Identification and analysis of nine metabolites of cyclosporine in whole blood by liquid chromatography. 1: Purification of analytical standards and optimization of the assay

We describe an extraction and an isocratic "high-performance" liquid-chromatographic (HPLC) separation of cyclosporine (CsA) and nine metabolites (M1, M8, M17, M18, M21, M25, M26, M203-218, and MUNDF1) from whole blood. Metabolites (for standards) were purified from human bile with liquid-liquid and solid-phase extractions, chromatographed on a cyanopropyl (CN) semipreparative HPLC column, and further purified on octyl, CN, and silica columns. The identity of each metabolite was verified with authentic standards on three chemically different HPLC columns and on the basis of cross-reactivity data from radioimmunoassay. For the routine analytical method, 1 mL of whole blood is diluted, hemolyzed, and applied to a Bond Elut CN (500 mg) cartridge to extract CsA, metabolites, and cyclosporin C, the internal standard. Interferences are removed by using four wash solutions and an additional cartridge of octyldecyl sorbent introduced prior to elution. Analytes are separated on a Zorbax CN analytical column maintained at 58 degrees C, with detection at 214 nm. Analytical recovery, as tested with three lots of CN sorbent, ranged from 47% to 95% for the 10 cyclosporines. Between-run CVs are less than 10% at 200 micrograms/L (concentration of each compound) and the standard curves are linear to 1500 micrograms/L. We also report a study of the separation mechanisms.     

Children's beliefs about punishment

It has been asserted that family violence is linked to the physical punishment of children. To explore children's views on different types of punishment, brief vignettes depicting a child misbehaving were presented to 201 9-12-year-olds who were asked to provide a "parental" response. Although few recommended physical punishment, the findings suggest that for some children physical punishment and aggression are associated.     

细胞因子激活骨髓免疫细胞的实验研究

目的：通过对骨髓单个核细胞在体外与不同细胞因子培养,了解不同细胞因子对骨髓淋巴细胞的激活能力和对骨髓干祖细胞的损伤情况。方法：将IL-1、IL-2、γ-IFN、CD3单抗进行不同组合后,在体外与骨髓单个核细胞分成对照组、IL-2组、CD3-AK、CIK组进行培养。培养过程中观察细胞形态和数量的变化,并在培养后检测免疫活性细胞的细胞毒性和造血干细胞的保存情况。结果：培养过程中对照组细胞数量减少;IL-2组细胞数量变化不明显;CD3-AK组、CIK组细胞数量显著增多,并出现较多的集聚成簇的淋巴样细胞,培养后其细胞毒性明显强于对照组及IL-2组,但细胞数量增加和细胞毒性无明性差异,培养后各组造血干细胞保存情况约16%～87%。结论：IL-2、CD3单抗在体外与骨髓单个核细胞培养后,即能激活免疫细胞增殖,又能保留足够的造血干细胞。     

High Rates of Spacer Fracture in the Setting of Extended Trochanteric Osteotomy With a Specific Thin-Core Articulating Antibiotic Hip Spacer

BackgroundTwo-stage revision remains the standard of care for prosthetic joint infection after total hip arthroplasty. However, there are substantial complications associated with articulating antibiotic hip spacers. Handmade and molded spacers have been shown to have higher rates of spacer fracture than antibiotic-coated prostheses (ACPs). The aim of this study is to review outcomes with an implant that is often categorized as an ACP spacer, the Zimmer-Biomet StageOne Select Femoral Spacer (ZBSO).MethodsA retrospective review was performed of 63 patients who underwent placement of a ZBSO. Patients were compared based on whether or not an extended trochanteric osteotomy (ETO) was performed using Fisher’s exact and t-tests.ResultsFive patients were excluded due to lack of follow-up or death shortly after stage 1 surgery, leaving 58 patients. Spacer fracture was noted in 5 of 58 patients (8.6%). Sixteen patients underwent ETO and 25.0% suffered a spacer fracture compared to 2.3% without ETO (odds ratio 13.7, P = .0248). There was no association between patient demographics or ETO length and spacer fracture. Two patients had periprosthetic fractures (3.4%) and 4 had dislocations (6.9%). Forty-nine patients (84.4%) went on to second-stage revision; of those 26.5% failed to clear the infection and required an average of 2.2 additional surgeries.ConclusionThe ZBSO spacer has overall complication rates similar to previously reported spacer series. Although the ZBSO looks like an ACP spacer, in the setting of ETO, it behaves like a molded or handmade spacer with a high rate of spacer fracture (25%) due to the small diameter of the core. This implant should be used with caution in combination with an ETO.     

Polymicrobial catheter sepsis in long term central venous catheters

We present 2 cases of polymicrobial catheter sepsis in patients with long term central venous catheters who were receiving home parenteral nutrition. Both patients were generally unwell with haemodynamic instability. Attempts at catheter salvage by combined antibiotic and fibrinolytic administration through the central line were unsuccessful and resulted in patient deterioration. Catheters were removed in both patients. We conclude that catheter salvage should be considered very carefully in patients with polymicrobial catheter sepsis and there should be a low threshold for catheter removal in these cases.     

Extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy for urinary calculi: comparison of immediate and long-term effects

Extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy have become widely used technologies for removal of urinary calculi, despite a lack of adequate evaluative studies. The possibility of long-term adverse effects of these treatments has been raised, particularly an increase in stone recurrence and development of hypertension following extracorporeal shock wave lithotripsy. We conducted a retrospective study of 1,000 patients treated with extracorporeal shock wave lithotripsy or percutaneous nephrostolithotomy for upper tract stone disease to assess immediate effectiveness and complications, with prospective follow-up to assess stone recurrence and development of hypertension. The effectiveness of each treatment (defined in terms of patients rendered stone-free or having only fragments at discharge) was similar for most stone types. While stone recurrence rates in the first 2 years after treatment were similar in the two groups, cumulative recurrence at 3 years was higher following extracorporeal shock wave lithotripsy compared to percutaneous nephrostolithotomy (39% vs. 23%, p = 0.04). However, logistic regression and Kaplan-Meier analyses showed no significant difference in clinically evident recurrence for patients treated with extracorporeal shock wave lithotripsy. Cumulative incidence of clinically evident stone recurrence did not differ significantly between patients with fragments at discharge (20%) and patients rendered stone-free (15%) (p = 0.24). There was no difference in the development of new hypertension requiring medical treatment. Our findings indicate that extracorporeal shock wave lithotripsy is effective and associated with lower short-term morbidity than percutaneous nephrostolithotomy. Stone fragments left behind by lithotripsy do not appear to confer significant risk of early stone recurrence. Further study is necessary to define long-term risk of recurrence following extracorporeal shock wave lithotripsy.