A phase I/II study of continuous infusion suramin in patients with hormone-refractory prostate cancer : toxicity and response

 Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis, but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer, with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations (275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment of suramin’s activity in hormone-refractory prostate cancer. Received: 9 June 1995/Accepted: 18 March 1996     

胃粘膜上皮“适应性细胞保护”机制防止胃肿瘤发生的作用

投用致癌剂的对照组其胃肿瘤发生率为22.2％。若同时给予40％Z醇液空腹灌胃,则胃肿瘤发生率达55.9％。如在给乙醇液前15分钟,先给予4％的辣椒煎液灌胃,则胃肿瘤发生率只有20.0％,相近于对照组的水平(后2组差别有极显著意义,P<0.01)。这种给损伤剂(乙醇)之前先给予微刺激剂(辣椒)所产生的胃粘膜的保护作用,是通过促使胃粘膜上皮细胞合成内源性前列腺素(PGs)来实现的,是一种“适应性细胞保护”机制。这种保护胃粘膜的作用可降低胃肿瘤的发生率。     

Corticofugal modulation of the information processing in the auditory thalamus of the cat

Summary Single unit activity of 355 cells was recorded in the auditory thalamus of anesthetized cats before, during, and after the inactivation by cooling of the ipsilateral primary auditory cortex (AI). Most of the units (n = 288) showed similar functional characteristics of firing before and after the cryogenic blockade of AI. The spontaneous firing rate remained unchanged by cooling in 20% of the units and decreased in the majority of them (60%). In some regions, i.e. dorsal division of the medial geniculate body (MGB), lateral part of the posterior group of the thalamus, and auditory sector of the reticular nucleus of the thalamus, the maximum firing rate evoked by white noise bursts was generally affected by cooling in the same direction and to the same extent as the spontaneous activity. Units in the ventral division of MGB showed a characteristic increase of signal-to-noise ratio during cortical cooling. The corticofugal modulation led to the appearance or disappearance of the best frequency of tuning in 51 units and changed it by more than 0.5 octave in 34 units. The bandwidths of different response patterns to pure tones stimulation were used to define a set of functional properties. During cryogenic blockade of AI, two cortically modulated sub-populations of units were usually distinguished that exhibited changes for a given functional property. The complexity and diversity of the effects of cortical inactivation suggest that the corticothalamic projection may be the support for selective operations such as an adaptive filtering of the incoming acoustic signal at the thalamic level adjusted as a function of cortical activity.     

罗衣适应模式在护理外固定支架固定胫骨骨折患者中的应用

目的：减少患者对外固定支架治疗胫骨骨折的恐惧心理，提高患者的适应能力，促进骨折愈合，预防并发症。方法：运用美国护理专家罗依的适应模式，分析113例患者受到的主要刺激，根据护理目标，制订具体护理措施，帮助患者找出适应性问题，做出适应性反应。结果：113例患者全部适应外固定支架的治疗，完成了护理目标。护理效果良好，早期即能下床活动，骨折愈合快，出院随访，无因该治疗方法出现并发症。结论：罗依的适应模式使患者配合护理，能不断识别环境中的新刺激，调整适应方式，做出适应性反应，达到预期目标。     

Real-time ocular artifact suppression using recurrent neural network for electro-encephalogram based brain-computer interface

The paper presents an adaptive noise canceller (ANC) filter using an artificial neural network for real-time removal of electro-oculogram (EOG) interference from electro-encephalogram (EEG) signals. Conventional ANC filters are based on linear models of interference. Such linear models provide poorer prediction for biomedical signals. In this work, a recurrent neural network was employed for modelling the interference signals. The eye movement and eye blink artifacts were recorded by the placing of an electrode on the forehead above the left eye and an electrode on the left temple. The reference signal was then generated by the data collected from the forehead electrode being added to data recorded from the temple electrode. The reference signal was also contaminated by the EEG. To reduce the EEG interference, the reference signal was first low-pass filtered by a moving averaged filter and then applied to the ANC. Matlab Simulink was used for real-time data acquisition, filtering and ocular artifact suppression. Simulation results show the validity and effectiveness of the technique with different signal-to-noise ratios (SNRs) of the primary signal. On average, a significant improvement in SNR up to 27 dB was achieved with the recurrent neural network. The results from real data demonstrate that the proposed scheme removes ocular artifacts from contaminated EEG signals and is suitable for real-time and short-time EEG recordings.     

基于自适应小波神经网络的心电图检测法

自适应小波神经网络检测法就是利用小波函数取代通常神经网络中隐层的作用函数来实现的，通过网络的学习自适应地调整尺度参数和时移因子，提高了特征提取能力，因此，该网络可提高心电信号的检测率和可靠性。     

Sustained Axial Loading Lengthens Arteries in Organ Culture

Although it has been recognized for many years that arteries in vivo exist under significant axial strain, studies of the adaptation of arteries to elevated axial strain have only recently been conducted. To determine the effects of sustained elevation of axial loading on arterial structure and function, axial stresses of 250 kPa or greater were applied to porcine common carotid arteries maintained in a perfusion organ culture system for 7 days at physiologic pressure and flow conditions. Our results demonstrated that axial stretch could lead to an increase in unloaded length that was proportional to the axial stretch ratio (stretched length divided by unloaded length) when the axial stretch ratio was above a threshold value of 2.14. Below this threshold, no significant length change occurred. Above this threshold, a significant increase in unloaded length (13 ± %,) and the number of smooth muscle cell nuclei (20 ± 7%) was observed. Permanent length change was associated with a significant decrease in axial stiffness, and the maximum elongation achieved was limited by rupture of the arterial wall. All tested arteries demonstrated good viability and strong vasomotor responses. These results show that arteries in organ culture can elongate under sustained axial loading.     

Adaptive filtering of canine electrogastrographic signals. Part 2: filter performance

The modified adaptive filter method described in Part 1 was applied to 16 stretches of (cutaneous) electrogastrographic signal of 17·07 min duration. A signal-to-noise ratio improvement of about 8 dB was achieved. The most characteristic feature of the filter method appeared to be that wave-form and phase of the gastric component of the electrogastrographic signal are preserved. It is concluded that the use of the modified adaptive filter forms a valuable tool in the study of the electrogastrographic signal.     

Adaptive Wiener Filtering for Improved Acquisition of Distortion Product Otoacoustic Emissions

An innovative acoustic noise canceling method using adaptive Wiener filtering (AWF) was developed for improved acquisition of distortion product otoacoustic emissions (DPOAEs). The system used one microphone placed in the test ear for the primary signal. Noise reference signals were obtained from three different sources: (a) pre-stimulus response from the test ear microphone, (b) post-stimulus response from a microphone placed near the head of the subject and (c) post-stimulus response obtained from a microphone placed in the subjects nontest ear. In order to improve spectral estimation, block averaging of a different number of single sweep responses was used. DPOAE data were obtained from 11 ears of healthy newborns in a well-baby nursery of a hospital under typical noise conditions. Simultaneously obtained recordings from all three microphones were digitized, stored and processed off-line to evaluate the effects of AWF with respect to DPOAE detection and signal-to-noise ratio (SNR) improvement. Results show that compared to standard DPOAE processing, AWF improved signal detection and improved SNR. © 1998 Biomedical Engineering Society. PAC98: 4364Jb, 4360-c, 8790+y     

On-line respiratory artefact removal via adaptive FIR filters in rheopneumographic measurement

Impedance rheopneumography is a simple non-invasive technique that can reflect the vascular condition in the human pulmonary circulatory system. However, the much larger and almost in-banding respiratory artefact present has greatly restricted its usefulness to only respiratory patients of a less severe type, in view of the existing practice of requiring the subject to stop breathing momentarily during measurement. Conventional fixed or adaptive filtering cannot satisfactorily remove the artefact in view of the non-time stationary characteristic of the latter. In the paper, a fast adaptive FIR filter design method, which is based on the filter coefficient look-up table (CLT) concept, is presented as a solution. The CLT is constructed with the coefficients indexed to the cut-off frequency to separate the two components of the plethysmogram. An on-line fast Fourier transform is calculated to track the cut-off frequency. This filter can adaptively change its coefficients, not only for different subjects, but also for the same subject during long-term monitoring. Results show that this filter design is capable of providing an almost respiratory artefact-free signal for a majority of patients. The high speed of implementation also renders it a possibility for real-time monitoring applications.