Population kinetics of gentamicin in neonates

A population kinetic analysis was carried out on sparse plasma gentamicin (GE) concentration data from 469 neonates obtained as part of a routine therapeutic drug monitoring (TDM) programme in the hospital neonatology unit.The best predictors of the kinetic parameters of the monoexponential model, volume of distribution (Vd) and clearance (CL), were the weight (WT) and gestational age (GA). Vd of the neonates was only related to WT, whereas the half-life was only related to the GA.     

The influence of pentoxifylline on motility and viability of spermatozoa from normozoospermic semen samples

In order to evaluate the effects of pentoxifylline on sperm motility and longevity, a controlled in-vitro study was conducted on normozoospermic donor semen samples using the Cellsoft automated system for sperm motility analysis. After incubation and selection, pentoxifylline was found to improve the recovery of spermatozoa and to increase their velocity. In the subgroup of progressively motile spermatozoa, curvilinear velocity was also enhanced. It is concluded that pentoxifylline has an effect on the vigour, but not on the pattern, of sperm motion. Pentoxifylline did not improve the motility characteristics of senescent spermatozoa in normozoospermic sperm samples. Sperm survival, as shown by supra-vital staining, and motility longevity both decreased with time after pentoxifylline treatment.     

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.     

输精管结扎干扰前列腺增生过程的机制探讨——精浆睾酮双氢睾酮的放射免疫测定

本文应用放射免疫测定的方法检测了13例输精管结扎后(平均15.3年,平均年龄50岁)的男性精浆双氢睾酮和睾酮的浓度,另取同年龄组男性13例作为对照。结果表明,精浆睾酮在结扎组(374.54p/ml)和正常对照组(315.64Pg/ml)中没有明显差异,而结扎组精浆中双氢睾酮(46.21pg/ml)却明显低子对照组(184.27pg/ml(p<0.01)。作者认为,输精管结扎对精浆DHT有长期影响,这可能是其对前列腺增生过程产生抑制作用的原因之一。     

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.     

Improvement in quality of cryopreserved human spermatozoa by swim-up before freezing

Selecting a population of spermatozoa by the swim-up technique yields, after freezing and thawing, a population of cells that contains proportionally more spermatozoa which are morphologically normal, fewer spermatozoa with damaged tail membranes, and a greater percentage of progressively motile spermatozoa with greater velocities and amplitudes of head displacement than those obtained after freezing and thawing the same semen samples in the normal way. This pattern was found for the semen from 10 patients and five volunteers. However, the cells selected by swim-up were as susceptible to the stresses caused by freezing and thawing as unselected spermatozoa in the original semen sample, and the improvement came from the better quality of the initial sample.     

A longitudinal study of semen quality in pesticide spraying danish farmers

It was hypothesized that occupational exposure to pesticides during a spraying season causes changes in semen quality that might be detected in a longitudinal study. We analyzed the within-person changes in semen quality and reproductive hormones across a spraying season in groups of farmers using and not using pesticides. A total of 248 men collected two semen samples (participation rate: 32%). The median sperm concentration declined significantly from the first to the second sample in both groups, but there was no statistical difference in the decline between the two groups, unadjusted or adjusted. Only minor changes were found in sperm morphology, vitality, motility, sperm chromatin denaturation (SCSA), and reproductive hormones, and the differences in changes between the two groups were nonsignificant, or, in the opposite direction to the expected. There was no relation between the changes in sperm parameters in relation to pesticide exposure variables. In conclusion, use of pesticides by Danish farmers is not a likely cause of short-term effects on semen quality and reproductive hormones.     

不同免疫抑制剂对肾移植患者精子参数的影响

目的:研究不同免疫抑制剂对肾移植患者精子运动功能的影响。方法:20例肾移植患者应用以普乐可复(FK506+霉酚酸酯+泼尼松)、17例应用环孢素(CsA+硫唑嘌呤+泼尼松)为主的免疫抑制治疗方案,15例正常男性为对照组。采用计算机辅助的精子分析系统分别检测精子活率、运动参数(前向运动百分率、直线速度VSL、曲线速度VCL、平均路径速度VAP)和精子形态。结果:3组精子活率[(81.7±5.7)%、(79.4±6.8)%、(83.8±6.0)%]、VCL[(24.1±8.6)%、(23.9±4.4)%、(24.8±4.2)%]和VAP[(19.7±6.6)%、(18.6±2.9)%、(21.0±4.0)%]差异均无显著性(P>0.05);FK506组的精子前向性运动百分率[(46.4±8.1)%]和VSL[(15.4±4.6)%]均显著高于CsA组[(33.3±6.4)%、(10.2±2.4)%],畸形率[(67.8±5.7)%]显著低于CsA组[(80.1±5.6%](P<0.05)。结论:FK506和霉酚酸酯的联合应用,有助于肾移植患者精子运动功能及形态的恢复。     

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.