Evaluation of hypothesis testing for comparing two populations using NONMEM analysis

In a simulation study of inference on population pharmacokinetic parameters, two methods of performing tests of hypotheses comparing two populations using NONMEM were evaluated. These two methods are the test based upon 95% confidence intervals and the likelihood ratio test. Data were simulated according to a monoexponential model and, in that context, power curves for each test were generated for (i)the ratio of mean clearance and (ii)the ratio of the population standard deviations of clearance. To generate the power curves, a range of these parameters was employed; other pharmacokinetic parameters were selected to reflect the variability typically present in a Phase II clinical trial. For tests comparing the means, the confidence interval tests had approximately the same power as the likelihood ratio tests and were consistently more faithful to the nominal level of significance. For comparison of the standard deviations, and when the volume of information available was relatively small, however, the likelihood ratio test was more able to detect differences between the two groups. These results were then compared to results on parameter estimation in order to gain insight into the question of power. As an example, the nonnormality of estimates of the ratio of standard deviations plays an important role in explaining the low power for the confidence interval tests. We conclude that, except for the situation of modeling standard deviations with only sparse information, NONMEM produces tests of significance that are effective at detecting clinically significant differences between two populations.Partial support from the Upjohn Company, NIH-BRSG SO RR 07066, and the Burroughs Wellcome Foundation.     

缺血－再灌注兔心肌肌浆网自由基的测定

应用电子自旋共振波谱仪（ＥＳＲ）直接检测了缺血－再灌注兔心肌肌浆网自由基的变化，以探讨肌质网系统与氧自由基的关系。实验中将２０只兔随机分为再灌注对照组、超氧化物歧化酶（ＳＯＤ）组、ＡＴＰ－氯化镁组和人参皂甙Ｒｅ组。实验结果，ｇ值２．００４６处为半醌自由基波谱，其相对浓度各组依次为７８．９４±２．１２６，１４．４６±２．８６，２０．６５±７．６５，１４．６６±３．６７（ｘ±ＳＤ），对照组与用药组均有显著性差异（Ｐ＜０．０５），表明缺血－再灌注兔心肌肌浆网产生大量的自由基，用ＥＳＲ可以直接检测到半醌自由基，外源性高能磷酸盐制剂ＡＴＰ－氯化镁及人参皂甙Ｒｅ与超氧化物歧化酶一样，发挥清除兔心肌肌浆网自由基的作用。     

Performance measurement of the microPET focus 120 scanner.

The microPET Focus 120 scanner is a third-generation animal PET scanner dedicated to rodent imaging. Here, we report the results of scanner performance testing. METHODS: A (68)Ge point source was used to measure energy resolution, which was determined for each crystal and averaged. Spatial resolution was measured using a (22)Na point source with a nominal size of 0.25 mm at the system center and various off-center positions. Absolute sensitivity without attenuation was determined by extrapolating the data measured using an (18)F line source and multiple layers of absorbers. Scatter fraction and counting rate performance were measured using 2 different cylindric phantoms simulating rat and mouse bodies. Sensitivity, scatter fraction, and noise equivalent counting rate (NECR) experiments were repeated under 4 different conditions (energy window, 250 approximately 750 keV or 350 approximately 650 keV; coincidence window, 6 or 10 ns). A performance phantom with hot-rod inserts of various sizes was scanned, and several animal studies were also performed. RESULTS: Energy resolution at a 511-keV photopeak was 18.3% on average. Radial, tangential, and axial resolution of images reconstructed with the Fourier rebinning (FORE) and filtered backprojection (FBP) algorithms were 1.18 (radial), 1.13 (tangential), and 1.45 mm full width at half maximum (FWHM) (axial) at center and 2.35 (radial), 1.66 (tangential), and 2.00 mm FWHM (axial) at a radial offset of 2 cm. Absolute sensitivities at transaxial and axial centers were 7.0% (250 approximately 750 keV, 10 ns), 6.7% (250 approximately 750 keV, 6 ns), 4.0% (350 approximately 650 keV, 10 ns), and 3.8% (350 approximately 650 keV, 6 ns). Scatter fractions were 15.9% (mouse phantom) and 35.0% (rat phantom) for 250 approximately 750 keV and 6 ns. Peak NECR was 869 kcps at 3,242 kBq/mL (mouse phantom) and 228 kcps at 290 kBq/mL (rat phantom) at 250 approximately 750 keV and 6 ns. Hot-rod inserts of 1.6-mm diameter were clearly identified, and animal studies illustrated the feasibility of this system for studies of whole rodents and mid-sized animal brains. CONCLUSION: The results of this independent field test showed the improved physical characteristics of the F120 scanner over the previous microPET series systems. This system will be useful for imaging studies on small rodents and brains of larger animals.     

Treatment of congenital cystic adenomatoid malformation-does resection in the early postnatal period increase surgical risk?

OBJECTIVE: The recent development of fetal ultrasonography has allowed for an increasing number of prenatal diagnoses for congenital cystic adenomatoid malformation (CCAM). However, the appropriate surgical timing of these patients has not been studied as of yet. The aim of this study is to suggest a safe strategy for the treatment of CCAM by identifying the relationship between the timing of surgery and postoperative outcome. METHODS: Between 1987 and 2003, 40 patients (28 males, 12 females) underwent surgical resection for CCAM. The mean age was 38.6+/-9.1 (2 days-13 years) months. CCAM was diagnosed by prenatal ultrasonography in eight patients. Early operations were performed in four out of the eight. Operation was deferred until 2-12 months of age for the remaining four patients. RESULTS: Type I CCAM was found in 20 patients, type II in 20 and no patient exhibited type III. Five patients had associated pectus excavatum anomaly. There were no cases of operative mortality. Seventeen minor postoperative complications developed in 16 patients (40.0%): prolonged chest tube drain in 10, wound infection in 4, and 1 case of pneumonia, empyema and pleural space, respectively. The average hospital stay was 11.8 (6-29) days. During the mean follow-up period of 67.5 months, one patient died of accidental aspiration 7 months after operation during the postoperative recovery course of Ravich operation for pectus excavatum. The remaining patients reported doing well with normal physical activity. All five patients who underwent surgery at the age of under 1 month did not exhibit increased postoperative morbidity. CONCLUSIONS: We concluded that surgery for CCAM could be safely performed in all age groups with satisfactory long-term outcomes. It is suggested that early elective surgical correction can be recommended for a patient whose diagnosis was made in utero.     

北京市东城区和平里社区居民慢性病防治探讨

为探索慢性病的防治方法，我们于１９８９￣１９９４年社区居民中开展了以高血压为主的循环系统慢性病防治课题，经过５年的干预，观察组与对照组居民及接受管理的高血压病人在减少吸烟，饮酒，控制食盐摄入，掌握慢性病防治知识等方面有显著性差异，取得了满意的结果，从而为今后全面开展慢性病防治积累了经验。     

复方山绿茶缓释袋泡剂的研究

用网状多孔性纤维包念材料制备的复方山绿茶缓袋泡剂，具有速释和缓释作用，在１－８ｈ内按埝级方式释药。Ｔ０．５为１．３ｈ，Ｔｄ为３．２ｈ，１－８ｈ的平均释药速率７２．３５ｍｇ／ｈ。与传统的半生药型袋泡剂比较，具有栽药量高，使用方便，性质稳定，疗效确切的优点。     

人细胞色素p450IA1基因cDNA的克隆和鉴定

在用３－甲基胆蒽诱导培养人羊膜ＦＬ细胞２４ｈ后，抽提细胞总ＲＮＡ并直接合成ｃＤＮＡ第一链。利用人工合成的一对寡核苷酸引物，采用ＰＣＲ技术特异性地扩增Ｃｙｔ ｐ５０ＩＡ１ ｃＤＮＡ。３０个循环后琼脂糖凝胶电泳显示１．５Ｋｂ大小片段，长度与预计相符。Ｓｏｕｔｈｅｒｎ杂交结果证实此片段确为Ｃｙｔ ｐ４５０ＩＡ１ ｃＤＮＡ。将此片段克隆至质粒ｐＧＥＭ－３Ｚ并进行部份序列分析。结果显示克隆片段包含Ｃｙｔ ｐ     

Ⅰ期非小细胞肺癌淋巴结微转移规律的研究

目的探讨几个问题：（1）Ⅰ期非小细胞肺癌淋巴结微转移比率；（2）淋巴结微转移与肿瘤大小、病理类型、细胞分化程度、部位、分型、分期进行Logstic回归分析，确定影响微转移的主要因素；（3）探讨微转移的方式、顺序。方法对91例非小细胞肺癌清扫的肺门和隆突下淋巴结进行MCK（AEI／AE3）免疫组化标志检测微转移的存在。另外收集45例肺部良性病变手术时切除的肺门淋巴结45枚和Ⅱ期、Ⅲ期肺癌常规病理检查阳性的肺门淋巴结45枚进行MCK（AEI／AE3）免疫组化（SP法）标志，分别作为阴性和阳性对照。结果45例肺部良性病变手术时切除的肺门淋巴结45枚进行MCK（AEI／AE3）免疫组化标志均为阴性；Ⅱ期和Ⅲ期常规病理检查阳性的肺门淋巴结45枚进行MCK（AEI／AE3）免疫组化标志均为阳性。91例Ⅰ期非小细胞肺癌总的微转移率为49％（45／91）。结论Ⅰ期非小细胞肺癌淋巴结中存在微转移；Ⅰb期非小细胞肺癌微转移率明显高于Ⅰa期；有必要对Ⅰb期非小细胞肺癌进行术后化疗；肿瘤分期和分化程度是影响淋巴结微转移的主要因素；淋巴结微转移遵循肺门到纵隔的途径；腺癌存在跳跃式微转移。