P53 mutation analysis of colorectal liver metastases: relation to actual survival, angiogenic status, and p53 overexpression.

PURPOSE: To correlate TP53 mutations with angiogenic status of the tumor and prognosis after liver surgery in patients with colorectal liver metastases and to correlate immunohistochemical staining of p53 protein with TP53 gene mutations. EXPERIMENTAL DESIGN: Tumors of 44 patients with surgically treated colorectal liver metastases were analyzed for (a) TP53 mutations using denaturing gradient gel electrophoresis followed by sequencing, (b) microvessel density using the hot spot overlap technique, (c) apoptotic rate in tumor cells and endothelial cells of tumor microvessels using double immunostaining for anti-cleaved caspase 3 and anti-CD34, and (d) expression of p53 protein using immunohistochemistry. RESULTS: TP53 mutations were detected in 36% of the metastases and occurred more frequently in liver metastases from left-sided colon tumors than from right-sided colon tumors (P = 0.04). In metastases with TP53 mutations, microvessel density was higher compared with tumors with wild-type p53. Endothelial cell apoptosis was not different in tumor microvessels from TP53-mutated versus nonmutated tumors. The 5-year actual survival was not influenced by TP53 mutational status, microvessel density, or endothelial cell apoptotic rate of the tumors. Based on immunohistochemical p53 overexpression, the positive and negative predictive values of TP53 mutations were 61% and 82%. CONCLUSIONS: In patients with surgically treated colorectal liver metastases, TP53 mutations and angiogenic status did not influence prognosis. Immunohistochemistry is not a reliable technique for detecting TP53 mutations.     

Recent progress and prospects in the electrode materials of flexible sodium-ion battery

1. Download : Download high-res image (311KB)
2. Download : Download full-size image

     

Thyroid Hormones and Cardiovascular Function and Diseases

Thyroid hormone (TH) receptors are present in the myocardium and vascular tissue, and minor alterations in TH concentration can affect cardiovascular (CV) physiology. The potential mechanisms that link CV disease with thyroid dysfunction are endothelial dysfunction, changes in blood pressure, myocardial systolic and diastolic dysfunction, and dyslipidemia. In addition, cardiac disease itself may lead to alterations in TH concentrations (notably, low triiodothyronine syndrome) that are associated with higher morbidity and mortality. Experimental data and small clinical trials have suggested a beneficial role of TH in ameliorating CV disease. The aim of this review is to provide clinicians dealing with CV conditions with an overview of the current knowledge of TH perturbations in CV disease.     

Pharmacokinetic profile of nomegestrol acetate and 17β-estradiol after multiple and single dosing in healthy women

BackgroundThe pharmacokinetics of the monophasic oral contraceptive nomegestrol acetate (NOMAC) plus 17β-estradiol (E₂) were investigated after a single dose and multiple dosing.Study designNOMAC/E₂ (2.5 mg/1.5 mg) was administered daily to healthy women (18–50 years, n= 23) for 24 days; blood samples for pharmacokinetic analysis were obtained on Day 24 and again, after a 10-day pill-free interval, on Day 35 after a single dose.ResultsNOMAC reached steady state after 5 days with mean ± standard deviation (SD) trough NOMAC concentration (C_av) of 4.4±1.4 ng/mL. On Day 24, mean±SD peak NOMAC concentration (C_max, 12.3±3.5 ng/mL) was reached in mean 1.5 h (t_max); the mean±SD elimination half-life (t_½) was 45.9±15.3 h. After a single dose, NOMAC mean±SD C_max was 7.2±2.0 ng/mL and mean±SD t_½ was 41.9±16.2 h. On Day 24, E₂ mean±SD C_av was 50.3±25.7 pg/mL; mean±SD C_max was 86.0±51.3 pg/mL. After a single dose, mean±SD E₂ C_max was 253±179 pg/mL.ConclusionsThese data demonstrate that NOMAC/E₂ has a pharmacokinetic profile consistent with once-daily dosing.     

Improvements in physical function and pain sustained for up to 10 years after knee or hip arthroplasty irrespective of mental health status before surgery

Background and purpose — There are concerns that mental health (MH) may influence outcomes of total knee arthroplasty (TKA) or total hip arthroplasty (THA). We examined effects of poor MH before surgery on long-term outcomes of osteoarthritis-related TKA or THA in women.

Patients and methods — The data were from 9,737 middle-aged participants (47–52 years) and 9,292 older participants (73–78 years) in the Australian Longitudinal Study on Women’s Health who completed surveys between 1998 and 2013. Dates of arthroplasties were obtained from the Australian Orthopaedics Association National Joint Replacement Registry. Participants without procedures were matched with participants with procedures. Trajectories of the Short-Form 36 scores for physical functioning, bodily pain, social functioning, and mental health based on mixed modeling were plotted for participants with and without surgery (stratified according to mental health, separately for TKA and THA, and for middle-aged and older participants).

Results — In middle-aged women with poor and good MH, TKA improved physical function and reduced bodily pain, with improvements sustained up to 10 years after surgery. TKA contributed to restoration of social function in women with good MH, but this was less clear in women with poor MH. In both MH groups, mental health appeared to be unaffected by TKA. Similar patterns were observed after THA, and in older women.

Interpretation — Recovery of physical and social function and reductions in pain were sustained for up to 10 years after surgery. Improvements in physical function and pain were also observed in women with poor mental health. Thus, in our view poor mental health should not be a contraindication for arthroplasty.