The effect of fentanyl coadministration on sneezing during nasal local anesthetic injection for plastic surgery under propofol-based intravenous sedation: A retrospective case-controlled study.

BACKGROUND: Injection of local anesthetic for surgical procedures on the skin of the nose under intravenous sedation can provoke sneezing, which can be hazardous to the patient, surgeon, and other staff. Yet, there is little information on factors that influence sneezing under these circumstances. The aim of our study was to investigate the influence of adding fentanyl to propofol-based sedation on the incidence of sneezing during local anesthetic injection on the nose for plastic surgery. METHODS: A retrospective chart review was conducted on 32 patients who had undergone plastic surgery procedures on the nose under local anesthetic with intravenous sedation. RESULTS: Twenty-two patients received fentanyl in addition to propofol. Of these, only two patients sneezed (9.1 percent). In contrast, nine out of the 10 patients who did not receive fentanyl sneezed (90 percent). This included two patients who had received midazolam and propofol. CONCLUSIONS: These findings indicate that there was a high rate of sneezing during nasal local anesthetic injections performed under propofol-based intravenous sedation, unless the sedation was supplemented with fentanyl. We now recommend the coadministration of fentanyl during nasal local anesthetic injections under propofol-based sedation. Further studies are required to determine whether this observation is related to the depth of sedation alone, or whether the reduction in sneezing is related to the coadministration of an opioid. Further studies should also investigate potential side effects of coadministration of fentanyl or other opioids.

Potent monoclonal antibody-mediated neutralization of a divergent Hendra virus variant.

Hendra virus (HeV) and Nipah virus (NiV) are deadly zoonotic Henipaviruses (HNVs) responsible for recurrent outbreaks in humans and domestic species of highly fatal (50 to 95%) disease. A HeV variant (HeV-g2) of unprecedented genetic divergence has been identified in two fatally diseased horses, and in two flying fox species in regions of Australia not previously considered at risk for HeV spillover. Given the HeV-g2 divergence from HeV while retaining equivalent pathogenicity and spillover potential, understanding receptor usage and antigenic properties is urgently required to guide One Health biosecurity. Here, we show that the HeV-g2 G glycoprotein shares a conserved receptor tropism with prototypic HeV and that a panel of monoclonal antibodies recognizing the G and F glycoproteins potently neutralizes HeV-g2­ and HeV G/F­mediated entry into cells. We determined a crystal structure of the Fab fragment of the hAH1.3 antibody bound to the HeV G head domain, revealing an antigenic site associated with potent cross-neutralization of both HeV-g2 and HeV. Structure-guided formulation of a tetravalent monoclonal antibody (mAb) mixture, targeting four distinct G head antigenic sites, results in potent neutralization of HeV and HeV-g2 and delineates a path forward for implementing multivalent mAb combinations for postexposure treatment of HNV infections.

The anti-inflammatory selective melanocortin receptor subtype 4 agonist, RO27-3225, fails to prevent acoustic trauma-induced tinnitus in rats.

In preliminary studies we have observed a massive microglial activation in the cochlear nucleus following acoustic trauma-induced tinnitus in rats, which suggests that inflammatory responses within the central auditory system may be involved in the development and maintenance of tinnitus. Recently, the anti-inflammatory properties of melanocortins (MCs), have gained increasing interest in pharmacology due to their promising therapeutic potential in the treatment of inflammatory-mediated diseases. Among the five subtypes of the MC receptor, MC3 and MC4 receptors are the predominant brain receptors and are thought to play an important role in brain inflammation and neuroprotection. Importantly, MC4 receptors have been found in the mouse and rat central auditory systems. In this study we investigated whether the MC4 receptor agonist, RO27-3225, injected s.c at a dose of 90 or 180µg/kg, 30min before acoustic trauma and then every 12h for 10 days, could prevent the development of acoustic trauma-induced tinnitus in rats, using a conditioned behavioural suppression model. Although evidence of tinnitus developed in the exposed-vehicle group compared to the sham-vehicle group (P≤0.03), in response to a 32kHz tone, there were no significant drug effects from treatment with RO27-3225, indicating that it did not confer any protection against the development of tinnitus in this animal model. This result suggests that the anti-inflammatory effects of MC4 receptor agonists may not be sufficient to prevent tinnitus.

Cannabis, tobacco smoking, and lung function: a cross-sectional observational study in a general practice population.

BACKGROUND: Health concerns around cannabis use have focused on the potential relationship with psychosis but the effect of cannabis smoking on respiratory health has received less attention. AIM: To investigate the association between tobacco-only smoking compared with tobacco plus cannabis smoking and adverse outcomes in respiratory health and lung function. DESIGN AND SETTING: The design was cross-sectional with two groups recruited: cigarette smokers with tobacco pack-years; cannabis smokers with cannabis joint-years. Recruitment occurred in a general practice in Scotland with 12 500 patients. METHOD: Exposures measured were tobacco smoking (pack-years) and cannabis smoking (joint-years). Cannabis type (resin, herbal, or both) was recorded by self-report. Respiratory symptoms were recorded using NHANES and MRC questionnaires. Lung function was measured by spirometry (FEV1/FVC ratio). RESULTS: Participants consisted of 500 individuals (242 males). Mean age of tobacco-only smokers was 45 years; median tobacco exposure was 25 pack-years. Mean age of cannabis and tobacco smokers was 37 years; median tobacco exposure was 19 pack-years, rising to 22.5 when tobacco smoked with cannabis. Although tobacco and cannabis use were associated with increased reporting of respiratory symptoms, this was higher among those who also smoked cannabis. Both tobacco and cannabis users had evidence of impaired lung function but, in fully adjusted analyses, each additional joint-year of cannabis use was associated with a 0.3% (95% confidence interval = 0.0 to 0.5) increase in prevalence of chronic obstructive pulmonary disease. CONCLUSION: In adults who predominantly smoked resin cannabis mixed with tobacco, additional adverse effects were observed on respiratory health relating to cannabis use.

COPD causation and workplace exposures: an assessment of agreement among expert clinical raters.

BACKGROUND: Although occupational exposure is a known risk factor for Chronic Obstructive Pulmonary Disease (COPD), it is difficult to identify specific occupational contributors to COPD at the individual level to guide COPD prevention or for compensation. The aim of this study was to gain an understanding of how different expert clinicians attribute likely causation in COPD. METHODS: Ten COPD experts and nine occupational lung disease experts assigned occupational contribution ratings to fifteen hypothetical cases of COPD with varying combinations of occupational and smoking exposures. Participants rated the cause of COPD as the percentage contribution to the overall attribution of disease for smoking, occupational exposures and other causes. RESULTS: Increasing pack-years of tobacco smoking was associated with significantly decreased proportional occupational causation ratings. Increasing weighted occupational exposure was associated with increased occupational causation ratings by 0.28% per unit change. Expert background also contributed significantly to the proportion of occupational causation rated, with COPD experts rating on average a 9.4% greater proportion of occupational causation per case. CONCLUSION: Our findings support the notion that respiratory physicians are able to assign attribution to different sources of causation in COPD, taking into account both smoking and occupational histories. The recommendations on whether to continue to work in the same job also differ, the COPD experts being more likely to recommend change of work rather than change of work practice.

Steroidogenic acute regulatory protein transcript abundance in the eel, Anguilla australis: changes during the induced reproductive cycle and effects of follicle-stimulating hormone during previtellogenesis.

Steroidogenic acute regulatory protein (StAR) mRNA levels in the eel ovary were assayed by quantitative PCR and related to plasma steroid levels throughout oogenesis in order to shed light on the previously considered 'aberrant' prematurational increase in plasma levels of estradiol-17ß (E2). Total ovarian StAR transcript abundance mirrored circulating levels of E2, but not of 11-ketotestosterone (11KT). The study was complemented by evaluation of in vitro effects of follicle-stimulating hormone (FSH) on ovarian StAR transcript abundance and on short-term ('acute') radiolabelled pregnenolone-supported steroid metabolism by ovarian fragments to understand how the production of steroids during previtellogenic oocyte growth is regulated. We observed a significant effect of FSH on StAR mRNA levels within 24h of incubation, but these were no longer evident by 4 days of culture. Unexpectedly, FSH had no effect on substrate-supported steroidogenesis, as comparable yields of steroid products were detected using semi-quantitative HPLC and scintillation counting. We conclude that the eel ovarian follicle can respond to FSH from a very early stage of development (early oil droplet stage) by increasing StAR mRNA levels, but that there is no evidence for acute effects of FSH on bioactive steroid production downstream of cytochrome P450 side-chain cleavage. Furthermore, the prematurational increase in StAR mRNA in vivo is in keeping with general teleost models and is likely to be a 'normal' response to reaching advanced stages of development.

The alpha subunit of eukaryotic initiation factor 2B (eIF2B) is required for eIF2-mediated translational suppression of vesicular stomatitis virus.

Eukaryotic translation initiation factor 2B (eIF2B) is a heteropentameric guanine nucleotide exchange factor that converts protein synthesis initiation factor 2 (eIF2) from a GDP-bound form to the active eIF2-GTP complex. Cellular stress can repress translation initiation by activating kinases capable of phosphorylating the alpha subunit of eIF2 (eIF2α), which sequesters eIF2B to prevent exchange activity. Previously, we demonstrated that tumor cells are sensitive to viral replication, possibly due to the occurrence of defects in eIF2B that overcome the inhibitory effects of eIF2α phosphorylation. To extend this analysis, we have investigated the importance of eIF2Bα function and report that this subunit can functionally substitute for its counterpart, GCN3, in yeast. In addition, a variant of mammalian eIF2Bα harboring a point mutation (T41A) was able overcome translational inhibition invoked by amino acid depravation, which activates Saccharomyces cerevisiae GCN2 to phosphorylate the yeast eIF2α homolog SUI2. Significantly, we also demonstrate that the loss of eIF2Bα, or the expression of the T41A variant in mammalian cells, is sufficient to neutralize the consequences of eIF2α phosphorylation and render normal cells susceptible to virus infection. Our data emphasize the importance of eIF2Bα in mediating the eIF2 kinase translation-inhibitory activity and may provide insight into the complex nature of viral oncolysis.

Endometrial ablation in England--coming of age? An examination of hospital episode statistics 1989/1990 to 2004/2005.

OBJECTIVE: To observe numbers and trends in endometrial ablation performed for heavy menstrual bleeding (HMB) in England. DESIGN: Examination of National Health Service (NHS) Hospital Episode Statistics. Number of hysterectomies and endometrial ablation procedures performed each year from 1989/1990 to 2004/2005. RESULTS: Hysteroscopic endometrial ablation peaked in 1992/1993 before falling significantly to a low in 1997/1998. Since then the total number of procedures has increased by 250% and of the 9701 endometrial ablations performed in 2004/2005 over half (5457) are now second-generation techniques. CONCLUSIONS: Endometrial ablation is now more common than hysterectomy for heavy menstrual bleeding and second-generation methods are now more commonly performed than hysteroscopic endometrial ablation. There is every indication that endometrial ablation will continue to increase in practice in England.