京剧嗓音的声学分析及音域特征

目的　从声学角度客观地检测京剧的嗓音特征 ,为京剧演唱者嗓音的训练和保护提供参考。方法　对 73名 1 6～ 5 7岁不同行当的专业京剧演员或学员 ,利用Dr Speech计算机频谱分析系统对元音 /a/、/i/歌唱舒适音和唱段进行声学参数的检测和分析。结果　各行当元音 /a/、/i/歌唱舒适音的基频 (fundamentalfrequency,F0 )分别是 :丑角 (2 72 6± 42 0 )Hz( x±s ,下同 )、(30 4 2± 2 2 1 )Hz;小生 (499 3± 34 0 )Hz,(485 4± 1 8 7)Hz;老生 (335 6± 6 0 0 )Hz,(31 7 9± 45 1 )Hz ;花脸 (31 9 0±6 1 3)Hz,(34 0 1± 6 8 8)Hz;老旦 (42 7 6± 47 2 )Hz,(437 7± 45 8)Hz ;花旦 (5 35 8± 48 8)Hz,(5 6 1 6± 2 9 2 )Hz ;青衣 (5 48 0± 6 9 5 )Hz,(5 43 5± 79 3)Hz;其它声学参数 :频率微扰 (pitchperiodperturbation,或Jitter)、振幅微扰 (amplitudeperturbation ,或Shimmer)和声门噪声能量 (也称标准化噪声能量级 ,normalizednoiseenergy ,NNE)均在软件提供的正常值范围内 ;京剧演员歌唱音域的跨度为 1 7～ 2 8个八度 ,最低音和多数最高音均比西洋唱法的高音声部相应的值高。结论　京剧嗓音有着独特的声学特征 ;结果对其嗓音的训练和保护有一定的临床参考     

多普勒组织显像评价高血压病心房内传导间期变化与房性心律失常的关系

目的　应用多普勒组织显像评价高血压病心房内传导间期变化与房性心律失常的关系 ;方法　利用超声多普勒组织显像法测量了 2 0例高血压病心房内传导间期与正常人对比分析 ;结果　高血压病心房内传导间期存在异常 ,心房内传导间期与左房内径大小无相关 (r =0 1,P >0 2 5 ) ,与左室舒张功能指标E A比值中度相关 (r=0 5 7,0 0 1

0 2 5 ) ;结论　高血压病房性心律失常与心房内传导异常及左室舒张功能有关 ,多普勒组织显像法是一种较好的测量高血压病心房内传导间期的方法     

急性心肌梗死早期QT间期JT间期离散度与近期严重心律失常的关系

目的 :探讨AMI早期QT间期离散度、JT间期离散度与严重心律失常的关系。方法 :测定 46例AMI患者心梗发生后第 3d的QT间期离散度 (QTd)和JT间期离度 (JTd)。并与30例正常人的对照组比较。结果 :AMI组QTd、JTd、QTcd较对照组显著增大 (P <0 0 1 )。住院期间严重室性心律失常发生组 (1 8例 )的QTd、JTd、QTcd较无严重室性心律失常组 (2 8例 )明显增大 (P <0 0 1 ) ,且发生室颤的 9例患者QTd、JTd、QTcd比无室颤的明显增大 (P <0 0 1 )。结论 :早期测定AMI患者QTd、JTd、QTcd对患者近期严重室性心律失常的发生有预测意义     

Comparison of the acute cardiotoxicity of the antimalarial drug halofantrine in vitro and in vivo in anaesthetized guinea-pigs

1. Several unrelated drugs have pro-arrhythmic activity associated with an ability to prolong the QT interval of the ECG. The aim of this work was to examine the effects of the antimalarial drug halofantrine in vivo and in vitro.
2. In anaesthetized guinea-pigs consecutive bolus doses of halofantrine (0.3, 1, 3, 10 and 30 mg kg⁻¹, i.v.) at 25 min intervals caused dose-dependent prolongation of the rate corrected QTc interval and bradycardia. The change in heart rate became significant after administration of 10 mg kg⁻¹ halofantrine (−23±9 beats min⁻¹) whereas the increase in QTc was significant with only 1 mg kg⁻¹ halofantrine (22±10 ms). It was only with the highest dose of halofantrine that the PR interval was increased (from 52±3 to 67±4 ms) and second degree atrioventricular (AV) block (type 1 Mobitz) occurred in all animals. No changes were observed in any parameters in a separate group of guinea-pigs which received vehicle (dimethylacetamide 60% propylene glycol 40%) at equivalent time points.
3. The blood concentrations of halofantrine ranged from 0.26±0.17 μM after administration of 0.3 mg kg⁻¹ to 2.79±0.87 μM after 30 mg kg⁻¹, i.v. There was a significant correlation between the blood concentrations of halofantrine and the changes in QTc interval.
4. In guinea-pig left papillary muscles the effective refractory period was increased significantly 60 min after addition of halofantrine; from 161±4 to 173±6 ms with 10 μM, 156±8 to 174±6 ms with 30 μM and 165±6 to 179±5 ms with 100 μM halofantrine. However, the vehicle (0.1% Tween 80 in DMSO; final concentration of vehicle in Krebs, 1%) also increased the effective refractory period from 164±5 to 173±6 ms. Similar results were obtained in right ventricular strips but left atrial effective refractory periods were not altered by either the vehicle or halofantrine.
5. The results of these experiments suggest that any direct effects that halofantrine may have had on the effective refractory period of cardiac muscle cannot be separated from those of the vehicle. The prolongation of QTc and consistent observation of AV block with halofantrine in anaesthetized guinea-pigs suggest that in vivo models may be more useful for further studies investigating the mechanisms underlying the cardiotoxicity of halofantrine.

     

Ventricular fibrillation related to reversal of the neuromuscular blockade in a patient with long QT syndrome

The long QT syndrome (LQTS) is associated with syncopal attacks or even sudden death at a young age due to ventricular fibrillation. We report a patient with an undiagnosed LQTS who had an episode of cardiac arrest during the final part of general anesthesia, immediately after the drugs for reversal of the neuromuscular blockade were given. We suggest that the administration of glycopyrronium might have been the provoking factor in this patient.     

Laboratory data in healthy volunteers: reference values, reference changes, screening and laboratory adverse event limits in Phase I clinical trials

Objective: Laboratory data are key evaluation procedures for Phase I clinical pharmacology for two reasons. Firstly, laboratory data are used within the screening process to exclude subjects with asymptomatic diseases, which could result in increased danger to themselves or confuse interpretation of the study results. Secondly, during study implementation, safety evaluation and in particular maximum tolerated dose determination have to be done by a case-by-case analysis, sometimes using laboratory adverse events (LAEs). Thus, relevant limits are needed to discriminate between a usual common variation and a significant abnormality, which is considered to be a LAE. This report presents laboratory data distribution, reference values and reference changes and, based on previously published new methods, suggests inclusion limits at screening and laboratory adverse event limits for analysis during study implementation. Subjects and methods: Nine hundred and twenty-seven young healthy male volunteers were recruited in one centre (Association de Recherche Thérapeutique). A standard screening process was carried out. Protocols were approved by the local ethics committee. Blood sampling was performed in the same conditions. Reference values (at screening and at baseline) were determined by a non-parametric procedure selecting 2.5% and 97.5% of the distribution of data. Reference changes were also defined as the 2.5–97.5% interval of distribution of the variations between the end of treatment and baseline. Inclusion limit and LAE limit methods of determination used had been specified in previous articles. Results: Detailed results of laboratory data distribution, reference values at screening and at baseline, reference changes, inclusion limits and LAE limits are presented in tables with number of subjects, mean, median, standard deviation, minimal and maximal values and the 2.5–97.5% interval for each laboratory parameter. Conclusion: The key aims of this paper are to provide clinical pharmacologists with data, reference values or changes obtained in the real conditions of Phase I study implementation, and to propose relevant limits, either for screening as inclusion limits, or during studies as LAE limits. Thus, these data, reference values and specific limits improve the capacity to screen healthy volunteers and to analyse LAEs during Phase I studies. Received: 30 July 1998 / Accepted in revised form: 25 November 1998     

Memory and the septo-hippocampal cholinergic system in the rat

This study examined the effects of intrahippocampal injections of scopolamine (a muscarinic antagonist drug) on performance of a working-memory task (contingently) reinforced T-maze alternation) and a reference-memory task (visual discrimination) by the same rats in the same maze. Rats in the first shipment were trained in delayed alternation, received bilateral implantation of cannulae aimed at the CA3 field of the dorsal hippocampus, and were tested for retention with 1 l microinjections of scopolamine (35 g) and saline on alternate days. These rats were then trained on visual discrimination and tested alternately under scopolamine or saline as described above. It was found that scopolamine impaired performance of delayed alternation to a greater extent than performance of visual discrimination. Data from rats in the second shipment replicated this finding, with the order of the tasks reversed, and, additionally, showed that delayed alternation, but not visual discrimination, was impaired at a dose of 12 g/l. A dose of 4 g/l had no effect on either task. It is concluded that performance of a workingmemory task is significantly more sensitive to disruption of cholinergic mechanisms in the hippocampus than performance of a reference-memory task.Supported by PHS Training Grant MH-14577. Now at the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA     

Predominantβ-adrenoceptor blocking effect of xamoterol averaged over the day in patients with mild to moderate heart failure: insight into the mechanism of its long-term clinical efficacy

Summary Xamoterol acts as a ₁-adrenoceptor agonist at low sympathetic activity and as an antagonist at high activity. Although its long-term efficacy has been proven in patients with mild to moderate heart failure, it remains unclear which effect, agonism or antagonism, accounts for its long-term activity.To clarify the effect of xamoterol on cardiac sympathetic activity in daily life, 24-h R-R interval histograms were obtained during administration of xamoterol 100 mg b. d. for 1 week to 10 patients with mild to moderate heart failure. Eight normal subjects were also studied as controls. To examine the relation between the effect of xamoterol and sympathetic activity, plasma noradrenaline (NA) levels were measured under 5 graded conditions simulating daily living.Xamoterol administration significantly decreased the standard deviation of the R-R interval, both in patients with heart failure and in normal subjects. The mean R-R interval, however, was increased in patients with heart failure, relative to normal subjects.In both groups, the R-R interval histograms had two peaks, i. e. a short daytime peak and a long night-time peak. Xamoterol decreased the median of the night-time peak without changing the daytime peak in normal subjects. In contrast, it increased the median of the daytime peak without producing a significant change in the nighttime peak in patients with heart failure. Levels of plasma NA were significantly higher in patients than in normal subjects under all conditions.Thus, in normal subjects xamoterol predominantly increased the slower heart rate at night with only a minor effect on the higher heart rate in the daytime, whereas it predominantly attenuated the daytime tachycardia induced by sympathetic stimulation in patients with heart failure.It is concluded that xamoterol tends overall to act as a-adrenoceptor antagonist during the day, especially in the daytime in patients with mild to moderate heart failure. Its antagonist rather than its agonist effect may account for the long-term efficacy of xamoterol in patients with mild to moderate heart failure.     

Effects of scopolamine on variable intertrial interval spatial alternation and memory in the rat

A repeated measures procedure, variable intertrial interval (ITI) spatial alternation, was used to assess scopolamine effects on memory, and to compare effects of the drug on discrimination processes with effects on storage. Rats learned in two stages to press left and right levers in alternation on discrete trials separated by 5 different ITI's ranging from 2.5 to 40 s and presented in random order during the experimental session. In the first stage, alternating discrimination, alternation was controlled by a light on over the correct lever at the time of the trial; in the second stage, variable ITI spatial alternation, a centrally located panel light signalled all trials and alternation was controlled by stimuli from prior trials (memory). Alternation response occurrence declined moderately (but significantly) with increasing ITI duration in both the alternating discrimination and variable ITI spatial alternation stages; response occurrence was also significantly decreased by scopolamine treatment in both stages. Accuracy of alternating discrimination performance was not significantly altered by either ITI duration or scopolamine treatment. Accuracy of variable ITI spatial alternation performance on a trial varied inversely with the duration of the ITI that preceded the trial. Scopolamine treatment significantly reduced accuracy of lever pressing in variable ITI spatial alternation but did not alter the slope of the curves relating accuracy to ITI duration. These effects indicate that the drug impaired discrimination processes but did not alter memory storage.