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Article ; Online: Dissecting Temporal Profiles of Neuronal and Axonal Damage After Mild Traumatic Brain Injury.

Bogoslovsky, Tanya / Diaz-Arrastia, Ramon

2016 Volume 73, Issue 5, Page(s) 506–507

MeSH term(s)	Axons ; Brain Concussion ; Brain Injuries ; Humans ; Neurons
Language	English
Publishing date	2016-03-24
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2702023-X
ISSN	2168-6157 ; 2168-6149
ISSN (online)	2168-6157
ISSN	2168-6149
DOI	10.1001/jamaneurol.2016.0290
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Article: Fluid Biomarkers of Traumatic Brain Injury and Intended Context of Use.

Bogoslovsky, Tanya / Gill, Jessica / Jeromin, Andreas / Davis, Cora / Diaz-Arrastia, Ramon

Diagnostics (Basel, Switzerland)

2016 Volume 6, Issue 4

Abstract: Traumatic brain injury (TBI) is one of the leading causes of death and disability around the world. The lack of validated biomarkers for TBI is a major impediment to developing effective therapies and improving clinical practice, as well as stimulating ... ...

Abstract	Traumatic brain injury (TBI) is one of the leading causes of death and disability around the world. The lack of validated biomarkers for TBI is a major impediment to developing effective therapies and improving clinical practice, as well as stimulating much work in this area. In this review, we focus on different settings of TBI management where blood or cerebrospinal fluid (CSF) biomarkers could be utilized for predicting clinically-relevant consequences and guiding management decisions. Requirements that the biomarker must fulfill differ based on the intended context of use (CoU). Specifically, we focus on fluid biomarkers in order to: (1) identify patients who may require acute neuroimaging (cranial computerized tomography (CT) or magnetic resonance imaging (MRI); (2) select patients at risk for secondary brain injury processes; (3) aid in counseling patients about their symptoms at discharge; (4) identify patients at risk for developing postconcussive syndrome (PCS), posttraumatic epilepsy (PTE) or chronic traumatic encephalopathy (CTE); (5) predict outcomes with respect to poor or good recovery; (6) inform counseling as to return to work (RTW) or to play. Despite significant advances already made from biomarker-based studies of TBI, there is an immediate need for further large-scale studies focused on identifying and innovating sensitive and reliable TBI biomarkers. These studies should be designed with the intended CoU in mind.
Language	English
Publishing date	2016-10-18
Publishing country	Switzerland
Document type	Review ; Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics6040037
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Article ; Online: Development of a systems-based in situ multiplex biomarker screening approach for the assessment of immunopathology and neural tissue plasticity in male rats after traumatic brain injury.

Bogoslovsky, Tanya / Bernstock, Joshua D / Bull, Greg / Gouty, Shawn / Cox, Brian M / Hallenbeck, John M / Maric, Dragan

Journal of neuroscience research

2017 Volume 96, Issue 4, Page(s) 487–500

Abstract: Traumatic brain injuries (TBIs) pose a massive burden of disease and continue to be a leading cause of morbidity and mortality throughout the world. A major obstacle in developing effective treatments is the lack of comprehensive understanding of the ... ...

Abstract	Traumatic brain injuries (TBIs) pose a massive burden of disease and continue to be a leading cause of morbidity and mortality throughout the world. A major obstacle in developing effective treatments is the lack of comprehensive understanding of the underlying mechanisms that mediate tissue damage and recovery after TBI. As such, our work aims to highlight the development of a novel experimental platform capable of fully characterizing the underlying pathobiology that unfolds after TBI. This platform encompasses an empirically optimized multiplex immunohistochemistry staining and imaging system customized to screen for a myriad of biomarkers required to comprehensively evaluate the extent of neuroinflammation, neural tissue damage, and repair in response to TBI. Herein, we demonstrate that our multiplex biomarker screening platform is capable of evaluating changes in both the topographical location and functional states of resident and infiltrating cell types that play a role in neuropathology after controlled cortical impact injury to the brain in male Sprague-Dawley rats. Our results demonstrate that our multiplex biomarker screening platform lays the groundwork for the comprehensive characterization of changes that occur within the brain after TBI. Such work may ultimately lead to the understanding of the governing pathobiology of TBI, thereby fostering the development of novel therapeutic interventions tailored to produce optimal tissue protection, repair, and/or regeneration with minimal side effects, and may ultimately find utility in a wide variety of other neurological injuries, diseases, and disorders that share components of TBI pathobiology.
MeSH term(s)	Animals ; Astrocytes/metabolism ; Astrocytes/pathology ; Biomarkers/metabolism ; Brain/physiopathology ; Brain Injuries, Traumatic/metabolism ; Brain Injuries, Traumatic/physiopathology ; Cerebral Cortex/metabolism ; Cerebral Cortex/pathology ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/pathology ; Immunohistochemistry/methods ; Male ; Neuroimaging/methods ; Oligodendroglia/metabolism ; Oligodendroglia/pathology ; Rats, Sprague-Dawley ; Tongue Diseases/metabolism ; Tongue Diseases/pathology
Chemical Substances	Biomarkers
Language	English
Publishing date	2017-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	195324-2
ISSN	1097-4547 ; 0360-4012
ISSN (online)	1097-4547
ISSN	0360-4012
DOI	10.1002/jnr.24054
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Article: Changes in Plasma von Willebrand Factor and Cellular Fibronectin in MRI-Defined Traumatic Microvascular Injury.

Sandsmark, Danielle K / Bogoslovsky, Tanya / Qu, Bao-Xi / Haber, Margalit / Cota, Martin R / Davis, Cora / Butman, John A / Latour, Lawrence L / Diaz-Arrastia, Ramon

Frontiers in neurology

2019 Volume 10, Page(s) 246

Abstract: The neuropathology of traumatic brain injury (TB) is diverse, including primary injury to neurons, axons, glial cells, vascular structures, and secondary processes, such as edema and inflammation that vary between individual patients. Traumatic ... ...

Abstract	The neuropathology of traumatic brain injury (TB) is diverse, including primary injury to neurons, axons, glial cells, vascular structures, and secondary processes, such as edema and inflammation that vary between individual patients. Traumatic microvascular injury is an important endophenotype of TBI-related injury. We studied patients who sustained a TBI requiring ER evaluation and had an MRI performed within 48 h of injury. We classified patients into 3 groups based on their MRI findings: (1) those that had evidence of traumatic microvascular injury on susceptibility or diffusion weighted MRI sequences without frank hemorrhage [Traumatic Vascular Injury (TVI) group; 20 subjects]. (2) those who had evidence of intraparenchymal, subdural, epidural, or subarachnoid hemorrhage [Traumatic Hemorrhage (TH) group; 26 subjects], and (3) those who had no traumatic injuries detected by MRI [MRI-negative group; 30 subjects]. We then measured plasma protein biomarkers of vascular injury [von Willebrand Factor (vWF) or cellular fibronectin (cFn)] and axonal injury (phosphorylated neurofilament heavy chain; pNF-H). We found that the TVI group was characterized by decreased expression of plasma vWF (
Language	English
Publishing date	2019-03-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2019.00246
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Article ; Online: Fluid Biomarkers of Traumatic Brain Injury and Intended Context of Use

Tanya Bogoslovsky / Jessica Gill / Andreas Jeromin / Cora Davis / Ramon Diaz-Arrastia

Diagnostics, Vol 6, Iss 4, p

2016 Volume 37

Abstract	Traumatic brain injury (TBI) is one of the leading causes of death and disability around the world. The lack of validated biomarkers for TBI is a major impediment to developing effective therapies and improving clinical practice, as well as stimulating much work in this area. In this review, we focus on different settings of TBI management where blood or cerebrospinal fluid (CSF) biomarkers could be utilized for predicting clinically-relevant consequences and guiding management decisions. Requirements that the biomarker must fulfill differ based on the intended context of use (CoU). Specifically, we focus on fluid biomarkers in order to: (1) identify patients who may require acute neuroimaging (cranial computerized tomography (CT) or magnetic resonance imaging (MRI); (2) select patients at risk for secondary brain injury processes; (3) aid in counseling patients about their symptoms at discharge; (4) identify patients at risk for developing postconcussive syndrome (PCS), posttraumatic epilepsy (PTE) or chronic traumatic encephalopathy (CTE); (5) predict outcomes with respect to poor or good recovery; (6) inform counseling as to return to work (RTW) or to play. Despite significant advances already made from biomarker-based studies of TBI, there is an immediate need for further large-scale studies focused on identifying and innovating sensitive and reliable TBI biomarkers. These studies should be designed with the intended CoU in mind.
Keywords	traumatic brain injury (TBI) ; biomarkers ; TBI management ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2016-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Cerebral Vascular Injury in Traumatic Brain Injury.

Kenney, Kimbra / Amyot, Franck / Haber, Margalit / Pronger, Angela / Bogoslovsky, Tanya / Moore, Carol / Diaz-Arrastia, Ramon

Experimental neurology

2016 Volume 275 Pt 3, Page(s) 353–366

Abstract: Traumatic cerebral vascular injury (TCVI) is a very frequent, if not universal, feature after traumatic brain injury (TBI). It is likely responsible, at least in part, for functional deficits and TBI-related chronic disability. Because there are multiple ...

Abstract	Traumatic cerebral vascular injury (TCVI) is a very frequent, if not universal, feature after traumatic brain injury (TBI). It is likely responsible, at least in part, for functional deficits and TBI-related chronic disability. Because there are multiple pharmacologic and non-pharmacologic therapies that promote vascular health, TCVI is an attractive target for therapeutic intervention after TBI. The cerebral microvasculature is a component of the neurovascular unit (NVU) coupling neuronal metabolism with local cerebral blood flow. The NVU participates in the pathogenesis of TBI, either directly from physical trauma or as part of the cascade of secondary injury that occurs after TBI. Pathologically, there is extensive cerebral microvascular injury in humans and experimental animal, identified with either conventional light microscopy or ultrastructural examination. It is seen in acute and chronic TBI, and even described in chronic traumatic encephalopathy (CTE). Non-invasive, physiologic measures of cerebral microvascular function show dysfunction after TBI in humans and experimental animal models of TBI. These include imaging sequences (MRI-ASL), Transcranial Doppler (TCD), and Near InfraRed Spectroscopy (NIRS). Understanding the pathophysiology of TCVI, a relatively under-studied component of TBI, has promise for the development of novel therapies for TBI.
MeSH term(s)	Animals ; Brain/blood supply ; Brain/pathology ; Brain Injuries/pathology ; Cerebrovascular Circulation/physiology ; Humans ; Microcirculation/physiology ; Vascular System Injuries/pathology
Language	English
Publishing date	2016-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	207148-4
ISSN	1090-2430 ; 0014-4886
ISSN (online)	1090-2430
ISSN	0014-4886
DOI	10.1016/j.expneurol.2015.05.019
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Article: The impact of

Sychev, Dmitriy Alekseevich / Levanov, Alexander Nikolaevich / Shelekhova, Tatiana Vladimirovna / Bochkov, Pavel Olegovich / Denisenko, Natalia Pavlovna / Ryzhikova, Kristina Anatolyevna / Mirzaev, Karin Badavievich / Grishina, Elena Anatolyevna / Gavrilov, Mikhail Alekseevich / Ramenskaya, Galina Vladislavovna / Kozlov, Aleksei Vladimirovich / Bogoslovsky, Tanya

Pharmacogenomics and personalized medicine

2018 Volume 11, Page(s) 127–137

Abstract: Background: Non-vitamin K oral anticoagulants (NOACs) are commonly used for prophylaxis of venous thromboembolism (VTE) in orthopedic patients. Despite known safety and high potency of NOACs, potential interactions of NOACs with genetic polymorphisms ... ...

Abstract	Background: Non-vitamin K oral anticoagulants (NOACs) are commonly used for prophylaxis of venous thromboembolism (VTE) in orthopedic patients. Despite known safety and high potency of NOACs, potential interactions of NOACs with genetic polymorphisms are poorly understood. Dabigatran etexilate is one of the most commonly prescribed direct thrombin inhibitors for the prevention of VTE. The objectives of this study were to assess the effect of Patients and methods: A total of 60 patients, aged 37-81 years, who underwent surgery for knee replacement have been included in the study. VTE prophylaxis was conducted via administration of dabigatran etexilate 220 mg once daily. Genotyping for carrier state of polymorphic variants such as rs1045642 and rs4148738 of the Results: Our study revealed that TT genotype of rs1045642 polymorphism of the Conclusion: Our findings indicate that the polymorphisms of
Language	English
Publishing date	2018-07-25
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2508173-1
ISSN	1178-7066
ISSN	1178-7066
DOI	10.2147/PGPM.S169277
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Article: Evolution of Traumatic Parenchymal Intracranial Hematomas (ICHs): Comparison of Hematoma and Edema Components.

Wilkes, Sean / McCormack, Erin / Kenney, Kimbra / Stephens, Brian / Passo, Ross / Harburg, Leah / Silverman, Erika / Moore, Carol / Bogoslovsky, Tanya / Pham, Dzung / Diaz-Arrastia, Ramon

Frontiers in neurology

2018 Volume 9, Page(s) 527

Abstract: This study seeks to quantitatively assess evolution of traumatic ICHs over the first 24 h and investigate its relationship with functional outcome. Early expansion of traumatic intracranial hematoma (ICH) is common, but previous studies have focused on ... ...

Abstract	This study seeks to quantitatively assess evolution of traumatic ICHs over the first 24 h and investigate its relationship with functional outcome. Early expansion of traumatic intracranial hematoma (ICH) is common, but previous studies have focused on the high density (blood) component. Hemostatic therapies may increase the risk of peri-hematoma infarction and associated increased cytotoxic edema. Assessing the magnitude and evolution of ICH and edema represented by high and low density components on computerized tomography (CT) may be informative for designing therapies targeted at traumatic ICH. CT scans from participants in the COBRIT (Citicoline Brain Injury Trial) study were analyzed using MIPAV software. CT scans from patients with non-surgical intraparenchymal ICHs at presentation and approximately 24 h later (±12 h) were selected. Regions of high density and low density were quantitatively measured. The relationship between volumes of high and low density were compared to several outcome measures, including Glasgow Outcome Score-Extended (GOSE) and Disability Rating Score (DRS). Paired scans from 84 patients were analyzed. The median time between the first and second scan was 22.79 h (25%ile 20.11 h; 75%ile 27.49 h). Over this time frame, hematoma and edema volumes increased >50% in 34 (40%) and 46 (55%) respectively. The correlation between the two components was low (
Language	English
Publishing date	2018-07-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2018.00527
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Article ; Online: Preservation and enumeration of endothelial progenitor and endothelial cells from peripheral blood for clinical trials.

Bogoslovsky, Tanya / Maric, Dragan / Gong, Yunhua / Qu, Baoxi / Yang, Kelly / Spatz, Maria / Hallenbeck, John / Diaz-Arrastia, Ramon

Biomarkers in medicine

2015 Volume 9, Issue 7, Page(s) 625–637

Abstract: Aims: Endothelial progenitor cells (EPCs) are markers of vascular repair. Increased numbers of circulating endothelial cells (ECs) are associated with endothelial damage.: Materials & methods: We enumerated EPC-EC by using Enrichment kit with ... ...

Abstract	Aims: Endothelial progenitor cells (EPCs) are markers of vascular repair. Increased numbers of circulating endothelial cells (ECs) are associated with endothelial damage. Materials & methods: We enumerated EPC-EC by using Enrichment kit with addition of anti-human CD146-PE/Cy7 from peripheral blood mononuclear cell (PBMC) isolated either by red blood cell (RBC) lysing solution or by Ficoll centrifugation, and from fresh and preserved samples. PBMCs were quantified by flow cytometry. Results: RBC lysis yielded higher percentage of PBMC (p = 0.0242) and higher numbers of PBMC/ml (p = 0.0039) than Ficoll. Absolute numbers of CD34(+)CD133(+)VEGFR2(+) and CD146(+)CD34(+)VEGFR2(+) were higher (p = 0.0117 for both), when isolated by RBC lysis than by Ficoll, when no difference in other subsets was found. Cryopreservation at -160°C and -80°C and short-term preservation at room temperature decreased EPC-EC. Conclusions: Our data support use of fresh samples and isolation of PBMC from human blood by RBC lysis for enumeration of EPC and EC.
MeSH term(s)	AC133 Antigen ; Adult ; Aged ; Antigens, CD/metabolism ; Antigens, CD34/metabolism ; CD146 Antigen/metabolism ; Cryopreservation ; Endothelial Cells/cytology ; Erythrocytes/cytology ; Female ; Ficoll/chemistry ; Flow Cytometry ; Glycoproteins/metabolism ; Humans ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/metabolism ; Male ; Middle Aged ; Peptides/metabolism ; Stem Cells/cytology ; Stem Cells/metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism
Chemical Substances	AC133 Antigen ; Antigens, CD ; Antigens, CD34 ; CD146 Antigen ; Glycoproteins ; PROM1 protein, human ; Peptides ; Ficoll (25702-74-3) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1)
Language	English
Publishing date	2015
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2481014-9
ISSN	1752-0371 ; 1752-0363
ISSN (online)	1752-0371
ISSN	1752-0363
DOI	10.2217/bmm.15.34
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Article ; Online: Reliability of the NINDS common data elements cranial tomography (CT) rating variables for traumatic brain injury (TBI).

Harburg, Leah / McCormack, Erin / Kenney, Kimbra / Moore, Carol / Yang, Kelly / Vos, Pieter / Jacobs, Bram / Madden, Christopher J / Diaz-Arrastia, Ramon / Bogoslovsky, Tanya

Brain injury

2017 Volume 31, Issue 2, Page(s) 174–184

Abstract: Background: Non-contrast head computer tomography (CT) is widely used to evaluate eligibility of patients after acute traumatic brain injury (TBI) for clinical trials. The NINDS Common Data Elements (CDEs) TBI were developed to standardize collection of ...

Abstract	Background: Non-contrast head computer tomography (CT) is widely used to evaluate eligibility of patients after acute traumatic brain injury (TBI) for clinical trials. The NINDS Common Data Elements (CDEs) TBI were developed to standardize collection of CT variables. The objectives of this study were to train research assistants (RAs) to rate CDEs and then to evaluate their performance. The aim was to assess inter-rater reliability (IRR) of CDEs between trained RAs and a neurologist and to evaluate applicability of CDEs in acute and sub-acute TBI to test the feasibility of using CDE CT ratings in future trials and ultimately in clinical practice. The second aim was to confirm that the ratings of CDEs reflect pathophysiological events after TBI. Methods and results: First, a manual was developed for application of the CDEs, which was used to rate brain CTs (n = 100). An excellent agreement was found in combined kappas between RAs on admission and on 24-hour follow-up CTs (Iota = 0.803 and 0.787, respectively). Good IRR (kappa > 0.61) was shown for six CDEs on admissions and for seven CDEs on follow-up CTs. Low IRR (kappa < 0.4) was determined for five CDEs on admission and for four CDEs on follow-up CT. Combined IRR of each assistant with the neurologist were good on admission (Iota = 0.613 and 0.787) and excellent on follow-up CT (Iota = 0.906 and 0.977). Second, Principal Component Analysis (PCA) was applied to cluster the rated CDEs (n = 255) and five major components were found that explain 53% of the variance. Conclusions: CT CDEs are useful in clinical studies of TBI. Trained RAs can reliably collect variables. PCA identifies CDE clusters with clinical and biologic plausibility. Abbreviations: RA, research assistant; CT, Cranial Tomography; TBI, Traumatic Brain Injury; CDE, Common Data Elements; IRR, inter-rater reliability; PCA, Principal Component Analysis; GCS, Glasgow Coma Scale; R, rater; CI, confidence interval; CCC, Concordance correlation coefficient; IVH, Intraventricular haemorrhage; DCA, Discriminant Component analysis; SAH, Subarachnoid Haemorrhage.
Language	English
Publishing date	2017
Publishing country	England
Document type	Journal Article
ZDB-ID	639115-1
ISSN	1362-301X ; 0269-9052
ISSN (online)	1362-301X
ISSN	0269-9052
DOI	10.1080/02699052.2016.1225989
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