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  1. Article: Increased Frataxin Expression Induced in Friedreich Ataxia Cells by Platinum TALE-VP64s or Platinum TALE-SunTag.

    Cherif, Khadija / Gérard, Catherine / Rousseau, Joël / Ouellet, Dominique L / Chapdelaine, Pierre / Tremblay, Jacques P

    Molecular therapy. Nucleic acids

    2018  Volume 12, Page(s) 19–32

    Abstract: Frataxin gene (FXN) expression is reduced in Friedreich's ataxia patients due to an increase in the number of GAA trinucleotides in intron 1. The frataxin protein, encoded by that gene, plays an important role in mitochondria's iron metabolism. Platinum ... ...

    Abstract Frataxin gene (FXN) expression is reduced in Friedreich's ataxia patients due to an increase in the number of GAA trinucleotides in intron 1. The frataxin protein, encoded by that gene, plays an important role in mitochondria's iron metabolism. Platinum TALE (plTALE) proteins targeting the regulatory region of the FXN gene, fused with a transcriptional activator (TA) such as VP64 or P300, were used to increase the expression of that gene. Many effectors, plTALE
    Language English
    Publishing date 2018-04-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2662631-7
    ISSN 2162-2531
    ISSN 2162-2531
    DOI 10.1016/j.omtn.2018.04.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: From gRNA Identification to the Restoration of Dystrophin Expression: A Dystrophin Gene Correction Strategy for Duchenne Muscular Dystrophy Mutations Using the CRISPR-Induced Deletion Method.

    Duchêne, Benjamin / Iyombe-Engembe, Jean-Paul / Rousseau, Joël / Tremblay, Jacques P / Ouellet, Dominique L

    Methods in molecular biology (Clifton, N.J.)

    2017  Volume 1687, Page(s) 267–283

    Abstract: The discovery of the CRISPR-Cas9 system raises hope for the treatment of many genetic disorders. We describe here an approach based on the use of a pair of single guide RNAs to form a hybrid exon that does not only restore the dystrophin gene reading ... ...

    Abstract The discovery of the CRISPR-Cas9 system raises hope for the treatment of many genetic disorders. We describe here an approach based on the use of a pair of single guide RNAs to form a hybrid exon that does not only restore the dystrophin gene reading frame but also results in the production of a dystrophin protein with an adequate structure of the central rod-domain, with a correct spectrin-like repeat. The therapeutic approach described here involved DMD patient cells having a deletion of exons 51-53 of the DMD gene.
    MeSH term(s) CRISPR-Cas Systems/genetics ; Dystrophin/genetics ; Exons ; Genetic Therapy/methods ; Humans ; Muscular Dystrophy, Duchenne/genetics ; Muscular Dystrophy, Duchenne/pathology ; Muscular Dystrophy, Duchenne/therapy ; Mutation ; RNA, Guide, CRISPR-Cas Systems/genetics
    Chemical Substances Dystrophin ; RNA, Guide, CRISPR-Cas Systems
    Language English
    Publishing date 2017-10-09
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-7374-3_19
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  3. Article ; Online: Current knowledge of MicroRNAs and noncoding RNAs in virus-infected cells.

    Ouellet, Dominique L / Provost, Patrick

    Methods in molecular biology (Clifton, N.J.)

    2010  Volume 623, Page(s) 35–65

    Abstract: Within the past few years, microRNAs (miRNAs) and other noncoding RNAs (ncRNAs) have emerged as elements with critically high importance in posttranscriptional control of cellular and, more recently, viral processes. Endogenously produced by a component ... ...

    Abstract Within the past few years, microRNAs (miRNAs) and other noncoding RNAs (ncRNAs) have emerged as elements with critically high importance in posttranscriptional control of cellular and, more recently, viral processes. Endogenously produced by a component of the miRNA-guided RNA silencing machinery known as Dicer, miRNAs are known to control messenger RNA (mRNA) translation through recognition of specific binding sites usually located in their 3' untranslated region. Recent evidences indicate that the host miRNA pathway may represent an adapted antiviral defense mechanism that can act either by direct miRNA-mediated modulation of viral gene expression or through recognition and inactivation of structured viral RNA species by the protein components of the RNA silencing machinery such as Dicer. This latter process, however, is a double-edge sword, as it may yield viral miRNAs exerting gene regulatory properties on both host and viral mRNAs. Our knowledge of the interaction between viruses and host RNA silencing machineries, and how this influences the course of infection, is becoming increasingly complex. This chapter aims to summarize our current knowledge about viral miRNAs/ncRNAs and their targets, as well as cellular miRNAs that are modulated by viruses upon infection.
    MeSH term(s) Base Sequence ; DNA Viruses/genetics ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Molecular Sequence Data ; RNA Interference ; RNA, Untranslated/genetics ; RNA, Untranslated/metabolism ; Retroviridae/genetics
    Chemical Substances MicroRNAs ; RNA, Untranslated
    Language English
    Publishing date 2010-03-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-60761-588-0_3
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  4. Article ; Online: Gene Editing for Duchenne Muscular Dystrophy Using the CRISPR/Cas9 Technology: The Importance of Fine-tuning the Approach.

    Tremblay, Jacques P / Iyombe-Engembe, Jean-Paul / Duchêne, Benjamin / Ouellet, Dominique L

    Molecular therapy : the journal of the American Society of Gene Therapy

    2016  Volume 24, Issue 11, Page(s) 1888–1889

    MeSH term(s) Animals ; CRISPR-Cas Systems ; Clustered Regularly Interspaced Short Palindromic Repeats ; Dystrophin ; Gene Editing ; Humans ; Mice ; Mice, Inbred mdx ; Muscular Dystrophy, Duchenne/genetics ; Muscular Dystrophy, Duchenne/therapy
    Chemical Substances Dystrophin
    Language English
    Publishing date 2016-11-11
    Publishing country United States
    Document type Letter
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1038/mt.2016.191
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5640: Show issues Location:
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  5. Article ; Online: Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry.

    Arizala, Jerlisa Ann C / Chomchan, Pritsana / Li, Haitang / Moore, Roger / Ge, Helen / Ouellet, Dominique L / Rossi, John J

    Journal of visualized experiments : JoVE

    2019  , Issue 148

    Abstract: The HIV-1 infectious cycle requires viral protein interactions with host factors to facilitate viral replication, packaging, and release. The infectious cycle further requires the formation of viral/host protein complexes with HIV-1 RNA to regulate the ... ...

    Abstract The HIV-1 infectious cycle requires viral protein interactions with host factors to facilitate viral replication, packaging, and release. The infectious cycle further requires the formation of viral/host protein complexes with HIV-1 RNA to regulate the splicing and enable nucleocytoplasmic transport. The HIV-1 Rev protein accomplishes the nuclear export of HIV-1 mRNAs through multimerization with intronic cis-acting targets - the Rev response element (RRE). A nucleolar localization signal (NoLS) exists within the COOH-terminus of the Rev arginine-rich motif (ARM), allowing the accumulation of Rev/RRE complexes in the nucleolus. Nucleolar factors are speculated to support the HIV-1 infectious cycle through various other functions in addition to mediating mRNA-independent nuclear export and splicing. We describe an immunoprecipitation method of wild-type (WT) Rev in comparison to Rev nucleolar mutations (deletion and single-point Rev-NoLS mutations) in the presence of HIV-1 replication for mass spectrometry. Nucleolar factors implicated in the nucleocytoplasmic transport (nucleophosmin B23 and nucleolin C23), as well as cellular splicing factors, lose interaction with Rev in the presence of Rev-NoLS mutations. Various other nucleolar factors, such as snoRNA C/D box 58, are identified to lose interaction with Rev mutations, yet their function in the HIV-1 replication cycle remain unknown. The results presented here demonstrate the use of this approach for the identification of viral/host nucleolar factors that maintain the HIV-1 infectious cycle. The concepts used in this approach are applicable to other viral and disease models requiring the characterization of understudied pathways.
    MeSH term(s) Cell Nucleolus/metabolism ; HIV-1/genetics ; HIV-1/physiology ; HeLa Cells ; Humans ; Immunoprecipitation ; Mass Spectrometry ; Mutation/genetics ; Protein Sorting Signals/genetics ; RNA, Viral/genetics ; Virus Replication/physiology ; rev Gene Products, Human Immunodeficiency Virus/metabolism
    Chemical Substances Protein Sorting Signals ; RNA, Viral ; rev Gene Products, Human Immunodeficiency Virus ; rev protein, Human Immunodeficiency Virus-1
    Language English
    Publishing date 2019-06-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Video-Audio Media
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/59329
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  6. Article: Identification of nucleolar factors during hiv-1 replication through rev immunoprecipitation and mass spectrometry

    Arizala, Jerlisa Ann C / Chomchan, Pritsana / Ge, Helen / Li, Haitang / Moore, Roger / Ouellet, Dominique L / Rossi, John J

    Journal of visualized experiments. 2019 June 26, , no. 148

    2019  

    Abstract: The HIV-1 infectious cycle requires viral protein interactions with host factors to facilitate viral replication, packaging, and release. The infectious cycle further requires the formation of viral/host protein complexes with HIV-1 RNA to regulate the ... ...

    Abstract The HIV-1 infectious cycle requires viral protein interactions with host factors to facilitate viral replication, packaging, and release. The infectious cycle further requires the formation of viral/host protein complexes with HIV-1 RNA to regulate the splicing and enable nucleocytoplasmic transport. The HIV-1 Rev protein accomplishes the nuclear export of HIV-1 mRNAs through multimerization with intronic cis-acting targets - the Rev response element (RRE). A nucleolar localization signal (NoLS) exists within the COOH-terminus of the Rev arginine-rich motif (ARM), allowing the accumulation of Rev/RRE complexes in the nucleolus. Nucleolar factors are speculated to support the HIV-1 infectious cycle through various other functions in addition to mediating mRNA-independent nuclear export and splicing. We describe an immunoprecipitation method of wild-type (WT) Rev in comparison to Rev nucleolar mutations (deletion and single-point Rev-NoLS mutations) in the presence of HIV-1 replication for mass spectrometry. Nucleolar factors implicated in the nucleocytoplasmic transport (nucleophosmin B23 and nucleolin C23), as well as cellular splicing factors, lose interaction with Rev in the presence of Rev-NoLS mutations. Various other nucleolar factors, such as snoRNA C/D box 58, are identified to lose interaction with Rev mutations, yet their function in the HIV-1 replication cycle remain unknown. The results presented here demonstrate the use of this approach for the identification of viral/host nucleolar factors that maintain the HIV-1 infectious cycle. The concepts used in this approach are applicable to other viral and disease models requiring the characterization of understudied pathways.
    Keywords cell nucleolus ; disease models ; Human immunodeficiency virus 1 ; mass spectrometry ; messenger RNA ; mutation ; nucleocytoplasmic transport ; precipitin tests ; virus replication
    Language English
    Dates of publication 2019-0626
    Size p. e59329.
    Publishing place Journal of Visualized Experiments
    Document type Article
    ISSN 1940-087X
    DOI 10.3791/59329
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Nucleolar Localization of HIV-1 Rev Is Required, Yet Insufficient for Production of Infectious Viral Particles.

    Arizala, Jerlisa Ann C / Takahashi, Mayumi / Burnett, John C / Ouellet, Dominique L / Li, Haitang / Rossi, John J

    AIDS research and human retroviruses

    2018  Volume 34, Issue 11, Page(s) 961–981

    Abstract: Combination antiretroviral therapy fails in complete suppression of HIV-1 due to drug resistance and persistent latency. Novel therapeutic intervention requires knowledge of intracellular pathways responsible for viral replication, specifically those ... ...

    Abstract Combination antiretroviral therapy fails in complete suppression of HIV-1 due to drug resistance and persistent latency. Novel therapeutic intervention requires knowledge of intracellular pathways responsible for viral replication, specifically those untargeted by antiretroviral drugs. An understudied phenomenon is the nucleolar localization of Rev phosphoprotein, which completes nucleocytoplasmic transport of unspliced/partially spliced HIV mRNA through multimerization with intronic cis-acting targets-the Rev-response element (RRE). Rev contains a nucleolar localization signal (NoLS) comprising the COOH terminus of the arginine-rich motif for accumulation within nucleoli-speculated as the interaction ground for Rev with cellular proteins mediating mRNA-independent nuclear export and splicing. Functionality of Rev nucleolar access during HIV-1 production and infection was investigated in the context of deletion and single-point mutations within Rev-NoLS. Mutations induced upon Rev-NoLS are hypothesized to inactivate the HIV-1 infectious cycle. HIV-1
    MeSH term(s) Amino Acid Motifs/genetics ; Cell Line ; Cell Nucleus/metabolism ; HIV Infections/virology ; HIV-1/genetics ; HIV-1/metabolism ; HIV-1/pathogenicity ; HIV-1/physiology ; Humans ; Mutation ; Nuclear Localization Signals/chemistry ; Nuclear Localization Signals/genetics ; RNA Splicing ; RNA, Viral/genetics ; RNA, Viral/metabolism ; Virion/metabolism ; Virus Integration ; Virus Replication ; rev Gene Products, Human Immunodeficiency Virus/genetics ; rev Gene Products, Human Immunodeficiency Virus/metabolism
    Chemical Substances Nuclear Localization Signals ; RNA, Viral ; rev Gene Products, Human Immunodeficiency Virus
    Keywords covid19
    Language English
    Publishing date 2018-07-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639130-8
    ISSN 1931-8405 ; 0889-2229
    ISSN (online) 1931-8405
    ISSN 0889-2229
    DOI 10.1089/AID.2017.0306
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    Zs.A 1928: Show issues Location:
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  8. Article ; Online: Gastric insufflation during cardiopulmonary resuscitation: A study in human cadavers.

    Savary, Dominique / Drennan, Ian R / Badat, Bilal / Grieco, Domenico L / Piraino, Thomas / Lesimple, Arnaud / Charbonney, Emmanuel / Fritz, Caroline / Delisle, Stephane / Ouellet, Paul / Mercat, Alain / Bronchti, Gilles / Brochard, Laurent / Richard, Jean-Christophe

    Resuscitation

    2019  Volume 146, Page(s) 111–117

    Abstract: ... 1.0 [0.8-4.1] vs. 5.9 [4.0-5.6] L; p < 0.05) while expired minute ventilation was slightly higher ... during continuous than interrupted CC (1.9 [1.4-2.8] vs. 1.6 [1.1-2.7] L/min; P < 0.05). In 2 additional ...

    Abstract Introduction: Bag-valve-mask ventilation is the first-line ventilation method during cardiopulmonary resuscitation (CPR). Risks include excessive volume delivery and gastric insufflation, the latter increasing the risk of pneumonia. The efficacy of ventilation can also be reduced by airway closure. We hypothesized that continuous chest compression (CC) could limit the risk of gastric insufflation compared to the recommended 30:2 interrupted CC strategy. This experimental study was performed in human "Thiel" cadavers to assess the respective impact of discontinuous vs. continuous chest compressions on gastric insufflation and ventilation during CPR.
    Methods: The 30:2 interrupted CC technique was compared to continuous CC in 5 non-intubated cadavers over a 6 min-period. Flow and Airway Pressure were measured at the mask. A percutaneous gastrostomy allowed measuring the cumulative gastric insufflated volume. Two additional cadavers were equipped with esophageal and gastric catheters instead of the gastrostomy.
    Results: For the 7 cadavers studied (4 women) median age of death was 79 [74-84] years. After 6 min of CPR, the cumulative gastric insufflation measured in 5 cadavers was markedly reduced during continuous CC compared to the interrupted CC strategy: (1.0 [0.8-4.1] vs. 5.9 [4.0-5.6] L; p < 0.05) while expired minute ventilation was slightly higher during continuous than interrupted CC (1.9 [1.4-2.8] vs. 1.6 [1.1-2.7] L/min; P < 0.05). In 2 additional cadavers, the progressive rise in baseline gastric pressure was lower during continuous CC than interrupted CC (1 and 2 cmH
    Conclusion: Continuous CC significantly reduces the volume of gas insufflated in the stomach compared to the recommended 30:2 interrupted CC strategy. Ventilation actually delivered to the lung is also slightly increased by the strategy.
    MeSH term(s) Aged ; Cadaver ; Cardiopulmonary Resuscitation/methods ; Female ; Gastric Dilatation/diagnosis ; Gastric Dilatation/etiology ; Gastric Dilatation/prevention & control ; Heart Arrest/therapy ; Heart Massage/methods ; Humans ; Male ; Noninvasive Ventilation/adverse effects ; Noninvasive Ventilation/methods ; Pulmonary Ventilation ; Research Design
    Language English
    Publishing date 2019-11-12
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 189901-6
    ISSN 1873-1570 ; 0300-9572
    ISSN (online) 1873-1570
    ISSN 0300-9572
    DOI 10.1016/j.resuscitation.2019.10.014
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    Zs.A 1048: Show issues Location:
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  9. Article ; Online: RNAi and small interfering RNAs in human disease therapeutic applications.

    Lares, Monica R / Rossi, John J / Ouellet, Dominique L

    Trends in biotechnology

    2010  Volume 28, Issue 11, Page(s) 570–579

    Abstract: Small interfering RNAs (siRNAs) have been shown to effectively downregulate gene expression in human cells, giving them potential to eradicate disease. Prospects for clinical applications are discussed in this review, along with an overview of recent ... ...

    Abstract Small interfering RNAs (siRNAs) have been shown to effectively downregulate gene expression in human cells, giving them potential to eradicate disease. Prospects for clinical applications are discussed in this review, along with an overview of recent history and our current understanding of siRNAs used for therapeutic application in human diseases, such as cancer and viral infections. Over recent years, progress has been made in lipids, ligands, nanoparticles, polymers and viral vectors as delivery agents and for gene-based expression of siRNA to enhance the efficacy and specificity of these methods while at the same time reducing toxicity. It has become apparent that given the recent advances in chemistry and delivery, RNAi will soon prove to be an important and widely used therapeutic modality.
    MeSH term(s) Biological Products/genetics ; Biological Products/pharmacokinetics ; Biological Products/therapeutic use ; Gene Knockdown Techniques ; Genetic Therapy/methods ; Humans ; RNA, Small Interfering/genetics ; RNA, Small Interfering/pharmacokinetics ; RNA, Small Interfering/therapeutic use
    Chemical Substances Biological Products ; RNA, Small Interfering
    Language English
    Publishing date 2010-09-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 47474-5
    ISSN 1879-3096 ; 0167-7799
    ISSN (online) 1879-3096
    ISSN 0167-7799
    DOI 10.1016/j.tibtech.2010.07.009
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    Zs.A 2750: Show issues Location:
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  10. Article: Retrospective analysis of the predictive factors of renal function loss after uninephrectomy in patients with chronic kidney disease G3 to G5.

    Dupuis, Dominique / Ouellet, Georges / Roy, Louise

    Canadian journal of kidney health and disease

    2015  Volume 2, Page(s) 52

    Abstract: Background: The rapid increase in glomerular filtration rate in a normal contralateral kidney after uninephrectomy is well known in living kidney donors but much less well described in chronic kidney disease (CKD). The purpose of this study is to ... ...

    Abstract Background: The rapid increase in glomerular filtration rate in a normal contralateral kidney after uninephrectomy is well known in living kidney donors but much less well described in chronic kidney disease (CKD). The purpose of this study is to determine the magnitude of this initial compensatory capacity in (CKD) groups 3 to 5 (G3 to G5) patients undergoing uninephrectomy and the clinical factors predicting it. This is a retrospective study of all cases (142) of uninephrectomy in patients with estimated glomerular filtration rate (eGFR; with MDRD equation) <60 ml/min/1.73 m(2), between 2003 and 2010, in two University of Montreal-affiliated teaching hospitals.
    Methods: Baseline eGFR, patients' comorbidities, and surgical characteristics and complications were noted. The change of eGFR after nephrectomy was evaluated; moreover, the expected post-op eGFR, i.e. without compensation by the contralateral kidney following surgery, was estimated in a sub-group of patients who had a preoperative renal scintigraphy and compared to the actual eGFR at hospital discharge.
    Results: The mean change of eGFR from baseline to hospital discharge was -5 ± 12 ml/min/1.73 m(2) (-11 %; 95 % CI -16 to -6 %; P < 0.001). In univariate and multivariate analyses, baseline eGFR did not influence significantly these results. However, in the multivariate model, radical nephrectomy vs. partial nephrectomy and preoperative hypertension predicted a worse renal outcome. In the sub-group of patients with preoperative renal scintigraphy, the actual eGFR at hospital discharge was also higher than expected from the renal split function (13 ml/min/1.73 m(2); 95 % CI 10 to 16; P < 0.001).
    Conclusions: After uninephrectomy, the contralateral kidney in patients with CKD G3 to G5 still has a clinically significant initial compensatory capacity. The compensation is statistically smaller if the patient had hypertension or a radical uninephrectomy. This initial compensation is rapid and most probably haemodynamic (hyperfiltration). However, most of the included patients had a CKD G3, limiting the strength of the conclusion for the G4 toG5 patients; the length of observation covers the early postoperative period, i.e. less than 2 weeks, in more than half of the cohort.
    Language English
    Publishing date 2015-12-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 2765462-X
    ISSN 2054-3581
    ISSN 2054-3581
    DOI 10.1186/s40697-015-0089-y
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