Diuretic and hypotensive actions of torasemide in hypertensive models of rat

The diuretic and the antihypertensive actions of torasemide were examined in renal and genetic hypertensive rats and compared to the effects of furosemide. Oral administration of torasemide (1 and 3 mg/kg) elicited a dose-dependent increase in the excretion of urine and electrolytes and elevated the urinary Na/K ratio in both renal and genetic hypertensive rats. Torasemide and furosemide had a similar maximum diuretic effect in the normotensive Wistar rat and the spontaneously hypertensive rat (SHR). However, the diuretic activity of furosemide was weaker in the renal hypertensive rat (RHR). Torasemide showed approximately 30 times greater diuretic potency than furosemide. Torasemide and furosemide demonstrated hypotensive action in hypertensive rat models, but not in the normotensive Wistar rat. Especially in the RHR, torasemide exhibited a more potent hypotensive action than furosemide. These results show that the diuretic and antihypertensive activities of torasemide are effective in various rat models of hypertension, while the diuretic activity of furosemide is weak in certain hypertensive rat models. © 1992 Wiley-Liss, Inc.     

青中年人群微量白蛋白尿患病率与心血管疾病危险因素的关系

目的　探讨微量白蛋白尿患病率与心血管疾病危险因素的关系。方法　选择 775例 (男 32 6例 ,女 4 4 9例 )年龄 2 0～ 5 0岁的社区人群 ,测定其体重指数 (BMI)、血压、空腹血糖、血脂谱 ;收集晨尿检测尿白蛋白、尿肌酐浓度 ,并计算尿白蛋白 /尿肌酐的比率。根据有无高血糖、高血压或高三酰甘油 /低高密度脂蛋白胆固醇 (高TG/低HDL C)血症分为 4组 ,即正常组 (A组 )、1种代谢紊乱组 (B组 )、2种代谢紊乱组 (C组 )及代谢综合征组 (D组 ) ,评价微量白蛋白尿与代谢紊乱的关系。结果　①糖尿病患者微量白蛋白尿的患病率为 2 2 .2 % ,显著高于正常血糖者 (5 .2 % ,P =0 .0 0 2 ) ;高TG/低HDL C血症者微量白蛋白尿的患病率为 8.3% ,显著高于正常血脂者 (4.0 % ,P =0 .0 12 ) ;高血压患者与正常血压者的差异无显著性。②随代谢紊乱加重 ,尿白蛋白浓度显著升高 (协方差分析 ,P <0 .0 1) ,微量白蛋白尿患病率升高 (趋势分析 ,P =0 .0 0 3)。③ 4组间尿肌酐浓度、尿白蛋白 /尿肌酐的差异无显著性。结论　①糖尿病、高TG/低HDL血症人群的微量白蛋白尿的发病率显著升高。②随代谢紊乱加重 ,微量白蛋白尿患病率亦升高     

不同类型精神分裂症患者脑脊液色氨酸及其与竞争性氨基酸比值对照研究

应用高压液相色谱（ＰＨＬＣ）对４２例阳性精神分裂症患者、２５例阴性精神分裂症患者及１０例健康正常对照组脑脊液中色氨酸（Ｔｒｙｔｏｐｈａｎ，ＴＲＰ）和酪氢酸（Ｔｙｒｏｓｉｎｅ，Ｔｙｒ）进行测试，其中ＴＲＰ／Ｔｙｒ被作为两者竞争指数，结果提示阳性、阴性精神分裂症患者脑脊液中Ｔｙｒ显著性降低，而ＴＲＰ则无显著性变化。但发现阳性精神分裂症患者的ＴＲＰ／Ｔｙｒ比值显著高于正常对照组，也显著高于阴性精神分裂症患者，本文结合ＴＲＰ／Ｔｙｒ的意义与价值进行了讨论。     

双水平压力调节通气与反比通气对健康及急性肺损伤犬心肺功能影响的比较研究

目的 :比较双水平压力调节 (BIPAP)通气和反比通气 (IRV)对心肺功能的影响。方法 :在两种通气模式 0、0 .5和 1.0 k Pa呼气末压 (EEP)时 ,分别测定健康犬及油酸诱发急性肺损伤犬的呼吸力学、血流动力学及血气分析各参数。结果 :无论有无急性肺损伤 ,BIPAP通气时平均气道压 (m Paw )均明显低于 IRV时(P均 <0 .0 5 )。给健康犬用 IRV通气时 ,上述 3种 EEP水平的 m Paw分别为 (0 .437± 0 .10 3) k Pa、(0 .811±0 .0 93) k Pa和 (1.36 0± 0 .119) k Pa;用 BIPAP通气时则分别降为 (0 .2 2 5± 0 .0 71) k Pa、(0 .6 11± 0 .10 5 ) k Pa和(1.10 7± 0 .0 89) k Pa。油酸诱发急性肺损伤后 ,m Paw分别由 IRV时 (0 .72 5± 0 .2 2 2 ) k Pa、(1.186± 0 .2 98) k Pa和 (1.6 0 0± 0 .10 0 ) k Pa降至 BIPAP时 (0 .35 0± 0 .12 9) k Pa、(0 .6 2 5± 0 .15 0 ) k Pa和 (1.12 5± 0 .0 96 ) k Pa;但两种通气模式中气道峰压、心排血量并无明显差异。另外 ,急性肺损伤时 ,BIPAP通气的动脉血氧分压 (Pa O2 )分别为 (9.10± 1.79) k Pa、(11.43± 1.80 ) k Pa和 (13.40± 3.2 0 ) k Pa,较 IRV时 Pa O2 (7.87± 2 .33) k Pa、(9.0 7±3.0 5 ) k Pa和 (9.71± 1.85 ) k Pa增高 (EEP 1.0 k Pa时 ,P <0 .0 5 )。结论 :     

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.     

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目的　探讨一种更精确而行之有效的测量甲状腺残留量的方法。方法　自 1996～ 2 0 0 1年对 15例原发性甲状腺功能亢进症病人于术前经CT对甲状腺进行体积测量 ,于双侧甲状腺次全切除术后 ,再用增强CT对上述病人残留甲状腺进行体积测量 ,并与术中测得残留量比较。结果　术中测得残留量 2 8～ 13 0 g ,术后CT测量为 3 4～ 16 6g ,二者之间有一定误差 (P =0 0 6 7) ,产生原因主要为术者对残留甲状腺背面气管旁沟处的不规则腺体测量不准确。体积切除率 83 1%～ 97 9% ,体积残留率 2 1%～ 17 9% ,活体组织相对体积质量 (1 0 5 4 8± 0 0 2 0 5 ) g/cm3 ,离体组织相对体积质量 (1 0 6 4 8± 0 0 188) g/cm3 。结论　CT测量更接近实际残留量 ,可重复性强 ,可比性强。体积残留率比腺体残留重量、手术切除率更具有个性化参考意义。     

Independent component analysis and clustering improve signal-to-noise ratio for statistical analysis of event-related potentials

OBJECTIVE: To evaluate the effectiveness of a new method of using Independent Component Analysis (ICA) and k-means clustering to increase the signal-to-noise ratio of Event-Related Potential (ERP) measurements while permitting standard statistical comparisons to be made despite the inter-subject variations characteristic of ICA. METHODS: Per-subject ICA results were used to create a channel pool, with unequal weights, that could be applied consistently across subjects. Signals derived from this and other pooling schemes, and from unpooled electrodes, were subjected to identical statistical analysis of the N170 own-face effect in a Joe/No Joe face recognition paradigm wherein participants monitored for a target face (Joe) presented amongst other unfamiliar faces and their own face. Results between the Joe, unfamiliar face and own face conditions were compared using Cohen's d statistic (square root of signal-to-noise ratio) to measure effect size. RESULTS: When the own-face condition was compared to the Joe and unfamiliar-face conditions, the channel map method increased effect size by a factor ranging from 1.2 to 2.2. These results stand in contrast to previous findings, where conventional pooling schemes failed to reveal an N170 effect to the own-face stimulus (Tanaka JW, Curran T, Porterfield A, Collins D. The activation of pre-existing and acquired face representations: the N250 ERP as an index of face familiarity. J Cogn Neurosci 2006;18:1488-97). Consistent with conventional pooling schemes, the channel map approach showed no reliable differences between the Joe and Unfamiliar face conditions, yielding a decrease in effect size ranging from 0.13 to 0.75. CONCLUSIONS: By increasing the signal-to-noise ratio in the measured waveforms, the channel pool method demonstrated an enhanced sensitivity to the neurophysiological response to own-face relative to other faces. SIGNIFICANCE: By overcoming the characteristic inter-subject variations of ICA, this work allows classic ERP analysis methods to exploit the improved signal-to-noise ratio obtainable with ICA.     

A Note on the Asymptotic Properties of Affected-sib-pair Linkage Tests

This article concerns the asymptotic properties of linkage tests for affected‐sib‐pair data under the null hypothesis of no linkage. We consider a popular single‐locus analysis model where the unknown parameters are the disease allele frequency, the three penetrances for the three genotypes at the disease locus, and the recombination fraction between the marker locus and the disease locus. These parameters are completely confounded under the null hypothesis of no linkage. We show that 1) If the total variance of the trait (i.e., the additive variance plus the dominance variance) is “separated” from 0, then the likelihood ratio statistic has an asymptotic 0.5χ²₀+ 0.5χ²₁ distribution; 2) If the prevalence of the trait is “separated” from 0 and the recombination fraction is fixed at 0, then the likelihood ratio statistic has an asymptotic distribution which is a mixture of χ²₀, χ²₁ and χ²₂ . The implications of these results are discussed.     

Digital computer analysis of dermatoscopical images of 260 melanocytic skin lesions; perimeter/area ratio for the differentiation between malignant melanomas and melanocytic nevi

BACKGROUND: Digital computer analysis of dermatoscopical images has been reported to facilitate the differential diagnosis of pigmented skin lesions in recent years. OBJECTIVE: The aim of our study was to perform digital computer analysis of a set of different melanocytic lesions and compare the objective results. METHODS: The set of 260 melanocytic lesions (150 excised difficult cases (46 melanomas, 47 atypical nevi, 57 common nevi and 110 unexcised common nevi) was automatically analysed by the digital dermatoscopical system microDERM. We searched for differences in asymmetry, size, compactness and colour distribution. Perimeter/area ratio was calculated. RESULTS: The perimeter/area ratio was detected as the most important criterion for differentiation between malignant and benign melanocytic lesions (sensitivity 91.3% and specificity 90.7% for malignant melanomas vs. all benign nevi; sensitivity 91.3% and specificity 80.8% for melanomas vs. clinically atypical nevi). Differences in size of the lesion, shape and asymmetry of colour were found and statistically verified. Using step-wise logistic regression the formula for calculation of probability of malignant nature of every analysed lesion was constructed. CONCLUSION: The perimeter/area ratio is a simple parameter for the differential diagnosis of melanocytic skin lesions.     

Ventricular enlargement, clinical correlates and treatment outcome in chronic schizophrenic inpatients.

The ventricle-brain ratio (VBR) of 42 chronic schizophrenic patients was compared with that of 42 age-matched medical controls. For the schizophrenics, the relationship of various clinical parameters to the VBR was assessed, and the outcome of 12 weeks of double-blind treatment with either risperidone or haloperidol. The results confirm that schizophrenic patients have slightly enlarged lateral ventricles compared with medical controls. Only for schizophrenics, an effect of age, but not of duration of illness, was noticed. This study does not support the validity of a clinical subdivision of chronic schizophrenic patients on the basis of the VBR. Neither negative, positive nor general psychopathological symptoms, as measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), were related to the VBR, nor were abnormal involuntary movements or extrapyramidal symptoms. No association between season of birth or a family history of major mental disorder and VBR could be demonstrated. Treatment response was predicted by the total PANSS score and the PANSS general psychopathology subscale score at baseline. There was a trend for patients with higher VBR to have a more or haloperidol). or haloperidol).