The limitations of peak nasal flow measurement

The Youlten Peak Nasal Flow Meter is a convenient device for obtaining objective measurements of nasal patency and gives static values which correlate well—though inversely—with resistance measured by rhinomanometry. In this study peak nasal flow and nasal resistance are compared before and after intranasal challenge using histamine. The comparatively small change in nasal resistance induced by low-dose histamine is not reliably detected by the peak flow meter. Large changes in nasal resistance with a higher dose of histamine are reflected by significant but small changes in peak nasal inspiratory flow. It is concluded that changes in nasal patency as measured by the Youlten meter are an insensitive measure of nasal patency compared with rhinomanometrically measured resistance changes. Continued use of the latter is recommended for physiological research.     

Monte Carlo法用于新生儿阿米卡星的群体药动学分析和认证(英文)

目的:用Monte Carlo算法编制群体药动学分析程序并认证该方法估计药动学参数和预测血药浓度的能力.方法:用阿米卡星作为模型药物,对来自42名新生儿共142对血药浓度时间数据进行分析;根据Sheiner等提出的群体药动学思想,我们编制了估计群体参数和个体参数的程序,目标函数最小值以Monte Carlo算法求得,方法的认证采用经典药动学 程序3p87作为对照,预测能力通过计算预测血药浓度的均方根误差(RMSD)和偏性(BIAS)来考察.结果:我们自编的程序运行稳定;本法提取的群体参数与3p87得到的一致,学习样本与认证样本的预测浓度与实测浓度显著相关(相关系数分别为0.995和0.990),预测误差大多数小于1 mg/L,认证样本RMSD和BIAS分别为0.58和-0.07 mg/L.结论:本法估计参数准确,预测血药浓度能力令人满意.     

离子导入对卡托普利透皮吸收的促进作用(英文)

目的:研究离子导入技术对卡托普利透皮吸收的促进作用。方法:应用离子导入技术研究了卡托普利体外透过大鼠离体皮肤的影响因素,并进行了卡托普利水凝胶贴片大鼠在体的试验,测定了血药浓度的变化。结果:离子导入技术可以有效地促进卡托普利的透皮吸收,透皮速率增加约7倍。药物贮库中的各种因素如pH,离子强度,药物浓度和电流强度均影响药物的透皮速率。随着pH的增加,离子强度的减小,药物浓度的增加及电流强度的增加,透皮速率也增加。大鼠在体试验也表明用药1h后血药浓度即可达到坪值(约0.9μg/mL),并在整个试验阶段维持稳定。结论:离子导入可以有效地促进卡托普利的透皮吸收。     

Effects of pH and Dose on Nasal Absorption of Scopolamine Hydrobromide in Human Subjects

Purpose. The present study was conducted to evaluate theeffects of formulation pH and dose on nasal absorption of scopolaminehydrobromide, the single most effective drug available for the prevention ofnausea and vomiting induced by motion sickness. Methods. Human subjects received scopolamine nasally at adose of 0.2 mg/0.05 mL or 0.4 mg/0.10 mL, blood samples were collected atdifferent time points, and plasma scopolamine concentrations were determinedby LC-MS/MS. Results. Following administration of a 0.2 mg dose, theaverage C_max values were found to be 262 ± 118, 419± 161, and 488 ± 331 pg/mL for pH 4.0, 7.0, and 9.0formulations, respectively. At the 0.4 mg dose the average C_maxvalues were found to be 503 ± 199, 933 ± 449, and 1,308± 473 pg/mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At a0.2 mg dose, the AUC values were found to be 23,208 ± 6,824, 29,145± 9,225, and 25,721 ± 5,294 pg.min/mL for formulation pH 4.0,7.0, and 9.0, respectively. At a 0.4 mg dose, the average AUC value wasfound to be high for pH 9.0 formulation (70,740 ± 29,381 pg.min/mL)as compared to those of pH 4.0 (59,573 ± 13,700 pg.min/mL) and pH 7.0(55,298 ± 17,305 pg.min/mL) formulations. Both the C_maxand AUC values were almost doubled with doubling the dose. On the otherhand, the average T_max values decreased linearly with a decreasein formulation pH at both doses. For example, at a 0.4 mg dose, the averageT_max values were 26.7 ± 5.8, 15.0 ± 10.0, and 8.8± 2.5 minutes at formulation pH 4.0, 7.0, and 9.0, respectively. Conclusions. Nasal absorption of scopolamine hydrobromidein human subjects increased substantially with increases in formulation pHand dose.     

Surface Active Agents as Enhancers of Alveolar Absorption

Purpose. Small solutes which are deposited in the alveoli by aerosolinhalation will be absorbed across the alveolo-capillary barrier.Inhalation of dioctyl sodium sulfosuccinate (DOSS) enhances absorptionwhile having little or no effect on lung function, suggesting that surfaceactive agents may be used as enhancers of alveolar absorption ofinhaled pharmaceuticals. The purpose of this study was to examinethe effects of a selection of different surface active agents onalveolar absorption. Methods. The absorption of ^99mTc-diethylene triamine pentaacetate(^99mTc-DTPA) from the lungs was studied in rabbits. We studied fivedifferent surface active agents: DOSS, sodium glycodioxycholate(GDCA), sodium lauryl sulphate (NaLS), lysophosphatidyl choline(LPC) and polyoxyethylene-23-laurylether (P23LE). Results. DOSS and GDCA both dramatically enhanced the absorptionof ^99mTc-DTPA. There was a moderate effect of NaLS, no significanteffect of LPC and P23LE reduced the rate of absorption. None of thecompounds affected gas exchange or lung compliance. Conclusions. There is a wide spectrum of effects of inhaled surfaceactive agents on the alveolar absorption of ^99mTc-DTPA. Ioniccompounds such as DOSS and GDCA have the greatest effect, and furtherstudies of these classes of surface active agents for use as enhancersof alveolar absorption of pharmaceuticals seem warranted.     

Inhibitory effect of erythromycin on interleukin-8 secretion from exudative cells in the nasal discharge of patients with chronic sinusitis

OBJECTIVES: The mechanism of the efficacy of long-term low-dose macrolide therapy for chronic sinusitis is not fully understood. The authors studied the inhibitory effect of erythromycin on interleukin-8 (IL-8) secretion from exudative cells in the nasal discharge of patients with chronic sinusitis. STUDY DESIGN AND METHODS: Exudative cells in the nasal discharge were isolated from six patients with nonallergic chronic sinusitis. The cells, more than 90% of which were neutrophils, were incubated with or without erythromycin in the presence of 10 micrograms/mL of lipopolysaccharide. The IL-8 concentrations in the culture supernatants were measured by enzyme-linked immunoassay. RESULTS: The amount of secreted IL-8 in the absence of erythromycin was 682 +/- 226 pg/10(6) cells/24 h. The IL-8 secretion was significantly reduced to 66 +/- 15% and 46 +/- 13% of the control in the presence of 10(-6) and 10(-5) M of erythromycin, respectively. CONCLUSION: Erythromycin may act as a biologic modulator that inhibits IL-8 secretion from exudative cells and thereby blocks the vicious circle of neutrophil recruitment and IL-8 generation in the inflammatory site in chronic sinusitis.     

Free secretory component as a standardization protein for nasopharyngeal specimens from children with upper respiratory tract infection

Free secretory component (FSC) has been recommended as a reliable protein for correction of the unknown dilution in tracheal aspirate samples from preterm infants. To investigate whether FSC would also provide a valid standardization protein for samples of nasopharyngeal secretions, this study determined the intersubject variation and the alteration over time in the concentrations of FSC in nasal secretions from 35 children (median age 14 months) who participated in an antibiotic efficacy trial. Nasopharyngeal aspirates were obtained at enrolment and after 2-3 d. FSC in the specimens was quantified by a direct enzyme immunoassay. The concentrations of FSC in the nasal secretions ranged from 0.08 to 189.6 μg ml^-1 (median 12.3 μg ml^-1); the ratio of the highest to the lowest concentrations was 2370, the difference between the 90th and 10th percentile concentrations was 189-fold and the difference between the 75th and 25th percentile values was 26. FSC concentrations were significantly lower in children aged ≤12 months (median 2.2 μg ml^-1) than in the older children (median 21.5 μg ml^-1; p = 0.035). Between the first and the follow-up specimens, 65% of the children had ≥2-fold difference in the levels of FSC in the secretions. Because an optimal standardization protein should show minimal variation between individuals and over time, FSC may not be a suitable protein for correction of the unknown dilution of nasopharyngeal specimens from children with upper respiratory tract infection.     

Dynamic cell cycle kinetics in vitro and in vivo in myelodysplastic syndromes with special reference to the influence of hematopoietic growth factors

We have investigated the effect of HGF in vivo and in vitro in MDS using a recently developed FCM assay involving the simultaneous measurement of cell surface antigens, DNA content, and BrdUrd or IodUrd incorporation. This allows for the determination of the dynamic cell kinetic parameters: LI, T_s, and T_pot and we observed that in vitro HGF stimulation resulted in a significant decrease in mean T_pot values from 6.6 to 3.5 days. Importantly, we demonstrated that in vivo GM-CSF administration to patients with RAEB resulted in a shortening of T_pot within the 2 first weeks of GM-CSF treatment.     

甲泼尼龙冲击疗法治疗杰杨-巴勒综合征

杰杨-巴勒综合征患者23例(男14,女9;平均年龄24±19a;病程9±12mo,)用甲泼尼龙冲击疗法治疗。甲泼尼龙1g或20mg/(kg·d)溶于5％葡萄糖溶液500mL中静滴,qd×3d,1mo后根据病情重复第2、3疗程,冲击间歇期口服泼尼松20-40mg/d维持。结果12例(52％)痊愈,9例(39％)显效,2例无效。值得临床试用。     

常年性鼻炎患者血清和鼻分泌物总IgE测定及其临床意义

应用ＥＬＩＳＡ法对２０例常年性变应性鼻炎、２４例可疑变应性鼻炎、１９例常年性非变应性鼻炎患者的血清及鼻分泌物总ＩｇＥ含量进行检测，并与１０例健康者对照。结果常年性变应性鼻炎患者血清总ＩｇＥ显著高于对照组（Ｐ＜０．０５），可疑变应性鼻炎组和常年性非变应性鼻炎组血清总ＩｇＥ与对照组无显著性差异（Ｐ＞０．０５）。各组鼻分泌物总ＩｇＥ与对照组无显著性差异（Ｐ＞０．０５）。同时讨论了影响因素。