats and radiosensitizing efficiency in the laboratory, suggest that Ro 03-8799 may prove to be much more effective sensitizer than misonidazole in man.

Adult↗

The concentration of desmethylmisonidazole in human tumours and in cerebrospinal fluid.

The concentration of desmethylmisonidazole (DESMISO) was determined in 60 biopsy samples taken from 13 human tumours and in cerebrospinal fluid (CSF) from 8 patients after oral administration. In comparison with misonidazole (MISO), peak concentrations in plasma were reached at earlier times and half-lives were shorter, so that the area under the curve of plasma concentration with time (AUC) was reduced by 45%; the AUC of CSF concentration with time was reduced by 67%. Between 1 and 2 h after administration of DESMISO, concentrations in tumours were generally 85-90% of those of MISO estimated approximately 4 h after it was given. The two drugs when tested in equimolar concentrations have been found in laboratory experiment to be equally potent as hypoxic cell radiosensitizers. Recognizing the lower mol. wt of DESMISO and the trend to higher concentrations in the more necrotic areas of the tumours studied equal doses by weight of the two drugs given orally may give equal radiosensitization of hypoxic cells in human tumours.

Breast Neoplasms↗

Radiation myelopathy in patients treated for carcinoma of bronchus using a six fraction regime of radiotherapy.

The adoption of a six-fraction regime of radiotherapy for patients with locally advanced carcinoma of the bronchus was followed by the appearance of radiation myelitis in eight cases. These were among a group of 130 patients given radiotherapy with anterior and posterior treatment fields, without shielding of the spinal cord. Radiation myelitis was found only in those where the calculated spinal-cord dose exceeded 3350 cGy (rad). The possible precipitating factors in the eight patients who suffered myelopathy were compared with those in the remaining 62 patients who also received spinal-cord doses calculated to be greater than 3350 cGy (rad). Only one difference was found--the haemoglobin concentration was significantly higher in those who suffered neuropathy compared with those who did not (P = 0.05).

Aged↗