Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study.

Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PHPT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A index cases and to characterize the former cases. An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registry data of index cases followed from 1974 to 2017. Ten cases presented with PHPT as their first manifestation of MEN 2A, yielding a prevalence of 0.9% (95% CI: 0.4-1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis. Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of index cases presenting with PHPT as first manifestation have synchronous MTC and are often node-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PHPT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resection of PHPT.S D received a national grant (AZV 16-32665A).S

Historical lead seals and the influence of disinfectants on the lead corrosion rate

Abstract Lead used to be a common material for setting seal to historical documents. Lead seals formed parts of historical documents as a guarantee of their legal validity. Disinfectants are commonly used during the restoration of historical documents. They successfully remove mould, bacteria and microscopic fungi from the surface of parchment documents. However, some disinfectants could also be a source of corrosion damage to lead seals. This work was carried out to examine possible corrosion damage to lead seals caused by disinfectants [a solution of carbethopendecinium bromide, a solution of glutaraldehyde, butanol (vapours), a solution of 1-propanol, 2-propanol + ethanol called Bacillol AF], which are commonly used during restoration of historical documents. The lead corrosion rates were determined by using lead resistometric probes. The solutions of carbethopendecinium bromide and glutaraldehyde increase the lead corrosion rate and corrosion products based on carbonates, nitrates and organic lead salts are formed on the lead surface. The most appropriate disinfectants for the restoration of historical documents with lead seals are alcohol-based solutions, such as butanol (vapours) and a solution of 1-propanol, 2-propanol and ethanol called Bacillol AF

<i>RET</i> Variants and Haplotype Analysis in a Cohort of Czech Patients with Hirschsprung Disease

<div><p>Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses in variable length of the intestine. This study investigated the influence and a possible modifying function of <i>RET</i> proto-oncogene's single nucleotide polymorphisms (SNPs) and haplotypes in the development and phenotype of the disease in Czech patients. Genotyping of 14 SNPs was performed using TaqMan Genotyping Assays and direct sequencing. The frequencies of SNPs and generated haplotypes were statistically evaluated using chi-square test and the association with the risk of HSCR was estimated by odds ratio. SNP analysis revealed significant differences in frequencies of 11 polymorphic <i>RET</i> variants between 162 HSCR patients and 205 unaffected controls. Particularly variant alleles of rs1864410, rs2435357, rs2506004 (intron 1), rs1800858 (exon 2), rs1800861 (exon 13), and rs2565200 (intron 19) were strongly associated with increased risk of HSCR (p<0.00000) and were over-represented in males vs. females. Conversely, variant alleles of rs1800860, rs1799939 and rs1800863 (exons 7, 11, 15) had a protective role. The haploblock comprising variants in intron 1 and exon 2 was constructed. It represented a high risk of HSCR, however, the influence of other variants was also found after pruning from effect of this haploblock. Clustering patients according to genotype status in haploblock revealed a strong co-segregation with several SNPs and pointed out the differences between long and short form of HSCR. This study involved a large number of SNPs along the entire <i>RET</i> proto-oncogene with demonstration of their risk/protective role also in haplotype and diplotype analysis in the Czech population. The influence of some variant alleles on the aggressiveness of the disease and their role in gender manifestation differences was found. These data contribute to worldwide knowledge of the genetics of HSCR.</p></div

Allelic distribution of single nucleotide polymorphisms in HSCR patients and controls.

<p>Allelic distribution of single nucleotide polymorphisms in HSCR patients and controls.</p

Haplotype blocks generated by the Haploview Programme in cohorts of HSCR patients and control population.

<p>The scheme is shown with confidence bounds. LD values are reported in D′.</p

Distribution of haplotypes and diplotypes of 5′ region haploblock in HSCR patients and controls.

<p>* Haplotypes/diplotypes with occurrence <2% in both cohorts are not included.</p

Allelic distribution of single nucleotide polymorphisms considering allelic distribution of haploblock-haplotypes TTAA and GCCG in patients with long-segment and short-segment form of HSCR.

<p>Allelic distribution of single nucleotide polymorphisms considering allelic distribution of haploblock-haplotypes TTAA and GCCG in patients with long-segment and short-segment form of HSCR.</p

Allelic distribution of single nucleotide polymorphisms of 5′ region haploblock in patients with long-segment and short-segment form of HSCR and in male and female HSCR patients.

<p>Allelic distribution of single nucleotide polymorphisms of 5′ region haploblock in patients with long-segment and short-segment form of HSCR and in male and female HSCR patients.</p

Allelic distribution of single nucleotide polymorphisms considering allelic distribution of haploblock-haplotypes TTAA and GCCG in HSCR patients and controls.

<p>Allelic distribution of single nucleotide polymorphisms considering allelic distribution of haploblock-haplotypes TTAA and GCCG in HSCR patients and controls.</p