ELLIPSE Study: A Phase 1 study evaluating the tolerance of bevacizumab nasal spray in the treatment of epistaxis in hereditary hemorrhagic telangiectasia

Background: Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited genetic vascular disorder in which epistaxis is the most frequent manifestation, responsible for high morbidity. Management of this symptom has no standard, and local treatments are often aggressive. Their efficacy is variable and has not been proven. Anti-angiogenic drugs, such as bevacizumab, are a new treatment strategy. Its systemic administration in patients with HHT improves liver damage-related symptoms and epistaxis. To limit the systemic adverse effects of bevacizumab and to ease administration, a local administration seems suitable. Primary objective: To evaluate the tolerance of increasing doses of bevacizumab administered as a nasal spray in patients with HHT-related epistaxis. Secondary objectives were to study the bioavailability and efficacy of bevacizumab against epistaxis when given as a nasal spray. Methodology: Phase 1, randomized, double-blind, placebo-controlled, monocentric study performed sequentially (dose escalation) on 5 groups of 8 patients. Each group was made up of 6 verum and 2 placebos. Five increasing doses of bevacizumab nasal spray (25 mg/mL) were evaluated: 12.5, 25, 50, 75 and 100 mg. Results: A total of 40 patients were included between October 2011 and October 2012. Bevacizumab nasal spray was well tolerated in all patients and the drug was not detected in their serum. No dose limiting toxicity was observed. No efficacy was observed at any dose in this study. Conclusion: Based on these results, bevacizumab nasal spray is a safe treatment of epistaxis in HHT. However, a randomized Phase 2 study is needed to determine its efficacy. Trial Registration: ClinicalTrials.gov Identifier #{"type":"clinical-trial","attrs":{"text":"NCT01507480","term_id":"NCT01507480"}}NCT01507480     

恶性疟原虫抗原表位的亚单位疫苗与DNA疫苗的联合免疫

构建了含有恶性疟原虫抗原基因 ( AWTE)的真核表达质粒 p CMV- AWTE,以及能在大肠杆菌中得到分泌性表达的原核表达质粒 p MC0 5 ,表达的蛋白 AWTE保持了疟原虫抗原的抗原性。将 p CMV- AWTE以及 AWTE两者混合各 1 0μg鼻腔免疫小鼠 ,一次后诱导机体产生了较高水平的体液免疫及细胞免疫     

Nasal Discs and the Vital Rates of Lesser Scaup

Nasal discs have been used to identify ducks in studies of survival and reproduction. To date, there has not been a comprehensive assessment of nasal-disc effects on the vital rates of wild ducks. We applied nasal discs to 603 juvenile and 784 adult lesser scaup (Aythya affinis) females from a population breeding in southwest Montana, USA, and released 1,399 juvenile and 71 adult females wearing only metal leg bands between June 2005 and September 2016. Using resighting, recapture, and hunter-recovery data collected from those individuals, we estimated survival and recovery probability with multistate capture-recapture models in Program MARK. We also assessed if recovery distance from our study site and pre-breeding and brood-rearing body condition were diminished for females wearing nasal discs. Model-averaged survival probabilities were 0.231 ± 0.035 (SE) for juveniles and 0.482 ± 0.019 for adults released with nasal discs. Survival was 1.8–3.4 times higher for females released with metal leg bands when compared to those released with nasal discs; survival of these juveniles was 0.433 ± 0.049 and 0.693 ± 0.039 for adults. We did not find evidence for recovery probability or recovery distance varying between females that wore nasal discs and those that did not. During the pre-breeding and brood-rearing seasons, we did not find females wearing nasal discs to be in lower body condition when compared to unmarked females. Our comprehensive assessment of nasal discs on wild lesser scaup suggests that survival probabilities estimated from nasal-marked study populations should be cautiously interpreted as minimum estimates. © 2021 The Wildlife Society.     

经鼻加温加湿高流量吸氧对重症肺炎伴呼吸衰竭患儿血气指标、肺功能及细胞因子水平的影响

摘要 目的：观察经鼻加温加湿高流量吸氧（HFNC）对重症肺炎伴呼吸衰竭患儿血气指标、肺功能及细胞因子水平的影响。方法：选取南京医科大学附属儿童医院2020年3月~2022年3月期间收治的86例重症肺炎伴呼吸衰竭患儿,按照随机数字表法分为经鼻持续气道正压通气（nCPAP）组和HFNC组,各为43例。对比两组临床相关指标、血气指标、肺功能及细胞因子水平,同时观察两组镇静剂使用、预后及并发症发生情况。结果：HFNC组的机械通气时间、咳嗽缓解时间、肺部啰音消失时间、入住儿童重症监护室（PICU）时间均短于nCPAP组（P<0.05）。两组患儿治疗后心率（HR）升高,呼吸频率（RR）下降,且HFNC组的变化大于nCPAP组（P<0.05）。两组患儿治疗后pH值、血氧分压（PO₂）、血氧饱和度（SpO₂）、氧合指数（OI）均升高,且HFNC组高于nCPAP组（P<0.05）。两组患儿治疗后用力肺活量（FVC）、1s用力呼气容积（FEV1）、用力呼气时最高呼气流速（PEF）升高,且HFNC组高于nCPAP组（P<0.05）。两组患儿治疗后降钙素原（PCT）、白细胞介素（IL-6）和肿瘤坏死因子（TNF-α）下降,且HFNC组低于nCPAP组（P<0.05）。HFNC组镇静剂使用、再住院例数均少于nCPAP组（P<0.05）。两组死亡例数、并发症发生率组间对比未见统计学差异（P>0.05）。结论：HFNC可有效缓解重症肺炎伴呼吸衰竭患儿的临床症状,改善血气指标、肺功能及细胞因子水平。     

难辨认孢子丝菌病临床分析

探讨孢子丝菌病不典型的临床表现.孢子丝菌病是皮肤科常见的一种深部真菌病,典型的皮肤科特征是慢性肉芽肿、溃疡性损害、炎性结节等.而部分孢子丝菌病的患者由于各种各样的原因导致皮损丧失特征性临床表现,给皮肤科医生尤其是临床经验尚不丰富的年轻医师于该病的诊断带来了一定的困难.本文所讨论的8例患者均为就诊于我科门诊并已确诊为孢子丝菌病病例,皮损与典型的孢子丝菌病皮损表现不相符,希望皮肤科医师在以后的临床工作中遇到一些不典型皮损但是综合患者病史、生活环境、诊治过程等情况可考虑到此种疾病,及时给予明确的诊断,使患者能够得到及时、有效的治疗.     

A study on the potential-dependence of proton block of sodium channels

Ionic currents through sodium channels in nodal membranes were measured under voltage clamp conditions both at normal and at low (4.8–4.9) external solution pH. The measurements of so-called ‘instantaneous’ currents were used to distinguish between the proton blockage in open channels and the influence of low pH on channel gating processes. It is shown that the amount of the proton blockage in open channels decreases as membrane potential becomes more positive. This result suggests that at least one of the acid groups accessible from the outside is located within the conducting pore. The influence of the other group(s) on the degree of potential-dependence of proton blockage is discussed.     

A new approach to pharmacological effects on ciliary beat frequency in cell cultures—exemplary measurements under Pelargonium sidoidesextract (EPs 7630)

The ciliary beat frequency (CBF) is an important parameter of the defence mechanism of the mucociliary system. We present a new method to determine pharmacological effects on CBF in vitro. Ciliated cell cultures of human nasal epithelium were obtained from partial resection of hyperplastic inferior turbinates in rhinosurgery. An adherent monolayer culture of ciliated cells was present after 10 days in vitro. This study exemplary examines, if a special extract from the roots of Pelargonium sidoides (EPs 7630) has an effect on the CBF in vitro. The influence of three concentrations of the extract (1, 30, 100 microg/ml) was tested. EPs 7630 significantly and concentration-dependently increased CBF to 123% at 30 microg/ml and to 133% at 100 microg/ml compared to the equilibration phase (100%). After rinsing with extract-free medium the CBF of cultured cells returned to nearly the normal range. In future, drug manipulation of the CBF by local application of rhinologics could be a new therapeutical concept in the treatment of upper airway diseases.     

Premaxillary-maxillary suture fusion and anterior nasal tubercle morphology in the chimpanzee

The anterior nasal spine (ANS) is considered by some to be a unique characteristic of modern humans; however, it has been reported to occur in chimpanzees. Among human populations, ANS size correlates with facial prognathism and timing of premaxillary-maxillary sutural fusion, which may have implications for models of midfacial growth. To investigate these questions, skulls from 55 chimpanzees (Pan troglodytes) (29 male, 26 female), ranging in age from infants to adults, were examined. None of the 55 specimens examined had a true ANS, but a number of specimens exhibited raised anterior nasal prominences or tubercles (ANT) on the nasal surface of the premaxilla. Female specimens had significantly (P less than .05) more ANTs and more extensive fusion of both the palatal and facial components of the suture than did the male specimens. Results from the present study document the presence of an ANT in a sample of chimpanzee crania and are consonant with associations predicted by a septal-traction model of midfacial growth.     

Influence of Chironomus plumosus larvae on ammonium flux and denitrification (measured by the acetylene blockage- and the isotope pairing-technique) in eutrophic lake sediment

Bythotrephes invaded Harp Lake, Ontario, Canada, in the early 1990s. Here we describe seasonal changes in the size, abundance and life history of the invader. The weight of Bythotrephes could be accurately estimated (r² =0.90) from the length of its body and the state of development of its brood, but substantial (22%) corrections for shrinkage in sugarformalin were required. The seasonality of the size and abundance of Bythotrephes was apparently regulated by the interaction of fish predation, temperature-mediated growth, the availability of the invader's prey, and switches in its reproductive biology. The vernal increase in the growth of the Bythotrephes population lagged behind increases in water temperature and abundances of preferred prey, most probably because of predation by lake herring (Coregonus artedi). Bythotrephes abundance increased rapidly in early July; however, the population maximum was brief. After the abundance of their preferred prey crashed in mid-July, Bythotrephes body size declined, and adult females switched from parthenogenic to resting egg production. Population size declined in consequence. In the summer, female Bythotrephes committed most of their energy to growth between instar I and II, but to egg production for instars II and III. The biology of the Harp Lake population differed from that observed in other recently invaded lakes in several ways – the lag in population growth in the spring, the small change in body size between instars II and III, the decline in body size in August, and the co-incident switch by mature females to resting egg production. These inter-lake differences in biology indicate we have more to learn about Bythotrephes before we can predict its influence on the inland lakes of North America.