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1.
J Urol ; : 101097JU0000000000004023, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717916

RESUMO

PURPOSE: Because multiple management options exist for clinical T1 renal masses, patients may experience a state of uncertainty about the course of action to pursue (ie, decisional conflict). To better support patients, we examined patient, clinical, and decision-making factors associated with decisional conflict among patients newly diagnosed with clinical T1 renal masses suspicious for kidney cancer. MATERIALS AND METHODS: From a prospective clinical trial, participants completed the Decisional Conflict Scale (DCS), scored 0 to 100 with < 25 associated with implementing decisions, at 2 time points during the initial decision-making period. The trial further characterized patient demographics, health status, tumor burden, and patient-centered communication, while a subcohort completed additional questionnaires on decision-making. Associations of patient, clinical, and decision-making factors with DCS scores were evaluated using generalized estimating equations to account for repeated measures per patient. RESULTS: Of 274 enrollees, 250 completed a DCS survey; 74% had masses ≤ 4 cm in size, while 11% had high-complexity tumors. Model-based estimated mean DCS score across both time points was 17.6 (95% CI 16.0-19.3), though 50% reported a DCS score ≥ 25 at least once. On multivariable analysis, DCS scores increased with age (+2.64, 95% CI 1.04-4.23), high- vs low-complexity tumors (+6.50, 95% CI 0.35-12.65), and cystic vs solid masses (+9.78, 95% CI 5.27-14.28). Among decision-making factors, DCS scores decreased with higher self-efficacy (-3.31, 95% CI -5.77 to -0.86]) and information-seeking behavior (-4.44, 95% CI -7.32 to -1.56). DCS scores decreased with higher patient-centered communication scores (-8.89, 95% CI -11.85 to -5.94). CONCLUSIONS: In addition to patient and clinical factors, decision-making factors and patient-centered communication relate with decisional conflict, highlighting potential avenues to better support patient decision-making for clinical T1 renal masses.

2.
PLoS One ; 18(4): e0284145, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37075048

RESUMO

PURPOSE: To evaluate the utility of immediate post-procedure computed tomography (IPP-CT) and routine one-hour chest radiography (1HR-CXR) for detecting and managing pneumothorax in patients undergoing computed tomography (CT)-guided percutaneous lung biopsy. MATERIALS AND METHODS: All CT-guided percutaneous lung biopsies performed between May 2014 and August 2021 at a single institution were included. Data from 275 procedures performed on 267 patients (147 men; mean age: 63.5 ± 14.1 years; range 18-91 years) who underwent routine 1HR-CXR were reviewed. Incidences of pneumothorax and procedure-related complications on IPP-CT and 1HR-CXR were recorded. Associated variables, including tract embolization methods, needle diameter/type, access site, lesion size, needle tract distance, and number of biopsy samples obtained were analyzed and compared between groups with and without pneumothorax. RESULTS: Post-procedure complications included pneumothorax (30.9%, 85/275) and hemoptysis (0.7%, 2/275). Pneumothorax was detected on IPP-CT and 1HR-CXR in 89.4% (76/85) and 100% (85/85), respectively. A chest tube was placed in 4% (11/275) of the cases. In 3.3% (9/275) of the cases, delayed pneumothorax was detected only on 1HR-CXR, but no patient in this group necessitated chest tube placement. The incidence of pneumothorax was not significantly different between tract embolization methods (p = 0.36), needle diameters (p = 0.36) and types (p = 0.33), access sites (p = 0.07), and lesion sizes (p = 0.88). On logistic regression, a lower biopsy sample number (OR = 0.49) was a protective factor, but a longer needle tract distance (OR = 1.16) was a significant risk factor for pneumothorax. CONCLUSION: Following CT-guided percutaneous lung biopsy, pneumothorax detected on IPP-CT strongly indicates persistent pneumothorax on 1HR-CXR and possible chest tube placement. If no pneumothorax is identified on IPP-CT, follow-up 1HR-CXR may be required only for those who develop symptoms of pneumothorax.


Assuntos
Pneumotórax , Radiografia Intervencionista , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Biópsia por Agulha/métodos , Estudos Retrospectivos , Radiografia Intervencionista/efeitos adversos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pneumotórax/diagnóstico por imagem , Pneumotórax/etiologia , Pneumotórax/epidemiologia , Biópsia Guiada por Imagem/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Fatores de Risco
4.
J Vasc Interv Radiol ; 34(1): 124-129, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36220607

RESUMO

PURPOSE: To investigate the safety and efficacy of attaching a weighted extension to the distal aspect of prefabricated gastrojejunostomy (GJ) tubes, and to determine whether this alteration reduces the occurrences of tip reflux into the esophagus or stomach. MATERIALS AND METHODS: This retrospective 1-way crossover study included 64 GJ tubes in 15 patients placed by multiple operators in the interventional radiology department at a single institution from July 1, 2019, to December 1, 2021. Patients were selected for a weighted tip extension if they required a GJ tube exchange because of the distal tip refluxing into the stomach or esophagus and were aged ≥18 years. These modified GJ tubes were prepared by cutting the distal end of a nasojejunal tube to a length of 10-15 cm and suturing to the distal aspect of the GJ tube. RESULTS: Of the 64 tubes studied, 37 had a weighted tip extension. The unmodified GJ tubes had a mean lifespan of 34.3 days, which was significantly shorter than the weighted tips (92.8 days; t test P = .001). There was 1 limited adverse event of abdominal pain and spasms that resolved after exchange with a shorter weighted extension. CONCLUSIONS: This study suggests that for patients who require a GJ tube replacement because of the tip refluxing proximally into the stomach or esophagus, the addition of a 10-15-cm weighted extension to the distal end of the GJ tube is safe and significantly improves the lifespan of the enteric tube.


Assuntos
Derivação Gástrica , Longevidade , Humanos , Adolescente , Adulto , Estudos Retrospectivos , Derivação Gástrica/efeitos adversos , Estudos Cross-Over , Intubação Gastrointestinal/efeitos adversos , Intubação Gastrointestinal/métodos
5.
Semin Intervent Radiol ; 38(5): 523-534, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34853498

RESUMO

As the basic units of biological organization, stem cells and their progenitors are essential for developing and regenerating organs and tissue systems using their unique self-renewal capability and differentiation potential into multiple cell lineages. Stem cells are consistently present throughout the entire human development, from the zygote to adulthood. Over the past decades, significant efforts have been made in biology, genetics, and biotechnology to develop stem cell-based therapies using embryonic and adult autologous or allogeneic stem cells for diseases without therapies or difficult to treat. Stem cell-based therapies require optimum administration of stem cells into damaged organs to promote structural regeneration and improve function. Maximum clinical efficacy is highly dependent on the successful delivery of stem cells to the target tissue. Direct image-guided locoregional injections into target tissues offer an option to increase therapeutic outcomes. Interventional radiologists have the opportunity to perform a key role in delivering stem cells more efficiently using minimally invasive techniques. This review discusses the types and sources of stem cells and the current clinical applications of stem cell-based therapies. In addition, the regulatory considerations, logistics, and potential roles of interventional Radiology are also discussed with the review of the literature.

8.
Semin Intervent Radiol ; 38(4): 397-404, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34629705

RESUMO

Transarterial radioembolization of primary and secondary hepatic malignancies utilizing yttrium-90 microspheres is a commonly performed treatment by interventional radiologists. Traditionally performed as a two-part procedure, a diagnostic angiography is performed 1 to 3 weeks prior to treatment with the injection of technetium-99m-macroaggregated albumin followed by planar scintigraphy in the nuclear medicine department. Careful attention must be paid to the details during the diagnostic angiography to ensure the delivery of a safe and optimal dose to the diseased liver and to minimize radiation-induced damage to both unaffected liver and adjacent structures. In this article, we will review the steps and considerations that must be made during the angiography planning and discuss current and future areas of research.

9.
J Vasc Interv Radiol ; 31(4): 667-673, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32113797

RESUMO

PURPOSE: To determine predictors of outcomes for patients who undergo computed tomography (CT)-guided percutaneous abdominal or pelvic drainage catheter placement and to identify which patients benefit from fluoroscopic drainage catheter interrogation (abscessogram). MATERIALS AND METHODS: A retrospective review of 383 patients (mean, 52 years old; range 8-89 years old; 158 males: 225 females) who underwent 442 CT-guided procedures and 489 catheter placements for fluid collections in the abdomen or pelvis from January 1, 2015, to December 31, 2016 was performed. Variables including underlying disease, fluid location, number of collections drained, number of catheter exchanges and follow-up abscessograms performed, catheter size, and fistula detection were analyzed to determine factors associated with fistula formation and increased catheter dwell time. RESULTS: A single abscessogram followed by catheter removal was performed for 217 catheters (44%). An increased number of abscessograms was significantly associated with drainage catheter size (P < .001) and presence of a fistula (P < .001). Fistulae were detected in 95 cases (19%) and were significantly associated with an increased number of drain exchanges (P < .001) and an underlying diagnosis of Crohn's disease (P = .02). Based on these data, a clinical algorithm for drain management is presented. CONCLUSIONS: Abscessograms performed after CT-guided percutaneous drainage catheter placement are useful to detect catheter malposition, occluded catheters, and fistulae but are not necessary for all patients. If performed selectively, particularly in patients with an underlying diagnosis of Crohn's disease or those at high risk for developing fistulae, unnecessary examinations can be avoided, reducing cost, extra hospital visits, and radiation dose.


Assuntos
Abscesso Abdominal/terapia , Drenagem , Radiografia Intervencionista , Tomografia Computadorizada por Raios X , Abscesso Abdominal/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Catéteres , Criança , Drenagem/efeitos adversos , Drenagem/instrumentação , Desenho de Equipamento , Falha de Equipamento , Feminino , Fístula/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pelve , Radiografia Intervencionista/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X/efeitos adversos , Resultado do Tratamento , Adulto Jovem
11.
Pediatr Radiol ; 50(4): 470-475, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31807854

RESUMO

BACKGROUND: In recent years, there has been a movement toward more judicious use of computed tomography (CT) imaging in an attempt to limit exposure of pediatric patients to ionizing radiation. The Image Gently Alliance and like-minded movements began advocating for safe and high-quality pediatric imaging worldwide in the late 2000s. OBJECTIVE: In the context of these efforts, we evaluate CT utilization rates in the pediatric emergency department at a major academic medical center. MATERIALS AND METHODS: We tracked utilization in several categories of CT, magnetic resonance imaging (MRI) and ultrasonography (US) between July 2008 and June 2017 and compared them with utilization rates from 2000 to 2006. RESULTS: A total of 4,955 pediatric patients underwent a total of 5,973 CT scans, 2,775 US studies and 293 MRI scans while in the pediatric emergency department during the 2008-2017 study period. We observed decreases in CT scans across all categories, ranging from a 19% decrease in abdominal CT to a 66% decrease in chest CT. Relatively greater decreases in CT scans were observed in patients younger than 3 years of age as compared to older children and adolescents. Abdominal and pelvic US increased. Brain MRI also increased over the final two years of the study. CONCLUSION: CT utilization decreased throughout the 2008-2017 study period.


Assuntos
Serviço Hospitalar de Emergência , Proteção Radiológica , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Centros Médicos Acadêmicos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Ultrassonografia/estatística & dados numéricos
12.
Nucl Med Commun ; 40(5): 532-538, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30920430

RESUMO

OBJECTIVE: The objective of this study was to analyze the uptake of rubidium in malignant tumors. PARTICIPANTS AND METHODS: Sixteen malignant lesions were included. Two radiologists compared each lesion to four references (subcutaneous fat, lung, mediastinal blood pool, and liver) at rest and stress and scored as 1-4. Maximum standardized uptake value (SUV) in each lesion and four references, as well as ratios of lesion SUV to SUV of each of the references, were calculated at rest and stress. We assessed an agreement for scores of reader 1 versus reader 2 (inter-reader) at rest and stress, scores at rest versus stress (intrapatient) for reader 1 and reader 2, and lesion SUV and respective ratios at rest and stress using paired t-test and Bland-Altman analyses. RESULTS: Fifteen (94%) out of 16 lesions had a score of 3 or 4 at rest or stress or both by at least one reviewer. We did not find evidence of inter-reader bias at rest or stress or intrapatient (rest vs. stress) bias for either reader. SUV ranged from 1.0 to 8.1 at rest and from 0.7 to 6.7 at stress. There was an excellent agreement between ratios of lesion SUV to lung SUV at rest versus stress. On the extreme, there was a poor agreement between ratios of lesion SUV to liver SUV at rest versus stress. Otherwise, the agreement was good for the majority of the results, and moderate for a few others. CONCLUSION: Malignant tumors can be readily depicted and quantified on rubidium PET/CT. Further research is needed.


Assuntos
Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioisótopos de Rubídio/metabolismo , Transporte Biológico , Humanos , Processamento de Imagem Assistida por Computador
14.
Urology ; 102: 36-37, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28088431
15.
Urology ; 102: 31-37, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28088432

RESUMO

OBJECTIVE: To evaluate the age-stratified prevalence of upper tract urothelial malignancies diagnosed on computed tomography urography in a large cohort of patients referred for initial evaluation of hematuria. MATERIALS AND METHODS: A total of 1123 consecutive adults without a history of urothelial cancer underwent initial computed tomography urography for gross hematuria (n = 652), microscopic hematuria (n = 457), or unspecified hematuria (n = 14) at a single institution from October 2006 to October 2012. Imaging findings suggestive of urothelial lesions were correlated with clinical information, including cystoscopy, cytology, and surgical pathology reports. Patients subsequently diagnosed with urothelial cancer following a normal radiographic evaluation were identified and analyzed. Age, gender, smoking history, and location and type of malignancy were analyzed. RESULTS: Upper tract urothelial cancer was detected in 4 (0.36%) patients, with a mean age of 66.5 years. All 4 patients presented with gross hematuria and were current or former smokers. None of the 535 patients under age 55 who underwent computed tomography urography were diagnosed with upper tract disease regardless of age, smoking history, or degree of hematuria. Likewise, no upper tract cancers were detected in patients referred for microscopic hematuria, regardless of age. CONCLUSION: Detection of upper tract urothelial cancer by computed tomography urography is exceedingly rare in patients presenting at a tertiary referral center with hematuria, particularly in the lower risk strata (younger age, microscopic hematuria). Further investigation into risk-stratified approaches to imaging for hematuria workup is warranted to minimize unnecessary costs and radiation exposure.


Assuntos
Carcinoma de Células de Transição/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Neoplasias Ureterais/diagnóstico por imagem , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/complicações , Carcinoma de Células de Transição/epidemiologia , Feminino , Hematúria/etiologia , Humanos , Neoplasias Renais/complicações , Neoplasias Renais/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Encaminhamento e Consulta , Estudos Retrospectivos , Centros de Atenção Terciária , Tomografia Computadorizada por Raios X , Neoplasias Ureterais/complicações , Neoplasias Ureterais/epidemiologia , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/epidemiologia , Urografia/métodos
16.
Invest Radiol ; 51(10): 661-5, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27548344

RESUMO

OBJECTIVE: The aim of this study was to examine and report 4 patients who developed symptomatology shortly after gadolinium-based contrast agent (GBCA) administration. MATERIALS AND METHODS: History taking and targeted physical examination were performed on 4 subjects who reported development of new disease features within hours to 4 weeks of having received an intravenous administration of GBCA. RESULTS: Two subjects were assessed at 2 months (patient P2mo) and at 3 months (patient P3mo) after GBCA administration (early stage), and 2 subjects were assessed at 7 years (patient P7yr) and 8 years (patient P8yr) after having received GBCA administration (late stage). Clinical features were similar between subjects, and included central torso pain (all), peripheral arm and leg pain (all), clouded mentation (n = 2), and distal arm and leg skin thickening and rubbery subcutaneous tissue (one early and both late subjects). Gadolinium was detected as follows: in a 24-hour urine specimen, 1 month after disease development (18 µg/24 hours and 82 µg/24 hours in patients P2mo and P3mo, respectively); hair (0.0007 µg/g) and urine (0.0644 µg/g) samples, 7 years after disease development (late stage, patient P7yr); and saphenous vein sample, 8 years after disease development (0.27 ± 0.007 ng/62 mg sample) (late stage, patient P8yr). CONCLUSIONS: Gadolinium toxicity may occur in subjects with normal renal function. Central torso and peripheral arm and leg distribution pain were common features. Distal arm and leg skin thickening and rubbery subcutaneous tissue were seen in late stages. Clouded mentation is also common. Vigilance to identify additional cases and investigate strategies for prevention and treatment is warranted to increase even further the safety of a very safe diagnostic procedure, GBCA-enhanced magnetic resonance imaging.


Assuntos
Meios de Contraste/intoxicação , Gadolínio/intoxicação , Dor/induzido quimicamente , Pele/efeitos dos fármacos , Adulto , Feminino , Humanos , Pessoa de Meia-Idade
17.
J Vasc Interv Radiol ; 25(11): 1801-6, 1807.e1-5, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25066590

RESUMO

PURPOSE: To determine if there was a difference in the level of knowledge about interventional radiology (IR) between medical students in preclinical years of training compared with medical students in clinical years of training at two medical schools and to compare awareness of IR based on the curriculum at each school: one with required radiology education and one without such a requirement. MATERIALS AND METHODS: An anonymous survey was distributed to students at two medical schools; the survey assessed knowledge of IR, knowledge of training pathways, and preferred methods to increase exposure. Responses of the preclinical and clinical groups were compared, and responses from the clinical groups at each school were compared. RESULTS: "Poor" or "fair" knowledge of IR was reported by 84% (n = 217 of 259) of preclinical students compared with 62% of clinical students (n = 110 of 177; P < .001). IR was being considered as a career by 11% of all students (15%, n = 40 of 259 preclinical; 5%, n = 9 of 177 clinical). The main reason respondents were not considering IR was "lack of knowledge" (65%, n = 136 of 210 preclinical; 20%, n = 32 of 162 clinical). Students in the clinical group at the institution with a required radiology rotation reported significantly better knowledge of IR than clinical students from the institution without a required clerkship (P = .017). CONCLUSIONS: There are significant differences in knowledge of IR between preclinical and clinical students. Required radiology education in the clinical years does increase awareness of IR.


Assuntos
Competência Clínica/estatística & dados numéricos , Radiologia Intervencionista/educação , Faculdades de Medicina , Estudantes de Medicina/estatística & dados numéricos , Coleta de Dados/métodos , Coleta de Dados/estatística & dados numéricos , Humanos , Internato e Residência/estatística & dados numéricos , North Carolina
18.
Diabetes ; 62(10): 3627-35, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23670970

RESUMO

Diabetes is a common age-dependent complication of cystic fibrosis (CF) that is strongly influenced by modifier genes. We conducted a genome-wide association study in 3,059 individuals with CF (644 with CF-related diabetes [CFRD]) and identified single nucleotide polymorphisms (SNPs) within and 5' to the SLC26A9 gene that associated with CFRD (hazard ratio [HR] 1.38; P = 3.6 × 10(-8)). Replication was demonstrated in 694 individuals (124 with CFRD) (HR, 1.47; P = 0.007), with combined analysis significant at P = 9.8 × 10(-10). SLC26A9 is an epithelial chloride/bicarbonate channel that can interact with the CF transmembrane regulator (CFTR), the protein mutated in CF. We also hypothesized that common SNPs associated with type 2 diabetes also might affect risk for CFRD. A previous association of CFRD with SNPs in TCF7L2 was replicated in this study (P = 0.004; combined analysis P = 3.8 × 10(-6)), and type 2 diabetes SNPs at or near CDKAL1, CDKN2A/B, and IGF2BP2 were associated with CFRD (P < 0.004). These five loci accounted for 8.3% of the phenotypic variance in CFRD onset and had a combined population-attributable risk of 68%. Diabetes is a highly prevalent complication of CF, for which susceptibility is determined in part by variants at SLC26A9 (which mediates processes proximate to the CF disease-causing gene) and at four susceptibility loci for type 2 diabetes in the general population.


Assuntos
Antiporters/genética , Quinase 5 Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Fibrose Cística/genética , Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleotídeo Único , Proteínas de Ligação a RNA/genética , Adolescente , Adulto , Fibrose Cística/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Razão de Chances , Transportadores de Sulfato , Estados Unidos/epidemiologia , tRNA Metiltransferases
19.
PLoS One ; 6(10): e25452, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21998660

RESUMO

Variability in cystic fibrosis (CF) lung disease is partially due to non-CFTR genetic modifiers. Mucin genes are very polymorphic, and mucins play a key role in the pathogenesis of CF lung disease; therefore, mucin genes are strong candidates as genetic modifiers. DNA from CF patients recruited for extremes of lung phenotype was analyzed by Southern blot or PCR to define variable number tandem repeat (VNTR) length polymorphisms for MUC1, MUC2, MUC5AC, and MUC7. VNTR length polymorphisms were tested for association with lung disease severity and for linkage disequilibrium (LD) with flanking single nucleotide polymorphisms (SNPs). No strong associations were found for MUC1, MUC2, or MUC7. A significant association was found between the overall distribution of MUC5AC VNTR length and CF lung disease severity (p = 0.025; n = 468 patients); plus, there was robust association of the specific 6.4 kb HinfI VNTR fragment with severity of lung disease (p = 6.2×10(-4) after Bonferroni correction). There was strong LD between MUC5AC VNTR length modes and flanking SNPs. The severity-associated 6.4 kb VNTR allele of MUC5AC was confirmed to be genetically distinct from the 6.3 kb allele, as it showed significantly stronger association with nearby SNPs. These data provide detailed respiratory mucin gene VNTR allele distributions in CF patients. Our data also show a novel link between the MUC5AC 6.4 kb VNTR allele and severity of CF lung disease. The LD pattern with surrounding SNPs suggests that the 6.4 kb allele contains, or is linked to, important functional genetic variation.


Assuntos
Fibrose Cística/genética , Repetições Minissatélites/genética , Mucina-5AC/genética , Polimorfismo de Nucleotídeo Único , Alelos , Fibrose Cística/patologia , Genótipo , Humanos , Pulmão/metabolismo , Pulmão/patologia , Fenótipo
20.
Nat Genet ; 43(6): 539-46, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21602797

RESUMO

A combined genome-wide association and linkage study was used to identify loci causing variation in cystic fibrosis lung disease severity. We identified a significant association (P = 3.34 × 10(-8)) near EHF and APIP (chr11p13) in p.Phe508del homozygotes (n = 1,978). The association replicated in p.Phe508del homozygotes (P = 0.006) from a separate family based study (n = 557), with P = 1.49 × 10(-9) for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family based study identified a significant quantitative trait locus on chromosome 20q13.2 (log(10) odds = 5.03). Our findings provide insight into the causes of variation in lung disease severity in cystic fibrosis and suggest new therapeutic targets for this life-limiting disorder.


Assuntos
Cromossomos Humanos Par 11 , Cromossomos Humanos Par 20 , Fibrose Cística/genética , Ligação Genética , Pneumopatias/genética , Adolescente , Adulto , Criança , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Fenótipo , Locos de Características Quantitativas
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