Successful Percutaneous Ablation of Ventricular Tachycardia in Congenitally Corrected Transposition of the Great Arteries, a Case Report

Ventricular tachycardia (VT) is rarely recognized in patients with congenitally corrected transposition of the great arteries (CCTGA). We describe a 48-year-old woman with CCTGA, systemic atrioventricular valve replacement for Ebsteinoid malformation of the valve, ventricular dysfunction and ventricular tachycardia related to the previous surgical scar. The patient had successful non-contact mapping and radiofrequency ablation of the offending tachycardia substrate.     

Adjacent organ involvement in Salmonella aortic aneurysms

Salmonella aortic aneurysms occasionally affect adjoining organs. This study reports on 2 elderly men with fatal cases of Salmonella enteritidis involving adjacent organs: aortobronchial fistula from a thoracic aneurysm, and renal involvement from an infrarenal aneurysm. The hope of averting a tragic outcome lies in prompt clinical and radiological recognition followed by effective medical and early surgical interventions.     

Pathophysiology of hereditary hemochromatosis

Hereditary hemochromatosis (HH) encompasses several inherited disorders of iron homeostasis characterized by increased gastrointestinal iron absorption and tissue iron deposition. The most common form of this disorder is HFE-related HH, nearly always caused by homozygosity for the C282Y mutation. A substantial proportion of C282Y homozygotes do not develop clinically significant iron overload, suggesting roles for environmental factors and modifier genes in determining the phenotype. Recent studies have demonstrated that the pathogenesis of nearly all forms of HH involves inappropriately decreased expression of the iron-regulatory hormone hepcidin. Hepcidin serves to decrease the export of iron from reticuloendothelial cells and absorptive enterocytes. Thus, HH patients demonstrate increased iron release from these cell types, elevated circulating iron, and iron deposition in vulnerable tissues. The mechanism by which HFE influences hepcidin expression is an area of current investigation and may offer insights into the phenotypic variability observed in persons with mutations in HFE.     

Effectiveness of anemia and chronic kidney disease as predictors for presence and severity of coronary artery disease in patients undergoing stress myocardial perfusion study

Chronic kidney disease (CKD) and anemia portend a higher risk of cardiac events and mortality. We sought to ascertain whether coronary artery disease (CAD) by myocardial perfusion single-photon emission computed tomography is more common in patients with CKD (glomerular filtration rate < or =60 ml/min/1.73 kg/m(2)) and/or anemia (hemoglobin level < or =13 g/L) and the impact of different degrees of CKD. One thousand five hundred eighty patients (mean age 65 +/- 10 years) underwent gated myocardial perfusion single-photon emission computed tomography and clinical evaluation. Patients were divided into 4 groups (group 1, no anemia/no CKD, n = 800; group 2, anemia/no CKD, n = 195; group 3, CKD/no anemia, n = 332; group 4, anemia/CKD, n = 253). Multivariate logistic regression analysis was undertaken to examine the association of these diagnoses with abnormal myocardial perfusion single-photon emission computed tomogram. Compared with patients with neither diagnosis, an abnormal scan was more common in those with anemia or CKD. Patients with anemia and CKD exhibited more severe CAD (mean summed stress score 6.8 vs 4.7, p <0.01). Established high-risk findings were more prevalent in patients with anemia and/or CKD, including a summed stress score > or =8, transient ischemic dilation, or a left ventricular ejection fraction < or =40% (group 1 28%, group 2 38%, group 3 38%, group 4 48%, all p values <0.01). Patients with moderate CKD demonstrated an increased risk of an abnormal scan (odds ratio 2.66, p <0.0001). After adjustment in multivariate analysis, anemia and CKD each remained predictors for an abnormal scan. The association was stronger in those with the 2 conditions (odds ratio for high-risk scan 1.89, p = 0.0002). In conclusion, in patients with suspected CAD, anemia and CKD are predictors of myocardial perfusion single-photon emission computed tomographic markers for worsened outcomes. The relation was independent of other risk factors, supporting the inclusion of anemia and CKD in global risk assessment for patients with suspected CAD.     

The effects of dobutamine on cardiac sympathetic activity in patients with congestive heart failure

OBJECTIVES: The goal of this work was to study the effects of short-term infusion of dobutamine on efferent cardiac sympathetic activity. BACKGROUND: Increased efferent cardiac sympathetic activity is associated with poor outcomes in the setting of congestive heart failure (CHF). Dobutamine is commonly used in the therapy of decompensated CHF. Dobutamine, through its effects on excitatory beta-receptors, may increase cardiac sympathetic activity. METHODS: Seven patients with normal left ventricular (LV) function and 13 patients with CHF were studied. A radiotracer technique was used to measure cardiac norepinephrine spillover (CANESP) before and during an intravenous infusion of dobutamine titrated to increase the rate of rise in LV peak positive pressure (+dP/dt) by 40%. RESULTS: Systemic arterial pulse pressure increased significantly in response to dobutamine in the normal LV function group (74 +/- 3 mm Hg to 85 +/- 3 mm Hg, p = 0.005) but remained unchanged in the CHF group. Dobutamine caused a significant decrease in LV end-diastolic pressure in the CHF group (14 +/- 2 mm Hg to 11 +/- 2 mm Hg, p = 0.02), an effect not observed in the normal LV group. In the normal LV function group, CANESP did not change in response to dobutamine (75 +/- 22 pmol/min vs. 72 +/- 22 pmol/min, p = NS). In contrast, dobutamine infusion was associated with a significant reduction in CANESP in patients with CHF (199 +/- 43 pmol/min to 128 +/- 30 pmol/min, p < 0.0009). CONCLUSIONS: Dobutamine infusion caused a significant sympatholytic response in patients with CHF. This sympathetic withdrawal response is probably related to reduction of LV filling pressures and/or activation of ventricular mechanoreceptors with dobutamine infusion.     

Systemic delivery of β-blockers via transdermal route for hypertension

Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later.     

Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design,characterization, in vitro and in vivo evaluation

Abstract

Naringenin (NRG), predominant flavanone in grapefruits, possesses anti-inflammatory, anti-carcinogenic, hepato-protective and anti-lipid peroxidation effects. Slow dissolution after oral ingestion due to its poor solubility in water, as well as low bioavailability following oral administration, restricts its therapeutic application. The study is an attempt to improve the solubility and bioavailability of NRG by employing self-nanoemulsifying drug delivery technique. Preliminary screening was carried out to select oil, surfactant and co-surfactant, based on solubilization and emulsification efficiency of the components. Pseudo ternary phase diagrams were constructed to identify the area of nanoemulsification. The developed self-nanoemulsifying drug delivery systems (SNEDDS) were evaluated in term of goluble size, globule size distribution, zeta potential, and surface morphology of nanoemulsions so obtained. The TEM analysis proves that nanoemulsion shows a droplet size less than 50?nm. Freeze thaw cycling and centrifugation studies were carried out to confirm the stability of the developed SNEDDS. In vitro drug release from SNEDDS was significantly higher (p?<?0.005) than pure drug. Furthermore, area under the drug concentration time-curve (AUC_0–24) of NRG from SNEDDS formulation revealed a significant increase (p?<?0.005) in NRG absorption compared to NRG alone. The increase in drug release and bioavailability as compared to drug suspension from SNEDDS formulation may be attributed to the nanosized droplets and enhanced solubility of NRG in the SNEDDS.