Pharmacokinetic characteristics and tolerability of a novel intravenous immunoglobulin preparation

In two independent trials 10 and 12 healthy volunteers received the novel intravenous immunoglobulin (IVIG) preparations BT 511 and BT 507, respectively. BT 511 contains 5 g human plasma proteins per 100 ml, more than 95% of which are immunoglobulins of the G class (IgG). BT 507 contains in addition 61 IU antibody against hepatitis B surface antigen (anti-HBs)·ml^–1. In trial I volunteers received 4.0 ml/kg (n+4) and 8.0 ml·kg^–1 (n+6) BT 511 to study the tolerability and the magnitude of the increase in immunoglobulins in plasma as well as their decline over 1 month. After administration of the lower dose, plasma IgG increased from 10.7 to 14.7 g·l^–1 directly after the infusion. Following the 8.0 ml·kg^–1 dose a more pronounced increase from 12.4 to 21.2 g·l^–1 was observed. No adverse events occurred. After 1 month IgG concentrations had almost reached baseline values at 12.2 g·l^–1 in the 4.0 ml·kg^–1 group, but were still significantly increased at 15.2 g·l^–1 after the high dose. There was a linear correlation between the maximal IgG plasma concentration and the subsequent decline of IgG during the 29-day observation period. After administration of BT 507 maximal anti-HBs concentrations of 1778 mU·ml^–1 occurred 1.4 h after termination of the infusion. The terminal elimination half-life was 22.4 days, and total clearance and volume of distribution were determined to be 0.122 ml·min^–1 and 5.41, respectively. The pharmacokinetic parameters calculated for anti-HBs as an indicator of IgG were in accordance with the pharmacokinetic behaviour of native IgG.     

On the synthesis of time‐varying LQG weights and noises along optimal control and state trajectories

A general approach to control non‐linear uncertain systems is to apply a pre‐computed nominal optimal control, and use a pre‐computed LQG compensator to generate control corrections from the on‐line measured data. If the non‐linear model, on which the optimal control and LQG compensator design is based, is of sufficient quality, and when the LQG compensator is designed appropriately, the closed‐loop control system is approximately optimal. This paper contributes to the selection and computation of the time‐varying LQG weighting and noise matrices, which determine the LQG compensator design. It is argued that the noise matrices may be taken time‐invariant and diagonal. Three very important considerations concerning the selection of the time‐varying LQG weighting matrices are turned into a concrete computational scheme. Thereby, the selection of the time‐varying LQG weighting matrices is reduced to selecting three scalar design parameters, each one weighting one consideration. Although the three considerations seem straightforward they may oppose one another. Furthermore, they usually result in time‐varying weighting matrices that are indefinite, rather than positive (semi) definite as required for the LQG design. The computational scheme presented in this paper addresses and resolves both problems. By two numerical examples the benefits of our optimal closed‐loop control system design are demonstrated and evaluated using Monte Carlo simulation. Copyright © 2005 John Wiley & Sons, Ltd.     

Does the shunt opening pressure influence the effect of shunt surgery in normal pressure hydrocephalus?

Summary Thirteen patients with normal pressure hydrocephalus were operated upon with an externally manoeuvrable shunt system (Sophy SU8) in order to investigate its influence on clinical outcome, intracranial pressure and cranial CT parameters. The opening pressure was set at high at surgery and lowered stepwise at intervals of three months to medium and low. The clinical condition, intracranial pressure and cranial CT parameters were examined at the end of the 3 months interval on each pressure level.The patients improved within the first 3 months inspite of an unchanged mean intracranial pressure and remained in a stable clinical condition during the rest of the study period. The intracranial pressure was significantly reduced at 9 months. The ventricular index, Evans index, temporal horn and third ventricle width were reduced 3 months post-operatively and did not change significantly during the rest of the study. The pre-operative third ventricle width was correlated to high psychometric test results after shunt surgery. Reduction in ventricular index, Evans index and third ventricle width after surgery correlated to improvement in psychometric scoring.The clinical improvement after shunt surgery for normal pressure hydrocephalus is seen within 3 months and is independent of the adjusted valve pressure.     

尼莫地平控制性降压对犬血流动力学的影响

在健康杂种犬10只中,分别以15、30、45μg/kg 尼莫地平静注行控制性降压,监测平均动脉压和其它血流动力学指标。结果表明,15μg/kg、30μg/kg 和 45μg/kg 静注后,平均动脉压1min 时分别下降19.44％、29.93％和33.60％,45min 恢复对照水平。降压期间除心输出量指数、每搏量指数和总外周阻力指数外,其它各项指标无显著性改变。因此,我们认为尼莫地平可试用于临床控制性降压,其效果有待临床进一步观察。     

Interaction of glucagon with artificial lipid bilayer membranes

The enhancement of fluorescence emission from the tryptophan residue of glucagon, the quenching of that emission with acrylamide and with 5-doxyl and 16-doxyl stearic acid, circular dichroism spectra, the release of 6-carboxytluorescein, and polarized infrared attenuated total reflection (IR-ATR) spectra were used to study the interaction of glucagon with intact lipid vesicles and flat bilayers. Dimyristoylphosphatidylcholine bound the peptide only below the main transition temperature, thus confirming earlier results of Epand et al. (1977). However, the peptide is also bound by vesicles of unsaturated lipids above their transition temperature, suggesting an influence of lipid area on the binding process. Circular dichroism showed that binding to such vesicles also increases the helix content of glucagon. The IR-ATR study and a comparison with dynorphin-A-(I-13)-tridecapeptide revealed profound differences in orientation of the two peptides. The dichroic ratios and the derived order parameters indicated an isotropic orientation of the helical segments of glucagon, but did not exclude a principal orientation of the molecules lying flat on the nienibrane surface. In contrast, the axis of the dynorphin helix is clearly oriented normal to the interface. The two peptides also differ in their rates of 6-carboxyfluorescein release, suggesting a deeper penetration of the primary amphiphilic helix of dynorphin A-(I-13) than of the secondary amphiphilic helix of glucagon.     

Synaptosomal Na, K-ATPase during forebrain ischemia in Mongolian gerbils

We studied the activity and kinetic parameters of synaptosomal Na, K-ATPase during 15 min of forebrain ischemia and following 60 min of reperfusion produced by reversible common carotid occlusion in Mongolian gerbils. A synaptosomal fraction was obtained by both differential centrifugation of brain tissue homogenate and centrifugation of crude mitochondrial fraction at a discontinual sucrose density gradient. We found two components of ATP concentration dependence of ATP hydrolysis that represent two types of ATP-binding sites: high affinity and low affinity. Neither ischemia nor reperfusion affected kinetic parameters of a high-affinity site. However, lowaffinity site parameters were affected by both ischemia and ischemia followed by reperfusion. Maximal velocity (V _max) decreased by 43 and 42% after ischemia and after ischemia/reperfusion, respectively. The apparentK _m for ATP decreased by 52% after ischemia and by 47% after ischemia/reperfusion. The apparent affinities for K⁺ and Na⁺ were determined from the ATP hydrolysis rate as a function of Na⁺ and K⁺ concentrations. We found the half-maximal activation constant for K⁺ (K _a K⁺) increased by 60% after ischemia and by 146% after ischemia/reperfusion. On the other hand, we found thatK _aNa⁺ decreased significantly after ischemia/reperfusion (16%). We concluded that it is the dephosphorylation step of the ATPase reation cycle that is primarily affected by both ischemia and ischemia/reperfusion. This might be caused by alteration of the protein molecule and/or its surroundings subsequent to ischemia.     

脉冲激光射线强化金属材料的几个问题

本文讨论了激光脉冲射线强化金属材料的几个问题:强化图形,材料性能,加工用量及表面涂层对被强化表面性能的影响。     

The haemodynamic response to the insertion of the laryngeal mask airway: a comparison with laryngoscopy and tracheal intubation

The haemodynamic response to the insertion of the laryngeal mask airway (LMA) was assessed and compared to that of laryngoscopy and tracheal intubation in a study of forty patients (ASA 1) randomly allocated into two groups and anaesthetised using a standard balanced anaesthetic technique. The results show that the changes in all cardiovascular parameters measured following LMA insertion were significantly less (P<0.05) when compared with those following laryngoscopy and tracheal intubation. We conclude that airway management with the LMA may be used to avoid the haemodynamic response to tracheal intubation where such a response is undersirable.     

AlEtCl2／t—BuCl引发α—蒎烯阳离子阳合的反应研究

在实验室绝热反应器中进行了乙苯脱氢制苯乙烯的反应动力学研究。根据不同反应机理，提出五种反应模型，经残差分析及模拟计算规律与实验规律的比较，确定Ｃａｒｒａ双曲模型为最佳反应动力学模型。通过对实验数据的回归拟合，经参数估计求得了速率方程的频率因子和活化能。     

Clinical response to local delivery of tetracycline in relation to overall and local periodontal conditions

Abstract The purpose of this study was to determine the clinical response to local delivery of tetracycline in relation to clinical and microbiological conditions of the other teeth. 4 deep pockets were monitored in 19 subjects with multiple deep periodontal lesions and high counts of P. gingivalis. In 9 patients (XT) only 2 of the selected lesions were treated by placement of tetracycline fibers (Actisite®). while the rest of the dentition was left untreated. In the other 10 patients, all teeth were supragingivally scaled and then treated by application of polymeric tetracycline HCl containing fibers, the whole dentition was subject to full mouth scaling and root planing, and the patients rinsed with 0.2% chlorhexidine (FT). A significant reduction in mean PPD was observed in all treated sites after two months. This reduction was maintained over the following 4 months. The magnitude of the effect was significantly greater in the FT group (1.74 mm) than in the LT group (0.88 mm). The mean attachment level changes were similar after 2 months in locally and fully treated subjects. A tendency of relapse was noted for treated sites in LT patients from month 2 to 6. A level of statistical significance was not reached for this effect. Data from measurements recorded at 6 sites around all teeth in the full mouth treated patients were analyzed using multiple linear regression. This analysis showed local changes in PPD and AL were significantly and strongly correlated with the baseline value of the respective parameter at the same site. In addition, more pocket depth reduction was noted if a site was not bleeding on probing at 6 months, if the location of a site was not approximal and if the tooth was not a second molar. Sites located on second molars showed also less AL gain than sites located on other teeth. Smokers showed significantly less reduction in PPD and significantly less AL gain. Furthermore, if subjects had a high % of pockets deeper than 4 mm at baseline they showed significantly less attachment gain.