中药复方962对老年大鼠外周血淋巴细胞DNA损伤的影响

目的：观察不同年龄组（4月和24月龄）大鼠和连续灌胃给予中药复方962 3个月的老年大鼠的外周血淋巴细胞DNA的损伤情况。方法：利用快速、灵敏的单细胞电泳技术结合激光扫描共聚焦显微镜来观察大鼠外周血淋巴细胞的DNA损伤,以彗星样细胞出现率（计数一定量细胞中彗星样细胞所占的比例）、占彗星长度（“彗星”电泳方向上的最大长度）和尾距（尾部DNA占总DNA的百分比与头尾部中心间距的乘积）来评价淋巴细胞DNA的损伤程度。结果：发现老年大鼠外周血淋巴细胞中彗尾样细胞出现率显著高于青年大鼠（P＜0．01）,复方962不仅能明显降低老年大鼠的淋巴细胞的彗尾样细胞出现率,而且能明显降低老年大鼠外周血彗星样细胞的总彗星长度和尾蹑（P＜0．01）。结论：实验表明复方962对老年大鼠淋巴细胞DNA的损伤有明显的保护作用。     

24-h pH monitoring is necessary to assess acid reflux suppression in patients with Barrett's oesophagus undergoing treatment with proton pump inhibitors

BACKGROUND: Control of acid reflux is the main objective of treatment for Barrett's oesophagus. However, as these patients have a reduced sensitivity to acid reflux, disappearance of symptoms may not correlate with efficient control of acid reflux. The aim of this study was to determine in a group of patients with Barrett's oesophagus whether treatment with proton pump inhibitors suppressed pathological acid reflux once the symptoms of reflux had been controlled and the associated inflammatory lesions cured. METHODS: Eighteen consecutive patients with Barrett's oesophagus were studied, all of whom presented with heartburn. Twenty-four-hour oesophageal pH monitoring before treatment showed pathological acid reflux in all cases: median percentage of total time with pH less than 4, 22 (range 8-52) per cent. All patients received proton pump inhibitors (dose 20-60 mg/day) until symptoms were controlled. RESULTS: While on therapy, pH was reduced (median percentage of total time with pH less than 4, 3 versus 22 per cent; P < 0.001). However, three patients had persistent pathological rates of acid reflux. CONCLUSION: Disappearance of symptoms is not a good indicator of control of pathological acid reflux in patients with Barrett's oesophagus. Twenty-four-hour pH monitoring should be performed for proper adjustment of the dose of medication.     

Effects of selective phosphodiesterase inhibitors on platelet-activating factor- and antigen-induced airway hyperreactivity, eosinophil accumulation, and microvascular leakage in guinea pigs

There is currently interest in the potential use of selective inhibitors of cyclic nucleotide phosphodiesterases (PDE) in the treatment of asthma. In this study we examined the effects of three selective PDE inhibitors, milrinone (PDE III), rolipram (PDE IV) and zaprinast (PDE V), on the broncoconstriction produced by antigen and histamine, the airway hyperreactivity and microvascular leakage after aerosol exposure to platelet-activating factor (PAF) and antigen, and the antigen-induced eosinophil infiltration in guinea-pig lung. Inhaled rolipram (0.01–10 mg ml^–1) inhibited dose dependently the bronchospasm produced by aerosol antigen (5 mg ml^–1) an anaesthetised, ventilated guinea-pigs. Rolipram (10 mg ml^–1) produced maximal inhibition of antigen-induced bronchoconstriction but only partial inhibition of the response to aerosol histamine (1 mg ml^–1). Milrinone and zaprinast (each 10 mg ml^–1) showed weak, or no, inhibitory effects against bronchoconstriction produced by aerosol antigen or histamine. Pretreatment with rolipram (10 mg kg^–1, i.p.) prevented airway hyperreactivity to histamine which develops 24 h after exposure of conscious guinea-pigs to aerosol PAF (500 g ml^–1) or antigen (5 mg ml^–1). The pulmonary eosinophil infiltration obtained with 24 h of antigen-exposure was inhibited by rolipram. In contrast, milrinone and zaprinast (each 10 mg kg^–1, i.p.) failed to reduce either the airway hyperreactivity of the eosinophil accumulation in these animals. Rolipram (1–10 mg ml^–1) reduced the extravasation of Evans blue after aerosol PAF (500 g ml^–1) at all airway levels while a lower dose (0.1 mg ml^–1) was only effective at intrapulmonary airways. Rolipram (0.01–1 mg ml^–1) markedly reduced airway extravasation produced by inhaled antigen (5 mg ml^–1). Zaprinast (1–10 mg ml^–1) was also effective against airway microvascular leakage produced by aerosol PAF or antigen while milrinone (10 mg ml^–1) had no antiexudative effect. These data support previous suggestions that pharmacological inhibition of PDE IV results in anti-spasmogenic and anti-inflammatory effects in the airways and may be useful in the treatment of asthma.     

Dynamic assessment of pelvic floor function in women using the intravaginal device test

The aim of the study was to assess pelvic floor function and dysfunction using intravaginal devices (IVD test). One hundred and eighty-five patients were evaluated, 65 (35.1%) in the control group without genital prolapse and 120 (64.9%) in the study group, with prolapse. Anatomic changes were evaluated on a scale described by Halban, and functional classification based on palpation of the muscles of the pelvic floor during contraction. Additionally, weighted vaginal devices were used to assess pelvic floor function. Statistic analysis was performed with the Spearman-Pearson correlation coefficient, the ² test and the response/ operator characteristic curve. There was an acceptable correlation between the IVD test and the functional classification of 0.75. Using this classification, the IVD test showed 86.58% sensitivity, 75.72% specificity, and had a positive predictive value 73.95% and a negative predictive value of 87.64%. Significant differences between pelvic floor muscle activity in those patients with and without genital prolapse were observed (X²=58.28, P=<0.005). It was concluded that pelvic floor assessment can be done through the evaluation of active muscle strength or pelvic floor integrity using the functional classification and the IVD test.EDITORIAL COMMENT: In 1988, Peattie and Plevnick introduced the use of weighted vaginal cones to exercise the pelvic floor muscles and treat stress urinary incontinence [1]. Contreras-Ortiz and Nuñez build on this earlier work, using a similar technique to assess pelvic floor muscle function and integrity. Specifically, pelvic floor function is assessed by a combination of digital palpation of the pubococcygeus muscle at rest and during contraction; pelvic floor integrity is assessed by the patient's ability to retain a weighted cone vaginally for 1 minute. Scoring of these two parameters can then be objectively followed for therapeutic response to treatment for urinary incontinence or pelvic relaxation. Many of us forget to palpate the pubococcygeus muscle at rest and during an elicited contraction during baseline or follow-up examination. As this study indicates, simple assessment of pelvic floor function and integrity is possible, and should be used both clinically and in research.     

ASTRO plenary: interfraction interval is a major determinant of late effects, with hyperfractionated radiation therapy of carcinomas of upper respiratory and digestive tracts: results from Radiation Therapy Oncology Group protocol 8313

A prospective, randomized, multi-institutional, Phase I(LE)/II trial of HFX was conducted by the RTOG between 1983 and 1987. Patients with histologically proven, inoperable squamous cell carcinoma of the upper respiratory and digestive tracts stratified by site, nodal status, and performance status, were assigned to one of three arms, were assigned to one of three arms, 67.2 Gy, 72.0 Gy, or 76.8 Gy. Fractions of 1.2 Gy were given twice daily, 5 days per week: intervals of 4 to 8 hours were permitted between fractions. After acceptable rates of acute normal tissue effects were found, the randomization was changed to evaluate a new higher total dose, 81.6 Gy. Of 479 patients entered, 447 were analyzed, 63 on 67.2 Gy, 129 on 72.0 Gy, 117 on 76.8 Gy, and 138 on 81.6 Gy. The treatment arms were well balanced with respect to pretreatment characteristics. Acute reactions consisted almost entirely of pseudomembranous inflammation. "Severe" (Grade 3) acute reactions were reported in 33% to 41% and grade 4 reactions were found in 0 to 3% of patients, with no differences in frequencies among the four arms. Toxicities that developed or persisted beyond 90 days after the first treatment (408 patients evaluable greater than 90 days) did not differ among arms: grade 3+ reactions occurred in 10% to 14%, and grade 4+ effects (necroses) were reported in 5% at 67.2 Gy, 3% at 72.0 Gy, 7% at 76.8 Gy, and 2% at 81.6 Gy. Grade 3+ acute reactions occurred in 40% of patients when the interfraction interval was less than or equal to 4.5 hours versus 31% with greater than 4.5 hours (p = .03). Interfraction intervals less than or equal to 4.5 hours were associated with higher frequencies of grade 4+ late effects in all four arms, 8% of 197 patients with less than or equal to 4.5 hours versus 1% of 211 patients with greater than 4.5 hours. Estimates of late toxicity at 1, 2, and 3 years were 5.5%, 9.8%, and 15.4% with intervals less than or equal to 4.5 hours, versus 1.7% at all three periods for greater than 4.5 hours (p = .006). Local-regional control at 2 years was 25% for the assigned dose of 67.2 Gy compared to 43% to 45% for the three higher doses (p = .01), but a similar comparison for survival showed no significant difference (p = .35). There was no evidence for an effect of interfraction interval on either local-regional control (p = .38) or survival (p = .28).(ABSTRACT TRUNCATED AT 400 WORDS)     

苦参素注射液的人体药动学

目的：建立测定苦参素血药浓度的HPLC法并研究苦参素注射液在健康人体内的药物动力学。方法：18名健康男性受试者，肌注300mg药物后，采用HPLC法测定血药浓度，用3p87软件经微机处理药－时数据。结果：苦参素注射液的体内过程符合二室模型。结论：此法提供了苦参素注射液在健康人体中的药动学数据。     

口服抗病毒新药——缬更昔洛韦

缬更昔洛韦 (valganciclovir)是抗病毒药更昔洛韦的前体药物 ,用于治疗AIDS病人发生的巨细胞病毒 (CMV)视网膜炎。缬更昔洛韦口服后迅速吸收 ,并水解为更昔洛韦 ,其口服给药的生物利用度较高 (60 % )。试验表明 ,口服缬更昔洛韦 (90 0mg)与静脉注射更昔洛韦 (5mg·kg-1) ,bid,3wk后改为 qd ,治疗 1 60例AIDS病人发生的CMV视网膜炎有相同疗效 ,且耐受性相似。缬更昔洛韦维持治疗中最常见的不良反应为中性粒细胞减少症、贫血、胃肠道反应 (腹泻、恶心、呕吐 )、发热、头痛和失眠等