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  1. Article ; Online: Genetic testing for familial hypercholesterolaemia: utility beyond diagnosis.

    Bigossi, Margherita / Siddiqui, Moneeza K

    European journal of preventive cardiology

    2022  Volume 31, Issue 7, Page(s) e59–e61

    MeSH term(s) Humans ; Hyperlipoproteinemia Type II/genetics ; Hyperlipoproteinemia Type II/diagnosis ; Genetic Testing/methods ; Genetic Predisposition to Disease ; Predictive Value of Tests ; Phenotype ; Mutation
    Language English
    Publishing date 2022-11-25
    Publishing country England
    Document type Journal Article ; Editorial ; Comment
    ZDB-ID 2626011-6
    ISSN 2047-4881 ; 2047-4873
    ISSN (online) 2047-4881
    ISSN 2047-4873
    DOI 10.1093/eurjpc/zwac258
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4686: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
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  2. Article: The cholesterol-lowering effect of statins is modified by

    Tornio, Aleksi / Bigossi, Margherita / Siddiqui, Moneeza K / Kennedy, Gwen / Melhem, Ala'a / Chourasia, Mehul K / Maroteau, Cyrielle / Pola, Roberto / Chasman, Daniel I / Doney, Alexander S F / Palmer, Colin N A

    Frontiers in pharmacology

    2023  Volume 14, Page(s) 1090010

    Abstract: Background/Aims: ...

    Abstract Background/Aims:
    Language English
    Publishing date 2023-03-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2023.1090010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A gene risk score using missense variants in SLCO1B1 is associated with earlier onset statin intolerance.

    Bigossi, Margherita / Maroteau, Cyrielle / Dawed, Adem Y / Taylor, Alasdair / Srinivasan, Sundararajan / Melhem, Alaa' Lufti / Pearson, Ewan R / Pola, Roberto / Palmer, Colin N A / Siddiqui, Moneeza K

    European heart journal. Cardiovascular pharmacotherapy

    2023  Volume 9, Issue 6, Page(s) 536–545

    Abstract: Background and aims: The efficacy of statin therapy is hindered by intolerance to the therapy, leading to discontinuation. Variants in SLCO1B1, which encodes the hepatic transporter OATB1B1, influence statin pharmacokinetics, resulting in altered plasma ...

    Abstract Background and aims: The efficacy of statin therapy is hindered by intolerance to the therapy, leading to discontinuation. Variants in SLCO1B1, which encodes the hepatic transporter OATB1B1, influence statin pharmacokinetics, resulting in altered plasma concentrations of the drug and its metabolites. Current pharmacogenetic guidelines require sequencing of the SLCO1B1 gene, which is more expensive and less accessible than genotyping. In this study, we aimed to develop an easy, clinically implementable functional gene risk score (GRS) of common variants in SLCO1B1 to identify patients at risk of statin intolerance.
    Methods and results: A GRS was developed from four common variants in SLCO1B1. In statin users from Tayside, Scotland, UK, those with a high-risk GRS had increased odds across three phenotypes of statin intolerance [general statin intolerance (GSI): ORGSI 2.42; 95% confidence interval (CI): 1.29-4.31, P = 0.003; statin-related myopathy: ORSRM 2.51; 95% CI: 1.28-4.53, P = 0.004; statin-related suspected rhabdomyolysis: ORSRSR 2.85; 95% CI: 1.03-6.65, P = 0.02]. In contrast, using the Val174Ala genotype alone or the recommended OATP1B1 functional phenotypes produced weaker and less reliable results. A meta-analysis with results from adjudicated cases of statin-induced myopathy in the PREDICTION-ADR Consortium confirmed these findings (ORVal174Ala 1.99; 95% CI: 1.01-3.95, P = 0.048; ORGRS 1.76; 95% CI: 1.16-2.69, P = 0.008). For those requiring high-dose statin therapy, the high-risk GRS was more consistently associated with the time to onset of statin intolerance amongst the three phenotypes compared with Val174Ala (GSI: HRVal174Ala 2.49; 95% CI: 1.09-5.68, P = 0.03; HRGRS 2.44; 95% CI: 1.46-4.08, P < 0.001). Finally, sequence kernel association testing confirmed that rare variants in SLCO1B1 are associated with the risk of intolerance (P = 0.02).
    Conclusion: We provide evidence that a GRS based on four common SLCO1B1 variants provides an easily implemented genetic tool that is more reliable than the current recommended practice in estimating the risk and predicting early-onset statin intolerance.
    MeSH term(s) Humans ; Genotype ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Liver-Specific Organic Anion Transporter 1/genetics ; Muscular Diseases/chemically induced ; Muscular Diseases/diagnosis ; Muscular Diseases/genetics ; Phenotype ; Risk Factors
    Chemical Substances Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Liver-Specific Organic Anion Transporter 1 ; SLCO1B1 protein, human
    Language English
    Publishing date 2023-05-28
    Publishing country England
    Document type Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2808613-2
    ISSN 2055-6845 ; 2055-6837
    ISSN (online) 2055-6845
    ISSN 2055-6837
    DOI 10.1093/ehjcvp/pvad040
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Hedgehog Signaling Pathway in Ischemic Tissues.

    Giarretta, Igor / Gaetani, Eleonora / Bigossi, Margherita / Tondi, Paolo / Asahara, Takayuki / Pola, Roberto

    International journal of molecular sciences

    2019  Volume 20, Issue 21

    Abstract: Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a ...

    Abstract Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in the ischemic condition is also presented.
    MeSH term(s) Animals ; Brain/metabolism ; Hedgehog Proteins/metabolism ; Humans ; Ischemia/metabolism ; Ischemia/pathology ; Muscle, Skeletal/metabolism ; Myocardium/metabolism ; Signal Transduction
    Chemical Substances Hedgehog Proteins
    Language English
    Publishing date 2019-10-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms20215270
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: A Single Center Retrospective Cohort Study Comparing Different Anticoagulants for the Treatment of Catheter-Related Thrombosis of the Upper Extremities in Women With Gynecologic and Breast Cancer.

    Porfidia, Angelo / Cammà, Giulia / Coletta, Nicola / Bigossi, Margherita / Giarretta, Igor / Lupascu, Andrea / Scaletta, Giuseppe / Porceddu, Enrica / Tondi, Paolo / Scambia, Giovanni / Ferrandina, Gabriella / Pola, Roberto

    Frontiers in cardiovascular medicine

    2022  Volume 9, Page(s) 880698

    Abstract: Background: Catheter-related thrombosis (CRT) of the upper extremities is a frequent complication among cancer patients that carry a central venous catheter (CVC) and may lead to pulmonary embolism (PE) and loss of CVC function. Despite its clinical ... ...

    Abstract Background: Catheter-related thrombosis (CRT) of the upper extremities is a frequent complication among cancer patients that carry a central venous catheter (CVC) and may lead to pulmonary embolism (PE) and loss of CVC function. Despite its clinical impact, no anticoagulant treatment scheme has been rigorously evaluated in these patients. In addition, there is no proven evidence that direct oral anticoagulants (DOACs) are efficacious and safe in this setting because cancer patients with CRT of the upper extremities were not included in the clinical trials that led to the approval of DOACs for the treatment of cancer-associated venous thromboembolism (VTE).
    Methods: We performed a single center retrospective cohort study on women with gynecologic or breast cancer treated with either low-molecular-weight heparin, fondaparinux, or DOACs for CRT of the upper extremities. Only patients who received anticoagulation at the proper therapeutic dose and for at least 3 months were included in the analysis. Effectiveness was evaluated in terms of preservation of line function, residual thrombosis, and recurrence of VTE (including PE). Safety was evaluated in terms of death, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB).
    Results: We identified 74 women who fulfilled the criteria to be included in the analysis. Of these, 31 (41.9%) had been treated with fondaparinux, 21 (28.4%) with enoxaparin, and 22 (29.7%) with the DOAC edoxaban. We found no differences between patients treated with the three different therapeutic approaches, in terms of preservation of line function, incidence of residual thrombosis, and VTE recurrence (including PE). Safety was similar as well, with no MBs recorded in any treatment group.
    Conclusion: These results, although retrospective and based on a relatively small sample size, indicate that, in women with gynecologic or breast cancer, CRT of the upper extremities may be treated with similar effectiveness and safety with fondaparinux, enoxaparin, and edoxaban. Further studies are needed to substantiate these findings.
    Language English
    Publishing date 2022-06-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2781496-8
    ISSN 2297-055X
    ISSN 2297-055X
    DOI 10.3389/fcvm.2022.880698
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Common Statin Intolerance Variants in

    Melhem, Alaa' Lutfi / Chourasia, Mehul Kumar / Bigossi, Margherita / Maroteau, Cyrielle / Taylor, Alasdair / Pola, Roberto / Dawed, Adem Y / Tornio, Aleksi / Palmer, Colin N A / Siddiqui, Moneeza K

    Frontiers in genetics

    2021  Volume 12, Page(s) 713181

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2021-10-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2021.713181
    Database MEDical Literature Analysis and Retrieval System OnLINE

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