Michael O'Keefe - Academia.edu (original) (raw)

Papers by Michael O'Keefe

Annals of Cardiothoracic Surgery, 2021

JACC: Clinical Electrophysiology, 2015

OBJECTIVES This study aimed to determine the spatiotemporal stability of rotors and other atrial ... more OBJECTIVES This study aimed to determine the spatiotemporal stability of rotors and other atrial activation patterns over 10 min in longstanding, persistent AF, along with the relationship of rotors to short cycle-length (CL) activity. BACKGROUND The prevalence, stability, and mechanistic importance of rotors in human atrial fibrillation (AF) remain unclear. METHODS Epicardial mapping was performed in 10 patients undergoing cardiac surgery, with bipolar electrograms recorded over 10 min using a triangular plaque (area: 6.75 cm 2 ; 117 bipoles; spacing: 2.5 mm) applied to the left atrial posterior wall (n ¼ 9) and the right atrial free wall (n ¼ 4). Activations were identified throughout 6 discrete 10-s segments of AF spanning 10 min, and dynamic activation mapping was performed. The distributions of 4,557 generated activation patterns within each mapped region were compared between the 6 segments. RESULTS The dominant activation pattern was the simultaneous presence of multiple narrow wave fronts (26%). Twelve percent of activations represented transient rotors, seen in 85% of mapped regions with a median duration of 3 rotations. A total of 87% were centered on an area of short CL activity (<100 ms), although such activity had a positive predictive value for rotors of only 0.12. The distribution of activation patterns and wave-front directionality were highly stable over time, with a single dominant pattern within a 10-s AF segment recurring across all 6 segments in 62% of mapped regions. CONCLUSIONS In patients with longstanding, persistent AF, activation patterns are spatiotemporally stable over 10 min. Transient rotors can be demonstrated in the majority of mapped regions, are spatiotemporally associated with

Journal of the American College of Cardiology, Jan 27, 2018

It is unclear whether the Ross procedure offers superior survival compared with mechanical aortic... more It is unclear whether the Ross procedure offers superior survival compared with mechanical aortic valve replacement (AVR). This study evaluated experience and compared long-term survival between the Ross procedure and mechanical AVR. Between 1992 and 2016, a total of 392 Ross procedures were performed. These were compared with 1,928 isolated mechanical AVRs performed during the same time period as identified using the University of Melbourne and Australia and New Zealand Society of Cardiac and Thoracic Surgeons' Cardiac Surgery Databases. Only patients between 18 and 65 years of age were included. Propensity-score matching was performed for risk adjustment. Ross procedure patients were younger, and had fewer cardiovascular risk factors. The Ross procedure was associated with longer cardiopulmonary bypass and aortic cross-clamp times. Thirty-day mortality was similar (Ross, 0.3%; mechanical, 0.8%; p = 0.5). Ross procedure patients experienced superior unadjusted long-term surviva...

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, Jan 12, 2018

The Ross procedure has demonstrated excellent results when performed in patients with aortic sten... more The Ross procedure has demonstrated excellent results when performed in patients with aortic stenosis or mixed aortic valve disease [aortic stenosis and aortic regurgitation (AR)]. However, due to its reported risk of late reoperation, it is not recommended under current guidelines for patients presenting with bicuspid aortic valve and pure AR. We have analysed our own results in light of this recommendation. Between 1993 and 2016, 129 consecutive patients with a mean age of 34.7 ± 10.6 years (range 16-64 years) presented with bicuspid aortic valve and pure AR and underwent the Ross procedure. Patients were reviewed annually and had 2nd yearly transthoracic echocardiograms during follow-up. The unit had a liberal reoperation policy where reoperation was performed if patients developed recurrent moderate or greater AR during follow-up. There was 1 inpatient death, and 3 late deaths over a mean follow-up duration of 9.6 ± 6.8 years. Late survival at 10 and 20 years post-surgery were 9...

Circulation. Arrhythmia and electrophysiology, 2014

The pulmonary vein-left atrial (PV-LA) junction is key in pathogenesis of AF, and acute stretch i... more The pulmonary vein-left atrial (PV-LA) junction is key in pathogenesis of AF, and acute stretch is an important stimulus to AF. We aimed to characterize the response of the junction to acute stretch, hypothesizing that stretch would result in electrophysiological changes predisposing to re-entry. Fifteen participants undergoing cardiac surgery underwent evaluation of the right superior PV-LA junction using an epicardial mapping plaque. In 10, this was performed before and after atrial stretch imposed by rapid volume expansion, and in 5, it was performed with an intervening observation period. Activation was characterized by conduction slowing and electrogram fractionation transversely across the PV-LA junction, with lines of block also demonstrated perpendicular to the junction. Conduction was decremental (plaque activation time 135.8 ± 46.8 ms with programmed extra stimuli at 10 ms above effective refractory period versus 66.1 ± 22.9 ms with pacing at 400 ms; P<0.001) and percen...

The Journal of thoracic and cardiovascular surgery, 2015

It is hypothesized that by performing radical aortic root manipulation and then autologous suppor... more It is hypothesized that by performing radical aortic root manipulation and then autologous support for the pulmonary autograft in the Ross procedure, this will maintain aortic root size and should, in turn, lead to the demonstrated low incidence of late aortic regurgitation and need for reoperation on the aortic root and valve. Aortic root size was measured echocardiographically both preoperatively and then at second yearly intervals in 322 consecutive patients who underwent a Ross operation between October 1992 and June 2013 with autologous support of the pulmonary autograft root using the patient's own aorta. This technique, a variant of the inclusion cylinder method, has been developed with the aim of minimizing prosthetic materials in the aortic root. Measures to reduce aortic root size included annulus reduction in 201 patients (62.4%) and reduction in aortic sinus or sinotubular junction in 159 patients (49.4%). Maximal aortic root diameter postoperatively at 5, 10, and 15...

Global cardiology science & practice, 2013

To report our experience with the Ross operation in patients with predominant aortic stenosis (AS... more To report our experience with the Ross operation in patients with predominant aortic stenosis (AS) using an inclusion cylinder (IC) method. Out of 324 adults undergoing a Ross operation, 204 patients of mean age of 41.3 years (limits 16-62) underwent this procedure for either AS or mixed AS and regurgitation (AS/AR) between October, 1992 and February, 2012, implanting the PA with an IC method. Clinical follow up and serial echo data for this group is 97% complete with late mortality follow up 99% complete. There has been zero (0%) early mortality, and late survival at 15 years is 98% (96%, 100%). Only one re-operation on the aortic valve for progressive aortic regurgitation (AR) has been required with freedom from re-operation on the aortic valve at 15 years being 99% (96%, 100%). The freedom from all re-operations on the aortic and pulmonary valves at 15 years is 97% (94%, 100%). Echo analysis at the most recent study shows that 98% have nil, trivial or mild AR. Aortic root size ha...

The Journal of infectious diseases, Jan 24, 2014

Human papillomavirus (HPV) causes external genital lesions (EGLs) in men, including condyloma an... more Human papillomavirus (HPV) causes external genital lesions (EGLs) in men, including condyloma and penile intraepithelial neoplasia (PeIN). We sought to determine the incidence of pathologically confirmed EGLs, by lesion type, among men in different age groups and to evaluate the HPV types that were associated with EGL development. HPV Infection in Men (HIM) study participants who contributed ≥2 visits from 2009-2013 were included in the biopsy cohort. Genotyping by an HPV line-probe assay was performed on all pathologically confirmed EGLs. Age-specific analyses were conducted for incident EGLs, with Kaplan-Meier estimation of cumulative incidence. This biopsy cohort included 2754 men (median follow-up duration, 12.4 months [interquartile range, 6.9-19.2 months]). EGLs (n = 377) were pathologically confirmed in 228 men, 198 of whom had incident EGLs. The cumulative incidence of any EGL was highest among men <45 years old and, for condyloma, decreased significantly over time wit...

Cancer prevention research (Philadelphia, Pa.), Jan 9, 2015

Persistent infection with oral HPV16 is believed to drive the development of most oropharyngeal c... more Persistent infection with oral HPV16 is believed to drive the development of most oropharyngeal cancers. However, patterns of oral HPV16 persistence remain understudied, particularly among HIV-negative individuals. Oral HPV16 persistence was evaluated among 1,626 participants of the HPV Infection in Men (HIM) Study. Twenty-three oral HPV16-positive men who provided an oral gargle sample on ≥2 study visits were included in the analysis. Archived oral samples from all follow-up visits were tested for HPV16 using Linear Array and INNO-LiPA detection methods. Persistence was evaluated using consecutive HPV16-positive visits held approximately 6 months apart and using the Kaplan-Meier method. Oral HPV16-positive men were aged 18 to 64 years [median, 36 years; interquartile range (IQR), 25-42] and were followed for a median of 44.4 months (IQR, 29.9-49.5). Of 13 incident infections, 4 (30.8%) persisted ≥12 months, 1 (10.0%) persisted ≥24 months, and none persisted ≥36 months [median infec...

Environmental Research, 2014

Dichlorodiphenyl dichloroethylene (DDE) and polychlorinated biphenyls (PCBs) can be passed from m... more Dichlorodiphenyl dichloroethylene (DDE) and polychlorinated biphenyls (PCBs) can be passed from mother to offspring through placental transfer or breastfeeding. Unknown is whether maternal levels can predict concentrations in adult offspring. To test the association between maternal blood levels of DDE and PCBs and adult female offspring levels of these compounds using data from the Michigan Fisheaters&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Cohort. DDE and PCB concentrations were determined in 132 adult daughters from 84 mothers. Prenatal exposures were estimated based on maternal DDE and PCB serum levels measured between 1973 and 1991. Levels in adult daughters were regressed on maternal and estimated prenatal exposure levels, adjusting for potential confounders using linear mixed models. Confounders included daughter&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s age, birth order, birth weight, number of pregnancies, the length of time the daughter was breast-fed, the length of time the daughter breast-fed her own children, last year fish-eating status, body mass index, and lipid weight. The median age of the participants was 40.4 years (range 18.4-65.4, 5-95 percentiles 22.5-54.6%, respectively). Controlling for confounders and intra-familial associations, DDE and PCB concentrations in adult daughters were significantly positively associated with estimated prenatal levels and with maternal concentrations. The proportion of variance in the adult daughters&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; organochlorine concentrations explained by the maternal exposure levels is approximately 23% for DDE and 43% for PCBs. The equivalent of a median of 3.67 μg/L prenatal DDE and a median of 2.56 μg/L PCBs were 15.64 and 10.49 years of fish consumption, respectively. When controlling for effects of the shared environment (e.g., fish diet) by using a subsample of paternal levels measured during the same time frames (n=53 and n=37), we determined that the direct maternal transfer remains important. Estimated intra-uterine DDE and PCB levels predicted concentrations in adult female offspring 40 years later. Interpretation of adverse health effects from intra-uterine exposures of persistent pollutants may need to consider the sustained impact of maternal DDE and PCB levels found in their offspring.

Biochemical and Biophysical Research Communications, 1997

Biochemical characterization has established the presence of two conformational forms of myotoxin... more Biochemical characterization has established the presence of two conformational forms of myotoxina.To test the hypothesis that this may be due tocis-transisomerization at Pro20, synthetic versions of myotoxinaand its Pro20→Gly structural homolog were folded, then purified using a two-step cation-exchange/reverse-phase perfusion chromatography method. The disulfide bond configuration for the folded proteins was found to be the same as that of native

Circulation. Arrhythmia and electrophysiology, 2014

The pulmonary vein-left atrial (PV-LA) junction is key in pathogenesis of AF, and acute stretch i... more The pulmonary vein-left atrial (PV-LA) junction is key in pathogenesis of AF, and acute stretch is an important stimulus to AF. We aimed to characterize the response of the junction to acute stretch, hypothesizing that stretch would result in electrophysiological changes predisposing to re-entry. Fifteen participants undergoing cardiac surgery underwent evaluation of the right superior PV-LA junction using an epicardial mapping plaque. In 10, this was performed before and after atrial stretch imposed by rapid volume expansion, and in 5, it was performed with an intervening observation period. Activation was characterized by conduction slowing and electrogram fractionation transversely across the PV-LA junction, with lines of block also demonstrated perpendicular to the junction. Conduction was decremental (plaque activation time 135.8 ± 46.8 ms with programmed extra stimuli at 10 ms above effective refractory period versus 66.1 ± 22.9 ms with pacing at 400 ms; P<0.001) and percen...

Annals of Cardiothoracic Surgery, 2021

JACC: Clinical Electrophysiology, 2015

OBJECTIVES This study aimed to determine the spatiotemporal stability of rotors and other atrial ... more OBJECTIVES This study aimed to determine the spatiotemporal stability of rotors and other atrial activation patterns over 10 min in longstanding, persistent AF, along with the relationship of rotors to short cycle-length (CL) activity. BACKGROUND The prevalence, stability, and mechanistic importance of rotors in human atrial fibrillation (AF) remain unclear. METHODS Epicardial mapping was performed in 10 patients undergoing cardiac surgery, with bipolar electrograms recorded over 10 min using a triangular plaque (area: 6.75 cm 2 ; 117 bipoles; spacing: 2.5 mm) applied to the left atrial posterior wall (n ¼ 9) and the right atrial free wall (n ¼ 4). Activations were identified throughout 6 discrete 10-s segments of AF spanning 10 min, and dynamic activation mapping was performed. The distributions of 4,557 generated activation patterns within each mapped region were compared between the 6 segments. RESULTS The dominant activation pattern was the simultaneous presence of multiple narrow wave fronts (26%). Twelve percent of activations represented transient rotors, seen in 85% of mapped regions with a median duration of 3 rotations. A total of 87% were centered on an area of short CL activity (<100 ms), although such activity had a positive predictive value for rotors of only 0.12. The distribution of activation patterns and wave-front directionality were highly stable over time, with a single dominant pattern within a 10-s AF segment recurring across all 6 segments in 62% of mapped regions. CONCLUSIONS In patients with longstanding, persistent AF, activation patterns are spatiotemporally stable over 10 min. Transient rotors can be demonstrated in the majority of mapped regions, are spatiotemporally associated with

Journal of the American College of Cardiology, Jan 27, 2018

It is unclear whether the Ross procedure offers superior survival compared with mechanical aortic... more It is unclear whether the Ross procedure offers superior survival compared with mechanical aortic valve replacement (AVR). This study evaluated experience and compared long-term survival between the Ross procedure and mechanical AVR. Between 1992 and 2016, a total of 392 Ross procedures were performed. These were compared with 1,928 isolated mechanical AVRs performed during the same time period as identified using the University of Melbourne and Australia and New Zealand Society of Cardiac and Thoracic Surgeons' Cardiac Surgery Databases. Only patients between 18 and 65 years of age were included. Propensity-score matching was performed for risk adjustment. Ross procedure patients were younger, and had fewer cardiovascular risk factors. The Ross procedure was associated with longer cardiopulmonary bypass and aortic cross-clamp times. Thirty-day mortality was similar (Ross, 0.3%; mechanical, 0.8%; p = 0.5). Ross procedure patients experienced superior unadjusted long-term surviva...

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, Jan 12, 2018

The Ross procedure has demonstrated excellent results when performed in patients with aortic sten... more The Ross procedure has demonstrated excellent results when performed in patients with aortic stenosis or mixed aortic valve disease [aortic stenosis and aortic regurgitation (AR)]. However, due to its reported risk of late reoperation, it is not recommended under current guidelines for patients presenting with bicuspid aortic valve and pure AR. We have analysed our own results in light of this recommendation. Between 1993 and 2016, 129 consecutive patients with a mean age of 34.7 ± 10.6 years (range 16-64 years) presented with bicuspid aortic valve and pure AR and underwent the Ross procedure. Patients were reviewed annually and had 2nd yearly transthoracic echocardiograms during follow-up. The unit had a liberal reoperation policy where reoperation was performed if patients developed recurrent moderate or greater AR during follow-up. There was 1 inpatient death, and 3 late deaths over a mean follow-up duration of 9.6 ± 6.8 years. Late survival at 10 and 20 years post-surgery were 9...

Circulation. Arrhythmia and electrophysiology, 2014

The pulmonary vein-left atrial (PV-LA) junction is key in pathogenesis of AF, and acute stretch i... more The pulmonary vein-left atrial (PV-LA) junction is key in pathogenesis of AF, and acute stretch is an important stimulus to AF. We aimed to characterize the response of the junction to acute stretch, hypothesizing that stretch would result in electrophysiological changes predisposing to re-entry. Fifteen participants undergoing cardiac surgery underwent evaluation of the right superior PV-LA junction using an epicardial mapping plaque. In 10, this was performed before and after atrial stretch imposed by rapid volume expansion, and in 5, it was performed with an intervening observation period. Activation was characterized by conduction slowing and electrogram fractionation transversely across the PV-LA junction, with lines of block also demonstrated perpendicular to the junction. Conduction was decremental (plaque activation time 135.8 ± 46.8 ms with programmed extra stimuli at 10 ms above effective refractory period versus 66.1 ± 22.9 ms with pacing at 400 ms; P<0.001) and percen...

The Journal of thoracic and cardiovascular surgery, 2015

It is hypothesized that by performing radical aortic root manipulation and then autologous suppor... more It is hypothesized that by performing radical aortic root manipulation and then autologous support for the pulmonary autograft in the Ross procedure, this will maintain aortic root size and should, in turn, lead to the demonstrated low incidence of late aortic regurgitation and need for reoperation on the aortic root and valve. Aortic root size was measured echocardiographically both preoperatively and then at second yearly intervals in 322 consecutive patients who underwent a Ross operation between October 1992 and June 2013 with autologous support of the pulmonary autograft root using the patient's own aorta. This technique, a variant of the inclusion cylinder method, has been developed with the aim of minimizing prosthetic materials in the aortic root. Measures to reduce aortic root size included annulus reduction in 201 patients (62.4%) and reduction in aortic sinus or sinotubular junction in 159 patients (49.4%). Maximal aortic root diameter postoperatively at 5, 10, and 15...

Global cardiology science & practice, 2013

To report our experience with the Ross operation in patients with predominant aortic stenosis (AS... more To report our experience with the Ross operation in patients with predominant aortic stenosis (AS) using an inclusion cylinder (IC) method. Out of 324 adults undergoing a Ross operation, 204 patients of mean age of 41.3 years (limits 16-62) underwent this procedure for either AS or mixed AS and regurgitation (AS/AR) between October, 1992 and February, 2012, implanting the PA with an IC method. Clinical follow up and serial echo data for this group is 97% complete with late mortality follow up 99% complete. There has been zero (0%) early mortality, and late survival at 15 years is 98% (96%, 100%). Only one re-operation on the aortic valve for progressive aortic regurgitation (AR) has been required with freedom from re-operation on the aortic valve at 15 years being 99% (96%, 100%). The freedom from all re-operations on the aortic and pulmonary valves at 15 years is 97% (94%, 100%). Echo analysis at the most recent study shows that 98% have nil, trivial or mild AR. Aortic root size ha...

The Journal of infectious diseases, Jan 24, 2014

Human papillomavirus (HPV) causes external genital lesions (EGLs) in men, including condyloma an... more Human papillomavirus (HPV) causes external genital lesions (EGLs) in men, including condyloma and penile intraepithelial neoplasia (PeIN). We sought to determine the incidence of pathologically confirmed EGLs, by lesion type, among men in different age groups and to evaluate the HPV types that were associated with EGL development. HPV Infection in Men (HIM) study participants who contributed ≥2 visits from 2009-2013 were included in the biopsy cohort. Genotyping by an HPV line-probe assay was performed on all pathologically confirmed EGLs. Age-specific analyses were conducted for incident EGLs, with Kaplan-Meier estimation of cumulative incidence. This biopsy cohort included 2754 men (median follow-up duration, 12.4 months [interquartile range, 6.9-19.2 months]). EGLs (n = 377) were pathologically confirmed in 228 men, 198 of whom had incident EGLs. The cumulative incidence of any EGL was highest among men <45 years old and, for condyloma, decreased significantly over time wit...

Cancer prevention research (Philadelphia, Pa.), Jan 9, 2015

Persistent infection with oral HPV16 is believed to drive the development of most oropharyngeal c... more Persistent infection with oral HPV16 is believed to drive the development of most oropharyngeal cancers. However, patterns of oral HPV16 persistence remain understudied, particularly among HIV-negative individuals. Oral HPV16 persistence was evaluated among 1,626 participants of the HPV Infection in Men (HIM) Study. Twenty-three oral HPV16-positive men who provided an oral gargle sample on ≥2 study visits were included in the analysis. Archived oral samples from all follow-up visits were tested for HPV16 using Linear Array and INNO-LiPA detection methods. Persistence was evaluated using consecutive HPV16-positive visits held approximately 6 months apart and using the Kaplan-Meier method. Oral HPV16-positive men were aged 18 to 64 years [median, 36 years; interquartile range (IQR), 25-42] and were followed for a median of 44.4 months (IQR, 29.9-49.5). Of 13 incident infections, 4 (30.8%) persisted ≥12 months, 1 (10.0%) persisted ≥24 months, and none persisted ≥36 months [median infec...

Environmental Research, 2014

Dichlorodiphenyl dichloroethylene (DDE) and polychlorinated biphenyls (PCBs) can be passed from m... more Dichlorodiphenyl dichloroethylene (DDE) and polychlorinated biphenyls (PCBs) can be passed from mother to offspring through placental transfer or breastfeeding. Unknown is whether maternal levels can predict concentrations in adult offspring. To test the association between maternal blood levels of DDE and PCBs and adult female offspring levels of these compounds using data from the Michigan Fisheaters&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Cohort. DDE and PCB concentrations were determined in 132 adult daughters from 84 mothers. Prenatal exposures were estimated based on maternal DDE and PCB serum levels measured between 1973 and 1991. Levels in adult daughters were regressed on maternal and estimated prenatal exposure levels, adjusting for potential confounders using linear mixed models. Confounders included daughter&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s age, birth order, birth weight, number of pregnancies, the length of time the daughter was breast-fed, the length of time the daughter breast-fed her own children, last year fish-eating status, body mass index, and lipid weight. The median age of the participants was 40.4 years (range 18.4-65.4, 5-95 percentiles 22.5-54.6%, respectively). Controlling for confounders and intra-familial associations, DDE and PCB concentrations in adult daughters were significantly positively associated with estimated prenatal levels and with maternal concentrations. The proportion of variance in the adult daughters&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; organochlorine concentrations explained by the maternal exposure levels is approximately 23% for DDE and 43% for PCBs. The equivalent of a median of 3.67 μg/L prenatal DDE and a median of 2.56 μg/L PCBs were 15.64 and 10.49 years of fish consumption, respectively. When controlling for effects of the shared environment (e.g., fish diet) by using a subsample of paternal levels measured during the same time frames (n=53 and n=37), we determined that the direct maternal transfer remains important. Estimated intra-uterine DDE and PCB levels predicted concentrations in adult female offspring 40 years later. Interpretation of adverse health effects from intra-uterine exposures of persistent pollutants may need to consider the sustained impact of maternal DDE and PCB levels found in their offspring.

Biochemical and Biophysical Research Communications, 1997

Biochemical characterization has established the presence of two conformational forms of myotoxin... more Biochemical characterization has established the presence of two conformational forms of myotoxina.To test the hypothesis that this may be due tocis-transisomerization at Pro20, synthetic versions of myotoxinaand its Pro20→Gly structural homolog were folded, then purified using a two-step cation-exchange/reverse-phase perfusion chromatography method. The disulfide bond configuration for the folded proteins was found to be the same as that of native

Circulation. Arrhythmia and electrophysiology, 2014

The pulmonary vein-left atrial (PV-LA) junction is key in pathogenesis of AF, and acute stretch i... more The pulmonary vein-left atrial (PV-LA) junction is key in pathogenesis of AF, and acute stretch is an important stimulus to AF. We aimed to characterize the response of the junction to acute stretch, hypothesizing that stretch would result in electrophysiological changes predisposing to re-entry. Fifteen participants undergoing cardiac surgery underwent evaluation of the right superior PV-LA junction using an epicardial mapping plaque. In 10, this was performed before and after atrial stretch imposed by rapid volume expansion, and in 5, it was performed with an intervening observation period. Activation was characterized by conduction slowing and electrogram fractionation transversely across the PV-LA junction, with lines of block also demonstrated perpendicular to the junction. Conduction was decremental (plaque activation time 135.8 ± 46.8 ms with programmed extra stimuli at 10 ms above effective refractory period versus 66.1 ± 22.9 ms with pacing at 400 ms; P<0.001) and percen...