A computer model for the clearance of insoluble particles from the tracheobronchial tree of the human lung

A multi-compartment model for the clearance of insoluble particles from the tracheobronchial tree of the human lung was created. As a significant innovation, the model considers specific mass transfer paths that may play an important role for slow bronchial clearance. These include the accumulation of particulate mass in the periciliary sol layer, an uptake of stored particles by airway macrophages, and the endocytosis of deposited mass by epithelial cells. Besides the gel layer representing fast mucociliary clearance, all cellular and extracellular units involved into the slow clearance process are described by respective compartments which are connected by specific transfer paths. The gastrointestinal tract (GIT), lymph nodes (LN), and blood capillaries are included into the model as final accumulation compartments, to which mass is transferred via the airway route and the transepithelial path. Besides a basic version of the model describing the whole tracheobronchial region by one set of compartments, also an advanced approach is introduced which, in accordance with the International Commission on Radiation Protection (ICRP), subdivides the conducting airways into a bronchial (BB) and bronchiolar (bb) part. Preliminary results were generated with MS-Excel from deposition data of 1-mummass median aerodynamic diameter (MMAD) particles, calculating local slow clearance fractions according to mathematical procedures introduced in previous publications. While mucociliary clearance is completely finished within 24h after exposure, slow clearance takes place in distinct phases and needs several days to weeks. This multi-stage event is also reflected in the respective retention curves which correspond well to previously published graphs.     

Suitability of the AUC Ratio as an Indicator of the Pharmacokinetic Advantage in HIPEC

The purpose of this study was to evaluate the area under the concentration-time curve (AUC) ratio as an optimal indicator of the pharmacokinetic advantage during hyperthermic intraperitoneal perioperative chemotherapy. The impact on the AUC ratio on the variables related to the calculation of systemic drug exposure, instillation time, and peripheral drug distribution was evaluated through simulations as well as through a retrospective analysis of studies published in the literature. Both model simulations and the retrospective analysis showed that the 3 variables evaluated had an impact on the AUC ratio value if the complete systemic exposure was not fully considered. However, when that complete systemic exposure was considered, none of these variables affected the AUC ratio value. AUC ratio is not a characteristic parameter of a drug if the calculated systemic drug exposure is not complete. Thus, AUC ratio is not valid for comparing the pharmacokinetic advantage of 2 drugs, and it should not be employed to prove whether a drug can be used in hyperthermic intraperitoneal perioperative chemotherapy safely with regard to toxicity. As an alternative, the study of the absorption rate constant and the bioavailability are proposed as the true and independent parameters that reflect the amount of drug absorbed.     

Comparative study of three methods of estimation of creatinine clearance in critically ill patients

Background

At the bedside, the reference method for creatinine clearance determination is based on the measurement of creatinine concentrations in urine and serum (mCrCl). Several models are available to calculate the creatinine clearance from the serum creatinine concentration. This observational survey aimed at testing the hypothesis that the proposed equations are unreliable to determine accurate creatinine clearance in patients admitted to intensive care unit (ICU).

Method

Creatinine clearance was determined by the use of mCrCl. Then, we compared three equations: Cockcroft-Gault (CG), Simplified Modification of Diet in Renal Disease (MDRDs), and Chronic Kidney Disease Epidemiology (CKD-EPI) in 156 consecutive patients within the first 24 hours after ICU admission. We tested the hypothesis that the three equations were equivalent. The agreement between the three equations was evaluated by linear regression and Bland and Altman analysis.

Results

Bland and Altman analysis showed similar agreement between the three equations. The biases and precisions were –4.8 ± 51, –1.3 ± 50, and 8.2 ± 44 for CG, MDRDs, and CKD-EPI equations, respectively (P > 0.05). The precisions were similar for the three equations (P > 0.05). The percentages of outliers at ± 30% were 44%, 45%, and 49% for CG, MDRDs, and CKD-EPI, respectively (P > 0.05).

Conclusion

Regarding the high percentage of outliers, the use of these equations cannot be recommended in ICU patients.     

Computer models versus reality: How well do in silico models currently predict the sensitization potential of a substance

National legislations for the assessment of the skin sensitization potential of chemicals are increasingly based on the globally harmonized system (GHS). In this study, experimental data on 55 non-sensitizing and 45 sensitizing chemicals were evaluated according to GHS criteria and used to test the performance of computer (in silico) models for the prediction of skin sensitization. Statistic models (Vega, Case Ultra, TOPKAT), mechanistic models (Toxtree, OECD (Q)SAR toolbox, DEREK) or a hybrid model (TIMES-SS) were evaluated. Between three and nine of the substances evaluated were found in the individual training sets of various models. Mechanism based models performed better than statistical models and gave better predictivities depending on the stringency of the domain definition. Best performance was achieved by TIMES-SS, with a perfect prediction, whereby only 16% of the substances were within its reliability domain. Some models offer modules for potency; however predictions did not correlate well with the GHS sensitization subcategory derived from the experimental data. In conclusion, although mechanistic models can be used to a certain degree under well-defined conditions, at the present, the in silico models are not sufficiently accurate for broad application to predict skin sensitization potentials.     

36例脊柱结核外科疗效分析

目的分析药物结合外科治疗脊柱结核的疗效。方法回顾分析2002年3月-2006年2月同对36例脊柱结核采用抗结核药物治疗同时，以后路T形切口一期病灶清除、自体颗粒骨填充钛网椎间植入、后路钉棒系统固定治疗的疗效。结果经1～3年随访，平均15个月，结核无复发，Cobb角术前平均32。，术后平均8°。随访期间矫正无丢失。结论该术式创伤小，操作简单，临床效果满意。     

蜂王浆对小鼠免疫功能的增强作用

蜂王浆2.5g/kg/d ig×8d,可增加小鼠iV碳粒的廓清速率,并能完全对抗可的松对碳粒廓清速率的抑制作用,使之恢复正常。蜂王浆还增强小鼠的羊红细胞(SRBC)致敏的足跖迟发性过敏反应(DTH),并使环磷酰胺所致DTH反应低下完全恢复正常。蜂王浆2.5g/kg/d ig×7d对正常及注射环磷酰胺所致免疫功能低下小鼠的溶血素形成无影响。     

海尔福口服液对O2^-清除率的实验研究

目的:探讨海尔福口服液对超氧阴离子自由基(O2-)的清除效果及其机理。方法:用AP-TEMED系统比色法测定海尔福口服液对O2-的清除率,并与维生素C及金银花提取液作对比分析。结果:海尔福口服液(内含金银花生药0.1g/ml)、金银花水提取液(含生药0.1g/ml)、维生素C(浓度1.0mg/ml)对O2-的清除率分别是(92.71±2.79)、(81.15±3.81)、(92.67±5.46),加样量分别为1.0、0.5、0.25、0.125ml时,它们的相关系数分别为0.9697、0.9959、0.9988,有直线相关关系;三种存放时间不同的金银花提取液对O2-的清除率分别是(81.15±3.81)、(87.70±1.41)、(37.94±11.79),差异显著(P<0.05和<0.01);海尔福口服液生产过程中的不同阶段对O2-的清除率无显著性差异(P>0.05);海尔福口服液的其余主要原料如茯苓、甘草等对O2-的清除率均较低。结论:海尔福口服液及其主要原料之一金银花提取液在体外对O2-均有明显的清除作用,其效果与浓度为1.0mg/ml的维生素C溶液接近;金银花原料短期存放功效无明显变化,长期存放对O2-的清除率明显降低;海尔福口服液在生产过程中的不同阶段对O2-的清除率无明显变化。     

Die Elimination von para-Aminohippursäure beim Kind

Zusammenfassung PAH ist ein Teststoff zur Prüfung der gesamten exkretorischen Leistung der Niere. Seine Elimination erfolgt innerhalb einer bestimmten Zeit, nämlich zwischen der 10. und 40. min nach rascher intravenöser Injektion konzentrationsabhängig, d. h., die Konzentrationskurve folgt einer Exponentialfunktion. Deshalb ist die Eliminationshalbwertszeit als Zeitclearance zur Beurteilung der Nierenfunktion geeignet, insbesondere für Kinder, da dieser Wert unabhängig von Körpergröße, Oberfläche und Gewicht ist. Vor der 10. min ist die Elimination durch Diffusionsvorgänge gestört, nach der 40. min folgt eine Abflachung der Kurve durch enterale Reabsorption, wie experimentell nachgewiesen wird.Methodische Untersuchungen zur Bestimmung und Beurteilung werden vorgelegt. An 174 Kindern werden altersbezogene Normwerte der Stoffwechselstandardgrößen der PAH ermittelt. Die Elimination erfolgt bei Neugeborenen erheblich langssamer als bei älteren Kindern. Die Normwerte älterer Kinder werden nach Abschluß des ersten Lebensjahres erreicht. Das Verteilungsvolumen entspricht etwa dem extracellulären Flüssigkeitsvolumen.Die Ergebnisse werden diskutiert und mit dem Umsatz anderer Stoffe verglichen.

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The elimination of para-amino hippuric acid in children

PAH is a suitable substance for the estimation of the excretory function of the kidney.It is eliminated within a certain period of time, namely between the 10th and 40th min following a rapid intravenous injection; from this it follows that the concentration curve follows an exponential function. For this reason the elimination half life is suitable for the examination of the kidney function, especially in children, since the value is independent of size, surface, or body weight.Before the 10th min the rate of elimination is unreliable due to diffusion processes, and after the 40th min the curve flattens due to enteral reabsorption, as is demonstrated experimentally.Some methodical investigations for the estimation and calculation of these values are presented. Normal values in relation to age were obtained from 174 children.In the newborn the rate of elimination is slower than in older children. The levels of older children are reached after the first year of life. The distribution volume corresponds to the extracellular fluid volume.

Herrn Professor Dr. F. H. Dost zum 60. Geburtstag gewidmet.     

Determination of the technetium-99m mercaptoacetyltriglycine plasma clearance in children by means of a single blood sample: a multicentre study

A multicentre European study was undertaken in order to determine a reasonable algorithm allowing the determination of overall technetium-99m mercaptoacetyltriglycine clearance using a single blood sample. Employing multiple blood sample clearance as a reference method, it was shown that an acceptable estimation of the MAG3 renal clearance could be obtained using a blood sample taken at any time between 30 and 40 min after tracer injection. After correction for body surface area, comparison of clearance determined using (a) the single blood sample and (b) the multiple blood samples provided a coefficient of correlation of 0.949 and an SEE of 27 ml/min. This algorithm is valid for clearance values higher than 100 ml/min/1.73 m² and for children older than 1 year of age.