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Presenting features and molecular genetics of primary hyperparathyroidism in the paediatric population.


  • 影响因子:5.04
  • DOI:10.1530/EJE-20-1119
  • 作者列表:"El Allali Y","Hermetet C","Bacchetta J","Amouroux C","Rothenbuhler A","Porquet-Bordes V","Champigny MA","Baron S","Barat P","Bony-Trifunovic H","Bourdet K","Busiah K","Cartigny-Maciejewski M","Compain F","Coutant R","Amsellem-Jager J","De Kerdanet M","Magontier N","Mignot B","Richard O","Rossignol S","Soskin S","Berot A","Naud-Saudreau C","Salles JP","Linglart A","Edouard T","Lienhardt-Roussie A
  • 发表时间:2021-02-01

Aim:To describe the presenting features and molecular genetics of primary hyperparathyroidism (PHPT) in the paediatric population. Methods:Retrospective study of 63 children diagnosed with primary PHPT from 1998 to 2018. Results:Compared to older children, infants were often asymptomatic (54% vs 15%, P = 0.002) with a milder form of PHPT. When symptomatic, children and adolescents mostly presented with non-specific complaints such as asthenia, depression, weight loss, vomiting or abdominal pain. A genetic cause of PHPT was identified in about half of this cohort (52%). The infancy period was almost exclusively associated with mutation in genes involved in the calcium-sensing receptor (CaSR) signalling pathway (i.e. CaSR and AP2S1 genes, 'CaSR group'; 94% of infants with mutations) whereas childhood and adolescence were associated with mutation in genes involved in parathyroid cell proliferation (i.e. MEN1, CDC73, CDKN1B and RET genes, 'cell proliferation group'; 69% of children and adolescents with mutations). Although serum calcium levels did not differ between the two groups (P = 0.785), serum PTH levels and the urinary calcium/creatinine ratio were significantly higher in 'cell proliferation group' patients compared to those in the 'CaSR group' (P = 0.001 and 0.028, respectively). Conclusion:Although far less common than in adults, PHPT can develop in children and is associated with significant morbidity. Consequently, this diagnosis should be considered in children with non-specific complaints and lead to monitoring of mineral homeostasis parameters. A genetic cause of PHPT can be identified in about half of these patients.


目的: 描述儿童原发性甲状旁腺功能亢进症 (PHPT) 的表现特征和分子遗传学。 方法: 对1998-2018年确诊为原发性PHPT的63例患儿进行回顾性研究。 结果: 与年龄较大的儿童相比,婴儿通常无症状 (54% vs 15%,P = 0.002),具有较轻形式的PHPT。当有症状时,儿童和青少年大多出现非特异性主诉,如虚弱、抑郁、体重减轻、呕吐或腹痛。在该队列的约一半 (52%) 中鉴定了PHPT的遗传原因。婴儿期几乎完全与参与钙敏感受体 (CaSR) 信号通路 (即CaSR和AP2S1基因,'CaSR组'; 94% 的婴儿有突变),而儿童期和青春期与涉及甲状旁腺细胞增殖的基因突变 (即MEN1、CDC73、CDKN1B和RET基因,'细胞增殖组'; 69% 的儿童和青少年有突变)。虽然两组之间的血清钙水平没有差异 (P = 0.785),但与 “casr组” 相比,“细胞增殖组” 患者的血清PTH水平和尿钙/肌酸酐比率显著更高 (分别为P = 0.001和0.028)。 结论: 尽管PHPT在儿童中的发病率远低于成人,但其在儿童中的发病率很高。因此,在患有非特异性主诉的儿童中应该考虑这种诊断,并导致矿物质稳态参数的监测。在这些患者中约一半可鉴定PHPT的遗传原因。



作者列表:["Juan-Carlos PM","Perla-Lidia PP","Stephanie-Talia MM","Mónica-Griselda AM","Luz-María TE"]

METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.

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作者列表:["Sawada H","Oeda T","Kohsaka M","Tomita S","Umemura A","Park K","Yamamoto K","Kiyohara K"]

METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.

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作者列表:["Louvrier A","Terranova L","Meyer C","Meyer F","Euvrard E","Kroemer M","Rolin G"]

METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.

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