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Open access

Ru-Xuan Zhao, Ting-Ting Shi, Sha Luo, Yun-Fu Liu, Zhong Xin, and Jin-Kui Yang

Background

Graves’ orbitopathy (GO) is an autoimmune disease with mechanical impairment of orbital muscles and lacrimal gland dysfunction. The frequently used methods of assessing GO activity include Clinical Activity Score (CAS), CT, and MRI. These approaches are mainly associated with orbital muscles; however, there are not many studies that focus on the lacrimal gland inflammation of GO patients.

Objective

The aim of this study is to assess the usefulness of 99mTc-DTPA single-photon emission (SPE) CT/CT in evaluating the lacrimal gland inflammation in GO, as compared with other methods.

Methods

A retrospective analysis of 48 patients with active GO compared with 33 controls was conducted. All subjects underwent clinical–endocrinological analyses, CAS evaluation, CT scans, and SPECT/CT examination. Lacrimal gland dimensions were determined and analyzed.

Results

The lacrimal glands in patients with GO were significantly larger in all measured dimensions (P  < 0.001) on CT scans relative to those in controls. Increased lacrimal gland diethylene triamine pentaacetic acid (DTPA) uptake ratios (P  < 0.001) were displayed in active GO patients compared to controls and were also correlated with thyrotropin receptor antibody levels. The cut-off value for discriminating active and inactive disease was calculated to be 1.735, with specificity of 82.6% and sensitivity of 74.2%. SPECT/CT uptake ratios and CAS values were positively correlated in all GO patients. SPECT/CT uptake ratios were also positively correlated with CT measurements including lacrimal gland volume and coronal width in GO patients.

Conclusions

These data indicated that lacrimal gland SPECT/CT images can serve as a good tool for assessing the inflammation and disease activity of GO.

Open access

Kevin D Cashman

Background

Internationally, concern has been repeatedly raised about the little notable progress in the collection, analysis and use of population micronutrient status and deficiency data globally. The need for representative status and intake data for vitamin D has been highlighted as a research priority for well over a decade.

Aim and methods

A narrative review which aims to provide a summary and assessment of vitamin D nutritional status data globally. This review divides the world into the Food and Agriculture Organisation’s (FAO) major regions: the Americas, Europe, Oceania, Africa and Asia. Emphasis was placed on published data on the prevalence of serum 25-hydroxyvitamin D (25(OH)D) < 25/30 and <50 nmol/L (reflecting vitamin D deficiency and inadequacy, respectively) as well as vitamin D intake, where possible from nationally representative surveys.

Results

Collating data from the limited number of available representative surveys from individual countries might suggest a relatively low overall prevalence of vitamin D deficiency in South America, Oceania and North America, whereas there is more moderate prevalence in Europe and Asia, and possibly Africa. Overall, the prevalence of serum 25(OH)D < 25/30 and <50 nmol/L ranges from ~5 to 18% and 24 to 49%, respectively, depending on FAO world region. Usual intakes of vitamin D can also vary by FAO world region, but in general, with a few exceptions, there are very high levels of inadequacy of vitamin D intake.

Conclusions

While the burden of vitamin D deficiency and inadequacy varies by world regions and not just by UVB availability, the global burden overall translates into enormous numbers of individuals at risk.

Open access

Xue-Lian Zhang, Xinyi Zhao, Yong Wu, Wen-qing Huang, Jun-jiang Chen, Peijie Hu, Wei Liu, Yi-Wen Chen, Jin Hao, Rong-Rong Xie, Hsiao Chang Chan, Ye Chun Ruan, Hui Chen, and Jinghui Guo

Objective

The beneficial effect of angiotensin(1–7) (Ang(1–7)), via the activation of its receptor, MAS-1, has been noted in diabetes treatment; however, how Ang(1–7) or MAS-1 affects insulin secretion remains elusive and whether the endogenous level of Ang(1–7) or MAS-1 is altered in diabetic individuals remains unexplored. We recently identified an important role of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl channel, in the regulation of insulin secretion. Here, we tested the possible involvement of CFTR in mediating Ang(1–7)’s effect on insulin secretion and measured the level of Ang(1–7), MAS-1 as well as CFTR in the blood of individuals with or without type 2 diabetes.

Methods

Ang(1–7)/MAS-1/CFTR pathway was determined by specific inhibitors, gene manipulation, Western blotting as well as insulin ELISA in a pancreatic β-cell line, RINm5F. Human blood samples were collected from 333 individuals with (n  = 197) and without (n  = 136) type 2 diabetes. Ang(1–7), MAS-1 and CFTR levels in the human blood were determined by ELISA.

Results

In RINm5F cells, Ang(1–7) induced intracellular cAMP increase, cAMP-response element binding protein (CREB) activation, enhanced CFTR expression and potentiated glucose-stimulated insulin secretion, which were abolished by a selective CFTR inhibitor, RNAi-knockdown of CFTR, or inhibition of MAS-1. In human subjects, the blood levels of MAS-1 and CFTR, but not Ang(1–7), were significantly higher in individuals with type 2 diabetes as compared to those in non-diabetic healthy subjects. In addition, blood levels of MAS-1 and CFTR were in significant positive correlation in type-2 diabetic but not non-diabetic subjects.

Conclusion

These results suggested that MAS-1 and CFTR as key players in mediating Ang(1–7)-promoted insulin secretion in pancreatic β-cells; MAS-1 and CFTR are positively correlated and both upregulated in type 2 diabetes.

Open access

Xiying Zeng, Yinxiang Huang, Mulin Zhang, Yun Chen, Jiawen Ye, Yan Han, Danyan Ma, Xin Zheng, Xiaohong Yan, and Changqin Liu

Objective

Anti-Müllerian hormone (AMH) is recognized as the most important biomarker for ovarian reserve. In this cross-sectional study, we aimed to explore the potential association of AMH with central obesity or general obesity in women with polycystic ovary syndrome (PCOS).

Methods

In this cross-sectional study, 179 patients with PCOS were enrolled and underwent anthropometric measurements (BMI and waist circumference (WC)) and serum AMH level detection. Pearson’s correlation and multivariable logistic regression analyses were performed to determine the associations of AMH with central obesity and general obesity.

Results

Subjects with increasing BMI showed significantly lower values of AMH (median (interquartile range (IQR)) 8.95 (6.03–13.60) ng/mL in normal weight group, 6.57 (4.18–8.77) ng/mL in overweight group, and 6.03 (4.34–9.44) ng/mL in obesity group, P = 0.001), but higher levels of systolic blood pressure, fasting insulin, total cholesterol, triglycerides, LDL-c, obesity indices (WC, hip circumferences, waist-to-hip ratio, waist-to-height ratio (WHtR), and Chinese visceral adiposity index (CVAI)). Compared with the group of PCOS women without central obesity, the group with central obesity had significantly lower value of AMH (median (IQR) 8.56 (5.29–12.96) ng/mL vs 6.22 (4.33–8.82) ng/mL; P = 0.003). Pearson’s correlation analysis showed that AMH was significantly and negatively correlated with BMI (r = −0.280; P < 0.001), WC (r = −0.263; P < 0.001), WHtR (r = −0.273; P < 0.001), and CVAI (r = −0.211; P = 0.006). Multivariate logistic regression analysis with adjustment for potential confounding factors showed that AMH was independently and negatively associated with central obesity but was not significantly associated with general obesity.

Conclusions

AMH was independently and negatively associated with central obesity. Closely monitoring the WC and AMH should be addressed in terms of assessing ovarian reserve in women with PCOS.

Open access

Yanmei Lou, Yanyan Zhang, Ping Zhao, Pei Qin, Changyi Wang, Jianping Ma, Xiaolin Peng, Hongen Chen, Dan Zhao, Shan Xu, Li Wang, Ming Zhang, Dongsheng Hu, and Fulan Hu

We aimed to assess the association between fasting plasma glucose (FPG) change trajectory and incident hypertension among Chinese population. This cohort study included 11,791 adults aged 18–80 years without hypertension at first entry and who completed at least four follow-ups between 2009 and 2016. Logistic regression was used to estimate odds ratios (ORs) and 95% CIs for the association between FPG change trajectory and probability of hypertension. During a median follow-up of 5.10 years (total person–years 61,887.76), hypertension developed in 2177 participants. After adjusting for baseline potential confounders, the probability of hypertension increased with the increasing FPG change trajectory (adjusted OR (aOR) 1.22, 95% CI 1.07–1.40), bell-shape trajectory (aOR 1.15, 95% CI 1.02–1.30) and other-shape trajectory (aOR 1.13, 95% CI 1.02–1.25) which showed a higher variability of FPG compared to the decreasing group. In addition, the increasing FPG change trajectory was associated with a higher probability of hypertension compared with the decreasing group regardless of age and BMI but was only significant in males and in those with normal FPG at baseline. Our study indicates that the increasing FPG change trajectory determines the highest risk of hypertension, demonstrating the importance of maintaining low and stable levels of FPG, especially in males and in those with normal FPG.

Open access

Alicia Romano, Juan Pablo Kaski, Jovanna Dahlgren, Nicky Kelepouris, Alberto Pietropoli, Tilman R Rohrer, and Michel Polak

Objective

The study aims to assess the cardiovascular safety of growth hormone (GH) treatment in patients with Noonan syndrome (NS) in clinical practice.

Design

The study design involves two observational, multicentre studies (NordiNet® IOS and the ANSWER Program) evaluating the long-term effectiveness and safety of GH in >38,000 paediatric patients, of which 421 had NS.

Methods

Serious adverse events, serious adverse reactions (SARs) and non-serious adverse reactions (NSARs) were reported by the treating physicians. Cardiovascular comorbidities at baseline and throughout the studies were also recorded.

Results

The safety analysis set comprised 412 children with NS (29.1% females), with a mean (s.d.) baseline age of 9.29 (3.88) years, treated with an average GH dose of 0.047 (0.014) mg/kg/day during childhood. Cardiovascular comorbidities at baseline were reported in 48 (11.7%), most commonly pulmonary valve stenosis (PVS) and atrial septal defects. Overall, 22 (5.3%) patients experienced 34 safety events. The most common were the NSARs: headache (eight events in seven patients) and arthralgia (five events in three patients). Two SARs occurred in one patient (brain neoplasm and metastases to spine). No cardiovascular safety events were recorded in patients with NS. Five cardiovascular comorbidities in five patients were reported after initiation of GH treatment: three cases of unspecified cardiovascular disease, one ruptured abdominal aortic aneurysm and one PVS.

Conclusions

GH treatment had a favourable safety profile in patients with NS, including those with cardiovascular comorbidities. Prospective studies are warranted to systematically assess the safety of GH treatment in patients with NS and cardiovascular disease.

Open access

Xiaoya Zheng, Shanshan Yu, Jian Long, Qiang Wei, Liping Liu, Chun Liu, and Wei Ren

Objective

Both primary thyroid lymphoma (PTL) and diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) are two rare malignant tumours with different therapies and prognoses. This study compared their clinical features.

Methods

From a retrospective review of the pathologic database at our institute between January 2015 and August 2020, 52 PTL patients and 40 DSVPTC patients were included. Demographic, clinical, laboratory and ultrasound data were extracted from electronic medical records. Statistical analyses were performed using GraphPad Prism 5.0.

Results

Both PTL and DSVPTC were more likely to occur in women (83.7 and 67.5%, respectively), but DSVPTC patients were younger (median age: 36 vs 64.5), had fewer compressive symptoms, and more frequently had neck lymph node metastasis than PTL patients. The prevalence of Hashimoto’s thyroiditis (HT) and hypothyroidism was significantly higher in PTL patients than in DSVPTC patients (31% vs 17.5%). Hyperthyroidism could only be found in DSVPTC patients, which accounted for 7.5%. Heterogeneous echogenicity and irregular edges were frequently observed in both PTL and DSVPTC. However, compared with PTL, DSVPTC exhibited smaller lesion sizes, higher frequencies of diffuse sonographic patterns and calcification and lower frequencies of hypoechoic features and internal blood flow signal. The overall survival rate with PTL was 77.23%, which was lower than that with DSVPTC (90.91%), but this difference was not significant (P  = 0.096).

Conclusion

Clinical characteristics such as age, compression symptoms, and sonographic features such as a large mass with heterogeneous echogenicity, hypoechoic, irregular edges, and calcification are helpful for impression diagnosis of PTL and DSVPTC before surgery.

Open access

Debra M Gordon, Pablo Beckers, Emilie Castermans, Sebastian J C M M Neggers, Liliya Rostomyan, Vincent Bours, Patrick Petrossians, Vinciane Dideberg, Albert Beckers, and Adrian F Daly

Objective

Screening studies have established genetic risk profiles for diseases such as multiple endocrine neoplasia type 1 (MEN1) and pheochromocytoma–paraganglioma (PPGL). Founder effects play an important role in the regional/national epidemiology of endocrine cancers, particularly PPGL. Founder effects in the Netherlands have been described for various diseases, some of which established themselves in South Africa due to Dutch emigration. The role of Dutch founder effects in South Africa has not been explored in PPGL.

Design

We performed a single-center study in South Africa of the germline genetic causes of isolated/syndromic neuroendocrine tumors.

Methods

Next-generation panel, Sanger sequencing and multiplex ligand-dependent probe amplification for endocrine neoplasia risk genes.

Results

From a group of 13 patients, we identified 6 with PPGL, 4 with sporadic or familial isolated pituitary adenomas, and 3 with clinical MEN1; genetic variants were identified in 9/13 cases. We identified the Dutch founder exon 3 deletion in SDHB in two apparently unrelated individuals with distinct ethnic backgrounds that had metastatic PPGL. Asymptomatic carriers with this Dutch founder SDHBexon 3 deletion were also identified. Other PPGL patients had variants in SDHB, and SDHD and three MEN1variants were identified among MEN1 and young-onset pituitary adenoma patients.

Conclusions

This is the first identification of a Dutch founder effect for PPGL in South Africa. Awareness of the presence of this exon 3 SDHB deletion could promote targeted screening at a local level. Insights into PPGL genetics in South Africa could be achieved by studying existing patient databases for Dutch founder mutations in SDHx genes.