Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin

Missense mutations in the cone opsins have been identified as a relatively common cause of red/green color vision defects, with the most frequent mutation being the substitution of arginine for cysteine at position 203 (C203R). When the corresponding cysteine is mutated in rhodopsin, it disrupts proper folding of the pigment, causing severe, early onset retinitis pigmentosa. While the C203R mutation has been associated with loss of cone function in color vision deficiency, it is not known what happens to cones expressing this mutant opsin. Here, we used high-resolution retinal imaging to examine the cone mosaic in two individuals with genes encoding a middle-wavelength sensitive (M) pigment with the C203R mutation. We found a significant reduction in cone density compared to normal and color-deficient controls, accompanying disruption in the cone mosaic in both individuals, and thinning of the outer nuclear layer. The C203R mosaics were different from that produced by another mutation (LIAVA) previously shown to disrupt the cone mosaic. Comparison of these mosaics provides insight into the timing and degree of cone disruption and has implications for the prospects for restoration of vision loss associated with various cone opsin mutations.     

Clinical factors predictive of insufficient liver enhancement on the hepatocyte-phase of Gd-EOB-DTPA-enhanced magnetic resonance imaging in patients with liver cirrhosis

Background

Estimating liver parenchymal enhancement prior to gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) imaging is crucial to accurate detection and characterization of focal hepatic lesions. We aimed to clarify the factors predictive of liver enhancement in a relatively large sample of patients.

Methods

Gd-EOB-DTPA-enhanced MR images of 328 patients with liver cirrhosis (Child–Pugh class A in 223 patients, class B in 71 patients, and class C in 34 patients) were analyzed retrospectively. The liver parenchymal signal intensity (SI) was measured in pre-contrast T1-weighted images and hepatocyte phase images. The relative enhancement (RE) was calculated: (hepatocyte phase SI–pre-contrast SI)/pre-contrast SI. We analyzed the correlation between hepatic function parameters and RE.

Results

RE of patients with Child–Pugh A cirrhosis was significantly higher than that of patients with Child–Pugh B or C cirrhosis (both P < 0.001). Among various clinical factors, platelet count, prothrombin activity, albumin, sodium, total bilirubin, aspartate aminotransferase, Model for End-stage Liver Disease (MELD) score, MELD-Na score, Child–Pugh score, and the presence of ascites were significantly correlated with RE. A multiple stepwise regression analysis revealed that MELD-Na, albumin, and the presence of ascites were the only factors that predicted liver parenchymal enhancement on hepatocyte-phase images.

Conclusion

The degree of liver parenchymal enhancement after Gd-EOB-DTPA administration was correlated with liver function parameters. Gd-EOB-DTPA-enhanced MR images require careful interpretation, particularly in patients with cirrhosis and clinical factors such as high MELD-Na score, hypoalbuminemia, or ascites.     

Twenty-Eight-Day Oral Toxicity,Genotoxicity, and Gender-Related Tissue Distribution of Silver Nanoparticles in Sprague-Dawley Rats

The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, and home products. However, while the population exposed to silver nanoparticles continues to increase with ever new applications, silver nanoparticles remain a controversial research area as regards their toxicity to biological systems. In particular, the oral toxicity of silver nanoparticles is of particular concern to ensure public and consumer health. Accordingly, this study tested the oral toxicity of silver nanoparticles (60 nm) over a period of 28 days in Sprague-Dawley rats following Organization for Economic Cooperation and Development (OECD) test guideline 407 with Good Laboratory Practice (GLP) application. Eight-week-old rats, weighing about 283 g for the males and 192 g for the females, were divided into four 4 groups (10 rats in each group): vehicle control, low-dose group (30 mg/kg), middle-dose group (300 mg/kg), and high-dose group (1000 mg/kg). After 28 days of exposure, the blood biochemistry and hematology were investigated, along with a histopathological examination and silver distribution study. The male and female rats did not show any significant changes in body weight relative to the doses of silver nanoparticles during the 28-day experiment. However, some significant dose-dependent changes were found in the alkaline phsophatase and cholesterol values in either the male or female rats, seeming to indicate that exposure to over more than 300 mg of silver nanoparticles may result in slight liver damage. There were no statistically significant differences in the micronucleated polychromatic erythrocytes (MN PCEs) or ratio of polychromatic erythrocytes among the total erythrocytes after silver nanoparticle exposure when compared with the control. Therefore, the present results suggest that silver nanoparticles do not induce genetic toxicity in male and female rat bone marrow in vivo. Nonetheless, the tissue distribution of silver nanopaticles did show a dose-dependent accumulation of silver content in all the tissues examined. In particular, a gender-related difference in the accumulation of silver was noted in the kidneys, with a twofold increase in the female kidneys when compared with the male kidneys.     

Kaposi's Varicelliform-Like Eruption in a Patient Treated with Everolimus for Metastatic Renal Cell Carcinoma: Report of a Rare Case

Kaposi''s varicelliform eruption is a cutaneous eruption caused by the herpes simplex virus and a few other viruses that infect persons with pre-existing dermatosis such as atopic dermatitis. We report the case of a 56-year-old man who was treated with the mammalian target of rapamycin inhibitor, everolimus, for metastatic renal cell carcinoma. He presented with painful, umbilicated vesicles and pustules on his face, genital region, forearms, and legs suggestive of Kaposi''s varicelliform eruption. He did not have a history of any visceral viral disease and pre-existing dermatosis. The diagnosis was based on the clinical features. He was treated with acyclovir for 7 days, with improvement of his skin lesions. We discuss the clinical manifestations of the Kaposi varicelliform-like eruption in an immunocompromised patient treated with everolimus.Key words: Kaposi''s varicelliform eruption, Renal cell carcinoma, Mammalian target of rapamycin inhibitor     

Association between aortic calcification and stable obstructive coronary artery disease

Aims

Atrial fibrillation and flutter remain an important cause of morbidity in adults with atrial septal defect (ASD). This study aimed at investigating predictors for late (≥ 1 month after repair) atrial arrhythmia.

Methods

Patients who underwent ASD closure after the age of 18 years, were selected through the databases of three medical centres in Belgium. Preprocedural, periprocedural and follow-up data were extracted. Univariate and multivariate Cox-regression analysis was performed. Kaplan-Meier analysis was performed for any independent predictor of late atrial arrhythmia.

Results

A total of 155 patients (38 men and 117 women) was included. Twenty-four patients (median age 48.3 years, range 19.9-79.8) underwent surgical and 131 (median age 57.6 years, range 18.2-86.9) underwent transcatheter closure. Thirty-nine patients (25.2%) presented with late atrial arrhythmia. Male gender (P = 0.008), creatinine (P = 0.002), atrial arrhythmia before (P < 0.0001) and within 1 month after repair (P = 0.001) and a mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg (P < 0.0001) correlated with late atrial arrhythmia in univariate Cox-regression analysis. Multivariate analysis showed that mPAP ≥ 25 mm Hg (HR 3.72; 95%CI 1.82-7.59; P < 0.0001) and the presence of atrial arrhythmia before (HR 3.22; 95%CI 1.56-6.66; P = 0.002) and within 1 month after repair (HR 2.08; 95%CI 2.08-15.92; P = 0.001) were predictive of late atrial arrhythmia. Kaplan-Meier analysis showed that patients with a mPAP ≥ 25 mm Hg had a higher risk at developing late atrial arrhythmia (P < 0.0001).

Conclusion

In patients with ASD type secundum, a mPAP ≥ 25 mm Hg is an independent predictor of late atrial arrhythmia. The presence of pulmonary hypertension before repair should raise awareness for atrial arrhythmias and may be used to guide therapy.     

A simplified method to determine left atrial volume and transport function using multi-slice computed tomography in patients with atrial fibrillation: comparison with transthoracic echocardiography

Although left atrial volumes (LAVs) and transport function can be accurately measured by multi-slice computed tomography (MSCT) during sinus rhythm, limited data are available for in patients with atrial fibrillation (AF). The aims of our study were to compare LAVs and function assessed by MSCT and transthoracic echocardiography (TTE) during AF, and to validate a simplified method to determine LAVs and functions using MSCT. A total of 150 consecutive AF patients who were scheduled to undergo catheter ablation were enrolled in this study. All subjects underwent MSCT and TTE on the same day. LAVs were measured by MSCT at every 10% of the R-R interval (10-phase analysis). LA transport function was assessed by measuring changes in LAVs. LAVs and functions were also assessed by TTE using a modified Simpson's method and an area-length method. Fifty patients were in sinus rhythm (SR) and 100 were in AF during their examinations. Although TTE underestimated the maximal LAV (LAV(max), by 38.3%) and overestimated the total LA emptying fraction (LAEF(total), by 61.1%) compared with MSCT, there were excellent correlations between TTE and MSCT. LAV(max) and the minimal LAV (LAV(min)) based on MSCT were determined at relatively constant cardiac phases during AF as well as SR (LAV(max); 40%, LAV(min); 100% of R-R interval, fixed-phase analysis). LAVs and LAEF(total) assessed by 10-phase analysis showed good correlations with those assessed by fixed-phase analysis (P < 0.001). LAVs and function assessed by MSCT correlated well with LAVs and functions assessed by TTE, irrespective of the underlying rhythm. Our results indicate that in the context of MSCT, fixed-phase analysis is a simple and reliable method to determine LAVs and function in patients with AF.     

Diffusion and Perfusion Characteristics of MELAS (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episode) in Thirteen Patients

Objective

We analyzed the diffusion and perfusion characteristics of acute MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode) lesions in a large series to investigate the controversial changes of the apparent diffusion coefficient (ADC) that were reported in prior studies.

Materials and Methods

We analyzed 44 newly appearing lesions during 28 stroke-like episodes in 13 patients with MELAS. We performed a visual assessment of the MR images including the ADC and perfusion maps, comparison of the ADC between the normal and abnormal areas, comparison of % ADC between the 44 MELAS lesions and the 30 acute ischemic infarcts. In addition, the patterns of evolution on follow-up MR images were analyzed.

Results

Decreased, increased, and normal ADCs were noted in 16 (36%), 16 (36%), and 12 (27%) lesions, respectively. The mean % ADC was 102 ± 40.9% in the MELAS and 64 ± 17.8% in the acute vascular infarcts (p < 0.001), while perfusion imaging demonstrated hyper-perfusion in six acute MELAS lesions. On follow-up images, resolution, progression, and tissue loss were noted in 10, 4, and 17 lesions, respectively.

Conclusion

The cytotoxic edema gradually evolves following an acute stroke-like episode in patients with MELAS, and this may overlap with hyper-perfusion and vasogenic edema. The edematous swelling may be reversible or it may evolve to encephalomalacia, suggesting irreversible damage.