[Investigations on the influence of different mouth and nose protection masks on the evidential breath alcohol measurement]. / Untersuchungen zum Einfluss verschiedener Mund-Nase-Schutzmasken auf die beweissichere Atemalkoholmessung.

On the occasion of a judicial expert opinion on the question of whether wearing a face mask can lead to a falsification of the breath alcohol value leading to detriment of the accused, an experimental series of tests was carried out under pandemic conditions on six healthy test subjects (four men, two women), who practiced low-risk recreational alcohol consumption. On each day of the study one specific mask type (surgical mask, textile mask, FFP2 mask) was examined. After ingestion of an individually calculated amount of alcohol and a 30-min absorption phase, 6 consecutive breath alcohol measurements were carried out at 30-min intervals, with one mask or no mask worn between measurements. Subsequently, pairs of values for periods with and without a mask were formed and the hourly breath alcohol elimination rates were calculated. As a result, the breath alcohol elimination rates with and without masks did not differ from each other. There were no error messages from the breathalyzer that can be attributed to the previous wearing of a mask.

[Trends in Abuse of Biogenic Drugs in Parts of Germany 2007-2013]. / Entwicklung des Missbrauchs psychotroper Pflanzen und Pilze in Deutschland ­ Interpretation der Zahlen aus 3 Giftinformationszentren für die Jahre 2007­2013.

AIM OF THE STUDY: Based on an abundance of information on the internet, psychotropic plants and mushrooms are of increasing relevance as legal and cheap alternatives to other illicit drugs. Due to the lack of a German database, the abuse of selected biogenic drugs using reported exposures to 3 German Poison Information Centres (PICs) was examined. METHODS: Information on abuse of biogenic drugs was collected from the German PICs in Berlin, Erfurt and Fribourg (2007-2013). RESULTS: 602 drug abuses were reported to the selected PICs. 52% reported consumption of tropane alkaloid-containing plants (Angel's trumpet, Thorn apple, Belladonna), 25% of psilocybin-containing mushrooms and 10% of nutmeg. Angel's trumpet was identified as the most abused plant. Consumers of tropane alkaloid-containing plants were mainly adolescents, whereas the majority of the abusers of psilocybin-containing mushrooms and nutmeg were rather young grown-ups and school children, respectively. A preponderance of moderate and severe effects (55%) could be noticed for exposures to tropane alkaloid-containing plants. More than 90% of suspected cases of tropane alkaloid-containing as well as psilocybin-containing plants abuse resulted in the treatment recommendation 'surveillance in hospital'. Mydriasis, hallucinations, tachycardia and agitation were the main symptoms after the abuse of biogenic drugs. CONCLUSIONS: The data from the PICs suggest abuse of biogenic drugs in parts of Germany. A decreasing trend is observed, probably caused by the competition with new synthetic designer drugs. The results underline the dominance of Angel's trumpet in the abuse of biogenic drugs and emphasize the importance of easy accessibility for the abuse of biogenic drugs. Unexpectedly, the number of nutmeg abuse cases increased during the investigated period.

Three fatalities associated with the synthetic cannabinoids 5F-ADB, 5F-PB-22, and AB-CHMINACA.

The use of synthetic cannabinoids (SC) has been widespread in certain groups of drug users for many years. In the scientific literature many intoxication cases and a number of fatalities after the use of synthetic cannabinoids were reported. In this paper three death cases are described with involvement of the synthetic cannabinoids 5F-PB-22, AB-CHMINACA, and 5F-ADB. The three cases occurred in the eastern region of Germany, which is known as a region of high methamphetamine abuse. All decedents were male, between 25 and 41 years old, and had a known history of drug use. Femoral blood concentrations of the synthetic cannabinoids were measured using a validated LC-MS/MS method. The concentration of 5F-PB-22 in the first case was 0.37ng/mL, the concentration of AB-CHMINACA in the second case was approximately 4.1ng/mL (extrapolated) and the 5F-ADB concentration in the third case was 0.38ng/mL. Compared to other published cases the concentrations in the here presented cases seem to be in the lower range. However, taking into account the scene of death, the results of the forensic autopsy and the full toxicological analysis, the deaths can be explained as a direct consequence of consumption of synthetic cannabinoids, although in case one and two relevant amounts of ethanol were found, and in case three trimipramine and olanzapine were present in non-toxic concentrations. It has to be noted that concentrations of synthetic cannabinoids in femoral blood cannot directly be judged as toxic or lethal due to the possibility of postmortem redistribution and the development of tolerance after frequent use. Therefore, all available information has to be considered carefully before stating SC use as the cause of death.

Context-dependent adaption of EpCAM expression in early systemic esophageal cancer.

The role of the epithelial cell adhesion molecule EpCAM in cancer progression remains largely unclear. High expression of EpCAM in primary tumors is often associated with more aggressive phenotypes and EpCAM is the prime epithelial antigen in use to isolate circulating tumor cells (CTCs) and characterize disseminated tumor cells (DTCs). However, reduced expression of EpCAM was associated with epithelial-to-mesenchymal transition (EMT) and reports on a lack of EpCAM on CTCs emerged. These contradictory observations might reflect a context-dependent adaption of EpCAM expression during metastatic progression. To test this, EpCAM expression was monitored in esophageal cancer at different sites of early systemic disease. Although most of the primary esophageal tumors expressed high levels of EpCAM, the majority of DTCs in bone marrow lacked EpCAM. In vitro, downregulation of EpCAM expression at the plasma membrane was observed in migrating and invading cells, and was associated with a partial loss of the epithelial phenotype and with significantly decreased proliferation. Accordingly, induction of EMT through the action of TGFß resulted in substantial loss of EpCAM cell surface expression on esophageal cancer cells. Knock-down or natural loss of EpCAM recapitulated these effects as it reduced proliferation while enhancing migration and invasion of cancer cells. Importantly, expression of EpCAM on DTCs was significantly associated with the occurrence of lymph node metastases and with significantly decreased overall survival of esophageal cancer patients. We validated this observation by showing that high expression of EpCAM promoted tumor outgrowth after xenotransplantation of esophageal carcinoma cells. The present data disclose a dynamic expression of EpCAM throughout tumor progression, where EpCAM(high) phenotypes correlate with proliferative stages, whereas EpCAM(low/negative) phenotypes associated with migration, invasion and dissemination. Thus, differing expression levels of EpCAM must be taken into consideration for therapeutic approaches and during clinical retrieval of disseminated tumor cells.

Escalation of methamphetamine-related crime and fatalities in the Dresden region, Germany, between 2005 and 2011.

Methamphetamine (MA), a central nervous system stimulating recreational drug, is a worldwide problem related to crime as well as forensic and health aspects. The data, exemplarily presented in this study for the Dresden region, Saxony, Germany, demonstrate the escalation of MA-related crime and fatalities between 2005 and 2011. Easy availability and an attractive price of MA in the Czech Republic are responsible for both the increase of the occurrence of MA in relation to the entire drug crime as well as the increase of the occurrence of MA-positive cases of driving under influence (DUI). Higher percentage of very pure MA on the Saxon drug market since 2010 seems to be the reason for the fatalities directly caused by MA in 2010 and 2011.

Simultaneous determination of drugs in human autopsy material using phase-optimized liquid chromatography.

In legal medicine in many cases drugs are detected in autopsy material without connection to the cause of death, and until now no further investigations have taken place. In our study more than 50 drugs were measured directly in several compartments. The deceased had received continual therapeutic treatment, treatment during an operation or an unsuccessful emergency therapy. Liquid-liquid extraction and an LC-MS/MS method were developed for the determination of these drug concentrations. When measuring many transitions in a biological matrix, two problems should be excluded: ion suppression and too few measurement points per peak. A relatively short operation time and sufficient separation were achieved by column, eluent and gradient optimization with POPLC (phase-optimized liquid chromatography). Various autopsy materials from about 170 cases were investigated. In particular, in nine cases with four or more simultaneously determined drugs, their distribution in the compartments is very interesting for pharmacokinetic examinations. The distribution patterns of the drugs in the compartments of one individual deceased were compared. This meant that the great differences between subjects that are normally encountered these studies could be excluded. Measurements of drug concentrations in human autopsy material deepens knowledge of the respective drugs' pharmacokinetics.

The effects of weightlessness on the human organism and mammalian cells.

It has always been a desire of mankind to conquest Space. A major step in realizing this dream was the completion of the International Space Station (ISS). Living there for several months confirmed early observations of short-term spaceflights that a loss of gravity affects the health of astronauts. Space medicine tries to understand the mechanism of microgravity-induced health problems and to conceive potent countermeasures. There are four different aspects which make space medicine appealing: i) finding better strategies for adapting astronauts to weightlessness; ii) identification of microgravity-induced diseases (e.g. osteoporosis, muscle atrophy, cardiac problems and others); iii) defining new therapies to conquer these diseases which will benefit astronauts as well as people on Earth in the end; and iv) on top of that, unveiling the mechanisms of weightlessness-dependent molecular and cellular changes is a requirement for improving space medicine. In mammalian cells, microgravity induces apoptosis and alters the cytoskeleton and affects signal transduction pathways, cell differentiation, growth, proliferation, migration and adhesion. This review focused on gravi-sensitive signal transduction elements and pathways as well as molecular mechanisms in human cells, aiming to understand the cellular changes in altered gravity. Moreover, the latest information on how these changes lead to clinically relevant health problems and current strategies of countermeasures are reviewed.

Distribution of metoprolol in human autopsy material.

In forensic medicine autopsy material is primarily investigated to find out the cause of death. But the results of corresponding toxicology measurements often involve more information. With screening methods drugs were detected not being related to the cause of death. Liquid/liquid extraction and LC/MS/MS methods were used for the determination of drug concentrations. In seven cases metoprolol could be determined in different autopsy materials. In all cases the dosage of the drug was unknown. In cases with oral application probably the patients took a normal customary continuous dosage. Intoxication with metoprolol could be excluded in all cases. The concentrations of metoprolol in blood were all in the therapeutic range. The time between oral intake and death was unknown. Therefore and because of the low number of cases statistic calculations were not meaningful and an individual case study was necessary. In three cases the highest concentration of metoprolol was found in the liver. Probably, metoprolol was taken shortly before the person died. In the other cases the highest concentration of metoprolol was found in urine. This means the elimination process of the drug predominated at the time of death. In all cases the concentrations of metoprolol were similar in the compartments heart blood, venous blood and brain. In this study it was possible to measure the distribution of metoprolol in human directly in several compartments. Measurement of drug concentrations in human autopsy material deepen the knowledge of its pharmacokinetics.

Distribution of metoprolol, tramadol, and midazolam in human autopsy material.

In this study it was possible to measure the distribution of metoprolol, tramadol, and midazolam in human directly in several compartments. In the legal medicine autopsy material is normally investigated to find out the cause of death. But the results of corresponding toxicology measurements often involve more information. With screening methods drugs were detected without connection to the cause of death. The deceased had either a continual therapeutic treatment, a treatment during an operation, or an unsuccessful urgent therapy. A liquid/liquid extraction and a LC/MS/MS method were developed for the determination of the drug concentrations. Different autopsy materials of about 120 cases were investigated. Most frequently the drugs metoprolol, tramadol, and midazolam could be proved and determined simultaneously. Metoprolol was found in seven cases, tramadol in seven cases and midazolam in thirteen cases. The dosage of the drugs was unknown. Therefore and because of the low number of cases statistic calculations were not meaningful and an individual case study was necessary. In all cases with oral metoprolol application the patients probably took a normal customary continuous dosage. The concentrations of tramadol in blood were in the toxic range in three cases. The distribution of tramadol in the compartments was independent of the dosage. The time between oral intake of metoprolol or tramadol and death was unknown. With the distribution pattern of metoprolol in the compartments it was possible to estimate the duration between drug intake and death. In most cases midazolam was given intravenously during an operation or an unsuccessful urgent therapy. Sometimes the time between dosage and death was documented. The duration between application of the drug and death played the crucial role for the distribution of midazolam in the compartments. Measurements of drug concentrations in human autopsy material deepen the knowledge of the respective drugs' pharmacokinetics.

Diagnostic and therapeutic use of membrane proteins in cancer cells.

As proteomics technologies develop, increasing number of membrane-associated proteins specific for cancer cells are being discovered. These proteins are of great interest, particularly because they are rich in targets for antibodies. Amongst them candidate biomarkers for early tumor diagnosis, prognosis and treatment have been detected. The suitability of several membrane-associated proteins as targets for drugs or antibodies has already been tested in preclinical and clinical studies. The results were encouraging in some cases, but not in all. They demonstrate that each type of tumor has its specific "Achilles heel", and that suitable targets of cancer diagnosis and therapy must be found for each kind of neoplasm. This implies that membrane-associated proteins for each type of tumor cell need to be investigated. This review describes the current technologies of membrane protein characterization in a first part and subsequently summarizes the membrane associated proteins currently being tested as targets for diagnosis and treatment in breast, prostate, thyroid, and colon cancer. Their function will be explained and their role in tumor biology will be discussed.

A comparative study of five fatal cases of Taxus poisoning.

The study presents five fatal cases of poisoning with Taxus spp., all of which were suicides of young people aged between 16 and 26 years. Yew leaves were consumed in four fatalities, whereas a mash from Taxus was ingested in one case. No relevant concentrations of alcohol, narcotic drugs, and pharmaceuticals were determined in postmortem toxicological screening. At forensic autopsy, a widely dilated pupil was found in two decedents. Furthermore, autopsy showed unspecific findings of intoxication in all cases: acute blood congestion of lungs, liver, kidney, and brain as well as dilated cardiac ventricles. No signs of violence could be found in any of the fatalities. Yew leaves were identified in four cases in the stomach and duodenum. 3,5-Dimethoxyphenol, the aglycon of the Taxus ingredient taxicatine, was determined as toxicological evidence for the absorption of yew ingredients. Taxus intoxication could be confirmed by 3,5-dimethoxyphenol concentrations in cardiac blood between 31 and 528 ng/ml for all cases. 3,5-Dimethoxyphenol was also detected in stomach contents as well as in urine, liver, kidneys, and brain samples. Based on the different concentrations of 3,5-dimethoxyphenol determined in the cardiac blood samples, it was concluded that the form of ingestion plays a decisive role in the process of poisoning. Finally, a toxic range for Taxus poisoning based on 3,5-dimethoxyphenol as marker substance is proposed as orientation.

Toll-like receptor expression and response to specific stimulation in adipocytes and preadipocytes: on the role of fat in inflammation.

Data in this study indicate that both adipocytes and preadipocytes express abroad set of TLRs and they also respond to specific stimulation by cytokine production. The may be of relevance to Crohn's disease and a suggests a closer link between adipose tissue and innate immunity.

A non-fatal oleander poisoning.

The study presents a case of non-fatal poisoning with oleander blooms in a 47-year-old female, with emphasis on the importance of toxicological service in a clinical emergency. After repeated vomiting at home, the patient was admitted at the hospital with cardiac symptoms more than 18 h after the ingestion. Serum samples were assayed immunochemically for digitoxin-related compounds by electrochemiluminescent immunoassay, and using HPLC/MS/MS analysis for oleandrin, the main cardiac glycoside of Nerium oleander. Confirming the non-specific immunoassay results, which are often clinically over-interpreted, oleandrin was detected by HPLC/MS/MS in the serum sample in a concentration of 1.6 ng/ml upon admission. Comparison with previous reports indicates that single compound analysis only permits a toxicological assessment for oleander poisoning and results in the proposal to classify an oleandrin level between 1.0 and 2.0 ng/ml as toxic blood plasma/serum concentration.

The Victorian Active Script Programme: promising signs for general practitioners, population health, and the promotion of physical activity.

BACKGROUND: The Active Script Programme (ASP) aimed to increase the number of general practitioners (GPs) in Victoria, Australia who deliver appropriate, consistent, and effective advice on physical activity to patients. To maximise GP participation, a capacity building strategy within Divisions of General Practice (DGPs) was used. The objectives of the programme were to (a) train and support GPs in advising sedentary patients, and (b) develop tools and resources to assist GPs. OBJECTIVE: To evaluate the effectiveness of the ASP. METHODS: A systems approach was used to promote capacity in Victorian general practice. Economic analyses were incorporated into the programme's evaluation. Participants were selected DGPs and their GP members. The programme worked with DGPs to train GPs and provide relevant resources. The main outcome measures were (a) changes in GP knowledge and behaviour and (b) cost effectiveness, based on modelled estimates of numbers of patients advised and adopting physical activity and gaining the associated health benefits. RESULTS: GP awareness and provision of physical activity advice increased. Although the programme's reach was modest, based on actual GP involvement, the cost effectiveness figures (138 Australian dollars per patient to become sufficiently active to gain health benefits, and 3647 Australian dollars per disability adjusted life year saved) are persuasive. CONCLUSIONS: The ASP increased DGPs' capacity to support GPs to promote physical activity. There is a strong economic argument for governments to invest in such programmes. However, caution is warranted about the maintenance of patients' activity levels. Programme refinement to encourage GPs to use community supports more effectively will guide future development. Further research on long term patient adherence through a multisectorial approach is warranted.

Obstructive jaundice secondary to lymphoma in childhood.

In children, biliary obstruction secondary to lymphoma is rare. Previous reports in adults and children suggest that these lymphomas are associated with a poor prognosis. The authors reviewed the medical records and imaging studies of 4 children treated for pancreaticobiliary lymphoma at our children's hospital over the past 10 years. All 4 presented with jaundice. Abdominal ultrasound scan and computed tomography (CT) scans were helpful in defining the anatomy of the obstruction. In the cases of involvement of the porta hepatis, the diagnosis was made by biopsy. In one child a mass was in the head of the pancreas, and evaluation of frozen section biopsy results were not diagnostic for lymphoma, and a major resection was performed. All the lymphomas were of nonHodgkin's B-cell type and one was a Burkitt's lymphoma. All responded promptly to chemotherapy. One child had a testicular relapse and currently is receiving additional therapy. Pancreaticobiliary lymphomas are an unusual cause of obstructive jaundice in children. Biopsy alone without resection or biliary drainage is recommended surgical therapy. Long-term survival rate in children with this disorder appears to be more promising than previously reported. J Pediatr Surg 36:1792-1795.

Polar nitrogen compounds and their behaviour in the drinking water treatment process.

Aliphatic and alicyclic amines as well as ethanolamines are extremely polar compounds, frequently found in the environment, and some of them have high toxicity. To address the contamination of selected German surface waters examined and the importance of bank filtration in Eastern Germany, investigations on the behaviour of polar organic nitrogen compounds during water treatment were carried out. Test conditions were designed appropriately for drinking water treatment conditions, and the tests were carried out using model water as well as bank filtrate. Test filter studies of microbial degradation of selected compounds demonstrated the following order of biodegradability: ethanolamine > dimethylamine > pyrrolidine > ethylenediamine. piperidine > diethylamine > morpholine > piperazine > cyclohexylamine. Flocculation tests using iron salts as well as aluminium salts as coagulants showed very low removal rates for the amines. The best results for the removal of the polar organic nitrogen compounds from the water were obtained using ozonation. Based on the reaction-rate constants, the order of degradation by ozone is: piperazine > morpholine > ethylenediamine > piperidine, cyclohexylamine > dimethylamine > ethanolamine > pyrrolidine > diethylamine. Disinfection by chlorine-containing agents under drinking water treatment conditions did not give effective elimination of the selected polar nitrogen compounds.

Laparoscopic versus open splenectomy in the pediatric population: a contemporary single-center experience.

The purpose of this study was to compare a recent contemporaneous experience between laparoscopic (LS) and open (OS) splenectomy in children. All splenectomy cases between 1994 and 1999 at our institution were reviewed. The study included open and laparoscopic cases performed according to surgeon preference. Emergency splenectomies for trauma were excluded. The patient record was reviewed for the diagnosis, indications, postoperative length of stay, operative technique, postoperative complications, blood loss/blood transfusion, total amount of parenteral narcotics, and time to resumption of oral intake. Chi-square and t tests were used to compare measured differences for statistical significance. Between May 1994 and December 1999, 52 splenectomies were performed at Vanderbilt Children's Hospital. Of these, 45 were elective operations with 29 open and 16 laparoscopic procedures. During four OS and five LS operations a concomitant cholecystectomy was performed. The median patient age was 9.2 years (range 0.5 to 17.3). There was no statistical difference between the two groups in terms of age, weight, American Society of Anesthesiologists class, or estimated blood loss. There were no immediate postoperative complications in either group. There were no conversions from LS to OS. The mean duration of surgery was 264 minutes (LS) versus 169 minutes (OS) (P < 0.05). The average time to first oral intake was shorter in patients undergoing LS (1.1 vs 1.6 days, P < 0.05) and the mean postoperative length of stay was also shorter in the LS group (1.3 vs 3.1 days, P < 0.05). The use of postoperative intravenous narcotics (in morphine-equivalent doses) was significantly less in LS patients than in OS patients (7.5 mg or 0.15 mg/kg vs 46.9 mg or 1.5 mg/kg, P < 0.001), as was the need for PCA pump analgesia (90% in the OS group vs 25% in LS group, P < 0.01). Overall the average hospital charge (anesthesia fee, narcotics charge, and hospital room charge) was $5400 (range $4240-6250) in the OS group and $4950 (range $4450-6240) in the LS group (P < 0.05). Among the nine patients undergoing splenectomy with cholecystectomy, findings between the OS and LS groups were similar except for one late complication consisting of a diaphragmatic hernia in an LS patient. Both LS and OS with or without a concomitant procedure can be accomplished safely in children. LS appears to result in longer operative times but shorter lengths of stay, earlier first oral intake, and significantly fewer requirements for intravenous narcotics; all of these contribute to a reduction in hospital charges compared with the open operation.