A quantitative approach to cytoarchitectonics

Summary The boundaries of iso- and allocortical areas of Microcebus murinus were analyzed with an automatic quantitative procedure using an image analyzer. The results are summarized in a cortical map and compared with a previous study of Microcebus murinus (Clark, 1931) and Galago demidovii (Zilles et al., 1979). A surprising correspondence could be observed between Microcebus and Galago with respect to the cortical areal pattern and the cytoarchitectonic structure of the various areas, including their position and extension, although both species are grouped into different suborders.Supported by Deutsche Forschungsgemeinschaft Zi 192/1 and 192/3     

Estimation of early-stage malfunction using implantable artificial heart sound in animal experiments

We have developed an automatic diagnosis system of an artificial heart in order to ensure the safety of the patient implanted with the artificial heart. The automatic diagnosis system is composed of an electro-stethoscope system, adaptive noise canceller (ANC), and artificial neural network (ANN). The ANC effectively eliminates ambient noise from the sound signal of the artificial heart detected by the electro-stethoscope, and a filtered sound signal is separated into each frequency components by fast Fourier transformation. Each frequency component of an artificial heart's acoustic signal is fed into the ANN in order to make a diagnosis of pump condition. The automatic diagnosis system was evaluated in mock circulatory tests and a long-term animal experiment using a goat implanted with an undulation pump ventricular assist device (UPVAD). In mock circulatory tests, the ANN was able to detect pump failing conditions, which were occlusion of inflow and outflow cannula and deterioration of the ball bearing. In a long-term animal experiment, after training the ANN using UPVAD's sound signal in normal condition, the diagnosis system continuously monitored UPVAD's sound signal detected by the electro-stethoscope placed on the surface of the left thoracic cavity of the goat. The UPVAD was stopped by rupture of a diaphragm in the pump on the ninth day of operation. We were able to identify initial signs of malfunction of the pump on the eighth day, while the UPVAD was able to operate normally. In conclusion, the automatic diagnosis system for malfunction of the artificial heart has enough performance to detect early stages of malfunction of the artificial heart, and it contributes to ensure the patient's safety.     

Alcohol effects on inhibitory control of attention: distinguishing between intentional and automatic mechanisms

Rationale Recent research has begun to explore the possibility that inhibitory mechanisms of selective attention are particularly susceptible to the impairing effects of moderate doses of alcohol. However, literature also suggests that automatic processes might be more resistant to this impairing effect than controlled processes.Objective The present study used a delayed ocular response task and a saccadic interference task to examine the effects of alcohol on both intentionally controlled and automatic inhibitory influences on selective attention.Materials and methods Twelve healthy adults performed both tasks under three doses of alcohol (0.0, 0.45, and 0.65 g/kg).Results The results showed that alcohol reduced intentional inhibitory control over selective attention but had no effect on automatic inhibitory influences.Conclusion The present investigation marks the first effort to directly compare alcohol effects on automatic and intentional inhibitory mechanisms of visual attention. The results suggest that attentional processes dependent on intentional inhibitory control may be more susceptible to the impairing effects of a moderate dose of alcohol than processes dependent on automatic inhibition.     

Does rapid dose titration affect the hepatic safety profile of Bosentan?

RATIONALE: Bosentan, a dual endothelin receptor antagonist, has proven efficacy in pulmonary hypertension. Due to an association with hepatic dysfunction, it is typically initiated at a sub-therapeutic dose for 4 weeks before titration to a therapeutic dose. At our institution some patients have undergone rapid titration, to potentially benefit from therapy earlier. This study assesses the impact of this practice on hepatic safety. METHOD: All patients initiated on bosentan therapy before April 2005 were included. Rapidly titrated patients achieved a therapeutic dose by 3 days, whereas standard titration patients were titrated at 4 weeks. All patients were monitored with monthly liver function tests. RESULTS: 149 patients commenced bosentan, of which 55 were rapidly titrated. At baseline, the two groups were similar in age, BMI, diagnosis, 6-min walking distance, alanine aminotransferase (ALT), cardiac index and pulmonary artery pressures. The rapid group had elevated right atrial pressures (9.7 mm Hg versus 7.4 mm Hg, p = 0.016) and worse WHO functional class (p = 0.008) and included less females (31% versus 69%, p = 0.024). The incidence of hepatic dysfunction in all patients was 12.8% at 12 months. There was no statistical difference in incidence between the rapid and standard groups (4% versus 11% at 3 months, p = 0.211 and 6% versus 15% at 12 months, p = 0.219). Of all patients on bosentan, hepatic dysfunction was most significantly associated with a higher baseline ALT (p = 0.021), female sex (p = 0.003) and underlying connective tissue disease (p = 0.025). Subgroup analysis suggested these factors were not confounders when comparing rapid and standard titration. CONCLUSIONS: Rapid and standard titration of bosentan resulted in similar hepatic safety profiles. Baseline ALT, female sex and the presence of connective tissue disease increased the risk of hepatic dysfunction independent of the titration method used.     

Feasibility of fully automated detection of fiducial markers implanted into the prostate using electronic portal imaging: a comparison of methods

PURPOSE: To investigate the feasibility of fully automated detection of fiducial markers implanted into the prostate using portal images acquired with an electronic portal imaging device. METHODS AND MATERIALS: We have made a direct comparison of 4 different methods (2 template matching-based methods, a method incorporating attenuation and constellation analyses and a cross correlation method) that have been published in the literature for the automatic detection of fiducial markers. The cross-correlation technique requires a-priory information from the portal images, therefore the technique is not fully automated for the first treatment fraction. Images of 7 patients implanted with gold fiducial markers (8 mm in length and 1 mm in diameter) were acquired before treatment (set-up images) and during treatment (movie images) using 1MU and 15MU per image respectively. Images included: 75 anterior (AP) and 69 lateral (LAT) set-up images and 51 AP and 83 LAT movie images. Using the different methods described in the literature, marker positions were automatically identified. RESULTS: The method based upon cross correlation techniques gave the highest percentage detection success rate of 99% (AP) and 83% (LAT) set-up (1MU) images. The methods gave detection success rates of less than 91% (AP) and 42% (LAT) set-up images. The amount of a-priory information used and how it affects the way the techniques are implemented, is discussed. CONCLUSIONS: Fully automated marker detection in set-up images for the first treatment fraction is unachievable using these methods and that using cross-correlation is the best technique for automatic detection on subsequent radiotherapy treatment fractions.     

Screening of Lipid Carriers and Characterization of Drug-Polymer-Lipid Interactions for the Rational Design of Polymer-Lipid Hybrid Nanoparticles (PLN)

Purpose The thermodynamics and solid state properties of components and their interactions in a formulation for polymer-lipid hybrid nanoparticles (PLN) were characterized for screening lead lipid carriers and rational design of PLN.Methods Verapamil HCl (VRP) was chosen as a model drug and dextran sulfate sodium (DS) as a counter-ionic polymer. Solubility parameters of VRP, VRP-DS complex, and various lipids were calculated and partition of VRP and VRP-DS in lipids was determined. Thermodynamics of VRP binding to DS was determined by isothermal titration calorimetry (ITC). The solid state properties of individual components and their interactions were characterized using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD).Results Dodecanoic acid (DA) was identified as the best lipid carrier among all lipids tested based on the solubility parameters and partition coefficients. VRP-DS complexation was a thermodynamically favorable process. Maximum binding capacity of DS and the highest drug loading capacity of DA were obtained at an equal ionic molar ratio of DS to VRP. In the PLN formulation, DA remained its crystal structure but had a slightly lower melting point, while VRP-DS complex was in an amorphous form.Conclusions Drug loading efficiency and capacity of a lipid matrix depend on the VRP-DS binding and the interactions of the complex with the lipid. A combined analysis of solubility parameters and partition coefficients is useful for screening lipid candidates for PLN preparation.     

相位整序信号平均技术用于全麻术中自主神经功能的评价

目的将相位整序信号平均技术(phase-rectified signal averaging,PRSA)应用于全麻术中,观察其评价自主神经活动变化的可行性。方法选择口腔颌面外科择期手术患者110例,男63例,女47例,年龄18~65岁,ASAⅠ或Ⅱ级。手术全程采集心电信号。从连续的心电信号中截取三个5min时段:术前(T0):患者麻醉前的清醒状态;术中(T1):手术开始25~30 min;术后(T2):手术结束,患者意识恢复。计算三个时间段心率变异性(heart rate variability,HRV)各项指标:心率减速力(deceleration capacity of heart rate,DC)、RR间期差值的均方根(RMSSD)、RR间期的标准差(SDNN)、散点图短轴(SD1)、散点图长轴(SD2)、总功率(total power,TP)、低频功率(low frequency power,LF)、高频功率(high frequency power,HF)。结果与T0时比较,T1、T2时DC、RMSSD、SDNN、SD1、SD2明显缩短,logTP、logLF和logHF明显减小(P0.05);与T1时比较,T2时DC、RMSSD、SDNN、SD1、SD2明显延长,logTP、logLF和logHF明显增大(P0.05);DC与RMSSD、SD1、logHF呈正相关(r=0.905、0.909、0.932,P0.01)。结论基于PRSA技术5分钟的DC值,与迷走神经活动性具有较好的相关性,用于术中观察自主神经活动是可行的。     

Automatic read-out device for ultraviolet-radiation polymer-film dosimeters

An automatic device for measuring the optical absorbance of polymer film used as an ultravioletradiation dosimeter is described. The automated mechanics are based on a commercial slide projector. The ultraviolet radiation is generated by a tungsten quartz-halogen bulb. The optical absorbance is determined by analogue logarithmic circuitry and the resultant value displayed on a digital panel meter. A digital printer or paper-tape punch may be used for hard-copy output. An uncertainty in measurement of 1% is obtained. The device temperature stability is such that this uncertainty can be maintained for analogue circuit temperatures of 20–40°C.     

Mechanical and electromyographic responses to stretch of the human anterior tibial muscle at different levels of contraction

Summary The EMG response and the mechanical response to 2 degree stretch of the human anterior tibial muscle was studied during contractions ranging from 0% to 80% of maximal voluntary contraction (MVC). The EMG response showed three distinct peaks M1, M2, and M3 with peak latencies of 59 ms, 86 ms, and 120 ms respectively. At low background torques M1 dominated while M2 and M3 were small or absent. M2 and M3 dominated above 40% of MVC and M2 in particular showed automatic gain compensation, i.e. it constituted a — more or less — constant proportion of the background EMG for all contraction levels. The ratio between M1 amplitude and background EMG steadily decreased with contraction level. Even though the summed contributions of M1, M2, and M3 to some degree showed automatic gain compensation, this was not the case for the mechanical response to stretch. Between 0% and 30% of MVC the reflex mediated mechanical response increased approximately in proportion to the contraction level, but the reflex mediated mechanical response peaked at 40% of MVC and declined to zero at 80% of MVC. This discrepancy between EMG and mechanical response was explained by a simple model. The regression line between rectified and filtered tibialis anterior EMG and torque was used to predict the mechanical response from the EMG response. At increasing contraction levels the twitch elicited by supramaximal electrical stimulation decreases, and we reduced the predicted mechanical response by the same factor as the twitch. This simple model predicted the mechanical response for all contraction levels, making it possible to assess the functionality of reflexes even when accurate measurements of muscle force or intrinsic muscle properties are not possible.