Bradykinin,a new potential mediator of inflammation-induced bone resorption

The effect of bradykinin and desArg⁹-bradykinin on bone was studied in cultures of calvarial bones taken from 6–7-day-old mice. Bradykinin, at and above a 3-nM concentration, caused a dose-dependent stimulation of bone mineral mobilization and matrix degradation. Bradykinin-stimulated resorption was inhibited by calcitonin, an increased concentration of phosphate in the culture medium, hydrocortisone, dexamethasone, indomethacin, meclofenamic acid, naproxen, and 5,8,11,14-eicosatetraenoic acid. The results suggest that bradykinin stimulates osteoclast-mediated bone resorption by a process that is dependent on endogenous prostaglandin production. The stimulatory effect of bradykinin, but not of parathyroid hormone and prostaglandin E₂, was potentiated by the angiotensin-converting enzyme inhibitor, BPP_5a. Treatment with carboxypeptidase B did not affect the capacity of the peptide to stimulated ⁴⁵Ca release. DesArg⁹-bradykinin (1 m̈mole/liter) stimulated ⁴⁵Ca release to the same degree as did bradykinin. Bradykinin (3 m̈M) did not affect the degradation of cartilage proteoglycans, as assessed by the release of ³⁵S-sulfate from prelabeled calf articular cartilage in organ culture. These findings suggest that generation of bradykinin in inflammatory lesions of rheumatoid arthritis and periodontitis may contribute to the bone resorptive process seen in the joints and alveolar bone; however, bradykinin does not directly activate chondrocytes into a catabolic state.     

The changing landscape for the management of patients with neovascular AMD: brolucizumab in clinical practice

Untreated neovascular age-related macular degeneration (nAMD) can lead to severe and permanent visual impairment. The chronic nature of the disease can have a significant impact on patients’ quality of life and an economic and time burden on medical retina (MR) services, with the care need outweighing the growth of resources that clinical services can access. The introduction of a new treatment into clinical services can be challenging, especially for services that are already under capacity constraints. Guidance for practical implementation is therefore helpful. Roundtable meetings, facilitated by Novartis UK, between a working group of MR experts with experience of leading and managing NHS retinal services in the intravitreal era were conducted between 2020 and 2021. These meetings explored various aspects and challenges of introducing a new anti-vascular endothelial growth factor (VEGF) therapy to the UK medical retina services. Provision of clear expert recommendations and practical guidance nationally, that can be adapted locally as required to support clinicians and healthcare professionals (HCPs), is valuable in supporting the introduction of a new anti-VEGF therapy within the NHS environment. The experts provide ophthalmologic HCPs with a collation of insights and recommendations to support the introduction and delivery of brolucizumab in their local service in the face of current and projected growth in demand for retina care.Subject terms: Macular degeneration, Education     

Opposing Effects of Prior Infection versus Prior Vaccination on Vaccine Immunogenicity against Influenza A(H3N2) Viruses

Prior vaccination can alternately enhance or attenuate influenza vaccine immunogenicity and effectiveness. Analogously, we found that vaccine immunogenicity was enhanced by prior A(H3N2) virus infection among participants of the Ha Nam Cohort, Viet Nam, but was attenuated by prior vaccination among Australian Health Care Workers (HCWs) vaccinated in the same year. Here, we combined these studies to directly compare antibody titers against 35 A(H3N2) viruses spanning 1968–2018. Participants received licensed inactivated vaccines containing A/HongKong/4801/2014 (H3N2). The analysis was limited to participants aged 18–65 Y, and compared those exposed to A(H3N2) viruses circulating since 2009 by infection (Ha Nam) or vaccination (HCWs) to a reference group who had no recent A(H3N2) infection or vaccination (Ha Nam). Antibody responses were compared by fitting titer/titer-rise landscapes across strains, and by estimating titer ratios to the reference group of 2009–2018 viruses. Pre-vaccination, titers were lowest against 2009–2014 viruses among the reference (no recent exposure) group. Post-vaccination, titers were, on average, two-fold higher among participants with prior infection and two-fold lower among participants with 3–5 prior vaccinations compared to the reference group. Titer rise was negligible among participants with 3–5 prior vaccinations, poor among participants with 1–2 prior vaccinations, and equivalent or better among those with prior infection compared to the reference group. The enhancing effect of prior infection versus the incrementally attenuating effect of prior vaccinations suggests that these exposures may alternately promote and constrain the generation of memory that can be recalled by a new vaccine strain.     

Percutaneous treatment of focal vs. diffuse in-stent restenosis: a prospective randomized comparison of conventional therapies.

Few randomized studies compare outcomes for focal vs. diffuse in-stent restenosis (ISR) using conventional treatments. The purpose of this study was to compare the rates of major adverse cardiac events (MACEs) for focal vs. diffuse ISR using conventional techniques. One hundred thirteen patients with ISR were prospectively classified as focal (< 10 mm) or diffuse (> 10 mm). Focal ISR was randomized to balloon angioplasty (n = 29) or restenting (n = 29) and diffuse ISR randomized to rotational atherectomy (n = 30) or restenting (n = 25). At 9 months, patients with focal ISR had higher survival free of MACEs than patients with diffuse ISR (86% vs. 63%; P < 0.005), with no difference between techniques. Only the presence of diffuse ISR was an independent predictor of MACE at 9 months. Thus, focal ISR has a low rate of MACE compared to diffuse ISR, which carries a high event rate regardless of treatment employed.     

Randomised comparative trial of thermal balloon ablation and levonorgestrel intrauterine system in patients with idiopathic menorrhagia

AIMS: To compare the effectiveness of thermal balloon ablation (TBA) and levonorgestrel intrauterine system (LNG-IUS) in the management of idiopathic menorrhagia and changes in pictorial blood loss assessment chart (PBAC) scores in patients who had failed on oral medical treatment. METHODS: Phase III, single-centre, open randomised controlled trial. Following full screening and evaluation of 104 women, 33 were randomised to TBA and 33 to LNG-IUS. Primary outcomes were changes in PBAC scores from baseline to 12 months. Secondary outcomes were changes in haemoglobin and serum ferritin, at six months, continuation with treatment and hysterectomy rates at two years and changes in PBAC scores at three, six and nine months. RESULTS: All patients randomised had a PBAC score of > or = 120. At all assessment times, median PBAC scores were less than baseline, the greatest reductions being seen at 12 months for both treatments. When the median PBAC for the LNG-IUS (26 (0-68)) was significantly different to the median PBAC for the TBA cohort (62 (0-142)) P < 0.001. Irregular bleeding problems were the most common reason for discontinuation of the LNG-IUS and resulted in more women (39.8%) seeking other treatment by two years than the TBA (23.1%) (P < 0.05) and more undergoing a hysterectomy (20.7% vs 13.3%, respectively) (p > 0.05). Patient acceptability of the LNG-IUS and TBA was similar at 12 and 24 months in terms of their perceived satisfaction of effect on menorrhagia. CONCLUSIONS: Both TBA and LNG-IUS achieved significant decreases in PBAC scores, with those for the LNG-IUS being significantly greater at 12 months. However, prolonged days of bleeding resulted in fewer women continuing with the LNG-IUS at two years.     

Nonsecular Medical Anthropology

ABSTRACT

A nonsecular medical anthropology insists on the ways medicine and science have constituted ‘the secular’ itself through the ‘secular self’—how medical knowing has been used to craft the secular political subject. As James Boon noted, too often in social theory, “religion gets safely tucked away—restricted theoretically to ‘meaning’ rather than power” (1998:245). The authors of the six articles in this special issue ‘untuck’ religiosity from within the norms and numbers of medicine itself, and examine how ‘secular’ medicine has relied on religious traditions to produce political secularity. These articles demonstrate that ‘secular’ medicine relies on religious others whose exclusion bespeaks latent religious commitments of citizenship in the modern political realm of health.