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71.
D?rthe Malzahn Martina Müller-Nurasyid Iris M Heid H-Erich Wichmann the KORA study group Heike Bickeb?ller 《European journal of human genetics : EJHG》2014,22(10):1217-1224
Among the single-nucleotide polymorphisms (SNPs) previously reported to be associated with body mass index (BMI) and obesity, we focus on a common risk variant rs7566605 upstream of the insulin-induced gene 2 (INSIG2) gene and a rare protective variant rs2229616 on the melanocortin-4 receptor (MC4R) gene. INSIG2 is involved in adipogenesis and MC4R effects hormonal appetite control in response to the amount of adipose tissue. The influence of rs2229616 (MC4R) on BMI and obesity has been confirmed repeatedly and insight into the underlying mechanism provided. However, a main effect of rs7566605 (INSIG2) is under debate because of inconsistent replications of association. Interaction of rs7566605 with age may offer an explanation. SNP–age and SNP–SNP interaction models were tested on independent individuals from three population-based longitudinal cohorts, restricting the analysis to an observed age of 25–74 years. KORA S3/F3, KORA S4/F4 (Augsburg, Germany, 1994–2005, 1999–2008), and Framingham-Offspring data (Framingham, USA, 1971–2001) were analysed, with a total sample size of N=6926 in the joint analysis. The effect of interaction between rs7566605 and age on BMI and obesity status is significant and consistent across studies. This new evidence for rs7566605 (INSIG2) complements previous research. In addition, the interaction effect of rs7566605 with the MC4R variant rs2229616 on BMI was observed. This effect size was three times larger than that in a previously reported single-locus main effect of rs2229616. This leads to the conclusion that SNP–age or SNP–SNP interactions can mask genetic effects for complex diseases if left unaccounted for. 相似文献
72.
Fabio Pagni Marta Jaconi Alberto Delitala Mattia Garancini Matteo Maternini Francesca Bono Alessandro Giani Andrew Smith the San Gerardo Hospital collaborators group 《Endocrine pathology》2014,25(3):288-296
The recent increase in the detection of papillary thyroid carcinoma (PTC) has been influenced by the finding of incidental tumours. To this group, carcinomas measuring less than 1 cm (the so-called microcarcinomas) as well as those above 1 cm belong. Analyzing a case series from our own experience, this paper focuses on the current pre-operative diagnostic challenges that can lead to PTC incidental discovery. For this retrospective study, 287 patients with a PTC diagnosis were selected. For each, the following variables were analysed: sex, age, ultrasound (US) appearance, number of thyroid nodules, PTC size, PTC variants and presence of other associated pathology. Pre-operative fine needle aspiration (FNA) results were classified according to the five-tiered SIAPEC system. For 281 patients, the US-guided FNA results were available. Cytohistological correlation was evaluated in terms of FNA sensitivity and false negative rate. An incidental PTC was found in 45.2 % of patients. The majority of these were due to unsuccessful US detection of malignant nodules (103 cases); incorrect cytological diagnosis was responsible for the other 24 cases. The most powerful clinical confounding factors were: multinodular background versus single nodule presentations (p?0.001) and histotype (follicular vs conventional variant, p?0.05). Of course, tumour size remains a strongly influential feature on pre-operative diagnosis, with greater difficulties arising for carcinomas <5 mm. Moreover, FNA sensitivity was lower also in large PTCs (>2 cm) due to tumour heterogeneity. Although with limitations related to the tumour’s intrinsic features and the thyroid background, US-guided FNA, especially if performed by a dedicated multidisciplinary team, is a powerful diagnostic tool for detecting malignant thyroid nodules. To the state of the art, we propose a practical clinical-pathological cut-off for this procedure, setting it at 5 mm. 相似文献
73.
Raheel A. Raja Kjeld Schmiegelow Birgitte K. Albertsen Kaie Prunsild Bernward Zeller Goda Vaitkeviciene Jonas Abrahamsson Mats Heyman Mervi Taskinen Arja Harila‐Saari Jukka Kanerva Thomas L. Frandsen the Nordic Society of Paediatric Haematology Oncology group 《British journal of haematology》2014,165(1):126-133
L‐asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Treatment is associated with several toxicities, including acute pancreatitis. Clinical course, presentation, re‐exposure to L‐asparginase after pancreatitis and risk of recurrent pancreatitis within an asparaginase‐intensive protocol has been poorly reported. Children (1–17 years) on the ongoing Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol with asparaginase‐associated pancreatitis (AAP) diagnosed between 2008 and 2012 were identified through the online NOPHO ALL toxicity registry. NOPHO ALL2008 includes eight or 15 doses of intramuscular pegylated L‐asparginase (PEG‐asparaginase) 1000 iu/m2/dose at 2–6 weeks intervals, with a total of 30 weeks of exposure to PEG‐asparaginase (clinicaltrials.gov no: NCT00819351). Of 786 children, 45 were diagnosed with AAP with a cumulative risk of AAP of 5·9%. AAP occurred after a median of five doses (range 1–13), and 11 d (median) from the latest administration of PEG‐Asparaginase. Thirteen patients developed pseudocysts (30%) and 11 patients developed necrosis (25%). One patient died from pancreatitis. Twelve AAP patients were re‐exposed to L‐asparginase, two of whom developed mild AAP once more, after four and six doses respectively. In conclusion, re‐exposure to PEG‐asparaginase in ALL patients with mild AAP seems safe. 相似文献
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76.
van Vollenhoven RF Geborek P Forslind K Albertsson K Ernestam S Petersson IF Chatzidionysiou K Bratt J;Swefot study group 《Lancet》2012,379(9827):1712-1720
77.
Sax PE DeJesus E Mills A Zolopa A Cohen C Wohl D Gallant JE Liu HC Zhong L Yale K White K Kearney BP Szwarcberg J Quirk E Cheng AK;GS-US-- study team 《Lancet》2012,379(9835):2439-2448
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