Publications by authors named "Lisa Ku"

11 Publications

  • Page 1 of 1

Massive air embolism from continuous venovenous haemofiltration causing electromechanical dissociation in a cardiac surgical patient.

Crit Care Resusc 2012 Jun;14(2):154-8

Department of Anaesthesia, Austin Hospital, Melbourne, VIC, Australia.

Venous air embolism is a rare but life-threatening complication of continuous venovenous haemofiltration. We report a case of massive venous air embolism associated with haemofiltration in a 75-year-old man after complicated cardiac surgery. Haemofiltration circuitry and air detector alarms are not infallible and air embolism should be considered in patients receiving such therapy who develop cardiopulmonary instability. We discuss our early intervention, which focused on restoration of the circulation, prevention of further air entry, retrieval of air and supportive care. The use of transoesophageal echocardiography for diagnosis of air embolism and to aid the insertion of a pulmonary artery catheter for air aspiration was essential for management.
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June 2012

Genetic counseling practice analysis.

J Genet Couns 2009 Jun 11;18(3):205-16. Epub 2009 Mar 11.

American Board of Genetic Counseling, Olathe, KS, USA.

The American Board of Genetic Counseling (ABGC) performed a genetic counseling practice analysis (PA) to determine the content of the certification examination. The ABGC-appointed PA Advisory Committee worked with psychometricians to develop a survey which was distributed to 2,038 genetic counselors in the United States and Canada. The survey was also accessible on the ABGC website. Multiple criteria were used to establish the significance of the tasks included in the survey. A total of 677 responses were used in the analysis, representing a 37.1% corrected response rate. Five major content domains with 143 tasks were identified in the PA. New certification test specifications were developed on the basis of PA results and will be used in developing future examination forms. In keeping with credentialing standards, ABGC plans to conduct a PA on a regular basis so that the content of the examination reflects current practice.
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http://dx.doi.org/10.1007/s10897-009-9216-1DOI Listing
June 2009

The impact of direct-to-consumer marketing of cancer genetic testing on women according to their genetic risk.

Genet Med 2008 Dec;10(12):888-94

Department of Epidemiology, Colorado School of Public Health-Denver, Aurora, Colorado 80045-0508, USA.

Purpose: To assess the impact of direct-to-consumer marketing for genetic testing among women of varying genetic risk for breast and ovarian cancer.

Methods: Telephone surveys were conducted with 315 women in Denver, Colorado, one target audience for the Myriad BRACAnalysis ad campaign. Genetic risk was determined from personal and family history and grouped by probability of having a BRCA1/2 mutation (low <5%, moderate 5-<10%, high > or =10%).

Results: High-risk women were more knowledgeable about BRACAnalysis and more likely to recall the media ads than were low-risk women (60 vs. 39%, P < 0.01). After seeing the ads, about 40% of women were more interested in testing and about 10% expressed increased worry about developing breast or ovarian cancer. Women across all risk groups overstated the benefits and appropriateness of testing. An equal percentage of high- and low-risk women (51 and 60%) felt that they would benefit from genetic testing.

Conclusion: The campaign effectively reached a large audience. Concern about breast cancer was not appreciably increased. A large percentage of low-risk women (not candidates for testing) expressed interest in testing, suggesting the campaign was too broad. A campaign targeted at high-risk women, who may benefit from testing might be preferred.
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http://dx.doi.org/10.1097/GIM.0b013e31818de6d7DOI Listing
December 2008

Danon disease presenting with dilated cardiomyopathy and a complex phenotype.

J Hum Genet 2007 ;52(10):830-835

University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.

X-linked dilated cardiomyopathy (XLCM) was first described in 1987 and associated with dystrophin gene (DMD) mutations a decade later in one of the original two families. Here we report long-term follow-up of the second family (XLCM-2), for which a DMD mutation was never found. Analysis of the lysosome-associated membrane protein-2 (LAMP-2) gene detected a novel mutation, confirming a diagnosis of Danon disease. The broad phenotype in this family included dilated and hypertrophic cardiomyopathy, cardiac pre-excitation, skeletal myopathy with high serum creatinine kinase, cognitive impairement (in males), and and a pigmentary retinopathy in affected females. Cardiac biopsy in a 13-month-old mutation-carrying male showed no vacuolization by standard histology. We conclude that XLCM may be the presenting sign of Danon disease and, in the presence of familial history of HCM, pre-excitation, skeletal muscle involvement and retinal pigmentary dystrophy should prompt LAMP-2 clinical testing. Furthermore, the absence of vacuolar myopathy in biopsies from young patients may not exclude Danon disease.
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http://dx.doi.org/10.1007/s10038-007-0184-8DOI Listing
December 2007

Prevalence of desmin mutations in dilated cardiomyopathy.

Circulation 2007 Mar 26;115(10):1244-51. Epub 2007 Feb 26.

University of Colorado at Denver and Health Sciences Center, Denver, Colo, USA.

Background: Desmin-related myofibrillar myopathy (DRM) is a cardiac and skeletal muscle disease caused by mutations in the desmin (DES) gene. Mutations in the central 2B domain of DES cause skeletal muscle disease that typically precedes cardiac involvement. However, the prevalence of DES mutations in dilated cardiomyopathy (DCM) without skeletal muscle disease is not known.

Methods And Results: Denaturing high-performance liquid chromatography was used to screen DES for mutations in 116 DCM families from the Familial Dilated Cardiomyopathy Registry and in 309 subjects with DCM from the Beta-Blocker Evaluation of Survival Trial (BEST). DES mutations were transfected into SW13 and human smooth muscle cells and neonatal rat cardiac myocytes, and the effects on cytoskeletal desmin network architecture were analyzed with confocal microscopy. Five novel missense DES mutations, including the first localized to the highly conserved 1A domain, were detected in 6 subjects (1.4%). Transfection of DES mutations in the 2B domain severely disrupted the fine intracytoplasmic staining of desmin, causing clumping of the desmin protein. A tail domain mutation (Val459Ile) showed milder effects on desmin cytoplasmic network formation and appears to be a low-penetrant mutation restricted to black subjects.

Conclusions: The prevalence of DES mutations in DCM is between 1% and 2%, and mutations in the 1A helical domain, as well as the 2B rod domain, are capable of causing a DCM phenotype. The lack of severe disruption of cytoskeletal desmin network formation seen with mutations in the 1A and tail domains suggests that dysfunction of seemingly intact desmin networks is sufficient to cause DCM.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.106.646778DOI Listing
March 2007

Lost in transition: challenges in the expanding field of adult genetics.

Am J Med Genet C Semin Med Genet 2006 Nov;142C(4):294-303

Adult Medical Genetics Program, Department of Medicine, University of Colorado Health Sciences, 12635 East Montview Boulevard, Aurora, CO 80045, USA.

It is increasingly clear that medical genetics has broad relevance in adult clinical medicine. More adult patients with genetic conditions are being recognized, genetic testing for adult-onset genetic conditions is expanding, and children with genetic conditions are now more likely to survive to adulthood. While the number of patients who could benefit from medical genetic services increases, adult care providers are less well educated about clinical genetics and are not sufficiently prepared to meet the growing needs of this population. Genetics professionals may also be ill-suited for this challenge, since geneticists and genetic counselors have traditionally had greater experience in pediatric and prenatal settings. Communication between primary care physicians who treat adults and the genetics community is currently suboptimal and the identification and subsequent referral of adult patients for genetic services need improvement. Finally, published guidelines that address how to deliver genetic services to adult patients are unavailable for many genetic conditions. In this article we address the challenges of transitioning genetics services from traditional, and largely pediatric-based models to paradigms that can best address the needs of adult patients with genetic conditions. Potential solutions and the practicality of implementation of a team-based approach to adult genetic medicine, including the application of genetic counseling, are also discussed.
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http://dx.doi.org/10.1002/ajmg.c.30105DOI Listing
November 2006

Ophthalmic manifestations of Danon disease.

Ophthalmology 2006 Jun;113(6):1010-3

Department of Ophthalmology, University of Colorado, Aurora, Colorado, USA.

Purpose: To describe the ophthalmic findings in patients with Danon disease, an X-linked condition causing cardiomyopathy in males and females.

Design: Retrospective case series.

Participants: Patients with genetically proven Danon disease.

Methods: Retrospective chart review of complete eye examinations including electroretinogram, visual fields, and fluorescein angiography.

Results: Five females (4 affected) and 2 affected males were examined. The 4 affected females demonstrated a peripheral pigmentary retinopathy. Lens changes, myopia, abnormal electroretinogram and visual fields were also found. The males demonstrated a near-complete loss of pigment in the retinal pigment epithelium.

Conclusion: We report the first description of a characteristic retinopathy in patients with Danon disease and the first extracardiac manifestations in affected females. Retinopathy potentially could be used to identify asymptomatic carriers.
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http://dx.doi.org/10.1016/j.ophtha.2006.02.030DOI Listing
June 2006

Thymopoietin (lamina-associated polypeptide 2) gene mutation associated with dilated cardiomyopathy.

Hum Mutat 2005 Dec;26(6):566-74

CU-Cardiovascular Institute, University of Colorado Health Sciences Center, Denver, Colorado, USA.

Thymopoietin or TMPO (indicated by its alternative gene symbol, LAP2, in this work) has been proposed as a candidate disease gene for dilated cardiomyopathy (DCM), since a LAP2 product associates with nucleoplasmic lamins A/C, which are encoded by the DCM gene LMNA. We developed a study to screen for genetic mutations in LAP2 in a large collection of DCM patients and families. A total of 113 subjects from 88 families (56 with familial DCM (FDC) and 32 with sporadic DCM) were screened for LAP2 mutations using denaturing high-performance liquid chromatography and sequence analysis. We found a single putative mutation affecting the LAP2alpha isoform in one FDC pedigree. The mutation predicts an Arg690Cys substitution (c.2068C>T; p.R690C) located in the C-terminal domain of the LAP2alpha protein, a region that is known to interact with lamin A/C. RT-PCR, Western blot analyses, and immunolocalization revealed low-level LAP2alpha expression in adult cardiac muscle, and localization to a subset of nuclei. Mutated Arg690Cys LAP2alpha expressed in HeLa cells localized to the nucleoplasm like wild-type LAP2alpha, with no effect on peripheral and nucleoplasmic lamin A distribution. However, the in vitro interaction of mutated LAP2alpha with the pre-lamin A C-terminus was significantly compromised compared to the wild-type protein. LAP2 mutations may represent a rare cause of DCM. The Arg690Cys mutation altered the observed LAP2alpha interaction with A-type lamins. Our finding implicates a novel nuclear lamina-associated protein in the pathogenesis of genetic forms of dilated cardiomyopathy.
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http://dx.doi.org/10.1002/humu.20250DOI Listing
December 2005

Alpha-myosin heavy chain: a sarcomeric gene associated with dilated and hypertrophic phenotypes of cardiomyopathy.

Circulation 2005 Jul;112(1):54-9

Familial Cardiomyopathy Registry Research Group, USA.

Background: Mutations in the beta-myosin heavy-chain (betaMyHC) gene cause hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy. In failing human hearts, downregulation of alphaMyHC mRNA or protein has been correlated with systolic dysfunction. We hypothesized that mutations in alphaMyHC could also lead to pleiotropic cardiac phenotypes, including HCM and DCM.

Methods And Results: A cohort of 434 subjects, 374 (134 affected, 214 unaffected, 26 unknown) belonging to 69 DCM families and 60 (29 affected, 30 unaffected, 1 unknown) in 21 HCM families, was screened for alphaMyHC gene (MYH6) mutations. Three heterozygous MYH6 missense mutations were identified in DCM probands (P830L, A1004S, and E1457K; 4.3% of probands). A Q1065H mutation was detected in 1 of 21 HCM probands and was absent in 2 unaffected offspring. All MYH6 mutations were distributed in highly conserved residues, were predicted to change the structure or chemical bonds of alphaMyHC, and were absent in at least 300 control chromosomes from an ethnically similar population. The DCM carrier phenotype was characterized by late onset, whereas the HCM phenotype was characterized by progression toward dilation, left ventricular dysfunction, and refractory heart failure.

Conclusions: This study suggests that mutations in MYH6 may cause a spectrum of phenotypes ranging from DCM to HCM.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.104.507699DOI Listing
July 2005

SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia.

Circulation 2004 Oct 4;110(15):2163-7. Epub 2004 Oct 4.

University of Colorado Cardiovascular Institute, Denver, Colo, USA.

Background: We studied a large family affected by an autosomal dominant cardiac conduction disorder associated with sinus node dysfunction, arrhythmia, and right and occasionally left ventricular dilatation and dysfunction. Previous linkage analysis mapped the disease phenotype to a 30-cM region on chromosome 3p22-p25 (CMD1E). This region also contains a locus for right ventricular cardiomyopathy (ARVD5) and the cardiac sodium channel gene (SCN5A), mutations that cause isolated progressive cardiac conduction defect (Lenegre syndrome), long-QT syndrome (LQT3), and Brugada syndrome.

Methods And Results: Family members were studied, and the positional candidate gene SCN5A was screened for mutations. We identified, by direct sequencing, a heterozygous G-to-A mutation at position 3823 that changed an aspartic acid to asparagine (D1275N) in a highly conserved residue of exon 21. This mutation was present in all affected family members, was absent in 300 control chromosomes, and predicted a change of charge within the S3 segment of domain III.

Conclusions: Our findings expand the clinical spectrum of disorders of the cardiac sodium channel to include cardiac dilation and dysfunction and support the hypothesis that genes encoding ion channels can be implicated in dilated cardiomyopathies.
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http://dx.doi.org/10.1161/01.CIR.0000144458.58660.BBDOI Listing
October 2004

Cardiology patient page. Familial dilated cardiomyopathy.

Circulation 2003 Oct;108(17):e118-21

University of Colorado Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Health Sciences Center, Denver, Colo 80010-7116, USA.

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http://dx.doi.org/10.1161/01.CIR.0000097493.70422.50DOI Listing
October 2003