Further studies on the chronotherapy of asthma with inhaled steroids: The effect of dosage timing on drug efficacy

Background: Chronotherapy studies with inhaled corticosteroids have shown optimal therapeutic benefit when steroids are administered four times per day (QID) or once daily at 3 PM.Objective: This study evaluated whether more convenient once-daily dosage times (8 AM and 5:30 PM) produce improvement in asthma equivalent to QID.Methods: Efficacy outcome measures included FEV₁, peak expiratory flow rates, bronchial responsiveness, use of β₂-agonists, nocturnal awakenings, and responses to a quality of life questionnaire. Systemic effects were blood eosinophil count, cortisol level, 24-hour urinary cortisol, and evaluation for oral candidiasis and dysphonia.Results: Baseline measurements for all three treatment groups were similar. For morning peak expiratory flow rate, significant improvement was seen for the QID group (p = 0.001) and the 5:30 PM group (p = 0.003), but not the 8 AM group (p = 0.75). For evening peak expiratory flow rate, significant improvement was seen for the QID group (p = 0.005) and the 5:30 PM group (p = 0.01), but not for the 8 AM group (p = 0.47). There were significant improvements in all other outcome variables for each group except PC₂₀. There was a significant improvement in PC₂₀ only in the QID group. The systemic effects of the three regimens were comparable.Conclusion: Dosing of inhaled steroid at 5:30 PM had no increased systemic effects and produced efficacy similar to QID dosing. Dosing at 8 AM did not produce results consistently comparable to QID dosing. Optimal once-daily dosing of inhaled steroid is between 3 PM and 5:30 PM.     

Intertubular growth in pure seminomas: associations with poor prognostic parameters

Clinical stage I seminomas are effectively treated with surgery raising concerns as to when to give adjuvant radiation therapy given the risk of secondary malignancies. A recent randomized trial found tumor size and rete testis invasion to be the strongest predictors of relapse in clinical stage I seminomas. These 2 parameters may be surrogate measures of tumor volume. Intertubular seminoma (ITS) of the testis describes the presence of neoplastic germ cells within the interstitium of the testis. These cells are detected away from the main macroscopic mass. Because ITS can infiltrate in a 3-dimensional fashion, it may also represent a measure of tumor volume not usually noted in standard pathology reporting. The goal of this study was to determine the incidence of ITS in pure seminomas and its association with other prognostic parameters. One hundred twenty consecutive pure seminomas surgically removed between 1998 and 2003 were evaluated. ITS was defined as the presence of an interstitial or intertubular growth pattern of tumor cells, which was noncontiguous with the main tumor and present at least 3 high-power fields away from the tumor mass. The average tumor size was 3.4 cm. Of the entire cohort of patients, which included pathological stages T1 through T3, 11% had invasion through the tunica albuginea, 51% had rete testis invasion, 51% had lymphovascular invasion, 93% had associated intratubular germ-cell neoplasia, and 36% had ITS. ITS was significantly associated with rete testis invasion ( P = .001). Logistic regression analysis looking at ITS, tumor size, patient age, and lymphovascular invasion revealed that only ITS was associated with rete testis invasion (RR, 4.1, P < .0001). ITS is present in a significant proportion of pure seminomas and has a significant association with rete testis invasion. The presence of ITS may therefore be an important prognostic factor, not only because it alters the calculated size of the tumor but also because it has an association with rete testis invasion.     

鼻咽癌调强放射治疗的剂量验证

目的:对接受调强放射治疗的鼻咽癌病人进行治疗前的剂量验证.材料和方法:利用电离室,胶片和验证模体对39个接受调强放射治疗的鼻咽癌患者,在治疗开始前进行绝对剂量和相对剂量验证.绝对剂量验证主要在两个位置进行:一个在等中心位置,另一个在离等中心4cm靠进腮腺的位置.相对剂量主要用体模对单野和整个计划的剂量分布进行验证.将得到的剂量分布利用分析软件与计划中的剂量分布进行分析比较.利用剂量偏差(dose difference)、吻合距离(distance to agreement,DTA)、γ指数等参数来测量剂量验证的偏差.结果:中心点和腮腺边上点的平均绝对误差分别为2.70%和3.03%.对于测量感兴趣区域(ROI,region of interested)的相对误差的测量,90%的测量都在设定的标准(3%,3 mm)之内,对于未能达到剂量偏差和间距偏差标准的区域,结合γ分析后一般也可以得到满意的结果.结论:验证结果表明实际测量剂量分布与计划计算的剂量分布符合的相当理想.     

Acute and Subacute Toxicity of Aspilia Africana Leaves

This study was designed to evaluate the toxicity of the aqueous extract of Aspilia africana leaves. Oral doses of 500 mg/kg and 1000 mg/kg were administered for 28 days to rats after every 2 days for sub-acute toxicity. For acute toxicity, 5 doses of 2, 4, 8, 12 and 16g/Kg body weight were investigated in mice. The control groups consisted of mice or rats administered with distilled water. The signs of toxicity fluctuated lightly from one mammal to another throughout the experiment. The liver, kidneys and heart weight of rats revealed no significant differences between the test groups and the control. The results indicated that the medium lethal dose (LD₅₀) was found to be greater in females than males with an average of 6.6g/Kg body weight for both sexes. Regardless of the significant differences observed at certain points in some biochemical parameters (ALT, AST, ALP, Creatinine and Glutathione); none showed any linear dose responsiveness. On the other hand, most of the parameters investigated were found to be gender dependent. These results suggested that A Africana can be classified among substances with low toxicity.     

X(γ)刀输出吸收剂量的测量与验证

目的：目前，国内X（γ）刀的国家检定规程正在起草之中，本文的目的是为X（γ）刀剂量测量提供合理的设备与吸收剂量计算方法。材料与方法：利用德国PTW-UNIDOS剂量仅与有效体积为0．015cc的针尖电离室及自制的小体积半导体探测器相匹配，在160mm直径的有机玻璃球形模体内测量X（γ）刀的输出吸收剂量，并验证其治疗计划的实际输出剂量，得到较满意的结果。结论：为了保证剂量的准确度，X（γ）刀治疗计划系统的实际输出剂量应定期在现场测量与验证，所用探测器的直径应小于射野直径的1／2，小灵敏体积的半导体探测器适宜X（γ）刀小野(如：Ф4mm)的测量。     

Development and characterization of DNAzyme candidates demonstrating significant efficiency against human rhinoviruses

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用PCR-SSCP分析检测睾丸女性化综合征患者雄激素受体基因突变

为进一步探讨睾丸女性化（Ｔｆｍ）综合征患者发病的分子机理，并为研究雄激素受体（ＡＲ）结构与功能关系提供资料，应用银染聚合酶链式反应－单链构象多态性（ＰＣＲ－ＳＳＣＰ）分析方法对４例Ｔｆｍ患者的ＡＲ基因８个外显子中的７个（Ｂ～Ｈ）分别进行了研究。结果表明，所有患者ＡＲ基因的上述外显子经ＰＣＲ扩增后均出现与外显子相应长度一致的条带，表明没有明显的缺失或插入突变。２例患者外显子Ｇ片段在行ＳＳＣＰ分析时分别有泳动变位，经ＤＮＡ双链循环测序证实两外显子各有一点突变（Ｖａｌ８６６Ｍｅｔ，Ｔ２９１９→Δ），这些突变均位于ＡＲ的雄激素结合区内。其中的缺失突变为国际上尚未报道过的新突变。研究表明，ＰＣＲ－ＳＳＣＰ分析是检测ＡＲ基因突变的快速、简便、可靠的方法。     

Pharmacokinetic studies of high-dose metoclopramide with and without forced diuresis

Summary The pharmacokinetics of high-dose metoclopramide (10 mg/kg body wt. in five infusions of 2 mg/kg body wt. each) was studied in 11 patients (5 females, 6 males) in two groups: group A with and group B (consisting of five patients) without forced diuresis. When the drug was infused, forced diuresis had no influence on the pharmacokinetics of metoclopramide (serum level after the 1st infusion was 851±361 ng/ml in group A versus 840±348 ng/ml in group B; after the 5th infusion it was 2,005±588 ng/ml in group A versus 2,463±1,350 ng/ml in group B). There were significant differences in the 24-h serum levels (582±308 ng/ml in group A versus 379±170 ng/ml in group B;P<0.05) and in the elimination half life (8.5±2.6 h in group A versus 6.1±1.1 h in group B;P<0.05). The results demonstrate that the dosage regimen originally suggested by Gralla for cytostatic drugs, with forced diuresis for high-dose metoclopramide therapy, may also be applied, with no dosage reduction, with to other cytostatic drugs which do not require forced diuresis.     

低剂量γ射线辐照对血清一氧化氮及一氧化氮合酶水平的影响

目的：观察低剂量γ射线照射人离体外周血对血清中一氧化氮（NO）和一氧化氮合酶（NOS）水平的影响。方法：采集10份健康献血员全血，肝素抗凝，然后采用γ射线照射，照射剂量率为17Gy／min，总吸收剂量为1Gy，分别于照射前及照射后1h，2h采用分光光度法检测血清中NO含量和NOS活性。结果：经γ射线照射1h后，血清中NO及NOS水平与照射前比较明显升高（P〈0.01）；照射后2h，血清中NOS水平与照射后1h比较无统计学差异（P〉0、05），但是还明显高于照射前的水平（P〈0．01）；在照射后2h，血清中NO含量与照射后1h比较明显降低（P〈0.01），但仍明显高于照射前水平（P〈0．01）。结论：采用剂量为1Gy的γ射线照射外周血，可引起血清中NO水平及NOS活性的显著升高．从而为低剂量辐照自体血回输对肿瘤的辅助治疗提供了理论支持。     

Effect of various doses of palm vitamin E and tocopherol on aspirin-induced gastric lesions in rats

This study examined the effects of vitamin E on the prevention of aspirin-induced gastric lesions. The study was divided into two phases. Phase 1 determined the effects of various doses of palm vitamin E on the factors affecting mucosal integrity. Thirty-two male rats of the Sprague-Dawley strain (200-250 g) were randomly divided into four groups. Group I was fed a normal diet (control), Groups II, III and IV were fed a diet supplemented with palm vitamin E in a dose of 60 mg/kg food, 100 mg/kg food and 150 mg/kg food, respectively. The rats were killed after 4 weeks of feeding for the determination of gastric malondialdehyde (MDA), acid and mucus content. There was a significant decrease in gastric MDA and gastric acid in all the palm vitamin E supplemented groups compared to control. However, these doses of palm vitamin E had no significant effect on gastric mucus. The phase 2 study determined the effect of multiple doses of palm vitamin E and tocopherol on the prevention of aspirin-induced gastric lesions. Fifty rats of the same weight and strain were randomized into seven groups. Group I was fed a normal diet; groups II to IV were fed with a palm vitamin E enriched diet in doses of 60 mg, 100 mg and 150 mg/kg food, respectively; groups V to VII were fed with a tocopherol-enriched diet in doses of 20 mg, 30 mg and 50 mg/kg food, respectively. After 4 weeks of feeding with the respective diets the rats were challenged with a single intra-gastric dose of 400 mg/kg body weight aspirin suspended in propylene glycol. The rats were killed 6 h post-aspirin exposure for the determination of gastric lesion index and gastric parameters as mentioned in the phase I study. The gastric lesions index was significantly lower in all the vitamin E groups compared to control. The lowest ulcer index was observed in the groups that received 100 mg of palm vitamin E and 30 mg tocopherol in the diet. However, there was no significant difference in ulcer indices between palm vitamin E and tocopherol-treated groups. The lower ulcer index was only accompanied by lower gastric MDA content. We conclude that both palm vitamin E in doses of 60 mg, 100 mg and 150 mg/kg food as well as tocopherol in doses of 20 mg, 30 mg and 50 mg/kg food are equally effective in preventing aspirin-induced gastric lesions. The most probable mechanism is through their ability in limiting the lipid peroxidation that is involved in aspirin-induced gastric lesions.