[Mentoring and workplace-based assessments for final year medical students : An effective way to increase satisfaction and competence?] / Mentoring und arbeitsplatzbasierte Prüfungen im Praktischen Jahr : Ein effektiver Weg zur Steigerung von Zufriedenheit und Kompetenz?

BACKGROUND: The final year of medical training in Germany is one of the least structured and standardized years of medical school. Medical students often complain about a lack of guidance, supervision and feedback. They are mostly asked to perform delegable nonmedical tasks even though student experiences in this period critically determine future decisions for certain medical specialties. Consequently, right from the beginning many young professionals feel overburdened especially by the time pressure of everyday clinical practice. The planned amendment of the medical licensing regulations will make competence-based training even more important. This article therefore aims to examine the extent to which a mentoring-based curriculum with workplace-based examinations during the final year of medical studies can make a valuable contribution to this. METHODS: After a needs assessment (structured literature search, results evaluation and focus groups with both students and medical specialists), a mentoring-based curriculum for final year medical students was developed following the Kern cycle. In 2 work sessions 10 discipline-specific competencies for the fields of anesthesiology, critical care, emergency and pain medicine were established and prioritized, which had to be mastered by every student independently at the end of the training period. Assessment of these competencies was performed on a regular basis by trained mentors in the form of workplace-based assessments (mini-clinical evaluation exercise, mini-CEX, direct observation of procedural skills, DOPS). Multiperspective evaluation was and is the foundation of continuous program development. By September 2019 a total of 40 students had completed the modified curriculum and were subsequently interviewed online about various aspects of the tertial. RESULTS: The response rate to the survey was 80% (n = 32). The gender ratio was balanced (male = 50%, female = 50%). Prioritization and assessment of 10 competencies by trained mentors enabled a focused, demand-driven and high-quality training of final year medical students. Surveyed students found the section mentoring and feedback to be very positive and it supported their learning success (grade 1.5). Despite firmly established feedback structures, in retrospect almost half (51.6%) wanted more structured feedback. Workplace-based assessments were mostly previously unknown (64.6%) but were experienced as helpful and meaningful (76.7%). Students felt confident and prepared for the final state examination (81.3%) and their career start (71.0%) after being part of the program. These findings were accompanied by a high level of satisfaction (grade 1.7) as well as a high recommendation rate for this institution (as a training program for final year medical students and as a career start for residents, both with 93.7%). Thus, the good evaluation results of the department before the start of the project could again be slightly improved. CONCLUSION: A demand-driven, mentoring-based curriculum with integrated workplace-based assessments not only led to high overall student satisfaction but also promoted the quality of teaching in an effective and resource-saving way. Mentoring promotes learning success mainly through feedback and individual learning support and also supports the communicative and social skills of students and mentors alike.

[Traumatology in the elderly : Multimodal prevention of delirium and use of augmentation techniques]. / Alterstraumatologie : Multimodale Delirprävention und Verwendung von Augmentationstechniken.

Recent data show that 20-80% of surgery patients are affected by delirium during inpatient clinical treatment. The medical consequences are often dramatic and include a 20 times higher mortality and treatment expenses of the medical unit increase considerably. At the University Hospital of Münster a multimodal and interdisciplinary concept for prevention and management of delirium was developed: all patients older than 65 years admitted for surgery are screened by a specialized team for the risk of developing delirium and treated by members of the team if there is a risk of delirium. Studies proved that by this multimodal approach the incidence of delirium was lowered and therefore the quality of medical care improved.When surgical treatment of fractures in the elderly is required, limited bone quality as well as pre-existing implants can complicate the procedure. Secondary loss of reduction after osteosynthesis and avulsion of the implant in particular must be prevented. Augmentation of the osteosynthetic implant with bone cement can increase the bone-implant interface and therefore stability can be improved. Additional intraoperative 3D imaging can be necessary depending on the localization of the fracture. In biomechanical studies we could prove greater stability in the osteosynthesis of osteoporotic fractures of the distal femur when using additional bone cement; therefore, the use of bone cement is an important tool, which helps to prevent complications in the surgical treatment of fractures in the elderly. Nevertheless, special implants and technical skills are required and some safety aspects should be considered.

[Perioperative adverse respiratory events in overweight and obese children]. / Atemwegskomplikationen bei übergewichtigen und adipösen Kindern.

BACKGROUND: Overweight and obesity are increasing problems in pediatric anesthesia. This observational study was designed to examine how airway-related complications occur in overweight children and adolescents during general anesthesia and if this is a relevant problem in Germany. METHODS: From October 2008 until August 2009, at the university clinic in Leipzig, 504 in- and outpatients, aged 2-18 years, ASA I-III, undergoing elective procedures (ENT and pediatric surgery), were observed. With the aid of special data sheets, the following parameters were determined: Mallampati Score, difficult mask ventilation and intubation, use of a Guedel/Wendl tube, Cormack-Lehane Score, number of intubation attempts, airway obstructions (broncho- and laryngospasms), coughing as a sign of airway irritation, and decreases in oxygen saturation >10 %. RESULTS: Overweight and obese children had a significantly higher Mallampati Score and a significantly higher prevalence of coughing (p < 0.05). None of the other parameters showed any significant differences between the groups. However, the incidence of desaturation was 9.5 % in overweight children and 6.3 % in children of normal weight, and that of airway obstructions was 4.1 vs 2.7 %. CONCLUSION: This study demonstrated a very low incidence of respiratory problems, which may be caused by the low proportion of morbidly obese children and the older age of overweight children in comparison with other studies.

Asymmetrical flow field-flow fractionation for the analysis of PEG-asparaginase.

Monomethoxypolyethylene glycol L-asparaginase (PEG-ASNASE) is the PEGylated version of the enzyme L-asparaginase (ASNASE). Both are used for remission induction in acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The treatment control is generally carried out by performing activity assays, though methods to determine the actual enzyme rather than its activity are rare. Using asymmetrical flow field-flow fractionation (AF4) offered the chance to develop a method capable of simultaneously measuring PEG-ASNASE and PEG. A method validation was performed in accordance with FDA guidelines for PEG-ASNASE from non-biological solutions. The method unfolded a linearity of 15-750 U/mL with coefficients of correlation of r(2)>0.99. The coefficients of variation (CV) for within-run and between-run variability were 1.18-10.15% and 2.43-8.73%, respectively. Furthermore, the method was used to perform stability tests of the product Oncaspar® (PEG-ASNASE) and estimation of the molecular weight by multi-angle light scattering (MALS) of stressed samples to correlate them with the corresponding activity. The findings indicate that Oncaspar® stock solution should not be stored any longer than 24 h at room temperature and cannot be frozen in pure aqueous media. The validated method might be useful for the pharmaceutical industry and its quality control of PEG-ASNASE production.

Patterns and determinants of new first-line antihyperglycaemic drug use in patients with type 2 diabetes mellitus.

AIMS: We evaluated the patterns and determinants that influence the selection, timing and duration of first-line antihyperglycaemic drug (AHD) treatment in patients with type 2 diabetes in Germany, focusing specifically on treatment-naive AHD initiators. METHODS: Pharmacy dispensing claims data were linked with a cohort of patients newly enrolled in a German Disease Management Program for type 2 diabetes (DMP-DM2) between 2003 and 2009. We examined uptake of first-line pharmacotherapy in previously unmedicated patients and identified predictors of receiving AHD therapy in general and metformin in particular using multivariable regression analyses. RESULTS: There were 27,138 unmedicated patients with type 2 diabetes and 47.0% of them were started on AHD treatment within 5 years after enrollment. Initial severity of diabetes was the major predictor of receiving first-line pharmacotherapy. Metformin accounted for 63% of newly prescribed AHD in 2003 and more than 80% in 2009 while sulfonylureas accounted for only 10%. Initiating metformin as first-line AHD was associated with younger age, higher BMI, lower HbA1c, and shorter diabetes duration (multivariate p<0.001 for all). Therapy switch or step-up was less frequent among metformin initiators than sulfonylurea initiators. CONCLUSIONS: The majority of patients were not started on AHD therapy within 5 years after enrollment. In line with recent therapy guidelines, current first-line antihyperglycaemic treatment was increasingly based on metformin. AHD initiators started on sulfonylurea were generally more advanced in their disease and were started later on primary pharmacotherapy.

Cancer detection rates following enrolment in a disease management programme for type 2 diabetes.

AIMS/HYPOTHESIS: Recent prospective studies found an elevated cancer risk shortly after diabetes diagnosis, and this was probably due to increased ascertainment. This study investigated whether site-specific cancer risks are also raised following enrolment in a disease management programme for type 2 diabetes mellitus (DMP-DM2). METHODS: We linked records from a DMP-DM2 to population cancer registry data. The study period was from June 2003 to December 2009. Standardised incidence ratios (SIRs) were calculated for time intervals following DMP enrolment using the cancer incidence rates of the general source population. Additionally, Poisson regression with natural splines was used to assess time-dependent cancer incidence by diabetes duration. RESULTS: There were 2,034 first invasive cancer cases identified over 163,738 person-years of follow-up. Pancreatic cancer risk was significantly increased mainly in the first year after enrolment (SIR 1.62); the increment was only seen for patients in whom diabetes had been diagnosed less than 1 year before DMP-DM2 enrolment. Risk of endometrial cancer was similarly raised in the first year after DMP-DM2 enrolment among individuals newly diagnosed with diabetes but decreased rapidly thereafter. There was no time dependence in the incidence of cancers of the liver, lung, colon, breast and prostate. CONCLUSIONS/INTERPRETATION: Enrolment in a DMP-DM2 did not appear to induce ascertainment bias for most cancers. Cancer risks were initially increased, especially for pancreatic cancer, potentially as a result of reverse causality. Ascertainment bias and time-dependent incidence of cancer appear to be less of a problem in settings using DMP-like structures for the study of the association between diabetes duration, glucose-lowering medication and cancer incidence.

[The PRISCUS list in clinical routine. Practicability and comparison to international PIM lists]. / Die PRISCUS-Liste im klinischen Test. Praktikabilität und Vergleich mit internationalen PIM-Listen.

BACKGROUND: Certain drugs are classified as potentially inappropriate medications (PIM) for the elderly. In 2010, the PRISCUS list was published, specifically designed for its applicability in the German pharmaceutical market. The aim of this study was to evaluate the PRISCUS list compared to international PIM lists. METHODS: Based on selected PIM lists (PRISCUS, STOPP/START, Beers), the medications of 308 patients at a clinic of geriatric rehabilitation were screened for PIMs. Applying START criteria, omission of indicated drug therapies was detected. RESULTS: Regarding the rate of PIM detection, the PRISCUS list was less sensitive than the application of STOPP criteria. While hospitalized, the mean number of administered PIMs per patient was 1.2 based on STOPP criteria and 0.5 based on the PRISCUS list. The lowest number of PIMs per patient was detected by applying the Beers list (0.4 PIMs). CONCLUSION: The Beers list should not be used in the German pharmaceutical market. The amendment of diagnosis-related STOPP criteria to the PRISCUS list would be useful to significantly advance therapeutic success and drug safety in the elderly.

[Deep sedation in neonates and infants for diagnostic procedures]. / Analgosedierung von Neugeborenen und Säuglingen für diagnostische Prozeduren.

Many diagnostic and interventional procedures in neonates and infants need to be performed under sedation. Depending on the level of sedation this can lead to a total immobilisation of the children combined with a reduction of stress and pain and good diagnostic conditions. Therefore a deep sedation often is comparable with general anaesthesia. When performing sedations, established safety standards need to be observed. Apart from a skilled physician, well defined structures and procedures for pre- and postprocedural care are necessary. This includes standardised monitoring, medications and adapted medical engineering. The article gives an overview of the principle requirements for the working area, the monitoring and the physician him/herself. Furthermore after an illustration of the widely used medications, guidance for the practical proceeding in common procedures is given. With such a professional management. it is possible to increase the quality and safety of care for the children and not least the satisfaction of the parents even more.

The management of hypertensive emergencies in children after stem cell transplantation.

AIM OF THE REVIEW: This work presents a short overview on the available data about drugs that are currently used to treat hypertensive emergencies in children with a focus on incidents after stem cell transplantation. It shows that the pediatric use of all hypotensive agents appears to be mainly based on personal experience of the attending physicians rather than on convincing clinical trials. METHOD: A literature search was performed in MEDLINE, through PubMed, using the medical subject headings (MeSH) hypertensive emergencies, nifedipine, nicardipine, and children. Further articles were identified by checking cross-references of articles and books. RESULTS: Hypertensive emergencies in children after stem cell transplantation usually have a renal etiology, because of the treatment with the calcineurin inhibitors cyclosporine and tacrolimus. In these severe cases an immediate action is necessary to avoid possible appearance or exacerbation of endorgan damage. Because of their mechanism of action and a potential nephroprotective effect calcium channel blockers may be particularly suitable in cases of hypertensive emergencies. An intravenous application of nifedipine may compensate the difficulties of accurate dosing, but keeping in mind possible severe side effects and the lack of published experience its use in children is at least questionable. Nicardipine appears to be the hypotensive agent of first choice. In adults, the treatment of hypertensive emergencies with intravenous nicardipine is well-documented, but for an evaluation of safety in pediatric use, the published studies and case reports appear to be barely adequate. CONCLUSION: The actual treatment approaches vary widely, demonstrating the lack of hard science on which current treatment of hypertensive emergencies in children is based. The hypotensive agent for the individual situation should be chosen considering the properties, side effects, the limited experiences with its use and the patient's anamnesis.

NMR probe for pressure-jump experiments up to 250 bars and 3 ms jump time.

We describe the design and performance of a pressure-jump instrument for time-resolved NMR experiments. Initial pressure of up to 250 bars can be produced by means of a HPLC pump and distilled water as a pressure-transmitting liquid. Fast pressure release at a time resolution of 3 ms is achieved using a fast acting valve driven by a piezostack close to the sample chamber. The pressure-jump cell is placed together with two valves in an especially designed NMR probe, which can be used in standard spectrometers with wide-bore magnets. All functions of the instrument are personal computer controlled. The equipment is designed for investigations on systems of biological interest, especially lipid-water dispersions. A theoretical consideration implies that probably the limited speed of valve opening determines the lower boundary of the jump time. The performance is illustrated by time-resolved NMR spectra across the phase transition of a phospholipid-water dispersion after a pressure jump from 100 bars to atmospheric pressure.

Population pharmacokinetics of enoxaparin in infants, children and adolescents during secondary thromboembolic prophylaxis: a cohort study.

BACKGROUND: Enoxaparin has been extensively studied in adults on its safety and efficacy during prevention of symptomatic thromboembolism when acute anticoagulation or secondary prevention is required as a result of venous thrombosis or stroke. In children, it is still used off-label and little is known about the pharmacokinetics in children. OBJECTIVES: The aim of the present study was to evaluate whether a once- or twice-daily dosing regimen would be feasible in children to achieve appropriate plasma levels of enoxaparin. PATIENTS/METHODS: A population pharmacokinetic model was developed using anti-factor (F)Xa activity data from 126 children (median age: 5.9 years) receiving enoxaparin either as a once- or twice-daily dosing regimen. RESULTS: A two-compartment model was adequate for describing the enoxaparin kinetics. Body weight proved to be the most predictive covariate for clearance and central volume of distribution: clearance 15 mL h⁻¹ kg⁻¹, central volume of distribution 169 mL kg⁻¹, intercompartmental clearance 58 mL h⁻¹, peripheral volume of distribution 10 L and absorption rate 0.414 h⁻¹. Interindividual variability was found to be 54% for clearance and 42% for volume of distribution. CONCLUSION: The model is capable of describing all age groups and dosing levels of our population and predicts 12 h and 24 h enoxaparin activities sufficiently. According to our results, a once-daily enoxaparin dosing regimen with frequent monitoring is feasible. In 53.2% of the patients the median 24 h trough level was above the desired range of 0.1 IU mL⁻¹ anti-FXa activity for prophylaxis therapy.

A 9-year single center experience with circumumbilical Ramstedt's pyloromyotomy.

INTRODUCTION: Pyloric stenosis is a common cause of vomiting in infancy and is usually treated with a Ramstedt's pyloromyotomy. In this study we retrospectively reviewed our experience with the circumumbilical incision for the treatment of pyloric stenosis with a particular emphasis on the relation between postoperative emesis and postoperative time to feeds. MATERIAL AND METHOD: The medical records of all patients undergoing pyloromyotomy for IHPS from January 2000 to December 2008 were reviewed retrospectively. Patient details were recorded and statistically analyzed using SPSS version 13. We reviewed our experience looking specifically at the postoperative time to initial feeds as a way of minimizing hospital stay. RESULTS: 513 patients' notes were available for the study. There were 440 males and 73 females (M:F ratio 6:1). Median age at operation was 40 days (2-194 days) and a positive family history was obtained in 11.9%. Median duration of symptoms was 10 days (range 1-60 days). There were 31 (6%) complications related to surgery. The average number of postoperative emesis episodes was 1.9. The median postoperative hospital stay was 2 days (1-60). The average time to feeding was 20 h (1-69). CONCLUSION: This is a large single-center retrospective study where, in the era of minimally invasive surgery, Ramstedt's pyloromyotomy via the circumumbilical approach has a low rate of complications and is a safe and feasible method to treat pyloric stenosis. The establishment of feeds soon after surgery minimizes the postoperative in-hospital stay.

Pharmacokinetic monitoring of intravenous cyclosporine A in pediatric stem-cell transplant recipients. The trough level is not enough.

In order to monitor CsA serum levels after SCT, trough levels (C0) are widely used. The aim of this study was to estimate the population and individual PK parameters for patients receiving intravenous CsA after SCT. In 27 pediatric patients after SCT receiving CsA (3 mg/kg/day) every 12 h, a total of 289 CsA concentrations was obtained. To describe the PK parameters of CsA, a two-compartment model with first order elimination was used. Covariate analysis identified body weight, age, and the co-administration with itraconazole and tobramycine as factors influencing the Cl. The statistical comparison of AUC, trough level, and C2 indicates a correlation between AUC and C2, but no correlation between the AUC and C0, r = 0.24 (p = 0.146) vs. r = 0.526 (p = 0.000692), respectively. Our results underscore the fact that CsA trough levels do not reflect the drug exposure in patients receiving intravenous CsA after SCT. By contrast, CsA blood levels measured 2-6 h after CsA infusion showed a better correlation with the AUC. Our data provide new information to optimize the balancing act between GvHD-prophylaxis, graft vs. leukemia effect, and CsA side-effects after SCT.

Monitoring paracetamol metabolism after single and repeated administration in pediatric patients with neoplastic diseases.

INTRODUCTION: Paracetamol (PCM) is frequently used in pediatric patients with neoplastic disease. It is metabolized mainly by conjugation, but at therapeutic concentrations, a small fraction of the drug undergoes oxidative metabolism via cytochrome P450 forming the hepatotoxic intermediate N-acetyl-p-benzo-quinone-imine (NAPQI) which is usually conjugated with glutathione and excreted as paracetamol mercapturate and paracetamol cysteine. OBJECTIVE: The aim of this monitoring study was to evaluate PCM metabolism with minimal intervention during routine treatment with single and repeated administration in patients undergoing antineoplastic therapy. METHOD: A total of 107 urine samples collected 4-12 h after PCM administration from 29 children undergoing antineoplastic treatment, and 10 children without antineoplastic treatment were analyzed for PCM, PCM glucuronide (PCM-G), PCM sulfate (PCM-S), PCM mercapturate (PCM-M) and PCM cysteine (PCM-C). RESULTS: The median (range) percentages for metabolites in urine were: a) in children with and without chemotherapy after the first administration: PCM: 0 (0-100) and 4 (0-11)%, PCM-G: 55 (0-88) and 51 (18 - 68)%, PCM-S: 30 (0-73) and 32 (22-57)%, PCM-(M+C): 13 (0-52) and 9 (0-24)%, respectively; b) after repeated administration in children with chemotherapy: PCM: 0 (0-51)%, PCM-G: 42 (7-100)%, PCM-S: 28 (0-70)%, PCM-(M+C): 24 (0-66)%. CONCLUSION: The pattern of PCM excretion in children undergoing antineoplastic treatment regimens is highly variable. Repeated administration is associated with a significant increase in the products of oxidative metabolism. This might indicate an increase in metabolism via the hepatotoxic NAPQI.

Plasma and tissue pharmacokinetics of epirubicin and Paclitaxel in patients receiving neoadjuvant chemotherapy for locally advanced primary breast cancer.

The objective of the study was to assess individual distribution of antineoplastic drugs into the tumor. Twelve advanced-stage primary breast cancer patients with neoadjuvant epirubicin+paclitaxel chemotherapy were studied. Plasma concentrations of epirubicin and paclitaxel were monitored for 24 h. Epirubicin concentrations in subcutaneous and tumor tissues were measured using microdialysis up to 12 h postdose. Epirubicin concentrations were described by a compartmental population pharmacokinetic model (NONMEM). Noncompartmental analysis was used for paclitaxel. Plasma pharmacokinetics corresponded to published data. Mean epirubicin exposure in the tumor and in subcutaneous tissue was very similar, but tissue Cmax and area under the curve values reached only (means) 1% and 11%, respectively, of plasma values. Epirubicin doses were significantly correlated to tumor exposure irrespective of body surface area. There is no specific barrier for epirubicin to reach primary breast cancer tumors.

Effects and interaction of 7-hydroxy methotrexate and methotrexate in leukaemic cells ex vivo measured by the thymidylate synthase inhibition assay.

In high dose therapy with methotrexate (MTX) the main metabolite 7-hydroxy-methotrexate (7-OH MTX) exceeds the plasma concentration of MTX achieving about tenfold higher levels. To investigate the interaction between 7-OH MTX and MTX ex vivo, the thymidylate synthase inhibition assay was used to quantify antifolate effects in patient blast samples, measuring the inhibition of the key enzyme thymidylate synthase (TS). In 18 leukemic samples (7 ALL, 11 AML) no dose-dependent TS inhibition was observed for 7-OH MTX. However, a statistically significant increase of TS inhibition (p<0.05) was observed for a 1:1 mixture of MTX and 7-OH MTX as compared to the effect of MTX alone. The half-maximal inhibitory concentrations in the short-exposure assay were 0.857 microM for MTX alone versus 0.088 microM for the 1:1 mixture with 7-OH MTX, respectively (p< or =0.05). This interaction was not observed with an excess of 7-OH MTX. Similar results were obtained in long exposure experiments. We conclude that there is a dose-dependent interaction between 7-OHMTX and MTX, despite the lack of TS inhibitory effects of the metabolite alone.

[Liposomal daunorubicine combined with cytarabine in the treatment of relapsed/refractory acute myeloid leukemia in children]. / Effektive Rezidivtherapie der akuten myeloischen Leukämie im Kindesalter mit liposomalem Daunorubicin und Cytarabin.

BACKGROUND: First-line treatment in AML commonly included high cumulative doses of anthracyclines with an increasing risk of cardiotoxicity. Liposomal daunorubicin (L-DNR) is thought to be less cardiotoxic without impairment of efficacy. METHODS: The AML-BFM REZ 97 study included two reinduction blocks with L-DNR (2 x 60 mg/m (2) n = 38, since 2/1999 3 x 60 mg/m (2) n = 31) combined with cytarabine (500 mg/m (2) 4 d). Children who achieved a second blast clearance were allocated to allogeneic stem cell transplantation either from a matched related (MRD) or a matched unrelated donor (MUD). Lack of a donor justified haploidentical SCT in early relapse (1st remission < 1 year) and autologous SCT in late relapse. PATIENTS: Between 1/1997 and 9/2001, 69 children were enrolled in the AML-BFM 97 relapse study. The median duration of first remission was 0.9 years. Forty-one patients had a remission of less than one year, 28 of more than a year. RESULTS: 46 children (67 %) achieved a second remission, defined as clearance of blasts in bone marrow and at least a partial hematological reconstitution. Seventeen of these children are alive (12 of 25 children receiving allogeneic SCT (MFD/MUD); 1 of 8 children after haploidentical SCT; 1 of 4 patients after autologous SCT and 3 of 9 patients treated with chemotherapy only). Further three children without 2nd remission survived after MFD-SCT (n = 2) or chemotherapy (n = 1; follow-up 0.3 to 0.7 years). Duration of first remission remains a significant prognostic factor. The pharmacokinetic investigation showed a high overall AUC of 234.6 mg/l h at a dose of 60 mg/m (2), and a volume of distribution of 1.98 l/m (2), which is much lower in comparison to conventional Daunorubicin. Regarding toxicity, the combination of L-DNR and cytarabine followed by SCT was feasible in experienced centers, however, acute complications like infection or septicemia in aplasia, mucositis and GvHD were common. By contrast, no clinical relevant cardiotoxicity was seen so far, but definitive results in long-term cardiotoxicity await a longer follow-up. In conclusion, L-DNR/cytarabine treatment induced a 2nd remission in most of the children with relapsed or refractory AML. It has to be followed by allogeneic SCT which enables long-term survival.

Quantification of daunorubicin and daunorubicinol in plasma by capillary electrophoresis.

Capillary electrophoresis (CE) with laser-induced fluorescence detection was applied to quantify daunorubicin and daunorubicinol in plasma. Separation was carried out in a 47 cm x 50 microm I.D. fused-silica capillary, with a running buffer. pH 5 containing 60 microM spermine and 70% acetonitrile. Sample preparation was done either by protein precipitation with acetonitrile or by liquid-liquid extraction. The assay can be applied in a concentration range from 40 mg/l down to 2 microg/l for daunorubicin and from 1 mg/l to 2 microg/l for daunorubicinol. Precision and accuracy were between 2.9 and 14.5% (n=6) on 1 day and between 1.0 and 14.7% from day to day (n=6) for both analytes. Thus, the CE method enables precise and accurate quantification of daunorubicin and daunorubicinol in small sample volumes over a wide concentration range.