A Tasmanian devil breeding program to support wild recovery.

Tasmanian devils are threatened in the wild by devil facial tumour disease: a transmissible cancer with a high fatality rate. In response, the Save the Tasmanian Devil Program (STDP) established an 'insurance population' to enable the preservation of genetic diversity and natural behaviours of devils. This breeding program includes a range of institutions and facilities, from zoo-based intensive enclosures to larger, more natural environments, and a strategic approach has been required to capture and maintain genetic diversity, natural behaviours and to ensure reproductive success. Laboratory-based research, particularly genetics, in tandem with adaptive management has helped the STDP reach its goals, and has directly contributed to the conservation of the species in the wild. Here we review this work and show that the Tasmanian devil breeding program is a powerful example of how genetic research can be used to understand and improve reproductive success in a threatened species.

Immune-endocrine interactions in marsupials and monotremes.

Interactions between the immune and endocrine systems are not well studied in marsupials and monotremes. One exception to this is the phenomenon of semelparity, which is well covered in the literature as this is an unusual reproductive strategy amongst mammals and is only observed in some dasyurid and didelphid marsupials. Thymus involution provides a direct link between the endocrine and immune systems and warrants further study in marsupials and monotremes. The thymus is a primary immune tissue which is essential for overall immune function. Whilst the organ is large in juvenile animals, it begins to involute around puberty due to the suppressive effects of sex steroids. Thymus involution has a significant effect on the immune system, as it signals the onset of immune aging and decline in function. The output of naïve T lymphocytes by the thymus decreases, increasing susceptibility of aged individuals to infection and cancers. Understanding the links between the immune and endocrine system in marsupials and monotremes may shed light on diseases such as devil facial tumour disease (DFTD) which threatens the future of the Tasmanian devil. We hypothesise that changes in sex hormones around puberty may drive changes in the immune system, such as thymus involution, which may make devils more susceptible to DFTD as they age. In addition, the Schwann cell origin of DFTD may enable tumours to respond to sex hormones, as occurs in similar cancers in humans.

"I guess you can interpret it in a number of ways like kind of a milder or the mildest form of dementia?": Multi-stakeholder perceptions of cognitive impairment.

INTRODUCTION: Mild cognitive impairment (MCI) has a high prevalence and is a risk factor for dementia. Furthering understanding of MCI has been identified as a public health priority. This research aimed to explore views about the causes of cognitive impairment and identify associations between cognitive impairment, dementia, and normative ageing. METHOD: Semi-structured qualitative interviews were conducted with 22 participants with different stakeholder perspectives on the area of MCI in England, and analysed thematically. RESULTS: Our analysis focuses on two main themes: 1) causes of cognitive impairment, and 2) ageing, dementia, and dying. Most participants viewed cognitive impairment as a transitional state between normative ageing and dementia. Participants expressed their fear of cognitive impairment and dementia, and made clear links between cognitive impairment and dying. Participants also showed an awareness of the links between lifestyle factors and cognitive health. However, linkage between lifestyle and cognition was discussed only when explicitly asked, suggesting that this was not especially salient for participants when considering the causes and risk factors for cognitive impairment. CONCLUSION: The results of this study highlight key areas for future public health initiatives, such as a focus on the multitude of benefits offered by adopting a healthy diet and physical exercise in reducing risk of cognitive impairment.

Patients' perceptions and experiences of taking oral glucose-lowering agents: a longitudinal qualitative study.

AIMS: The aims of this study were to examine Type 2 diabetic patients' expectations, perceptions and experiences of oral glucose-lowering agents (OGLAs), including their reasons for taking/not taking these drugs as prescribed and to provide recommendations for developing interventions to improve OGLA adherence. METHODS: Longitudinal, qualitative study using repeat in-depth interviews with patients (n = 20) over 4 years following clinical diagnosis. Respondents were recruited from primary and secondary care settings across Lothian, Scotland, UK. RESULTS: Despite experiences of side-effects, dislikes and concerns about taking multiple drugs and a belief that OGLAs could themselves cause one's diabetes to progress, most respondents appeared motivated to take these drugs as prescribed. This motivation seemed to arise from respondents' experiences of taking OGLAs and observing them to 'work'. Some respondents described feeling better after taking OGLAs, others, typically those who were asymptomatic, used blood glucose self-monitoring and/or glycated haemoglobin results to observe and evidence the effects of their OGLAs. Most respondents demonstrated a 'passive' expectation that health professionals should be responsible for decisions about medications. Hence, non-adherence typically resulted from forgetfulness rather than ambivalence about either medication or consultation style. Respondent concern about OGLA's largely centred upon lack of knowledge about the medication and what to do when doses were missed. CONCLUSION: The findings call for multifaceted strategies to promote adherence. These could include education to address misconceptions and advise patients how to respond to missed doses; reminders to help patients remember to take their drugs; and structured feedback on the impact of OGLAs on glycaemic control.

Cathelicidins in the Tasmanian devil (Sarcophilus harrisii).

Tasmanian devil joeys, like other marsupials, are born at a very early stage of development, prior to the development of their adaptive immune system, yet survive in a pathogen-laden pouch and burrow. Antimicrobial peptides, called cathelicidins, which provide innate immune protection during early life, are expressed in the pouch lining, skin and milk of devil dams. These peptides are active against pathogens identified in the pouch microbiome. Of the six characterised cathelicidins, Saha-CATH5 and 6 have broad-spectrum antibacterial activity and are capable of killing problematic human pathogens including methicillin-resistant S. aureus and vancomycin-resistant E. faecalis, while Saha-CATH3 is active against fungi. Saha-CATH5 and 6 were toxic to human A549 cells at 500 µg/mL, which is over seven times the concentration required to kill pathogens. The remaining devil cathelicidins were not active against tested bacterial or fungal strains, but are widely expressed throughout the body, such as in immune tissues, in digestive, respiratory and reproductive tracts, and in the milk and pouch, which indicates that they are likely also important components of the devil immune system. Our results suggest cathelicidins play a role in protecting naive young during pouch life by passive immune transfer in the milk and may modulate pouch microbe populations to reduce potential pathogens.

A prospective randomized comparison of fine needle aspiration biopsy and fibreoptic bronchoscopy in the investigation of peripheral pulmonary opacities.

Twenty-nine patients, aged 66(+/- 7) years with a peripheral pulmonary opacity (mean diameter 3.6 +/- 1.8 cm) believed to be a tumor, were randomly allocated to initial investigation by either fibreoptic bronchoscopy or percutaneous fine needle aspiration biopsy, the latter performed under fluoroscopic control. The patients proceeded to the alternative investigation in the event of the first failing to achieve a diagnosis. Malignancy was confirmed by the initial procedure in 14/15 patients randomized to fine needle aspiration biopsy but only in 1/14 patients randomized to fibreoptic bronchoscopy (P less than 0.01). Overall, these figures were 25/28 fine needle aspiration biopsy and 2/15 fibreoptic bronchoscopy (P less than 0.01). These results confirm the clinical suspicion that fine needle aspiration biopsy is far more likely than fibreoptic bronchoscopy to establish the presence of malignancy in peripheral pulmonary opacities.

Issues of cause and control in patient accounts of Type 2 diabetes.

Patients experience considerable difficulties in making and sustaining health-related lifestyle changes. Many Type 2 diabetes patients struggle to follow disease risk-management advice even when they receive extensive information and support. Drawing on a qualitative study of patients with Type 2 diabetes, the paper uses discourse analysis to examine their accounts about disease causation and disease management, and the implications for how they respond to their condition and health services advice. As it is a multifactorial disease, biomedical discourse around Type 2 diabetes is complex. Patients are encouraged to grasp the complicated message that both cause and medical outcomes related to their condition are partly, but not wholly, within their control. Discursive constructions identified from respondent accounts indicate how these two messages are deployed variously by respondents when accounting for disease causation and management. While these constructions (identified in respondent accounts as 'Up to me' and 'Down to them') are a valuable resource for patients, equally they may be deployed in a selective and detrimental way. We conclude that clear messages from health professionals about effective disease management may help patients to position themselves more effectively in relation to their condition. More importantly, they might serve to hinder the availability of inappropriate and potentially harmful patient positions where patients either relinquish responsibility for disease management or reject all input from health professionals.

Diabetes service provision: a qualitative study of newly diagnosed Type 2 diabetes patients' experiences and views.

AIMS: To explore newly diagnosed Type 2 diabetes patients' views about Scottish diabetes services at a time when these services are undergoing a major reorganization. To provide recommendations to maximize opportunities brought by the devolvement of services from secondary to primary healthcare settings. METHODS: Qualitative panel study with 40 patients newly diagnosed with Type 2 diabetes, recruited from hospital clinics and general practices in Lothian, Scotland. Patients were interviewed three times over 1 year. The study was informed by grounded theory, which involves concurrent data collection and analysis. RESULTS: Patients were generally satisfied with diabetes services irrespective of the types of care received. Most wanted their future care/review to be based in general practice for reasons of convenience and accessibility, although they disliked it when appointments were scheduled for different days. Many said they lacked the knowledge/confidence to know how to manage their diabetes in particular situations, and needed access to healthcare professionals who could answer their questions promptly. Patients expressed a need for primary care professionals who had diabetes expertise, but who had more time and were more accessible than general practitioners. Patients who had encountered practice lead nurses for diabetes spoke particularly positively of these professionals. CONCLUSIONS: Nurses with diabetes training are particularly well placed to provide information and support to patients in primary care. Ideally, practices should run 'one-stop' diabetes clinics to provide structured care, with easily accessible dietetics, podiatry and retinopathy screening. Newly diagnosed patients may benefit from being made more aware of specific services provided by charitable organizations such as Diabetes UK.

Effects of long-term inhaled salbutamol therapy on the provocation of asthma by histamine.

Eight patients with asthma in remission were treated for 4 wk with a regular beta 2 stimulant. (salbutamol, 200 microgram) given 4 times/day by aerosol. Histamine provocation tests were performed at the beginning and at the end of the treatment period, and again 2 wk after cessation of treatment. Throughout the 6-wk period, the patients recorded peak expiratory flow (PEF) at home twice daily before and after inhaling 200 microgram of salbutamol. No significant differences were seen in the average PEF values or in the bronchodilator responses. There were no changes in the bronchial sensitivity to histamine during the study, and the protective effect of inhaled salbutamol against histamine provocation was preserved after the period of regular therapy. The results suggested that the regular use of a selective beta2 stimulant by inhalation in conventional therapeutic amounts in patients with asthma is unlikely to produce clinically important tolerance or increased susceptibility to an asthma-provoking stimulus.

A dose response study of oxitropium bromide in chronic bronchitis.

In a dose response study 12 patients with chronic bronchitis and airflow obstruction received inhaled placebo and incremental doses of oxitropium bromide. Significant improvements in peak expiratory flow rate, forced expiratory volume in one second, and forced vital capacity were recorded at all times up to 10 hours after all doses of oxitropium bromide. Oxitropium bromide is an effective bronchodilator in chronic bronchitis with an optimal dose of 400-600 micrograms.

Assessment of variability of exercise tolerance limited by breathlessness.

A sequence of questions was designed to quantify the within subject variation of exercise tolerance limited by breathlessness, to serve as a guide to variation in airflow limitation for epidemiological purposes. The questions seek answers about breathlessness in relation to various levels of attempted activity when the subjects are at their best and at their worst. The difference between exercise tolerance at best and exercise tolerance at worst (variation in exercise tolerance) was expressed on a scale ranging from 0 (no variation) to 6 (greatest variation). The effectiveness of these questions has been assessed in 68 patients with airflow limitation attending a chest clinic, by comparing the results with variation in peak expiratory flow rate (PEF). Variation in PEF was expressed as the standard deviation of the first 24 PEF recordings from each patient (equivalent to four days' recordings). There was a highly significant relation between the measure of variation in exercise tolerance obtained from the questionnaire and PEF variation, though each point on the scale of variation in exercise tolerance covered a wide range of variation in PEF. The questions give some guide to the variation in airflow limitation and in combination with other questions may be helpful in epidemiological studies.

'Urine testing is a waste of time': newly diagnosed Type 2 diabetes patients' perceptions of self-monitoring.

AIMS: To date, there is no convincing evidence that non-insulin treated patients who undertake self-blood glucose monitoring (SBGM) have better glycaemic control than those who test their urine. This has led to a recommendation that non-insulin dependent patients undertake urine testing, which is the cheaper option. This recommendation does not take account of patients' experiences and views. This study explores the respective merits of urine testing and SBGM from the perspectives of newly diagnosed patients with Type 2 diabetes. METHODS: Qualitative study using repeat in-depth interviews with 40 patients. Patients were interviewed three times at 6-monthly intervals over 1 year. Patients were recruited from hospital clinics and general practices in Lothian, Scotland. The study was informed by grounded theory, which involves concurrent data collection and analysis. RESULTS: Patients reported strongly negative views of urine testing, particularly when they compared it with SBGM. Patients perceived urine testing as less convenient, less hygienic and less accurate than SBGM. Most patients assumed that blood glucose meters were given to those with a more advanced or serious form of diabetes. This could have implications for how they thought about their own disease. Patients often interpreted negative urine results as indicating that they could not have diabetes. CONCLUSIONS: Professionals should be aware of the meanings and understandings patients attach to the receipt and use of different types of self-monitoring equipment. Guidelines that promote the use of consistent criteria for equipment allocation are required. The manner in which negative urine results are conveyed needs to be reconsidered.

A comparison of oxitropium bromide and ipratropium bromide in asthma.

Oxitropium bromide is a derivative of scopolamine and is an anticholinergic drug. Twenty asthmatics completed the study in which they received, in randomised double-blind fashion, placebo, ipratropium bromide 80 micrograms, and oxitropium bromide 200 micrograms. The patients recorded peak expiratory flow immediately before inhalation and up to 10 h afterwards. PEF were significantly higher than placebo between 10 min and 10 h, for both active treatments. There were no significant differences between values on oxitropium bromide and ipratropium bromide at any time points. Side effects were minimal and oxitropium bromide is an effective bronchodilator in asthma.

Sustained-release theophylline in chronic bronchitis.

Twenty-one patients with chronic bronchitis entered a double-blind, cross-over study in which they received sustained-release theophylline ('Nuelin'SA) 350 mg daily for 4 days followed by 700 mg daily for 4 days and matching placebo tablets for 8 days with one week separation. Seventeen patients completed the study. Three patients receiving higher doses for weight than the mean for the group were withdrawn because of side-effects. Mild side-effects only were reported in six other patients. Theophylline given twice daily produced a steady-state mean serum concentration of 13.9 micrograms/ml, 13 patients having concentrations inthe range of 10-20 micrograms/ml. There was no demonstrable improvement of symptoms but pulmonary function measurements in the clinic at the end of active treatment showed a statistically significant improvement in PEFR, 1-second forced expiratory volume and forced vital capacity.

A single dose of sulfametopyrazine versus 7 days of ampicillin in acute on chronic bronchitis.

Forty-two patients with acute on chronic bronchitis received in double-blind fashion either a single dose of 2 g of sulfametopyrazine or ampicillin 250 mg thrice daily for 7 days. There were no significant differences between treatments in the number of patients achieving white sputum, the time to do so, or the incidence of pathogens at the end of treatment. Blood levels of sulfametopyrazine between 8 and 24 hours and on the seventh day were likely to result in sputum concentration adequate to kill Haemophilus influenzae.