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Zusammenfassung Ziel Analyse der Wirkungen sensomotorischen Trainings in Kombination mit einem gerätegestützten Krafttraining auf das Gleichgewicht, die Kraft der unteren Extremitäten sowie polyneuropathische Beschwerden bei Brustkrebspatientinnen in der Rehabilitation. Methoden Brustkrebspatientinnen (n=52) wurden während einer dreiwöchigen stationären Anschlussheilbehandlung in der medizinischen Trainingstherapie (3 TE/Woche) in zwei Gruppen randomisiert. Die Untersuchungsgruppe (n=27) absolvierte ein sensomotorisches Training mit einem anschließenden gerätegestützten Krafttraining, die Kontrollgruppe (n=25) nur ein gerätegestütztes Krafttraining. Vor Beginn und nach Beendigung des Trainingszeitraums wurden das dynamische und funktionelle Gleichgewicht sowie die isokinetische Maximalkraft gemessen. Zudem wurden anhand einer Skala die polyneuropathischen Beschwerden der Patientinnen (n=31 mit diagnostizierter Polyneuropathie; davon: SMT=19; KG=12) erhoben. Ergebnisse Im Trainingsexperiment zeigte sich ein signifikanter Haupteffekt, d. h., dass sowohl die Trainings- als auch die Kontrollgruppe signifikante Verbesserungen bezüglich der Gleichgewichts- und Kraftleistung sowie der polyneuropathischen Beschwerden erreichten. Allerdings konnte kein Interaktionseffekt nachgewiesen werden, die Kombination aus sensomotorischem und gerätegestütztem Training zeigte folglich keine Vorteile. Demgegenüber erwiesen sich Alter, Körpergröße und teilweise der BMI als relevante Kovariate. Dies erlaubt die Schlussfolgerung, dass einerseits in der Trainingstherapie Methodenvielfalt möglich, andererseits aber das jeweils ausgewählte Trainingsprogramm individuell anzupassen ist. Schlussfolgerung Bei einem geringen Zeit- und Kostenaufwand entsteht durch sensomotorisches Training ein erkennbarer Effekt auf das Wohlbefinden von Krebskranken, speziell bei Polyneuropathie. Insofern ist es erstrebenswert, dass sporttherapeutisches Personal Krebskranke über die Vorteile sensomotorischen Trainings aufklärt und sie in entsprechenden Übungen unterweist.

Ruckenschmerzen sind zu einer Volkskrankheit geworden und fuhren zu vielen Fehltagen in der Erwerbstatigkeit. Dies erfordert effektive und effiziente Therapieformen, zu denen auch Krafttraining gehort. Da sich EMS-Training seit einigen Jahren einer zunehmenden Beliebtheit erfreut, stellt sich die Frage, ob mittels dieser neueren Methode des Krafttrainings Effekte auf den Ruckenschmerz erzielen lassen. Wie wirkt sich ein 10-wochiges EMS-Training auf die Kraftausdauer der Rumpfbeuge- und Rumpfstreckmuskulatur, auf die subjektive Wahrnehmung der physischen Konstitution sowie auf das subjektive Belastungsempfinden und die Bewaltigung der Alltagsanforderungen von Lehrkraften aus? Es handelt sich um eine multimethodische Pilotstudie, die sich aus drei replizierten Interventionsstudien mit je zwei Messzeitpunkten zusammensetzt. Mittels verschiedener Datenerhebungsinstrumente (Kraftausdauertests, Fragebogen und Leitfadeninterviews) wurden das Kraftniveau relevanter Muskelgruppen, das subjektive Schmerzempfinden sowie Aktivitaten des taglichen Lebens gemessen, individuelle Einschatzungen erhoben und in einer Gesamtbewertung zusammengefuhrt. Mittels t‑Tests konnten bezuglich der gemessenen Parameter zwar keine signifikanten Verbesserungen nachgewiesen werden, dennoch lagen die Effekte des EMS-Trainings im Bereich mittel bis hoch. Zu vermuten ist, dass dies den kleinen Stichproben geschuldet ist. Eine qualitative Analyse der subjektiven Einschatzungen von EMS-Training zeigte durchweg positive individuelle Wahrnehmungen, jedoch kaum Auswirkungen auf die Belastungssituationen im Alltag.

Phenytoin (PHT) is one of the most often used critical dose drugs, where insufficient or excessive dosing can have severe consequences such as seizures or toxicity. Thus, the monitoring and precise measuring of PHT concentrations in patients is crucial. This study develops and validates an LC-MS/MS method for the measurement of phenytoin concentrations in different body compartments (i.e., human brain dialysate, blood, and saliva) and compares it with a formerly developed GC-MS method that measures PHT in the same biological matrices. The two methods are evaluated and compared based on their analytical performance, appropriateness to analyze human biological samples, including corresponding extraction and cleanup procedures, and their validation according to ISO 17025/FDA Guidance for Industry. The LC-MS/MS method showed a higher performance compared with the GC-MS method. The LC-MS/MS was more sensitive, needed a smaller sample volume (25 µL) and less chemicals, was less time consuming (cleaning up, sample preparation, and analysis), and resulted in a better LOD (r2 > 0.995 for all tested matrices (blood, saliva, and dialysate). For larger sample numbers as in pharmacokinetic/pharmacodynamic studies and for bedside as well as routine analyses, the LC-MS/MS method offers significant advantages over the GC-MS method.

To investigate the potential of N-acetyltaurine (NAcT) in blood as a biomarker for alcohol uptake, a previously published LC-MS/MS method for urine was modified to simultaneously detect NAcT and ethyl glucuronide (EtG). The method was applied in a drinking study and by analyzing 147 forensic case samples. In the drinking study, contrary to EtG, NAcT proved to be an endogenous substance, which was present at 22 ± 7 ng/mL (13-31 ng/mL) in the blood after 2 weeks of abstinence. A moderate increase in NAcT to 40 ± 10 ng/mL (27-57 ng/mL) was observed after drinking. Within 24 h, the NAcT concentrations declined to starting concentrations in seven out of eight subjects. Peak EtG concentrations (c¯max) of 445 ± 101 ng/mL (278-662 ng/mL) were reached. While EtG in blood can be used to detect alcohol consumption even if ethanol is already eliminated, some of the maximum NAcT concentrations after a single ethanol dose were in the range of endogenous levels detected prior to the start of drinking in other subjects. In the 147 blood samples, the following concentrations were found: blood alcohol concentration (BAC): 1.22 ± 0.95 g/kg (0-3.46 g/kg); NAcT: 37.8 ± 18.4 ng/mL (12.1-109 ng/mL); EtG: 1149 ± 1121 ng/mL (0-5950 ng/mL). ROC curve analysis for BAC thresholds at 0.8 and 1.6 g/kg were performed for EtG and NAcT. Due to the presence of endogenous NAcT levels resulting in a lower sensitivity and selectivity when compared to EtG, and due to a minor increase in concentration after alcohol uptake, the usefulness of NAcT as an alcohol biomarker in blood is very limited.

Key Clinical Message Acute life‐threatening intoxications with insecticides are rare. We report a case of accidental near‐fatal thiacloprid intoxication with mass spectrometry‐based analytical confirmation. The initial clinical presentation resembled imminent brain death and/or severe postanoxic encephalopathy. Prolonged supportive treatment resulted in full recovery underlining intoxication as an important differential diagnosis in unclear coma.

„Functional training“ erfreut sich groser Beliebtheit – was steckt hinter dem Hype um diese neuartige Trainingsmethode? Wie wirkt sich ein individuell konzipiertes, funktionelles Trainingsprogramm im Vergleich zu einem standardisierten, gerategestutzten Zirkelkrafttraining auf den FMS-Score aus? Quasiexperimentelle Interventionsstudie im Feld. Analyseinstrument bildet der „functional movement screen“ (FMS), der die Haltung, Statik, Bewegungsamplitude sowie die Stabilitat des Sportlers in Zeitlupe untersucht. Mittels einer Varianzanalyse mit Messwiederholung konnte fur beide Trainingsgruppen (funktionelles & gerategestutztes Training) ein Haupteffekt „Training“ festgestellt werden. Daruber hinaus zeigte sich ein Interaktionseffekt „Training*Gruppe“: Die funktionell trainierende Gruppe erzielte einen groseren Trainingseffekt als die Probanden, die ein gerategestutztes Krafttraining durchgefuhrten. Des Weiteren konnte festgestellt werden, dass das Geschlecht keinen Einfluss auf das Testergebnis hatte. Bezuglich der Zufriedenheit mit der durchgefuhrten Studie wurde ein signifikanter Einfluss festgestellt. Wenn auch einen geringen und nicht-signifikanten Einfluss hatten die tatsachlich absolvierten Trainingseinheiten auf das Ergebnis der Studie.

Analysis of cannabis has gained new importance worldwide, mainly for quality control within the legalized recreational and medical cannabis industry, but also for forensic differentiation between drug-type cannabis and legal products such as fiber hemp and CBD-rich/THC-poor cannabis. We herein present an HPLC-DAD method for quantitative analysis of major neutral and acidic cannabinoids in herbal cannabis and hashish: Δ9-tetrahydrocannabinol (THC), Δ9-tetrahydrocannabinolic acid A (THCA), cannabidiol (CBD), cannabidiolic acid (CBDA), and cannabinol (CBN). Plant material was dried, homogenized and extracted with a mixture of methanol/hexane. Chromatographic separation of the analytes was achieved on a core-shell C8 column using gradient elution with water/acetonitrile containing 0.1% formic acid. The analytical run time was 13 min and analytes were detected at 210 nm. The method is selective, sensitive, accurate, and precise, as confirmed through validation according to ICH and AOAC guidelines. Linearity in herbal cannabis ranged from 0.04 to 4.00% for the neutral cannabinoids, and from 0.40 to 20% for the acids. Linear ranges in hashish samples were 0.13–13.33% and 1.33–66.66%, respectively. The presented method was successfully applied to characterize 110 cannabis samples seized by the Swiss police, demonstrating its applicability for routine cannabis potency testing in the forensic setting.

For driving aptitude assessment (DAA), the analysis of several alcohol biomarkers is essential for the detection of alcohol intake besides psycho-medical exploration. In Switzerland, EtG in hair (hEtG) is often the only direct marker for abstinence monitoring in DAA. Therefore, the suitability of phosphatidylethanol (PEth) was investigated as additional biomarker. PEth 16:0/18:1 and 16:0/18:2 were determined by online-SPE-LC-MS/MS in 136 blood samples of persons undergoing DAA and compared to hEtG, determined in hair segments taken at the same time. With a PEth 16:0/18:1 threshold of 210 ng/mL for excessive alcohol consumption, all (n = 30) but one tested person also had hEtG values ≥30 pg/mg. In 54 cases, results are not in contradiction to an abstinence as neither PEth (

Phosphatidylethanol (PEth) is considered as specific biomarker of alcohol consumption. Due to accumulation after repeated drinking, PEth is suitable to monitor long-term drinking behavior. To examine the applicability of PEth in "driving under the influence of alcohol" cases, 142 blood samples with blood alcohol concentrations (BAC) ranging from 0.0-3.12 ‰ were analyzed for the presence of PEth homologues 16:0/18:1 (889 ± 878 ng/mL; range

The synthetic tryptamine 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT) has recently been abused as a hallucinogenic drug in Germany and Switzerland. This study presents a case of 5-MeO-MiPT intoxication and the structural elucidation of metabolites in pooled human liver microsomes (pHLM), blood, and urine. Microsomal incubation experiments were performed using pHLM to detect and identify in vitro metabolites. In August 2016, the police encountered a naked man, agitated and with aggressive behavior on the street. Blood and urine samples were taken at the hospital and his premises were searched. The obtained blood and urine samples were analyzed for in vivo metabolites of 5-MeO-MiPT using liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS). The confiscated pills and powder samples were qualitatively analyzed using Fourier transform infrared (FTIR), gas chromatography-mass spectrometry (GC-MS), LC-HRMS/MS, and nuclear magnetic resonance (NMR). 5-MeO-MiPT was identified in 2 of the seized powder samples. General unknown screening detected cocaine, cocaethylene, methylphenidate, ritalinic acid, and 5-MeO-MiPT in urine. Seven different in vitro phase I metabolites of 5-MeO-MiPT were identified. In the forensic case samples, 4 phase I metabolites could be identified in blood and 7 in urine. The 5 most abundant metabolites were formed by demethylation and hydroxylation of the parent compound. 5-MeO-MiPT concentrations in the blood and urine sample were found to be 160 ng/mL and 3380 ng/mL, respectively. Based on the results of this study we recommend metabolites 5-methoxy-N-isopropyltryptamine (5-MeO-NiPT), 5-hydroxy-N-methyl-N-isopropyltryptamine (5-OH-MiPT), 5-methoxy-N-methyl-N-isopropyltryptamine-N-oxide (5-MeO-MiPT-N-oxide), and hydroxy-5-methoxy-N-methyl-N-isopropyltryptamine (OH-5-MeO-MiPT) as biomarkers for the development of new methods for the detection of 5-MeO-MiPT consumption, as they have been present in both blood and urine samples.

An HPLC-DAD method for the quantitative analysis of Δ(9)-tetrahydrocannabinol (THC), Δ(9)-tetrahydrocannabinolic acid-A (THCA-A), cannabidiol (CBD), and cannabinol (CBN) in confiscated cannabis products has been developed, fully validated and applied to analyse seized cannabis products. For determination of the THC content of plant material, this method combines quantitation of THCA-A, which is the inactive precursor of THC, and free THC. Plant material was dried, homogenized and extracted with methanol by ultrasonication. Chromatographic separation was achieved with a Waters Alliance 2695 HPLC equipped with a Merck LiChrospher 60 RP-Select B (5μm) precolumn and a Merck LiChroCart 125-4 LiChrospher 60 RP-Select B (5μm) analytical column. Analytes were detected and quantified using a Waters 2996 photo diode array detector. This method has been accepted by the public authorities of Switzerland (Bundesamt für Gesundheit, Federal Office of Public Health), and has been used to analyse 9092 samples since 2000. Since no thermal decarboxylation of THCA-A occurs, the method is highly reproducible for different cannabis materials. Two calibration ranges are used, a lower one for THC, CBN and CBD, and a higher one for THCA-A, due to its dominant presence in fresh plant material. As provider of the Swiss proficiency test, the robustness of this method has been tested over several years, and homogeneity tests even in the low calibration range (1%) show high precision (RSD≤4.3%, except CBD) and accuracy (bias≤4.1%, except CBN).

A 16-year-old Caucasian male with a known history of depressive disorders but no other diseases was found at home unconscious (Glasgow Coma Scale score, 7), bradycardic (heart rate, 45 b.p.m.), tachypnoic (respiratory rate, 30/min), and cyanotic. At admission to the emergency department of a regional hospital, the patient was hypotensive (70/30 mmHg), and his electrocardiogram revealed a broad-complex tachycardia with a heart rate of 155 b.p.m. The patient was endotracheally intubated and underwent repeated electrical and pharmacological (amiodarone, 300 mg i.v.; magnesium, 2 g i.v.) cardioversion attempts. Subsequently, tachycardia degenerated into bradycardic sinus rhythm with atrioventricular blockade and finally asystole. Following 30 min of cardiopulmonary resuscitation including 6 mg epinephrine i.v. and 3 mg atropine i.v., return of spontaneous circulation was achieved. Since broad-complex brady-/tachyarrhythmia persisted (Figure 1), and the patient required high-dosed epinephrine (3600 µg/h), he was transferred to the intensive care unit of a tertiary care university hospital. Activated charcoal (75 g) was administered by nasogastric tube because of a high suspicion of intoxication. Shortly after arrival at the admitting intensive care unit, the patient repeatedly needed mechanical and pharmacological resuscitation because of intermittent bradycardic episodes/asystoles. Since external pacing failed, a transvenous pacemaker was inserted, and mild hypothermia (33°C) was induced for neuroprotection. In view of the ongoing need for high-epinephrine dosages (1200–2000 µg/h), aggravating lactic acidosis (pH, 7.24; ![Graphic][1] , 16.2 mmol/L; base deficit, −10.7 mmol/l; lactate, 12.3 mmol/l) and persistent hypokalaemia (3.2 mmol/l), a 4.5 h haemodialysis session with a high-flux filter was … [1]: /embed/inline-graphic-1.gif

Delta-9-tetrahydrocannabinolic acid A (THCA-A) is the biosynthetic precursor of delta-9-tetrahydrocannabinol (THC) in cannabis plants, and has no psychotropic effects. THCA-A can be detected in blood and urine, and several metabolites have been identified. THCA-A was also shown to be incorporated in hair by side stream smoke to a minor extent, but incorporation via blood stream or sweat seems unlikely. The detection of THCA-A in biological fluids may serve as a marker for differentiating between the intake of prescribed THC medication – containing only pure THC – and cannabis products containing THC besides THC-acid A and other cannabinoids. However, the knowledge about its usefulness in forensic cases is very limited. The aim of the present work was the development of a reliable method for THCA-A determination in human blood or plasma using LC–MS/MS and application to cases of driving under the influence of drugs. Fifty eight (58) authentic whole blood and the respective plasma samples were collected from drivers suspected of driving under the influence of cannabis from the region of Bern (Switzerland). Samples were first tested for THC, 11-OH-THC and THC-COOH, and then additionally for THCA-A. For this purpose, the existing LC–MS/MS method was modified and validated, and found to be selective and linear over a range of 1.0 to 200 ng/mL (the correlation coefficients were above 0.9980 in all validation runs). Limit of detection (LOD) and limit of quantification (LOQ) were 0.3 ng/mL and 1.0 ng/mL respectively. Intra- and inter-assay accuracy were equal or better than 90% and intra- and inter-assay precision were equal or better than 11.1%. The mean extraction efficiencies were satisfactory being equal or higher than 85.4%. THCA-A was stable in whole blood samples after 3 freeze/thaw cycles and storage at 4 °C for 7 days. Re-injection (autosampler) stability was also satisfactory. THC was present in all blood samples with levels ranging from 0.7 to 51 ng/mL. THCA-A concentrations ranged from 1.0 to 496 ng/mL in blood samples and from 1.4 to 824 ng/mL in plasma samples. The plasma:blood partition coefficient had a mean value of 1.7 (±0.21, SD). No correlation was found between the degree of intoxication or impairment stated in the police protocols or reports of medical examinations and the detected THCA-A-concentration in blood.

Proper hemodynamics is a major issue in research of heart valve bio-prostheses. In the examination of these, the bending deformation and fluttering of heart valve cusps is an interesting and influential aspect. An analysis of the deformation can support the understanding of correlations between hemodynamics and occurring mechanical stress. This contribution describes an approach to determine the dynamic bending deformation of aortic heart valve bio-prostheses in high speed video recordings and to compare different fluttering characteristics. The bioprostheses are recorded in an artificial circulation setup and observed during the opening and closure of a systolic phase. Based on a segmentation of the orifice area, a distance signal is derived for each cusp relative to a base line given by the commissure points. This distance signal describes the static bending deformation of the cusps in one image frame. By observing the deformation during the phase of maximal flow, the dynamics of the cusps can be determined over time. The resulting fluttering is quantified by a frequency analysis of the time dependent distance signal. Thus, significant fluttering characteristics can be modeled and compared.

Lipocalin-2 (Lcn2) expression contributes to ischemia and reperfusion injury (IRI) by enhancing pro-inflammatory responses. The aim of this work was to elucidate the regulation of Lcn2 during hypoxia and its effects on the expression of key chemokines and adhesion molecules. Lcn2 wt and Lcn2(-/-) mice were used in a heterotopic heart transplantation model. Quantitative RT-PCR was applied for chemokine gene expression analysis. Reporter gene studies were used to elucidate the regulation of the Lcn2 promoter by hypoxia. HIF-1β expression led to a 2.4-fold induction of the Lcn2 promoter. Apart from an earlier onset of granulocyte infiltration in the Lcn2 wt setting after 2 h of reperfusion compared with the Lcn2(-/-) setting (P < 0.013), exogenous application of recombinant Lcn2 revealed a trend toward increase of granulocyte infiltration. Analyzed chemokines were expressed significantly higher in the Lcn2 wt setting at 2 h of reperfusion (P ≤ 0.05). The number of apoptotic cells observed in Lcn2(-/-) grafts was significantly higher than in the Lcn2 wt setting. Our results indicate that Lcn2 affects granulocyte infiltration in the reperfused graft by modulating the expression of chemokines, their receptors and the apoptotic rate.

The fluttering of heart valve leaflets is an important aspect regarding the hemodynamics of biological artificial heart valves. Endoscopic high speed recordings allow capturing, visualization and analysis of heart valve movements with significant temporal resolution. In this contribution, a method is presented to determine the fluttering of the leaflets by analyzing the pixel frequency. The intensity value of each image pixel is observed over time and analyzed using Fourier transform. With synthetic sequences the reliability of the method has been proven. First results with ex-vivo recordings show the feasibility to determine fluttering of heart valve leaflets.

The opening and closure intervals of heart valves are important factors regarding an optimal blood flow. Using endoscopic video recordings of heart valves, digital kymography can be a method to visualize and to describe the opening and closure intervals. Based on an adequate segmentation of the kymograms, a quantitative description becomes available for the opening and closure characteristics. Furthermore, by normalizing the measured results, comparisons of mean heart valve oscillations can be achieved. Here, a comparison of artificial with native heart valves obtained under physiological conditions, indicates clear differences in the opening and closure intervals.

Summary: Purpose: We present three children with severe therapy-refractory epilepsy who tolerated valproate (VPA) well in various combinations with other antiepileptic drugs (AEDs) but developed typical VPA side effects in combination with topiramate (TPM). Methods: The clinical symptoms began with apathy in all three children; two of them also had hypothermia. Furthermore all children had elevated blood ammonia levels, one child in combination with increased liver transaminases and one with thrombocytopenia. Results: All children recovered completely after discontinuation of VPA or TPM. Conclusions: TPM seems likely to enhance the risk of side effects usually attributed to VPA and not described in TPM monotherapy. Our case reports suggest that possible adverse effects of VPA should be given particular attention when VPA is combined with TPM.