Live/Real Time Three‐Dimensional Transesophageal Echocardiographic Assessment of Ventricular Septal Volume and Mass before and after Myectomy in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common genetically transmitted cardiomyopathy. In patients resistant to medical management, myectomy is the surgical procedure of choice to reduce the symptoms of left ventricular outflow obstruction. Two‐dimensional transesophageal echocardiography (2DTEE) has become part of the operative procedure by decreasing the incidence of postoperative complications. However, because of the three‐dimensional geometry of left ventricular outflow tract, it is unable to comprehensively assess the location and severity of the obstruction and to provide accurate guidance during myectomy. In this study, 10 patients with HCM underwent live/real time three‐dimensional transesophageal echocardiography (3DTEE) intra‐operatively to measure the volume of the resected septum. This volume correlated well with the volume of the resected septal muscle directly obtained using a graduating cylinder containing water (r = 0.9, P < 0.000). 3DTEE may be potentially used as an adjunct to guide the surgeon in performing an adequate myectomy with a lower incidence of residual obstruction and complications such as an iatrogenic ventricular septal defect.     

Deletion of the Uracil Permease Gene Confers Cross-Resistance to 5-Fluorouracil and Azoles in Candida lusitaniae and Highlights Antagonistic Interaction between Fluorinated Nucleotides and Fluconazole

We characterized two additional membrane transporters (Fur4p and Dal4p) of the nucleobase cation symporter 1 (NCS1) family involved in the uptake transport of pyrimidines and related molecules in the opportunistic pathogenic yeast Candida lusitaniae. Simple and multiple null mutants were constructed by gene deletion and genetic crosses. The function of each transporter was characterized by supplementation experiments, and the kinetic parameters of the uptake transport of uracil were measured using radiolabeled substrate. Fur4p specifically transports uracil and 5-fluorouracil. Dal4p is very close to Fur4p and transports allantoin (glyoxyldiureide). Deletion of the FUR4 gene confers resistance to 5-fluorouracil as well as cross-resistance to triazoles and imidazole antifungals when they are used simultaneously with 5-fluorouracil. However, the nucleobase transporters are not involved in azole uptake. Only fluorinated pyrimidines, not pyrimidines themselves, are able to promote cross-resistance to azoles by both the salvage and the de novo pathway of pyrimidine synthesis. A reinterpretation of the data previously obtained led us to show that subinhibitory doses of 5-fluorocytosine, 5-fluorouracil, and 5-fluorouridine also were able to trigger resistance to fluconazole in susceptible wild-type strains of C. lusitaniae and of different Candida species. Our results suggest that intracellular fluorinated nucleotides play a key role in azole resistance, either by preventing azoles from targeting the lanosterol 14-alpha-demethylase or its catalytic site or by acting as a molecular switch for the triggering of efflux transport.     

Late-presenting complete heart block after pediatric cardiac surgery

Late presenting complete heart block after pediatric cardiac surgery is a rare complication and its management is well defined once the initial diagnosis in made timely and appropriately. In this report we described a child who underwent atrioventricular septal defect repair with a normal sinus rhythm during the postoperative period, as well as during the first 2 years of follow up.She subsequently developed complete heart block with bradycardia that required insertion of a pacemaker. Here we discuss this unusual late-presenting complication, possible risk factors, and management.     

Tissue Doppler assessment of left ventricular diastolic function in rheumatic mitral stenosis

BackgroundLeft ventricular systolic and diastolic functions are reported to be altered in mitral stenosis. Although conventional Doppler ultrasound recording of transmitral flow is used in the assessment of left ventricular diastolic function, yet, in patients with mitral stenosis, it is altered by mitral stenosis itself and thus precludes the proper assessment of LV diastolic function.Aim of the workThe aim of this work is to assess LV diastolic function using pulsed tissue Doppler interrogation of mitral annulus motion in patients with rheumatic mitral stenosis.Patients and methodsTwelve patients with established diagnosis of rheumatic mitral stenosis in normal sinus rhythm were obtained from outpatient clinic of Cardiology Department in Mansura specialized hospital. Thirteen age and sex matched controls with completely normal echo-Doppler study were taken for comparison. All patients were subjected to thorough history taking including dyspnea grading according to NYHA score, clinical examination, 12 lead surface electrocardiogram and most importantly echo-Doppler study.ResultsWe found statistically significant higher peak mitral annular E_a velocity from septal, anterior, inferior and lateral portions of the mitral annulus in controls compared with mitral stenosis patients as well as their averaged values. There is no statistically significant difference regarding peak mitral annular A_a velocity from septal, anterior, inferior and lateral portions of the mitral annulus between both groups as well as their averaged values. The ratio of early to late mitral annular velocities from all recorded sites was statistically significantly higher in the controls compared with mitral stenosis patients.ConclusionsTDI of mitral annulus may provide potential diagnostic role for assessment of LV diastolic function in patients with mitral stenosis.     

Bromuconazole-induced hepatotoxicity is accompanied by upregulation of PXR/CYP3A1 and downregulation of CAR/CYP2B1 gene expression

Despite widespread use of bromuconazole as a pesticide for food crops and fruits, limited studies have been done to evaluate its toxic effects. Here, we evaluated the hepatotoxic effect of bromuconazole using classical toxicological (biochemical analysis and histopathological examination) and gene-based molecular methods. Male rats were treated either orally or topically with bromuconazole at doses equal to no observed adverse effect level (NOAEL) and 1/10 LD50 for 90?d. Bromuconazole increased activities of liver enzymes (ALT, AST, ALP, and ACP), and levels of bilirubin. It also induced hepatic oxidative stress as evidenced by significant decrease in the activities of superoxide dismutase (SOD), and significant increase in levels of malondialdehyde (MDA) in liver. In addition, bromuconazole caused an increase in liver weights and necrobiotic changes (vacuolation and hepatocellular hypertrophy). It also strongly induced the expression of PXR and its downstream target CYP3A1 gene as well as the activity of CYP3A1. However, it inhibited the expression of CAR and its downstream target CYP2B1 gene without significant changing in CYP2B1 activity. Overall, the oral route showed higher hepatotoxic effect and molecular changes than the dermal route and all changes were dose dependent. This is the first investigation to report that bromuconazole-induced liver oxidative damage is accompanied by upregulation of PXR/CYP3A1 and downregulation of CAR/CYP2B1.