Preclinical evaluation of coronary vascular function after cardioplegia with HTK and different antioxidant additives.

OBJECTIVE: Due to limited resources, improvement of preservation solutions is still of great importance in cardiac transplant surgery. New additives with antioxidant properties were tested with respect to coronary function of isolated rat hearts. METHODS: Bretschneider HTK solution containing none or an antioxidant additive (deferoxamine, trolox or LK 616) was used for 8h cold cardioplegia. After reperfusion with Krebs-Henseleit buffer (KHB), we assessed vascular dilator capacity (bradykinin, adenosine triphosphate, reactive hyperemia), myocardial function (left ventricular developed pressure, heart rate, oxygen consumption) and release of biochemical markers (aspartate aminotransferase, creatine kinase, lactate dehydrogenase, troponin, adenosine). RESULTS: Bradykinin- and adenosine triphosphate-induced vasodilations were largely reduced in hearts stored 8h in traditional HTK as compared to unstored controls. Storage in HTK+LK 616 significantly improved bradykinin-induced vasodilation. Vasodilation toward ATP was best preserved in hearts stored in HTK+deferoxamine. Deferoxamine and trolox, both improved reactive hyperaemic response during reperfusion. Left ventricular pressure development was significantly reduced after 8h cardioplegia, but no difference existed between different cardioplegia groups. Release of biochemical markers of tissue injury was similar in all cardioplegia groups. After storage in HTK+LK 616 (100 microM), however, heart marker release was slightly augmented as compared to HTK. CONCLUSIONS: Despite similar myocardial function and marker release, coronary vascular function after cardioplegic storage may profit by addition of iron chelators (or antioxidants) to traditional HTK solution.     

Seven DNA polymorphisms in the LDL receptor gene: application to the study of familial hypercholesterolemia in Spain

We have performed restriction fragment length polymorphism (RFLP) analysis at the low density lipoprotein receptor (LDLR) locus in order to investigate the molecular genetics of familial hypercholesterolemia (FH) in Spain. Firstly, a sample of 50 unrelated patients with a clinical diagnosis of FH was screened for the presence of major rearrangements at this locus by Southern blot analysis of Bgt II digested genomic DNA. Four different mutations were detected, accounting for 8% of the mutant alleles in the Spanish FH sample. Then, we determined the relative allele frequency and estimated linkage disequilibrium between seven RFLPs of the LDLR gene in the remaining 46 FH patients and in 61 normolipidemic controls. Hindi, Avail, Pvu II, Msp I, and Nco I are the most polymorphic sites with individual PIC values higher than 0.28, whereas the Taq I and Stu I sites display low levels of polymorphism. The usefulness of the seven RFLPs to confirm a clinical diagnosis of FH was investigated in 15 FH-families, consisting of 118 individuals, in whom the presence of Familial Defective Apolipoprotein B-100 (FDB) due to the apoB₃₅₀₀ mutation was excluded. Independent haplotypes were constructed for 71 chromosomes: 15 FH and 56 control haplotypes. A total of 14 different haplotypes was found. In 12 families, clinical diagnosis of FH was confirmed by cosegregation analysis, which makes these RFLPs useful for studying the inheritance of the LDLR gene in 80% of Spanish families with FH. Comparison of haplotypes found in the Spanish sample with those found in Swiss and Norwegians suggests heterogeneity of haplotypes among European populations.     

Unilateral Meesmann‘s dystrophy

We report the first case of a unilateral microcysticMeesmann‘s epithelial dystrophy, observed in the left cornea of a 43-year-old patient. The diagnosis was verified histologically by the unilateral occurrence of a ’peculiar substance‘ within epithelial cysts and within the cytoplasm of the corneal epithelial cells. In an attempt to resolve thepatient‘s frequent corneal erosions, we performed an autologous stem cell transplantation from the non-involved right eye. The results are, so far, satisfactory. This revised version was published online in August 2006 with corrections to the Cover Date.     

Lactone, 16. Mitt.: Synthese von 4,9-Dihydropyrano[3,4-b]indol-1(3H)-onen aus α-Ethoxalyl-δ-valerolacton

Lactones, XVI: Synthesis of 4,9-Dihydropyrano[3,4-b]indol-1(3H)-ones from α-Ethoxalyl-δ-valerolactone Treatment of α-ethoxalyl-δ-valerolactone (1) with diazotized anilines and indolization of the intermediate hydrazones 4 leads to the pyranoindolones 5 . Compared to the recently reported reaction of α-ethoxalyl-γ-butyrolactone with arylhydrazines²⁾, this synthesis is more versatile with regard to variation of substituents at the aromatic ring. Stereochemistry and reactivity of the α-arylhydrazonolactones are discussed.     

Checklist for the qualitative evaluation of clinical studies with particular focus on external validity and model validity

Background  

It is often stated that external validity is not sufficiently considered in the assessment of clinical studies. Although tools for its evaluation have been established, there is a lack of awareness of their significance and application. In this article, a comprehensive checklist is presented addressing these relevant criteria.     

Incidence and Clinical Significance of Ventricular Late Potentials in Idiopathic Dilated Cardiomyopathy Compared to Coronary Artery Disease

Objective: This prospective study was designed to compare incidence and clinical significance of ventricular late potentials between patients with idiopathic dilated cardiomyopathy (IDC) and postinfarct patients (CAD) using exactly the same method of signal-averaged electrocardiography (SAECG) in both patient groups. Methods: Time-domain analysis of SAECG was performed in 120 consecutive patients with IDC, 120 patients with CAD, and 60 healthy controls. Ventricular late potentials were detected in 27 of 120 patients with IDC (23%) compared to 41 of 120 patients with CAD (34%; P < 0.05). Results: Ventricular late potentials were found in 2 of 60 controls (3%). During 15 ± 7 months follow-up, serious arrhythmic events occurred in 17 of 120 patients with IDC (14%) and in 13 of 120 patients with CAD (11%). The sensitivity of ventricular late potentials for future arrhythmic events was 35% for IDC compared to 77% for CAD (P < 0.05). The positive predictive value of late potentials detected by time-domain analysis was 22% for IDC versus 24% for CAD (P = ns). Conclusion: In this selected patient population with IDC and CAD, time-domain analysis of SAECG revealed a lower incidence of ventricular ate potentials in patients with IDC as compared to postinfarct patients. Whereas ventricular late potentials had a high sensitivity but a low positive predictive value for identification of postinfarct patients with serious arrhythmic events during follow-up, both sensitivity and positive predictive value of ventricular late potentials for future serious arrhythmic events were low in the setting of IDC.