Recurrent neuroendocrine adenoma of the middle ear: A case report

Les historiens, qui sont rarement des oiseaux de très bon augure pour la vitalité des croyances qu’ils étudient, ont beaucoup écrit, depuis les années 1970, sur le purgatoire, ce troisième « lieu » de l’au-delà catholique, situé entre enfer et paradis. Support d’une dévotion très populaire, il a connu en Europe trois pics successifs de popularité, à la fin du Moyen Âge, au xviie et au xixe siècles. Le dogme et la croyance ont ainsi puissamment structuré dans la longue durée le rapport aux morts dans les sociétés de culture catholique, en leur conférant une « utilité » particulière, à la fois matérielle, institutionnelle, pastorale et anthropologique, que cet article s’efforce d’explorer.Historians are people who rarely contribute to the continued vitality of the beliefs they study. Since the 1970’s they have written a lot about purgatory, the third place in the catholic beyond. This is situated in between hell and paradise. The belief was the basis of a very popular cult which peaked in popularity in three different periods, one at the end of the Middle Ages, another in the seventeenth and a third in the nineteenth century. The dogma and the belief in purgatory have thus for long periods powerfully structured the relation to the dead in catholic cultures and have given these a particular “usefulness” whether this concerns material, institutional, pastoral or anthropological aspects. The paper attempts to explore these issues

Mild forms of hypophosphatasia mostly result from dominant negative effect of severe alleles or from compound heterozygosity for severe and moderate alleles

<p>Abstract</p> <p>Background</p> <p>Mild hypophosphatasia (HPP) phenotype may result from <it>ALPL </it>gene mutations exhibiting residual alkaline phosphatase activity or from severe heterozygous mutations exhibiting a dominant negative effect. In order to determine the cause of our failure to detect a second mutation by sequencing in patients with mild HPP and carrying on a single heterozygous mutation, we tested the possible dominant effect of 35 mutations carried by these patients.</p> <p>Methods</p> <p>We tested the mutations by site-directed mutagenesis. We also genotyped 8 exonic and intronic <it>ALPL </it>gene polymorphisms in the patients and in a control group in order to detect the possible existence of a recurrent intronic mild mutation.</p> <p>Results</p> <p>We found that most of the tested mutations exhibit a dominant negative effect that may account for the mild HPP phenotype, and that for at least some of the patients, a second mutation in linkage disequilibrium with a particular haplotype could not be ruled out.</p> <p>Conclusion</p> <p>Mild HPP results in part from compound heterozygosity for severe and moderate mutations, but also in a large part from heterozygous mutations with a dominant negative effect.</p

Clinical, biochemical and genetic spectrum of low alkaline phosphatase levels in adults

Background: Low serum levels of alkaline phosphatase (ALP) are a hallmark of hypophosphatasia. However, the clinical significance and the underlying genetics of low ALP in unselected populations are unclear. Methods: In order to clarify this issue, we performed a clinical, biochemical and genetic study of 42 individuals (age range 20–77 yr) with unexplained low ALP levels. Results: Nine hadmild hyperphosphatemia and three hadmild hypercalcemia. ALP levelswere inversely correlated with serum calcium (r = -0.38, p = 0.012), pyridoxal phosphate (PLP; r = -0.51, p = 0.001) and urine phosphoethanolamine (PEA; r = -0.49, p = 0.001). Although many subjects experienced minor complaints, such as mild musculoskeletal pain, none hadmajor health problems.Mutations in ALPL were found in 21 subjects (50%), including six novelmutations. All but one,were heterozygousmutations.Missensemutations were themost common (present in 18 subjects; 86%) and themajority were predicted to have a damaging effect on protein activity. The presence of amutated allelewas associated with tooth loss (48% versus 12%; p=0.04), slightly lower levels of serumALP (p=0.002), higher levels of PLP (p b 0.0001) and PEA (p b 0.0001), aswell asmildly increased serum phosphate (p=0.03). Ten individuals (24%) had PLP levels above the reference range; all carried a mutated allele. Conclusion: One-half of adult individuals with unexplained low serum ALP carried an ALPL mutation. Although the associated clinicalmanifestations are usuallymild, in approximately 50% of the cases, enzyme activity is lowenough to cause substrate accumulation and may predispose to defects in calcified tissues