Phenytoin-valproate interaction: importance of saliva monitoring in epilepsy

Sodium valproate is often used with phenytoin when epilepsy cannot be controlled by a single drug. Sodium valproate depresses phenytoin protein binding and so invalidates plasma phenytoin monitoring as a means of determining precise phenytoin dosage requirements. Plasma and saliva phenytoin and plasma valproate concentrations were measured in 42 patients with epilepsy receiving both drugs. Phenytoin protein binding was also measured by ultrafiltration in 19 of these patients and 19 patients taking phenytoin alone. Saliva phenytoin concentration bore the same close correlation to unbound (therapeutically active) phenytoin in patients receiving both drugs as it did in patients receiving phenytoin alone, whereas plasma total phenytoin did not. The same therapeutic range for saliva phenytoin (4-9 mumol/1; 1-2 microgram/ml) was therefore valid in both groups. The depression of phenytoin binding was directly related to the plasma concentration of valproate both in random samples taken from the 42 patients and in samples taken throughout the day in two of these patients. This was confirmed in vitro. Even when the concentration of valproate is known the degree of binding cannot be predicted. Saliva rather than plasma monitoring of phenytoin treatment is therefore valuable in the presence of valproate and with reduced phenytoin binding from any cause.     

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.     

A single-dose comparison of four slow-release theophylline preparations in normal subjects

The plasma theophylline concentrations produced by 4 different slow release formulations, Theograd, Theodur, Theolair-SR and Rona-slophylline were measured over a 24-hr period in 8 healthy subjects. All 4 preparations maintained plasma levels over 12 hr and had similar AUC values when the difference in theophylline content was taken into account. Paired saliva and plasma theophylline concentrations gave a ratio of 1: 0·38, saliva: plasma, but with a large inter and intra individual variation.     

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.     

Increasing saliva (free) oestriol to progesterone ratio in late pregnancy: a role for oestriol in initiating spontaneous labour in man?

Oestriol and progesterone concentrations were measured in samples of saliva obtained daily from six normal women during the final four weeks before the spontaneous onset of labour. Progesterone concentrations were found to plateau whereas oestriol concentrations continued to rise so that the mean ratio of saliva oestriol to progesterone increased from 0.80 to 1.43 between 29 days and one day before labour. Saliva oestriol concentrations were 15 times higher than saliva oestradiol concentrations. As saliva steroid concentrations reflect the unbound unconjugated (free) plasma steroid concentrations these data suggest that a changing ratio of oestriol to progesterone may play a part in initiating spontaneous labour in man.     

Gentamicin: use of a programmable calculator to determine dosages from pharmacokinetic data for individual patients.

Gentamicin, an antibiotic frequently used in the treatment of gram-negative infections, has a narrow therapeutic index, so the correct prediction of its serum concentrations is important. Recent studies have emphasized the dubious accuracy of commonly used formulas, and computer programs that provide pharmacokinetic data for individual patients from multiple blood samples have helped to adjust dosages but are expensive. This study tested the applicability of a method using only two blood samples and a programmable calculator to estimate pharmacokinetic parameters for individual patients and adjust dosages to aim at peak and trough serum levels of 6 and 1 micrograms/ml respectively. In the 48 patients with normal renal function this method produced peak serum concentrations of gentamicin within 1 microgram/ml of the desired level in 22 (46%) and therapeutic peak concentrations (between 4 and 10 micrograms/ml) in all the patients. In 10 patients with renal failure it produced peak serum concentrations within 1 microgram/ml of the desired value in 4 and therapeutic serum concentrations in 7. Two patients had peak concentrations below 4 micrograms/ml and one had a peak concentration above 10 micrograms/ml. Two of the three patients whose serum levels were outside the therapeutic range had unstable renal insufficiency. Thus, patients with renal insufficiency need continued monitoring of the serum level of gentamicin, particularly when their renal function is changing.     

Oral aminophylline therapy. Increased dosage requirements in children

While monitoring oral aminophylline (theophylline ethylenediamine) therapy, larger doses (milligrams per kilogram) were necessary for children than for adults to achieve similar therapeutic serum levels. The mean apparent theophylline clearance (ATC) determined in 59 children was significantly higher (P less than .001) than determined in 114 adults (84.8 versus 51.4 ml/hr/kg). Additionally, the younger children (1 to 9 years) eliminated theophylline more rapidly than the older children (0 to 18 years) (93.8 versus 77.3 ml/hr/kd). When initiating continuous oral aminophylline therapy, dosage guidelines, based on the mean ATC calculated for each group, were predicted, and trough theophylline serum levels of 10mug/ml were obtained. The guidelines for aminophylline were 28.0, 23.2, and 15.6 mg/kg/day administered in four divided doses for the younger children, older children, and adults, respectively. Monitoring of serum levels is suggested to further individualize the patient's aminophyline therapy.     

Comparison of the effect of oxitropium bromide and of slow-release theophylline on nocturnal asthma

The effects of a new inhaled antimuscarinic drug, oxitropium bromide, and of a slow-release theophylline preparation upon nocturnal asthma were compared in a placebo-controlled double-blind study. Two samples were studied: 12 patients received oxitropium at 600 micrograms (6 subjects) or at 400 micrograms t.i.d. (6 subjects) whereas 11 received theophylline at 300 mg b.i.d. Morning dipping, assessed by the fall in peak flow overnight, was significantly reduced in the periods when either active drug was taken, whereas no difference was noticed during the placebo administration. No significant difference was noticed between results obtained with either active drug, as well as with either dosage of oxitropium. No subject reported side effects of oxitropium, as compared to three subjects reporting nausea, vomiting and tremors after theophylline. Oxitropium proves to be a valuable alternative to theophylline in nocturnal asthma, since it is equally potent, safer and does not require the titration of dosage.     

唾液检测的应用进展

唾液检测是一种近年兴起的、研究比较热门的医学检查方法. 唾液中存在反映全身健康状况的生物标志物,其蕴含着大量的生物信息. 与尿液标本相比,唾液具有可实时采样的优点. 与血清标本相比,唾液采集安全方便,无创伤,无血源性疾病传播的危险,患者无痛苦,易于接受. 唾液检测正成为当前无创检验领域最具潜力和应用前景的研究热点. 总结回顾唾液检测技术的发展现状,及其在疾病诊治、药物水平检测、心理学研究、法医取证、职业和环境医学及中医辨证客观化研究方面的进展,可为进一步研究提供参考.     

Relation of oral dose of oxtriphylline to serum theophylline level.

Serum theophylline levels were studied in relation to oral doses of oxtriphylline in 30 patients with reversible airway obstruction. A wide scattering of levels was observed and was attributed to widely differing rates of metabolism of the drug. From the data obtained it was concluded that the most commonly prescribed daily dose of oxtriphylline, 800 mg, will produce a therapeutic level of theophylline in only about one quarter of patients. A daily starting dose of 15 to 20 mg/kg, however, will produce therapeutic levels in approximately one third of patients without significant toxic effects. Once the patient's conditions is stable the serum theophylline concentration should be measured; if it is subtherapeutic the dose of oxtriphylline should be increased slowly and the serum theophylline concentration remeasured until a level of 10 to 20 microgram/ml is achieved.     

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.     

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）。     

康复新液对头颈部肿瘤放疗后重度放射性口腔黏膜炎的治疗作用及对唾液腺的保护作用

目的 探讨康复新液对头颈部肿瘤放疗后重度放射性口腔黏膜炎的治疗作用及对唾液腺的保护作用.方法 选取2016年10月—2019年10月在鄂东医疗集团市中心医院完成根治性放疗且发生重度放射性口腔黏膜炎的116例头颈部肿瘤患者,按随机数字表法将所有患者分为治疗组和对照组,每组各58例.在常规治疗的基础上,治疗组给予康复新液含...     

先声咳喘灵口服液对哮喘大鼠作用机制研究

目的: 研究先声咳喘灵口服液对哮喘模型大鼠抗哮喘作用的机制?方法:60只健康大鼠随机分为对照组?模型组?治疗组,每组20只?建立由卵蛋白致敏并诱发的支气管哮喘模型(40只),其中治疗组连续7天使用先声咳喘灵口服液(10 ml/kg)灌胃治疗?并采用ELISA法检测大鼠血清中细胞因子白介素(IL)-4?IL-5?IL-13的含量?结果:治疗组大鼠哮喘症状有明显改善,与哮喘组相比治疗组大鼠血清中IL-4?IL-5?IL-13的含量明显下降?结论:抑制细胞因子IL-4?IL-5及IL-13的合成可能为先声咳喘灵口服液抗哮喘的作用机制之一?     

Therapeutic drug monitoring of saquinavir in patients during protease inhibitor therapy with saquinavir alone or in combination with ritonavir or nelfinavir

Therapeutic drug monitoring is essential in HIV-patients undergoing highly active antiretroviral therapy (HAART). Saquinavir (SQV) is used alone or in combination with ritonavir (RTV) or nelfinavir (NLF), respectively, in the context of the HAART drug regimen. The achievable SQV concentration range in clinical practice remains to be elucidated. A non-randomized prospecitve clinical trial 19 patients (group I) receiving SQV (1x600 mg/d Invirase or Fortovase), 29 patients (group II) receiving SQV (2x600 mg/d Fortovase) plus RTV (2x400 mg/d Norvir), and 21 patients (group III) receiving SQV (2x600 mg/d Fortovase) plus NLF (2x750 mg/d Viracept) was conducted to determine SQV plasma concentrations. SQV levels were determined as trough levels during routine outpatient visits. Analysis was performed by HPLC with UV detection. The lowest SQV plasma levels were found in group I (95% CI 89-177 ng/ml). Significantly higher SQV levels were found in group III (combination with NLF) ranging from 242 to 398 ng/ml (95% CI) and in group II (combination with RTV) ranging from 1354 to 1747 ng/ml (95% CI). The IC 50% of 54 ng/ml was not reached in at least one sample during the study (mean duration of study 16+/-10 months) in 14/19 patients of group I, 9/29 patients in group II and 13/21 patients in group III, respectively. A positive correlation between patient compliance, defined by SQV levels in the 95% CI of the used combination, and the HIV RNA plasma level was found. The presented data confirm that therapy with SQV alone may not be effective, since trough levels are near the lower limit of antiretroviral efficacy. Although the combination of SQV with NLF results in higher SQV plasma concentrations in a bid regimen, in more than 60% of the patients SQV concentrations below IC 50 level were detected during the twelve-months study period. The combination of SQV with RTV yields the highest SQV-trough levels. SQV concentrations below the IC 50 were seen in only 31% of patients with the SQV/RTV combination. In conclusion, therapeutic drug monitoring allows an efficient surveillance of patients compliance. In addition, therapeutic drug monitoring represents a valuable tool for management of HAART in patients receiving a complex comedication or suffering from advanced liver disease.     

唾液与血清肾功能检测指标的相关性

目的 通过检测唾液与血清中肾功能指标的相应数据，从中探讨其相关性，为临床提供一条肾功能检查的新逢径，方法 对54例患者于同日清晨采集唾液与血清并同步进行UN，CRE，HCO3^-，K^＋，GLU检测，然后进行唾液与血清检测指标的相关性分析，并进行统计学处理。结果 唾液与血清UN，CRE有显著相关性（r=0．957，P〈0．01；r=0．929，P〈0．01）．HCO3^-，K^＋，GLU无相关性（P〉0．05）．结论 唾液中UN,CRE的检测数据可以作为评价肾功能的指标应用于临床。     

唾液在临床疾病诊断中的研究进展

唾液是口腔腺体分泌的一种重要的生物流体物质,当机体发生某种疾病时,唾液中某些成分会发生变化,唾液中发生变化的这些生物标志物在血液中均可检测到,只是浓度较低。对唾液分泌通路、唾液中生物标志物与疾病相关性的深入研究以及敏感的分子诊断技术的应用,使唾液作为标本用于疾病的诊断成为可能,同时也将开辟疾病快速无创诊断的新途径。     

唾液SIgA含量与儿童复发性腮腺炎关系的研究

目的 探讨唾液分泌型免疫球蛋白A（SIgA）含量与儿童复发性腮腺炎的关系。方法 采用ELISA法定量测定45例复发性腮腺炎患儿唾液SIgA含量，并与36例非复发性腮腺炎患儿作比较。结果 复发性腮腺炎患儿平均唾液SIgA含量为375．19±209．69μg／ml，显著高于非复发性腮腺炎患儿（217．07±186．52μg／m1），差异具有显著性（P〈0．001）。结论 检测复发性腮腺炎患儿唾液SIgA含量对观察病程和预后有重要的临床价值。     

石椒草咳喘颗粒联用氟替卡松防治儿童哮喘分析

目的 探讨石椒草咳喘颗粒对儿童哮喘的防治作用,减少哮喘儿童的用药副作用.方法 首次就诊的哮喘急性发作期患儿,初期均吸入沙丁胺醇气雾剂,按常规处理,A组口服石椒草咳喘颗粒8 g/次,1日3次;B组口服缓释茶碱0.1 g/次,12h1次;2组均用氟替卡松气雾剂吸入,每日1次,125 μg/次,疗程均为1个月.结果 治疗后A、B 2组患儿临床症状、体征均明显好转,A组、B组间无明显差异（P〉0.05）.结论 应用石椒草咳喘颗粒与缓释茶碱相比,在儿童哮喘的防治上无显著差异,且未发现副作用.     

A role for the adrenal cortex in the onset of cystic ovarian follicles in the sow

The corticotrophin (ACTH)-adrenal cortical axis has previously been implicated in the onset of cystic ovaries in the sow. In view of the role of the ACTH-adrenal cortical axis in stress, two sows were subjected to an elevated environmental temperature of 32 degrees C for three hours daily during the follicular phase of the estrous cycle. Plasma concentrations of glucocorticosteroids and progesterone fluctuated markedly in one sow that developed cystic ovaries. Concentrations of these hormones did not vary greatly in the other sow that did not develop cystic follicles. Exposure to an environmental temperature of 32 degrees C for three hours or injection of 1 IU/kg bodyweight of ACTH for each of two ovariectomized sows resulted in an elevation in progesterone values to 5-7 ng/ml plasma from basal levels of 1-2 ng/ml and a rise in total glucocorticosteroids from basal levels of 1 or 2 microgram/100 ml plasma to 4-10 microgram/100 ml. Injection of 2 mg/kg bodyweight of progesterone and 4 mg/kg bodyweight of cortisol into the ovariectomized sows was found to approximate these elevations in plasma steroid values. When either progesterone or cortisol was injected daily during the follicular phase into two intact sows in two successive experiments at these dosage levels, similarly elevated plasma steroid concentrations were seen and cystic ovarian follicles resulted. The results suggest that glucocorticosteroids and progesterone of adrenal origin may be involved in the onset of cystic ovaries in the sow.