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.     

Oxidation of L-lysine derivatives to L-α-aminoadipamic acid (homoglutamine) derivatives with KMnO 4

A new route to L-homoglutamine (L-α-aminoadipamic acid) derivatives is presented via preferential KMnO₄ oxidation in acidic media of the e-methylene group in H-L-Lys(Z)-OH and Z-L-Lys(Z)-OH. The main oxidation products are 5-benzyloxy-carbonylcarbamoyl-2-aminopentanoic acid (H-L-Aad(NHZ)-OH) 2 and 5-benzyl-oxycarbonylcarbamoyl-2-benzyloxycarbonylaminopentanoic acid (Z-L-Aad(NHZ)-OH) 10 , respectively, in which the intact benzyloxycarbonyl protection is now attached to the nitrogen atom of the δ-amide group. The accompanying hydrolysis of the labile N-protected amide group and the continuing oxidation, however, diminish the quantity of 2 and 10 in the reacting mixture. Therefore, to obtain fair yields of these products, useful in peptide synthesis, involving homoglutamic acid and homoglutamine (H-L-Aad(NHZ)-OH and Z-L-Aad(NHZ)-OH contain carboxylic groups in differential form) a compromise must be reached and the oxidation process stopped at the right moment. Besides the desired oxidation product involving the transformation of the e-methylene group into the carbonyl group, a number of side products formed by oxidation of the α-carbon atom (derivatives of δ-aminovaleric acid) and e, α-carbon atoms (derivatives of glutaric acid) have been isolated and identified.     

Radiofrequency Catheter Ablation of Atrial Flutter Induces the Release of Platelet and Leukocyte-Derived Procoagulant Microparticles and a Prothrombotic State

Background: To assess the extent of endothelium, platelet, and leukocyte damage and coagulation activation induced by radiofrequency catheter ablation (RF) of atrial flutter. In the vasculature, procoagulant microparticles (MPs) are reliable markers of vascular damage. They provide an additional phospholipidic surface, enabling the assembly of the enzyme complexes of blood coagulation and consequent thrombin generation.
Methods: MPs were measured in the venous blood of 33 patients with isthmus-dependent atrial flutter undergoing RF before (RF₀), immediately after (RF₁), and at day 1 (RF₂) thereafter. Concentrations of PAI-1, vWF, and D-dimers were simultaneously determined. MPs procoagulant activities were determined using a functional prothrombinase assay. RF induces an early rise of platelet-derived MPs (platelet), vWF Ag, and D-dimers levels, which is concomitant with the decrease of PAI-1 concentrations. Conversely, no significant changes in endothelial-derived MPs could be evidenced. At RF₂, sustained elevation of leukocytes-derived MPs, vWF, and D-dimers testified to an ongoing prothrombotic status.
Conclusion: RF ablation of common flutter induces a prothrombotic state and the release of platelet and leukocyte-derived procoagulant microparticles. Whereas this activation of blood coagulation could be viewed as clinically marginal in right-sided procedures, its relevance in left-sided procedures should be established.     

Does Atrial Fibrillation Beget Ventricular Fibrillation in Patients with Acute Myocardial Infarction?

Background: Atrial fibrillation (AF) is associated with increased mortality and a higher complication rate postmyocardial infarction (MI), but the exact mechanisms are unknown. We investigated whether AF predisposes to ventricular arrhythmia in postmyocardial infarct patients, thereby accounting for increased mortality. Methods: Five hundred consecutive patients admitted to our coronary care unit with acute MI were monitored for in‐hospital arrhythmias. Detailed information was also compiled on past history, co‐morbidities, electrolyte disturbances, drug therapies, and ejection fraction. Mortality data were collected for an average of 5.5 years. Results: The results have shown that the incidence of ventricular fibrillation (VF) is much greater in patients presenting with AF (P = 0.03) and multivariate analysis has shown that AF is independently associated with the development of VF. This association occurs principally in patients who are admitted with AF (P = 0.01) rather than those who develop it during their admission, although these patients are also at mildly increased risk. The increased incidence of VF does account for increased mortality in the AF patients but does not explain all of their excess risk. There was no association between AF and ventricular tachycardia (VT); P = 0.50. Conclusions: In conclusion, AF on admission to the hospital with acute MI is associated with an increased risk of VF and subsequent mortality.     

Decreased Expression of Endometrial Decay Accelerating Factor (DAF), a Complement Regulatory Protein,in Patients With Luteal Phase Defect

PROBLEM : We investigated the level of decay accelerating factor (DAF) in the endometrium of luteal phase defect (LPD) patients, before and after treatment with progesterone. METHODS : Endometrial samples from fourteen normal-cycling controls and six samples from infertility patients with LPD before and four samples after progesterone treatment were stained by anti-DAF IgG using immunohistochemistry. RESULTS : Mean DAF OD in LPD patients was 15% compared to 60% in the control group. The mean DAF OD was 88% after treatment with progesterone. CONCLUSION : Results support interpretation that progesterone upregulates DAF while decreased progesterone may be associated with reduced expression of the DAF in LPD patients.     

Lymphocyte subpopulations in full-term septic neonates

PURPOSE: To estimate the absolute leukocyte and lymphocyte counts and relative and absolute sizes of CD19+ B lymphocytes, CD3+, CD4+, CD8+ and CD3+/HLA-DR+ T lymphocytes in full-term septic neonates and the influence of some perinatal risk factors on these lymphocyte subsets. METHODS: Twenty-one septic and mechanically ventilated full-term neonates (13 boys and eight girls) and 15 healthy full-term neonates born vaginally with an Apgar score > 9 and without hyperbilirubinemia were investigated. Two-color flow cytometric immunophenotyping with appropriate antibody panels using lysed whole vein blood was performed. RESULTS: The mean relative and absolute sizes of CD19+ B lymphocytes, CD3+/CD8+ and CD3+/HLA-DR+ T lymphocytes in septic neonates did not differ significantly from control. In contrast, the mean relative sizes of CD3+ and CD3+/CD4+ T lymphocytes and the CD4+/CD8+ ratio in septic neonates were significantly higher than in healthy neonates. With regard to the absolute size in septic neonates, only CD4+ T cells were significantly higher compared with the control group. Perinatal risk factors (birth asphyxia, gestation and delivery complications) had no significant effect on the relative and absolute counts of all estimated lymphocyte subpopulations in septic neonates. CONCLUSIONS: Increases in the relative sizes of CD3+ and CD3+/CD4+ T lymphocytes and the CD4+/CD8+ ratio in full-term septic neonates provides important information about changes in cell-mediated immunity during the early neonatal period.