肺表面活性物质对兔胎粪吸入综合征模型的临床疗效评价

目的　探讨肺表面活性物质气管冲洗治疗兔胎粪吸入综合征 (MAS)的疗效。方法　 13只日本家兔MAS模型随机分成 2组。实验组 7只 ,用肺表面活性物质气管冲洗。给予稀释的肺表面活性物质 8ml/ kg(含量 6 mg/ml) ,分 5个体位分次注入气管内 ,每次注入后给予 8次球囊加压给氧 ,并给予气管内吸引 3次。对照组 6只 ,仅给予呼吸支持和气管内吸引。结果　实验组兔动脉血氧分压 (Pa O2 )和动脉 /肺泡氧分压比 (a/ APO2 )较对照组明显上升 ,有显著性差异 ,P<0 .0 5。并持续到 2 .5小时。结论　肺表面活性物质气管内冲洗具有改善 MAS兔呼吸系统气体交换和排出胎粪颗粒的作用。     

Pulmonary surfactant as vehicle for intratracheally instilled tobramycin in mice infected with Klebsiella pneumoniae.

1. The use of pulmonary surfactant has been proposed as a vehicle for antibiotic delivery to the alveolar compartment of the lung. This study investigated survival rates of mice with a respiratory Klebsiella pneumoniae infection treated intratracheally with tobramycin using a natural exogenous surfactant preparation as vehicle. 2. At day 1 after infection, animals were injected intratracheally with 20 microliters of the following solutions: (1) a mixture of surfactant (500 micrograms) and tobramycin (250 micrograms); (2) tobramycin (250 micrograms) alone; (3) surfactant (500 micrograms) alone; and (4) NaHCO3 buffer (control, sham-treatment). A fifth group received no treatment (control). Deaths were registered every 12 h for 8 consecutive days. 3. The results show an increased survival in the group receiving the surfactant-tobramycin mixture compared to the group receiving tobramycin alone (P < 0.05), the group receiving surfactant alone (P < 0.01) and the control groups (P < 0.01). It is concluded that intratracheal instillation of surfactant-tobramycin is superior to tobramycin alone in protecting animals from death due to a respiratory Klebsiella pneumoniae infection.     

Lung clearance of intratracheally instilled 99mTc-tobramycin using pulmonary surfactant as vehicle

1. The use of pulmonary exogenous surfactant as a vehicle for intratracheally administered antibiotics to improve local antimicrobial therapy has been proposed. The present study investigated lung clearance rates in the rat of intratracheally instilled technetium labelled tobramycin with and without the addition of surfactant to the antibiotic solution. 2. The influence of surfactant on 99mTc-tobramycin lung clearance rates was studied dynamically with a gamma-camera in anaesthetized spontaneously breathing animals and in mechanically ventilated animals. 3. The results show that instillation of 99mTc-tobramycin with use of surfactant as vehicle significantly increases 99mTc-tobramycin lung clearance compared to instillation of 99mTc-tobramycin solution alone (P=0.006 between the two spontaneously breathing groups of animals and P=0.02 between the two ventilated groups of animals, ANOVA for repeated time measurements). The half life (t1/2) of composite clearance curves in spontaneous breathing animals was 147 min for animals receiving 99mTc-tobramycin versus 61 min for animals receiving 99mTc-tobramycin with surfactant. In mechanically ventilated animals this was 163 min versus 51 min, respectively. 4. It is concluded that exogenous surfactant, used as vehicle for intratracheally instilled 99mTc-tobramycin, increases lung clearance rate of 99mTc-tobramycin in rats.     

Use of surfactant in the prevention and treatment of neonatal respiratory distress syndrome

The rationale for surfactant therapy in premature infants is presented, along with a discussion of the characteristics of surfactant and a review of clinical trials of surfactant for the prevention and treatment of neonatal respiratory distress syndrome (RDS). RDS is a major complication of prematurity, affecting up to 40,000 infants in the United States and Canada annually. Poor lung compliance due to a functional or quantitative deficiency of surfactant causes progressive collapse of the lungs. Surfactant, a mixture of phospholipids, neutral lipids, and proteins synthesized by pneumocytes during gestation, reduces surface tension and stabilizes alveoli, which increases lung compliance and decreases the work of breathing. Mammalian, human, and artificial surfactants are being investigated for use in premature infants. Several controlled trials of exogenous surfactant therapy have demonstrated reductions in mortality and pulmonary air-leak phenomena and improved gas exchange, but these results are not seen consistently, and no significant reductions in bronchopulmonary dysplasia have been observed. Surfactant has no appreciable toxicity, although the potential for immunogenicity exists. Typical doses range from 60 mg to 200 mg/kg administered endotracheally either before the first breath or after development of RDS. Surfactant is a safe investigational agent that appears promising for the prevention and treatment of neonatal RDS, although additional clinical trials with long-term follow-up are needed to determine its true efficacy.     

Ofloxacin intravenous

The physical and chemical compatibility of ofloxacin (infusion solution 100 ml=200 mg) with amoxicillin, amoxicillin+clavulanic acid, flucloxacillin, tobramycin, gentamicin, clindamycin, vancomycin, ceftazidime and piperacillin was investigated. Upon admixture with flucloxacillin a precipitate formed between 7 and 24 hours. No other physical or chemical incompatibilities were observed with any of the other combinations. Ofloxacin may be safely combined with the tested antimicrobial drugs, except for flucloxacillin.     

Ofloxacin intravenous

The physical and chemical compatibility of ofloxacin (infusion solution 100 ml=200 mg) with amoxicillin, amoxicillin+clavulanic acid, flucloxacillin, tobramycin, gentamicin, clindamycin, vancomycin, ceftazidime and piperacillin was investigated. Upon admixture with flucloxacillin a precipitate formed between 7 and 24 hours. No other physical or chemical incompatibilities were observed with any of the other combinations. Ofloxacin may be safely combined with the tested antimicrobial drugs, except for flucloxacillin.     

Contrasting respirable quartz and kaolin retention of lecithin surfactant and expression of membranolytic activity following phospholipase A2 digestion.

Respirable-sized quartz, a well-established fibrogenic mineral dust, is compared with kaolin in erythrocyte hemolysis assays after treatment with saline dispersion of dipalmitoyl phosphatidylcholine, a primary phospholipid component of pulmonary surfactant. Both dusts are rendered inactive after treatment, but the membranolytic activity is partly to fully restored after treatment with phospholipase A2, an enzyme normally associated with cellular plasma membranes and lysosomes. Phospholipid-coated dusts were incubated for periods of 2-72 h at a series of applied enzyme concentrations, and the adsorbed lipid species and hemolytic activity were quantitated at each time for both dusts. Surfactant was lost more readily from quartz than from kaolin, with consequent more rapid restoration of mineral surface hemolytic activity for quartz. Interactions of surfactant and mineral surface functional groups responsible for the mineral-specific rate differences, and implications for determining the mineral surface bioavailability of silica and silicate dusts, are discussed.     

经鼻持续正压通气佐以肺表面活性物质治疗新生儿急性呼吸衰竭的应用观察

目的 观察经鼻持续正压通气佐以肺表面活性物质治疗新生儿急性呼吸衰竭的临床疗效.方法 对我院2009年9月至2013年5月采取经鼻持续正压通气佐以肺表面活性物质治疗的43例急性呼吸衰竭新生儿的临床资料进行回顾性分析,观察其疗效情况.结果 临床总有效率79.07％,死亡率9.30％;治疗24 h后,Pa02、PC02、PaOJFi02、pH、R及HR较治疗前均显著改善（P＜0.05）.结论 经鼻持续正压通气佐以肺表面活性物质治疗新生儿急性呼吸衰竭疗效确切,值得临床借鉴.     

Antibacterial activity of aztreonam: a synthetic monobactam. A comparative study with thirteen other antibiotics

The in vitro activity of aztreoman (SQ 26, 776), a new monocyclic beta-lactam antimicrobial agent, was determined against 1720 bacteria, all clinical isolates, and compared with that of thirteen beta-lactam and aminoglycoside antibiotics. Aztreonam inhibited 90% of Citrobacter diversus, Citrobacter freundii, Enterobacter agglomerans, E. coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii, Proteus rettgeri, Proteus vulgaris and Salmonella sp. by less than or equal to 0.4 micrograms ml-1. This activity was superior to moxalactam, piperacillin, cefamandole, cefoperazone, cefoxitin, cefsulodin, ceftazidime and aminoglycoside antibiotics. Aztreonam was as active as moxalactam against Enterobacter aerogenes, Enterobacter cloacae and Shigella species. Pseudomonas aeruginosa strains resistant to moxalactam, piperacillin, cefamandole, cefoperazone, cefotaxime, cefoxitin, cefsulodin and ceftazidime were inhibited by aztreonam 50% by 6.3 micrograms ml-1 and 90% by 16 micrograms ml-1. Aztreonam was as active as ceftazidime against Serratia marcescens, all strains were inhibited by 3.1 micrograms ml-1 and 90% by 1.6 micrograms ml-1. There was no major difference between MBC and MIC values of aztreonam and the effect of inoculum size upon MIC values was observed at 10(7) CFU.     

Effects of iron depletion on antimicrobial activities against planktonic and biofilm Pseudomonas aeruginosa

Objectives Iron plays an important role in the development of Pseudomonas aeruginosa biofilm. Here we evaluated effects of iron depletion on the antimicrobial activity of ceftazidime, tobramycin and ciprofloxacin against planktonic and biofilm Pseudomonas aeruginosa. Methods We tested the sensitivities of wild‐type PAO1, type‐IV pilus mutant PAO‐ΔpilHIJK and the quorum‐sensing mutant PAO‐JP2 P. aeruginosa planktonic cultures and biofilms to antibiotics under iron‐depleted conditions. Key findings In planktonic bacteria, the minimum concentration that inhibited visible growth (MIC) of ciprofloxacin was increased slightly in an iron‐depleted environment in all three strains, whereas the MIC of tobramycin was similar in iron‐depleted and control environments. The MIC of ceftazidime increased in the PAO‐JP2 strain when iron was depleted. Tobramycin achieved the best bactericidal effect in biofilms. Viable counts were reduced by one log under iron‐depleted conditions in all three strains when tobramycin reached 4 MIC and when ceftazidime and ciprofloxacin reached 8 MIC. Conclusions This study suggests that once the biofilm is formed, iron depletion may only slightly promote the bactericidal effect of antibiotics on PAO1, PAO‐ΔpilHIJK and PAO‐JP2. Although these changes were relatively small, iron as one of the environmental factors should not be ignored when evaluating bactericidal effect of antibiotics. The combination of an iron chelator and antibiotics may have therapeutic value under certain bacterial growth conditions.     

Dose-response comparisons of five lung surfactant factor (LSF) preparations in an animal model of adult respiratory distress syndrome (ARDS).

1. We have examined the effects of five different lung surfactant factor (LSF) preparations in the rat lung lavage model. In this model repetitive lung lavage leads to lung injury with some similarities to adult respiratory distress syndrome with poor gas exchange and protein leakage into the alveolar spaces. These pathological sequelae can be reversed by LSF instillation soon after lavage. 2. The tested LSF preparations were: two bovine: Survanta and Alveofact: two synthetic: Exosurf and a protein-free phospholipid based LSF (PL-LSF) and one Recombinant LSF at doses of 25, 50 and 100 mg kg-1 body weight and an untreated control group. 3. Tracheotomized rats (10-12 per dose) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths min-1, inspiration expiration ratio of 1:2, peak inspiratory pressure (PIP) of 28 cmH2O at positive end-expiratory pressure (PEEP) of 8 cmH2O. Two hours after LSF administration, PEEP and in parallel PIP was reduced from 8 to 6 (1st reduction), from 6 to 3 (2nd reduction) and from 3 to 0 cmH2O (3rd reduction). 4. Partial arterial oxygen pressure (PaO2, mmHg) at 5 min and 120 min after LSF administration and during the 2nd PEEP reduction (PaO2(PEEP23/3)) were used for statistical comparison. All LSF preparations caused a dose-dependent increase for the PaO2(120'), whereas during the 2nd PEEP reduction only bovine and recombinant LSF exhibited dose-dependency. Exosurf did not increase PaO2 after administration of the highest dose. At the highest dose Exosurf exerted no further improvement but rather a tendency to relapse.(ABSTRACT TRUNCATED AT 250 WORDS)     

不同通气方式联合肺表面活性物质治疗新生儿呼吸窘迫综合征的效果评价

目的：探讨不同通气方式联合肺表面活性物质治疗新生儿呼吸窘迫综合征的有效性及临床价值。方法选择本院2010年1月~2013年1月收治入院的呼吸窘迫综合征新生儿230例,随机分为观察组和对照组各115例,观察组采用鼻塞持续气道正压通气结合肺表面活性物质治疗,对照组采用常规机械通气结合肺表面活性物质治疗,比较两组患儿的临床治疗效果及不良反应情况。结果观察组应用肺表面活性物质后2~3h皮肤颜色转红,经皮血氧饱和度逐渐升高。6 h后动脉血氧分压（PaO2）、动脉/肺泡血氧分压比值（a/A PO2）明显上升,氧合指数（OI）逐渐降低,与治疗前比较,差异有统计学意义（P〈0.05）;治疗后两组间PaO2、a/A PO2、OI比较,差异有统计学意义（P〈0.05）。观察组治疗后吸入氧浓度（FiO2）及呼气末正压（PEEP）逐渐降低,与治疗前比较,差异有统计学意义（P〈0.05）;治疗后两组FiO2比较,差异有统计学意义（P〈0.05）,PEEP比较,差异无统计学意义（P〉0.05）。结论鼻塞持续气道正压通气结合肺表面活性物质能有效改善新生儿呼吸窘迫综合征患儿肺顺应性及氧合功能,降低不良反应发生率,适合在临床上推广应用。     

表面活性剂对两性霉素B溶解行为的影响

目的:研究不同表面活性剂对两性霉素B溶解行为的影响。方法:选用非离子表面活性剂司盘-20、吐温-40、吐温-60、吐温-80、泊洛沙姆188,阳离子表面活性剂十六烷基三甲基氯化铵,阴离子表面活性剂十二烷基磺酸钠、脱氧胆酸钠及两性离子表面活性剂卵磷脂,配成系列浓度的表面活性剂溶液,通过紫外分光光度法,以最大增溶百分比为指标考察其对两性霉素B溶解度的影响。结果:在0.2～4mg·mL-1浓度范围内,各表面活性剂最大增溶百分比司盘-20为1365.44%(4mg·mL-1)、吐温-40为353.46%(0.8mg·mL-1)、吐温-60为1165.30%(4mg·mL-1)、吐温-80为973.46%(0.4mg·mL-1)、泊洛沙姆188为1527.95%(4mg·mL-1)、十二烷基磺酸钠为1199.16%(4mg·mL-1)、脱氧胆酸钠为88.62%(4mg·mL-1)、十六烷基三甲基氯化铵为1671.68%(4mg·mL-1)、卵磷脂为314.36%(4mg·mL-1)。结论:本试验中,表面活性剂司盘-20、吐温-60、吐温-80、泊洛沙姆188、十二烷基磺酸钠、脱氧胆酸钠、十六烷基三甲基氯化铵对两性霉素B具有显著的增溶效果;而吐温-40、脱氧胆酸钠、卵磷脂增溶效果不明显。     

Perinatal sidestream cigarette smoke exposure and the developing pulmonary surfactant system in rats.

1. Epidemiological studies have strongly implicated passive smoking with increased incidence of various respiratory diseases in children. Our earlier studies have shown that chronic exposure to tobacco smoke significantly changes the composition and the surface activity of the pulmonary surfactant in adult rats. The aim of the present study was to determine if perinatal exposure to sidestream cigarette smoke influences the composition and function of pulmonary surfactant system in developing rat pups. 2. Pregnant Sprague Dawley rats were exposed to sidestream cigarette smoke in a whole body exposure chamber for a total of 6 h each day and the pups born to these dams were further exposed to sidestream smoke for 2 h/day during postnatal period. Exposure of animals to smoke was ascertained by measuring their plasma cotinine. Surfactant analysis was performed on bronchoalveolar lavage fluids (BALF) collected from pups on postnatal day 1, 3, 7, 14, 21 and 35. The phospholipid (PL) content, percentage disaturated phosphatidylcholine (DSPC) and surfactant proteins (SP-A and SP-B) in BALF surfactant preparations from sham and smoke-exposed pups were compared. 3. Significant differences between the two groups were observed at two exposure points: a reduced level of SP-A on day 1, and, a higher level of SP-A and PLs on day 21, in smoke-exposed pups. Surface activity analysis of the surfactant films by pulsating bubble surfactometer did not show any significant differences between the sham and smoke-exposed groups at any exposure point. 4. The results indicate that perinatal exposure to sidestream smoke is capable of producing biochemical changes in the composition of pulmonary surfactant at different stages of development but these changes do not influence surface tension reducing properties of the surfactant.     

肺表面活性物质分别联合BiPAP、CPAP对新生儿呼吸窘迫综合征肺功能的影响

目的 探究肺表面活性物质分别联合BiPAP、CPAP对新生儿呼吸窘迫综合征肺功能的影响.方法 收集我院2015年1月至2019年12月收治的新生儿呼吸窘迫综合征患儿80例,采用随机数字表法分为BP组、CP组,各40例.其中BP组予以肺表面活性物质联合BiPAP,CP组予以肺表面活性物质联合CPAP,比较两组患者治疗前后...     

Postdeposition dispersion of aerosol medications using surfactant carriers

Inhaled aerosol drugs provide a means of directly treating the lungs; however, aerosol deposition and drug distribution can be nonuniform, especially in obstructive lung disease. We hypothesize that surfactant-based aerosol carriers will disperse medications over airway surfaces after deposition through surface tension driven flows, increasing dose uniformity and improving drug distribution into underventilated regions. We considered saline and surfactant aerosol delivery via cannula onto several model airway surfaces including porcine gastric mucus (PGM) and both cystic fibrosis (CF) and non-CF human bronchial epithelial cells (HBEs). Fluorescent dye and microspheres (d = 100 nm, 1 mum) were used to qualitatively and quantitatively assess postdeposition dispersion. Aerosol volume median diameters were in the 1-4 mum range. The tested surfactants included sodium dodecyl sulfate (SDS), cetyl trimethyl ammonium bromide (CTAB), tyloxapol, and calfactant. All surfactants tested on PGM (tyloxapol, calfactant, SDS, and CTAB) significantly increased dispersion area versus saline with all markers (2-20-fold increases; all p < 0.04). Both surfactants tested on CF HBEs (tyloxapol and calfactant) significantly increased dispersion area versus saline with all markers (1.6-4.1-fold increases; all p 相似文献   

儿科处方/医嘱前置审核规则设置的实践与分析

目的：探讨气管内滴入牛肺表面活性剂辅助经鼻双相正压通气（N-BiPAP）治疗胎粪吸入综合征的疗效。方法：选取2016年2月至2019年1月我院收治的98例胎粪吸入综合征患儿,采用简单随机法分为对照组（n=48）和观察组（n=50）,对照组给予N-BiPAP治疗,观察组给予气管内滴入牛肺表面活性物质（70~100 mg/kg）辅助N-BiPAP治疗,比较两组患儿通气时间、氧疗时间、血气分析结果、血清炎症因子水平及并发症发生情况。结果：与治疗前比较,治疗后两组患儿动脉二氧化碳分压（PaCO2）、降钙素原（PCT）、白细胞介素-6（IL-6）、C反应蛋白（CRP）水平降低,动脉血氧分压（PaO2）、氧合指数（OI）水平升高（P均<0.05）,观察组PaCO2、PCT、IL-6、CRP水平低于对照组,PaO2、OI水平高于对照组（P均<0.05）;观察组通气时间、氧疗时间均短于对照组,并发症发生率低于对照组（P均<0.05）。结论：应用气管内滴入牛肺表面活性物质辅助N-BiPAP治疗胎粪吸入综合征的疗效确切,可显著改善血气状态和体内炎症水平,促进患儿早日康复。     

肺表面活性物质治疗新生儿肺透明膜病的疗效观察

目的：观察肺表面活性物质治疗新生儿肺透明膜病的疗效。方法参照组患儿均送入新生儿CCU病房实施重症监护。给予其常规的保暖、静脉营养、感染防控、水电及酸碱平衡维系及其他相应对症治疗,同时应用CPAP辅助呼吸治疗。临床组在参照组的常规治疗方案及CPAP辅助呼吸的基础上,额外应用肺表面活性物质进行治疗。比照两组临床疗效及血气指标中血液pH、PaO2及PaCO2的治疗前后改善情况。最后统计两组CPAP呼吸辅助总时长及吸氧总时长。结果临床组总有效率为94.03%,显著高于参照组的71.64%（P＜0.05）。两组治疗前pH、PaO2及PaCO2三个指标相比无显著差异,治疗后均较治疗前相比显著改善（P＜0.05）,且临床组其改善幅度显著优于参照组（P＜0.05）。临床组其CPAP呼吸辅助总时长及吸氧总时长均显著少于参照组（P＜0.05）。结论新生儿肺透明膜病应用肺表面活性物质其临床疗效显著,可迅速恢复患儿的自主呼吸功能。     

Protein- and lipid modification of natural bovine surfactant. Effects in experimental lung failure with special consideration of the response in neonates

Surfactant therapy does not lead to a uniform, optimal and sustained effect on gas exchange in neonatal respiratory distress syndrome (RDS) and acute respiratory distress syndrome (ARDS). The aim of the present study therefore was to compare the effects of a lipid-enriched and protein-modified natural surfactant preparations with a licensed, clinically used bovine surfactant preparation - SF-Ril (Alveofact). METHODS: SF-Ril was enriched with phosphatidylglycerol, sphingomyeline, phosphatidylethanolamine plasmalogen, phosphatidylethanolamine. Furthermore, SF-Ril was modified with increased surfactant protein B (SP-B)/surfactant protein C (SP-C) content and finally a mercaptoethanol (ME) treated preparation for breaking the sulfhydril bondage of SP-B/SP-C by chemical reduction in methylene chloride using ME was developed. Finally ME was removed by vacuum extraction. These modified surfactants were tested at a dosage of 100 mg/ kg each in a model of respiratory failure induced by lung lavage in male adult rats and compared with SF-Ril at an identical dosage. Mechanical ventilation was standardised with fraction of inspiratory oxygen (FiO2) 1.0 and time-cycled pressure limited ventilation 16/0.8 cmH2O before and 26/6 cmH2O (peak inspiratory pressure/positive endexpiratory pressure) after lung lavage (target arterial oxygen pressure [pa02] < 100 mmHg), respiratory rate 36/min, inspiration/expiration time ratio 1:2. RESULTS: During the observation period of 120 min, the sphingomyeline substituted and protein-modified (ME reduced) surfactant preparations exerted improved and sustained oxygenation compared with SF-Ril. Similar effects were observed for tidal volumes. All other preparations were equal or inferior to SF-Ril in our model. CONCLUSION: For the development of surfactant preparations less prone for inactivation the above mentioned data may provide useful information, provided they can be confirmed in further investigations employing other alternative models.     

气道滴入肺表面活性物质和吸入一氧化氮治疗经气道肺泡灌洗诱发 …

目的：比较单独或联合应用气道滴入肺表面活性物质（Ｓｕｒｆ）和吸入一氧化氮（ｉＮＯ）对急性呼吸窘迫综合征的疗效。方法：成年兔反复气道生理盐水灌洗,去除内源Ｓｕｒｆ,经机械通气诱发急性肺损伤和呼吸衰竭,随机分组给予：ｉＮＯ０．８μｍｏｌ．Ｌ＾－１;Ｓｕｒｆ磷脂１００ｍｇ．ｋｇ＾－１;联合应用ｉＮＯ和Ｓｕｒｆ;或不约药对通气８小时生存率以联合治疗组为最高,Ｓｕｒｆ组及联合治疗组的氧合指数（ＯＩ）、肺顺应