Image cytometric analysis of p53 and mdm-2 expression in primary and recurrent mucoepidermoid carcinoma of parotid gland: immunohistochemical study

<p>Abstract</p> <p>Aims and Objectives</p> <p>This study aims to analyze immunocytochemically p53 aberrant expression and mdm-2 expression in primary and recurrent mucoepidermoid carcinoma (MEC) of parotid gland and to ascertain if expression of these markers correlates with tumor behavior, clinical outcome, histological grade and local recurrence.</p> <p>Methods</p> <p>20 cases histologically diagnosed as primary MEC with different grades were included in the study. Out of 20 cases, 7 were classified as grade I, 8 as grade II and 5 as grade III. Immunohistochemical staining of these 20 primary cases as well as 6 recurrent cases with anti-p53 and anti-mdm-2 antibodies was carried out. Area fraction of immunopositivity was estimated by image analysis software.</p> <p>Results</p> <p>16/20 primary cases were p53 +ve (80%). The p53 positive cases included 3 cases classified as grade (I), 8 cases as grade (II) and 5 cases as grade (III). All 6 recurrent cases were p53 +ve. On the other hand, 14/20 primary and only 2/6 recurrent cases were mdm-2 +ve. The mdm-2 +ve primary cases included 2 classified as grade (I), 7 as grade (II) and 5 as grade (III). 12 primary MEC showed co-expression of both p53 and mdm-2 of which 2 cases showed local recurrence.</p> <p>Conclusions</p> <p>these data suggested that expression of p53 and mdm-2 in primary and recurrent MEC correlates with the high histological grade. P53 aberrant expression is not only considered as an early event in MEC carcinogenesis but also correlates to tumor behavior and local recurrence. Mdm-2 overexpression is correlated to pathogenesis of MEC. However, no strong evidence was found between mdm-2 expression and MEC local recurrence.</p

Prediction of sinus rhythm maintenance following DC-cardioversion of persistent atrial fibrillation – the role of atrial cycle length

BACKGROUND: Atrial electrical remodeling has been shown to influence the outcome the outcome following cardioversion of atrial fibrillation (AF) in experimental studies. The aim of the present study was to find out whether a non-invasively measured atrial fibrillatory cycle length, alone or in combination with other non-invasive parameters, could predict sinus rhythm maintenance after cardioversion of AF. METHODS: Dominant atrial cycle length (DACL), a previously validated non-invasive index of atrial refractoriness, was measured from lead V1 and a unipolar oesophageal lead prior to cardioversion in 37 patients with persistent AF undergoing their first cardioversion. RESULTS: 32 patients were successfully cardioverted to sinus rhythm. The mean DACL in the 22 patients who suffered recurrence of AF within 6 weeks was 152 ± 15 ms (V1) and 147 ± 14 ms (oesophagus) compared to 155 ± 17 ms (V1) and 151 ± 18 ms (oesophagus) in those maintaining sinus rhythm (NS). Left atrial diameter was 48 ± 4 mm and 44 ± 7 mm respectively (NS). The optimal parameter predicting maintenance of sinus rhythm after 6 weeks appeared to be the ratio of the lowest dominant atrial cycle length (oesophageal lead or V1) to left atrial diameter. This ratio was significantly higher in patients remaining in sinus rhythm (3.4 ± 0.6 vs. 3.1 ± 0.4 ms/mm respectively, p = 0.04). CONCLUSION: In this study neither an index of atrial refractory period nor left atrial diameter alone were predictors of AF recurrence within the 6 weeks of follow-up. The ratio of the two (combining electrophysiological and anatomical measurements) only slightly improve the identification of patients at high risk of recurrence of persistent AF. Consequently, other ways to asses electrical remodeling and / or other variables besides electrical remodeling are involved in determining the outcome following cardioversion

Home medicines reviews following acute coronary syndrome: study protocol for a randomized controlled trial

Background: Despite continual improvements in the management of acute coronary syndromes, adherence to guideline-based medications remains suboptimal. We aim to improve adherence with guideline-based therapy following acute coronary syndrome using an existing service that is provided by specifically trained pharmacists, called a Home Medicines Review. We have made two minor adjustments to target the focus of the existing service including an acute coronary syndrome specific referral letter and a training package for the pharmacists providing the service.Methods/Design: We will be conducting a randomized controlled trial to compare the directed home medicines review service to usual care following acute coronary syndromes. All patients aged 18 to 80 years and with a working diagnosis of acute coronary syndrome, who are admitted to two public, acute care hospitals, will be screened for enrolment into the trial. Exclusion criteria will include: not being discharged home, documented cognitive decline, non-Medicare eligibility, and presence of a terminal malignancy. Randomization concealment and sequence generation will occur through a centrally-monitored computer program. Patients randomized to the control group will receive usual post-discharge care. Patients randomized to receive the intervention will be offered usual post-discharge care and a directed home medicines review at two months post-discharge. The study endpoints will be six and twelve months post-discharge. The primary outcome will be the proportion of patients who are adherent to a complete, guideline-based medication regimen. Secondary outcomes will include hospital readmission rates, length of hospital stays, changes in quality of life, smoking cessation rates, cardiac rehabilitation completion rates, and mortality.Discussion: As the trial is closely based on an existing service, any improvements observed should be highly translatable into regular practice. Possible limitations to the success of the trial intervention include general practitioner approval of the intervention, general practitioner acceptance of pharmacists' recommendations, and pharmacists' ability to make appropriate recommendations. A detailed monitoring process will detect any barriers to the success of the trial. Given that poor medication persistence following acute coronary syndrome is a worldwide problem, the findings of our study may have international implications for the care of this patient group.Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12611000452998. © 2012 Bernal et al; licensee BioMed Central Ltd

Indices of electrical and contractile remodeling during atrial fibrillation in man

Atrial electrical and contractile remodeling have been demonstrated to coincide during atrial fibrillation (AF) in experimental studies. We explored whether electrical and contractile remodeling correlate in man and explored its clinical implications. METHODS: Forty-nine patients with persistent AF were studied. Electrical remodeling was assessed noninvasively using spectral analysis to estimate the average fibrillatory rate (AFR). Atrial contractility was assessed by transesophageal echocardiography (TEE) measurement of left atrial appendage outflow velocity (LAAOV). RESULTS: The AFR was 403+/-43 fibrillations per minute (fpm) and the LAAOV was 0.27+/-0.14 m/s. A significant correlation was found between AFR and LAAOV (r=-0.47, P=0.001). In patients with a LAAOV>or=0.25 m/s, the AFR was 387+/-48 fpm compared to 419+/-31 fpm among patients with LAAOV<0.25 m/s (P<0.01). CONCLUSIONS: This study demonstrates that indices of electrical and contractile remodeling are strongly correlated in persistent AF in man. The interindividual overlap, however, is too large to allow predictions of LAAOV based on fibrillatory frequency alone

Atrial fibrillation signal organization predicts sinus rhythm maintenance in patients undergoing cardioversion of atrial fibrillation.

Electrical remodelling is believed to influence the outcome following cardioversion of patients with persistent atrial fibrillation (AF). However, the results in clinical studies are conflicting. We assessed the hypothesis that non-invasively obtained atrial fibrillatory organization can be used as a predictor of sinus rhythm (SR) maintenance. METHODS AND RESULTS: Fifty-four patients (37 men, age 67+/-11) with persistent AF (median duration 3 months, 1 day to 18 months), without anti-arrhythmic drug treatment, referred for cardioversion were studied. Assessment of the atrial harmonic decay was made by time-frequency analysis of the ECG. At 1-month follow-up, 30 patients had relapsed into AF. The mean harmonic decay at inclusion of those relapsing into AF was 1.5+/-0.3 compared with 1.1+/-0.3 among those maintaining SR (P=0.0004). Using a cut-off value of harmonic decay <or=1.5 to determine suitability for cardioversion would have resulted in a clinically useful discriminator (sensitivity=92%, specificity=47%, PPV=59%, and NPV=88%). CONCLUSION: This study shows that patients relapsing rapidly to AF have a higher harmonic decay than those maintaining SR. The degree of AF signal organization (harmonic decay) was a superior discriminator to other patient parameters. Further studies are needed to confirm these results and to determine the electrophysiological correlate of harmonic decay

Echocardiographic right ventricular strain from multiple apical views is superior for assessment of right ventricular systolic function

Background: Right ventricular (RV) systolic function is an important determinant of outcome in patients with pulmonary hypertension (PH). Conventional echocardiographic measures of RV are mainly based on longitudinal contractility. Recently, measurement of RV global longitudinal strain derived from multiple windows (RVGLS) has emerged as an option but has not been well evaluated. The aim of the present study was to evaluate which echocardiographic RV function parameter correlates best with RV ejection fraction derived from cardiac magnetic resonance imaging (RVEFCMR). Methods and results: Fifty-five patients evaluated for PH underwent RV assessment with echocardiography and CMR. Conventional echocardiographic parameters of RV function including tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (S′), RV fractional area change (RVFAC) and RV index of myocardial performance (RIMP). RVGLS was measured from three separate apical views using a 17-segment model and strain from the lateral free wall was calculated separately (RVfree). The study included 55 patients, whereas assessment of RVGLS could be obtained in 29 patients. The Pearson correlation coefficient with RVEFCMR was strong for RVGLS (r = 0·814, P<0·001) and RVfree (r = 0·778, P<0·001), modest for RVFAC (r = 0·681, P<0·001), TAPSE (r = 0·592, P<0·001) and RIMP (r=−0·521, P<0·01), and weak for S′ (r = 0·385, P<0·01). Conclusion: The echocardiographic RV measures, RVGLS and RVfree correlated well with RVEFCMR, whereas correlation with TAPSE, RIMP and S′ was unsatisfactory. Our findings suggest that RVGLS and RVfree are the preferred echocardiographic methods for clinical practice. RVfree is easiest to perform but RVGLS could provide incremental value in selected patients