Autocrine regulation of wound healing by ATP release and P2Y2 receptor activation.

AIMS: Application of exogenous nucleotides can modulate wound healing via the activation of purinergic receptors. However, evidence for the release of endogenous nucleotides and the subsequent activation of purinergic receptors in this process has not been well defined. Therefore, the current study aimed to investigate wound-mediated nucleotide release and autocrine purinergic signalling during HaCaT keratinocyte wound closure following scratch injury. MAIN METHODS: An in vitro scratch wound apparatus was employed to study wound healing over 24-h in the presence of modulators of ATP release, P2 receptors and pathways downstream of P2 receptor activation. KEY FINDINGS: Adenosine 5'-triphosphate (ATP) was released from scratched cells. The ectonucleotidase apyrase and pharmacological inhibition of the nucleotide release hemichannel, pannexin-1, decreased wound closure over time. The non-selective P2Y receptor antagonist suramin and the selective P2Y2 receptor antagonist AR-C118925XX, but not other P2 antagonists, decreased wound closure. AR-C118925XX decreased wound closure in a concentration-dependent fashion. However, exogenous P2Y2 receptor agonists, ATP or uridine 5'-triphosphate, did not enhance wound closure. PCR and immunoblotting confirmed P2Y2 receptor expression in HaCaT cells. U73122, a phospholipase C antagonist, and 2-aminoethoxydiphenylborate, an inositol 1,4,5-trisphosphate receptor-sensitive Ca2+-release channel antagonist, decreased wound closure consistent with P2Y2 receptor activation. Absence of extracellular or intracellular Ca2+ or inhibition of intracellular Ca2+-release also impaired wound closure. SIGNIFICANCE: These data describe a novel autocrine signalling mechanism in which wound-mediated release of endogenous ATP in response to mechanical scratching of HaCaT cells activates P2Y2 receptors to facilitate wound closure.

How do the characteristics of breast cancer diagnostic assessment programmes influence service delivery: A mixed methods study.

Diagnostic assessment programmes (DAPs) coordinate multidisciplinary teamwork (MDT), and improve wait times and patient satisfaction. No research has established optimal DAP design. This study explored how DAP characteristics influence service delivery. A mixed methods case study of four breast cancer DAPs was conducted including qualitative interviews with health-care providers and retrospective chart review. Data were integrated using multiple approaches. Twenty-three providers were interviewed; 411 medical records were reviewed. The number of visits and wait times from referral to diagnosis and consultation were lowest at a one-stop model. DAP characteristics (rural-remote region, human resources, referral volume, organisation of services, adherence to service delivery targets and one-stop model) may influence service delivery (number of visits, wait times). MDT, influenced by other DAP characteristics (co-location of staff, patient navigators, team functioning), may also influence service delivery. While the one-stop model may be ideal, all sites experienced similar and unique challenges. Further research is needed to understand how to optimise the organisation and delivery of DAP services. Measures reflecting individual, team and patient-reported outcomes should be used to assess the effectiveness and impact of DAPs in addition to more traditional measures such as wait times.

Cost analysis of breast cancer diagnostic assessment programs.

OBJECTIVES: Diagnostic assessment programs (daps) appear to improve the diagnosis of cancer, but evidence of their cost-effectiveness is lacking. Given that no earlier study used secondary financial data to estimate the cost of diagnostic tests in the province of Ontario, we explored how to use secondary financial data to retrieve the cost of key diagnostic test services in daps, and we tested the reliability of that cost-retrieving method with hospital-reported costs in preparation for future cost-effectiveness studies. METHODS: We powered our sample at an alpha of 0.05, a power of 80%, and a margin of error of ±5%, and randomly selected a sample of eligible patients referred to a dap for suspected breast cancer during 1 January-31 December 2012. Confirmatory diagnostic tests received by each patient were identified in medical records. Canadian Classification of Health Intervention procedure codes were used to search the secondary financial data Web portal at the Ontario Case Costing Initiative for an estimate of the direct, indirect, and total costs of each test. The hospital-reported cost of each test received was obtained from the host-hospital's finance department. Descriptive statistics were used to calculate the cost of individual or group confirmatory diagnostic tests, and the Wilcoxon signed-rank test or the paired t-test was used to compare the Ontario Case Costing Initiative and hospital-reported costs. RESULTS: For the 191 identified patients with suspected breast cancer, the estimated total cost of $72,195.50 was not significantly different from the hospital-reported total cost of $72,035.52 (p = 0.24). Costs differed significantly when multiple tests to confirm the diagnosis were completed during one patient visit and when confirmatory tests reported in hospital data and in medical records were discrepant. The additional estimated cost for non-salaried physicians delivering diagnostic services was $28,387.50. CONCLUSIONS: It was feasible to use secondary financial data to retrieve the cost of key diagnostic tests in a breast cancer dap and to compare the reliability of the costs obtained by that estimation method with hospital-reported costs. We identified the strengths and challenges of each approach. Lessons learned from this study have to be taken into consideration in future cost-effectiveness studies.

Violence among female stalkers.

BACKGROUND: Female stalkers account for 10-25% of all stalking cases, yet little is known about risk factors for female stalking violence. This study identifies risk factors for female stalking violence and contrasts these with risk factors for male stalking violence. METHOD: Seventy-one female and 479 male stalkers presenting to police in Sweden and a specialist stalking clinic in Australia were investigated. Univariate comparisons of behaviour by gender, and comparisons between violent and non-violent female stalkers, were undertaken. Logistic regression was then used to develop a predictive model for stalking violence based on demographic, offence and clinical characteristics. RESULTS: Rates of violence were not significantly different between genders (31% of males and 23% of females). For both men and women, violence was associated with a combination of a prior intimate relationship with the victim, threats and approach behaviour. This model produced receiver operating characteristic (ROC) curves with area under the curve (AUC)=0.80 for female stalkers and AUC=0.78 for male stalkers. The most notable gender difference was significantly higher rates of personality disorder among women. High rates of psychotic disorder were found in both genders. Stalking violence was directly related to psychotic symptoms for a small number of women. CONCLUSIONS: Similar risk factors generally predict stalking violence between genders, providing initial support for a similar approach to risk assessment for all stalkers. The most notable gender difference was the prevalence of personality and psychotic disorders among female stalkers, supporting an argument for routine psychiatric assessment of women charged with stalking.

Violence in stalking situations.

BACKGROUND: Stalking is often viewed as a precursor to violence, but determining which stalkers might attack is a difficult task. This study overcomes shortfalls in previous investigations by adopting a pseudo-prospective design and examining potential risk factors for different types of stalker. METHOD: Demographic, behavioural and diagnostic information was collected from stalkers referred to a community forensic mental health service (n=211). Potential risk factors for stalking violence were identified using odds ratios and chi2 tests, and entered into logistic regression models. Model utility was assessed using receiver operating characteristic curves. RESULTS: Amongst Rejected ex-intimate stalkers, violence was best predicted by previous violence, making threats and being employed (area under the curve=0.75), while for stalkers with other motives and relationships to the victim, being aged less than 30 years, substance use at the time of stalking and prior violence best predicted stalking violence (area under the curve=0.80). CONCLUSIONS: Stalkers at increased risk of violence can be accurately identified by examining motivational and relationship type in conjunction with specific relevant risk factors. Previous violence is a particularly important risk factor, as are threats amongst ex-intimate stalkers. Approach behaviours and psychosis were shown to be less useful in predicting violence.

The prevalence of clinically significant anaemia and haemoglobinopathy in children requiring dental treatment under general anaesthesia: a retrospective study of 1000 patients.

There is little information on the possible value of screening children who are liable to haemoglobinopathies as part of pre-operative assessment for dental treatment under general anaesthesia. The present retrospective investigation examined, first, the number of patients having low haemoglobin levels among 1000 patients who had undergone haematological investigation prior to general anaesthesia in a dental outpatient unit, and, secondly, the subsequent clinical management of these patients. Haemoglobin levels of 10.0 g/dl or less were found in 31 children: 13 Asian, 7 Afro-Caribbean, 5 Mediterranean, 3 Arabic, 1 white Caucasian and 2 Oriental children. In addition, 17 patients had sickle-cell trait and 2 had beta-thalassaemia trait, but there was no relationship between the presence of haemoglobinopathy and low levels of haemoglobin. The planned general anaesthesia was undertaken for 22 of the 31 children who had low levels of haemoglobin and for the 19 children with haemoglobinopathy. Only 6 children ultimately did not undergo general anaesthesia, all failing to return. It is concluded that pre-anaesthetic haematological assessment of children needing minor dental surgery is rarely of any significant clinical value.

Comparison of alfentanil with suxamethonium in facilitating nasotracheal intubation in day-case anaesthesia.

We have performed a prospective study in 100 adults (ASA I or II) undergoing day-case dental extraction to compare the conditions for intubation and the postoperative sequelae of suxamethonium and alfentanil as adjuncts to propofol. The patients were allocated randomly to two groups comparable in age, sex and weight. Successful intubation was achieved in 100% of the suxamethonium group and 90% of the alfentanil group. Of the patients who received suxamethonium, 74% developed myalgia on the day after surgery, compared with 20% in the alfentanil group (P < 0.001). The proportion of patients who developed sore throat was also less in the alfentanil group than in the suxamethonium group (P < 0.05). The proportion of patients who complained of nausea in the two groups was not significantly different. We conclude that alfentanil, as an adjunct to propofol to facilitate tracheal intubation, is more acceptable to patients than suxamethonium in anaesthesia for day-case surgery.

Mycotoxins in animal feeds and toxic fungi in Queensland 1971-80.

During the years 1971 to 1980, 355 samples of animal feeds submitted to this laboratory in connection with suspected mycotoxicoses were analysed for aflatoxins. Most major Queensland agricultural crops were represented. Aflatoxins were detected in 67 samples, 45 of which were peanut meals and by-products (55% of all peanut materials analysed). Of 200 Aspergillus flavus isolates cultured on maize meal, aflatoxins were produced by 49%. Ochratoxin A was detected in one sample of another 25 feeds analysed for the compound. Ochratoxin A was produced by 28% of 47 A. ochraceus isolates, and two Fusarium equiseti isolates produced zearalenone. The present situation with regard to mycotoxins and mycotoxicosis in Queensland is briefly reviewed.