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1.
Medicine (Baltimore) ; 102(47): e36142, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38013300

RESUMO

The anterior lumbar interbody fusion (ALIF) procedure involves several surgical specialties, including general, vascular, and spinal surgery due to its unique approach and anatomy involved. It also carries its own set of complications that differentiate it from posterior lumbar fusion surgeries. The demonstrated benefits of treatment guidelines, such as Enhanced Recovery after Surgery in other surgical procedures, and the lack of current recommendations regarding the anterior approach, underscores the need to develop protocols that specifically address the complexities of ALIF. We aimed to create an evidence-based protocol for pre-, intra-, and postoperative care of ALIF patients and implementation strategies for our health system. A 12-member multidisciplinary workgroup convened to develop an evidence-based treatment protocol for ALIF using a Delphi consensus methodology and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system for rating the quality of evidence and strength of protocol recommendations. The quality of evidence, strength of the recommendation and specific implementation strategies for Methodist Health System for each recommendation were described. The literature search resulted in 295 articles that were included in the development of protocol recommendations. No disagreements remained once the authors reviewed the final GRADE assessment of the quality of evidence and strength of the recommendations. Ultimately, there were 39 protocol recommendations, with 16 appropriate preoperative protocol recommendations (out of 17 proposed), 9 appropriate intraoperative recommendations, and 14 appropriate postoperative recommendations. This novel set of evidence-based recommendations is designed to optimize the patient's ALIF experience from the preoperative to the postoperative period.


Assuntos
Fusão Vertebral , Humanos , Fusão Vertebral/métodos , Vértebras Lombares/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/cirurgia , Região Lombossacral/cirurgia , Procedimentos Neurocirúrgicos , Resultado do Tratamento , Literatura de Revisão como Assunto
2.
Healthcare (Basel) ; 9(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34574927

RESUMO

Patient experience is critically important on both clinical and business levels to healthcare organizations, medical groups, and physician practices. We sought to understand whether a relationship exists between patient satisfaction scores in different settings for medical providers who practice in multiple settings (such as in the ambulatory setting and the hospital) within a system. Press Ganey (PG) ambulatory and hospital-based patient satisfaction surveys of a neurosurgery practice were retrospectively compared. Questions and sections related to the care provider, likelihood to recommend, and overall experience were examined. The ambulatory dataset included 2270 surveys, and the hospital dataset included 376. Correlation analysis of hospital survey patients who also completed an ambulatory survey (N = 120) was conducted, and weak, yet statistically significant, negative correlations between hospital "Likelihood to Recommend" and ambulatory "Care Provider Overall" (r = -0.20421, p = 0.0279), "Likelihood to Recommend" (r = -0.19622, p = 0.0356), and "Survey Overall" (r = -0.28482, p = 0.0019) were found. Our analyses found weak, yet significant, negative correlations between ambulatory and hospital PG scores. This could suggest that patient perception established in ambulatory and clinic settings could translate to a patient's perception of their hospital experience and subsequent satisfaction scores.

3.
Neurosurgery ; 84(2): 442-450, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29608699

RESUMO

BACKGROUND: Development of proximal junctional kyphosis (PJK) after correction of adult spinal deformity (ASD) undermines sagittal alignment. Minimally invasive anterior column realignment (ACR) is a powerful tool for correction of ASD; however, long-term PJK rates are unknown. OBJECTIVE: To characterize PJK after utilization of ACR in ASD correction. METHODS: A retrospective multi-institution cohort analysis per STROBE criteria was conducted of all patients who underwent lateral lumbar interbody fusion (LLIF) or ACR for ASD from 2010 to 2015. All patients obtained preoperative and follow-up upright radiographs, assessing spinal alignment and development of PJK. Patients without proper imaging or minimum 1-yr follow-up were excluded. RESULTS: A total of 73 of 112 patients who underwent either LLIF or ACR for ASD met inclusion criteria. Mean follow-up was 22.8 mo. There was significant improvement of all spinopelvic parameters. Overall, PJK and proximal junctional failure (PJF) rates were 20.5% and 11%, respectively. The incidence of PJK increased with greater corrective surgery (0% LLIF, 30% ACR, 42.9% ACR + posterior column osteotomy (PCO); P < .001). PJF rates increased (0% LLIF, 11% ACR, 40% ACR + PCO; P = .005). Risk factors included location of the upper-instrumented vertebra at T10-L1 vs L2-L4 (P = .007), age (P = .029), severity of ASD, and overcorrection of sagittal imbalance. CONCLUSION: The incidence of PJK after minimally invasive ACR is slightly lower than reported after open surgery but greater than in LLIF only and increases with PCO utilization. The PJK rate increases when crossing the TL junction, sagittal imbalance severity, and overcorrection. Elderly patients are at an increased risk, suggesting need for age appropriate correction goals.


Assuntos
Cifose/etiologia , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/métodos , Complicações Pós-Operatórias/etiologia , Curvaturas da Coluna Vertebral/cirurgia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Cifose/epidemiologia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Coluna Vertebral/cirurgia
4.
J Neurosurg Spine ; 29(3): 339-343, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29932358

RESUMO

Various complications of prone positioning in spine surgery have been described in the literature. Patients in the prone position for extended periods are subject to neurological deficits and/or loss of intraoperative signals due to compression neuropathies, but positioning-related spinal deficits are rare in the thoracolumbar deformity population. The authors present a case of severe kyphoscoliotic deformity with critical thoracolumbar stenosis in which, during the use of a hinged open frame in the prone position, complete loss of intraoperative neural monitoring signals occurred while the frame was flexed into kyphosis to facilitate exposure and instrumentation placement. When the frame was reset to a neutral position, evoked potentials returned to baseline and the operation proceeded without complications. This case represents, to the authors' knowledge, the first report of loss of evoked potentials due to an alteration of prone positioning on a hinged open frame. When positioning patients in such a manner, careful attention should be directed to intraoperative signals in patients with critical stenosis and kyphotic deformity.


Assuntos
Monitorização Neurofisiológica Intraoperatória , Cifose/cirurgia , Decúbito Ventral , Escoliose/cirurgia , Fusão Vertebral/instrumentação , Adulto , Eletromiografia , Potencial Evocado Motor/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Humanos , Cifose/diagnóstico por imagem , Laminectomia , Imageamento por Ressonância Magnética , Masculino , Escoliose/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
5.
World Neurosurg ; 91: 199-204, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27046014

RESUMO

OBJECTIVE: To report the cranial center of mass (CCOM) progression in surgically treated patients for adult spinal deformity (ASD). The C7 plumb line/sagittal vertical axis (SVA) has important relationships with patient-reported outcomes; however, this has not yet been defined for CCOM. METHODS: Patients with consecutive ASD who were undergoing surgery greater than 5 levels of fusion between 2007 and 2012 and had radiographic, clinical, and outcomes data spanning ≥2 years were analyzed, retrospectively. Radiographic parameters were obtained preoperatively and at 6 weeks, 1 year, and 2 years postoperatively. Statistical analysis included descriptives (measures of central tendency, dispersion, frequencies), independent Student t tests, χ(2) square, Pearson correlation, and Kaplan-Meyer curve. RESULTS: Fifty-eight patients (10 male, 48 female) with a mean age of 60.5 years (range, 27-81 years) were reviewed. The mean preoperative SVA was 7.40 cm (SD = 5.51; 37/58 [63.8%] malalignment), and mean CCOM was 10.0 cm (SD = 6.58; 47/58 [81%] malalignment). Six-week postoperative SVA and CCOM was -0.17 cm (SD = 3.3) and 2.5 cm (SD = 4.11), respectively. SVA malalignment was 12.7% and CCOM malalignment was 38.2% at 6 weeks postop. Six week (absolute), 6-week change, and patient number at 6 weeks who were CCOM malaligned was significant compared with SVA (P = 0.003, P < 0.001, P < 0.001, respectively). SRS appearance worsened as preoperative SVA and CCOM increased (P < 0.05), and 2-year SRS appearance and mental health was worsened as 2-year SVA and CCOM increased (P < 0.05). SVA malalignment was 8 and 10 at 1 and 2 years, respectively, and CCOM malalignment was 24 and 32, respectively. Kaplan-Meier curve demonstrates persistent malalignment of CCOM at 6 weeks if not corrected. CONCLUSION: CCOM alignment restoration is an important parameter in ASD, and malalignment is consistent over time.


Assuntos
Medidas de Resultados Relatados pelo Paciente , Crânio/diagnóstico por imagem , Curvaturas da Coluna Vertebral/diagnóstico por imagem , Curvaturas da Coluna Vertebral/cirurgia , Fusão Vertebral/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Clin Spine Surg ; 29(3): 95-107, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26945131

RESUMO

The treatment of adult degenerative scoliosis begins in the outpatient setting when evaluating a patient both radiographically. Assessing the flexibility of the deformity is essential in determining what techniques will be required to achieve the goals of correction. Ultimately the surgeon's comfort and experience and the patient's medical risk stratification determine the strategy needed to address either a focal pathology or ultimate deformity correction.


Assuntos
Escoliose/patologia , Adulto , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Escoliose/diagnóstico por imagem , Escoliose/cirurgia
7.
J Clin Neurosci ; 22(3): 519-25, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25533212

RESUMO

Patients who undergo craniotomy for brain neoplasms have a high risk of developing venous thromboembolism (VTE), including deep vein thromboses (DVT) and pulmonary emboli (PE). The reasons for this correlation are not fully understood. This retrospective, single-center review aimed to determine the risk factors for VTE in patients who underwent neurosurgical resection of brain tumors at Northwestern University from 1999 to 2010. Our cohort included 1148 patients, 158 (13.7%) of whom were diagnosed with DVT and 38 (3.3%) of whom were diagnosed with PE. A variety of clinical factors were studied to determine predictors of VTE, including sex, ethnicity, medical co-morbidities, surgical positioning, length of hospital stay, tumor location, and tumor histology. Use of post-operative anticoagulants and hemorrhagic complications were also investigated. A prior history of VTE was found to be highly predictive of post-operative DVT (odds ratio [OR]=7.6, p=0.01), as was the patient's sex (OR=14.2, p<0.001), ethnicity (OR=0.5, p=0.04), post-operative intensive care unit days (OR=0.2, p=0.003), and tumor histology (OR=-0.16, p=0.01). Contrary to reports in the literature, the data collected did not indicate that the administration of post-operative medical prophylaxis for VTE was significant in preventing their formation (OR=-0.14, p=0.76). Hemorrhagic complications were low (2.2%) and resultant neurologic deficit was lower still (0.7%). The study indicates that patients with high-grade primary brain tumors and metastatic lesions should receive aggressive preventative measures in the post-operative period.


Assuntos
Neoplasias Encefálicas/cirurgia , Craniotomia/efeitos adversos , Embolia Pulmonar/etiologia , Tromboembolia Venosa/etiologia , Trombose Venosa/etiologia , Adulto , Idoso , Anticoagulantes/uso terapêutico , Feminino , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Embolia Pulmonar/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/prevenção & controle
8.
J Neurooncol ; 120(2): 347-52, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25062669

RESUMO

Patients with high-grade glioma are at elevated risk of venous thromboembolism (VTE). The relationship between VTE and survival in glioma patients remains unclear, as does the optimal protocol for chemoprophylaxis. The purpose of this study was to assessthe incidence of and risk factors associated with VTE in patients with high-grade glioma, and the correlation between VTE and survival in this population. Furthermore, we sought to define a protocol for perioperative DVT prophylaxis. This was a retrospective review of patients who underwent craniotomy for resection of high-grade glioma (WHO grade III or IV) at Northwestern University between 1999 and 2010. A total of 336 patients met inclusion criteria. 53 patients developed postoperative VTE (15.7 %). Median survival was 12.0 months and was not significantly different between VTE(+) and VTE(-) patients. Demographics and surgical factors were not significantly correlated with VTE development. Prior history of VTE was highly predictive of postoperative VTE (OR 7.1, p < .01), as was seizure (OR 2.4, p = .005). Increased duration of postoperative ICU stay was also a risk factor for VTE (p = .025). 25 patients in our study received prophylactic anticoagulation(pAC) with either heparin or enoxaparin. Early initiation of pAC was associated with decreased incidence of VTE (p = .042). There were no hemorrhagic complications in patients receiving pAC. VTE is a common complication in high-grade glioma patients. Early initiation of anticoagulation is safe and may decrease the risk of VTE. We recommend initiation of chemoprophylaxis on postoperative day 1 in patients without contraindication.


Assuntos
Glioma/complicações , Complicações Pós-Operatórias , Tromboembolia Venosa/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Craniotomia , Feminino , Seguimentos , Glioma/mortalidade , Glioma/patologia , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Tromboembolia Venosa/mortalidade , Adulto Jovem
9.
Neurosurg Clin N Am ; 25(2): 219-31, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24703442

RESUMO

The lateral transpsoas approach to the lumbar spine has become an increasingly popular method to achieve fusion. Although this approach requires less tissue dissection, a smaller incision, decreased operative time, reduced blood loss and postoperative pain, and shorter hospital stay, it carries the potential for serious neurologic and visceral complications. This article reviews these complications in detail and proposes mechanisms for their avoidance.


Assuntos
Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Fusão Vertebral , Humanos , Vértebras Lombares/patologia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Neurocirúrgicos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/cirurgia , Fusão Vertebral/métodos , Resultado do Tratamento
10.
Neurosurg Clin N Am ; 25(2): 233-45, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24703443

RESUMO

Posterior approaches for decompression in minimally invasive spine surgery are increasingly used for a wide range of pathology. Surgeons and patients must understand these risks in order to identify, manage, and ideally prevent complications. Technical intraoperative complications, recurrences and reoperations, infections, and medical complications associated with the surgery are considered for common posterior minimally invasive decompression procedures of the cervical and lumbar spine. Methods of possibly avoiding these complications are also discussed. This article then aggregates the relevant data to allow concise understanding of the complications associated with these procedures.


Assuntos
Descompressão Cirúrgica , Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Procedimentos Neurocirúrgicos , Complicações Pós-Operatórias/prevenção & controle , Descompressão Cirúrgica/métodos , Humanos , Complicações Intraoperatórias/prevenção & controle , Vértebras Lombares/patologia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Neurocirúrgicos/métodos
11.
Neurosurg Clin N Am ; 25(2): 353-60, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24703453

RESUMO

The lateral transpsoas approach for interbody fusion is a minimally invasive technique that has been gaining increasing popularity in the management of a variety of spinal degenerative disorders. Recently, there has been increasing utilization of this technique in the management of adult deformity. The authors present a review of the current evidence of using the lateral lumbar transpsoas approach in the correction of adult degenerative scoliosis.


Assuntos
Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Fusão Vertebral , Ensaios Clínicos como Assunto , Humanos , Vértebras Lombares/patologia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Escoliose/cirurgia , Fusão Vertebral/métodos , Resultado do Tratamento
12.
J Clin Neurosci ; 20(10): 1350-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23835467

RESUMO

A new generation of oral anticoagulants, namely direct thrombin inhibitors and factor Xa inhibitors, have recently been approved for clinical use in patients with atrial fibrillation. These novel families of drugs have been shown to have favorable efficacy and safety profiles in multiple clinical settings, particularly in the prevention of atrial fibrillation-related stroke, and are likely to become part of everyday practice, making a crossover to neurosurgical patients inevitable. Concern has risen regarding the complexity of managing intracranial and intraspinal hemorrhages related to these drugs. This review aims to provide an update on the most recent advances in oral anticoagulant drug therapy from a neurosurgeon's perspective. We discuss current evidence for the use of these novel agents, their limitations, existing methods of drug-level monitoring, and controversies related to anticoagulation reversal. We also discuss specific topics such as anticoagulation resumption after intracranial or intraspinal bleeding, perioperative anticoagulant administration, and the possibility of combination with tissue plasminogen activator in the setting of acute ischemic stroke. A special focus is given to the incidence of intracranial and intraspinal hemorrhage associated with each drug.


Assuntos
Anticoagulantes/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Ensaios Clínicos como Assunto , Hemorragia/tratamento farmacológico , Humanos , Neurocirurgia
13.
J Neurointerv Surg ; 5(3): e14, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22442404

RESUMO

BACKGROUND AND IMPORTANCE: Extracranial carotid artery atherosclerotic stenosis typically occurs at the junction of the common carotid, external carotid and internal carotid arteries. Although rare, anatomical arterial variants can influence surgical strategy and can have a significant impact on surgical complications and patient outcome. An unusual case of atherosclerotic stenosis of the internal carotid artery (ICA) at the origin of a pharyngo-occipital variant off of the ICA is reported here. CLINICAL PRESENTATION: A 60-year-old man presented with symptomatic severe left cervical ICA stenosis. The stenosis was related to the origin of the pharyngo-occipital common trunk which arose from the ICA rather than the typical origin off of the external carotid artery. The patient underwent successful left carotid endarterectomy with special attention to this variant anatomy. CONCLUSION: Anomalies of the extracranial ICA, although rare, can influence the location of atherosclerotic disease and the surgical endarterectomy strategy. A detailed anatomical study should be performed prior to surgery to minimize risk and improve patient outcome.


Assuntos
Artéria Carótida Interna/anormalidades , Artéria Carótida Interna/cirurgia , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Endarterectomia das Carótidas/métodos , Lobo Occipital/irrigação sanguínea , Faringe/irrigação sanguínea , Artéria Carótida Interna/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Occipital/diagnóstico por imagem , Faringe/diagnóstico por imagem , Radiografia
14.
Environ Health Perspect ; 120(10): 1385-90, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22784691

RESUMO

BACKGROUND: Winter temperature inversions-layers of air in which temperature increases with altitude-trap air pollutants and lead to higher pollutant concentrations. Previous studies have evaluated associations between pollutants and emergency department (ED) visits for asthma, but none have considered inversions as independent risk factors for ED visits for asthma. OBJECTIVE: We aimed to assess associations between winter inversions and ED visits for asthma in Salt Lake County, Utah. METHODS: We obtained electronic records of ED visits for asthma and data on inversions, weather, and air pollutants for Salt Lake County, Utah, during the winters of 2003 through 2004 to 2007 through 2008. We identified 3,425 ED visits using a primary diagnosis of asthma. We used a time-stratified case-crossover design, and conditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to estimate rate ratios of ED visits for asthma in relation to inversions during a 4-day lag period and prolonged inversions. We evaluated interactions between inversions and weather and pollutants. RESULTS: After adjusting for dew point and mean temperatures, the OR for ED visits for asthma associated with inversions 0-3 days before the visit compared with no inversions during the lag period was 1.14 (95% CI: 1.00, 1.30). The OR for each 1-day increase in the number of inversion days during the lag period was 1.03 (95% CI: 1.00, 1.07). Associations were only apparent when PM10 and maximum and mean temperatures were above median levels. CONCLUSIONS: Our results provide evidence that winter inversions are associated with increased rates of ED visits for asthma.


Assuntos
Poluentes Atmosféricos/toxicidade , Asma/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Tempo (Meteorologia) , Adolescente , Adulto , Poluentes Atmosféricos/análise , Asma/etiologia , Criança , Pré-Escolar , Estudos Cross-Over , Feminino , Temperatura Alta , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Razão de Chances , Estações do Ano , Utah/epidemiologia , Adulto Jovem
15.
Am J Respir Crit Care Med ; 172(1): 39-44, 2005 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-15805188

RESUMO

RATIONALE: Approximately 10% of patients who have a spontaneous pneumothorax have a positive family history. OBJECTIVES: We sought to identify DNA sequence variations that confer susceptibility to pneumothoraces. METHODS: We collected 12 families that had at least 2 first-degree relatives with a spontaneous pneumothorax. All affected family members had no obvious stigmata of known genetic disorders associated with pneumothoraces. We used haplotype analysis, DNA sequencing, and restriction fragment analysis of mutations to evaluate the individuals in these families. MAIN RESULTS: In 2 of the 12 families the disorder cosegregated with markers flanking a candidate locus, FLCN. Sequencing the linked alleles revealed 2 mutations predicted to introduce premature stop codons in 2 of the 12 families. Most mutations in FLCN cause a rare disease, Birt-Hogg-Dubé syndrome, characterized by autosomal dominant inheritance of multiple benign skin lesions, renal tumors, pulmonary blebs, and pneumothoraces. None of the family members with the nonsense mutations had the skin manifestations of Birt-Hogg-Dubé syndrome or renal cancer. Pathologic examination of lung tissue from three affected nonsmokers revealed blebs and underlying emphysema. CONCLUSIONS: Isolated familial spontaneous pneumothorax can be caused by mutations of the FLCN gene. Because development of a pneumothorax and/or pulmonary blebs may be the earliest or the only clinical manifestation of FLCN mutations, pulmonologists should be alert to the contribution of this gene toward this familial form of emphysema.


Assuntos
Códon sem Sentido , Estrona/genética , Pneumotórax/genética , Adulto , Feminino , Genes Dominantes , Haplótipos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Linhagem , Polimorfismo de Fragmento de Restrição , Proteínas/genética , Proteínas Proto-Oncogênicas , Enfisema Pulmonar/genética , Análise de Sequência de RNA , Inquéritos e Questionários , Proteínas Supressoras de Tumor
16.
Nat Genet ; 37(2): 161-5, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15654334

RESUMO

The low-density lipoprotein receptor (LDLR) prevents hypercholesterolemia and atherosclerosis by removing low-density lipoprotein (LDL) from circulation. Mutations in the genes encoding either LDLR or its ligand (APOB) cause severe hypercholesterolemia. Missense mutations in PCSK9, encoding a serine protease in the secretory pathway, also cause hypercholesterolemia. These mutations are probably gain-of-function mutations, as overexpression of PCSK9 in the liver of mice produces hypercholesterolemia by reducing LDLR number. To test whether loss-of-function mutations in PCSK9 have the opposite effect, we sequenced the coding region of PCSK9 in 128 subjects (50% African American) with low plasma levels of LDL and found two nonsense mutations (Y142X and C679X). These mutations were common in African Americans (combined frequency, 2%) but rare in European Americans (<0.1%) and were associated with a 40% reduction in plasma levels of LDL cholesterol. These data indicate that common sequence variations have large effects on plasma cholesterol levels in selected populations.


Assuntos
População Negra/genética , LDL-Colesterol/sangue , Códon sem Sentido , Serina Endopeptidases/genética , Adulto , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Pró-Proteína Convertase 9 , Pró-Proteína Convertases
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