Abstract:
BACKGROUND:Local anesthetics (LA) work by blocking sodium conductance through voltage-gated sodium channels. Complete local anesthetic resistance is infrequent, and the cause is unknown. Genetic variation in sodium channels is a potential mechanism for local anesthetic resistance. A patient with a history of inadequate loss of sensation following LA administration underwent an ultrasound-guided brachial plexus nerve block with a complete failure of the block. We hypothesized that LA resistance is due to a variant form of voltage-gated sodium channel. METHODS:Whole-Exome Sequencing. The patient and her immediate family provided consent for exome sequencing, and they were screened with a questionnaire to identify family members with a history of LA resistance. Exome sequencing results for four individuals were referenced to the 1000 Genomes Project and the NHLBI ESP to identify variants associated with local anesthetic resistance present in less than 1% of the general population and located in functional regions of the genome. RESULTS:Exome sequencing of the four family members identified one genetic variant in the voltage-gated sodium channel shared by the three individuals with LA resistance but not present in the unaffected family member. Specifically, we noted the A572D mutation in the SCN5A gene encoding for Nav1.5. CONCLUSIONS:We identified a genetic variant that is associated with LA resistance in the gene encoding for Nav1.5. We also demonstrate that Nav1.5 is present in human peripheral nerves to support the plausibility that an abnormal form of the Nav1.5 protein could be responsible for the observed local anesthetic resistance.
journal_name
Minerva Anestesioljournal_title
Minerva anestesiologicaauthors
Clendenen N,Cannon AD,Porter S,Robards CB,Parker AS,Clendenen SRsubject
Has Abstractpub_date
2016-10-01 00:00:00pages
1089-1097issue
10eissn
0375-9393issn
1827-1596pii
R02Y9999N00A16053101journal_volume
82pub_type
杂志文章abstract::The case of a woman of 27 affected by the Prader-Willi syndrome who underwent general anaesthesia for dental surgery is reported. The patient presented severe mental retardation, small stature, moderate muscular hypotonia, hyperphagia, obesity, and diabetes mellitus. Premedication consisted of diazepam and atropine; a...
journal_title:Minerva anestesiologica
pub_type: 杂志文章
doi:
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journal_title:Minerva anestesiologica
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journal_title:Minerva anestesiologica
pub_type: 杂志文章
doi:
更新日期:1990-12-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 杂志文章
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更新日期:1997-05-01 00:00:00
abstract:: ...
journal_title:Minerva anestesiologica
pub_type: 信件
doi:10.23736/S0375-9393.19.13663-2
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journal_title:Minerva anestesiologica
pub_type: 杂志文章
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journal_title:Minerva anestesiologica
pub_type: 历史文章,杂志文章,评审
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更新日期:2000-10-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 杂志文章,评审
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更新日期:2007-06-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 杂志文章,评审
doi:
更新日期:2002-05-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00
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pub_type: 杂志文章,多中心研究
doi:
更新日期:2013-12-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 杂志文章,随机对照试验
doi:10.23736/S0375-9393.18.12291-7
更新日期:2018-11-01 00:00:00
abstract::Pulmonary gas exchange is regularly impaired during general anaesthesia with mechanical ventilation. This results in decreased oxygenation of blood. Major causes are collapse of lung tissue (atelectasis) and airway closure. Collapsed lung tissue is present in 90% of all subjects, both during spontaneous breathing and ...
journal_title:Minerva anestesiologica
pub_type: 杂志文章,评审
doi:
更新日期:2002-05-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 杂志文章
doi:10.23736/S0375-9393.20.14138-5
更新日期:2020-06-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:2003-03-01 00:00:00
abstract::The successful management of 2 cases of rare myopathies, who underwent hemithyroidectomy, is here reported. Anaesthesia was induced with TPS and fentanyl, and maintained with isoflurane. Neuromuscular blockade was achieved by atracurium; neuromuscular monitoring by Neurostar-Medeleck was performed. This intraoperative...
journal_title:Minerva anestesiologica
pub_type: 杂志文章
doi:
更新日期:1991-07-01 00:00:00
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pub_type: 杂志文章,随机对照试验
doi:
更新日期:2010-09-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 杂志文章,随机对照试验
doi:
更新日期:2009-12-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 杂志文章
doi:
更新日期:1981-08-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 杂志文章,评审
doi:
更新日期:1998-04-01 00:00:00
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pub_type: 杂志文章,评审
doi:
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journal_title:Minerva anestesiologica
pub_type: 杂志文章,随机对照试验
doi:
更新日期:2015-04-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1998-07-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1995-09-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 杂志文章,评审
doi:
更新日期:1999-05-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 杂志文章
doi:
更新日期:2012-02-01 00:00:00
abstract:BACKGROUND:Labile iron is important in the pathogenesis of acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) and hepcidin control iron metabolism and are upregulated during renal stress. However, higher levels of urinary NGAL are associated with AKI severity whereas higher urinary hepcidin le...
journal_title:Minerva anestesiologica
pub_type: 杂志文章
doi:
更新日期:2015-11-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 杂志文章,随机对照试验
doi:
更新日期:2016-11-01 00:00:00
abstract:BACKGROUND:The coronary sinus oxygen saturation (SO2) can affect the oxygen saturation of the superior vena cava (superior cava SO2) and the pulmonary artery (pulmonary artery SO2), causing a gradient between the latter two (ΔSO2), as has been observed in different physiological and pathological conditions. The objecti...
journal_title:Minerva anestesiologica
pub_type: 杂志文章
doi:
更新日期:2011-06-01 00:00:00
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journal_title:Minerva anestesiologica
pub_type: 杂志文章
doi:
更新日期:2005-10-01 00:00:00