Hair analysis of antidepressants and antipsychotics—Overview of quantitative data

Antidepressant and antipsychotic drugs are regularly encountered in different aspects of forensic toxicology, and some cases require the examination of hair samples. In this study, common antidepressant and antipsychotic drugs regarding hair concentrations over the past decades were reviewed. Although numerous publications around method validations, case reports, or controlled dose studies were found, apparently there is a lack of comprehensive data for many substances. Information on the hair length and dosage across the publications varied largely, and case numbers were generally low except for several retrospective controlled dose studies. Many substances were described only in method validations or case reports, and data were obtained from small case numbers. On the contrary, clozapine, haloperidol, amitriptyline, nortriptyline, risperidone and its metabolite, methylphenidate, citalopram, chlorpromazine, chlorprothixene, and quetiapine had a well‐founded database as these substances were investigated in controlled dose studies with higher case numbers. Given the advancements made in analytical techniques over the past years, gas chromatography–mass spectrometry and liquid chromatography with tandem mass spectrometry techniques were the methods of choice and allowed the detection of chemical compounds at low concentrations. The controversy around a potential use of hair analysis to estimate the dosage remains as dose‐concentration studies provided divergent results. A harmonization on the investigated hair length as well as on the extraction protocol would be of favor to achieve better comparability. Although hair analysis research focused mainly on drug abuse, availability of more data on antidepressants and antipsychotics would help to gain better knowledge and assist other forensic investigators.     

Solid‐phase extraction–liquid chromatography–tandem mass spectrometry method for the qualitative analysis of 61 synthetic cannabinoid metabolites in urine

This article comprises the development and validation of a protocol for the qualitative analysis of 61 phase I synthetic cannabinoid metabolites in urine originating from 29 synthetic cannabinoids, combining solid‐phase extraction (SPE) utilizing a reversed phase silica‐based sorbent (phenyl) with liquid chromatography–tandem mass spectrometry (LC?MS/MS). Validation was performed according to the guidelines of the German Society of Toxicological and Forensic Chemistry. Sufficient chromatographic separation was achieved within a total runtime of 12.3 minutes. Validation included specificity and selectivity, limit of detection (LOD), recovery and matrix effects, as well as auto‐sampler stability of processed urine samples. LOD ranged between 0.025 ng/mL and 0.5 ng/mL in urine. Recovery ranged between 43% and 97%, with only two analytes exhibiting recoveries below 50%. However, for those two analytes, the LODs were 0.05 ng/mL in urine. In addition, matrix effects between 81% and 185% were determined, whereby matrix effects over 125% were observed for 10 non‐first‐generation synthetic cannabinoid metabolites. The developed method enables the rapid and sensitive detection of synthetic cannabinoid metabolites in urine, complementing the spectrum of existing analytical tools in forensic case work. Finally, application to 61 urine samples from both routine and autopsy case work yielded one urine sample that tested positive for ADB‐PINACA N‐pentanoic acid.     

Thrombolysis in acute stroke under dual antiplatelet therapy: perspectives arising from translational studies

正We have recently established a mouse model of focal stroke under dual antiplatelet therapy (DAPT) to study tissue plasminogen activator (tPA)-associated hemorrhagic transformation.The purpose of this short perspective is to discuss the rationale for establishing the model,highlighting its relevance for addressing unresolved clinical questions.Hemorrhagic conversion of the ischemic stroke remains one of the major liabilities of thrombolytic therapy with tPA,contributing to unfavorable outcomes and failed regeneration.This was recognized early on,and the resulting restrictions on t PA usage have led to only a minor percentage of stroke patients receiving any kind of     

Degeneration of the Cerebellum in Huntington's Disease (HD): Possible Relevance for the Clinical Picture and Potential Gateway to Pathological Mechanisms of the Disease Process

Huntington's disease (HD) is a polyglutamine disease and characterized neuropathologically by degeneration of the striatum and select layers of the neo‐ and allocortex. In the present study, we performed a systematic investigation of the cerebellum in eight clinically diagnosed and genetically confirmed HD patients. The cerebellum of all HD patients showed a considerable atrophy, as well as a consistent loss of Purkinje cells and nerve cells of the fastigial, globose, emboliform and dentate nuclei. This pathology was obvious already in HD brains assigned Vonsattel grade 2 striatal atrophy and did not correlate with the extent and distribution of striatal atrophy. Therefore, our findings suggest (i) that the cerebellum degenerates early during HD and independently from the striatal atrophy and (ii) that the onset of the pathological process of HD is multifocal. Degeneration of the cerebellum might contribute significantly to poorly understood symptoms occurring in HD such as impaired rapid alternating movements and fine motor skills, dysarthria, ataxia and postural instability, gait and stance imbalance, broad‐based gait and stance, while the morphological alterations (ie ballooned neurons, torpedo‐like axonal inclusions) observed in the majority of surviving nerve cells may represent a gateway to the unknown mechanisms of the pathological process of HD.     

Comparing the effect of positioning on cerebral autoregulation during radical prostatectomy: a prospective observational study

Journal of Clinical Monitoring and Computing - Surgery in the prolonged extreme Trendelenburg position may lead to elevated intracranial pressure and compromise cerebral hemodynamic regulation. We...     

Repetitive jumping and sprinting until exhaustion alters hamstring reflex responses and tibial translation in males and females

The incidence of anterior cruciate ligament injuries is considerably higher in females than in males and the underlying mechanisms are still under debate. Research indicates that the neuromuscular system of females and males might respond differently to the same fatigue protocol due to differences in muscle activation during movement tasks. This study analyzed sex differences in hamstring reflex responses and posterior‐anterior tibial translation (TT) before and after fatiguing exercise. We measured the isolated movement of the tibia relative to the femur as a consequence of mechanically induced TT in standing subjects as well as muscle activity of the hamstrings before and after repetitive jumping and sprinting until exhaustion. Muscle fatigue delayed reflex onset latencies in females and males. A reduction in reflex responses associated with an increased TT was observed after fatiguing exercise for both sexes. Data indicate that the used fatigue protocol altered the latency and magnitude of reflex responses as well as TT in females and males. Based on the results of previous research and the outcome of this study, it might be that sex‐specific effects of fatigue on reflex activity and mechanical stability of the knee depend on the kind of fatiguing exercise. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1687–1692, 2015.