Plasma and urine profiles of Δ9-tetrahydrocannabinol and its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol after cannabis smoking by male volunteers to estimate recent consumption by athletes
Brenneisen R.,University of Bern |
Meyer P.,University of Bern |
Chtioui H.,University Hospital of Berne |
Saugy M.,Swiss Laboratory for Doping Analyses |
Kamber M.,Antidoping Switzerland
Analytical and Bioanalytical Chemistry | Year: 2010
Since 2004, cannabis has been prohibited by the World Anti-Doping Agency for all sports competitions. In the years since then, about half of all positive doping cases in Switzerland have been related to cannabis consumption. In doping urine analysis, the target analyte is 11-nor-9-carboxy- Δ9-tetrahydrocannabinol (THC-COOH), the cutoff being 15 ng/mL. However, the wide urinary detection window of the long-term metabolite of Δ9-tetrahydrocannabinol (THC) does not allow a conclusion to be drawn regarding the time of consumption or the impact on the physical performance. The purpose of the present study on light cannabis smokers was to evaluate target analytes with shorter urinary excretion times. Twelve male volunteers smoked a cannabis cigarette standardized to 70 mg THC per cigarette. Plasma and urine were collected up to 8 h and 11 days, respectively. Total THC, 11-hydroxy-Δ9-tetrahydrocannabinol (THC-OH), and THC-COOH were determined after hydrolysis followed by solid-phase extraction and gas chromatography/mass spectrometry. The limits of quantitation were 0.1-1.0 ng/mL. Eight puffs delivered a mean THC dose of 45 mg. Plasma levels of total THC, THC-OH, and THC-COOH were measured in the ranges 0.2-59.1, 0.1-3.9, and 0.4-16.4 ng/mL, respectively. Peak concentrations were observed at 5, 5-20, and 20-180 min. Urine levels were measured in the ranges 0.1-1.3, 0.1-14.4, and 0.5-38.2 ng/mL, peaking at 2, 2, and 6-24 h, respectively. The times of the last detectable levels were 2-8, 6-96, and 48-120 h. Besides high to very high THC-COOH levels (245 ± 1,111 ng/mL), THC (3 ± 8 ng/mL) and THC-OH (51 ± 246 ng/mL) were found in 65 and 98% of cannabis-positive athletes' urine samples, respectively. In conclusion, in addition to THC-COOH, the pharmacologically active THC and THC-OH should be used as target analytes for doping urine analysis. In the case of light cannabis use, this may allow the estimation of more recent consumption, probably influencing performance during competitions. However, it is not possible to discriminate the intention of cannabis use, i.e., for recreational or doping purposes. Additionally, pharmacokinetic data of female volunteers are needed to interpret cannabis-positive doping cases of female athletes. © 2010 Springer-Verlag.
Persson J.,Skåne University Hospital |
Imboden S.,University Hospital of Berne |
Reynisson P.,Skåne University Hospital |
Andersson B.,Skåne University Hospital |
And 2 more authors.
Gynecologic Oncology | Year: 2012
Objective. To assess the accuracy and reproducibility of robot-assisted laparoscopic abdominal fertility sparing radical trachelectomy in women with early stage cervical cancer. Methods. Relevant prospective clinical data from 13 consecutive women planned for robotic radical trachelectomy between 2007 and 2012 were compared with retrospective data from 12 consecutive women planned for vaginal radical trachelectomy between 2000 and 2007. The first follow up on all women included a similar vaginal ultrasonographic measurement of the remaining cervical length and the position of the cerclage, enabling a direct comparison. Peri- and postoperative clinical data were evaluated. Results. The remaining cervical length was equal between the robotic and vaginal procedures (mean 11 mm, range 8-13 mm; mean 11 mm, range 5-19 mm respectively, p = 0.92). The distance from the cerclage to the inner cervical os was significantly shorter and less variable in the robot group (robot mean 2 mm, range of 1-4 mm, vaginal mean 4 mm, range 2-7 mm, p = 0.003). Rejection of the cerclage (n = 3) and/or cervical stenosis (n = 3) was diagnosed in four women, all of whom in the vaginal group, between one and 13 months after surgery. Conclusions. Robotic trachelectomy is equally reproducible and accurate as the vaginal trachelectomy in terms of the remaining cervical length and results in a significantly more precise placement of the cerclage. © 2012 Elsevier Inc. All rights reserved.
Korner M.,University of Bern |
Christ E.,University Hospital of Berne |
Wild D.,University of Basel |
Reubi J.C.,University of Bern
Frontiers in Endocrinology | Year: 2012
Peptide hormones of the glucagon-like peptide (GLP) family play an increasing clinical role, such as GLP-1 in diabetes therapy. Moreover, GLP receptors are overexpressed in various human tumor types and therefore represent molecular targets for important clinical applications. In particular, virtually all benign insulinomas highly11o1 verexpress GLP-1 receptors (GLP-1R).Targeting GLP-1R with the stable GLP-1 analogs 111In-DOTA/DPTA-exendin-4 offers a new approach to successfully localize these small tumors.This non-invasive technique has the potential tore place the invasive localization of insulinomas by selective arterial stimulation and venous sampling. Malignant insulinomas, in contrast to their benign counterparts, express GLP-1R in only one-third of the cases, while they more often express the somatostatin type 2 receptors. Importantly, one of the two receptors appears to be always expressed in malignant insulinomas. The GLP-1R overexpression in selected cancers is worth to be kept in mind with regard to the increasing use of GLP-1 analogs for diabetes therapy. While the functional role of GLP-1R in neoplasia is not known yet, it may be safe to monitor patients undergoing GLP-1 therapy carefully. © 2012 Körner, Christ, Wild and Reubi.
Sarikaya H.,University of Zürich |
Sarikaya H.,University Hospital of Berne
Drugs and Aging | Year: 2013
Stroke is a common cause of death and persisting disability worldwide, and thrombolysis with intravenous alteplase is the only approved treatment for acute ischaemic stroke. Older age is the most important non-modifiable risk factor for stroke, and demographic changes are also resulting in an increasingly ageing population. However, clinical trial evidence for the use of intravenous alteplase is limited for the older age group where stroke incidence is highest. In this article, the current evidence regarding the safety and efficacy of intravenous thrombolytic therapy in stroke patients aged ≥80 years is critically analysed and the gap in current knowledge highlighted. In summary, intravenous thrombolysis in stroke patients aged ≥80 years seems to be associated with less favourable clinical outcomes and higher mortality than in younger patients, which is consistent with the natural course in untreated patients. The risk of symptomatic intracranial haemorrhage does not appear to be significantly higher in the elderly group, suggesting that intracranial bleeding complications are unlikely to outweigh the potential benefit in this age group. Overall, withholding thrombolytic treatment in ischaemic stroke on the basis of advanced age alone is no longer justifiable. © 2013 Springer International Publishing Switzerland.
Huber G.F.,University of Zürich |
Albinger-Hegyi A.,University of Zürich |
Soltermann A.,University of Zürich |
Roessle M.,University of Zürich |
And 5 more authors.
Cancer | Year: 2011
BACKGROUND: The objective of this study was to link expression patterns of B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and p16 to patient outcome (recurrence and survival) in a cohort of 252 patients with oral and oropharyngeal squamous cell cancer (OSCC). METHODS: Expression levels of Bmi-1 and p16 in samples from 252 patients with OSCC were evaluated immunohistochemically using the tissue microarray method. Staining intensity was determined by calculating an intensity reactivity score (IRS). Staining intensity and the localization of expression within tumor cells (nuclear or cytoplasmic) were correlated with overall, disease-specific, and recurrence-free survival. RESULTS: The majority of cancers were localized in the oropharynx (61.1%). In univariate analysis, patients who had OSCC and strong Bmi-1 expression (IRS >10) had worse outcomes compared with patients who had low and moderate Bmi-1 expression (P =.008; hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.167-2.838); this correlation was also observed for atypical cytoplasmic Bmi-1 expression (P =.001; HR, 2.164; 95% CI, 1.389-3.371) and for negative p16 expression (P <.001; HR, 0.292; 95% CI, 0.178-0.477). The combination of both markers, as anticipated, had an even stronger correlation with overall survival (P <.001; HR, 8.485; 95% CI, 4.237-16.994). Multivariate analysis demonstrated significant results for patients with oropharyngeal cancers, but not for patients with oral cavity tumors: Tumor classification (P =.011; HR, 1.838; 95%CI, 1.146-2.947) and the combined marker expression patterns (P <.001; HR, 6.254; 95% CI, 2.869-13.635) were correlated with overall survival, disease-specific survival (tumor classification: P =.002; HR, 2.807; 95% CI, 1.477-5.334; combined markers: P =.002; HR, 5.386; 95% CI, 1.850-15.679), and the combined markers also were correlated with recurrence-free survival (P =.001; HR, 8.943; 95% CI, 2.562-31.220). CONCLUSIONS: Cytoplasmic Bmi-1 expression, an absence of p16 expression, and especially the combination of those 2 predictive markers were correlated negatively with disease-specific and recurrence-free survival in patients with oropharyngeal cancer. Therefore, the current results indicate that these may be applicable as predictive markers in combination with other factors to select patients for more aggressive treatment and follow-up. Cancer 2011;. © 2011 American Cancer Society. B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) expression and the absence of p16 expression were correlated negatively with disease-specific survival and recurrence-free survival in patients with oropharyngeal cancer. The results from this study indicated that Bmi-1 and p16 may have value as predictive markers in combination with other factors to select patients for more aggressive treatment and follow-up. Copyright © 2011 American Cancer Society.
Reubi J.C.,University of Bern |
Waser B.,University of Bern |
Cescato R.,University of Bern |
Gloor B.,University Hospital of Berne |
And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010
Context: Somatostatin receptor subtype 2 (sst2) is widely expressed in neuroendocrine tumors and can be visualized immunohistochemically at the cell membrane for diagnostic purposes. Recently, it has been demonstrated in animal sst2 tumor models in vivo that somatostatin analog treatment was able to induce a complete internalization of the tumor sst 2. Patients and Methods: In the present study, we evaluated whether sst2 expressed in neuroendocrine tumors of patients treated with octreotide are also internalized. Tumor samples were assessedinpatientsthatweretreatedwithvariousoctreotidemodalities beforeandduringsurgeryand compared with tumor samples from untreated patients. Sst2 immunohistochemistry was performed in all samples with three different sst2 antibodies (R2-88, UMB-1, and SS-800). Sst2 receptor expression was confirmed by immunoblotting and in vitro receptor autoradiography. Results: Patients receiving a high dose of octreotide showed predominantly internalized sst2, and patients with a low dose of octreotide had a variable ratio of internalized vs. membranous sst2, whereas untreated patients had exclusively membranous sst2. The internalized sst2 receptor corresponded to a single sst2 band in immunoblots and to sst2 receptors in in vitro receptor autoradiography. Although generally found in endosome-like structures, internalized sst2 receptors were also identified to a small extent in lysosomes, as seen in colocalization experiments. Conclusion: It is the first evidence showing that sst2 receptors can be internalized in sst 2-expressing neuroendocrine tumors in patients under octreotide therapy, providing clues about sst2 receptor biology and trafficking dynamics in patients. Copyright © 2010 by The Endocrine Society.
Krejci V.,University of Washington |
Krejci V.,University Hospital of Berne |
Vannucci A.,University of Washington |
Abbas A.,University of Washington |
And 2 more authors.
Liver Transplantation | Year: 2010
Arterial pressure-based cardiac output monitors (APCOs) are increasingly used as alternatives to thermodilution. Validation of these evolving technologies in high-risk surgery is still ongoing. In liver transplantation, FloTrac-Vigileo (Edwards Life-sciences) has limited correlation with thermodilution, whereas LiDCO Plus (LiDCO Ltd.) has not been tested intraoperatively. Our goal was to directly compare the 2 proprietary APCO algorithms as alternatives to pulmonary artery catheter thermodilution in orthotopic liver transplantation (OLT). The cardiac index (CI) was measured simultaneously in 20 OLT patients at prospectively defined surgical landmarks with the LiDCO Plus monitor (CIL) and the FloTrac-Vigileo monitor (CIV). LiDCO Plus was calibrated according to the manufacturer's instructions. FloTrac-Vigileo did not require calibration. The reference CI was derived from pulmonary artery catheter intermittent thermodilution (CI TD). CIV-CITD bias ranged from -1.38 (95% confidence interval = -2.02 to -0.75 L/minute/m2, P = 0.02) to -2.51 L/minute/m2 (95% confidence interval = 3.36 to -1.65 L/minute/m 2, P < 0.001), and CIL-CITD bias ranged from -0.65 (95% confidence interval = -1.29 to -0.01 L/minute/m2, P = 0.047) to -1.48 L/minute/m2 (95% confidence interval = -2.37 to -0.60 L/minute/m2, P < 0.01). For both APCOs, bias to CITD was correlated with the systemic vascular resistance index, with a stronger dependence for FloTrac-Vigileo. The capability of the APCOs for tracking changes in CITD was assessed with a 4-quadrant plot for directional changes and with receiver operating characteristic curves for specificity and sensitivity. The performance of both APCOs was poor in detecting increases and fair in detecting decreases in CITD. In conclusion, the calibrated and uncalibrated APCOs perform differently during OLT. Although the calibrated APCO is less influenced by changes in the systemic vascular resistance, neither device can be used interchangeably with thermodilution to monitor cardiac output during liver transplantation. © 2010 AASLD.
Szucs-Farkas Z.,University Hospital of Berne |
Patak M.A.,University Hospital of Berne |
Yuksel-Hatz S.,University Hospital of Berne |
Ruder T.,University Hospital of Berne |
Vock P.,University Hospital of Berne
European Radiology | Year: 2010
Objective: To retrospectively analyze the performance of a commercial computer-aided diagnosis (CAD) software in the detection of pulmonary nodules in original and energy-subtracted (ES) chest radiographs. Methods: Original and ES chest radiographs of 58 patients with 105 pulmonary nodules measuring 5-30 mm and images of 25 control subjects with no nodules were randomized. Five blinded readers evaluated firstly the original postero-anterior images alone and then together with the subtracted radiographs. In a second phase, original and ES images were analyzed by a commercial CAD program. CT was used as reference standard. CAD results were compared to the readers' findings. True-positive (TP) and false-positive (FP) findings with CAD on subtracted and non-subtracted images were compared. Results: Depending on the reader's experience, CAD detected between 11 and 21 nodules missed by readers. Human observers found three to 16 lesions missed by the CAD software. CAD used with ES images produced significantly fewer FPs than with non-subtracted images: 1.75 and 2.14 FPs per image, respectively (p=0.029). The difference for the TP nodules was not significant (40 nodules on ES images and 34 lesions in non-subtracted radiographs, p=0.142). Conclusion: CAD can improve lesion detection both on energy subtracted and non-subtracted chest images, especially for less experienced readers. The CAD program marked less FPs on energy-subtracted images than on original chest radiographs. © 2009 European Society of Radiology.
Lienhard D.,University Hospital of Berne |
Lauterburg M.,University Hospital of Berne |
Escher G.,University Hospital of Berne |
Frey F.J.,University Hospital of Berne |
Frey B.M.,University Hospital of Berne
PLoS ONE | Year: 2012
Besides the kidneys, the gastrointestinal tract is the principal organ responsible for sodium homeostasis. For sodium transport across the cell membranes the epithelial sodium channel (ENaC) is of pivotal relevance. The ENaC is mainly regulated by mineralocorticoid receptor mediated actions. The MR activation by endogenous 11β-hydroxy-glucocorticoids is modulated by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). Here we present evidence for intestinal segment specific 11β-HSD2 expression and hypothesize that a high salt intake and/or uninephrectomy (UNX) affects colonic 11β-HSD2, MR and ENaC expression. The 11β-HSD2 activity was measured by means of 3H-corticosterone conversion into 3H-11-dehydrocorticosterone in Sprague Dawley rats on a normal and high salt diet. The activity increased steadily from the ileum to the distal colon by a factor of about 3, an observation in line with the relevance of the distal colon for sodium handling. High salt intake diminished mRNA and protein of 11β-HSD2 by about 50% (p<0.001) and reduced the expression of the MR (p<0.01). The functionally relevant ENaC-β and ENaC-γ expression, a measure of mineralocorticoid action, diminished by more than 50% by high salt intake (p<0.001). The observed changes were present in rats with and without UNX. Thus, colonic epithelial cells appear to contribute to the protective armamentarium of the mammalian body against salt overload, a mechanism not modulated by UNX. © 2012 Lienhard et al.
Marti G.,University Hospital of Berne |
Fattinger K.,University Hospital of Berne |
Zimmermann H.,University Hospital of Berne |
Exadaktylos A.,University Hospital of Berne
Human and Experimental Toxicology | Year: 2013
Ritalin® (methylphenidate) is an amphetamine-like prescription stimulant commonly used in the treatment of attention deficit hyperactivity disorder in children and adults. Recently, the recreational use of Ritalin has increased, particularly among young adults. Well-known symptoms of intoxication include signs of sympathetic nervous stimulation, such as agitation, anxiety, tachycardia, hypertension, headache, tremor, and dizziness. This case report describes oral dyskinesia as a rare presentation of Ritalin intoxication, with the review of pathophysiology and some epidemiological data. © The Author(s) 2013.