The role of cardiopulmonary exercise testing in evaluating children with exercise induced dyspnoea

Exercise induced dyspnoea (EID) is a common manifestation in children and adolescents. Although EID is commonly attributed to exercise induced bronchoconstriction, several conditions other than asthma can cause EID in otherwise healthy children and adolescents. Cardiopulmonary exercise testing (CPET) offers a non-invasive comprehensive assessment of the cardiovascular, ventilatory and metabolic responses to exercise and is a powerful diagnostic and prognostic tool. CPET is a reproducible, non-invasive form of testing that allows for comparison against age- and gender-specific norms. CPET can assess the child’s exercise capacity, determine the limiting factors associated with this, and be used to prescribe individualised interventions. EID can occur due to asthma, exercise induced laryngeal obstruction, breathing pattern disorders, chest wall restriction and cardiovascular pathology among other causes. Differentiating between these varied causes is important if effective therapy is to be initiated and quality of life improved in subjects with EID.     

单眼散光弱视儿童对比敏感度的研究

目的：分析探讨单眼散光弱视患儿对比敏感度（CS）视功能的受损特点。方法：对正常儿童组36例、单眼散光弱视组34例、单眼非散光弱视组33例,共103例,用静态F.A.C.T图表和计算机Gabor斑CS检查程序分别检查患儿对侧眼、弱视眼及90°和180°两主子午线方向上的对比敏感度。结果：①单眼散光弱视组和单眼非散光弱视组的对侧眼、弱视眼的CS值在所有空间频率均较正常组的CS降低（P〈0.05）,表现为中、高空间频率区CS的明显受损（P〈0.01）。②单眼散光弱视组的弱视眼在90°和180°两主子午线方向上的对比敏感度有显著差异（P〈0.01）。结论：弱视儿童的对侧眼不正常。用计算机Gabor斑检查可以了解弱视散光儿童不同子午线上的CS存在的差异,明确定位弱子午线,并可以针对子午线性弱视,进一步开展知觉学习的治疗。     

Bullous pemphigoid induced by vildagliptin: a report of three cases

To report three cases of bullous pemphigoid in patients treated with vildagliptin. Case 1: An 86‐year‐old woman presented with bullous pemphigoid after 1 month of treatment with vildagliptin and metformin. After introduction of clobetasol, the symptoms resolved although vildagliptin was continued. However, the skin lesions reappeared 3 months later. Sustained remission was achieved only after definitive withdrawal of vildagliptin. Case 2: A 79‐year‐old man presented with bullous pemphigoid after 37‐month treatment with gliclazide, vildagliptin and metformin. The disease at first responded to clobetasol but 3 months later the lesions reappeared. They finally regressed when the gliptin was discontinued. Case 3: A 77‐year‐old woman, treated with gliclazide and vildagliptin for 26 months, presented with bullous pemphigoid, which responded well to discontinuation of the gliptin and topical clobetasol. Gliptins are new molecules for treatment of type 2 diabetes mellitus, which have been suspected of implication in bullous pemphigoid. Such cases have been described in the literature (seven with vildagliptin and three with sitagliptin). In nine of these cases, the gliptin was associated with metformin, but the latter had never been considered responsible. The mechanism implicated in the development of bullous pemphigoid has not yet been clearly identified, but may involve a modified immune response or alteration of the antigenic properties of the epidermal basement membrane. These reports support the risk of bullous pemphigoid in patients exposed to gliptins.     

肺纤维化患者血清及诱导痰肺表面活性蛋白水平测定及意义

目的检测特发性肺纤维化患者急性加重期血清及诱导痰肺表面活性蛋白D(SP-D)水平并探讨其临床治疗意义。方法选择特发性肺纤维化患者急性加重期住院治疗26例,分别收集纳入患者入院时及治疗后病情缓解血清及诱导痰液标本,采用酶联免疫吸附试验检测血清及诱导痰SP-D水平。选择42例健康人群作为对照组。结果特发性肺纤维化患者急性加重期及病情缓解期血清SP-D平均水平分别为(196±82)、(125±69)ng/mL,健康对照组为(96±47)ng/mL,诱导痰SP-D平均水平为(153±71)、(106±64)ng/mL,急性加重期与缓解期及健康对照组SP-D水平比较差异有统计学意义(P0.05)。结论血清SP-D检测可作为特发性肺纤维化患者急性加重诊断的生物学指标。     

In Vivo Evaluation of a Closed Loop Monitoring Strategy for Induced Paralysis

Objective. Reliable closed loop infusion systems for regulating paralysis level can be a great convenience to the anesthesiologists in automating their task. This paper describes the in vivo performance evaluation of a self-tuning controller that is designed to accommodate large varations in patient drug sensitivity, drug action delays and environmental interfering noise. Methods. The infusion system was evaluated in six adult mongrel dogs. Following the manual induction of paralysis by an anesthesiologist, the controller regulated the infusion of vecuronium to maintain a desired level of paralysis. The integrated EMG response of the hypothenar muscle to a train-of-four stimulation of the ulnar nerve quantified the depth of paralysis. The controller's robustness was tested by contaminating the sensed twitch signal with electrocautery noise and electrode disconnection. Results. The controller reached the initial level of paralysis of 100% in about 4.0 minutes and arrived at the desired level of 90% with an overshoot of 6.38% (±6.82). It maintained the desired level of paralysis with a 2.04% (±1.20) mean offset at 90% and 0.4% (±0.5) mean offset at 80% steady state level, respectively. The mean infusion rate to sustain 90% and 80% paralysis were 2.70 (±2.05) and 2.15 (±2.57) ((mg/kg)/min), respectively. Conclusions. The system adapted to a large variation in the sample subject drug sensitivity. It remained stable despite large amplitude disturbances and maintained the paralysis at the desired level following the removal of the disturbances.     

Exercise‐induced wheeze: Fraction of exhaled nitric oxide‐directed management

Background and objective: Exercise‐induced wheeze (EIW) is common. Several treatment options exist. Patients with low fraction of exhaled nitric oxide (F_ENO) are unlikely to be steroid‐responsive and might benefit from non‐steroidal therapies. We assessed: the efficacy of cromoglycate, formoterol and montelukast in patients with EIW and low F_ENO (<35 ppb) in a randomized cross‐over trial, and the efficacy of inhaled corticosteroid in a high F_ENO (>35 ppb) group. Methods: Patients had EIW and airway hyperresponsiveness (AHR) to mannitol and/or exercise. Those with low F_ENO (n = 19) received cromoglycate (20 mg inh. bd + before challenge tests), formoterol (12 µg inh. bd + before challenge tests) and montelukast (10 mg p.o. od), each for 2 weeks. Those with high F_ENO (n = 20) took inhaled fluticasone (500 µg) daily for 4 weeks. Primary end‐points were: 50% reduction in maximum FEV₁ %fall (clinical protection) and decrease in AHR to mannitol. Results: In patients with low F_ENO, cromoglycate, formoterol and montelukast significantly decreased AHR to mannitol in 63%, 61% and 47% of patients, respectively. In this group, the magnitude of exercise‐induced bronchoconstriction (EIB) was significantly reduced with montelukast and formoterol; between‐treatment differences were not significant. Of 6/19 with low F_ENO and EIB, protection occurred in 67% (cromoglycate), 83% (formoterol) and 50% (montelukast), respectively. In the high F_ENO group, AHR to mannitol and EIB decreased significantly with fluticasone (P < 0.001, P = 0.005, respectively), and protection occurred in 7/8 (88%) with EIB. Conclusions: In patients with EIW and low F_ENO, the number of ‘responders’ to cromoglycate, formoterol and montelukast was similar. In a high F_ENO population the response to inhaled corticosteroid was highly significant and comparable to previous studies.     

A ferric chloride induced arterial injury model used as haemostatic effect model

Summary.  A number of experimental bleeding models have been applied to animal models of haemophilia in order to evaluate the acute haemostatic effect of procoagulant compounds. In contrast, in vivo thrombosis models (including the FeCl₃ induced injury model) have mainly been used to study antithrombotic pharmacological intervention. However, as there are limitations to existing bleeding models and as new recombinant FVIII, FIX, and FVIIa variants with increased and prolonged activity are generated there is an increasing need for new and optimized in vivo animal models for testing the efficacy of these haemostatic drug candidates. This led us to look at existing thrombosis models in a new perspective. We have studied the effect of a FeCl₃ induced arterial injury in both F8-KO and F9-KO mice using optimized conditions where exposure to FeCl₃ induces occlusion within 4.2 ± 0.2 min in wild type mice with a normal coagulation system. In contrast, no occlusion was observed in haemophilic mice providing a therapeutic window in the model making it suitable for pharmacological testing of therapeutic intervention. We demonstrate that replacement therapy with a clinical relevant dose of rFVIII (Advate® 20–80 U kg⁻¹) and rFIX [(0.75 mg kg⁻¹ BeneFIX®) ∼50 IU kg⁻¹] restored coagulation and normalized the time to occlusion following FeCl₃ induced injury in F8-KO mice and restored coagulation and nearly normalized the time to occlusion in F9-KO mice. In conclusion, we have demonstrated that under optimized conditions the FeCl₃ induced arterial injury model provides a therapeutic window that makes it an useful effect model for evaluation of the haemostatic potential of procoagulant drugs.     

静脉水化联合碱化预防高危患者对比剂诱发肾病的作用

目的探讨静脉水化联合碱化治疗预防高危患者对比剂诱发肾病的临床效果。方法选择行经皮冠状动脉介入诊疗,对比剂肾病发生风险评分系统评分≥11分的患者80例,治疗组40例,给予0.9%氯化钠溶液1mL·kg-1·h-1的静脉注射12h,联合30mL碳酸氢钠快速静脉注射;对照组40例,仅给予0.9%氯化钠溶液1mL·kg-1·h-1静脉注射12h的水化治疗,比较两组治疗后生化检验结果和对比剂诱发肾病发生率。结果治疗组介入治疗后尿pH值及肾小球率过滤比对照组高,血清肌酐浓度比对照组低,差异有统计学意义[7.11±0.72vs.5.46±0.61,P0.05;37.91%±7.48%vs.30.11%±7.54%,P0.05;(1.40±0.19)mg/Lvs.(1.69±0.22)mg/L,P0.05]。治疗组对比剂诱发肾病发生2例,占5%(2/40),对照组发生8例,占20%(8/40),两者比较,差异有统计学意义(P0.05)。结论静脉水化联合碱化治疗可更有效地防止高危患者经皮冠状动脉介入治疗后对比剂诱发肾病的发生。     

哮喘患者呼出气冷凝液及诱导痰中超敏C反应蛋白相关性研究

目的探讨哮喘患者呼出气冷凝液和诱导痰中超敏C反应蛋白含量相关性。方法随机选择60位哮喘患者,分别在急性期和缓解期检测超敏C反应蛋白在呼出气冷凝液(exhaled breath condensate,EBC)及诱导痰(induced sputum,IS)中含量,研究两者相关性。结果急性期哮喘患者EBC中hs-CRP的含量(重度组0.32±0.02 mg/L,中度组0.28±0.04 mg/L)均高于缓解期含量(重度组0.20±0.04 mg/L,中度组0.18±0.02 mg/L;均P0.05)及健康对照组0.08±0.01 mg/L(P0.05);急性期哮喘患者IS中hs-CRP含量(重度组2.7±0.1 mg/L,中度组2.0±0.16 mg/L)也均高于缓解期(重度组1.2±0.15 mg/L,中度组1.4±0.12 mg/L;均P0.05)及健康对照组0.4±0.05 mg/L(P0.05);中、重度组EBC和诱导痰中hs-CRP含量在治疗前、后均具有显著正相关性。结论哮喘患者EBC中超敏C反应蛋白检测可用于评价气道炎症水平,其临床价值可与诱导痰中超敏C反应蛋白检测相媲美。