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Article ; Online: DIC-Like Syndrome Following Administration of ChAdOx1 nCov-19 Vaccination.

Casucci, Gerardo / Acanfora, Domenico

2021 Volume 13, Issue 6

Abstract: In recent weeks, adverse reactions have been reported after administration of Oxford-AstraZeneca chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19 (AZD1222), in particular thrombus formation, which has led several European Countries to discontinue ... ...

Abstract	In recent weeks, adverse reactions have been reported after administration of Oxford-AstraZeneca chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19 (AZD1222), in particular thrombus formation, which has led several European Countries to discontinue administration of this vaccine. On March 8, 2021, the European Medicines Agency Safety Committee did not confirm this probable association. We report the case of a patient who developed disseminated intravascular coagulation after the first dose of Oxford-Astra Zeneca vaccine, which resolved in a few days with the administration of dexamethasone and enoxaparin. This work demonstrates the safety of the Oxford-Astra Zeneca vaccine and that any development of side effects can be easily managed with a prompt diagnosis and in a short time with a few commonly used drugs.
MeSH term(s)	COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Clinical Laboratory Techniques ; Dexamethasone/therapeutic use ; Disseminated Intravascular Coagulation/diagnosis ; Disseminated Intravascular Coagulation/drug therapy ; Disseminated Intravascular Coagulation/etiology ; Enoxaparin/therapeutic use ; Female ; Humans ; Middle Aged ; SARS-CoV-2/immunology ; Vaccination
Chemical Substances	COVID-19 Vaccines ; Enoxaparin ; Dexamethasone (7S5I7G3JQL) ; ChAdOx1 COVID-19 vaccine (B5S3K2V0G8)
Language	English
Publishing date	2021-06-01
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13061046
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: DIC-Like Syndrome Following Administration of ChAdOx1 nCov-19 Vaccination

Casucci, Gerardo / Acanfora, Domenico

Viruses. 2021 June 01, v. 13, no. 6

2021

Abstract: In recent weeks, adverse reactions have been reported after administration of Oxford–AstraZeneca chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19 (AZD1222), in particular thrombus formation, which has led several European Countries to discontinue ... ...

Abstract	In recent weeks, adverse reactions have been reported after administration of Oxford–AstraZeneca chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19 (AZD1222), in particular thrombus formation, which has led several European Countries to discontinue administration of this vaccine. On March 8, 2021, the European Medicines Agency Safety Committee did not confirm this probable association. We report the case of a patient who developed disseminated intravascular coagulation after the first dose of Oxford-Astra Zeneca vaccine, which resolved in a few days with the administration of dexamethasone and enoxaparin. This work demonstrates the safety of the Oxford-Astra Zeneca vaccine and that any development of side effects can be easily managed with a prompt diagnosis and in a short time with a few commonly used drugs.
Keywords	Pan troglodytes ; dexamethasone ; disseminated intravascular coagulation ; enoxaparin ; patients ; thrombosis ; vaccination ; vaccines
Language	English
Dates of publication	2021-0601
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13061046
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The Cross-Talk between Age, Hypertension and Inflammation in COVID-19 Patients: Therapeutic Targets.

Casucci, Gerardo / Acanfora, Domenico / Incalzi, Raffaele Antonelli

Drugs & aging

2020 Volume 37, Issue 11, Page(s) 779–785

Abstract: This paper presents a brief overview of the complex interaction between age, hypertension, the renin-angiotensin-aldosterone system (RAAS), inflammation, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Coronavirus disease 2019 ( ...

Abstract	This paper presents a brief overview of the complex interaction between age, hypertension, the renin-angiotensin-aldosterone system (RAAS), inflammation, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Coronavirus disease 2019 (COVID-19) is more frequent and more severe in comorbid elderly patients, especially those with hypertension, diabetes, obesity, or cardiovascular diseases. There are concerns regarding the use of RAAS inhibitors in patients with COVID-19. Some physicians have considered the need for interrupting RAAS inhibition in order to reduce the possibility of SARS-CoV2 entering lung cells after binding to angiotensin-converting enzyme 2 (ACE2) receptors. We offer a different point of view in relation to the need for continuing to use RAAS inhibitors in patients with COVID-19. We focused our article on elderly patients because of the distinctive imbalance between the immune response, which is depressed, and the exacerbated inflammatory response, 'inflammaging', which makes the geriatric patient an appropriate candidate for therapeutic strategies aimed at modulating the inflammatory response. Indeed, COVID-19 is an inflammatory storm that starts and worsens during the course of the disease. During the COVID-19 pandemic, various therapeutic approaches have been tested, including antiviral drugs, interferon, anti-interleukins, hydroxychloroquine, anti-inflammatories, immunoglobulins from recovered patients, and heparins. Some of these therapeutic approaches did not prove to be beneficial, or even induced serious complications. Based on current evidence, in the early stages of the disease modulation of the inflammatory response through the inhibition of neprilysin and modulation of the RAAS could affect the course and outcome of COVID-19.
MeSH term(s)	Aged ; Angiotensin Receptor Antagonists/pharmacology ; Angiotensin-Converting Enzyme 2 ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Betacoronavirus/drug effects ; Betacoronavirus/physiology ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Coronavirus Infections/metabolism ; Coronavirus Infections/virology ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/immunology ; Humans ; Hypertension/drug therapy ; Immunologic Factors/pharmacology ; Inflammation/drug therapy ; Inflammation/immunology ; Neprilysin/antagonists & inhibitors ; Pandemics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/immunology ; Pneumonia, Viral/metabolism ; Pneumonia, Viral/virology ; Renin-Angiotensin System/drug effects ; SARS-CoV-2
Chemical Substances	Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Immunologic Factors ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Neprilysin (EC 3.4.24.11)
Keywords	covid19
Language	English
Publishing date	2020-10-21
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	1075770-3
ISSN	1179-1969 ; 1170-229X
ISSN (online)	1179-1969
ISSN	1170-229X
DOI	10.1007/s40266-020-00808-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Sacubitril/valsartan in COVID-19 patients: the need for trials.

Acanfora, Domenico / Ciccone, Marco Matteo / Scicchitano, Pietro / Acanfora, Chiara / Casucci, Gerardo

European heart journal. Cardiovascular pharmacotherapy

2020 Volume 6, Issue 4, Page(s) 253–254

MeSH term(s)	Aminobutyrates ; Angiotensin Receptor Antagonists ; Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Drug Combinations ; Humans ; Neprilysin ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2 ; Tetrazoles ; Valsartan
Chemical Substances	Aminobutyrates ; Angiotensin Receptor Antagonists ; Drug Combinations ; Tetrazoles ; Valsartan (80M03YXJ7I) ; Neprilysin (EC 3.4.24.11) ; sacubitril and valsartan sodium hydrate drug combination (WB8FT61183)
Keywords	covid19
Language	English
Publishing date	2020-05-05
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	2808613-2
ISSN	2055-6845 ; 2055-6837
ISSN (online)	2055-6845
ISSN	2055-6837
DOI	10.1093/ehjcvp/pvaa044
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Article ; Online: Neprilysin inhibitor-angiotensin II receptor blocker combination (sacubitril/valsartan): rationale for adoption in SARS-CoV-2 patients.

Acanfora, Domenico / Ciccone, Marco Matteo / Scicchitano, Pietro / Acanfora, Chiara / Casucci, Gerardo

European heart journal. Cardiovascular pharmacotherapy

2020 Volume 6, Issue 3, Page(s) 135–136

MeSH term(s)	Aminobutyrates ; Angiotensin Receptor Antagonists ; Animals ; Apolipoproteins ; Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Drug Combinations ; Humans ; Inflammation ; Mice ; Neprilysin ; Pandemics ; Plaque, Atherosclerotic ; Pneumonia, Viral ; SARS Virus ; SARS-CoV-2 ; Tetrazoles ; Valsartan
Chemical Substances	Aminobutyrates ; Angiotensin Receptor Antagonists ; Apolipoproteins ; Drug Combinations ; Tetrazoles ; Valsartan (80M03YXJ7I) ; Neprilysin (EC 3.4.24.11) ; sacubitril and valsartan sodium hydrate drug combination (WB8FT61183)
Keywords	covid19
Language	English
Publishing date	2020-04-13
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2808613-2
ISSN	2055-6845 ; 2055-6837
ISSN (online)	2055-6845
ISSN	2055-6837
DOI	10.1093/ehjcvp/pvaa028
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Article: A Systematic Review of the Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation Patients with Diabetes Using a Risk Index.

Acanfora, Domenico / Ciccone, Marco Matteo / Carlomagno, Valentina / Scicchitano, Pietro / Acanfora, Chiara / Bortone, Alessandro Santo / Uguccioni, Massimo / Casucci, Gerardo

Journal of clinical medicine

2021 Volume 10, Issue 13

Abstract: Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with ... ...

Abstract	Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI =Rate of EventsRate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.
Language	English
Publishing date	2021-06-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm10132924
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Article ; Online: The Cross-Talk between Thrombosis and Inflammatory Storm in Acute and Long-COVID-19: Therapeutic Targets and Clinical Cases.

Acanfora, Domenico / Acanfora, Chiara / Ciccone, Marco Matteo / Scicchitano, Pietro / Bortone, Alessandro Santo / Uguccioni, Massimo / Casucci, Gerardo

Viruses

2021 Volume 13, Issue 10

Abstract: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the ... ...

Abstract	Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants-and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state.
MeSH term(s)	Anticoagulants/therapeutic use ; Blood Coagulation/drug effects ; Blood Coagulation Disorders/drug therapy ; COVID-19/complications ; COVID-19/drug therapy ; Endothelial Cells ; Factor Xa Inhibitors/therapeutic use ; Heparin, Low-Molecular-Weight/therapeutic use ; Humans ; Inflammation/drug therapy ; Male ; Middle Aged ; SARS-CoV-2/pathogenicity ; Systemic Inflammatory Response Syndrome/drug therapy ; Systemic Inflammatory Response Syndrome/immunology ; Systemic Inflammatory Response Syndrome/physiopathology ; Thrombosis/drug therapy ; Thrombosis/immunology ; Thrombosis/physiopathology
Chemical Substances	Anticoagulants ; Factor Xa Inhibitors ; Heparin, Low-Molecular-Weight
Language	English
Publishing date	2021-09-23
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13101904
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Article: The Cross-Talk between Thrombosis and Inflammatory Storm in Acute and Long-COVID-19: Therapeutic Targets and Clinical Cases

Acanfora, Domenico / Acanfora, Chiara / Ciccone, Marco Matteo / Scicchitano, Pietro / Bortone, Alessandro Santo / Uguccioni, Massimo / Casucci, Gerardo

Viruses. 2021 Sept. 23, v. 13, no. 10

2021

Abstract	Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants—and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; adhesion ; anticoagulants ; chemokine CXCL4 ; coagulation ; death ; disseminated intravascular coagulation ; enoxaparin ; inflammation ; leukocytes ; patients ; pharmacodynamics ; risk ; storms ; therapeutics ; thrombin ; thrombosis
Language	English
Dates of publication	2021-0923
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13101904
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Neprilysin inhibitor-angiotensin II receptor blocker combination (sacubitril/valsartan)

Acanfora, Domenico / Ciccone, M. M. / Scicchitano, Pietro / Acanfora, / C., Casucci

rationale for adoption in SARS-CoV-2 patients

2020

Abstract: On 11 March 2020, the World Health Organization (WHO) declared the corona virus disease 2019 (COVID-19) outbreak as a ‘pandemic’.1 No valid therapy for COVID-19 is actually available. Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is ... ...

Abstract	On 11 March 2020, the World Health Organization (WHO) declared the corona virus disease 2019 (COVID-19) outbreak as a ‘pandemic’.1 No valid therapy for COVID-19 is actually available. Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is empirically treated with antivirals, antimalarics,tocilizumab, etc.2 Production of a vaccine for COVID-19 has been attempted, although approval needs time. We describe a possible, alternative approach for treating COVID-19. Lymphocyte count hasbeen associated with increased disease severityrisk.3 Patients who died from COVID-19 showed a significantly lower lymphocyte count than survivors, therefore this should be closelymonitored.3 Repletion of lymphocytes couldprobably have beneficial effects on recovery. A recent hypothesis suggests that the inhibition of the angiotensin 1 receptor (AT1R) may provide benefits to COVID-19 patients.4 Thishypothesis is based on the observation that the SARS-CoV-2 virus uses angiotensin-converting enzyme 2 (ACE2) as a receptor to bind thevirus to the bronchial cell membrane. Theenzymes ACE and ACE2 belong to the samepeptidase family but have two very different physiological functions. ACE cleaves angiotensin I to generate angiotensin II (Ang II), whichbinds to and activates AT1R, and thus promoting vasoconstriction. ACE2 cleaves Ang II and generates angiotensin 1-7, a powerful vasodilator acting through Mas receptors. AT1R antagonists are widely used in hypertensive patientsbut they increase the ACE2 cardiac expressionin rats5 and the urinary concentration of ACE2.6 It has been demonstrated that the binding ofvirus to ACE2 leads to ACE2 down-regulation.
Keywords	RAAS ; renin–angiotensin–aldosterone system ; SacVal ; sacubitril/valsartan ; covid19
Subject code	610
Language	English
Publishing country	it
Document type	Article ; Online
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Article ; Online: Biomarkers in cardiac rehabilitation: can they be applied in clinical practice?

Acanfora, Domenico / Fuschillo, Salvatore / Provitera, Vincenzo / Motta, Andrea / Maniscalco, Mauro

Biomarkers in medicine

2019 Volume 13, Issue 9, Page(s) 701–705

MeSH term(s)	Biomarkers/analysis ; Cardiac Rehabilitation/methods ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/therapy ; Exercise Therapy ; Humans ; Precision Medicine
Chemical Substances	Biomarkers
Language	English
Publishing date	2019-06-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2481014-9
ISSN	1752-0371 ; 1752-0363
ISSN (online)	1752-0371
ISSN	1752-0363
DOI	10.2217/bmm-2019-0185
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