Ventricular Tachycardia in an Elderly Male With Brugada Syndrome.

We present a case of Brugada syndrome in a 74-year-old patient who presented with urine retention and incidentally found to have non-sustained ventricular tachycardia (NSVT) on electrocardiogram (ECG) and telemetry. To reveal characteristic type 1 Brugada pattern, right-pericardial lead was placed in the third right intercostal space. No antiarrhythmics were started, a loop recorder was implanted, and on follow-up episodes of self-terminating sustained ventricular tachycardia (VT) were noted. The patient was started on quinidine with resolution of VT.

Swallowing-induced atrial tachycardia: A rare demonstration on fluoroscopic esophagram.

BACKGROUND: Swallowing-associated arrhythmias are rare and most commonly present as atrial tachycardias. METHODS: We present a case of a 45-year-old female who experienced frequent episodes of palpitations and dyspnea occurring immediately after swallowing solid food. She was noted to have atrial tachycardia with deglutition that was recorded on the 12-lead electrocardiogram. She underwent fluoroscopic esophagram that demonstrated atrial tachycardia as the barium passed through the distal esophagus and gastroesophageal junction. CONCLUSION: Swallowing induced arrhythmias occur rarely and can be confirmed by EKG obtained during deglutition. Gastroesophageal evaluation is required to rule out primary esophageal disorders. Treatment of such arrhythmias is required if symptoms are intractable and can include pharmacotherapy and radiofrequency ablation.

Benign Metastasizing Leiomyoma Causing Severe Tricuspid Regurgitation and Heart Failure.

We present the case of a 51-year-old woman with severe tricuspid valve regurgitation due to aseptic tricuspid valve vegetation. She presented with bilateral lower extremity edema and a tricuspid valve vegetation was found on echocardiography. Initially, infectious and autoimmune causes of valve vegetation were considered; however, on biopsy, the mass was ultimately found to be a benign metastasizing leiomyoma (BML). Additional history revealed clinical features consistent with uterine leiomyomas, which metastasized to all leaflets the tricuspid valve, causing symptoms of heart failure. Benign metastasizing leiomyoma is rare itself, but when found, typically presents as asymptomatic pulmonary nodules. Mechanism of spread is unknown. Diagnosis is typically made long after a hysterectomy or fibroidectomy, but in our case, the BML was found prior to an actual fibroid diagnosis. By comparison, metastasis to the heart is extremely rare and has a higher potential for morbidity. Our patient required open heart surgery and tricuspid valve replacement for management of her symptoms, but her risk of further or recurrent metastasis going forward is unknown. Management strategy to prevent metastases in such cases of aggressive disease is not an established protocol and needs to be further studied.

Management of Unoperated Tetralogy of Fallot in a 59-Year-Old Patient.

Tetralogy of Fallot is the most common cyanotic congenital heart defect consisting of an overriding aorta, right ventricular outflow obstruction, ventricular septal defect, and right ventricular hypertrophy. Without surgical management, approximately only 3% of patients survive past the age of 40 years. Cases of unoperated patients reaching adulthood have been reported; however, few studies describe treatment guidelines for surgical or therapeutic management. In this article, we report the case of a 59-year-old Hispanic male with unoperated tetralogy of Fallot presenting to our cardiology clinic for initial workup and management.

Effusive-constrictive pericarditis, hepatitis, and pancreatitis in a patient with possible coxsackievirus B infection: a case report.

BACKGROUND: Coxsackie B is a viral pathogen that presents with various invasive diseases in adults. Historically, the majority of adult cases with pericarditis or myocarditis have been attributed to coxsackievirus B. The presentation of this viral infection causing effusive-constrictive pericarditis, hepatitis or pancreatitis is rare. This case report is the first to describe a patient with concomitant effusive-constrictive pericarditis, hepatitis and pancreatitis from possible coxsackievirus B infection. CASE PRESENTATION: A 26-year old female was admitted to our hospital with the diagnosis of effusive-constrictive pericarditis complicated by tamponade and cardiac arrest. An emergent pericardiocentesis was performed successfully. Hepatitis and pancreatitis were also identified in our patient. After an extensive workup, coxsackievirus B infection was suspected by positive serum complement fixation antibody titers. Our patient made a full recovery and was discharged from the hospital. CONCLUSION: Clinical suspicion of effusive-constrictive pericarditis with tamponade from coxsackievirus B should be considered in patients presenting with chest pain, dyspnea, jugular venous distention, hypotension, ST segment elevation on electrocardiogram, and ventricular interdependence with septal shift during diastole on transthoracic echocardiogram. Initial diagnoses of effusive-constrictive pericarditis resembling cardiac tamponade, hepatitis and pancreatitis can be challenging, and this case highlights the need for healthcare professionals to be cognizant of the association between these unusual clinical presentations and coxsackievirus B infection.

Left Ventricular Septolateral Mechanical Delay Is Associated with Reduced Long-Term Survival in Systolic Heart Failure with Narrow QRS Duration: Nine-Year Outcome in 109 Patients.

BACKGROUND: The long-term prognostic importance of left ventricular (LV) dyssynchrony in patients with systolic heart failure is not known. We investigated this question in 109 consecutive patients with systolic heart failure with an LV ejection fraction (EF) ≤35% and QRS duration <130 ms. METHODS: The cohort is a prospective series of 109 patients with EF ≤35% and QRS duration <130 ms who did not receive a defibrillator. Onset to onset septolateral and anteroposterior mechanical delays were computed from tissue Doppler velocity signals of the four quadrants of the mitral annulus and related to mortality. RESULTS: Patient characteristics included age 53 ± 12 years, 73% male, 23% with coronary artery disease, LVEF 24 ± 7%, LV end-diastolic dimension 64 ± 9 mm, LV end-systolic dimension 55 ± 9 mm, QRS duration 107 ± 30 ms, and 92 with QRS duration <120 ms. Over a follow-up of 9 years, there were 51 deaths. Univariate predictors of mortality included LV septolateral delay (HR 1.01 per ms, P < 0.0001), anteroposterior delay (P = 0.003), and age (P = 0.005), but not EF, LV size, or QRS duration. Using Cox regression analysis, LV septolateral delay was an independent predictor of higher mortality (P = 0.0005) after adjusting for age, gender, EF, LV size, QRS duration, coronary artery disease, diabetes mellitus, and use of beta blockers or angiotensin-converting enzyme inhibitors. CONCLUSION: In patients with heart failure, LVEF ≤35% and QRSd < 130 ms, LV mechanical dyssynchrony is a strong and independent predictor of long-term mortality.

Structural determinants of photoreactivity of triplex forming oligonucleotides conjugated to psoralens.

Triplex-forming oligonucleotides (TFOs) with both DNA and 2'-O-methyl RNA backbones can direct psoralen photoadducts to specific DNA sequences. However, the functional consequences of these differing structures on psoralen photoreactivity are unknown. We designed TFO sequences with DNA and 2'-O-methyl RNA backbones conjugated to psoralen by 2-carbon linkers and examined their ability to bind and target damage to model DNA duplexes corresponding to sequences within the human HPRT gene. While TFO binding affinity was not dramatically affected by the type of backbone, psoralen photoreactivity was completely abrogated by the 2'-O-methyl RNA backbone. Photoreactivity was restored when the psoralen was conjugated to the RNA TFO via a 6-carbon linker. In contrast to the B-form DNA of triplexes formed by DNA TFOs, the CD spectra of triplexes formed with 2'-O-methyl RNA TFOs exhibited features of A-form DNA. These results indicate that 2'-O-methyl RNA TFOs induce a partial B-to-A transition in their target DNA sequences which may impair the photoreactivity of a conjugated psoralen and suggest that optimal design of TFOs to target DNA damage may require a balance between binding ability and drug reactivity.

Modulation of psoralen DNA crosslinking kinetics associated with a triplex-forming oligonucleotide.

A triplex-forming oligonucleotide (TFO), HPRT3, conjugated to a psoralen derivative, was designed to target a psoralen reaction site within the HPRT gene. HPRT3 bound with high affinity to a synthetic duplex target sequence. At a uniform UVA radiation dose, the ratio of psoralen monoadducts (MA) to interstrand crosslinks decreased and inverted with increasing TFO concentration. As the TFO concentration increased from 10 nm to 10 microm, the efficiency of psoralen MA formation remained relatively constant but the efficiency of interstrand crosslink formation increased several-fold. Neither shortening the TFO to reduce its dissociation constant nor altering the DNA sequences flanking the TFO binding site altered the concentration dependence of MA and crosslink yields. The psoralen photokinetics associated with 10 nm HPRT3 converted to those associated with 10 microm HPRT3 with the addition of other unrelated TFOs at 10 microm that do not specifically interact with the HPRT3 target sequence. Glycerol at concentrations of 0.5% (vol/vol) or higher also mimicked high TFO concentrations in enhancing crosslink formation. These results demonstrate that while psoralen may be targeted to react at a particular sequence by TFOs, photoreactivity associated with triplex formation is also modulated by sequence-independent factors that may affect the local macromolecular environment.

Fluorescence dynamics of three UV-B sunscreens.

Polarity of the surrounding medium affects the excited states of UV-B sunscreens. Therefore understanding excited state processes in a mixed polarity model system similar to skin is essential. We report the excited state lifetimes, quantum yields, radiative and non-radiative rates of three sunscreens. Among the three UV-B sunscreens studied, octyl salicylate emits from a single excited state, while padimate O and octyl methoxy cinnamate show multiple states. The radiative rates of salicylate and cinnamate are approximately constant, while that of padimate O depends strongly on solvent. The non-radiative rates of all sunscreens vary with solvent polarity. Compared to salicylate and cinnamate, padimate O is complex to analyze because of its two emission peaks and one peak's strong dependence on the dielectric constant. High absorbance, broad absorption peak with small fluorescence quantum yield, and low radiative rate make octyl methoxy cinnamate a superior UV-B sunscreen ingredient. The complexity in excited-state analysis shows that the lifetimes of the sunscreens are critical parameters, in addition to absorbance and quantum yield. Fluorescence lifetime substantiates the use of polystyrene nanospheres as a model host to study the photo-physical properties of sunscreen in a heterogeneous environment.

A new method to test the effectiveness of sunscreen ingredients in a novel nano-surface skin cell mimic.

Photophysical properties of sunscreens are commonly studied in solvent media, which do not mimic the skin, or in complex artificial skin systems, which are difficult to handle. In an earlier study, we showed that polystyrene nanosphere suspensions mimic the mixed polarity environment of skin cell systems. This paper presents a new method to quantify the effectiveness of sunscreens in the polystyrene nanosphere environment. This method utilizes the intrinsic UV-B fluorescence of polystyrene nanospheres. We studied three UV-B sunscreens by this new method and compared their extinction coefficients with observed values in solvent. The values follow the trend observed in solvents, but the ratio of their extinction coefficient in solvent to the value obtained by this new method is 1.3-1.8 instead of 1. This difference might be caused by the mixed polarity or the microgeometry of the nanosphere system. Regardless of the difference in the extinction coefficients, this new system can be used to test hundreds of chemicals for their sunscreening potential in a cost-effective way. One marked advantage of this new method is its ability to test both hydrophobic and hydrophilic sunscreening chemicals in the same environment. This is virtually impossible for current solvent-based models, which require different solvents for hydrophobic and hydrophilic chemicals. The new method also allows the simultaneous evaluation of a host of photophysical properties of sunscreening chemicals.

Fluorescence of sunscreens adsorbed to dielectric nanospheres: parallels to optical behavior on hacat cells and skin.

Sunscreens applied to the skin are retained primarily in the stratum corneum, where they adsorb and act as a barrier preventing UV penetration to deeper layers. Photophysical properties of sunscreens have traditionally been studied either in solvents, which are very different from skin, or in skin or complex artificial skin systems, which are difficult to handle. The purpose of this study was to determine whether polystyrene nanospheres could serve as an improvement over solvents for evaluation of the photophysical properties of sunscreens without the presence of autofluorescence from and interactions with specific skin biomolecules. We used HaCat cells and excised skin for this comparative study with nanospheres. Fluorescence spectral properties of common hydrophobic sunscreens octyl salicylate, padimate O (2-ethylhexyl-4-dimethylaminobenzoate) and octyl methoxycinnamate adsorbed to 220 nm polystyrene spheres are similar to those of sunscreens adsorbed to HaCat cells and excised skin. Specifically, similarity in the emission peaks and their approximate positions, excitation peak positions and a measurable reduction in scattering upon sunscreen addition suggest that polystyrene nanospheres constitute a useful system to evaluate the photophysical properties of topical sunscreens and may serve as a model system for high-throughput evaluation of potential sunscreens. An unexpected result of this comparative study was the observation of an increase in a specific skin component emission caused by addition of padimate O.

Optical spectroscopy of hydrophobic sunscreen molecules adsorbed to dielectric nanospheres.

Fluorescence and absorption spectra of hydrophobic sunscreens, weakly fluorescent octyl methoxycinnamate, moderately fluorescent octyl salicylate and highly fluorescent 2-ethylhexyl-4-(dimethylamino)benzoate (padimate O) adsorbed to dielectric microspheres in aqueous suspension, have been compared with spectra in organic solution. The fluorescence of adsorbed salicylate and padimate is enhanced compared with fluorescence in methanol: about a factor of 6 and 30 in terms of fluorescence yield per molecule of salicylate and padimate, respectively. Cinnamate, which has a low fluorescence yield, does not show a comparable fluorescence enhancement. The fluorescence amplification is independent of sphere diameter from 30 to 1500 nm, at least for salicylate. The enhancement, as well as the location of absorption spectral peaks, is consistent with a low-dielectric constant environment of the molecules, in spite of the presumed location near the interface between polystyrene (epsilon = 2.4-3.8) and water (epsilon = 78). The adsorbed state of these sunscreens represents a proposed improved in vitro model for the environment of sunscreens in vivo, as well as a general model for chromophores in heterogeneous environments.