[New psychoactive substances in emergency medicine]. / Neue Psychoaktive Substanzen in der Notfallmedizin.

New psychoactive substances (NPS) are a heterogeneous group of synthetic intoxicating substances. What they have in common is their "new" appearance as a narcotic drug. Many of them imitate known drugs; some of them are derivatives of substances developed as drugs many years ago. Changed or completely newly developed chemical structures often give the NPS a massively increased effect. This includes not only the effects desired by the consumer, but also the undesirable effects with sometimes fatal consequences. The use of NPS has been an increasing phenomenon for years. In 2018, 2.6% of German adults had already had experience with NPS. NPS-intoxicated persons represent a challenge for the treating physicians not only because of the heterogeneity of the substances, but also because of the unpredictable effects for the users. The clinical assessment is often made more difficult due to the presence of a mixed intoxication. Only systemic toxicological analysis-generally not readily available-provides safety, as conventional rapid or bedside tests do not record many substances. There is no global definition of NPS. A practical, clinical classification differentiates into four groups: synthetic stimulants, synthetic cannabinoids, synthetic hallucinogens, and synthetic sedatives.

Proposed pipelines and environmental justice: Exploring the association between race, socioeconomic status, and pipeline proposals in the United States.

The current natural gas and oil boom in North America requires new pipelines which pose environmental risks from the wellhead to their destinations. The environmental justice literature suggests that minority populations, people with low socio-economic status, and rural communities are disproportionally exposed to risks associated with potentially harmful land uses. Using data from the 2015 five-year American Community Survey and pipeline route data compiled by The FracTracker Alliance, this study tests whether the above assumptions are true for proposed FERC permitted natural gas transmission pipelines in the United States for which planned routes have been made available. Using binary logistic regression, the study provides only limited, and in some cases contradictory, support for these hypotheses. Although a higher share of highly educated residents significantly decreases the likelihood of a pipeline proposal in a census tract, a higher poverty rate also significantly lowers this probability. Only the share of Black and Asian residents is significantly (negatively) associated with pipeline proposals. However, to test whether this holds true for built pipelines, reliable routing data are needed, which are considered confidential in the United States.

[Bonzai, lead and bath salt-poisoning with new and old drugs : Synthetic amphetamines, cathinones, cannabinoids and opioids-an overview]. / Bonzai, Blei und Badesalz ­ Vergiftungen mit neuen und alten Drogen : Synthetische Amphetamine, Cathinone, Cannabinoide und Opioide ­ eine Übersicht.

BACKGROUND: There has been an increase in the number of serious poisonings and deaths after the use of new psychoactive substances (NPS). These are usually bought online: sometimes legally, often illegally or "in the grey area". OBJECTIVES: Characteristics of different NPS. Legal status concerning the New Psychoactive Substances Act (NpSG). Risk assessment of several substance groups, possible complications of acute poisonings, therapeutic recommendations. MATERIALS AND METHODS: Literature search and evaluation of own case data. Discussion of official statistics, literature and expert recommendations. RESULTS: There has been an increase in the number of poisonings with NPS and associated deaths: in Germany in 2016 there were 98 deaths compared to 39 deaths in 2015. Serious acute poisonings require intensive care therapy. Therapy is usually symptomatic. Referring to the drugs discussed in this article an antidote is only available for the synthetic opioid: naloxone. CONCLUSIONS: With the NpSG being in force since the end of 2016, the number of severe intoxications with NPS will probably (not immediately) decrease. It remains to be seen if the increasing number of fatalities will decrease again. Consultation with a poison centre is recommended in cases of suspected intoxication with NPS. Diagnosis and therapy can then be discussed. Toxicological screening may be false negative because many synthetic drugs are not detected in standard analysis. The NPS often require a special analysis.

Heritability of Caffeine Metabolism: Environmental Effects Masking Genetic Effects on CYP1A2 Activity but Not on NAT2.

Heritability of caffeine pharmacokinetics and cytochrome P450 1A2 (CYP1A2) activity is controversial. Here, we analyzed the pharmacokinetics of caffeine, an in vivo probe drug for CYP1A2 and arylamine N-acetyltransferase 2 (NAT2) activity, in monozygotic (MZ) and dizygotic (DZ) twins. In the entire group, common and unique environmental effects explained most variation in caffeine area under the curve (AUC). Apparently, smoking and hormonal contraceptives masked the genetic effects on CYP1A2 activity. However, when excluding smokers and users of hormonal contraceptives, 89% of caffeine AUC variation was due to genetic effects and, even in the entire group, 8% of caffeine AUC variation could be explained by a CYP1A1/1A2 promotor polymorphism (rs2470893). In contrast, nearly all of the variations (99%) of NAT2 activity were explained by genetic effects. This study illustrates two very different situations in pharmacogenetics from an almost exclusively genetic determination of NAT2 activity with no environmental modulation to only moderate genetic effects on CYP1A2 activity with strong environmental modulation.

A retrospective, semi-quantitative image quality analysis of cone beam computed tomography (CBCT) and MSCT in the diagnosis of distal radius fractures.

OBJECTIVE: To compare image quality and diagnostic validity of CBCT and MSCT for distal radius fractures. METHODS: 35 CBCT and 33 MSCT scans were retrospectively reviewed with a visual grading scale regarding the depiction of cortical bone, trabecular bone, articular surfaces, and soft tissue. The extent and type of artefacts was analyzed. Agreement on AO classification and measurement of cortical disruption and length of the fracture gap was determined. Fracture reduction was evaluated in post-treatment x-rays. Statistical analysis was performed with visual grading characteristics (VGC), chi square tests, and Kendall's coefficient of concordance. RESULTS: CBCT performed significantly worse for cortical bone, articular surfaces, and especially soft tissue. Trabecular bone showed no significant difference. Significantly more CBCT images showed artefacts. Physics-based artefacts were the most common. CBCT scans also showed motion artefacts. There was no significant difference in agreement on AO classification. The agreement on measurements was substantial for both modalities. Slightly more fractures that had undergone MSCT imaging showed adequate reduction. CONCLUSION: This initial study of an orthopaedic extremity CBCT scanner showed that the image quality of a CBCT scanner remains inferior for most structures at standard settings. Diagnostic validity of both modalities for distal radius fractures seems similar. KEY POINTS: • Subjectively, CBCT remains inferior to MSCT in depicting most structures. • Similar diagnostic validity for CBCT and MSCT imaging of distal radius fractures. • CBCT is a possible alternative to MSCT in musculoskeletal imaging. • Visual grading characteristics (VGC) analysis proves useful in analyzing visual grading scales.

NMDA receptor blockade by memantine does not prevent adaptation to recurrent hypoglycaemia in healthy men.

AIMS: Recurrent hypoglycaemia leads to an attenuation of hypoglycaemic symptoms and hormonal counterregulatory responses. This phenomenon poses a severe problem in the treatment of patients with diabetes mellitus, but the underlying neuroendocrine mechanisms are unclear. On the basis of animal experimental findings, we hypothesized that counterregulatory attenuation represents a basic adaptive learning process relying on synaptic long-term potentiation or depression. If so, attenuation should be prevented by blocking glutamatergic N-methyl-D-aspartate (NMDA) receptors. METHODS: Sixteen healthy young men participated in two conditions, separated by 4 weeks. Participants received the NMDA antagonist memantine over 5 days (15 mg/day) in one condition and placebo in the other one. After 3 days of drug administration, participants underwent two hypoglycaemic clamps on day 4 and another one on day 5. We assessed blood concentrations of counterregulatory hormones (cortisol, ACTH, epinephrine, norepinephrine, growth hormone and glucagon) as well as subjective symptoms of hypoglycaemia and word-list recall as an indicator of short-term memory. RESULTS: Counterregulatory responses of all hormones as well as neuroglycopenic and autonomic symptom ratings showed robust attenuation following the third as compared to the first hypoglycaemia (p < 0.05). NMDA receptor antagonization by memantine impaired memory function but did not alter any neuroendocrine measure of counterregulatory attenuation (p > 0.17). CONCLUSIONS: Attenuation of the endocrine as well as symptomatic counterregulatory response to recurrent hypoglycaemia is not prevented by the NMDA receptor blocker memantine. Our results do not support the view that adaptation to repeated hypoglycaemia relies on NMDA receptor-mediated plastic processes involving long-term potentiation or depression.

[Psychometric properties of the pain drawing and the Ransford technique in patients with chronic low back pain]. / Gütekriterien der qualitativen Bewertung von Schmerzzeichnungen (Ransford-Methode) bei Patienten mit Rückenschmerzen.

BACKGROUND: The aim of our study was the analysis of the psychometric properties of the Ransford technique which is a qualitative scoring method of the pain drawing. It has been suggested that this method could be used as a brief screening technique for psychological involvement in pain complaints. METHODS: 109 patients with chronic back pain filled in the pain drawing which was rated according to the technique described by Ransford and colleagues in 1976. As external criterium of validity we chose a differentiated expert rating of psychological interference. RESULTS: The Ransford technique showed moderate to good coefficients of reliability (re-test, inter and intra-rater). On the other hand, the Ransford technique demonstrated very low indices of validity in order to give a prognosis about psychological interference. Sensitivity and specificity of the Ransford technique demonstrated inadequate values, which furthermore were independent from cut-off points. CONCLUSION: The pain drawing and the Ransford technique are not sufficiently sensitive and therefore allow no screening for psychological interference in complaints of back pain.

Modelling gradient elution of bioactive multicomponent systems in non-linear ion-exchange chromatography.

A theoretical framework for the ion-exchange behaviour of bioactive substances in non-linear ion-exchange chromatogaphy is described. The aim of the study was the creation of a model basis to support a process design for production-scale ion-exchange chromatography. The theory can be applied to a whole variety of biological substances, such as amino acids, polysaccharides, peptides and proteins and either isocratic or gradient elution can be carried out. The influence of the eluent concentration on the ion-exchange as well as on the characteristic charge was considered. Experimental measurements showed a strong non-linear ion-exchange equilibrium with a transition from a Langmuir-type to a sigmoidal isotherm at higher eluent concentrations. Hereby, the compound binds to the surface though it is not ionic. Therefore, the model considered the possibility of ion-exchange as well as adsorption. A simplified distribution of the counter-ions based on the Gouy-Chapman theory with a discrete distribution of the counter-ions was used. The theory was extended by a selectivity in the double layer to allow specific adsorption. Calculations of adsorption-elution cycles showed, in agreement with the experimental observations, the development of non-linear elution profiles with a desorption fronting. As a result, the column loading and the eluent concentration were varied. The effect of contaminants, in this case sodium ions, was investigated and included in the model. Finally, the model was extended to multicomponent systems to investigate the effect of side components on the retention behaviour. The development of the characteristic elution profiles and the effect of the column loading on the separation are discussed. Calculated concentration profiles along the column at discrete time steps were used to reveal the influence of side components and the underlying separation mechanism. The simulations provided a new insight into the phenomena involved in biochromatography and make convenient design concepts at least doubtful as the separation is in this case mainly determined by the loading step and not by the choice of the elution gradient.

Influence of the diluent on the effect of highly diluted histamine on basophil activation.

BACKGROUND: In modern pharmaceutical practice, it is common to use purified ethanol and purified water for the preparation of homeopathic dilutions. Hahnemann in 1827 recommended good brandy as a diluent. Brandy contains a lot of accompanying substances in addition to ethanol. PURPOSE OF THE STUDY: The research question was whether different diluents influence the effectiveness of high dilutions, especially above Avogadro's number. We compared two dilution media to investigate the diluent's influence. Within the limitations of the test-system, the dilution media were as similar to good brandy as possible and like purified ethanol. Dilutions of histamine were prepared with both media. As test-system, we used modified basophil activation in an in vitro cell system. Basophils are activated by anti-immunoglobulin E (anti-IgE). The activation of basophils is inhibited by prior incubation with histamine. The reduction in activation was measured with different dilutions of histamine. The test system used a 3-colour flow cytometric method. The interleukin-3 (IL-3) receptor CD123 was used to identify basophils in the leukocyte mixture. The CD63 surface marker was used for quantification of activated basophils. RESULTS: With higher concentrations of histamine, we observed inhibition on optimally anti-IgE-stimulated basophil activation with a clear concentration dependency. With low concentrations of histamine (up to 10(-31)), we also observed inhibition of IgE-mediated basophil activation. Differences were observed between the dilution media. CONCLUSION: The preliminary results support the hypothesis that the dilution medium may influence the effects of high dilutions. This could be of importance for homeopathic pharmaceutical practice as well as for ultra-high dilution experiments. The refined basophil test system proved to be highly sensitive and reliable. Further studies are needed.

Influence of the diluent on the effect of highly diluted histamine on basophil activation

The research question was whether different diluents influence the effectiveness of high dilutions, especially above Avogadro's number. We compared two dilution media to investigate the diluent's influence. Within... (AU)

Sensitive flow cytometric method to test basophil activation influenced by homeopathic histamine dilutions.

OBJECTIVE: In an experimental setting, human basophil degranulation was triggered by anti-IgE to measure the effects from homeopathic solutions in an in-vitro cell system. A 3-color flow cytometric method with enhanced accuracy was established. As an example we looked at the influence of histamine on anti-IgE activation of basophils. METHODS: Basophils were identified in the flow cytometer by their physical properties in the forward and side scatter light depiction and by gating on CD2(-), CD14(-), CD16(-), CD19(-), HLA-DR(-) negative and CD123-positive cells. CD63 expression on the cell surface of the anti-IgE-activated basophils served as an activation marker. RESULTS: With this method we were able to study basophil function of the 0.6-3.9% basophils out of the mononuclear blood cell fraction and to document their activation status upon anti-IgE activation. Optimal activation occurs at 0.6 microg/ml final anti-IgE concentration; not less than 10,000 basophils have to be counted per batch to reduce the variation of the measurement. The fixation method was able to stabilize activation for two days. After investigation and reduction of the source of measurement variability, an unequivocally inhibited basophil activation was documented in a partly optimized system with homeopathic dilutions of histamine (10(-22)M, 10(-23)M, 10(-24)M, and 10(-25)M histamine). Dilutions greater than 10(-20)M histamine (Avogadro's number 6.02 x 10(23)) account for less than 1.36 molecules of histamine in the test sample, indicating a true homeopathic effect. CONCLUSIONS: This test system is adequate for studying the effects of highly diluted mediators on basophil activation by anti-IgE. The systematic application of this experimental arrangement is recommended to study the effects of homeopathic dilutions on basophils.

Preparative enantioseparation by simulated moving bed chromatography.

Simulated moving bed (SMB) chromatography was invented in the 1960s in the petrochemical industry and has since then been widely used to produce petrochemicals and sugars at the multi-ton scale. In the early 1990s its principle could be successfully adapted to chromatographic enantioseparation, due to developments in system design, chiral stationary phase synthesis and improvements in modelling and simulation of non-linear chromatographic behaviour. Since then a lot of separation systems have been brought into production, which are reviewed. In addition new developments are outlined in the field of system design and stationary phase development.

Pregnancy-associated plasma protein-E (PAPP-E).

A full-length cDNA encoding a novel human protein was cloned from placenta cDNA. The corresponding 1542 amino acid protein sequence was termed 'pregnancy-associated plasma protein-E' (PAPP-E) as it shows a 62% homology to the human pregnancy-associated plasma protein-A (PAPP-A) that is a diagnostic marker for trisomies, especially Down syndrome. The conserved domain structure contains five motifs related to the short consensus repeats of complement proteins and selectins, three motifs related to the lin-notch motifs of proteins regulating early tissue differentiation, and a putative zinc-binding motif and active site of the metzincin-superfamily of metalloproteases. The PAPP-E gene was localized to chromosome 1q23-25. Northern blot analysis showed that PAPP-E is predominantly expressed in placenta.

[Arteriosclerosis vascular changes as an expression of the local effect of mechanical continuous stress--observations of the femoral artery of marathon runners]. / Arteriosklerotische Wandveränderungen als Ausdruck lokal einwirkender mechanischer Dauerbelastung--Beobachtungen an den Aa. femorales von Marathonläufern.

The arteries of the thigh of 126 male marathon runners at the age of 41.6 +/- 11.3 years were examined with B-Scan-ultrasound. 32 (62.1%) persons were found with arteriosclerotical plaques. All of them were older than 35 years, so the number of arteriosclerosis in this group increases to 36.4 percent (n = 88). 38 persons were younger than 35 years. Persons with plaques started training about 10.9 years later than those without plaques. Correlations of plaques and age, age of starting training, years of training and km/year were found. The numbers of riskfactors showed significant differences between both groups but the correlation of "having no risk factor" and arteriosclerotical plaques was higher than the correlations of nicotine, hypertension, hypercholesterolemia and plaques. It seems that marathon running itself is a risk factor of developing arteriosclerotical plaques in the femoral arteries particularly if the age of starting training is higher than 30 years.