Care,agency and criminality: Making sense of authorised extended distribution in the accounts of key stakeholders

IntroductionOne of the current harm reduction debates in Australia concerns the legalisation of the extended distribution of sterile needles and syringes, a practice that is currently unlawful in most Australian settings.MethodsWe used data from a unique pilot program of authorised extended distribution to document the opinions held by 22 key stakeholders -service staff, drug users and police - about the risks and benefits of authorisation, and to analyse the ways in which drug users were understood within these.ResultsOpinions were strongly in favour of authorising extended distribution, based on the belief that this would reduce the transmission of hepatitis C. However, stakeholders also identified that distributors risked attention from police and some noted that the consequences of this would be borne by distributors themselves and not the services that support them. These opinions rested on specific assumptions about people who inject, some of which reflect negative constructions of drug users as a source of danger to the public or as helpless ‘addicts’ with little control over their risk reduction. But there were other representations that positioned drug users more positively as responsible agents with a strong duty of care to themselves and others whose choices are often limited by inadequate service structures. Staff participants drew on these understandings in careful and strategic ways, arguing for the rationality and expertise of drug users, while also problematizing the individualised approach that any form of authorised extended distribution might take.ConclusionWe argue that localised and incremental changes such as those that took place to support this pilot project, and the extensive support for extended distribution among stakeholders in this study including police, creates meaningful opportunities to think about extended distribution differently, which can in turn support conditions for future discussions about legislative change.     

Ghrelin attenuates secondary brain injury following intracerebral hemorrhage by inhibiting NLRP3 inflammasome activation and promoting Nrf2/ARE signaling pathway in mice

Ghrelin, a brain-gut peptide, has been proven to exert neuroprotection in different kinds of neurological diseases; however, its role and the potential molecular mechanisms in secondary brain injury (SBI) after intracerebral hemorrhage (ICH) are still unknown. In this study, we investigate whether treatment with ghrelin may attenuate SBI in a murine ICH model, and if so, whether the neuroprotective effects are due to the inhibition of nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation and promotion of nuclear factor-E2-related factor 2 (Nrf2)/antioxidative response element (ARE) signaling pathway. Stereotactically intrastriatal infusion of autologous blood was performed to mimic ICH. Ghrelin was given intraperitoneally immediately following ICH and again 1 h later. Results showed that ghrelin attenuated neurobehavioral deficits, brain edema, hematoma volume, and perihematomal cell death post-ICH. Ghrelin inhibited the NLRP3 inflammasome activation and subsequently suppressed the neuroinflammatory response as evidenced by reduced microglia activation, neutrophil infiltration, and pro-inflammatory mediators release after ICH. Additionally, ghrelin alleviated ICH-induced oxidative stress according to the chemiluminescence of luminol and lucigenin, malondialdehyde (MDA) content, and total superoxide dismutase (SOD) activity assays. These changes were accompanied by upregulation of Nrf2 expression, Nrf2 nuclear accumulation, and enhanced Nrf2 DNA binding activity, as well as by increased expressions of Nrf2 downstream target antioxidative genes, including NAD(P)H quinine oxidoreductase-1 (NQO1), glutathione cysteine ligase regulatory subunit (GCLC), and glutathione cysteine ligase modulatory subunit (GCLM). Together, our data suggested that ghrelin protected against ICH-induced SBI by inhibiting NLRP3 inflammasome activation and promoting Nrf2/ARE signaling pathway.     

甲状旁腺切除术用于难治性肾性继发性甲状旁腺功能亢进的安全性及近远疗效

背景与目的:甲状旁腺切除术(PTX)是治疗药物不能控制的难治性肾性继发性甲状旁腺功能亢进症(SHPT)的重要手段,但PTX术后仍有可能发生永久性甲状旁腺功能减退,无动力性骨病或难治性骨软化症,且国内尚缺乏对PTX术后远期的疗效观察的研究。本研究进一步评价PTX治疗难治性肾性SHPT的安全性与近远期疗效。方法:纳入2011年1月—2014年12月在安徽医科大学第二附属医院行PTX治疗的139例伴有难治性肾性SHPT的维持性透析患者。收集患者术前及术后3 d、6个月及1、2、3年的临床资料、血全段甲状旁腺激素(iPTH)、血钙、血磷、血红蛋白(Hb)及红细胞压积(Hct)等,观察并记录术后症状缓解情况、术后并发症和随访情况。结果:139例患者的PTX手术成功率为95.7%(133/139),术中共计切除甲状旁腺腺体537枚,平均切除3.86枚/例。12例(8.6%)术后发生一过性喉返神经损伤,其中声音嘶哑9例(6.5%),饮水呛咳3例(2.2%),未予处理术后3个月内均自行好转。术后低钙血症或缺乏维生素D者120例(86.3%),给予西那卡塞、补钙及补充活性维生素D治疗后得到有效控制。全组未发生切口感染、出血、窒息及甲状腺功能减退等外科并发症。患者的贫血状况均有不同程度地改善,Hb和Hct术后6个月明显升高并在随访期间保持稳定;术后iPTH明显降低,术后3 d的血钙、磷、钙磷乘积水平最低,随访3年仍低于手术前,所有变化与术前均有统计学差异(均P0.05)。随访期间无死亡病例。患者术前的骨痛、顽固性皮肤瘙痒、失眠、异位钙化、肌无力伴萎缩症状在术后1 d即明显缓解;身高缩短、骨骼畸形患者随访期间无进行性加重;纳差、全身营养状况及自理能力术后3个月内不同程度地改善。11例(7.9%)持续性SHPT,包括4例(2.9%)术中未完全切除甲状旁腺腺体,1例(0.7%)术中1枚腺体较小而未切除完全,6例(4.3%)术后检查存在纵隔异位甲状旁腺。随访期间,5例(3.5%)腺体未切除完全者的iPTH均800 pg/mL,肌无力及顽固性皮肤瘙痒临床症状明显,再次行PTX;6例(4.3%)存在异位甲状旁腺腺体者,因手术风险较大患者拒绝再次手术,予以药物治疗;8例(5.8%)术后复发,其中6例(4.3%)系前臂移植物复发所致,均在局麻下行前臂皮下移植物切除;2例(1.4%)系颈部原位残留腺体过度增生,予以二次手术,术后症状缓解。所有进行二次手术的患者在随访结束时无明显的临床症状,均未复发。结论:PTX可改善难治性肾性SHPT患者临床症状、贫血及钙磷代谢,且近远期疗效均较好,是治疗难治性SHPT的安全有效方法。     

Effect of postural changes on aldosterone to plasma renin ratio in patients with suspected secondary hypertension

AimsTo study the influence of postural changes on aldosterone to renin ratio (ARR) in patients with suspected secondary hypertension and to evaluate the sensitivity and specificity of the recommended seated ARR compared to supine and upright ARR for primary aldosteronism screening.MethodsFifty-three hypertensive patients were prospectively hospitalized for secondary hypertension exploration (age: 51 ± 12, 66% males). After withdrawal of drugs interfering with renin angiotensin system, plasma aldosterone and direct renin concentration were measured in the morning, at bed after an overnight supine position, then out of bed after 1 hour of upright position and finally 2 hours later after 15 minutes of seating. Minimal renin value was set at 5 μUI/mL.ResultsReferring to ARR cut-off of 23 pg/μUI, the sensitivity of seated ARR was 57.1% and specificity was 92.3%. The negative and positive predictive values were 95.1% and 45.2% respectively. Compared to these results, a cut-off of 19 improved sensitivity to 85.7% with a specificity of 89.7%. Negative and positive predictive values were 98.3% and 41.1% respectively. Seated ARR mean value was lower than supine and upright ARR mean values, due to an overall increase in renin at seating compared to the supine position by factor 1.9 while aldosterone just slightly increased by factor 1.2. Seated ARR correlated to supine and upright ARR: correlation coefficients (r) 0.90 and 0.93 respectively (P < 0.001).ConclusionsCurrent recommended measurement of ARR in the seating position is fairly correlated to supine and upright ARR. A suggested cut-off value of 19 instead of 23 pg/μUI increased the discriminating power of this test.