Cocaine adulteration with the anthelminthic tetramisole (levamisole/dexamisole): Long‐term monitoring of its intake by chiral LC–MS/MS analysis of cocaine‐positive hair samples

Recent studies indicate that not only the anthelminthic levamisole but also the racemate tetramisole (R‐/S‐phenyltetraimidazothiazole, PTHIT) was found as an adulterant for cocaine. We herein report on the investigation of the prevalence of PTHIT among cocaine‐positive hair samples and the discrimination of the presence of its stereoisomers levamisole and dexamisole. Cocaine‐positive hair samples were collected in a forensic context in 2015 and mainly 2017 (n = 724). Cocaine and PTHIT concentrations have been determined by achiral liquid chromatography–tandem mass spectrometry (LC–MS/MS). For distinction of levamisole/dexamisole chiral LC–MS/MS was performed. Cocaine hair concentrations ranged from 500 (cut‐off) to approximately 800 000 pg/mg. The study demonstrates a strong prevalence of PTHIT in cocaine users' hair (87%, n = 627). PTHIT hair concentrations ranged from below LLOQ 3.5 to approximately 61 000 pg/mg (median: 260 pg/mg). Surprisingly, enantiomeric ratios of levamisole/dexamisole ranged from 0.17 to 1.34 (median: 0.63). Therefore, PTHIT‐adulterated street cocaine samples (n = 24) seized between 2013 and 2016 were tested. Samples mainly contained racemic tetramisole (87.5%), only one sample contained levamisole only and two samples contained non‐racemic PTHIT. Our experiments suggest that the presence of tetramisole in biological samples may have hitherto been underestimated. Most probably higher dexamisole than levamisole concentrations in hair specimens arise from stereoselective metabolism and/or elimination. This is particularly important in light of the different pharmacological activities of the two enantiomers and potentially different adverse effects. Toxicological interpretations in intoxication cases with adulterated cocaine should not only consider levamisole but also tetramisole and terminology in scientific contributions should be used accordingly.     

Time-course of the electrophysiological maturation and integration of transplanted cardiomyocytes

Electrophysiological maturation and integration of transplanted cardiomyocytes are essential to enhance safety and efficiency of cell replacement therapy. Yet, little is known about these important processes. The aim of our study was to perform a detailed analysis of electrophysiological maturation and integration of transplanted cardiomyocytes. Fetal cardiomyocytes expressing enhanced green fluorescent protein were transplanted into cryoinjured mouse hearts. At 6, 9 and 12days after transplantation, viable slices of recipient hearts were prepared and action potentials of transplanted and host cardiomyocytes within the slices were recorded by microelectrodes. In transplanted cells embedded in healthy host myocardium, action potential duration at 50% repolarization (APD50) decreased from 32.2±3.3ms at day 6 to 27.9±2.6ms at day 9 and 19.6±1.6ms at day 12. The latter value matched the APD50 of host cells (20.5±3.2ms, P=0.78). Integration improved in the course of time: 26% of cells at day 6 and 53% at day 12 revealed no conduction blocks up to a stimulation frequency of 10Hz. APD50 was inversely correlated to the quality of electrical integration. In transplanted cells embedded into the cryoinjury, which showed no electrical integration, APD50 was 49.2±4.3ms at day 12. Fetal cardiomyocytes transplanted into healthy myocardium integrate electrically and mature after transplantation, their action potential properties after 12days are comparable to those of host cardiomyocytes. Quality of electrical integration improves over time, but conduction blocks still occur at day 12 after transplantation. The pace of maturation correlates with the quality of electrical integration. Transplanted cells embedded in cryoinjured tissue still possess immature electrophysiological properties after 12days.     

Bacterial community profiles of endodontic abscesses from Brazilian and USA subjects as compared by denaturing gradient gel electrophoresis analysis

This study compared the bacterial community profiles of the microbiota associated with acute apical abscesses from Brazilian and USA patients using denaturing gradient gel electrophoresis (DGGE). DNA was extracted from purulent exudate aspirates and part of the 16S rRNA gene was amplified by polymerase chain reaction and separated by DGGE. The resulting banding patterns, which were representative of the bacterial community structures in samples from the two locations, were then compared. Distinct DGGE banding patterns were observed from different samples. Ninety-nine bands with distinct positions in the gels were detected, of which 27 were found only in the USA samples and 13 were exclusive to Brazilian samples. Four of the 59 shared bands showed very discrepant findings with regard to prevalence in the two locations. Cluster analysis of DGGE banding profiles showed a great variability in the bacterial populations associated with teeth with abscesses regardless of the geographical location. Two big clusters, one for each location, were observed. Other clusters contained a mixture of samples from the two locations. The results of the present study demonstrated a great variability in the bacterial community profiles among samples. This indicates that the bacterial communities of abscesses are unique for each individual in terms of diversity. The composition of the microbiota in some samples showed a geography-related pattern. Furthermore, several bands were exclusive for each location and others were shared by the two locations and showed great differences in prevalence.     

Novel targets in deep brain stimulation for movement disorders

The neurosurgical treatment of movement disorders, primarily via deep brain stimulation (DBS), is a rapidly expanding and evolving field. Although conventional targets including the subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) for Parkinson’s disease and ventral intermediate nucleus of the thalams (VIM) for tremor provide substantial benefit in terms of both motor symptoms and quality of life, other targets for DBS have been explored in an effort to maximize clinical benefit and also avoid undesired adverse effects associated with stimulation. These novel targets primarily include the rostral zona incerta (rZI), caudal zona incerta (cZI)/posterior subthalamic area (PSA), prelemniscal radiation (Raprl), pedunculopontine nucleus (PPN), substantia nigra pars reticulata (SNr), centromedian/parafascicular (CM/PF) nucleus of the thalamus, nucleus basalis of Meynert (NBM), dentato-rubro-thalamic tract (DRTT), dentate nucleus of the cerebellum, external segment of the globus pallidus (GPe), and ventral oralis (VO) complex of the thalamus. However, reports of outcomes utilizing these targets are scattered and disparate. In order to provide a comprehensive resource for researchers and clinicians alike, we have summarized the existing literature surrounding these novel targets, including rationale for their use, neurosurgical techniques where relevant, outcomes and adverse effects of stimulation, and future directions for research.

     

Somatosensory evoked potentials following tibial nerve stimulation. Method and normal values in relation to physical variables

Somatosensory evoked potentials were recorded in 40 healthy subjects (age: 22-63 years) with gluteal, lumbar, cervical and cortical surface electrodes after stimulation of the tibial nerve. Normal latency values were established in relationship to height and also for the amplitudes of the different components; the latencies of the cortical P40, N50 and P60 were significantly dependent on height, the latency of the cervical N33, the lumbar N22 and the gluteal Ng were dependent on the distance (stimulation--to recording point). The central conduction time showed no dependence on back length. Age dependence (in relation to normal height) was found only in the case of cortical P60.     

General and Acute Care Surgical Procedures in Patients with Left Ventricular Assist Devices

Background

Left ventricular assist devices (LVADs) have become common as a bridge to heart transplant as well as destination therapy. Acute care surgical (ACS) problems in this population are prevalent but remain ill-defined. Therefore, we reviewed our experience with ACS interventions in LVAD patients.

Methods

A total of 173 patients who received HeartMate^® XVE or HeartMate^® II (HMII) LVADs between December 2001 and March 2010 were studied. Patient demographics, presentation of ACS problem, operative intervention, co-morbidities, transplantation, complications, and survival were analyzed.

Results

A total of 47 (27 %) patients underwent 67 ACS procedures at a median of 38 days after device implant (interquartile range 15–110), with a peri-operative mortality rate of 5 % (N = 3). Demographics, device type, and acuity were comparable between the ACS and non-ACS groups. A total of 21 ACS procedures were performed emergently, eight were urgent, and 38 were elective. Of 29 urgent and emergent procedures, 28 were for abdominal pathology. In eight patients, the cause of the ACS problem was related to LVADs or anticoagulation. Cumulative survival estimates revealed no survival differences if patients underwent ACS procedures (p = 0.17). Among HMII patients, transplantation rates were unaffected by an ACS intervention (p = 0.2).

Conclusions

ACS problems occur frequently in LVAD patients and are not associated with adverse outcomes in HMII patients. The acute care surgeon is an integral member of a comprehensive approach to effective LVAD management.     

Interventional treatment of arterio-venous malformations

Background

Due to their hemodynamic effects and tendency to progress, the majority of congenital arterio-venous malformations (AVM) require treatment. AVM are classified according to clinical severity (Schobinger classification, stages I–V) and angiographic appearance (types I–IV).

Treatment

Endovascular embolization is the treatment of choice. However, because complications such as necrosis and neuropathy occur in up to 15% of cases, treatment is challenging and is dependent on the angiographic appearance. Critical for treatment success is elimination of the so-called nidus, which is the location of the short circuit connection between the artery and the often extended aneurysm-like drainage vein. Embolization of only the feeding artery without the actual nidus or the incomplete elimination of drainage veins should be avoided. Absolute 96?% alcohol in addition to coiling of the nidus has been established as the most effective technique.

Conclusion

Unlike other embolic agents, alcohol leads to a definitive destruction of the vessel wall. Recanalization and recurrence are excluded due to adequate elimination of the nidus.