Krause, Cindy

[["dc.bibliographiccitation.firstpage","158"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Pharmacopsychiatry"],["dc.bibliographiccitation.lastpage","159"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Sommer, M."],["dc.contributor.author","Dieterich, A."],["dc.contributor.author","Krause, C."],["dc.contributor.author","Rüther, E."],["dc.contributor.author","Wiltfang, J."],["dc.date.accessioned","2017-09-07T11:44:41Z"],["dc.date.available","2017-09-07T11:44:41Z"],["dc.date.issued","2001"],["dc.description.abstract","Mirtazapine is an antidepressive agent with proven efficacy [1] [4]. Frequent side effects include sleepiness, sedation, agitation, confusion, increased appetite, weight gain, and edema. Less frequent side-effects are orthostatic hypotension, mania, epileptic seizures, tremor, muscle-jerking, granulocytopenia, increase of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and exanthema [2] [5]. To our knowledge, pancreatitis as a side-effect of mirtazapine has not been described before. In this communication, we will report on a case of subclinical pancreatitis in a patient with a past history of alcohol abuse. The pancreatitis was temporarily related to the combination of mirtazapine treatment and oral food, it ceased 10 days after stopping mirtazapine. There was no alcohol consumption during the entire observation period.A 54-year-old unemployed hairdresser was admitted to the Department of Psychiatry at the University of Göttingen for a severe episode of a recurrent major depressive disorder (DSM IV 296.33). He had a history of unipolar depression, with previous hospitalizations for depressive episodes in March and October of 1999. He also had a history of alcohol dependence (DSM IV 303.90) dating from adolescence with alcohol-related hallucinations (DSM IV 291.3) which were found to be responsive to pimozide in 1998. Alcohol consumption was stopped after detoxification in August, 1998. On the present admission, the treatment consisted of citalopram at 60 mg, pimozide at 1 mg, and aspirin at 100 mg. Because of the severity of the depressive episode, we decided to add mirtazapine, which had never been tried on this patient. We chose a rapid dosage increase of 15 mg per day up to 60 mg given once a day at nighttime. On day 4, an increase of lipase and pancreas-specific amylase was found after routine blood-sampling, and a further increase of these two enzymes was observed on day 5 (Fig. [1]). We stopped oral food supply that day, and pancreas enzyme serum levels returned to normal on day 7. After introduction of restricted oral food on day 8, however, enzyme serum levels increased again. Although previous reports of elevation of pancreas enzymes related to mirtazapine had not been reported either in the literature or by Organon Pharma, Inc., Munich, we decided to stop mirtazapine on day 14 despite a marked clinical improvement in the depressive symptoms. Serum levels returned to normal levels at day 24, and a reintroduction of unrestricted oral feeding on day 27 caused only a minor increase of serum levels lasting for 3 days. Subsequent samples revealed no abnormalities in the pancreas enzyme serum levels. Samples of AST, ALT, total bilirubin, alkaline phosphatase, gamma glutamyltransferase, C-reactive protein levels and the number of leukocytes taken on day 1 and daily between day 9 and day 34 were within normal limits. The serum ethanol was below a detectable level (< 0.02 ‰) at either sample (day 1, 9, and daily from day 13 to 34). Clinically, the patient never had any subjective complaints of abdominal pain or bowel dysfunction, and only mild pain on epigastral palpation. An abdominal ultrasound on day 6 revealed no sign of pancreatitis. Since the patient's depressive symptoms were largely improved, we decided not to administer any other antidepressive drugs. The patient was discharged on day 34, and will be seen regularly on an outpatient basis.In this patient, a subclinical elevation of pancreas enzyme serum levels was temporarily associated with mirtazapine treatment and oral food which ceased after mirtazapine was stopped. There was no clinical or biochemical evidence for current alcohol consumption. Mirtazapine is known to interact with enzymes of hepatic metabolization [2], but to our knowledge, there have been no cases of mirtazapine-related pancreatitis published as yet. A contact with the AMSP drug safety program (see Grohmann et al. [3]) revealed one previously unreported case of mirtazapine-related increase of serum lipase in a 48-year-old women with depression after a rapid dosage increase to 60 mg per day within one week. In this patient, the gamma glutamyltransferase was slightly increased; pancreas-specific amylase was not assessed. That patient also had subclinical pancreatitis, and there were no known risk factors such as alcohol abuse history. Lipase and gamma glutamyltransferase returned no normal values after mirtazapine cessation. The mechanism underlying mirtazapine-related pancreatitis remains obscure, and may not necessarily be mirtazapine-specific, since the contact to the AMSP program also revealed 2 cases of paroxetine-related pancreatitis; there are also reports of pancreatitis as a result of tricyclic antidepressant overdoses [6] [7].We hypothesize that our patient's previous alcohol abuse had caused lasting subclinical damage to his pancreas and, therefore, lowered the threshold for medication-related pancreatitis. On the basis of our observation and our literature research, we recommend pancreas enzyme serum level monitoring and slow dosage increase when introducing mirtazapine in patients with possible or known pancreas dysfunction.Fig. 1 Upper part: pancreas-specific amylase (left ordinate) and lipase (right ordinate), lower part: daily mirtazapine dose (left ordinate) and food (right ordinate). Food quality is rated as: 0 = no oral food; 1 = tea and bread; 2 = fat-free, very light food; 3 = low-fat, light food; and 4 = unrestricted oral food. Note the increase in pancreas enzyme serum levels associated with mirtazapine and oral food exposure."],["dc.identifier.doi","10.1055/s-2001-15877"],["dc.identifier.gro","3151729"],["dc.identifier.pmid","11518479"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8549"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","0176-3679"],["dc.title","Subclinical Pancreatitis Related to Mirtazapine - A Case Report"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","869"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Inherited Metabolic Disease"],["dc.bibliographiccitation.lastpage","876"],["dc.bibliographiccitation.volume","39"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Dechent, Peter"],["dc.contributor.author","Krause, Cindy"],["dc.contributor.author","Ohlenbusch, Andreas"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:44:32Z"],["dc.date.available","2017-09-07T11:44:32Z"],["dc.date.issued","2016"],["dc.description.abstract","Defects in the biogenesis of peroxisomes cause a clinically and genetically heterogeneous group of neurometabolic disorders, the Zellweger syndrome spectrum (ZSS). Diagnosis predominantly is based on characteristic clinical symptoms, a typical biochemical profile, as well as on identification of the molecular defect in any of the 12 known human PEX genes. The diagnostic workup can be hindered if the typical clinical symptoms are missing and predicting the clinical course of a given patient is almost unfeasible. As a safe and noninvasive method to analyze specific chemical compounds in localized brain regions, in vivo proton magnetic resonance spectroscopy (MRS) can provide an indication in this diagnostic process and may help predict the clinical course. However, to date, there are very few reports on this topic. In this study, we performed localized in vivo proton MRS without confounding contributions from T1- and T2-relaxation effects at 2 Tesla in a comparably large group of seven ZSS patients. Patients' absolute metabolite concentrations in cortical gray matter, white matter, and basal ganglia were assessed and compared with age-matched control values. Our results confirm and extend knowledge about in vivo MRS findings in ZSS patients. Besides affirmation of nonspecific reduction of N-acetylaspartate + N-acetylaspartylglutamate (tNAA) in combination with lipid accumulation as a diagnostic hint for this disease group, the amount of tNAA loss seems to reflect disease burden and may prove to be of prognostic value regarding the clinical course of an already diagnosed patient."],["dc.identifier.doi","10.1007/s10545-016-9965-6"],["dc.identifier.gro","3141599"],["dc.identifier.isi","000386383500011"],["dc.identifier.pmid","27488561"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/10"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Springer"],["dc.relation.eissn","1573-2665"],["dc.relation.issn","0141-8955"],["dc.title","Diagnostic and prognostic value of in vivo proton MR spectroscopy for Zellweger syndrome spectrum patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2398"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Leukemia"],["dc.bibliographiccitation.lastpage","2406"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Hehlmann, R."],["dc.contributor.author","Lauseker, M."],["dc.contributor.author","Saußele, S."],["dc.contributor.author","Pfirrmann, M."],["dc.contributor.author","Krause, S."],["dc.contributor.author","Kolb, H. J."],["dc.contributor.author","Neubauer, A."],["dc.contributor.author","Hossfeld, D. K."],["dc.contributor.author","Nerl, C."],["dc.contributor.author","Gratwohl, A."],["dc.contributor.author","Baerlocher, G. M."],["dc.contributor.author","Heim, D."],["dc.contributor.author","Brümmendorf, T. H."],["dc.contributor.author","Fabarius, A."],["dc.contributor.author","Haferlach, C."],["dc.contributor.author","Schlegelberger, B."],["dc.contributor.author","Müller, M. C."],["dc.contributor.author","Jeromin, S."],["dc.contributor.author","Proetel, U."],["dc.contributor.author","Kohlbrenner, K."],["dc.contributor.author","Voskanyan, A."],["dc.contributor.author","Rinaldetti, S."],["dc.contributor.author","Seifarth, W."],["dc.contributor.author","Spieß, B."],["dc.contributor.author","Balleisen, L."],["dc.contributor.author","Goebeler, M. C."],["dc.contributor.author","Hänel, M."],["dc.contributor.author","Ho, A."],["dc.contributor.author","Dengler, J."],["dc.contributor.author","Falge, C."],["dc.contributor.author","Kanz, L."],["dc.contributor.author","Kremers, S."],["dc.contributor.author","Burchert, A."],["dc.contributor.author","Kneba, M."],["dc.contributor.author","Stegelmann, F."],["dc.contributor.author","Köhne, C.A."],["dc.contributor.author","Lindemann, H. W."],["dc.contributor.author","Waller, C. F."],["dc.contributor.author","Pfreundschuh, M."],["dc.contributor.author","Spiekermann, K."],["dc.contributor.author","Berdel, W. E."],["dc.contributor.author","Müller, L."],["dc.contributor.author","Edinger, M."],["dc.contributor.author","Mayer, J."],["dc.contributor.author","Beelen, D. W."],["dc.contributor.author","Bentz, M."],["dc.contributor.author","Link, H."],["dc.contributor.author","Hertenstein, B."],["dc.contributor.author","Fuchs, R."],["dc.contributor.author","Wernli, M."],["dc.contributor.author","Schlegel, F."],["dc.contributor.author","Schlag, R."],["dc.contributor.author","de Wit, M."],["dc.contributor.author","Trümper, L."],["dc.contributor.author","Hebart, H."],["dc.contributor.author","Hahn, M."],["dc.contributor.author","Thomalla, J."],["dc.contributor.author","Scheid, C."],["dc.contributor.author","Schafhausen, P."],["dc.contributor.author","Verbeek, W."],["dc.contributor.author","Eckart, M. J."],["dc.contributor.author","Gassmann, W."],["dc.contributor.author","Pezzutto, A."],["dc.contributor.author","Schenk, M."],["dc.contributor.author","Brossart, P."],["dc.contributor.author","Geer, T."],["dc.contributor.author","Bildat, S."],["dc.contributor.author","Schäfer, E."],["dc.contributor.author","Hochhaus, A."],["dc.contributor.author","Hasford, J."],["dc.date.accessioned","2019-11-25T13:09:15Z"],["dc.date.accessioned","2021-10-27T13:21:33Z"],["dc.date.available","2019-11-25T13:09:15Z"],["dc.date.available","2021-10-27T13:21:33Z"],["dc.date.issued","2017"],["dc.description.abstract","Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival."],["dc.identifier.doi","10.1038/leu.2017.253"],["dc.identifier.isbn","28804124"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16719"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92031"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","1476-5551"],["dc.relation.issn","1476-5551"],["dc.relation.issn","0887-6924"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.subject.ddc","610"],["dc.title","Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3844"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","3857"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Krause, Cindy"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Woehler, Andrew"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:47:08Z"],["dc.date.available","2017-09-07T11:47:08Z"],["dc.date.issued","2013"],["dc.description.abstract","In humans, the concerted action of at least 13 different peroxisomal PEX proteins is needed for proper peroxisome biogenesis. Mutations in any of these PEX genes can lead to lethal neurometabolic disorders of the Zellweger syndrome spectrum (ZSS). Previously, we identified the W313G mutation located within the SH3 domain of the peroxisomal protein, PEX13. As this tryptophan residue is highly conserved in almost all known SH3 proteins, we investigated the pathogenic mechanism of the W313G mutation and its role in PEX13 interactions and functions in peroxisome biogenesis. Here, we report for the first time that human PEX13 interacts with itself in peroxisomes in living cells. We demonstrate that the import of PTS1 (peroxisomal targeting signal 1) proteins is specifically disrupted when homooligomerization of PEX13 is interrupted. Live cell FRET microscopy in living cells as well as co-immunoprecipitation experiments reveal that the highly conserved W313 residue is important for self-association of PEX13 but is not required for interaction with PEX14, a well-established interaction partner at the peroxisomal membrane. Experiments with truncated constructs indicate that although the W313G mutation resides in the C-terminal SH3 domain, the N-terminal half is necessary for peroxisomal localization, which in turn appears to be crucial for homooligomerization. Furthermore, rescue of homooligomerization in the W313G mutant cells through complementation with truncation constructs restores import of peroxisomal matrix proteins. Taken together, the thorough analyses of a ZSS patient mutation unraveled the general cell biological function of PEX13 and its mechanism in the import of peroxisomal matrix PTS1 proteins."],["dc.identifier.doi","10.1093/hmg/ddt238"],["dc.identifier.gro","3142277"],["dc.identifier.isi","000325163900003"],["dc.identifier.pmid","23716570"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6498"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0964-6906"],["dc.title","Functional analysis of PEX13 mutation in a Zellweger syndrome spectrum patient reveals novel homooligomerization of PEX13 and its role in human peroxisome biogenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","741"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","European Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","748"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Krause, Cindy"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:47:27Z"],["dc.date.available","2017-09-07T11:47:27Z"],["dc.date.issued","2009"],["dc.description.abstract","Zellweger syndrome spectrum (ZSS) comprises a clinically and genetically heterogeneous disease entity, which is caused by mutations in any of the 12 different human PEX genes leading to impaired biogenesis of the peroxisome. Patients potentially suffering from ZSS are diagnosed biochemically by measuring elevated levels of very long chain fatty acids, pristanic acid and phytanic acid in plasma and serum and reduced levels of ether phospholipids in erythrocytes. Published reports on diagnostic procedures for ZSS patients are restricted either to biochemical markers or to defined mutations in a subset of PEX genes. Clarification of the primary genetic defect in an affected patient is crucial for genetic counselling, carrier testing or prenatal diagnosis. In this study, we present a rational diagnostic strategy for patients suspected of ZSS. By combining cell biology and molecular genetic methods in an appropriate sequence, we were able to detect the underlying mutation in various PEX genes within adequate time and cost. We applied this method on 90 patients who presented at our institute, Department of Pediatrics and Pediatric Neurology at Georg August University, and detected 174 mutant alleles within six different PEX genes, including two novel deletions and three new missense mutations in PEX6. Furthermore, this strategy will extend our knowledge on genotype-phenotype correlation in various PEX genes. It will contribute to a better understanding of ZSS pathogenesis, allowing the investigation of the effects of diverse mutations on the interaction between PEX proteins and peroxisomal function in vivo. European Journal of Human Genetics (2009) 17, 741-748; doi: 10.1038/ejhg.2008.252; published online 14 January 2009"],["dc.identifier.doi","10.1038/ejhg.2008.252"],["dc.identifier.gro","3143108"],["dc.identifier.isi","000266289100009"],["dc.identifier.pmid","19142205"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/586"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1018-4813"],["dc.title","Rational diagnostic strategy for Zellweger syndrome spectrum patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]