J.L. Moore

MACROPHAGE-ELECTROPHORETIC-MOBILITY (M.E.M.) TEST FOR MALIGNANT DISEASE: An Independent Confirmation

Abstract The validity of a new in-vitro bloodtest for cancer, which depends on the sensitisation of the patients lymphocytes to a common antigen apparently present in human tumours, has been independently confirmed.

In vitro chemosensitivity testing in chronic lymphocytic leukaemia patients

Twenty-nine samples from eighteen patients with chronic lymphocytic leukaemia (CLL) were used in a direct comparison of in vitro response to chlorambucil measured in a metabolic (MTT) and dye exclusion (D.Ex) assay. Reduced ability to produce formazan corresponded to a reduced number of dye-excluding viable cells and a significant correlation was found between dose-response measured in the two assays. Initial low absorbance values obtained with untreated control cells in the MTT assay were effectively overcome by increasing both the cell seeding density and MTT exposure time with the consequent increase in assay sensitivity. The MTT assay provided qualitatively similar dose-response data to that obtained in the D.Ex assay. A wide range in in vitro response was seen for both pretreatment and treatment patient groups. In vitro dose-responses were seen to coincide with decreasing or stable white cell counts, taken around the time of sampling, in samples from 4 patients. Less marked dose-responses were observed for 2 patients considered clinically resistant to chlorambucil. The MTT assay would seem, therefore, to be applicable to in vitro assay of cell response in CLL.

Oxygen Equilibration Problems in the Determination of K for HeLa S 3 (OXF)

HeLa S 3 (OXF) cells attached to polystyrene Petri dishes could not be used to investigate radiosensitivity at low oxygen concentrations because of the oxygen dissolved in the polystyrene matrix. An estimation of K in the formula R 1 = S max /S = M([O] + K)/M[O] + K was made for mammalian cells attached to glass Petri dishes, but it was dependent on various factors, the most important being the depth of medium over the cells at the time of irradiation. Oxygen equilibration was via diffusion, therefore a correction for the oxygen concentration differences between the gas phase and the cells was made; a K value of 12 w moles/l was obtained which is appreciably higher than other reported values. Although an estimate of the errors on this value was not made, all measurements fell within the range 8·5 and 17·5 w moles/l. These results highlight the difficulties of making precise radiobiological observations at low oxygen concentrations for mammalian cells attached to Petri dishes.

Misonidazole in patients receiving radical radiotherapy: Pharmac-okinetic effects of phenytoin tumor response and neurotoxicity

In 1978, a pilot study began of 29 patients with advanced tumors of the head and neck. The study showed a initial peripheral neuropathy rate of 55%, despite a dose limitation of 12g/m2 of misonidazole. Tumor response at 9 months was most encouraging. We are now able to examine tumor response and persistence of neuropathy in these patients 2 1/2 years after radical radiotherapy. The results are comparable with those obtained with hyperbaric oxygen in a clinical trial at this center during the 1970s. Neuropathy was a serious side effect but the drug phenytoin has been shown to shorten the half-life of misonidazole. We have examined the effect of phenytoin on the pharmacokinetics of misonidazole in 13 patients who received radical radiotherapy for advanced head and neck tumors or oesophageal tumors. Misonidazole was given in multiple doses, i.e. daily or weekly as it would be used in conventional therapy. Phenytoin was given either daily throughout treatment, or it was withdrawn during treatment. There were dramatic changes in the half-life of misonidazole, but the concentration at the time of irradiation was little affected. The significant changes in the half-life of misonidazole and the increased concentration of the metabolite desmethylmisonidazole are discussed.

Pilot study of radiotherapy with misonidazole in head and neck cancer.

Twenty-nine patients with advanced carcinoma of the upper air and food passages were treated by radiotherapy using a 10-fraction three-week scheme, giving 1.2 g/m2 of misonidazole 4 h before each treatment. Complete tumour regression was observed in 24 of the patients, and at a nine-month follow-up the local tumour control rate is 60%. Sixteen patients developed evidence of peripheral neuropathy. A prospective random controlled trial is recommended to confirm the apparently improved local tumour control from the use of misonidazole in this study.

SPECIFIC ABSORPTION RATE AND TISSUE TEMPERATURE IN LOCAL HYPERTHERMIA

Specific absorption rate (SAR) and tissue temperature were measured for a total of 83 treatments in 33 patients who received local hyperthermia treatment for cancer. The patients were grouped into three categories according to tumor size. Hyperthermia was induced by 13.56 MHz electromagnetic energy applied using capacitive coupling. A method is described for evaluating SAR from the tissue temperature traces at any time in the treatment when a step change is made in applied power. The method is possible only if the temperature traces are free from interference and the total power delivered to the patient is monitored. Mean values of SAR ranged from 4.6 to 89 W kg-1 depending on the treatment site. Satisfactory heating was achieved for superficial tumors, with temperatures greater than 42 degrees C being recorded in 69% of treatments. For axillary nodes only 4% of treatments exceeded 42 degrees C. For cervix tumors an idealized tumor model was used to estimate tumor temperature from the temperature and SAR measured in the adjacent normal tissue. From the model it appears necessary either to raise the systemic temperature to 40 degrees C or to increase the SAR by at least a factor of 4 to obtain a temperature of 42 degrees C in a typical tumor. Measurements of SAR and temperature are essential for feedback control of computer models which, in principle, could provide a complete distribution of temperature during a hyperthermia treatment. Furthermore, measured SAR provides a direct comparison of the power deposition from different treatment machines in a clinical environment. The data presented form a basis for comparison with the clinical use of other heating systems.

DRUG TESTING USING A SOFT AGAR STEM CELL ASSAY ON PATIENT AND XENOGRAFT TUMOR MATERIAL

Since 1981 we have received 50 tumor samples from 10 different sites; over half were breast or ovary. Of the 27 that were considered suitable for cloning, 11 produced colony formation and 6 of these were drug tested. One ovarian granulosa cell tumor and its xenograft (V7) were tested against several cytotoxic agents. During a period of 16 months, sensitivity to cisplatin was relatively stable but sensitivity to vinblastine was markedly changed when the original tumor cells and original cells stored in liquid nitrogen were compared with xenograft cells. These changes may be related to patient treatments prior to tumor sample collection. This xenograft V7 exhibited chromosome karyotype and iso-enzyme Glucose-6-phosphate dehydrogenase consistent with it being of human origin. Gross histology of original tumor and xenograft were similar. Chemosensitization in vivo of a breast xenograft (Hx99) to melphalan by misonidazole was investigated. Misonidazole at a total dose of 0.5 g/kg given prior to melphalan (14 mg/kg) was an effective chemosensitizer.

A novel dye exclusion assay for measurement of cell response following in vitro exposure to radiation or drugs.

A novel dye exclusion assay based on differential staining of fixed cells has been evaluated using the MOLT4 (T-lymphoblastic leukaemia) and DAUDI (Burkitt lymphoma) cell lines. Reproducible differential staining was found with fixed samples kept for up to 2 months. A small increase (less than 13%) in the proportion of stained cells was observed over the first 30 days in fixative. Reproducible dose-response data were obtained with cells treated with radiation or drugs and assayed after 4 days in culture. This ability to fix cells prior to measurement of viability is of general use particularly where time constraints prevent haemocytometer counting. More specifically, it may have potential use in the field of chemosensitivity testing particularly where large sample numbers require rapid processing.

Independent living in care homes for older people

Purpose – The purpose of this paper is to investigate how care homes can be de-institutionalised and what factors are key in independence for residents? Design/methodology/approach – This paper takes the form of a review of the current life of residents in care homes with insight from My Home Life Cymru. Findings – This research identifies eight best practice themes which together form a vision for care homes in the twenty-first century. Originality/value – Care homes play an important role in social care, providing services to some of our most vulnerable citizens. By focusing on the quality of life in care homes for older people, we can play a part in delivering services that people want, in the way that they want them.