Publications by authors named "James E Kelly"

The Minnesota Department of Health measured levels of perfluoroalkyl acids (PFAAs) in house dust at homes in communities impacted by PFAA-contaminated soil and drinking water to determine whether PFAAs in soil outside the home are associated with concentrations in dust. House dust samples from both interior living spaces and entryways to the yard were collected and analyzed separately based on the presumption that PFAAs in entryway dust may better reflect "track-in" of PFAAs into the home from contaminated soil or lawns irrigated with contaminated water. PFAA detections and concentrations in living rooms were significantly higher compared to entryways; and concentrations in both sampling locations were higher than corresponding soil concentrations, suggesting that interior sources were the main contributors to PFAAs in house dust.

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The decades-long disposal of manufacturing waste containing perfluoroalkyl substances (PFAS) in landfills resulted in contamination of groundwater serving as the drinking water supply for the eastern Twin Cities metropolitan region. While measures were taken to reduce the levels of PFAS in the drinking water, questions remained about possible non-drinking water pathways of exposure in these communities. The Minnesota Department of Health (MDH) investigated whether PFAS in water used for yard and garden irrigation results in elevated concentrations of PFAS in soil and home-grown produce.

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Background: Susceptibility-weighted imaging is a relatively new magnetic resonance imaging sequence that can identify lesions of multiple sclerosis in adults. This study was designed to determine if susceptibility-weighted imaging is a useful discriminator between children who develop multiple sclerosis and children with monophasic acute disseminated encephalomyelitis.

Methods: Eighteen children who presented with acute central nervous system demyelination and had a brain magnetic resonance imaging study including susceptibility-weighted imaging within 6 months of the first clinical attack were studied.

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Infection with multidrug resistant Burkholderia cepacia presents a therapeutic challenge in patients with cystic fibrosis. In this study, we present a case of progressive cervical osteomyelitis secondary to B cepacia that failed surgical drainage and extended therapy with meropenem, piperacillin-tazobactam, doxycycline, and aminoglycosides. Temocillin (Negaban) was successfully used to clear the infection.

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Objectives: To determine the prevalence of white matter lesions (WMLs) and infarcts in children with migraine and whether pediatric migraine could be a risk factor for silent ischemic lesions or stroke.

Methods: Prospectively collected data from 1,008 pediatric patients with headache were reviewed. The MRI data were collected and retrospectively reviewed.

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The treatment of heart failure (HF) is challenging and morbidity and mortality are high. The goal of this study was to determine if inhibition of the late Na(+) current with ranolazine during early hypertensive heart disease might slow or stop disease progression. Spontaneously hypertensive rats (aged 7 mo) were subjected to echocardiographic study and then fed either control chow (CON) or chow containing 0.

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Background And Aim: The role of imaging for the detection of vascular lesions in patients with intracerebral hemorrhage (ICH) is poorly defined. A study was undertaken to compare the yield of digital subtraction angiography (DSA) in patients with ICH with intraventricular hemorrhage (IVH) and those without IVH.

Methods: The DSA database at our institution was reviewed for patients who underwent DSA for acute spontaneous ICH over a period of 68 months.

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Defects in excitation-contraction coupling have been reported in failing hearts, but little is known about the relationship between these defects and the development of heart failure (HF). We compared the early changes in intracellular Ca(2+) cycling to those that underlie overt pump dysfunction and arrhythmogenesis found later in HF. Laser-scanning confocal microscopy was used to measure Ca(2+) transients in myocytes of intact hearts in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) at different ages.

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Background: Abnormalities in intracellular calcium (Ca) cycling during Ca overload can cause triggered activity because spontaneous calcium release (SCR) activates sufficient Ca-sensitive inward currents to induce delayed afterdepolarizations (DADs). However, little is known about the mechanisms relating SCR and triggered activity on the tissue scale.

Methods And Results: Laser scanning confocal microscopy was used to measure the spatiotemporal properties of SCR within large myocyte populations in intact rat heart.

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Background: A number of defects in excitation-contraction coupling have been identified in failing mammalian hearts. The goal of this study was to measure the defects in intracellular Ca(2+) cycling in left ventricular epicardial myocytes of the whole heart in an animal model of congestive heart failure (CHF).

Methods And Results: Intracellular Ca(2+) transients were measured using confocal microscopy in whole rat hearts from age-matched Wistar-Kyoto control rats and spontaneously hypertensive rats at approximately 23 months of age.

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Pathological conditions, including ischemia and heart failure, are associated with altered sodium channel function and increased late sodium current (I(Na,L)), leading to prolonged action potential duration, increased intracellular sodium and calcium concentrations, and arrhythmias. We used anemone toxin (ATX)-II to study the effects of increasing I(Na,L) on intracellular calcium cycling in rat isolated hearts. Cardiac contraction was abolished using paralytic agents.

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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 and TWA in whole heart. We used laser-scanning confocal microscopy to measure intracellular Ca(2+) (Ca(i)(2+)) cycling in individual myocytes of fluo-4 AM-loaded rat hearts and simultaneously recorded pseudo-ECGs to investigate changes in CaTs and late-phase repolarization, respectively, during baseline and rapid pacing under control and either globally acidic or globally ischemic conditions.

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Males and females show distinct differences in action potential waveform, ion channel expression patterns, and ECG characteristics. However, it is not known how sex-based differences in Ca2+ cycling might contribute to these differences in electrophysiological activity. The goal of this study was to investigate the differences in cellular Ca2+ transients in males and females and to examine how these might contribute to electrophysiological function.

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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 ventricular regions are unknown. The goal of this study was to measure cellular activity in intact myocardium during rapid pacing and arrhythmias.

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Although the negative inotropic effects of both acute and chronic ethanol (EtOH) exposure are well known, little is known concerning the acute-to-chronic transition of such effects. In this study, our objective was to address this question by detailing the effects that acute EtOH exposure induces on cellular excitation-contraction (EC) coupling and, subsequently, comparing whether and how such changes translate to the early chronic EtOH condition in a rat model known to develop alcohol-induced cardiomyopathy. Acute EtOH exposure, as formerly reported, indeed induced dose-dependent negative inotropic changes in cellular EC coupling, manifest as reductions in cell shortening, Ca2+ transient amplitude, Ca2+ decay rate, and sarcoplasmic reticulum Ca2+ content of isolated rat ventricular cardiac myocytes.

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The inotropic and toxic effects of cardiac glycosides are thought to be related to their ability to inhibit the Na,K-ATPase. We examined the effects of ouabain and its analogs on sarcoplasmic reticulum (SR) Ca(2+) release in intact cat ventricular myocytes under Na(+)-free conditions and in myocytes in which the sarcolemma was permeabilized using saponin so that cytoplasmic ionic composition was fixed by the bath solutions. We also compared ouabain actions in cat myocytes to those in rat myocytes because the latter is considered to be a glycoside-insensitive species.

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Recent functional magnetic resonance imaging (fMRI) studies using mixed blocked/event-related designs have shown activity consistent with separable sustained task-related processes and transient trial-related processes. In the mixed design, control blocks are intermixed with task blocks, during which trials are presented at varying intervals. Two studies were conducted to assess the ability of this design to detect and dissociate sustained task-related from transient trial-related activity.

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The question of whether pediatric and adult neuroimaging data can be analyzed in a common stereotactic space is a critical issue for developmental neuroscience. Two studies were performed to address this question. In Study 1, high-resolution structural MR brain images of 20 children (7-8 years of age) and 20 young adults (18-30 years of age) were transformed to a common space.

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We investigated the possibility that the Ca(2+) channel agonist FPL-64176 (FPL) might also activate the cardiac sarcoplasmic reticulum (SR) Ca(2+) release channel ryanodine receptor (RyR). The effects of FPL were tested on single channel activity of purified and crude vesicular RyR (RyR2) isolated from human and dog hearts using the planar lipid bilayer technique. FPL (100-200 microM) increased single channel open probability (P(o)) when added to the cytoplasmic side of the channel (P(o) = 0.

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This study examined the effects of quinidine, quinine, and the quaternary quinidine derivative, quinidinium, on the conductance and activity of purified cardiac sarcoplasmic reticulum calcium release channels/ryanodine receptors (RyR) incorporated into planar lipid bilayers. Quinidine (50-500 microM) reduced the single-channel open probability in a voltage- and concentration-dependent manner. Reduction of channel activity was evident only at positive holding potentials where current flow is from the cytoplasmic to luminal side of the channel and when the drug was present only on the cytoplasmic face of the channel.

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This study investigated the effects of cardiac glycosides on single-channel activity of the cardiac sarcoplasmic reticulum (SR) Ca2+ release channels or ryanodine receptor (RyR2) channels and how this action might contribute to their inotropic and/or toxic actions. Heavy SR vesicles isolated from canine left ventricle were fused with artificial planar lipid bilayers to measure single RyR2 channel activity. Digoxin and actodigin increased single-channel activity at low concentrations normally associated with therapeutic plasma levels, yielding a 50% of maximal effect of approximately 0.

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