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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
PubMed1986

A comparison of the tumour concentrations obtainable with misonidazole and Ro 03-8799.

Both Ro 03-8799 and misonidazole were administered to six patients before tumour sampling. Using similar doses, tumour concentrations of Ro 03-8799 were approximately double those of misonidazole. Examination of the data with regard to the relative sensitising efficiencies of these two compounds gives us, as a conservative estimate, a factor of 1.6 in favour of Ro 03-8799. From these observations it is predicted that, when given with radiotherapy in a 25-fraction course Ro 03-8799, is likely to be at least five times more effective as a hypoxic cell sensitiser than misonidazole.

Adult↗
PubMed1986

A comparative study of Ro 03-8799: racemic mixture and enantiomers.

The maximum single dose of the 2-nitroimidazole hypoxic cell radiosensitiser Ro 03-8799 is limited to 1 g/m2 by the occurrence of a well characterised acute syndrome of sweating, nausea and mental changes. In an attempt to increase the tolerable dose, the clinical toxicity of the racemic mixture was compared with that of the R- and S-enantiomers of Ro 03-8799. Twelve patients received escalating alternate doses of racemic mixture and R- or S-enantiomer, the dose levels being 0.25 g/m2, 0.5 g/m2, 0.75 g/m2 and 1.0 g/m2. Careful monitoring of the acute syndrome failed to demonstrate any consistent differences between racemic mixture and either enantiomer. This would suggest that the toxicity is not mediated via any specific central nervous system receptor. It is concluded that separation of Ro 03-8799 into its enantiomers will not enable a clinically useful increase in dosage.

Dose-Response Relationship, Drug↗
PubMed1985

Chemical sensitizers for hypoxic cells: a decade of experience in clinical radiotherapy.

The clinical work with chemical agents to restore the radiosensitivity of hypoxic cells began in 1973 with metronidazole, misonidazole was first given in 1974. The results so far recorded of the clinical trials with misonidazole have been generally disappointing. Only in 5 of 32 studies analyzed have significant benefits been shown to suggest real advantage with the use of misonidazole. Hypoxic cells must exist in all human tumours presenting for treatment and it is, however, probable that the oxygen effect is an important one at all dose fractionation regimes employed in radiotherapy but, after conventional fractionated radiotherapy, hypoxia may be a reason for failure in only a proportion of cases. The most important factor underlying the failure of misonidazole to achieve useful advantage is undoubtedly the low radiosensitizing concentrations achievable with the permitted dose of this neurotoxic drug. New drugs are under development and some have different dose-limiting toxicity. Those showing promise at this time are the Stanford compound, SR-2508, which is being extensively studied in the United States and the Roche compound, Ro 03-8799, which is being studied in the United Kingdom. It is possible that the greatest sensitization with the greatest tolerance will be achieved by a combination of drugs.

Adrenal Cortex Hormones↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1983

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↗
PubMed1983

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↗
PubMed1982

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↗