The initial aim of this study was to examine the expression profiles of P53 and its upstream genes, downstream genes, and cell cycle regulators to determine whether these markers are useful for making a differential diagnosis among the benign, borderline, and malignant ovarian epithelial tumors. Between borderline and malignant tumors, the increased expression levels of P53, Bax, Cyclin E, and cyclin-dependent kinase-2 as well as the decreased expression levels of growth arrest and DNA damage (GADD45) and murine double minute-2 (MDM2) were significantly associated with malignancy (P < 0.01, each). Using the receiver operating curve (ROC), the most reliable cutoff value of the added-up staining scores of those markers was 4.5 with 79% sensitivity and 89% specificity for malignancy. Between benign and borderline tumors, the P21 and Bax expression levels were significantly higher in borderline tumors, whereas the Bcl-2 expression level was much higher in benign tumors (P < 0.01, each). Using the ROC, the cutoff value of the added-up staining scores used to discriminate between the two groups was 2.5 with 70% sensitivity and 74% specificity for borderline tumors. Thus, for the differential diagnosis between borderline and malignant tumors, the cutoff value 4.5 of the cumulative staining scores can be used. However, the cutoff value 2.5 for discrimination between benign and borderline tumors may not be useful because of its relatively low sensitivity and specificity. In addition, the P53, GADD45, Cyclin E, and MDM2 expression levels in malignant ovarian tumors might be useful for determining the histologic grade and type.
SUMMARYWhat is known and objective: Higher rate of statin-related hepatotoxicity has been reported for Koreans than for Westerners. Moreover, statin-related aminotransferase elevation for those who show borderline levels of aspartate transaminase (AST) and alanine transaminase (ALT) (≤33 of UNL) at baseline has not been fully investigated. Methods: Post-statin changes AST/ALT levels during the first year for 21 233 Korean outpatients at two large academic teaching hospitals from January 2009 to December 2013 were analysed using electronic health record data. The date of the first statin prescription was set as baseline. We also performed a comparative analysis of statin-related AST/ALT elevations according to the type of statin, followed by an analysis of clinical risk factors. Results and discussion: The progression rate to abnormal AST/ ALT values [>33 the upper normal limit (UNL)] was significantly higher (2Á4-16% vs. 0Á3-1Á7%, P < 0Á001) in subjects with borderline (>31, but ≤33 of UNL) compared with normal AST/ ALT values at baseline. Those with normal baseline AST/ALT did not show significantly different progression rate between different statin medications (P = 0Á801). However, patients taking pitavastatin (HR = 0Á76, P = 0Á657) were least likely to develop abnormal AST/ALT, whereas those taking fluvastatin (HR = 2Á96, P = 0Á029) were the most likely to develop abnormal AST/ALT compared with atorvastatin for patients who were with baseline borderline AST/ALT. However, given the small sample sizes and the observational nature of our study, these need further study. What is new and conclusion: It is advisable to regularly monitor AST/ALT levels even in patients with AST/ALT increases >31. Future studies should aim to determine the possible risk factors for each specific statin type by analysing various confounding variables. WHAT IS KNOWN AND OBJECTIVEMany studies have demonstrated that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, also known as statins, can help prevent cardiovascular disorders by effectively reducing lowdensity lipoprotein cholesterol (LDL-C).1-3 However, various adverse effects have also been reported with statin medications.4-7 One of the most frequent side effects is hepatotoxicity accompanied by increased levels of aspartate aminotransferase (AST) or alanine aminotransferase (ALT). Several studies have reported rates of asymptomatic elevation of aminotransferases under 3%, [8][9][10] although clinically apparent drug-induced liver injury is rare. 11The National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP III) guidelines 12 recommend examining AST/ ALT 12 weeks after beginning a statin prescription and, if AST/ ALT levels have increased to over three times the upper normal limit (UNL), to advise discontinuation of the statin. If AST/ALT levels have increased to higher than normal levels but less than three times the UNL, discontinuing the statin prescription is not necessary, but physicians are advised to reexamine AST/ALT at the next visit. In the 2013 ...
The initial aim of this study was to examine the expression profiles of P53 and its upstream genes, downstream genes, and cell cycle regulators to determine whether these markers are useful for making a differential diagnosis among the benign, borderline, and malignant ovarian epithelial tumors. Between borderline and malignant tumors, the increased expression levels of P53, Bax, Cyclin E, and cyclin-dependent kinase-2 as well as the decreased expression levels of growth arrest and DNA damage (GADD45) and murine double minute-2 (MDM2) were significantly associated with malignancy (P < 0.01, each). Using the receiver operating curve (ROC), the most reliable cutoff value of the added-up staining scores of those markers was 4.5 with 79% sensitivity and 89% specificity for malignancy. Between benign and borderline tumors, the P21 and Bax expression levels were significantly higher in borderline tumors, whereas the Bcl-2 expression level was much higher in benign tumors (P < 0.01, each). Using the ROC, the cutoff value of the added-up staining scores used to discriminate between the two groups was 2.5 with 70% sensitivity and 74% specificity for borderline tumors. Thus, for the differential diagnosis between borderline and malignant tumors, the cutoff value 4.5 of the cumulative staining scores can be used. However, the cutoff value 2.5 for discrimination between benign and borderline tumors may not be useful because of its relatively low sensitivity and specificity. In addition, the P53, GADD45, Cyclin E, and MDM2 expression levels in malignant ovarian tumors might be useful for determining the histologic grade and type.
Tuberculosis hemeprint may allow us to screen primary TB with acceptable sensitivity and specificity using combination of TB-specific CPD and calculated parameters.
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