Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.     

The influence of socioeconomic and nutritional status on menarche in Nigerian school girls

Two once-daily electroconvulsive shocks (ECS) produced retrograde amnesia in rats trained on a Hebb-Williams maze; Verapamil (12.5 mg/kg, i.p.) or felodipine (10 mg/kg, p.o.) administered half an hour before each ECS attenuated this ECS-induced amnesia. Hence, these drugs may hold promise for the containment of amnesia induced by electroconvulsive therapy (ECT). Speculatively, one or more of several mechanisms may be involved: cerebral vasodilatation, enhancement of cholinergic tone, and inhibition of calcium-mediated impairment of neuronal function. These drugs may also act by attenuating the systolic surge in blood pressure during ECT, thereby decreasing edema due to cerebral hyperperfusion, as well as decreasing the possible transfer of potentially neurotoxic macromolecules through a putative breach in the blood-brain barrier.     

The 9p21 region in bladder cancer cell lines: large homozygous deletion inactivate the CDKN2, CDKN2B and MTAP genes

Homozygous and hemizygous deletions of 9p21 are the earliest and most common genetic alteration in bladder cancer. The identification of two cell cycle regulators, CDKN2 and CDKN2B, that map to the common region of deletion has prompted the hypothesis that they are critical tumor suppressor genes in this malignancy. However, controversy as to whether these genes are the only or even the most important target in bladder cancer oncogenesis remains. To more clearly determine the effect of these 9p21 alterations, we mapped the homozygous deletions and performed a detailed mutational and expression analysis for CDKN2, CDKN2B and a closely linked gene, methylthioadenoside phosphorylase (MTAP), in 16 established bladder cancer cell lines. Nine of the 16 lines exhibit large (30 to > 2000 kb) homozygous deletions on 9p21. All deletions include at least one exon of CDKN2, eight of nine include CDKN2B, and six of nine include MTAP. MTAP function correlates with the genomic deletions. SSCP and sequence analysis does not reveal any inactivating point mutations of CDKN2 or of CDKN2B in any of the cell lines without homozygous deletions, and all express the CDKN2 and the CDKN2B mRNA as well as the encoded p16 protein. The p16 protein levels vary widely and are correlated with absent pRb expression. We conclude that the 9p21 deletions in bladder cancer usually inactivate the CDKN2. CDKN2B, and MTAP genes but that CDKN2 is the most common target. Other mechanisms for inactivating this gene in bladder cancer appear to be uncommon.     

Linkage mapping of fifty-eight new rat microsatellite markers

Fifty-eight new anonymous simple sequence repeats (SSR) were generated and mapped to various rat chromosomes. Among them two genes (rat homologs for human cadherin-14 and mouse fibroblast growth factor-related protein) were mapped on Chromosomes (Chrs) 2 and 11 respectively. The majority of markers were generated from a small insert genomic library specific to Chr 11, 13, 14, and 15. Twenty new markers were mapped to Chr 13, which is known to contain a blood pressure quantitative trait locus (QTL). Several approaches to obtain microsatellite markers are described. The protocols and newly generated markers should be useful for ongoing rat genome project.     

The sanatorium-health resort treatment of children with thyroid hyperplasia

A favourable effect of sanatorium treatment on the key body functions was found in children with thyroid hyperplasia consequent to environmental pollution due to Chernobyl accident. It is emphasized that balneofactors in the above children should be used in sparing regimens.     

Isomerization of n-hexane over mono- and bimetallic Pd–Pt catalysts supported on ZrO2–Al2O3–WOx prepared by sol–gel

The catalytic performance of mono- and bimetallic Pd (0.6, 1.0 wt.%)–Pt (0.3 wt.%) catalysts supported on ZrO₂ (70, 85 wt.%)–Al₂O₃ (15, 0 wt.%)–WO_x (15 wt.%) prepared by sol–gel was studied in the hydroisomerization of n-hexane. The catalysts were characterized by N₂ physisorption, XRD, TPR, XPS, Raman, NMR, and FT-IR of adsorbed pyridine. The preparation of ZrW and ZrAlW mixed oxides by sol–gel favored the high dispersion of WO_x and the stabilization of zirconia in the tetragonal phase. The Al incorporation avoided the formation of monoclinic-WO₃ bulk phase. The catalysts increased their S_BET for about 15% promoted by Al₂O₃ addition. Various oxidation states of WO_x species coexist on the surface of the catalysts after calcination. The structure of the highly dispersed surface WO_x species is constituted mainly of isolated monotungstate and two-dimensional mono-oxotungstate species in tetrahedral coordination. The activity of Pd/ZrW catalysts in the hydroisomerization of n-hexane is promoted both with the addition of Al to the ZrW mixed oxide and the addition of Pt to Pd/ZrAlW catalysts. The improvement in the activity of Pd/ZrAlW catalysts is ascribed to a moderated acid strength and acidity, which can be correlated to the coexistence of W⁶⁺ and reduced-state WO_x species (either W⁴⁺ or W⁰). The addition of Pt to the Pd/ZrAlW catalyst does not modify significantly its acidic character. Selectivity results showed that the catalyst produced 2MP, 3MP and the high octane 2,3-dimethylbutane (2,3-DMB) and 2,2-dimethylbutane (2,2-DMB) isomers.