Anorectic sibutramine detected in a Chinese herbal drug for weight loss

In the presented case, a young healthy woman had ordered a Chinese herbal medicine, called "LiDa Dai Dai Hua Jiao Nang", via internet. She took this product for approximately 1 week, but on the second day she developed severe headache, vertigo and sensation of numbness. After discontinuing medication, symptoms disappeared within 2 days. For identification of the ingredients, a urine sample as well as a sample of the "LiDa" capsule were analysed by GC-MS and HPLC-DAD. One major ingredient was detected in urine as well as in the "LiDa" capsule and was identified as sibutramine. Quantification by HPLC-DAD yielded 27.4 mg sibutramine base, which is approximately two times the amount of the highest authorized single dose available on the pharmaceutical market in Germany. This case demonstrates a common problem with herbal medicines, where adulterations with synthetic therapeutic substances can lead to severe side effects and/or potentially fatal interactions with conventional medicines.     

Survival of severe amlodipine intoxication due to medical intensive care

We report the case of attempted suicide with amlodipine, chlorthalidone and mefenamic acid and subsequent medical intensive care measures which resulted in total recovery of a 42-year-old male. After admission to the medical intensive care unit the intoxicated patient was deeply hypotensive and needed fluid replacement, dobutamine and norepinephrine. Additionally insulin and calcium gluconate were given. Since hypotension persisted and the patient developed oliguria, terlipressin was applied and finally showed an effect on blood pressure and on urinary output. A volume overload of 7 L in the first 24 h resulted in a pulmonary edema. The patient was started on non-invasive ventilation with continuous positive airway pressure (CPAP) and frusemide was added to the therapy with good success. Quantitative determination of amlodipine in plasma samples was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The highest amlodipine concentrations was measured in the plasma sample collected approximately 8 h after ingestion of the drug, and was 393 microg/L. Four days later, it was possible to stop the treatment with catecholamines, at that time the amlodipine plasma concentration had declined to 132 microg/L, still tenfold higher than therapeutic (5-18 microg/L). Elimination half-life of amlodipine is approximately 55 h. After 6 days in the intensive care unit the patient was transferred to psychiatric treatment. Intensive care management and plasma levels in this intoxication case are compared to data from literature on other cases.     

The potential of venous air embolism ascending retrograde to the brain

A bench study was performed to investigate the potential of air bubbles entering a central vein via a central venous catheter to ascend retrograde to the brain. The results support the hypothesis that air bubbles may rise retrograde against the venous blood flow, depending on bubble size, central vein diameter and cardiac output. A review of radiological findings in published case reports indicates that the occurrence of retrograde cerebral air embolism is underestimated.     

mtDNA investigations after differential lysis

In order to gain information regarding the ethnic origin of an unknown offender in a murder case it was necessary to sequence the HV1 and 2 regions of the mitochondrial DNA (mtDNA). The only evidentiary material that could be linked to the suspect was DNA, extracted from spermatozoa after differential lysis. The observed mtDNA sequences were identical to the sequences of the victim. Therefore, we had to check if this was a coincidence or the result of a technical limitation of the testing procedure. Subsequently, we performed a systematic study. In cases with complete separation of sperm and female cells it wasn't possible to obtain a mtDNA sequence for the sperm fraction. This phenomena is based on the loss of the sperm's flagellum and mid-piece during the first lysis step and a concomitant loss of the sperm's mitochondria. In our murder case, a minor carry-over of female cells to the sperm fraction was responsible for the sequencing result.     

Neo-Voluntarism: A New European Social Policy Regime?

Abstract: The essay begins with a recapitulation of core institutional properties of the European Union as they have evolved over several decades. The leading insight deriving from this exercise is that European social policy will always, for all practical purposes, be made simultaneously at two levels, a supranational one and a national one, and will be shaped by complex interactions between them and among the national systems situated in the integrated market economy of the Union. Proceeding from here, the remainder of the paper examines the two levels of social policy-making, beginning with the supranational and moving on to the national, in an effort to identify the kinds of policies that are most likely to emerge given the constraints and opportunities offered by the institutional framework.     

Time-dependent immunohistochemical detection of proinflammatory cytokines (IL-1beta,IL-6, TNF-alpha) in human skin wounds

The proinflammatory cytokines interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) hold important functions in the early and late courses of inflammation, trauma and wound healing. In the present study, human skin wounds due to sharp force (n = 105) were collected during surgery and autopsy. The wound age mainly varied from several minutes to 5 h, some specimens aged up to 6 weeks. Control specimens from uninjured skin were available in each case. After preparation of cryostat sections, immunohistochemistry was performed according to the APAAP technique, using monoclonal and polyclonal antibodies. The results were evaluated semiquantitatively. All markers were weakly expressed in normal human skin constitutively. However, the staining pattern changed significantly in vital wounds concerning epidermal layers, subepidermal cells, vessels and sweat glands. IL-1beta and IL-6 showed enhanced expression after 15 and 20 min at the earliest (increase of epidermal reactivity). After 30-60 and 60-90 min, respectively, marked expression was observed with these markers. Similar alterations were detectable with TNF-alpha after 15 and 60-90 min. The reactivity of all three markers persisted over several hours, then decreased to basal levels again and sometimes reappeared after days and in granulation tissue. Leukocytes reacting with IL-1beta and IL-6 appeared after approximately 2 h. CONCLUSION: proinflammatory cytokines can serve as a useful tool for the estimation of vitality and wound age, in particular in the early post-traumatic interval prior to leukocyte reaction. Autolysis did not play a role in the samples investigated (postmortem interval up to 8 days). Problems could sometimes rise from constitutive expression. Therefore, it is recommended to examine control samples from the same individual and to compare the reactivity with wound specimens.     

Analysis of crisis intervention processes

The remediation processes in psychosocial crisis intervention were modeled focusing on cognitive orientation. Frequent observations and subsequent process modeling constitute a novel approach to process research and reveal process-outcome associations. A sample of 40 inpatients who were assigned to treatment in a crisis intervention unit was monitored in order to study the process of crisis intervention. The process data consisted of patients' self-ratings of the variables mood, tension, and cognitive orientation, which were assessed three times a day throughout hospitalization (M = 22.6 days). Linear time series models (vector autoregression) of the process data were computed to describe the prototypical dynamic patterns of the sample. Additionally, the outcome of crisis intervention was evaluated by pre-post questionnaires. Linear trends were found pointing to an improvement of mood, a reduction of tension, and an increase of outward cognitive orientation. Time series modeling showed that, on average, outward cognitive orientation preceded improved mood. The time series models partially predicted the treatment effect, notably the outcome domain "reduction of social anxiety," yet did not predict the domain of symptom reduction. In conclusion, crisis intervention should focus on having patients increasingly engage in outward cognitive orientation in order to stabilize mood, reduce anxiety, and activate their resources.     

Why Methods Matter in European Legal Scholarship

Both in the United States and in Europe, there is a debate on methodology in legal research. Doctrinalists and multidisciplinarians appear to be in different camps fighting over the ‘true nature’ of legal scholarship. We wonder where this renewed attention for methodology is coming from and what is behind it. Should European legal scholars follow certain colleagues in the United States who believe that doctrinal research is dead and should we all engage in law and … research now? If not, does this imply that there is nothing wrong with mainstream European doctrinal legal scholarship? We believe the latter is not the case. Our hypothesis is that an ongoing instrumentalisation of law and legal research decreases the attention for methodology, for theory building, and for keeping enough professional distance to one's object of research. This threatens to result in a creeping process of herd behaviour, in copy pasting the methodology of judicial lawmaking to legal scholarship and in a lack of transparency and methodological justification in scholarly legal publications. What is desperately needed is more reflection on methodology and theory building in European legal scholarship.     

Phenibut screening and quantification with liquid chromatography–tandem mass spectrometry and its application to driving cases

An analytical strategy for identification by an LC–MS/MS multitarget screening method and a suitable LC–MS/MS based quantification were developed for the psychotropic drug phenibut. The samples analyzed were collected during traffic control and were associated with driving under the influence of drugs. A positive sample for phenibut was identified in a single case of driving under the influence. The quantification revealed a drug concentration of 1.9 μg/mL. An interaction with blood alcohol (BAC = 0.10%) was discussed as the explanation of the way of driving and deficit manifestations observed (swaying, nystagmus, quivering of the eyelid, and reddened eyes). According to the available information, the quantified phenibut concentration could be explained by an intake of four tablets (self-reported) during the day containing 250 mg of the drug. Chromatography was performed with a Luna 5 μm C18 (2) 100 A, 150 mm × 2 mm analytical column, and a buffer system consisted of 10 mM ammonium acetate and 0.1% acetic acid (v/v) included in mobile phases marked as A (H₂O/methanol = 95/5, v/v) and B (H₂O/methanol = 3/97, v/v). An effective limit of detection (LOD = 0.002 μg/mL) could be achieved for the multitarget screening method. The quantification of phenibut was performed on a second LC–MS/MS system with LOD/LOQ values of 0.22/0.40 μg/mL. Since phenibut quantification data are rare, the presented information can be used with caution for evaluation of positive cases in the future.     

New challenges for copyright protection - Co-Reach in IPR in New Media Workshop II

The Co-Reach IPR in New Media organised a workshop on ISP Liability in London on December 7, 2010 and an EU-China Copyright Policy meeting in Vienna from December 9-12, 2010. The Workshops come at the crucial time when new regulations are being crafted to tighten copyright protection in cyberspace.