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71.
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Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism 总被引:3,自引:0,他引:3
Baron J; Winer KK; Yanovski JA; Cunningham AW; Laue L; Zimmerman D; Cutler GB Jr 《Human molecular genetics》1996,5(5):601-606
Parathyroid hormone secretion is negatively regulated by a 7- transmembrane
domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that
activating mutations in this receptor might cause autosomal dominant
hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified,
in two families with ADHP, heterozygous missense mutations in the
Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of
50 normal controls had either mutation. We also identified a de novo,
missense Ca(2+)-sensing receptor mutation in a child with severe sporadic
hypoparathyroidism. The amino acid substitution in one ADHP family affected
the N-terminal, extracellular domain of the receptor. The other mutations
involved the transmembrane region. Unlike patients with acquired
hypoparathyroidism, patients with these mutations had hypercalciuria even
at low serum calcium concentrations. Their greater hypercalciuria
presumably reflected activation of Ca(2+)-sensing receptors in kidney
cells, where the receptor negatively regulates calcium reabsorption. This
augmented hypercalciuria increases the risk of renal complications and thus
has implications for the choice of therapy.
相似文献
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International statistical classification of diseases and related health problems coding underestimates the incidence and prevalence of acute kidney injury and chronic kidney disease in general medical patients 下载免费PDF全文
Soe Ko Sudharsan Venkatesan Kushma Nand Vicki Levidiotis Craig Nelson Edward Janus 《Internal medicine journal》2018,48(3):310-315
Background
The international classification of diseases (ICD) code is frequently used to identify renal impairment in epidemiological research. However, Australian studies examining accuracy of this administrative data in coding kidney injury are lacking.Aims
To compare the ICD 10 coding with the kidney disease: improving global outcomes (KDIGO) criteria in diagnosing acute kidney injury (AKI) and/or chronic kidney disease (CKD).Methods
A retrospective study of 325 patients admitted to general medicine during January 2012 was performed. Sensitivity and specificity of ICD 10 in identifying AKI and CKD were calculated using KDIGO as gold standard.Results
The sensitivities of ICD 10 in identifying AKI and CKD were low for both (59.5% and 54.1%), but the specificities were high (86.2% and 90.2%). Using KDIGO criteria, we identified 72 AKI (22%), 56 CKD (17%), 64 AKI on CKD (19%) and 133 controls (40%). Compared to the control group, patients with AKI and AKI on CKD had longer length of stay (3.2 vs 4.9 days and 3.2 vs 4.8 days, P = 0.20). Renal impairment groups had increased in‐hospital mortality rate (5% control, 6% AKI, 10% CKD, 9% AKI on CKD) and re‐admission rate within 30 days (13% control, 20% AKI, 25% CKD, 26% AKI on CKD). After adjusting for age, gender and comorbidities, the difference in outcomes was not statistically significant.Conclusion
This study shows that ICD 10 fails to identify almost half of the patients with AKI (40.5%) and CKD (45.9%) in our cohort. A total of 60% had evidence of renal impairment as defined by KDIGO. 相似文献75.
Influence of metabolic syndrome and race on the relationship between intensive blood pressure control and cardiovascular outcomes in the SPRINT cohort 下载免费PDF全文
76.
Cluster‐Randomized Trial of a Behavioral Intervention to Incorporate a Treat‐to‐Target Approach to Care of US Patients With Rheumatoid Arthritis 下载免费PDF全文
Leslie R. Harrold Ani John Christine J. Barr Kevin Soe Robert Magner Katherine C. Saunders Eric M. Ruderman Tmirah Haselkorn Jeffrey D. Greenberg Allan Gibofsky J. Timothy Harrington Joel M. Kremer 《Arthritis care & research》2018,70(3):379-387
Objective
To assess the feasibility and efficacy of implementing a treat‐to‐target approach versus usual care in a US‐based cohort of rheumatoid arthritis patients.Methods
In this behavioral intervention trial, rheumatology practices were cluster‐randomized to provide treat‐to‐target care or usual care. Eligible patients with moderate/high disease activity (Clinical Disease Activity Index [CDAI] score >10) were followed for 12 months. Both treat‐to‐target and usual care patients were seen every 3 months. Treat‐to‐target providers were to have monthly visits with treatment acceleration at a minimum of every 3 months in patients with CDAI score >10; additional visits and treatment acceleration were at the discretion of usual care providers and patients. Coprimary end points were feasibility, assessed by rate of treatment acceleration conditional on CDAI score >10, and achievement of low disease activity (LDA; CDAI score ≤10) by an intent‐to‐treat analysis.Results
A total of 14 practice sites per study arm were included (246 patients receiving treat‐to‐target and 286 receiving usual care). The groups had similar baseline demographic and clinical characteristics. Rates of treatment acceleration (treat‐to‐target 47% versus usual care 50%; odds ratio [OR] 0.92 [95% confidence interval (95% CI) 0.64, 1.34]) and achievement of LDA (treat‐to‐target 57% versus usual care 55%; OR 1.05 [95% CI 0.60, 1.84]) were similar between groups. Treat‐to‐target providers reported patient reluctance and medication lag time as common barriers to treatment acceleration.Conclusion
This study is the first to examine the feasibility and efficacy of a treat‐to‐target approach in typical US rheumatology practice. Treat‐to‐target care was not associated with increased likelihood of treatment acceleration or achievement of LDA, and barriers to treatment acceleration were identified. 相似文献77.
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Anna-Kaisa Eerola Henni Ruokolainen Ylermi Soini Hannu Raunio Paavo PÄÄKKÖ 《Pathology oncology research : POR》1999,5(3):179-186
In order to test the hypothesis that increased apoptotic activity is connected with neuroendocrine differentiation and low
differentiation degree in large cell carcinoma (LCLC) and is regulated by bcl-2 family proteins, we analysed the extent of
apoptosis and tumor necrosis and their relation to the expression of bcl-2, bax, bak and mcl-1 in 35 LCLCs, of which 20 were
classified as large cell neuroendocrine lung carcinomas (LCNEC) and 15 as large cell non-neuroendocrine lung carcinomas (LCNNEC).
The extent of apoptosis was determined by detecting and counting the relative and absolute numbers of apoptotic cells and
bodies using in situ 3′-end labelling of the apoptotic DNA. The extent and intensity of expression of the bcl-2, bax, bak
and mcl-1 proteins were studied by immunohistochemistry. Also the relative volume density of necrosis was evaluated and correlated
with the other parameters. Finally, all the parameters were evaluated as prognostic markers and correlated with data on the
survival of the patients. Relatively high apoptotic indices were seen in both tumor types (average for both 2.53%, range 0.09–27.01%).
Significantly higher bcl-2 and bak indices were detected more often in LCNECs than in LCNNECs. Immunohistochemically detected
bax, bcl-2 and bak expression was independent of apoptotic index in both tumor types, while there was a statistically significant
positive association between mcl-1 expression and apoptotic index in LCNNEC but not in LCNEC. There was a statistically significant
association between high apoptotic index and shortened survival in LCLC. However, no association was found between tumor stage
and apoptosis. The patients with LCNEC and low bcl-2 protein expression had a significantly shorter survival time than those
with high bcl-2 indices. There was also a clear association between shortened survival and necrotic LCNNEC. LCLCs show relatively
high apoptotic activity, which is associated with shortened survival. The expression of bcl-2, bak and mcl-1 is associated
with neuroendocrine differentiation in LCLC. Finally, our results support some previous reports suggesting that bcl-2 expression
in combination with some other markers involved in apoptosis and/or proliferation may be of prognostic value in cases of lung
carcinoma with neuroendocrine differentiation. 179-186, 1999) 相似文献