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INTRODUCTION There is overwhelming medical and scientific consensus that cigarette smoking causes lung cancer, heart disease, emphysema, and other serious diseases in smokers. In the Total Exposure Study, 29 biomarkers of potential harm (BOPH) were measured in a cross-sectional sample of 3,585 adult smokers (AS) and 1,077 nonsmokers (NS). The BOPH included(More)
This report describes a new method for estimating the retention of selected mainstream smoke constituents in the respiratory tract of adult smokers during cigarette smoking. Both particulate-phase (PP) constituents including nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N'-nitrosonornicotine (NNN), two tobacco-specific nitrosamines(More)
Optical mapping studies have suggested that intracellular Ca2+ and T-wave alternans are linked through underlying alternations in Ca2+ cycling-inducing oscillations in action potential duration through Ca2+-sensitive conductances. However, these studies cannot measure single-cell behavior; therefore, the Ca2+ cycling heterogeneities within microscopic(More)
Cigarette smoke is a complex aerosol that includes a gas vapor phase and a particulate phase. Inclusion of activated carbon in the cigarette filter can reduce some of the gas-phase smoke constituents implicated as toxicologically relevant. The present study evaluated exposure to selected gas-phase constituents when adult smokers switched to prototype(More)
Cardiac cellular Ca(2+) transient (CaT) alternans and electrocardiographic T-wave alternans (TWA) often develop in myocardial ischemia, but the mechanisms for this relationship have not been elucidated. Acidosis is a major component of ischemia, but there is no direct evidence linking acidosis-induced cellular CaT alternans to ischemia-induced CaT alternans(More)
Optical mapping of intact cardiac tissue reveals that, in some cases, intracellular calcium (Ca) release can alternate from one beat to the next in a large-small-large sequence, also referred to as Ca transient (CaT) alternans. CaT alternans can also become spatially phase-mismatched within a single cell, when one part of the cell alternates in a(More)
Alkylating agents occur in the environment and are formed endogenously. Tobacco smoke contains a variety of alkylating agents or precursors including, among others, N-nitrosodimethylamine (NDMA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), acrylonitrile and ethylene oxide. We developed and validated a method for the simultaneous determination of(More)
Normal cardiac rhythm is one of the most fundamental physiologic phenomena, emerging early in the establishment of the vertebrate body plan. The developmental pathways underlying the patterning and maintenance of stable cardiac electrophysiology must be extremely robust, but are only now beginning to be unraveled. The step-wise emergence of automaticity, AV(More)
Cardioembolic stroke is a major cause of morbidity and mortality in patients with atrial fibrillation (AF). The left atrial appendage (LAA) is the prominent source of clot formation. While systemic anticoagulation is the current standard of care, anticoagulants carry many contraindications and possible complications. Techniques for elimination of the LAA(More)
Urinary excretion of nicotine and its five major metabolites (nicotine-N-glucuronide, cotinine, cotinine-N-glucuronide, trans-3'-hydroxycotinine, and trans-3'-hydroxycotinine-O-glucuronide), expressed as nicotine equivalents (NE), has been used as a biomarker of smoking-related nicotine exposure. In this open-label, single center study, we investigated the(More)