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1.  Reflections on Addiction in Students Using Stimulants for Neuroenhancement: A Preliminary Interview Study 
BioMed Research International  2015;2015:621075.
The use of stimulants for the purpose of pharmacological neuroenhancement (NE) among students is a subject of increasing public awareness. The risk of addiction development by stimulant use for NE is still unanswered. Therefore, face-to-face interviews were carried out among 18 university students experienced in the nonmedical use of methylphenidate and amphetamines for NE assessing aspects of addiction. Interviews were tape-recorded, verbatim-transcribed, and analyzed using a qualitative approach. The interviews showed that participants—the majority had current or lifetime diagnoses of misuse or addiction to alcohol or cannabis—reported an awareness of the risk of addiction development associated with stimulant use and reported various effects which may increase their likelihood of future stimulant use, for example, euphoric effects, increase of self-confidence, and motivation. They also cited measures to counteract the development of addiction as well as measures taken to normalize again after stimulant use. Students were convinced of having control over their stimulant use and of not becoming addicted to stimulants used for NE. We can conclude that behavior and beliefs of the students in our sample appear to be risky in terms of addiction development. However, long-term empirical research is needed to estimate the true risk of addiction.
PMCID: PMC4433654  PMID: 26064931
2.  Life context of pharmacological academic performance enhancement among university students – a qualitative approach 
BMC Medical Ethics  2014;15:23.
Academic performance enhancement or cognitive enhancement (CE) via stimulant drug use has received increasing attention. The question remains, however, whether CE solely represents the use of drugs for achieving better academic or workplace results or whether CE also serves various other purposes. The aim of this study was to put the phenomenon of pharmacological academic performance enhancement via prescription and illicit (psycho-) stimulant use (Amphetamines, Methylphenidate) among university students into a broader context. Specifically, we wanted to further understand students’ experiences, the effects of use on students and other factors, such as pressure to perform in their academic and private lives.
A sample of 18 healthy university students reporting the non-medical use of prescription and illicit stimulants for academic performance enhancement was interviewed in a face-to-face setting. The leading questions were related to the situations and context in which the students considered the non-medical use of stimulants.
Based on the resultant transcript, two independent raters identified six categories relating to the life context of stimulant use for academic performance enhancement: Context of stimulant use beyond academic performance enhancement, Subjective experience of enhancement, Timing of consumption, Objective academic results, Side effects, Pressure to perform.
The answers reveal that academic performance enhancement through the use of stimulants is not an isolated phenomenon that solely aims at enhancing cognition to achieve better academic results but that the multifaceted life context in which it is embedded is of crucial relevance. The participants not only considered the stimulants advantageous for enhancing academic performance, but also for leading an active life with a suitable balance between studying and time off. The most common reasons given for stimulant use were to maximize time, to increase motivation and to cope with memorizing. According to the interviews, there is a considerable discrepancy between subjective experiences and objective academic results achieved.
PMCID: PMC3973848  PMID: 24606831
Cognitive enhancement; Academic performance enhancement; Stimulants; Ethics; Attitudes; Life impact; University students
3.  Attitudes towards prescribing cognitive enhancers among primary care physicians in Germany 
BMC Family Practice  2014;15:3.
Primary care physicians are gate keepers to the medical system having a key role in giving information and prescribing drugs to their patients. In this respect they are involved in claims of patients/clients for pharmacological Cognitive Enhancement (CE). Therefore, we studied the knowledge of primary care physicians about CE and their attitudes toward prescribing CE drugs to healthy subjects.
A self-report paper-and-pencil questionnaire and case vignettes describing a hypothetical CE drug were sent out to all 2,753 registered primary care physicians in Rhineland Palatine, Germany. 832, i.e. 30.2% filled in the questionnaire anonymously.
96.0% of all participating physicians had already heard about CE. However, only 5.3% stated to be very familiar with this subject and 43.5% judged themselves as being not familiar with CE. 7.0% had been asked by their clients to prescribe a drug for CE during the last week, 19.0% during the last month, and 40.8% during the last year. The comfort level to prescribe CE drugs was very low and significantly lower than to prescribe sildenafil (Viagra®). Comfort level was mainly affected by the age of the client asking for prescription of CE drugs, followed by the availability of non-pharmacological alternatives, fear of misuse of the prescribed drug by the client and the missing indication of prescribing a drug.
Although a relatively high proportion of primary care physicians have been asked by their clients to prescribe CE drugs, only a small proportion are well informed about the possibilities of CE. Since physicians are gate keepers to the medical system and have a key role regarding a drugs’ prescription, objective information should be made available to physicians about biological, ethical and social consequences of CE use.
PMCID: PMC3890504  PMID: 24397728
Cognitive enhancement; Primary care physician(s); Prescription drug(s)
4.  Associations between Physical and Cognitive Doping – A Cross-Sectional Study in 2.997 Triathletes 
PLoS ONE  2013;8(11):e78702.
This study assessed, for the first time, prevalence estimates for physical and cognitive doping within a single collective of athletes using the randomized response technique (RRT). Furthermore, associations between the use of legal and freely available substances to improve physical and cognitive performance (enhancement) and illicit or banned substances to improve physical and cognitive performance (doping) were examined.
An anonymous questionnaire using the unrelated question RRT was used to survey 2,997 recreational triathletes in three sports events (Frankfurt, Regensburg, and Wiesbaden) in Germany. Prior to the survey, statistical power analyses were performed to determine sample size. Logistic regression was used to predict physical and cognitive enhancement and the bootstrap method was used to evaluate differences between the estimated prevalences of physical and cognitive doping.
2,987 questionnaires were returned (99.7%). 12-month prevalences for physical and cognitive doping were 13.0% and 15.1%, respectively. The prevalence estimate for physical doping was significantly higher in athletes who also used physical enhancers, as well as in athletes who took part in the European Championship in Frankfurt compared to those who did not. The prevalence estimate for cognitive doping was significantly higher in athletes who also used physical and cognitive enhancers. Moreover, the use of physical and cognitive enhancers were significantly associated and also the use of physical and cognitive doping.
The use of substances to improve physical and cognitive performance was associated on both levels of legality (enhancement vs. doping) suggesting that athletes do not use substances for a specific goal but may have a general propensity to enhance. This finding is important for understanding why people use such substances. Consequently, more effective prevention programs against substance abuse and doping could be developed.
PMCID: PMC3827233  PMID: 24236038
5.  Use of illicit and prescription drugs for cognitive or mood enhancement among surgeons 
BMC Medicine  2013;11:102.
Surgeons are usually exposed to high workloads leading to fatigue and stress. This not only increases the likelihood of mistakes during surgery but also puts pressure on surgeons to use drugs to counteract fatigue, distress, concentration deficits, burnout or symptoms of depression. The prevalence of surgeons taking pharmacological cognitive enhancement (CE) or mood enhancement (ME) drugs has not been systematically assessed so far.
Surgeons who attended five international conferences in 2011 were surveyed with an anonymous self-report questionnaire (AQ) regarding the use of prescription or illicit drugs for CE and ME and factors associated with their use. The Randomized Response Technique (RRT) was used in addition. The RRT guarantees a high degree of anonymity and confidentiality when a person is asked about stigmatizing issues, such as drug abuse.
A total of 3,306 questionnaires were distributed and 1,145 entered statistical analysis (response rate: 36.4%). According to the AQ, 8.9% of all surveyed surgeons confessed to having used a prescription or illicit drug exclusively for CE at least once during lifetime. As one would expect, the prevalence rate assessed by RRT was approximately 2.5-fold higher than that of the AQ (19.9%; 95% confidence interval (CI), 15.9% to 23.9%, N = 1,105). An even larger discrepancy between the RRT and AQ was observed for the use of antidepressants with a 6-fold higher prevalence (15.1%; 95% CI, 11.3% to 19.0%, N = 1,099) as compared to 2.4% with the AQ. Finally, logistic regression analysis revealed that pressure to perform at work (odds ratio (OR): 1.290; 95% CI, 1.000 to 1.666; P = 0.05) or in private life (OR: 1.266; 95% CI, 1.038 to 1.543; P = 0.02), and gross income (OR: 1.337; 95% CI, 1.091 to 1.640; P = 0.005), were positively associated with the use of drugs for CE or ME.
The use of illicit and prescription drugs for CE or ME is an underestimated phenomenon among surgeons which is generally attributable to high workload, perceived workload, and private stress. Such intake of drugs is associated with attempts to counteract fatigue and loss of concentration. However, drug use for CE may lead to addiction and to overestimation of one’s own capabilities, which can put patients at risk. Coping strategies should be taught during medical education.
PMCID: PMC3635891  PMID: 23570256
Cognitive enhancement; Surgeon(s); Prescription drug(s); Stimulant(s)
6.  Macro-AST: misleading finding in an adolescent with MCAD-deficiency 
BMC Gastroenterology  2012;12:119.
MCAD-deficiency is the most common inborn error of fatty acid oxidation now included in many newborn screening programms using MS/MS. During prolonged catabolic episodes, patients may suffer from metabolic decompensation with dysfunction of liver, skeletal- and heart muscle as well as brain. In anabolism, neither clinical symptoms nor biochemical signs of organ dysfunction occur.
Case presentation
We report a female patient with MCAD-deficiency in whom at the age of 11 years isolated AST-elevation was found without any clinical or biochemical signs of organ dysfunction. We showed by polyethylene glycol precipitation that macro-AST formation was responsible for this biochemical finding. AST was probably complexed with immunoglobulins possibly related to an allergic disposition. Macro-AST formation is not a special feature of MCAD-deficiency but rather a non-specific, coincidental finding which also occurs in healthy individuals. The general practitioner consulted by the patient before coming to our outpatient clinic for inborn errors of metabolism was worried that isolated AST-elevation indicated cell damage in MCAD-deficiency. He ordered further diagnostic tests like ultrasound, ECG and echocardiography without any pathology.
In isolated AST-elevation, macro-AST has to be considered in order to avoid unnecessary, costly and invasive evaluation. This is not only true for healthy persons but for patients with chronic diseases like MCAD as well.
PMCID: PMC3503801  PMID: 22935320
Macro-AST; MCAD-deficiency; Liver; Heart; Muscle; Immunoglobulin
7.  What Users Think about the Differences between Caffeine and Illicit/Prescription Stimulants for Cognitive Enhancement 
PLoS ONE  2012;7(6):e40047.
Pharmacological cognitive enhancement (CE) is a topic of increasing public awareness. In the scientific literature on student use of CE as a study aid for academic performance enhancement, there are high prevalence rates regarding the use of caffeinated substances (coffee, caffeinated drinks, caffeine tablets) but remarkably lower prevalence rates regarding the use of illicit/prescription stimulants such as amphetamines or methylphenidate. While the literature considers the reasons and mechanisms for these different prevalence rates from a theoretical standpoint, it lacks empirical data to account for healthy students who use both, caffeine and illicit/prescription stimulants, exclusively for the purpose of CE. Therefore, we extensively interviewed a sample of 18 healthy university students reporting non-medical use of caffeine as well as illicit/prescription stimulants for the purpose of CE in a face-to-face setting about their opinions regarding differences in general and morally-relevant differences between caffeine and stimulant use for CE. 44% of all participants answered that there is a general difference between the use of caffeine and illicit/prescription stimulants for CE, 28% did not differentiate, 28% could not decide. Furthermore, 39% stated that there is a moral difference, 56% answered that there is no moral difference and one participant was not able to comment on moral aspects. Participants came to their judgements by applying three dimensions: medical, ethical and legal. Weighing the medical, ethical and legal aspects corresponded to the students' individual preferences of substances used for CE. However, their views only partly depicted evidence-based medical aspects and the ethical issues involved. This result shows the need for well-directed and differentiated information to prevent the potentially harmful use of illicit or prescription stimulants for CE.
PMCID: PMC3386931  PMID: 22768218
8.  Candidate Gene Sequencing of SLC11A2 and TMPRSS6 in a Family with Severe Anaemia: Common SNPs, Rare Haplotypes, No Causative Mutation 
PLoS ONE  2012;7(4):e35015.
Iron-refractory iron deficiency anaemia (IRIDA) is a rare disorder which was linked to mutations in two genes (SLC11A2 and TMPRSS6). Common polymorphisms within these genes were associated with serum iron levels. We identified a family of Serbian origin with asymptomatic non-consanguineous parents with three of four children presenting with IRIDA not responding to oral but to intravenous iron supplementation. After excluding all known causes responsible for iron deficiency anaemia we searched for mutations in SLC11A2 and TMPRSS6 that could explain the severe anaemia in these children.
We sequenced the exons and exon–intron boundaries of SLC11A2 and TMPRSS6 in all six family members. Thereby, we found seven known and fairly common SNPs, but no new mutation. We then genotyped these seven SNPs in the population-based SAPHIR study (n = 1,726) and performed genetic association analysis on iron and ferritin levels. Only two SNPs, which were top-hits from recent GWAS on iron and ferritin, exhibited an effect on iron and ferritin levels in SAPHIR. Six SAPHIR participants carrying the same TMPRSS6 genotypes and haplotype-pairs as one anaemic son showed lower ferritin and iron levels than the average. One individual exhibiting the joint SLC11A2/TMPRSS6 profile of the anaemic son had iron and ferritin levels lying below the 5th percentile of the population's iron and ferritin level distribution. We then checked the genotype constellations in the Nijmegen Biomedical Study (n = 1,832), but the profile of the anaemic son did not occur in this population.
We cannot exclude a gene-gene interaction between SLC11A2 and TMPRSS6, but we can also not confirm it. As in this case candidate gene sequencing did not reveal causative rare mutations, the samples will be subjected to whole exome sequencing.
PMCID: PMC3324414  PMID: 22509377
9.  Gastric lactobezoar - a rare disorder? 
Gastric lactobezoar, a pathological conglomeration of milk and mucus in the stomach of milk-fed infants often causing gastric outlet obstruction, is a rarely reported disorder (96 cases since its first description in 1959). While most patients were described 1975-1985 only 26 children have been published since 1986. Clinically, gastric lactobezoars frequently manifest as acute abdomen with abdominal distension (61.0% of 96 patients), vomiting (54.2%), diarrhea (21.9%), and/or a palpable abdominal mass (19.8%). Respiratory (23.0%) and cardiocirculatory (16.7%) symptoms are not uncommon. The pathogenesis of lactobezoar formation is multifactorial: exogenous influences such as high casein content (54.2%), medium chain triglycerides (54.2%) or enhanced caloric density (65.6%) of infant milk as well as endogenous factors including immature gastrointestinal functions (66.0%), dehydration (27.5%) and many other mechanisms have been suggested. Diagnosis is easy if the potential presence of a gastric lactobezoar is thought of, and is based on a history of inappropriate milk feeding, signs of acute abdomen and characteristic features of diagnostic imaging. Previously, plain and/or air-, clear fluid- or opaque contrast medium radiography techniques were used to demonstrate a mass free-floating in the lumen of the stomach. This feature differentiates a gastric lactobezoar from intussusception or an abdominal neoplasm. Currently, abdominal ultrasound, showing highly echogenic intrabezoaric air trapping, is the diagnostic method of choice. However, identifying a gastric lactobezoar requires an investigator experienced in gastrointestinal problems of infancy as can be appreciated from the results of our review which show that in not even a single patient gastric lactobezoar was initially considered as a possible differential diagnosis. Furthermore, in over 30% of plain radiographs reported, diagnosis was initially missed although a lactobezoar was clearly demonstrable on repeat evaluation of the same X-ray films. Enhanced diagnostic sensitivity would be most rewarding since management consisting of cessation of oral feedings combined with administration of intravenous fluids and gastric lavage is easy and resolves over 85% of gastric lactobezoars. In conclusion, gastric lactobezoar is a disorder of unknown prevalence and is nowadays very rarely published, possibly because of inadequate diagnostic sensitivity and/or not yet identified but beneficial modifications of patient management.
PMCID: PMC3307440  PMID: 22216886
gastric lactobezoar; formula preparation; acute abdomen; dehydration; immature gastrointestinal functions; underdiagnosed entity; conservative management
10.  Unusual infections: Femoral abscess due to Nocardia abscessus in a patient suffering from metastatic peripheral bronchial carcinoma and hygienic consequences 
During the course of a peripheral bronchial carcinoma with pulmonary and cerebral metastases a femoral abscess developed in a 49 year-old patient after radio- and chemotherapy. A bacterial strain, which was isolated four times from a deep wound of the left thigh was tentatively identified as a member of the genus Nocardia on the basis of selected phenotypic and chemotaxonomic characteristics. The isolate was confirmed to belong to Nocardia abscessus by 16S rRNA gene sequencing. This species had previously been described as the causative agent of soft tissue infections. Although rare, nocardia soft tissue infections as complication of systemic nocardiosis are typical air born infections of immuncompromised patients and need specific attention. Infection prevention can be realized by restriction of soil and aerosol (builder's dust) together with antibiotic intervention (oral administration of trimethoprim/sulfamethoxazole).
PMCID: PMC3252651  PMID: 22242084
Nocardia abscessus; chemotaxonomy; 16S rRNA gene sequencing; nocardiosis; femoral abscess
11.  Antibodies against CD20 or B-Cell Receptor Induce Similar Transcription Patterns in Human Lymphoma Cell Lines 
PLoS ONE  2011;6(2):e16596.
CD20 is a cell surface protein exclusively expressed on B cells. It is a clinically validated target for Non-Hodgkin's lymphomas (NHL) and autoimmune diseases. The B cell receptor (BCR) plays an important role for development and proliferation of pre-B and B cells. Physical interaction of CD20 with BCR and components of the BCR signaling cascade has been reported but the consequences are not fully understood.
In this study we employed antibodies against CD20 and against the BCR to trigger the respective signaling. These antibodies induced very similar expression patterns of up- and down-regulated genes in NHL cell lines indicating that CD20 may play a role in BCR signaling and vice versa. Two of the genes that were rapidly and transiently induced by both stimuli are CCL3 and CCL4. 4 hours after stimulation the concentration of these chemokines in culture medium reaches a maximum. Spleen tyrosine kinase Syk is a cytoplasmic tyrosine kinase and a key component of BCR signaling. Both siRNA mediated silencing of Syk and inhibition by selective small molecule inhibitors impaired CCL3/CCL4 protein induction after treatment with either anti-CD20 or anti-BCR antibodies.
Our results suggest that treatment with anti-CD20 antibodies triggers at least partially a BCR activation-like response in NHL cell lines.
PMCID: PMC3041769  PMID: 21364752
12.  Impact of left ventricular lead position on the efficacy of cardiac resynchronisation therapy: a two‐dimensional strain echocardiography study 
Heart  2007;93(10):1197-1203.
Definition of the optimal left ventricular (LV) lead position in cardiac resynchronisation therapy (CRT) is desirable.
To define the optimal LV lead position in CRT and assess the effectiveness of CRT depending on the LV lead position using new myocardial deformation imaging.
Myocardial deformation imaging based on tracking of acoustic tissue pixels in two‐dimensional echocardiographic images (EchoPAC, GE ultrasound) was performed in 47 patients with heart failure at baseline and during CRT. In a 36‐segment LV model the segment with the latest peak systolic circumferential strain before CRT was determined. The segment with maximal temporal difference in peak systolic circumferential strain on CRT compared with before CRT was assumed to be the LV lead position. The optimal LV lead position was defined as concurrence or immediate neighbouring of the segment with the latest contraction before CRT and those with assumed LV lead location.
25 patients had optimal and 22 non‐optimal LV lead positions. Before CRT, the LV ejection fraction (EF) and peak oxygen consumption (Vo2max) were similar in patients with optimal and non‐optimal LV lead positions (mean (SD) EF = 31.4 (6.1)% vs 30.3 (6.5)% and Vo2max = 14.2 (1.8) vs 14.0 (2.1) ml/min/kg, respectively). At 3 months on CRT, EF increased by 9 (2)% vs 5 (3)% and Vo2max by 2.0 (0.8) vs 1.1 (0.5) ml/min/kg in the optimal vs non‐optimal LV lead position groups, respectively (both p<0.001).
Concordance of the LV lead site and location of the latest systolic contraction before CRT results in greater improvement in EF and cardiopulmonary workload than the non‐optimal LV lead position.
PMCID: PMC2000938  PMID: 17309913
echocardiography; heart failure; pacing
13.  Archaeal Transcription: Function of an Alternative Transcription Factor B from Pyrococcus furiosus▿  
Journal of Bacteriology  2007;190(1):157-167.
The genome of the hyperthermophile archaeon Pyrococcus furiosus encodes two transcription factor B (TFB) paralogs, one of which (TFB1) was previously characterized in transcription initiation. The second TFB (TFB2) is unusual in that it lacks recognizable homology to the archaeal TFB/eukaryotic TFIIB B-finger motif. TFB2 functions poorly in promoter-dependent transcription initiation, but photochemical cross-linking experiments indicated that the orientation and occupancy of transcription complexes formed with TFB2 at the strong gdh promoter are similar to the orientation and occupancy of transcription complexes formed with TFB1. Initiation complexes formed by TFB2 display a promoter opening defect that can be bypassed with a preformed transcription bubble, suggesting a mechanism to explain the low TFB2 transcription activity. Domain swaps between TFB1 and TFB2 showed that the low activity of TFB2 is determined mainly by its N terminus. The low activity of TFB2 in promoter opening and transcription can be partially relieved by transcription factor E (TFE). The results indicate that the TFB N-terminal region, containing conserved Zn ribbon and B-finger motifs, is important in promoter opening and that TFE can compensate for defects in the N terminus through enhancement of promoter opening.
PMCID: PMC2223750  PMID: 17965161
14.  Prospective evaluation of small bowel preparation with bisacodyl and sodium phosphate for capsule endoscopy 
AIM: To determine the effect of Prepacol®, a combination of sodium phosphate and bisacodyl, on transit and quality of capsule endoscopy (CE).
METHODS: Fivety two consecutive patients were included in this prospective study. CE was performed following a 12 h fasting period. Twenty six patients were randomized for additional preparation with Prepacol®. The quality of CE was assessed separately for the proximal and the distal small bowel by 3 experienced endoscopists on the basis of a graduation which was initially developed with 20 previous CE.
RESULTS: Preparation with Prepacol® accelerated small bowel transit time (262 ± 55 min vs 287 ± 97 min), but had no effect on the quality of CE. Visibility was significantly reduced in the distal compared to the proximal small bowel.
CONCLUSION: The significantly reduced visibility of CE in the distal small bowel allocates the need for a good preparation. Since Prepacol® has no beneficial effect on CE the modality of preparation and the ideal time of application remains unclear. Further standardized examinations are necessary to identify sufficient preparation procedures and to determine the impact of the volume of the preparation solution.
PMCID: PMC2701528  PMID: 18395907
Small bowel; Capsule endoscopy; Preparation; Laxative; Visibility; Transit time

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