Susan P. McGorray

Abnormal Coronary Vasomotion as a Prognostic Indicator of Cardiovascular Events in Women Results From the National Heart, Lung, and Blood Institute–Sponsored Women’s Ischemia Syndrome Evaluation (WISE)

Background—Coronary vascular dysfunction has been linked to atherosclerosis and adverse cardiovascular outcomes in men, but these relationships have not been firmly established in women. Methods and Results—As part of the Women’s Ischemia Syndrome Evaluation (WISE) sponsored by the National Heart, Lung, and Blood Institute, 163 women referred for clinically indicated coronary angiography underwent coronary reactivity assessment with quantitative coronary angiography and intracoronary Doppler flow before and after intracoronary administration of acetylcholine, adenosine, and nitroglycerin and were then followed up for clinical outcomes. History of hypertension was present in 61%, dyslipidemia in 54%, diabetes in 26%, and current tobacco use in 21% of women enrolled. Seventy-five percent had no or only mild epicardial coronary artery disease (CAD). Over a median follow-up of 48 months, events occurred in 58 women. On bivariate analysis, women with an event had significantly less change in coronary cross-sectional area (&Dgr;CSA) in response to acetylcholine (P =0.0006) and nitroglycerin (P =0.04). In addition, women with abnormal coronary dilator response to acetylcholine had less time free from cardiovascular events (P =0.004). In multivariable analysis, after controlling for age, hypertension, diabetes, dyslipidemia, tobacco use, and CAD severity, %&Dgr;CSA with acetylcholine (P =0.001) independently predicted events. When the outcome was restricted to only death, myocardial infarction, congestive heart failure, and stroke, %&Dgr;CSA with acetylcholine remained a significant predictor (P =0.006). Conclusions—In women in this study, impaired coronary vasomotor response to acetylcholine was independently linked to adverse cardiovascular outcomes regardless of CAD severity.

β1‐Adrenergic Receptor Polymorphisms and Antihypertensive Response to Metoprolol

Marked interpatient variability exists in blood pressure response to β‐blocker monotherapy. We tested the hypothesis that 2 common polymorphisms in the gene for β1‐adrenergic receptor are associated with antihypertensive response to metoprolol in patients with uncomplicated hypertension.

Anteroposterior skeletal and dental changes after early Class II treatment with bionators and headgear.

In this study we examined anteroposterior cephalometric changes in children enrolled in a randomized controlled trial of early treatment for Class II malocclusion. Children, aged 9.6 +/- 0.8 years at the start of study, were randomly assigned to control (n = 81), bionator (n = 78), and headgear/biteplane (n = 90) treatments. Cephalograms were obtained initially, after Class I molars were obtained or 2 years had elapsed, after an additional 6 months during which treated subjects were randomized to retention or no retention and after a final 6 months without appliances. Calibrated examiners, blinded to group, used Johnstons analysis to measure anteroposterior cephalometric changes. Statistical analysis was used to determine annual skeletal and dental changes during treatment, retention, and follow-up, and overall. Our data reveal that both bionator and head-gear treatments corrected Class II molar relationships, reduced overjets and apical base discrepancies, and caused posterior maxillary tooth movement. The skeletal changes, largely attributable to enhanced mandibular growth in both headgear and bionator subjects, were stable a year after the end of treatment, but dental movements relapsed.

Dobutamine Stress Echocardiography in Women With Chest Pain Pilot Phase Data from the National Heart, Lung and Blood Institute Women's Ischemia Syndrome Evaluation (WISE)

OBJECTIVES The aim of this project was to assess the utility of dobutamine stress echocardiography (DSE) for evaluation of women with suspected ischemic heart disease. BACKGROUND Most investigations addressing efficacy of diagnosis and treatment of coronary artery disease (CAD) have been performed in predominantly male populations. As part of the Womens Ischemia Syndrome Evaluation (WISE) study, DSE was assessed in women participating at the University of Florida clinical site. METHODS Women with chest pain or other symptoms suggestive of myocardial ischemia and clinically indicated coronary angiography were eligible for the WISE study. Enrolled subjects underwent DSE using a modified protocol. Coronary stenosis was assessed by core laboratory quantitative coronary angiography (QCA). RESULTS The 92 women studied ranged in age from 34 to 82 years (mean 57.5). All women had > or = 1 major risk for CAD, and most (89, 97%) had > or = 2 risk factors. In 78 women (85%), left ventricular wall motion was normal at baseline and during peak infusion. The remaining 14 women had wall motion abnormalities during DSE. By QCA, 25 women (27%) had > or = 50% coronary stenosis, including 10 with single-vessel obstruction. Dobutamine stress echocardiography was abnormal in 10 of these 25 women, yielding overall sensitivity of 40%, and 60% for multivessel stenosis. Exclusion of women with inadequate heart rate response yielded overall sensitivity of 50%, and 81.8% for multivessel stenosis. Dobutamine stress echocardiography was normal in 54 of the 67 women with < 50% coronary narrowing, specificity 80.6%. CONCLUSIONS Dobutamine stress echocardiography reliably detects multivessel stenosis in women with suspected CAD. However, DSE is usually negative in women with single-vessel stenosis, and in the larger subset without coronary stenosis. Ongoing protocols of the WISE study are expected to improve diagnostic accuracy in women with single-vessel disease, as well as provide important data in the substantial number of women with chest pain but without epicardial coronary artery stenosis.

Comparison of peer assessment ratings (PAR) from 1-phase and 2-phase treatment protocols for class II malocclusions

The purpose of this study was to compare the dentoalveolar outcomes after 1-phase and 2-phase orthodontic treatment of Class II malocclusions. Class II subjects (n = 208) were randomized to 1-phase or 2-phase treatment with either bionator or headgear/biteplate. The peer assessment rating (PAR) was calculated from pretreatment, prephase 2, and final study models. Chi-square, Kruskal-Wallis, and Wilcoxon rank sum tests were used to evaluate the differences among treatment groups, sexes, races, pretreatment, mandibular plane angle, severity, and compliance. Spearman rank correlation coefficients were used to examine relationships between PAR at different times. The dropout rate of 24.6% did not adversely affect the ability to detect differences of clinical importance or impact treatment groups disproportionately. There were no significant differences with respect to initial PAR or final PAR among the 3 treatment protocols. The 2 early treatment groups had lower PAR scores than the 1-phase group before phase 2 (P =.0001). Lower PAR scores were achieved at both the beginning and end of phase 2 in girls (P =.03; P =.02, respectively). There were differences in the pre-phase-2 and post-phase-2 PAR scores based on initial severity (P =.0006; P =.02, respectively), with greater improvement in the patients whose malocclusions were less severe initially. Mandibular plane angle had no effect on pre-phase-2 or post-phase-2 PAR scores. These results do not support the hypothesis that different dentoalveolar outcomes are obtained between 2-phase and 1-phase treatment of Class II malocclusions.

Risk factors associated with temporomandibular joint sounds in children 6 to 12 years of age.

The relationship between temporomandibular joint (TMJ) sounds and a persons dental and skeletal characteristics is poorly understood. In this study, data were obtained from 3428 grade schoolchildren (mean age = 9.0 years, SD = 0.8, range 6 to 12 years), without a history of orthodontic treatment. Each child had been examined independently by one of six orthodontists to assess: TMJ sounds (none, click, crepitus), gender, age, race (white/black), skeletal relationships (convexity, maxillary, and mandibular positions), malocclusion (molar class, overjet, overbite, anterior crowding, posterior crossbite), maximum opening, chin trauma (none, cut, scar), and history of lower facial trauma. Temporomandibular joint sounds were present in 344 children (10.0% of the sample); 276 (8.1%) had an isolated unilateral sound, 254 (7.4%) had unilateral clicking, 50 (1.5%) had bilateral clicking, 22 (0.6%) had unilateral crepitus, and 11 (0.3%) had bilateral crepitus. Univariate analyses compared children with and without sounds for each variable; logistic regression analyses examined the relationship between groups of variables and TMJ sounds. The prevalence of TMJ sounds was associated with examiner (chi 2 = 23.4, df = 5, p < 0.001); increased prevalence of TMJ sounds occurred in children with maxillary anterior crowding (t = 2.8, p < 0.006), mandibular anterior crowding (t = 3.0, p < 0.002), and increased maximum opening (t = 4.7, p < 0.001). In contrast to other reports on children, the prevalence of joint sounds was not associated with age, race, gender, or molar class.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of a Recombinant Adeno-Associated Virus Type 2 Reference Standard Material

A recombinant adeno-associated virus serotype 2 Reference Standard Material (rAAV2 RSM) has been produced and characterized with the purpose of providing a reference standard for particle titer, vector genome titer, and infectious titer for AAV2 gene transfer vectors. Production and purification of the reference material were carried out by helper virus-free transient transfection and chromatographic purification. The purified bulk material was vialed, confirmed negative for microbial contamination, and then distributed for characterization along with standard assay protocols and assay reagents to 16 laboratories worldwide. Using statistical transformation and modeling of the raw data, mean titers and confidence intervals were determined for capsid particles ({X}, 9.18 x 10¹¹ particles/ml; 95% confidence interval [CI], 7.89 x 10¹¹ to 1.05 x 10¹² particles/ml), vector genomes ({X}, 3.28 x 10¹⁰ vector genomes/ml; 95% CI, 2.70 x 10¹⁰ to 4.75 x 10¹⁰ vector genomes/ml), transducing units ({X}, 5.09 x 10⁸ transducing units/ml; 95% CI, 2.00 x 10⁸ to 9.60 x 10⁸ transducing units/ml), and infectious units ({X}, 4.37 x 10⁹ TCID₅₀ IU/ml; 95% CI, 2.06 x 10⁹ to 9.26 x 10⁹ TCID₅₀ IU/ml). Further analysis confirmed the identity of the reference material as AAV2 and the purity relative to nonvector proteins as greater than 94%. One obvious trend in the quantitative data was the degree of variation between institutions for each assay despite the relatively tight correlation of assay results within an institution. This relatively poor degree of interlaboratory precision and accuracy was apparent even though attempts were made to standardize the assays by providing detailed protocols and common reagents. This is the first time that such variation between laboratories has been thoroughly documented and the findings emphasize the need in the field for universal reference standards. The rAAV2 RSM has been deposited with the American Type Culture Collection and is available to the scientific community to calibrate laboratory-specific internal titer standards. Anticipated uses of the rAAV2 RSM are discussed.

Monitoring uterine activity during labor: a comparison of 3 methods

OBJECTIVE Tocodynamometry (Toco; strain gauge technology) provides contraction frequency and approximate duration of labor contractions but suffers frequent signal dropout, necessitating repositioning by a nurse, and may fail in obese patients. The alternative invasive intrauterine pressure catheter (IUPC) is more reliable and adds contraction pressure information but requires ruptured membranes and introduces small risks of infection and abruption. Electrohysterography (EHG) reports the electrical activity of the uterus through electrodes placed on the maternal abdomen. This study compared all 3 methods of contraction detection simultaneously in laboring women. STUDY DESIGN Upon consent, laboring women were monitored simultaneously with Toco, EHG, and IUPC. Contraction curves were generated in real-time for the EHG, and all 3 curves were stored electronically. A contraction detection algorithm was used to compare frequency and timing between methods. Seventy-three subjects were enrolled in the study; 14 were excluded due to hardware failure of 1 or more of the devices (n = 12) or inadequate data collection duration (n = 2). RESULTS In comparison with the gold-standard IUPC, EHG performed significantly better than Toco with regard to the Contractions Consistency Index (CCI). The mean CCI for EHG was 0.88 ± 0.17 compared with 0.69 ± 0.27 for Toco (P < .0001). In contrast to Toco, EHG was not significantly affected by obesity. CONCLUSION Toco does not correlate well with the gold-standard IUPC and fails more frequently in obese patients. EHG provides a reliable noninvasive alternative, regardless of body habitus.

Symptoms, myocardial ischaemia and quality of life in women: Results from the NHLBI-sponsored WISE Study

AIMS Our goal was to evaluate health-related quality of life (QOL) in women undergoing angiography for suspected ischaemia. METHODS AND RESULTS QOL measurements were obtained in 406 women with chest pain symptoms in the Womens Ischemia Syndrome Evaluation (WISE). QOL measures included a general rating (GR), Duke Activity Status Index (DASI), and the Beck Depression Inventory (BDI). Higher scores on the GR and DASI are indicative of better QOL and functioning. Higher scores on the BDI indicate more symptoms of depression. Women were stratified by the presence and absence of obstructive angiographic coronary artery disease (CAD) and by the presence and absence of myocardial ischaemia. Women with angiographic obstructive CAD had lower DASI and higher BDI scores compared to women without obstructive CAD (both P<0.05). Stratification by the presence and absence of ischaemia demonstrated that women with ischaemia had better QOL, evidenced by higher GR QOL scores and lower BDI scores (both P<0.05) than women without ischaemia. Symptoms of angina were significant independent predictors of QOL scores (P<0.001). CONCLUSIONS Chest pain symptoms have a significant impact on health-related QOL in women undergoing coronary angiography for suspected myocardial ischaemia andare more important determinants of QOL than the underlying conditions of CAD or ischaemia.

Dysplasia and cytologic findings in 4,589 young women enrolled in diethylstilbestrol-adenosis (DESAD) project.

Abstract This report presents the cytologic findings and the rates of dysplasia for 4,589 young women enrolled in the National Cooperative Diethylstilbestrol-Adenosis (DESAD) Project. Mucinous columnar cells and/or metaplastic squamous cells with or without mucinous droplets were encountered in 22% of vaginal scrape smears from all diethylstilbestrol (DES)-exposed participants identified by review of prenatal records and in 43% of women in whom vaginal epithelial changes (VEC) were observed by colposcopy or by iodine staining. The frequency of cellular findings in the vaginal scrape smears was closely related to the timing of the administration of the DES to the mother. With increasing age of the daughters, the overall frequencies of both the mucinous and metaplastic cells decreased; relative to each other, an increasing proportion was metaplastic squamous cells. These data suggest that, as the women grow older, vaginal adenosis regresses by the process of squamous metaplasia. Endometrial type cells were found in 2% of vaginal scrape smears. Their cyclical occurrence during the menstrual cycle and lack of correlation with the presence of VEC indicated an origin from the uterine corpus rather than the tuboendometrial type of adenosis. Squamous cell dysplasia of the vagina and cervix was detected by biopsy or scrape smear specimens in 1.8% of DES-exposed women in the record review group. The rate in unexposed women was twice as high. In general, the rates of dysplasia were higher in the cervix than vagina, and the more severe degrees of dysplasia were encountered only in those women who were referred to the DESAD Project or who themselves requested entry. Four patients who were referred or who themselves requested entry were found to have clear cell adenocarcinoma of the vagina. The vaginal smear provided the first clue to the presence of an abnormality in three of them.