Clinical,biochemical and histological analysis of seven patients with cholesteryl ester storage disease

Lysosomal acid lipase (LAL) deficiency leads to two phenotypically different diseases: cholesteryl ester storage disease (CESD) and Wolman's disease. Lysosomal acid lipase hydrolyzes cholesteryl esters and triglycerides. Deficiency of LAL results in intralysosomal storage of cholesteryl esters and triglycerides. CESD has a chronic and benign course and is characterized by hepatomegaly and mild hypercholesterolemia. It leads to fibrosis (cirrhosis) and early atherosclerosis. This report presents the clinical, biochemical and microscopic data of seven patients with CESD followed up over 10 years. The physical development of all the study children remained within the normal range; 7 patients had hepatomegaly and 6 also had splenomegaly. Three patients had normal cholesterol, triglycerides and transaminases values; the other four had slightly elevated levels for these parameters. The activity of LAL in all patients was reduced to below 30% of the lower normal value. Histologically, cholesteryl crystals and lipid storage vacuoles in Kupffer cells were present in all examined patients except one. Accumulation of cholesteryl esters was visible on thin-layer chromatography of lipid extracts obtained from liver biopsies.     

The association of –262C/T polymorphism in the catalase gene and delayed graft function of kidney allografts

Background: Catalase is an intracellular antioxidant enzyme that is mainly located in cellular peroxisomes and in the cytosol. This enzyme plays a significant role in the development of tolerance to oxidative stress in the adaptive response of cells and tissues. The aim of the present study was to examine the association between the –262C/T polymorphism in the catalase gene and delayed graft function (DGF), acute rejection and chronic allograft nephropathy of kidney allografts. Methods: One hundred eighty‐seven recipients of first renal transplants were included in the study. The histories of the patients were analysed regarding DGF, acute rejection and chronic allograft nephropathy. The polymorphism –262C/T in the catalase gene was analysed using the polymerase chain reaction – restriction fragment length polymorphism (PCR‐RFLP) method. Results: The risk of DGF was significantly lower in T allele carriers compared with CC homozygotes: odds ratio = 0.34, 95% confidence interval = 0.17–0.67, P = 0.001. There were no statistically significant associations between the studied polymorphism and acute rejection or chronic allograft nephropathy. Conclusion: The results of this study suggest that –262C/T polymorphism in the catalase gene is associated with DGF in kidney allograft recipients.     

The Role of Anti-α-Enolase Autoantibodies in Pathogenicity of Autoimmune-Mediated Retinopathy

Autoantibodies against α-enolase, a glycolytic enzyme, have been frequently associated with visual loss and retinal degeneration in patients with autoimmune and cancer-associated retinopathy; however their role in the pathogenicity of retinopathy has not been fully explained. Thus, we examined the causative role of anti-enolase antibodies on retinal cells. In the in vitro studies reported here, we found that Enol-1 monoclonal antibody against α-enolase significantly inhibited the catalytic function of enolase, which resulted in the depletion of glycolytic ATP. Enol-1 significantly increased intracellular Ca²⁺, which led to Bax translocation to the mitochondria, and the release of cytochrome c into the cytoplasm—events that correlated with the initiation of apoptosis. Normal IgG did not induce intracellular calcium or reduce cytosolic ATP. L-type voltage-gated calcium channel blockers (nifedipine, D-cis-diltiazem, and verapamil) were effective in blocking the Ab-induced intracellular Ca²⁺ rise and induction of Bax. Based on these findings we propose that chronic access of autoantibodies to the retina results in the inhibition of enolase catalytic function, depletion of ATP, and elevation in intracellular Ca²⁺, leading to deregulation of glycolysis in retinal neurons and their destruction.     

Coronary Venous Retention—A Feature in Heart Failure as Evidenced by Mean of Cardiac Computed Tomography

Background: Whether the functional status of the heart can influence the coronary venous system itself has not yet been examined. In order to answer this question, we used multislice computed tomography (CT) imaging. Purpose: To answer the question of whether the heart failure (HF) is associated with significant anatomical changes in the coronary venous system? Methods: In 136 (aged 56.6±11.5) patients, a 64‐slice CT was performed. Patients were divided into three groups according their ejection fraction. In each case, nine 3D volume rendering reconstructions, using a 2‐mm layer with electrocardiographic‐gating, were created at 0% to 90% R‐R intervals (step 10%). The visualization of coronary veins (CVs) was graded independently by two experts trained in multislice computed tomography on a 0–5 point scale (0—not visible/lack of vein; 5—smoothly bordered vascular structure). Results: The average number of visible CVs per case was 3.44 in the HF group and 2.72 in patients with a normal ejection fraction (P = 0.0246). The statistical correlation between a reduction in ejection fraction and the increase in the number of veins was found (r =?0.2446, P < 0.05). For two of seven common variants of the coronary venous system at least two target veins (posterolateral and lateral) for cardiac resynchronization were presented. Conclusions: The statistically higher number of veins in patients with heart failure may suggest an association between a failing heart and cardiac venous retention. (PACE 2012;35:1472–1479)     

Neuraminidase deficiency presenting as a nephrosialidosis: The first case detected in Poland

A defect of lysosomal neuraminidase (sialidase N-acetyl-neuramine acid hydrolase EC 3.2.1.18) leads to a wide spectrum of phenotypes, the most severe of which is nephrosialidosis. A 4-year-old boy of related parents, born at term with hydrops fetalis, is reported. Hydrocephalus was detected at 2 months of age. The child's course over 3 years was characterized by slow growth and psychomotor development. He had mild hepatosplenomegaly, joint restriction, gingival hypertrophy, lens opacities and cherry-red spot. Coarse facial features and depressed nasal bridge were discreet. At the age of 3.5 years, he developed gradual progressive edema, decreased activity and increased fatigue. A diagnosis of nephrotic syndrome was made because of massive proteinuria. Thin-layer chromatography of urinary oligosaccharides revealed the presence of several abnormal sialyloligosaccharides. The diagnosis was confirmed by measurement of neuraminidase activity in cultured skin fibroblasts.     

Heart Rate Turbulence Impairment and Ventricular Arrhythmias in Patients with Systemic Sclerosis

Background: Arrhythmias, conduction disturbances, and cardiac autonomic nervous system dysfunction are the most frequent cardiovascular complications in systemic sclerosis (scleroderma). The aim of the study was to assess heart rate turbulence (HRT) in systemic sclerosis patients and to identify the relationship between HRT and occurrence of arrhythmias. Methods: Forty‐five patients with scleroderma (aged 54.6 ± 14.7 years) and 30 healthy sex‐ and age‐matched subjects were examined. In addition to routine studies, 24‐hour Holter monitoring with assessment of HRT was performed. Results: As compared to controls, HRT was significantly impaired in systemic sclerosis patients. Abnormal HRT defined as turbulence onset (TO) ≥0.0% and/or turbulence slope (TS) ≤2.5 ms/RR (ms/RR interval) was found in 19 (42%) scleroderma patients and in no members of the control group. Serious ventricular arrhythmias Lown class IV (VA‐LownIV), for example, couplets and/or nonsustained ventricular tachycardias, were observed in 16 (36%) scleroderma patients. The median value of TS was significantly lower in systemic sclerosis patients with VA‐LownIV than in patients without VA‐LownIV (3.68 vs 7.00 ms/RR, P = 0.02). The area under curve of ROC analysis for prediction of VA‐LownIV was 0.72 (95% confidence interval [CI] 0.56–0.87) and revealed that TS <9.0 ms/RR was associated with VA‐Lown IV occurrence, with sensitivity of 93.7% and specificity of 44.8%. Univariate and multivariate analyses confirmed that lower values of TS were associated with VA‐LownIV occurrence (odds ratio 1.52, 95% CI 1.09–2.12, P = 0.01). Conclusions: Patients with systemic sclerosis are characterized by significant HRT impairment. Assessment of HRT and especially TS is useful in the identification of patients at risk for ventricular arrhythmias. (PACE 2010; 920–928)     

A User‐Friendly Method of Cardiac Venous System Visualization in 64‐Slice Computed Tomography

Background: Previsualization of the cardiac venous system is very important for some techniques, for example, cardiac resynchronization therapy (CRT). The aim of this study was to propose a new, user‐friendly method of cardiac venous system visualization in 64‐slice computed tomography (CT). Methods: In 112 patients (66 M) aged 58 ± 11 standard deviation, a 64‐slice CT with a retrospective electrocardiogram gating was performed due to a suspicion of ischemic heart disease. Special attention was paid to the requirements for image reconstruction useful for CRT. Results: In 74% of the patients, it was possible to obtain similar images to those during the CRT implantation procedure within anterior‐posterior, left anterior oblique, and right anterior oblique views. The coronary sinus was clearly visible in all cases, the ostium measured 12.9 ± 5.9 mm, and the angle of entrance 99 ± 12 degrees. In all patients it was possible to demonstrate more than one vein; in 95%, at least one vein was clearly visible in the target area. Among the target veins, the posterolateral vein was visible most frequently (78%) in the cases as well as the lateral vein (78%). Conclusion: The proposed scheme in 64‐slice computed tomography enables images to be generated similar to the intraoperative fluoroscopy, which can be useful in techniques where previsualization of the cardiac venous system is recommended.