The effect of red blood cell age on coagulation

Background

Packed red blood cell (PRBC) units stored and unused at community hospitals are transferred to trauma centers near the end of their shelf storage life, because of a higher likelihood of utilization before expiration without consideration of coagulation system effects. This study was conducted to determine if the stored age of PRBC units has an effect on coagulation.

Methods

Single-donor citrate/phosphate/dextrose-preserved, PRBCs, and fresh frozen plasma (FFP) were recalcified in an in vitro model. The activated clotting time (ACT) was measured using the microsample method on days 3, 19, 20, and 33 from the date of donation.

Results

The ACT was prolonged as the age of PRBCs increased while other factors were held constant. ACTs on days 19, 20, and 33 were prolonged relative to day 3. Measurements taken on day 33 were significantly prolonged relative to day 20.

Conclusions

Increasing age of PRBCs measured from the date of donation adversely affects the global coagulation status. This study suggests that we should re-evaluate current blood banking and transfusion practices in trauma care.     

Degradable cisplatin-releasing core-shell nanogels from zwitterionic poly(beta -aminoester)-graft-PEG for cancer chemotherapy

Cisplatin conjugated onto macromolecules or loaded in micelles can be preferentially delivered to tumors to minimize its toxicity to healthy tissues and increase its drug efficacy. Herein, we report cisplatin-containing nanogels possibly useful for targeted delivery of cisplatin. Carboxylic acid-functionalized poly(β -aminoester)graft-poly(ethylene glycol) copolymers were synthesized by cocondensation polymerization of piperazine with 2,2-bis(acryloxymethyl)propionic acid, PEG 2,2-bis(acryloxymethyl)propionate macromonomer (mPEG). The graft copolymers formed 100-200 nm nanogels with low size-distribution by the complexation of their carboxylic groups with cisplatin. The nanogels were negatively charged and had a PEG outer layer. Thus, they had “stealth properties” suitable for in vivo applications. The nanogels had significantly lower in vitro cytotoxicity to SKOV-3 ovarian cancer cells than free cisplatin, but similar anticancer activity toward SKOV-3 tumors xenografted to immunocompromised mice.     

Busunfall auf der Autobahn A14 bei Bernburg

On 18.06.2007 one of the most severe coach accidents in the Federal Republic of Germany for 15 years occurred on the motorway A14 in Saxony-Anhalt. The accident occurred in the catchment area of a hospital for routine care in the city of Bernburg. The article presents the accident site, the alarm routes as well as the rescue tactics during the course of the rescue operation and discusses the aspects and conclusions drawn from this mass casualty incident. The dispatchment of a large number of emergency physicians from the hospital anaesthesia department to organize immediate care and transferral of the injured patients to different hospitals proved to be especially helpful.     

Development of a Novel Oral Cavity Compartmental Absorption and Transit Model for Sublingual Administration: Illustration with Zolpidem

Intraoral (IO) delivery is an alternative administration route to deliver a drug substance via the mouth that provides several advantages over conventional oral dosage forms. The purpose of this work was to develop and evaluate a novel, physiologically based oral cavity model for projection and mechanistic analysis of the clinical pharmacokinetics of intraoral formulations. The GastroPlus™ Oral Cavity Compartmental Absorption and Transit (OCCAT™) model was used to simulate the plasma concentration versus time profiles and the fraction and rate of intraoral drug transit/absorption for Intermezzo® sublingual tablets (zolpidem tartrate). The model was evaluated by the goodness-of-fit between simulated and observed concentrations and the deviation of key PK parameters (e.g., C_max, T_max, and AUC). In addition, a sensitivity analysis was conducted to demonstrate the interplay and impact of key modeling parameters on the fraction absorbed via oral mucosa (F_{a_IO}). The OCCAT™ model captured the observed pharmacokinetics for Intermezzo® sublingual tablets (R² > 0.9). The predicted deviations (%) for C_max, AUC_0–inf, AUC_0–20 min, and T_max were 5.7, 28.0, 11.8, and 28.6%, respectively, indicating good prediction accuracy. The model also estimated ~18% of total drug was absorbed via the IO route. Furthermore, the sensitivity analysis indicated that the F_{a_IO} was not only associated with drug diffusivity and unbound fraction in epithelium tissue (f_ut) but also depended on the physicochemical properties of compounds for IO delivery (e.g., solubility and logD_pH = 7.4). The novel physiologically based IO absorption OCCAT™ model showed satisfactory performance and will be helpful to guide development of future intraoral formulations.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-015-9727-7) contains supplementary material, which is available to authorized users.KEY WORDS: diffusivity, intraoral delivery, oral cavity compartmental absorption and transit (OCCAT™) model, unbound fraction in epithelium tissue, zolpidem     

Typical image of splenic hydatidosis

This is a typical case of a splenic hydatid cysts. We present the clinical features, the diagnostic work-up and the management of the disease.