Salivary theophylline estimation in the management of asthma in children.

Simultaneous sampling was performed to determine whether saliva could replace plasma in the monitoring of theophylline dosages. Forty-eight children with moderate to severe asthma received oral theophylline preparation (usually sustained release) on a daily basis. They provided simultaneous saliva and plasma samples at routine out-patient visits. Saliva and plasma theophylline concentrations showed a wide variation between individuals, and their ratios also differed. Saliva theophylline concentrations below 7 micrograms/ml reflect plasma concentrations below 10 micrograms/ml, i.e. sub-therapeutic, while saliva concentrations above 7 micrograms/ml are consistent with therapeutic dosage. Estimation of saliva theophylline concentration on routine visits avoids the discomfort of blood sampling. It reflects whether daily oral theophylline dosage in childhood asthma is below or within the therapeutic range. The need for changes in dosage and the degree of patient-compliance with therapy can be usefully indicated.     

Sustained release choline theophyllinate in nocturnal asthma

Nocturnal wheeze is common in patients with asthma, and slow release theophyllines may reduce symptoms. As theophyllines are stimulants of the central nervous system the effect of 10 days' twice daily treatment with sustained release choline theophyllinate or placebo on symptoms, overnight bronchoconstriction, nocturnal oxygen saturation, and quality of sleep were studied in a double blind crossover study in nine stable patients with nocturnal asthma (five men, four women, age range 23-64 years; forced expiratory volume in one second (FEV1) 0.85-3.8 1; vital capacity 1.95-6.1 1). When treated with the active drug all patients had plasma theophylline concentrations of at least 28 mmol/l (5 micrograms/ml) (peak plasma theophylline concentrations 50-144 mmol/l (9-26 micrograms/ml]. Morning FEV1 was higher when treated with sustained release choline theophyllinate (2.7 (SEM 0.3) 1) than placebo (2.1 (0.3) 1) (p less than 0.01). Both daytime and nocturnal symptoms were reduced when the patients were treated with sustained release choline theophyllinate and subjective quality of sleep was improved (p less than 0.002). When treated with the active drug, however, quality of sleep determined by electroencephalography deteriorated with an increase in wakefulness and drowsiness (p less than 0.05) and a reduction in non-rapid eye movement sleep (p less than 0.005). Treatment with choline theophyllinate had no effect on either the occurrence or the severity of transient nocturnal hypoxaemic episodes or apnoeas or hypopnoeas. In conclusion, sustained release choline theophyllinate prevents overnight bronchoconstriction, but impairs quality of sleep defined by electroencephalography.     

Ipratropium bromide in patients with nocturnal asthma

Fourteen patients with nocturnal asthma were recruited to a two period crossover trial which compared a run-in period on nightly salbutamol (200 micrograms) with a period on nightly ipratropium bromide (160 micrograms) and a period on nightly salbutamol plus ipratropium at night. Morning dipping, as assessed by the fall in peak flow overnight, was significantly reduced in the periods when ipratropium bromide was taken. Peak flow in the morning and also at night was improved when taking ipratropium bromide. Ipratropium bromide in adequate dosage appears to be effective in reducing morning dipping in asthma.     

Serum theophylline concentrations during multiple dosing with two sustained release methylxanthine preparations in normal subjects.

In normal subjects, receiving multiple dosing regimens with Slophyllin and Phyllocontin in does calculated to give either 4 mg/kg or 6mg/kg theophylline free acid twice daily, serum theophylline concentrations were frequently less than 8 mg/l. Accumulation of the serum theophylline trough concentration occurred during the first 3 days of multiple dosing, and was followed by subsequent stabilization or even decline in serum theophylline trough concentrations. Side effects were noted with both Slophyllin and Phyllocontin, but only on the higher dosage regimens; they occurred within 24--48 hr of starting the drug, and tended to diminish if dosing was continued. The accumulation effect of serum theophylline concentrations may explain the timing of adverse effects, and should be avoided by starting methylxanthine therapy at a low dose. This may be increased after a few days. Further dosage adjustment may be necessary in some patients and should be facilitated by measurement of serum theophylline trough concentrations.     

夜间哮喘呼气流速峰值及呼吸驱动昼夜节律的研究

目的：探讨夜间哮喘（nocturnal asthma,NA)患者呼气流速峰值与呼吸驱动的昼夜节律及二者的相关性。方法：研究对象分3组：夜间哮喘组（n=10)，哮喘非夜间发作组（n=10)，健康对照组（n=10)。采用西德CUSTO肺功能仪及Jaeger呼吸驱动测试仪分别于4时，8时，16时，22时测定肺功能－呼气流速峰值（PEF）及呼吸驱动－气道闭合压（P0．1）。结果：夜间哮喘组和健康对照组PEF均于16时达峰值，4时降到最低，夜间哮喘组最高值与最低值之间差异有显著性（P＜0．01），健康对照组无显著差异（P＞0．05）。哮喘非夜间发作组夜间PEF无降低。3组P0．1均未发现明显昼夜节律。PEF与呼吸驱动亦无显著相关性（P＞0．05）。结论：夜间哮喘患者PEF呈昼夜节律改变，P0．1未发现明显昼夜节律，且二者无显著相关性。     

Salbutamol: comparison of bronchodilating effect of inhaled powder and aerosol in asthmatic subjects.

In the treatment of asthma salbutamol can be administered as an aerosol with a metered-dose inhaler or as a powder with a breath-actuated device (Rotahaler). The two forms of the drug were compared in a double-blind placebo-controlled study involving 10 asthmatic adults who were known to respond to salbutamol. The bronchodilating effect of the aerosol and the powder at doses of 200 micrograms and of the powder at doses of 200 and 400 micrograms was compared, bronchodilation being measured in terms of forced expiratory volume and vital capacity. The response was far greater to salbutamol than to placebo, but there was no significant difference between the two forms of the drug or between the lower and higher doses of powder. No side effects were observed.     

A comparative study of bronchodilator effects of carbuterol and ephedrine.

The bronchodilator effect of carbuterol hydrochloride, a new adrenergic agonist, was compared with that of ephedrine sulfate in 12 patients with bronchial asthma. A 2-mg dosage of carbuterol hydrochloride, three times daily, was used in comparison with a 25-mg dosage of ephedrine sulfate, three times daily. The drugs were orally administered for ten-day periods in a double-blind, randomized manner. After carbuterol therapy, the mean increases in forced expiratory volume in one second and midmaximal expiratory flow rate were significantly greater in a four-hour period than those noticed with ephedrine. A decrease in bronchodilator response to both drugs was noticed on the tenth day. No side effects were noticed with carbuterol at the aforementioned dosage. The results of our study indicate that carbuterol is a safer and more effective bronchodilator than ephedrine.     

A comparison of regular with intermittent bronchodilators in asthma patients on inhaled steroids

The aim of this study was to compare the effect of regular versus intermittent (p.r.n.) bronchodilators on bronchial reactivity and asthma control in patients on concomitant inhaled corticosteroids. We studied 12 patients with asthma in a prospective, randomised, single-blind, single-dummy, three-period crossover trial comparing placebo (2 puffs t.d.s.), salbutamol (200μg t.d.s.) and oxitropium bromide (200μg t.d.s.) for 28 days each. Computerised spirometry and bronchial reactivity to histamine were obtained on entry and after each treatment period. Symptom scores, use of rescue bronchodilator and peak expiratory flow rates were recorded daily. There were no significant differences in bronchial hyperreactivity between the salbutamol, oxitropium and placebo treatment periods. There were no significant differences in baseline FEV₁, FEF_25–75%, symptom scores, use of rescue bronchodilator or morning and evening PEFR between treatment periods. Intermittent beta agonist therapy is as effective as regular therapy in terms of asthma control and bronchial hyperreactivity in patients on concomitant inhaled corticosteroid therapy. Since intermittent therapy achieves similar results with significantly lower beta agonist consumption, the data support current recommendations that beta agonists should be taken on a p.r.n. basis in asthma patients on inhaled steroids.     

Acute asthma: emergency department management and prospective evaluation of outcome.

To determine the current management of acute asthma in the emergency department and to evaluate outcome we reviewed the charts of 99 patients aged 15 to 55 years who presented to the emergency department of a tertiary referral, university-affiliated hospital and were subsequently discharged with a diagnosis of acute asthma. Outcome was evaluated prospectively, with a structured questionnaire, by telephone. During the visit pulsus paradoxus was documented in four patients. Spirometry was done in 63 patients; postbronchodilator values ranged from 0.9 to 4.1 L. A total of 92 patients received inhaled bronchodilator therapy, most by wet nebulization. Sixteen patients received anticholinergic agents and three received theophylline. Ingested corticosteroids were given to 27 patients. Of the 71 patients contacted, a mean of 12 days after the visit, 26 (37%) had sought further medical attention, 19 at the emergency department; 9 had required admission. Forty-six patients reported that their condition had improved, but over 60% continued to have cough, sputum production, nocturnal waking and early-morning chest tightness. The results indicate that asthma continues to be undertreated in the emergency department and highlight the importance of routine spirometry in all patients and the need for systemic corticosteroid therapy.     

茶碱对慢性哮喘和肺功能改善的作用

目的 了解茶碱在慢性哮喘轻症患者临床症状缓解和气道炎症抑制作用的机制。方法选择41例慢性哮喘的第1级及第2级中的轻症患者,口服缓释茶碱每天4～6mg／kg.b．w．,每12h 1次,连用16周。对照组15例,未服药治疗。对比评估临床症状,检测晨间最大呼气流黄（PEFa）、用力肺活量（FVC）、1秒钟用力呼气容积（FEV1）、1秒钟用力呼气容积降低20％所需药物累积量（PD20）,静脉血T细胞亚群（CD3^＋、CD4^＋,CD8^＋）的变化。结果 经茶碱口服治疗后,临床症状评分、PD20、PEFnm、FEV1,CD3^＋、CD4^＋与对照组比较差异有显著意义。结论 慢性哮喘轻症患者小剂量茶碱口服治疗16周后,哮喘患者临床症状有明显改善,气道高反应性与对照组比较得到改善（P〈0．01）。     

β2肾上腺素受体多肽16位基因型与夜间哮喘表现型的关系

目的探讨β2肾上腺素受体(β2AR)16、27位基因多态性与夜间哮喘表现型的关系.方法以最大呼气流速(PEFR)为标准,将49例哮喘患者分为夜间哮喘组(25例)和非夜间哮喘组(24例).用PCR产物直接测序确定β2AR 16、27位基因型分布,以及分析两个位点各种基因型与两组病例PEFR、第一秒用力呼气量(FEV1)以及用药情况之间的关系.结果以PEFR为标准,夜间哮喘组PEFR在夜间平均下降33.6%,非夜间哮喘组下降7.0%,二者差异显著(P<0.001).夜间哮喘组和非夜间哮喘组(白天)基础FEV1分别为73.7 %和85.8 %,也具有显著性差异(P<0.001).Gly16的等位基因频率在夜间哮喘组56.0%明显较非夜间哮喘组22.9%高(P<0.05),Gly16集中分布于夜间哮喘组.27位点的多态性在两组间无显著性差异.结论β2 AR Gly16基因型与夜间哮喘可能有关系.     

Value of combining B2 sympathomimetic metered aerosol and oral theophylline in children with asthma

We report the results of a double blind controlled trial on 12 children with clinical asthma. Each child received three different treatment regimens; terbutaline sulphate 0.5 mg (Bricanyl) via a metered aerosol; orally administered theophylline 5 mg/kg (Somophyllin); or a combination of both. As expected, the metered aerosol therapy produced significantly greater early bronchodilatation than therapy with theophylline alone. In addition, the combined therapy produced a significantly greater bronchodilatation after three hours than the metered aerosol alone (P less than 0.05). This trend was also observed after one and two hours, but did not reach significance (0.1 greater than P greater than 0.05). We conclude that there is value in combining a B2 sympathomimetic metered aerosol and oral theophylline in children with asthma.     

全膝关节置换术中关节周围镇痛的应用研究

目的 观察关节周围注射复方镇痛药在全膝关节置换术(TKA)术中的应用价值.方法 选择2007年3至6月间完成的TKA骨性关节炎(OA)患者36例(36膝)被前瞻性随机分为两组:注射组(A组,17例)和非注射组(B组,19例).A组术中于关节及切口周围浸润注射(罗哌卡因200 mg+吗啡5 mg+1:1000肾上腺素0.3 ml+生理盐水)100 ml复方镇痛注射液.B组不注射,术后两组均统一配置自控硬膜外镇痛(PCEA).比较术后两组的疼痛视觉模拟评分(VAS)、开启PCEA的时间和PCEA的麻醉药总用量、关节活动度(ROM)、切口引流量和上消化道等不良事件和术后并发症等情况.结果 A组PCEA开启时间为4～12 h(P50=8),B组为3～6 h(P50=5),两组差异有统计学意义(P＜0.05).A组24 h和总的PCEA麻醉药用量为均少于B组(P＜0.05);术后6 h和12 hVAS评分A组优于B组.两组术前基线资料、伤口引流量、ROM、术后不良事件及并发症情况差异无统计学意义.结论 TKA术中关节周围镇痛可延长PCEA开启时间,减少麻醉药用量和缓解术后早期疼痛,是TKA镇痛的有效方法之一.     

麝香风湿胶囊的急性及长期毒性研究

目的：探讨麝香风湿胶囊的毒性,为临床用药提供安全性资料。方法：进行小鼠急性毒性及大鼠长期毒性试验。结果：小鼠灌胃给药的最大耐受量（ＭＴＤ）为１２ ｇ／ｋｇ。大鼠慢性毒性试验给药组分别灌胃给药４．０ ｇ／（ｋｇ·ｄ）,和２．０ ｇ／（ｋｇ·ｄ）的受试品,连续８ 周,未见动物死亡,血液学及血液生化学各项指标试验组和对照组比较无显著性差异（Ｐ＞ ０．０５）,病理组织学检查,高剂量组未见明显病理改变。结论：提示麝香风湿胶囊临床口服用药安全范围大     

不同剂量布地奈德雾化与强的松口服治疗哮喘急性发作的疗效比较

目的探讨雾化吸入布地奈德混悬液（BIS）治疗支气管哮喘急性发作的起始剂量及量效关系,以及BIS雾化与强的松（PRED）口服的疗效差异。方法 86例支气管哮喘急性发作患者随机分为4组。BIS1、BIS2、BIS3组分别予定量雾化吸入BIS 6 mg/d、4 mg/d、2 mg/d;PRED组予以30 mg强的松片每日顿服。以哮喘急性发作临床指标评分、肺功能指标FEV1（%pred）、PEF（%pred）、FEF（25-75）%（%pred）以及SpO2等为评价指标,观察治疗前和治疗4 h后、第2天、第7天等不同时段评价指标的改善情况。结果雾化吸入BIS及口服PRED均能迅速改善病情;治疗4 h后以及第2天时各组间临床评分、肺功能、SpO2改善的差值无统计学意义;第7天时各组间临床评分、SpO2改善的差值无统计学意义,FEV1（%pred）、PEF（%pred）、FEF（25-75）%（%pred）改善的差值呈BIS1〉BIS2〉BIS3,在BIS1及PRED组间差异无统计学意义。结论增大BIS雾化吸入剂量在一定程度上能提高疗效;雾化吸入BIS 6 mg/d与口服PRED 30 mg/d疗效相当。     

Intranasal treatment with luteinising hormone releasing hormone agonist in women with endometriosis

An agonist analogue of luteinising hormone releasing hormone (buserelin) was successfully used to treat women with endometriosis. A dose of 200 micrograms administered intranasally thrice daily was found to be effective in five patients, in whom the endometriotic lesions resolved after six months' treatment. Failure occurred in a sixth patient, who received only 400 micrograms once daily. Anovulation was induced in all subjects together with suppression of menstruation after the first month of treatment. Symptoms of abdominal pain, dysmenorrhoea, and dyspareunia were relieved during treatment, and one previously infertile patient conceived within two months of stopping treatment. No side effects were reported with this dosage, and the results suggest a new form of treatment for patients with endometriosis.     

茶碱联用沙美特罗／替卡松粉吸入剂对哮喘患者肺功能和气道炎症的影响

目的观察茶碱联用沙美特罗／替卡松粉吸入剂（SFC）对哮喘患者临床控制情况、肺功能和诱导痰炎性标志物的影响。方法146例哮喘患者使用茶碱缓释片（200rag，每日2次），联用SFC（50／250txg，每日2次），治疗24周，记录治疗结束时的完全控制病例数、治疗前后患者的肺功能、诱导痰嗜酸细胞（Eos，瑞氏染色）和嗜酸细胞阳离子蛋白（ECP，荧光免疫法）水平。将142例单独使用SFC（50／250μg，每日2次）的患者作为对照组。结果茶碱联用SFC组和对照组治疗结束时临床控制病例数分别为61例和59例，组间比较差异无统计学意义（P〉0．05）。茶碱联用SFC组患者治疗后25％--75％之间用力肺活量时的呼吸流速（FEF25%-75%）占预计值百分比[（66．7±18．2）％]明显高于对照组[（56．6±17．4）％]（P〈0．01），而诱导痰Eos数量[（4．1±2．3）％]和ECP水平[（63．9±39．4）μg／L]明显低于对照组[（6．2±2．7）％和（90．3±46．2）μg/L]（均P〈0．01）。结论茶碱联用沙美特罗／替卡松粉吸入剂能更好地控制哮喘小气道功能和气道炎症。     

Theophylline blood levels in Sri Lankan asthmatics: comparison of two methods of assay

OBJECTIVES: To assay theophylline blood levels in a sample of Sri Lankan chronic asthmatics taking oral theophylline, and to evaluate a simple and cost effective ultraviolet spectrophotometric assay for theophylline levels in blood. SETTING: Chronic asthmatics taking oral theophylline attending medical clinics at the National Hospital of Sri Lanka (NHSL) were recruited for the study. Blood samples were collected from recruited patients on their subsequent clinic visit. DESIGN AND METHODS: A cross-sectional study of theophylline blood levels. Blood samples were assayed for trough theophylline levels using two methods: an automated homogeneous enzyme immunoassay (EMIT), and a low cost ultraviolet spectrophotometric method. RESULTS: Only 2 patients of the 24 had theophylline blood levels in the accepted therapeutic range (10 to 20 micrograms/ml) (3.4); 19 patients had levels under 5 micrograms/ml. A correlation coefficient of 0.99 was obtained in the statistical comparison of the two methods, indicating that the spectrophotometric method has similar accuracy as the reference EMIT assay. CONCLUSIONS: The results signal a need for monitoring of theophylline in asthmatics when accepted clinical indications are present. The ultraviolet spectrophotometric method is ideal to initiate therapeutic drug monitoring (TDM) in the country because of its low cost (about Rs. 55 per assay), requiring only a UV recording spectrophotometer.     

硫酸沙丁胺醇气雾剂吸入与茶碱控释片治疗急性老年哮喘的疗效对比分析

目的：探究硫酸沙丁胺醇气雾剂吸入与茶碱控释片治疗急性老年哮喘的疗效对比。方法方便选取该院2013年1月—2016年1月收治患急性老年哮喘患者78例作为研究对象,随机分为吸入组和口服组,每组39例。吸入组给予硫酸沙丁胺醇气雾剂吸入治疗,联合组给予硫酸沙丁胺醇气雾剂联合茶碱控释片治疗,观察两组患者治疗后肺功能水平、动脉血气分析、不良反应及治疗效果。结果联合组FEV1/FVC、FEV1%、Pa2O2、PaCO2均优于吸入组,联合组总有效率为94.87%明显高于吸入组82.05%,证明联合组较吸入组治疗显著,组间对比显示P<0.05。结论硫酸沙丁胺醇气雾剂联合茶碱控释片可有效缓解老年急性哮喘的动脉血气及肺部功能,降低老年患者呼吸困难所感到的痛苦感,提升自身生活质量,并提升临床治疗效果,值得广大呼吸科医师积极推广应用。     

Theophylline-induced behavior change in children. An objective evaluation of parents' perceptions.

OBJECTIVE--To evaluate children who take theophylline for the presence of behavioral side effects and to determine whether the beliefs about these side effects held by their parents are supported by their own observations. DESIGN--A double-blind, placebo-controlled, randomized, crossover protocol. Under both study conditions the children completed tests that measured their attention, impulsivity, memory, activity level, and mood, while the parents rated their behavior. PATIENTS--The subjects were 8- to 12-year-old children with asthma whose parents had observed adverse behavioral side effects while the children were taking theophylline. Among cited side effects were impulsivity, hyperactivity, altered mood, and impaired attention. RESULTS--No differences related to treatment could be detected from the parent questionnaires or from six of nine scores of the psychological evaluation of the children. The children, however, made fewer attention errors and showed a mild increase in anxiety and hand tremor of the dominant hand while they were receiving theophylline. All mean changes were small. No significant relationship was found between theophylline concentrations in the serum and degree of change in mood or attention. Eleven of 42 participants were disqualified for noncompliance during the study. CONCLUSION--Parental beliefs about the side effects experienced by their children are not supported by their own observations performed through a blinded protocol. These results are in conflict with reports of a high incidence of adverse behavioral side effects attributed to theophylline therapy.