治疗类风湿关节炎中药组分配伍方案的研究

目的：基于丰富的中医药文献数据,为治疗类风湿关节炎中药化学组分配伍方案的研究提供新思路。方法：从治疗类风湿关节炎的临床文献出发,以证候、方剂、中药、化学组分和药理作用为要素,筛选出针对类风湿关节炎的不同证候的以某一核心方为中心的一类方剂的化学组分,再结合西医治疗类风湿关节炎所用药物具有的药理作用,最后从文献报道的化学组分组合中提出组分配伍方案。结果：根据治疗类风湿关节炎风湿热郁证的除弊汤为核心的一组方剂,提出了6个组分配伍方案。结论：本研究提出的基于文献的组分配伍方案的研究方法具有一定的实用性。     

The emergence of multiword utterances in children with Down syndrome

Morphosyntax is one of the most impaired aspects of language development in children with Down syndrome. The present study aimed to assess the emergence of multiword utterances in this population. Sixteen Italian-speaking children with Down syndrome were followed from 36 to 48 months of age. Data derived from an analysis of their spontaneous productions showed that although the mean productivity of multiword utterances increased over the three time points (36, 42 and 48 months), different growth patterns of early syntactic development could be identified: (1) null or marginal development; (2) a gradual increase in multiword production over time; (3) an increase in the production of more complex multiword utterances and a decrease or inverted U-shaped profile in the production of simpler multiword productions; (4) an inverted U-shaped profile in multiword productions. In addition, children showed an improvement in their ability to express different semantic functions by word combinations. Significant relationships were found between early syntactic skills and both the child’s vocabulary size and developmental age.

A better knowledge of the acquisition pace and content of word combinations could allow more effective rehabilitative treatment during the first steps of children’s syntactic development.     

The effect of fixed combination of fluticasone and salmeterol on asthma drug utilization,asthma drug cost,and episodes of asthma exacerbations

ABSTRACT

Objective: This study evaluated the use and drug costs of inhaled corticosteroids (ICSs), long-acting β₂-agonists (LABAs), and fluticasone propionate and salmeterol in a fixed-dose combination (FSC) and their relationship to asthma exacerbations before and after the market introduction of FSC in April 2001.

Methods: This is a retrospective analysis of employer-sponsored health insurance claims filed between January 1, 1998, and December 31, 2003 to detect impact of introduction of FSC (approved by the US Food and Drug Administration in August 2000) on utilization and cost of FSC, any ICS (excluding FSC), and any LABA (excluding FSC) along with utilization of medical services related to asthma exacerbations. Asthma medications were identified using National Drug Codes and Redbook, whereas asthma exacerbations were identified using ICD?9?CM primary diagnosis code 493.x. These medical and pharmacy claims were converted to rates per 100 asthma office visits.

Results: For all ICSs, the average pharmacy claims per 100 office visits increased from 383 in the year before FSC was introduced to 407 (120 [29.5%] were for FSC and 287 [70.5%] were for single-entity ICSs) in 2003. LABA prescribing increased from 72 in the year before FSC to 147 (120 from FSC, 27 single-entity LABA) in 2003 (?p < 0.001). An additional $13?511 per 100 asthma office visits was spent on the FSC product (?p < 0.001). After the introduction of FSC, there was no significant difference in asthma admissions (?p = 0.17), whereas emergency department (ED) visits increased by 0.92 visits per 100 office visits (?p = 0.03). The diagnosis and severity of asthma was inferred from the pharmacy claims and patients with chronic obstructive pulmonary disease could not be excluded. In addition, the study was not designed to assess the impact of other asthma medications on the disease and/or associated costs, and patient adherence to claimed medication could not be monitored.

Conclusions: The introduction of FSC was associated with increased LABAs/FSC patient exposure and expenditure with no change in asthma hospitalizations and an increase in ED visits.     

萜烯类经皮渗透促进剂的研究与应用进展

透皮给药系统可有效避免肝脏首过效应及胃肠道降解，调控释药速率和血药浓度，降低不良反应及用药频率，提高患者顺应性。但角质层的屏障作用和药物的低渗透量，使其应用受到限制。萜烯类经皮渗透促进剂具有毒性低，促透能力强，可改善皮肤通透性，对亲水、亲脂药物均有促渗作用，低浓度高促透性的特点，在透皮给药系统中日益发挥着重要作用，显示出良好的应用前景。对其来源、分类、促透机制、实际应用、选择评价及应用前景进行综述。     

非洛地平与美托洛尔复方透皮贴剂的药代动力学和生物利用度评价

目的研究非洛地平(Fel)与美托洛尔(Met)复方透皮贴剂(Fel+Met-P)在兔体内的药代动力学和生物利用度。方法6只健康新西兰白兔分2次实验,先后分别随机交叉单次给予Fel+Met-P(1+10),(3+30)和(9+90)mg.kg-1,和随机交叉单次给予Fel+Met静脉注射液〔Fel+Met-I,(0.2+2)mg.kg-1〕、口服混悬液〔Fel+Met-S,(1+10)mg.kg-1〕及2药市售缓释片〔Fel+Met-T,(1+10)mg.kg-1〕,气相色谱-电子捕获法分别测定血浆中Fel和Met浓度,DAS软件计算药代动力学参数并进行生物利用度评价。结果Fel+Met-P血药浓度可平稳维持2～3d。在Fel+Met-P不同剂量组,Fel和Met的血药峰浓度(cmax)、血药-时曲线下面积(AUC)(0→60)和AUC(0→∞)分别随Fel+Met-P剂量增加而增大,且均与剂量(D)呈良好线性关系,Fel的回归方程为cmax=6.6342D+4.355(r=0.9969)和AUC(0→∞)=295.08D+92.322(r=0.9963),Met为cmax=8.4628D+51.528(r=0.9957)和AUC(0→∞)=315.14D+1474.8(r=0.9993);不同剂量组之间Fel和Met的达峰时间(tmax)、平均吸收时间(MAT)、平均驻留时间〔MRT(0→60)和MRT(0→∞)〕及各自绝对生物利用度均无显著性差异。与Fel+Met-S和Fel+Met-T比较,Fel+Met-P3个剂量组Fel和Met的tmax和MRT(0→∞)均延长,tmax分别为(21.5±8.1)～(27.0±12.3)和(25.3±14.4)～(37.5±10.0)h,MRT(0→∞)分别为(28.5±2.7)～(31.8±0.8)和(28.1±4.4)～(31.8±1.3)h;与Fel+Met-S比较,Fel的绝对生物利用度分别为Fel+Met-S的2.25,2.75和2.28倍,Met分别为Fel+Met-S的2.10,1.90和1.64倍;与Fel+Met-T比较,Fel的绝对生物利用度无明显变化,Met分别为Fel+Met-T的2.13,1.93和1.67倍。结论Fel+Met-P在兔体内具有缓释长效药代动力学特征,达到了提高药物生物利用度、延长药物体内驻留时间、维持平稳血药浓度和方便用药新剂型的设计目的。     

Interactions between amphotericin B and nitroimidazoles against Candida albicans

Summary. This work proved that nitroimidazole antiprotozoal agents, such as metronidazole, ornidazole, secnidazole and tinidazole, in concentrations of up to 64 μg ml^-1 did not present any antifungal activity against 17 strains of Candida albicans. The combination of each drug with amphotericin B showed the occurrence of variable interactions according to the studied strain. Promising results were observed based on synergistic and additive interactions of the polyene with the metronidazole; the inhibitory and lethal activities of the drugs were potentiated against all strains in concentrations reachable in vivo.
Zusammenfassung. In der vorliegenden Studie konnte gezeigt werden, daß die Nitroimidazol-Antiparasitika Metronidazol, Ornidazol, Secnidazol und Tinidazol in Konzentrationen bis zu 64 μg ml^-1 allein keine antimyzetische Aktivität gegen 17 C. albicans -Stämme aufwiesen. Die Anwendung dieser Agenzien gemeinsam mit Amphotericin B zeigte unterschiedliche Wirkungen auf die untersuchten Stämme. Erfolgversprechende Ergebnisse wurden als synergistische und additive Effekte bei der Kombination der einzelnen Nitroimidazole mit Amphotericin B beobachtet. Konzentrationen, die in vivo anwendbar sind, potenzierten die inhibitorischen und letalen Aktivitäten der Agenzien gegen alle untersuchten C. albicans -Stämme.     

Need Stable Diabetics Mix their Insulins?

Ten insulin-dependent diabetics taking twice-daily mixtures of soluble and isophane insulin were studied in a double-blind crossover trial to examine the effect on their glycaemic control of a fixed-mixture preparation (containing either 50% soluble, 50% isophane or 30% soluble, 70% isophane) given in the same total dose as each patient's usual mixture. The mean (+/- S.E.M.) of eight daily blood glucose determinations when the patients' usual mixtures were pre-mixed by the hospital pharmacy was 7.6 +/- 0.7 mmol/l, 7.8 +/- 0.8 mmol/l when the fixed-mixture preparation was used and 8.0 +/- 0.5 mmol/l when the patients drew up and mixed the insulins themselves. Individual glucose profiles on each of the three regimens expressed as mean modified log 'M' indices were 1.26 +/- 0.14, 1.29 +/- 0.16 and 1.37 +/- 0.14, respectively. Thus, the patients studied were as well controlled on a fixed-mixture preparation as on their usual 'tailormade' insulin regimens.     

Effects of the combination of camptothecin and doxorubicin or etoposide on rat glioma cells and camptothecin-resistant variants

From the rat C6 glioma cell line in culture, we selected camptothecin-resistant variants by growth in the presence of increasing amounts of this drug (C6(CPT10), C6(CPT50)and C6(CPT100), growing respectively with 10, 50 and 100 ng ml(-1)camptothecin). The degree of resistance to camptothecin ranged between 15-fold (C6(CPT10)) and 30-fold (C6(CPT50)and C6(CPT100)). The C6(CPT10)cell line presented a collateral sensitivity to etoposide (3.6-fold), while the C6(CPT50)and C6(CPT100)cell lines were cross-resistant to etoposide (1.8-fold) The resistant lines were characterised by a two-fold reduced content and catalytic activity of topoisomerase I, and C6(CPT50)and C6(CPT100)presented a significant increase in topoisomerase IIalpha content and catalytic activity and a marked overexpression of P-glycoprotein. We explored the cytotoxicity of combinations of a topoisomerase I inhibitor (camptothecin) and a topoisomerase II inhibitor (doxorubicin or etoposide) at several molar ratios, allowing the evaluation of their synergistic or antagonistic effects on cell survival using the median effect principle. The simultaneous combination of camptothecin and doxorubicin or etoposide was additive or antagonistic in C6 cells, slightly synergistic in the C6(CPT10)line and never more than additive in the C6(CPT50)and C6(CPT100)cell lines. The sequential combination of doxorubicin and camptothecin gave additivity in the order camptothecin --> doxorubicin and antagonism in the order doxorubicin --> camptothecin. Clinical protocols combining a topoisomerase I and a topoisomerase II inhibitor should be considered with caution because antagonistic effects have been observed with combinations of camptothecin and doxorubicin.     

Therapy of infections in neutropenic patients: Results with gentamicin in combination with cephalothin or chloramphenicol

Gentamicin in combination with cephalothin (Gent-Ceph) or with chloramphenicol (Gent-Chloro) was utilized in the treatment of 55 infections occurring in 49 cancer patients. Responses were obtained in 78% of the infections treated with Gent-Ceph and in 64% of those treated with Gent-Chloro. Pneumonia and septicemia were the most common infections in this study. Among the cases of pneumonia, 64% responded to Gent-Ceph and 67% to Gent-Chloro. Among the cases of septicemia, 88% responded to Gent-Ceph and 50% to Gent-Chloro. All of the identified organisms producing infection were gram-negative bacilli. Of these, E. coli was the most common. All organisms were resistant to cephalothin in vitro, and only 41% of them were resistant to chloramphenicol. However, resistant organisms responded significantly better to the Gent-Ceph combination (p < 0.025). Also, response to therapy among patients with severe neutropenia (< 100 neutrophils/mm³) was better for those patients treated with Gent-Ceph (p = 0.07). The combination of gentamicin with cephalothin or with chloramphenicol did not increase the frequency of side effects expected from gentamicin alone. No significant hematological toxicity was seen among those patients treated with chloramphenicol. Gentamicin in combination with cephalothin or chloramphenicol is an effective and safe antibiotic combination against gram-negative bacilli infections occurring in cancer patients. The efficacy of Gent-Ceph in patients with severe neutropenia is particularly advantageous.