急性早幼粒细胞白血病化疗后弥漫性肺泡出血一例并文献复习

目的:总结一例急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)诱导化疗后合并弥漫性肺泡出血(diffuse alveolar hemorrhage,DAH)的诊治体会,提高对APL并发DAH的认识。方法:报道一例APL患者经维A酸(all-trans retinoic acid,ATRA)联合去甲氧柔红霉素化疗后并发DAH的症状和体征、实验室检查结果、治疗措施。结果:该患者在ATRA化疗后出现发热、咳嗽、咯血、呼吸困难、双肺湿性啰音、低氧血症,X线胸片示弥漫性浸润影,诊断DAH,立即给予激素、高流量吸氧及强有力的抗感染治疗后病情好转。结论:DAH为恶性血液病化疗后少见却易致命的并发症,早期诊断、及时激素治疗可有效提高患者生存率,改善预后。     

注射低分子肝素致皮下出血的原因分析

目的　分析低分肝素不同注射方法致皮下出血的原因。方法　应用“2种方法”的比较 ,观察皮下出血的例次。结果　治疗组 35 0例次和改进组 36 4例次皮下出血率比较 ,P <0 0 1,差异具有统计学意义。结论　采用特殊的皮下注射方法 ,可以显著降低皮下出血的发生率。     

芬太尼与舒芬太尼用于全麻苏醒期躁动的比较

目的:比较芬太尼、舒芬太尼经鼻腔给药和静脉注射用于治疗瑞芬太尼复合全麻苏醒期烦躁的效果.方法:选择瑞芬太尼复合全麻下行腹腔镜胆囊切除术出现苏醒期躁动的患者160例,随机均分为4个组:芬太尼经鼻腔给药组(A组),芬太尼静脉注射组(B组),舒芬太尼经鼻腔给药组(C组),舒芬太尼静脉注射组(D组),于停止泵注瑞芬太尼前5 m...     

Diffuse Pulmonary Hemorrhage after Streptokinase Administration for Acute Myocardial Infarction

Fibrinolytic drug therapy has markedly reduced morbidity and mortality from acute myocardial infarction. As with any other drug therapy, however, benefits are maximal when patients at higher risk for complications can be identified and treatment decisions modified to reduce the chance of adverse events. Streptokinase, a commonly used and inexpensive thrombolytic, is known to cause both bleeding and immunologic complications, and coexistent conditions predisposing to either are considered relative or absolute contraindications to its use. We report an unusual case of immune-mediated diffuse pulmonary hemorrhage following streptokinase administration for acute myocardial infarction in a patient with pulmonary infection and concurrent cutaneous infection. We propose that these infections constitute additional risk factors and may be used to identify patients at higher risk of this complication from streptokinase.     

经鼻靶向给予降钙素基因相关肽对蛛网膜下腔出血后海马区细胞凋亡的影响

目的 探讨经鼻靶向中枢给予降钙素基因相关肽（calcitonin gene-related peptide,CGRP）对海马细胞凋亡和脑损伤的作用。方法 枕大池2次注血法制作蛛网膜下腔出血（subarach-noid hemorrhage,SAH）模型。将48只♂ Wistar大鼠随机分为正常对照组、SAH组、生理盐水（NS）+SAH组（经鼻给予NS）、CGRP+SAH组（经鼻给予CGRP）,每组12只。于第2次注血3 d后,采用免疫荧光技术检测海马组织中bcl-2和caspase-3的蛋白表达。结果 免疫荧光染色显示bcl-2和caspase-3在正常对照组大鼠海马组织中只观察到极少量表达;SAH组、NS+SAH组bcl-2和caspase-3蛋白表达明显增多;与SAH组和NS+SAH组相比较,经鼻给予CGRP治疗后,bcl-2表达显著升高,caspase-3表达水平显著降低,差异均具有统计学意义（P<0.01）。结论 CGRP经鼻靶向中枢给药能有效抑制SAH大鼠海马组织细胞凋亡,对脑损伤具有显著保护作用。     

三组方案治疗肝硬化上消化道出血的效果分析

目的 评价3组方案治疗肝硬化上消化道出血的疗效、不良反应及成本-效果.方法 对167例肝硬化上消化道出血患者在常规治疗基础上,随机分为3组,分别使用不同的治疗方案(Ⅰ组:小剂量垂体后叶素 硝酸甘油 法莫替丁;Ⅱ组:奥曲肽 法莫替丁;Ⅲ组:奥曲肽 奥美拉唑).现察其疗效及不良反应,并运用药物经济学成本-效果分析方法进行回顾性分析.结果 3组总有效率分别为90.7%,93.0%和98.2%,其差异无显著性意义(P＞0.05).Ⅰ组中13例有轻度副作用,Ⅱ组、Ⅲ组无副作用.3组成本-效果比分别为26.84,14.14和61.47,Ⅰ组明显优于Ⅱ组、Ⅲ组(P＜0.05).结论 3组方案均为肝硬化上消化道出血安全、有效的治疗方法,可根据患者具体情况灵活选用.     

Risk Factors for Androgen Deficiency with Daily Opioid Use; Co-trimoxazole and Sudden Cardiac Death in Patients Receiving ACE Inhibitors; Clindamycin-Induced Myelosuppression; Apixaban-Induced Diffuse Alveolar Hemorrhage; DRESS Syndrome Induced by Allopurinol

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: ude.elpmet@onacnamm). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.     

Intranasal formulations: promising strategy to deliver vaccines

Introduction: The emergence of new diseases and the lack of efficient vaccines against numerous nontreatable pathogens require the development of novel vaccination strategies. To date, only a few mucosal vaccines have been approved for humans. This was in part due to i) the use of live attenuated vaccines, which are not suitable for certain groups of individuals, ii) safety concerns derived from implementation in humans of some mucosal vaccines, iii) the poor stability, absorption and immunogenicity of antigens delivered by the mucosal route and iv) the limited number of available technologies to overcome the bottlenecks associated with mucosal antigen delivery. Recent advances make feasible the development of efficacious mucosal vaccines with adequate safety profile. Thus, currently intranasal vaccines represent an attractive and valid alternative to conventional vaccines.

Areas covered: The present review is focused on the potentials and limitations of market-approved intranasal vaccines and promising candidates undergoing clinical investigations. Furthermore, emerging strategies to overcome main bottlenecks including efficient breaching of the mucosal barrier and safety concerns by implementation of new adjuvants and delivery systems are discussed.

Expert opinion: The rational design of intranasal vaccines requires an in-depth understanding of the anatomic, physicochemical and barrier properties of the nasal mucosa, as well as the molecular mechanisms governing the activation of the local innate and adaptive immune system. This would provide the critical knowledge to establish effective approaches to deliver vaccine antigens across the mucosal barrier, supporting the stimulation of a long-lasting protective response at both mucosal and systemic levels. Current developments in the area of adjuvants, nanotechnologies and mucosal immunology, together with the identification of surface receptors that can be exploited for cell targeting and manipulating their physiological properties, will become instrumental for developing a new generation of more effective intranasal vaccines.     

Intranasal delivery of stem cells to the brain

INTRODUCTION: Stem cell-based therapy has proved to be a promising treatment option for neurological disorders. However, there are difficulties in successfully administrating these stem cells. For example, the brain-blood barrier impedes the entrance of stem cells into the CNS after systemic administration. Direct transplantation or injection may result in brain injury, and these strategies are clinically less feasible. Intranasal administration is a non-invasive and effective alternative for the delivery of drugs, vector-encoded viruses or even phages to the CNS. Recent studies have in fact demonstrated that stem cells may enter the CNS after intranasal administration. These results suggest that intranasal delivery may provide an alternative strategy for stem cell-based therapy. AREAS COVERED: This review summarizes current studies that have applied the intranasal delivery of stem cells into the brain. In addition, the distribution and fate of stem cells in the brain and the potential opportunities as well as challenges of intranasal stem cell delivery are also discussed. EXPERT OPINION: Intranasal delivery of stem cells is a new method with great potential for the transplantation of stem cells into the brain, and it may provide an extraordinary approach to overcoming the existing barriers of stem cell delivery for the treatment of many neurological disorders. This potential benefit emphasizes the importance of future research into intranasal delivery of stem cells.     

Intranasal delivery of stem cells to the brain

Introduction: Stem cell-based therapy has proved to be a promising treatment option for neurological disorders. However, there are difficulties in successfully administrating these stem cells. For example, the brain–blood barrier impedes the entrance of stem cells into the CNS after systemic administration. Direct transplantation or injection may result in brain injury, and these strategies are clinically less feasible. Intranasal administration is a non-invasive and effective alternative for the delivery of drugs, vector-encoded viruses or even phages to the CNS. Recent studies have in fact demonstrated that stem cells may enter the CNS after intranasal administration. These results suggest that intranasal delivery may provide an alternative strategy for stem cell-based therapy.

Areas covered: This review summarizes current studies that have applied the intranasal delivery of stem cells into the brain. In addition, the distribution and fate of stem cells in the brain and the potential opportunities as well as challenges of intranasal stem cell delivery are also discussed.

Expert opinion: Intranasal delivery of stem cells is a new method with great potential for the transplantation of stem cells into the brain, and it may provide an extraordinary approach to overcoming the existing barriers of stem cell delivery for the treatment of many neurological disorders. This potential benefit emphasizes the importance of future research into intranasal delivery of stem cells.     

Intoxication of Crotalaria pallida seeds to growing broiler chicks

The adverse effects of feeding Crotalaria pallida (CP) seeds to chicks was investigated in a 21-day randomized trial of 4 dietary treatments (control, 1,2 and 3% ground CP seeds). Mortality rates in birds fed 0, 1, 2, and 3% dietary CP were 0, 2.1, 6.2, and 16.7%, respectively. Body weight gain and feed efficiency were adversely affected by all levels of inclusion of CP seeds, but feed intake was decreased only by dietary levels of 2 and 3%. Dietary CP of 2 and 3% increased the relative weight of lung, heart and spleen. Relative liver weight was increased by 2% dietary CP, but decreased by 3% CP. At day 14, serum GGT was increased by 2 and 3% dietary CP; serum ALT was significantly increased by 3% CP. No differences in ALT, AST or GGT were observed at day 21. Dietary levels equal to or greater than 1% CP are toxic for growing broiler chicks.     

芬太尼丙泊酚预防气管插管加压反应的临床体会

目的:避免全麻气管插管时的血压增高,心率增快。方法:芬太尼2μg/kg,丙泊酚1~1.5 mg/kg,全麻诱导,气管插管。结果:全部病例全麻诱导前到插管时血压、心率差均数t检验P<0.01,存在非常显著性差异,而从插管时到插管后5 min血压、心率t检验P>0.05,差异无显著性,说明此方法可以有效降低诱导插管时的血压、心率,控制加压反应,而且插管后血压、心率无反弹,大大减轻了气管插管时的心血管反应。结论:在全麻诱导期调整和加用芬太尼2μg/kg,丙泊酚1~1.5 mg/kg,有效避免了全麻气管插管引起的血压急剧升高和心率增快、平均动脉压升高等心血管副反应,进一步提高了手术麻醉期的安全性。     

Effects of Intranasal Exposure to Spores ofStachybotrys atrain Mice

The effects of highly toxic and nontoxic spores ofStachybotrys atrawere investigated in mice after six intranasal administrations of 1 × 10⁵and 1 × 10³spores in phosphate-buffered saline during a 3-week period. Toxic spores contained the trichothecene mycotoxins, satratoxins G and H, as well as the immunosuppressant stachybotrylactones and -lactams. No trichothecenes were detected in the nontoxic spores, and they contained only minor amounts of stachybotrylactones and -lactams. In mice injected with toxic and nontoxic spores, the platelet count was decreased and leucocyte and erythrocyte counts, hemoglobin concentration, and hematocrit were increased. No IgG antibodies toS. atrawere detected in sera of mice exposed intranasally to spores. No histological changes were detected in spleen, thymus, or intestines of mice. The mice receiving 1 × 10⁵toxic spores intranasally developed severe inflammatory changes within both bronchioles and alveoli. Hemorrhage was detected in alveoli. The mice receiving 1 × 10⁵nontoxic spores also developed inflammatory changes in the lungs, but these changes were significantly milder than those in mice receiving toxic spores. The mice receiving 1 × 10³toxic spores developed inflammatory changes in the lungs that were less severe than those in the mice receiving 1 × 10⁵toxic spores. No inflammatory changes were detected in the mice receiving 1 × 10³of nontoxic spores. The present findings indicate that exposure toS. atraspores containing toxins (satratoxins) can be a significant health risk.     

Prospects for Intranasal Delivery of Neuropeptides to the Brain

Pharmaceutical Chemistry Journal - Intranasal administration (INA) of medicines has the advantages of being noninvasive, painless, simple, and convenient. The basic approaches to solving problems...     

Intranasal delivery of biologics to the central nervous system

Treatment of central nervous system (CNS) diseases is very difficult due to the blood-brain barrier's (BBB) ability to severely restrict entry of all but small, non-polar compounds. Intranasal administration is a non-invasive method of drug delivery which may bypass the BBB to allow therapeutic substances direct access to the CNS. Intranasal delivery of large molecular weight biologics such as proteins, gene vectors, and stem cells is a potentially useful strategy to treat a variety of diseases/disorders of the CNS including stroke, Parkinson's disease, multiple sclerosis, Alzheimer's disease, epilepsy, and psychiatric disorders. Here we give an overview of relevant nasal anatomy and physiology and discuss the pathways and mechanisms likely involved in drug transport from the nasal epithelium to the CNS. Finally we review both pre-clinical and clinical studies involving intranasal delivery of biologics to the CNS.     

Alveolar permeability to protein in rats differentially susceptible to ozone

Sprague-Dawley rats susceptible (DS) to NaCl-induced hypertension suffer higher mortality when exposed daily to 2.0 ppm ozone than do hypertension-resistant (DR) rats, independent of salt in the diet or systemic blood pressure. To investigate one possible contribution to this differential sensitivity to ozone, alveolar permeabilities to serum albumin were measured both in ozone-exposed and in control DS and DR rats. Female rats aged 5-7 weeks maintained on a low-salt (0.4% NaCl) diet were injected intravenously with 125I-bovine serum albumin and were then exposed to either 2.0 ppm ozone or air for 5 h. After pentobarbital anesthesia, the rats were exsanguinated and their lungs were lavaged in situ with saline. Lavage fluids and blood samples were measured for radioactivity using a NaI-well gamma counter. The results indicated that while DS and DR control rats have similar pulmonary permeabilities to 125I-albumin, the lungs of the ozone-exposed DS animals were 63% (p less than 0.02) more permeable than those of DR rats exposed to ozone. Sloughing of epithelial tissue, mucous formation and an accumulation of macrophages in the end-airways were more pronounced among ozone-exposed DS animals than in DR-ozone-exposed rats. This increased damage among DS rats correlated well with the increased protein permeability levels. In similar studies, Sprague-Dawley (D) rats were more variable in their response to ozone than either inbred strain. However, the results appeared generally more like those of the DS animals, suggesting that the trait selected by inbreeding may have been resistance rather than sensitivity to ozone-induced lung injury.     

Complications of Oral Exposure to Fentanyl Transdermal Delivery System Patches

Purpose

Fentanyl is a synthetic opioid available therapeutically as an intravenous, transbucal, or transdermal preparation. It is also used as a drug of abuse through a variety of different methods, including the oral abuse of transdermal fentanyl patches. This is a series of patients with oral fentanyl patch exposure reported to our center and represents the first series of oral fentanyl patch exposures collected outside of the postmortem setting.

Methods

In this series, we examined the New York Poison Control Center database for all cases of oral abuse of fentanyl reported between January 2000 and April 2008.

Results

Twenty cases were reported, nine were asymptomatic or had symptoms of opioid withdrawal; 11 had symptoms of opioid intoxication. Eight patients were administered naloxone and all showed improvement in clinical status. Only one case resulted in a confirmed fatality—this patient had an orally adherent patch discovered at intubation.

Conclusions

Oral exposure may result in life-threatening toxicity. Patients should be closely assessed and monitored for the opioid toxidrome, and if symptomatic, should be managed with opioid antagonists and ventilatory support.     

走向优质监管的有益探索——2008年药品监管改革的若干观察

对于中国药品监管而言,刚刚过去的2008年注定将成为具有标志性意义的一年,这一年不仅是中国药监系统建立的十年之庆,而且伴随着风雪和地震灾害突然而至、北京奥运顺利举行、国务院机构改革大幕拉开、世界金融危机扩散、新医改方案讨论步入纵深等众多重要外部环境因素的影响,从而也给刚刚开始走向科学监管、创建优质监管体系的中国药品监管带来了一系列的机遇和挑战.     

芬太尼不同给药速度对诱发咳嗽反应的影响

目的观察麻醉诱导时不同给药速度输注芬太尼对诱发咳嗽反应(fentanyl cough reflx,FCR)的影响,选择最佳的给药速度。方法选择择期手术60例全麻患者随机分成3组:Ⅰ组30 s内经静脉直接注射芬太尼4μg/kg;Ⅱ组以120滴的滴速滴入芬太尼4μg/kg;Ⅲ组以60滴的滴速滴入芬太尼4μg/kg;记录患者是否发生咳嗽及呛咳的程度。并同时记录芬太尼注射前、后的血压、心率、呼吸和脉搏血氧饱和度,以及药物不良反应。结果Ⅰ组患者FCR发生率为75%,Ⅱ组为5%,三组为0,且Ⅰ组的呛咳程度显著高于Ⅱ组(P<0.01)。Ⅰ组在给药后多伴有心率增快、血压增加,与其他两组比较有显著性差异(P<0.05)。结论经外周静脉30 s秒内直接注射芬太尼4μg/kg时FCR的发生率高,120滴及60滴侧管滴注芬太尼明显降低患者咳嗽的发生率或不发生,提高了麻醉的安全性。