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.     

Correlations Between the Localization of Accessory Atrioventricular Pathway and Doppler Indices of Left Ventricular Output and Function in Patients With Wolff-Parkinson-White Syndrome

Left ventricular (LV) output and function was investigated, using pulsed Doppler echocardiography in 52 patients with various localizations of accessory AV pathway (AP) in sinus rhythm and during paroxysm of AV reentrant tachycardia. In patients with sinus rhythm and ventricular preexcitation the most marked decrease in LV output and function (reduced aortic flow peak velocity [PV], mean acceleration [MA], stroke distance [SD], minute distance [MD], and lengthened time to peak velocity [TTP]) was noted in the presence of right parietal AP and less marked changes (decreased MA, lengthened TTP)--in the presence of posteroseptal AP, in comparison with the controls (P less than 0.005). During antidromic tachycardia the pronounced decrease in PV, MA, SD, and MD was noted, especially in patients with left parietal and posteroseptal AP, while in the case of right parietal AP changes in MA and MD were insignificant. During orthodromic tachycardia the decrease in LV function was less marked and no significant differences in the magnitude of LV output and function changes were found in various localizations of AP, except MA, which was more severely decreased in patients with posteroseptal AP. We conclude, that the alterations in Doppler indices of LV output and function are related to the localization of AP during AV reentrant tachycardia and regular sinus rhythm.     

Changes of Left Ventricular Diastolic Filling After Sublingual Nitroglycerin in Determining the Severity of Coronary Artery Disease

The aim of the study was to evaluate the left ventricular (LV) diastolic filling (DF) in patients with 1, 2, and 3 vessel and left main (LM) coronary artery disease (CAD) and to determine the response of LV DF to nitroglycerin in age-matched patient groups. The study covers 74 patients with CAD including ten patients with 1 vessel CAD, ten patients with 2 vessel CAD, 43 patients with 3 vessel CAD, and 11 patients with LM CAD who underwent Doppler echocardiographic measurements of early (E) and late (A) diastolic transmitral velocities, their ratio (E/A) and deceleration time (DT) of E before and after sublingual administration of 0.5 mg nitroglycerin. Baseline studies did not reveal any significant differences in E, A, and DT between groups. Baseline E/A ratio differed between 1, 2, and 3 vessel and LM CAD patients (1.07 ± 0.10; 0.89 ± 0.07; 0.87 ± 0.05 vs 0.67 ± 0.06, P < 0.05). After nitroglycerin, significant differences in E between 1 vessel CAD and all the remaining groups, also between 2 and 3 vessel CAD and LM CAD patient groups (50.1 ± 2.4 cm/sec vs 39.6 ± 2.6; 38.4 ± 1.8; 30.2 ± 3.3 cm/sec and 39.6 ± 2.6; 38.4 ± 1.8 cm/sec vs 30.2 ± 3.3 cm/sec, respectively) were observed. A velocity did not differ significantly between the groups, DT differed between 1 vessel CAD and LM CAD patients (162.2 ± 14.6 msec vs 117.0 ± 12.1 msec), differences in E/A ratio appeared between 1 vessel and the remaining groups (1.13 ± 0.10 vs 0.72 ± 0.08; 0.70 ± 0.05 and 0.55 ± 0.07). Thus, Doppler LV DF indices, except E/A ratio, were not sensitive in reflecting the severity of CAD. Therefore, nitroglycerin resulted in more marked decrease of LV DF indices in patients with more severe CAD and in revealing differences between patients with 1, 2, and 3 vessel and LM CAD. These data suggest that a nitroglycerin Doppler test may be proposed for the assessment of the severity of CAD.     

TREATMENT OF SKIN AGING WITH TOPICAL ESTROGENS

Background. The coincidence of climacteric symptoms and the beginning of skin aging suggests that estrogen deficiency may be a common and important factor in the perimenopausal woman. Often hormones have been considered important in endogenous aging of the skin, but their role has not been clearly defined. Therefore, we investigated, whether topical treatment of the skin with estrogen could reverse some of the changes in the aging skin. Materials and Methods. The effects of 0.01% estradiol and 0.3% estriol compounds were compared in 59 preclimacteric women with skin aging symptoms. Monthly determinations of estrodiol (E2), follicle-stimulating hormone (FSH), and prolactin (PRL) were done and the monthly clinical monitoring was supplemented by measurements of skin hydration by corneometry and profilometry. In 10 patients, skin biopsies were taken for immunohistochemical determination of collagen types I and III. Results. After treatment for 6 months, elasticity and firmness of the skin had markedly improved and the wrinkle depth and pore sizes had decreased by 61 to 100% in both groups. Furthermore, skin moisture had increased and the measurement of wrinkles using skin profilometry, revealed significant, or even highly significant, decreases of wrinkle depth in the estradiol and the estriol groups, respectively. On immunohistochemistry, significant increases of Type III collagen labeling were combined with increased numbers of collagen fibers at the end of the treatment period. As to hormone levels, only those of PRL had increased significantly and no systemic hormonal side effects were noted. Conclusion. Both estrogen compounds were found to be highly effective in preventing or treating skin aging in perimenopausal women, clinically, by measurement data, and by an increase in collagen Type III.     

Synthesis and biological evaluation of human preproenkephalin (100-111) and its analogs*

The dodecapeptide sequence, Tyr-Gly-Gly-Phe-Met-Lys-Arg-Tyr-Gly-Gly-Phe-Met (BI), which is totally conserved in the primary structures of human, bovine, rat, and toad preproenkephalins, has been synthesized by the solid-phase method. Coupling reactions were achieved by using symmetrical anhydrides of tert.-butyloxycarbonylamino acids preformed with N-tert.-butyl,N′-methylcarbodiimide. 6-Arg and 7-Lys analogs have also been obtained. The peptides show opiate activity in both GPI and MVD assay, and possess antinociceptive properties as estimated by the hot-plate test in mice when applied intracisternally.     

Electrostimulated Cardiomyoplasty: From Experimental to Clinical Studies

Cardiomyoplasty is a method for managing patients with dilated cardiomyopathy. We evaluated the means of carbon fiber electrode stimulation of the nerve to the latissimus dorsi muscle (LDM) in dogs to increase skeletal muscle contractility. Histochemical examination of biopsies of muscle electrically conditioned by a single pulse stimulator via the thoracodorsal nerve demonstrated transformation of muscle into fatigue resistant slow fibers without damage to muscle or nerve tissue. Canine experiments confirmed that carbon fibers are one of the best electrodes for chronic LDM stimulation. Between 1988 and 1992, we operated on ten patients, New York Heart Association (NYHA) Class III (4 patients) and Class IV (6 patients), with a mean left ventricular ejection fraction (LVEF) of 23%. The indications for Cardiomyoplasty were idiopathic (7 patients) and ischemic (3 patients) cardiomyopathy refractory to maximum medical therapy. The operative procedure was performed via median sternotomy (5 patients) and left thoracotomy (5 patients). There was one operative mortality and two additional deaths during the late follow-up period. The mean postoperative LVEF increased to 27%. Functional class, quality-of-life, and ventricular performance were improved after Cardiomyoplasty. Two of the surviving patients are in NYHA Class I, four in Class II, and one in Class III.     

Visfatin and endothelial function in dialyzed patients

Aim: Visfatin is an adipocytokine that has recently generated much interest. The aim of the study was to assess visfatin in correlation with markers of endothelial damage and inflammation in haemodialyzed and peritoneally dialyzed patients. Methods: Visfatin, leptin, apelin and adiponectin, markers of coagulation (thrombin–antithrombin complexes (TAT), prothrombin fragments 1+2 (F1+2)), fibrinolysis (tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI‐1)), endothelial function/injury (Von Willebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), CD146) and inflammation (high‐sensitivity C‐reactive protein (hsCRP), tumour necrosis factor‐α (TNF‐α) and interleukin (IL)‐6) were assessed. Results: Triglycerides, hsCRP, creatinine, IL‐6, TNF‐α, vWF, F1+2, TAT, thrombomodulin, ICAM, VCAM, CD146, PAI‐1, leptin, adiponectin and visfatin were elevated in dialyzed patients over controls. Visfatin correlated significantly, in univariate analysis, in haemodialyzed patients with markers of endothelial damage/inflammation (CD146, ICAM, IL‐6), other adipocytokines, Kt/V and dialysis vintage, and tended to correlate with hsCRP. In peritoneally dialyzed patients, visfatin correlated significantly with haemoglobin, and markers of endothelial damage. In the healthy volunteers visfatin correlated significantly with ICAM, creatinine and IL‐6. In multiple regression analysis in HD patients visfatin was only independently related to Kt/V, dialysis vintage and IL‐6. Conclusion: Elevated visfatin related to markers of inflammation might represent a novel link between inflammation and adipocytokines in dialyzed patients. Time on dialyses and dialysis adequacy may influence visfatin in dialyzed patients due to the decreased clearance of visfatin.     

An overview of oral health promotion in adolescents

Objective.  The aim of this study was to overview the effectiveness of different strategies used to promote oral health in adolescents.
Methods.  A search of the MEDLINE via OVID database was performed through September 2007. The studies aiming to modify oral health-related lifestyle in adolescents with experimental pre- to post-test controlled study design were targeted. Oral health-related knowledge, attitudes, oral hygiene status, gingival health, and caries status were used as outcome measures for the evaluation of changes in adolescent oral health-related behaviour.
Results.  All studies evaluating knowledge showed cognitive gains. Only slight or no improvement in attitude was reported. The average improvement in oral hygiene was 30–50%. A wide range 0–50% of the effects on gingival health was presented. However, the relapse in oral hygiene status towards baseline values was also observed. Only studies employing professionally applied preventive measures in conjunction with educational activities reported significantly lower caries incidence.
Conclusion.  The limited success of the behavioural interventions and the lack of diversity in methods used do not allow identification of the best ways to promote oral health towards adolescents. Therefore, alternative approaches for oral health promotion in adolescents should be explored.