Shu Fen Wung

Nurses transforming health care using genetics and genomics

Nurses are well positioned to incorporate genetic and genomic information across all aspects of the United States (U.S.) health care system. Nurses, the most trusted health professionals [1], make unique contributions to the field of human genetics and genomics and complement the work of other health care providers to improve the health of the public. Health care benefits greatly from the unprecedented and ongoing work elucidating the genetic/genomic basis of health, illness, disease risk, and treatment response. The progress in genetics and genomics is applicable to the entire spectrum of health care and all health professionals and as such to the entire nursing profession (2.9 million) [2] in the United States regardless of role, clinical specialty, or academic preparation. The majority of disease risk, health conditions and the therapies used to treat those conditions have a genetic and/or genomic element influenced by environmental, lifestyle, and other factors therefore impacting the entire nursing profession [3]. Nurses have intimate knowledge of the patient’s, family’s, and community’s perspectives; an understanding of biologic underpinnings; experience with genetic/genomic technologies and information; skills in communication and building coalitions; and most importantly, the public’s trust. Across the lifespan, nursing focuses on health promotion and disease prevention, which is an integral component of genetic/genomic health care practices. Awareness of nurses’ strengths and skills, together with the recognition that prevention is the hallmark of genetic/genomic health care, will inform public policymaking groups as they address issues that affect heath care practice in the area of genetics/genomics. Policy making process will be informed with new insights will be gained with inclusion of nurses and professional nursing organizations. These policies can facilitate the ability of U.S. health care systems to use genetic/genomic knowledge to promote health and manage disease.

Accuracy of the EASI 12-lead electrocardiogram compared to the standard 12-lead electrocardiogram for diagnosing multiple cardiac abnormalities.

This study was performed to compare a derived 12-lead electrocardiogram (ECG) using a simple 5-electrode lead configuration (EASI 12-lead) with the standard ECG for multiple cardiac diagnoses. Accurate diagnosis of arrhythmias and ischemia often require analysis of multiple (ideally, 12) ECG leads; however, continuous 12-lead monitoring is impractical in hospital settings. EASI and standard ECGs were compared in 540 patients, 426 of whom also had continuous 12-lead ST segment monitoring with both lead methods. Independent standards relative to a correct diagnosis were used whenever possible, for example, echocardiographic data for chamber enlargement-hypertrophy, and troponin levels for acute infarction. Percent agreement between the 2 methods were: cardiac rhythm, 100%; chamber enlargement-hypertrophy, 84%-99%; right and left bundle branch block, 95% and 97%, respectively; left anterior and posterior fascicular block, 97% and 99%, respectively; prior anterior and inferior infarction, 95% and 92%, respectively. There was very little variation between the 2 lead methods in cardiac interval measurements; however, there was more variation in P, QRS, and T-wave axes. Of the 426 patients with ST monitoring, 138 patients had a total of 238 ST events (26, acute infarction; 62, angioplasty-induced ischemia; 150, spontaneous transient ischemia). There was 100% agreement between the 2 methods for acute infarction, 95% agreement for angioplasty-induced ischemia, and 89% agreement for transient ischemia. EASI and standard 12-lead ECGs are comparable for multiple cardiac diagnoses; however, serial ECG changes (eg, T-wave changes) should be assessed using one consistent 12-lead method.

Bedside diagnosis of myocardial ischemia with ST-segment monitoring technology: Measurement issues for real-time clinical decision making and trial designs

Monitoring of the ST segment is a valuable tool for guiding clinical decision making and evaluating anti-ischemia interventions in clinical trials; however, measurement issues hamper its diagnostic accuracy. This study reports the frequency and type of false positives and other measurement issues we have encountered during 12-lead ST-segment monitoring of patients in a cardiac care unit. Of 292 patients, 117 (40%) had one or more false positive events during an average of 41 hours of ST-segment monitoring, for a total of 506 false positive events. The 506 false positive events included 167 (36%) due to body positional change; 132 (26%) due to sudden increase in QRS complex/ST-segment voltage; 96 (19%) due to transient arrhythmia or pacing; 80 (16%) due to heart rate change in steeply sloped ST-segment contours; 26 (5%) due to a noisy signal; and 5 (1%) due to lead misplacement. It is concluded that many conditions in addition to myocardial ischemia can cause transient ST-segment deviation in patients with unstable coronary syndromes. Accurate ST-segment monitoring requires expertise in electrocardiogram interpretation, an understanding of the patients clinical situation, and knowledge of the functions and limitations of the ST-segment monitoring system.

New electrocardiographic criteria for posterior wall acute myocardial ischemia validated by a percutaneous transluminal coronary angioplasty model of acute myocardial infarction

The standard 12-lead electrocardiogram (ECG) fails to detect ST-segment elevation in patients with posterior wall acute myocardial ischemia. However, additional posterior leads V(7-9) provide limited additional diagnostic information to the standard 12-lead ECG when an ischemic criterion of 1-mm ST elevation is used. No study is available to delineate the ischemic criteria in the posterior electrocardiographic leads. Continuous 15-lead ECGs (standard 12 lead + V(7-9)) were recorded in 53 subjects undergoing elective left circumflex coronary angioplasty (posterior ischemia model). ST amplitudes (J + 60 ms) at preangioplasty baseline were subtracted from maximal ST amplitudes during balloon occlusion to create a positive or negative change score (DeltaST) for each of the 15 leads. During 53 left circumflex occlusions, 26 subjects (49%) had DeltaST elevation of > or = 1 mm and 24 subjects (45%) had DeltaST elevation ranging from 0.5 to 0.95 mm in > or = 1 posterior leads. Five subjects (9%) had DeltaST elevation of > or = 1 mm in the posterior leads without DeltaST elevation anywhere in any of the 12 leads. The sensitivity in detecting myocardial ischemia using 15-lead ECGs (58%) was not statistically different from the standard 12-lead ECG (49%) (p = 0.06). Adjusting the ischemic criterion from 1 to 0.5 mm in V(7-9) significantly improved the sensitivity from 49% in the 12-lead ECG to 94% in the 15-lead ECG (p = 0.000). In addition, 12 subjects (23%) had posterior ST-segment elevation without anterior ST-segment depression. Thus, posterior leads V(7-9) contribute significant additional diagnostic information above and beyond the standard 12-lead ECG only when a new ischemic criterion of 0.5 mm instead of 1 mm ST elevation is applied to the posterior leads.

Comparison of 18-lead ECG and selected body surface potential mapping leads in determining maximally deviated ST lead and efficacy in detecting acute myocardial ischemia during coronary occlusion

Kornreich identified 6 body surface potential mapping (BSPM) leads outside the standard 12-lead electrocardiographic (ECG) sites for optimal recognition of ST segment elevation (+) and depression (-) during acute ischemia in anterior, inferior, and posterior myocardial zones (A+, A-, I+, I-, P+, P-). No comparison has been made between the 6 selected BSPM leads and 18-lead ECG (12 + V3-5R + V7-9) in detecting acute myocardial ischemia during coronary occlusion. Continuous 18-lead ECG and 6 selected BSPM leads were recorded in 68 patients (77 vessels) undergoing coronary angioplasty during balloon occlusion. Ischemia was defined as ST segment deviation (deltaST) > or = 100 microV > or = 1 lead from the preinflation baseline. The 18-lead ECG was a more frequent source of the maximal deltaST lead during left anterior descending artery, right coronary artery, and left circumflex artery occlusion (71 [92%]) than the 6 selected BSPM leads (5 [7%]). The 18-lead ECG was more efficacious than the 6 selected BSPM leads for detecting acute myocardial ischemia in the group as whole. The 18-lead ECG was also more efficacious for detecting right ventricular ischemia associated with proximal right coronary artery occlusion and for detecting ST segment elevation during left circumflex artery occlusion. Our findings indicate that the 18-lead ECG is the most frequent source of maximally deviated lead and is more efficacious in detecting myocardial ischemia during balloon occlusion than the 6 selected BSPM leads. The 6 selected BSPM leads do not add information above and beyond the 12- or 18-lead ECG, and thus cannot be recommended as optimal sites for continuous ST segment monitoring of patients with acute coronary syndromes.

The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion

BackgroundLipoprotein Lipase (LPL), a key enzyme in lipid metabolism, catalyzes the hydrolysis of triglycerides (TG) from TG-rich lipoproteins, and serves a bridging function that enhances the cellular uptake of lipoproteins. Abnormalities in LPL function are associated with pathophysiological conditions, including familial combined hyperlipidemia (FCH). Whereas two LPL susceptibility alleles were found to co-segregate in a few FCH kindred, a role for common, protective alleles remains unexplored. The LPL Ser447Stop (S447X) allele is associated with anti-atherogenic lipid profiles and a modest reduction in risk for coronary disease. We hypothesize that significant depletion of the 447X allele exists in combined hyperlipidemia cases versus controls. A case-control design was employed. The polymorphism was assessed by restriction assay in 212 cases and 161 controls. Genotypic, allelic, and phenotypic associations were examined.ResultsWe found evidence of significant allelic (447Xcontrol: 0.130 vs. 447Xcase: 0.031, χ2 = 29.085; 1df; p < 0.001) and genotypic association (SS: 0.745 vs. 0.939, and SX+XX: 0.255 vs. 0.061) in controls and cases, respectively (χ2 = 26.09; 1df; p < 0.001). In cases, depletion of the 447X allele is associated with a significant elevation in very-low-density lipoprotein cholesterol (VLDL-C, p = 0.045). Consonant with previous studies of this polymorphism, regression models predict that carriers of the 447X allele displayed significantly lower TG, low-density lipoprotein cholesterol (LDL-C) and TG/high-density lipoprotein cholesterol (HDL-C) ratio.ConclusionThese findings suggest a role for the S447X polymorphism in combined hyperlipidemia and demonstrate the importance of evaluating both susceptibility and protective genetic risk factors.

Comparison of anterior chamber depth of normal and keratoconus eyes using scheimpflug photography

Objectives To compare the corneal anterior chamber depth (ACD) adjusted by age and sex in normal and keratoconus eyes. Methods Scheimpflug photography with the Oculus Pentacam was used to measure the ACD of 162 normal and 41 keratoconus patients. Results Univariate analysis showed that the mean ACD of 162 normal subjects (3.18 ± 0.32 mm) was borderline significantly less than in 41 keratoconus patients (3.28 ± 0.40 mm; P=0.079). However, we found that sex (P=0.001) and age (P<0.001) are significantly related to ACD in all patients. Women with normal eyes had a significantly lower mean ACD (3.13 ± 0.34 mm) than men (3.27 ± 0.28 mm, P=0.008). Women with keratoconus eyes also had a lower mean ACD (3.16 ± 0.39 mm) than men with keratoconus (3.42 ± 0.36 mm, P=0.032). Bivariate regression showed that with each additional year of aging, the ACD was decreased by an average of 0.012 mm in a normal eye (P<0.001) and by 0.014 mm in a keratoconus eye (P<0.001). Regression analysis showed that sex (P=0.003), age (P<0.001), and keratoconus (P=0.003) are all significant variables for determining ACD. After adjusting for age and sex, keratoconus eyes had a significantly higher mean ACD (3.34 ± 0.34 mm) than normal eyes (3.18 ± 0.28 mm) (P=0.003). Conclusions Sex, age, and keratoconus are all significant variables for ACD. After adjusting for age, keratoconus eyes of both genders had a significantly higher ACD than normal eyes of both genders. Women showed lower mean ACD than men in both normal and keratoconus eyes.

Obstructive sleep apnea hypopnea syndrome and metabolic syndrome: A synergistic cardiovascular risk factor

Purpose: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality for adults in the United States. One risk factor for CVD is metabolic syndrome, which encompasses obesity, hypertension, insulin resistance, proinflammatory state, and prothrombotic state. A lesser‐understood risk factor is obstructive sleep apnea hypopnea syndrome (OSAHS). This article explores the physiological consequences of the interaction between OSAHS and metabolic syndrome on the cardiovascular system. Data sources: Search terms “metabolic syndrome,”“obstructive sleep apnea,”“cardiovascular disease,”“diabetes,”“obesity,” and “atherosclerosis,” were used. Studies involving children were excluded. Conclusions: Both metabolic syndrome and OSAHS have significant impact on the cardiovascular system; however, when both conditions are present together, the impact is synergistic and CVD risk is multiplied. Treatment with continuous positive airway pressure (CPAP) reduces the global burden of CVD risk. Implications for practice: Providers need to screen patients routinely for both metabolic syndrome and OSAHS. Treatment should include CPAP, weight reduction, oral appliances, and/or upper airway surgeries with concurrent management for metabolic syndrome. Future research should further elucidate the mechanisms of action by which OSAHA and metabolic syndrome contribute to CVD. This understanding can lead to more stringent guidelines on the management of metabolic syndrome and OSAHS.

Corneal endothelial cell count in keratoconus patients after contact lens wear.

Purpose. The influence of contact lenses on healthy corneal endothelium has been well documented, but little is known about the effect of contact lens wear on the corneal endothelial cells of patients with keratoconus. This cross-sectional comparative study was conducted to determine quantitative characteristics of corneal endothelial cells of 100 patients with keratoconus with or without contact lenses. Methods. A Humphrey Atlas corneal topographer was used to map the keratoconic cornea. The corneal apex of the cone was located by using the axial topography map. The Konan SP-9000 Noncon Robo Pachy specular microscope and the Konan SP-400 specular microscopes were used to photograph the endothelium at the apex of the cone, and the average endothelial cell count was obtained. Patients were categorized into four groups based on the types of contact lenses worn: no contact lenses, SofLens 66 toric contact lenses, SoftPerm contact lenses, and FluoroPerm 30 aspheric rigid gas-permeable (RGP) contact lenses. Analysis of variance was used to determine differences in endothelial cell counts among groups. Results. After controlling for age and severity of keratoconus, patients who wore SoftPerm contact lenses had 18% lower endothelial cell counts (2,157 ± 442) than did patients without contact lenses (2,538 ± 398). These patients also had 15% lower endothelial cell counts than did patients who wore soft toric disposable contact lenses (2,483 ± 292). There was a 7% lower endothelial cell count in the group wearing aspheric RGP contact lenses than in the group that did not wear contact lenses, and a 5% lower endothelial cell count in the group wearing aspheric RGP contact lenses than in the group that wore soft toric contact lenses, but these differences were not statistically significant. Conclusions. Patients with keratoconus who wear SoftPerm contact lenses have a significantly lower endothelial cell count than those patients with keratoconus who do not wear lenses, or who wear soft toric disposable contact lenses or RGP contact lenses.

Gender and ethnic differences in a case-control study of dyslipidemia: using the apolipoprotein A-V gene as an exemplar in cardiovascular genetics.

Common, complex genetic disorders such as coronary heart disease (CHD) frequently show large population differences, contributing to health disparities. It is also well known that CHD risk factor profiles and the frequency of coronary events differ by gender. Study of premature CHD has revealed that apolipoproteins are important discriminating factors for distinguishing individuals with CHD. Recent findings indicated that apolipoprotein A-V (APOA-V) gene promoter polymorphisms are an important determinant of plasma triglycerides (TG) and lipoprotein cholesterol, and a risk factor for CHD. Variations in APOA-V may have varying impacts in different ethnic groups. The purpose of this interdisciplinary genetic research project was to determine (1) the association of the APOA-V polymorphisms with lipoprotein profiles, and (2) the gender and ethnic differences in the T-1131C promoter polymorphism of the APOA-V gene in individuals with dyslipidemia versus controls. Results indicate that the minor -1131C allele (CC homozygotes + CT heterozygotes) was associated with elevated plasma TG (p = 0.007), very low density lipoprotein (VLDL)–TG (p = 0.019), LDL-TG (p = 0.004), high-density-lipoprotein (HDL)-TG (p < 0.001), and VLDL-cholesterol (p = 0.008). We found a striking elevation in the frequency of the minor C allele in Asians (p < 0.001) compared to Europeans. We also found a significant difference in genotype frequency between men and women in Asians (p = 0.031) and Europeans (p < 0.01). Remarkably, Asian women with the C allele have a 36% increase in TG compared to Asian women homozygous for the T allele. In summary, we found significant ethnic-specific and gender-based differences in the frequency of the minor allele of the -1131 APOA-V gene promoter polymorphism. Identification of genetic variations among ethnic groups and between genders may have significant potential for a better understanding of the development of cardiovascular disease.