What is the role of doctors in respect of suspects with mental health and intellectual disabilities in police custody?

People with severe mental illness and intellectual disabilities are overrepresented in the criminal justice system worldwide and this is also the case in Ireland. Following Ireland's ratification of the United Nations' Convention on the Rights of People with Disabilities in 2018, there has been an increasing emphasis on ensuring access to justice for people with disabilities as in Article 13. For people with mental health and intellectual disabilities, this requires a multi-agency approach and a useful point of intervention may be at the police custody stage. Medicine has a key role to play both in advocacy and in practice. We suggest a functional approach to assessment, in practice, and list key considerations for doctors attending police custody suites. Improved training opportunities and greater resources are needed for general practitioners and psychiatrists who attend police custody suites to help fulfill this role.

The effect of radiation and cytotoxic platinum compounds on the growth of normal and tumour bladder explant cultures.

Using an explant tissue culture model developed by this group for use with human surgical and biopsy specimens, data are presented showing the response of normal and tumor bladder urothelium to radiation in combination with cis- and carboplatin. Cellular response is measured after two weeks in culture as a reduction in the extent of outgrowth from the explant. The outgrowth has been shown to be growing and to be epithelial. Results showed that when either drug or radiation is used singly, the tumour is resistant to treatment while the normal cells are severely affected. However, appropriate combinations of either drug with radiation reverse the unfavourable therapeutic ratio and result in higher tumour cell kill. The model may be useful for investigating mechanisms of radiation/chemotherapy action at the cellular level and, if integrated into appropriate clinical trials, may serve as an easy-to-use in vitro test for optimising single agent or combination therapy regimens.

Optimisation of media for the culture of normal human epithelial cells from oesophageal mucosa.

A technique has been developed which allows growth and histology/cytochemistry of primary oesophageal mucosal explant cultures to be monitored over four weeks. The paper describes experiments designed to optimise media and culture conditions. The results suggest that optimal growth can be obtained in media containing RPMI 1640, and 10% horse or newborn calf serum. McCoy's 5A medium or Dulbecco's modified MEM could be substituted for RPMI but Iscove's serum-free medium or Ham's nutrient mixture inhibited growth or promoted fibroblast contamination. The essential additive appeared to be insulin while selenium was highly toxic to the cells. Hydrocortisone or EGF improved growth slightly under some conditions. Neither transferrin nor cholera toxin had any beneficial effect. None of the cell culture flask coating agents improved attachment or growth.

Enhanced proliferation of cells from human tissue explants following irradiation in the presence of environmental carcinogens.

A method which allows growth of normal human tissue to be studied in vitro is used to investigate possible interactive effects of radiation and environmentally important carcinogens on oesophageal and urothelial cell growth. Carcinogens chosen were selected for their known or suspected effect on the oesophageal mucosa or urothelium in vivo. The results indicate that with carcinogens alone concentrations can be identified that result in increased proliferation of cells. With radiation alone inhibition of cell proliferation occurs at all dose points examined. However, at precise combinations of radiation and carcinogen, greatly enhanced cell proliferation could be detected, suggesting a synergistic interaction between the two agents. The results may have implications for the design and interpretation of experiments aimed at elucidating early or premalignant changes in epithelial tissues and may indicate hitherto unsuspected interactions between radiation and environmentally important carcinogens.

The effect of radiation on the growth of normal and malignant human oesophageal explant cultures pre-treated with bleomycin.

Since all known chemotherapy and radiation treatments affect normal cells to a certain extent, the establishment of favourable differential sensitivities is fundamental to the success of treatment with a particular agent. This type of information can be gained by animal testing and using cultured cells, but ultimately use of the agent in the patient is the only way to determine the response. We have developed a model for testing the response of oesophageal explants from tumour and surrounding normal tissue in the same patient to chemotherapy and radiation, both singly and in combination. The test allows treatment combinations, time and order of administration of agents to the tissue to be accurately controlled. Cytotoxicity, determined by measuring the area of outgrowth from an explant 2 weeks after plating, is the most useful short-term end-point, although many others are possible. Results showing the differential cytotoxicity of bleomycin with and without radiation in squamous and adenocarcinoma of the oesophagus and surrounding normal tissue from the same patient indicate that tumour cells are relatively resistant to radiation alone, that low levels of bleomycin with or without radiation preferentially spare tumour cells and that high levels, in combination with any dose of radiation tested, but not without radiation, spare the normal cells and give a significantly high amount of relative tumour cell kill. Bleomycin must be added to the cells just before or just after irradiation to obtain the normal-tissue sparing effect. The technique may be a useful method for indicating the best approaches to the optimization of combined therapy regimes.

Radiation-induced outgrowth inhibition in explant cultures from surgical specimens of five human organs.

An explant outgrowth technique to determine the radiation response of five different human organs (bladder, oesophagus, colon, breast and thyroid) is described. In each case except thyroid, where malignancies are rare, data are presented for normal and malignant tissue. Results show that variations in response, consistent with those observed in vivo, can be measured. Tumours were in all cases highly resistant to radiation relative to their corresponding normal tissue. Possible reasons for this are discussed. The method may prove useful in the prediction of the radiobiological response for tumour and surrounding normal tissue where post-operative therapy is planned.

Differential response of normal and tumour oesophageal explant cultures to radiation.

An in vitro method is described which allows radiation dose response data to be obtained for samples of oesophageal mucosa obtained from patients undergoing resection for adeno or squamous cell carcinoma. Data are obtained using a growth endpoint from explant cultures and may be expressed in terms of absolute growth inhibition or reduced rate of growth. Radiation dose response curves suggest that cell survival is in the range expected for mammalian cells but that, as is found clinically, tumour cells are far more resistant to radiation than normal cells. The technique provides a means of assessing differential radiation response in normal and tumour tissues from the same patient, as it is unusual for both to be amenable to clonogenic assay.