ABSTRACT
This work aims to search for markers suitable for the screening of bladder cancer, which should be specific, sensitive, reproducible, non-invasive and at acceptable cost. The study included 50 patients diagnosed as bladder cancer [35 TCC, 15 SCC] of different stages and grades, 30 patients with various urothelial diseases, besides 20 apparently healthy subjects of matched age and sex to the malignant group. A random midstream urine sample was collected in a sterile container for the determination of telomerase by RT-PCR, keratin 19 by ELSA CYFRA 21-i IRMA kit, keratin 20 by RT-PCR and immunohistochemical staining, and urine cytology. For all parameters [telomerase, Ki9, K20 and cytology] the malignant group was significantly different from both the benign and the control groups. None of the four studied parameters was correlated to the stage of the disease, and when it comes to grade, only Ki9 showed a significant positive correlation with grade both in TCC and SCC. When ROC curves for all parameters were compared, Ki9 had the largest area under the curve, and then comes K20. K 19 may be used as a biological marker for the diagnosis of bladder cancer Ki9 could not be used for differential diagnosis of different types of bladder cancer, meanwhile it could be a marker for differentiation that decreases in less differentiated tumors. As a tumor marker, K20 reflects inability to differentiate tumor type or grade in TCC, while in SCC of the bladder it is correlated with the grade. As a method, RT-PCR is superior to immunostaining for the detection of bladder cancer, meanwhile K20 immunohistochemistry [IHC] results were much better than urine cytology as a bladder cancer screening test. Haematuria and inflammation reduced the specificity of telomerase assay, which reduced its validity as a tumor marker of bladder cancer. Ki9 and K20 are the best candidates as screening tests for the diagnosis of bladder cancer, representing the highest sensitivity and specificity, beside the radiological and histopathology. Meanwhile, telomerase, although it was a sensitive enough marker, it reflected a high false positive rate
Subject(s)
Humans , Male , Female , Telomerase/urine , Keratins/urine , Biomarkers, Tumor , Keratins, Type I/urine , Polymerase Chain ReactionABSTRACT
Congestive heart failure is related to contraction and relaxation abnormalities of the ventricle. Isolated analysis of either mechanism may not be reflective of overall cardiac dysfunction: [Recently, a new non invasive Doppler derived index; myocardial performance index [MPI] or total ejection isovolumic index [TEI], which incorporates both systolic and diastolic myocardial performance has been proposed]. It is defined as the sum of isovolumic contraction time [ICT]and isovolumic relaxation time [IRT]divided by ejection time [ET]. In the present study, TEI index was compared with conventional echocardiographic/ Doppler parameters .and plasma B-type natriuretic peptide [BNP] levels in 30 patients with NYHA class 11-1V heart failure, before and after low dose dobutamine stress echocardiography [DSE], which has become accepted in the evaluation of cardiac functional reserve. The mean resting value of the TEI index was significantly higher in patients with advanced NYHA functional class IV [0.94 +/- 0.14] compared with those in class 111[0.78 +/- 0.2] and class 11 [0.61=0.02]. There was a significant negative correlation between TEI index with LVEF [r= -0.39, p< 0.05] and FS [r= -0.34, p<0.05]. The mean resting value of BNP in HF patients was significantly higher than that in controls, and its highest value was in patients in NYHA functional class IV [288 +/- 137.9pg/ml]. Inotropic challenge with dobutamine resulted in a marked improvement of the TEI index [% change -19.9; p< 0.05], and a shortening of the ICT [% change -17.31; p < 0.05] and the IRT [% change -17.01; P<0.05] and an insignificant increase of the ET. The myocardial contractile reserve [MCR] - defined as increment of more than 20% of resting left ventricular ejection fraction - showed significant improvement [% change +23.25; p< 0.05]. We concluded that TEI index is a simple and reproducible measure of cardiac function. It is a sensitive indicator of the effect of inotropic stimulation on global left ventricular function. Larger scale use of this protocol that combined TEI index, BNP and low dose DSE might be useful in HF, as it complements the information provided by other variables used in the diagnosis and functional assessment of heart failure