Attitudes of Australian Heroin Users to Peer Distribution of Naloxone for Heroin Overdose: Perspectives on Intranasal Administration

Naloxone distribution to injecting drug users (IDUs) for peer administration is a suggested strategy to prevent fatal heroin overdose. The aim of this study was to explore attitudes of IDUs to administration of naloxone to others after heroin overdose, and preferences for method of administration. A sample of 99 IDUs (median age 35 years, 72% male) recruited from needle and syringe programs in Melbourne were administered a questionnaire. Data collected included demographics, attitudes to naloxone distribution, and preferences for method of administration. The primary study outcomes were attitudes of IDUs to use of naloxone for peer administration (categorized on a five-point scale ranging from “very good idea” to “very bad idea”) and preferred mode of administration (intravenous, intramuscular, and intranasal). The majority of the sample reported positive attitudes toward naloxone distribution (good to very good idea: 89%) and 92% said they were willing to participate in a related training program. Some participants raised concerns about peer administration including the competence of IDUs to administer naloxone in an emergency, victim response on wakening and legal implications. Most (74%) preferred intranasal administration in comparison to other administration methods (21%). There was no association with age, sex, or heroin practice. There appears to be strong support among Australian IDU for naloxone distribution to peers. Intranasal spray is the preferred route of administration. Kerr and Kelly are with the Joseph Epstein Centre for Emergency Medicine Research, Sunshine Hospital, St. Albans, Victoria, Australia; Kerr and Kelly are with the The University of Melbourne, Melbourne, Victoria, Australia; Dietze is with the Burnet Institute, Melbourne, Victoria, Australia; Dietze and Jolley are with the Monash Institute of Health Services Research, Melbourne, Victoria, Australia.     

The EpiSkin phototoxicity assay (EPA): development of an in vitro tiered strategy using 17 reference chemicals to predict phototoxic potency.

The aim of the study was to investigate the ability of human reconstructed epidermis EpiSkin(LM) to identify the phototoxic potency of topically or systemically applied chemicals (EPA: EpiSkin phototoxicity assay). Three classes, according to their available human phototoxic potential, were evaluated: systemic phototoxic compounds, topical phototoxic chemicals and non-phototoxic compounds. Non-cytotoxic concentrations of chemicals were applied topically or directly added to the underlying culture medium in order to mimic a systemic-like administration. Following treatment, tissues were exposed to non-cytotoxic dose of UVA (50 J cm(-2)). Cell viability and pro-inflammatory mediators (IL-1alpha) were investigated 22 h after UVA exposure. Our results show that the phototoxic potential of chemicals can be determined using cell viability combined with inflammatory mediator measurements (cytokine IL-1alpha) in a 3-D epidermis model. Moreover, the EPA was able to discriminate efficiently between phototoxic and non-phototoxic products. Furthermore, the EPA is sensitive to the administration route in the prediction of the phototoxic potency of the tested chemical. Differences observed between the two routes of administration (topical or systemic-like) may be linked in part to chemicals bioavailability which depends on specific penetration potential, epidermis barrier function and also on keratinocytes absorption/metabolization processes. Results were very promising and showed a very good sensitivity (92.3%) and an excellent specificity (100%) with an overall accuracy of 94.1%. The performances of the EPA showed that the EpiSkin(LM) model is an interesting tool able to integrate decision-making processes to address the question of phototoxicity linked to the application site.     

Activin A stimulates catecholamine secretion from rat adrenal chromaffin cells: a new physiological mechanism

Activin A is a member of the transforming growth factor-beta family and has known roles in the adrenal cortex, from which activin A is secreted. We aimed to find whether activin A induces secretion of catecholamines from chromaffin cells of the adrenal medulla, which neighbours the adrenal cortex in vivo. Using carbon fibre amperometry, we were able to measure catecholamine secretion in real-time from single chromaffin cells dissociated from the rat adrenal medulla. Activin A stimulated catecholamine secretion in a rapid and dose-dependent manner from chromaffin cells. This effect was fully reversible upon washout of activin A. The minimum dose at which activin A had a maximal effect was 2 nM, with an EC50 of 1.1 nM. The degree of secretion induced by activin A (2 nM) was smaller than that due to membrane depolarization caused by an increase in the external K+ concentration from 5 to 70 mM. No response to activin A was seen when Ca2+ channels were blocked by Cd2+ (200 microM). We conclude from these findings that activin A is capable of stimulating a robust level of catecholamine secretion from adrenal chromaffin cells in a concentration-dependent manner. This occurs via the opening of voltage-gated Ca2+ channels, causing Ca2+ entry, thereby triggering exocytosis. These findings illustrate a new physiological role of activin A and a new mechanism in the control of catecholamine secretion from the adrenal medulla.     

Previous induced abortions and the risk of very preterm delivery: results of the EPIPAGE study

OBJECTIVES: To evaluate the risk of very preterm birth (22-32 weeks of gestation) associated with previous induced abortion according to the complications leading to very preterm delivery in singletons. DESIGN: Multicentre, case-control study (the French EPIPAGE study). SETTING: Regionally defined population of births in France. SAMPLE: The sample consisted of 1943 very preterm live-born singletons (< 33 weeks of gestation), 276 moderate preterm live-born singletons (33-34 weeks) and 618 unmatched full-term controls (39-40 weeks). METHODS: Data from the EPIPAGE study were analysed using polytomous logistic regression models to control for social and demographic characteristics, lifestyle habits during pregnancy and obstetric history. The main mechanisms of preterm delivery were classified as gestational hypertension, antepartum haemorrhage, fetal growth restriction, premature rupture of membranes, idiopathic preterm labor and other causes. MAIN OUTCOME MEASURES: Odds ratios for very preterm birth by gestational age and by pregnancy complications leading to preterm delivery associated with a history of induced abortion. RESULTS: Women with a history of induced abortion were at higher risk of very preterm delivery than those with no such history (OR + 1.5, 95% CI 1.1-2.0); the risk was even higher for extremely preterm deliveries (< 28 weeks). The association between previous induced abortion and very preterm delivery varied according to the main complications leading to very preterm delivery. A history of induced abortion was associated with an increased risk of premature rupture of the membranes, antepartum haemorrhage (not in association with hypertension) and idiopathic spontaneous preterm labour that occur at very small gestational ages (< 28 weeks). Conversely, no association was found between induced abortion and very preterm delivery due to hypertension. CONCLUSION: Previous induced abortion was associated with an increased risk of very preterm delivery. The strength of the association increased with decreasing gestational age.     

Noninvasive assessment of arterial stiffness and risk of atherosclerotic events in children

Noninvasive assessment of vascular dysfunction in the pediatric population has taken advantage of the development of high-resolution ultrasound techniques. The most frequently used methods are the quantification of flow-mediated endothelium-dependent dilation of the brachial artery and measurement of the intima-media thickening of the carotid artery. Both reduced flow-mediated dilation and increased intima-media thickness have been proven to correlate with late cardiovascular events and/or mortality in adults. As these noninvasive methods can easily be applied in children, there have been recent investigations in high-risk pediatric patients harboring classical cardiovascular risk factors. Endothelial dysfunction and increased thickness of the intima media are currently observed in children with familial hypercholesterolemia, obesity, and type 1 diabetes mellitus. The association of early vascular dysfunction with a known risk factor is an important issue as these anomalies precede the formation of atherosclerotic plaques. Therefore, they may help in stratification of the risk for cardiovascular event and to better tailor therapeutic interventions in at risk children. Finally, these methods have been applied in specific pediatric populations, such as children with end-stage renal disease, chronic parenteral nutrition, HIV infection, and coarctation of the aorta. In these conditions, endothelial dysfunction and vascular remodeling are also present early in life and these data raise new possibilities in the understanding of the pathogenesis of atherosclerosis in these populations.     

Ectopic bone formation by microporous calcium phosphate ceramic particles in sheep muscles

Calcium phosphate ceramics are widely used in bone reconstructive surgery because of their osteconductive properties. However, these materials generally lack osteoinductive properties required to support bone healing in large defects. In this article, we study the osteoinductive potential of calcium phosphate ceramic particles implanted for 6 months into the dorsal muscles of eight adult female sheep. Microporous biphasic calcium phosphate (MBCP) granules of 1–2 mm composed of hydroxyapatite and beta-tricalcium phosphate (60/40) had macropores of 450 μm, micropores of 0.43 μm, and a specific surface area of 1.8 m²/g. After 6 months in the back muscles of sheep, the explants composed of MBCP granules were hard and encapsulated by normal muscle tissue. Ectopic bone formation with Haversian structures was observed in close contact with the MBCP granules in histological sections. Back-scattered electron microscopy and micro-computed tomography indicated that approximately 10% of well-mineralized bone with mature osteocytes had formed between or upon the granules. The ectopic bone showed trabeculae bridging the MBCP granules. Both the number and thickness of the trabeculae formed between the MBCP particles were comparable to those measured in spongious bone. The overall results therefore confirmed the presence of mature bone after intramuscular implantation of MBCP granules. The different hypotheses explaining ectopic bone formation induced by MBCP granules are discussed. Synthetic bone substitutes with osteoinductive properties could be used in bone reconstructive surgery.