The gene for polycomb group protein enhancer of zeste homolog 2 (EZH2) is amplified in late-stage prostate cancer

Overexpression of the polycomb group protein enhancer of zeste homologue 2 (EZH2) has been found in several malignancies, including prostate cancer, with an aggressive phenotype. Amplification of the gene has previously been demonstrated in several malignancies, but not in prostate cancer. Our goal was to evaluate the gene copy number and expression alterations of EZH2 in prostate cancer. The copy number of EZH2 in cell lines (LNCaP, DU145, PC‐3, 22Rv1), xenografts (n = 10), and clinical tumors (n = 191) was studied with fluorescence in situ hybridization. All cell lines had a gain of EZH2. Eight of the ten xenografts showed an increased copy number of the gene, including one case of high‐level amplification (≥5 copies of the gene and EZH2/centromere ratio ≥2). 34/125 (27%) of untreated prostate carcinomas showed increased copy number, but only one case of low‐level amplification (≥5 copies of the gene and EZH2/centromere ratio <2), whereas half (25/46) of the hormone‐refractory carcinomas showed increased copy number, including seven cases of low‐level amplification and three cases of high‐level amplification (P < 0.0001). Expression of EZH2 was significantly (P = 0.0009) higher in hormone‐refractory prostate cancer compared with that in benign prostatic hyperplasia or untreated cancer, according to quantitative real‐time RT‐PCR assay. Also, the expression of EZH2 protein was found to be higher in hormone‐refractory tumors than in hormone‐naïve tumors by immunohistochemistry. The EZH2 gene amplification was significantly (P < 0.05) associated with increased EZH2 protein expression. The data show that amplification of the EZH2 gene is rare in early prostate cancer, whereas a fraction of late‐stage tumors contains the gene amplification leading to the overexpression of the gene, thus indicating the importance of EZH2 in the progression of prostate cancer. © 2006 Wiley‐Liss, Inc.     

Usefulness of T-wave loop and QRS complex loop to predict mortality after acute myocardial infarction

The aim of the study was to assess whether parameters based on the T-wave loop and QRS loop predict mortality, and cardiac mortality in particular, during follow-up of consecutive survivors of acute myocardial infarction (AMI). Patients with AMI (n = 437), treated according to contemporary guidelines, underwent digital high-resolution electrocardiography in orthogonal Frank leads (X, Y, Z) 5 to 14 days after AMI. Several T-wave and QRS loop parameters, such as the width and height of the loops and their ratio, T-wave loop dispersion (TWLD), QRS loop dispersion, and co-sine of the angle between the main vectors of the T-wave and QRS loops (TCRT), were calculated using a custom-made software package. During an average follow-up period of 43 +/- 14 months, 53 patients (12%) died. Of these 53 deaths, 35 were cardiac. TWLD and TCRT were the T-wave loop/QRS loop parameters that best predicted for cardiac mortality on univariate comparison (35.4 +/- 5.62 vs 32.8 +/- 2.87 for TWLD, p < 0.001 and -0.135 +/- 0.665 vs -0.657 +/- 0.518 for TCRT, p < 0.001, alive vs cardiac death, respectively). After adjustment for clinical risk markers in the Cox regression analysis, TWLD still significantly predicted for cardiac mortality (p < 0.05); however, TCRT had lost its predictive power. TWLD did not have significant univariate or multivariate association with noncardiac mortality. In conclusion, TWLD that describes the shape of the T-wave loop is a specific predictor of cardiac death and independent of the clinical risk markers in the current treatment era of patients with AMI.     

Differences in the activation patterns between sustained and self-terminating episodes of human ventricular fibrillation

BACKGROUND. Experimental studies have suggested that R-R interval dynamics during ventricular fibrillation (VF) have organized features, but whether dynamic behavior of non-sustained VF differs from sustained VF is unknown. AIM. The purpose of this study was to investigate whether the dynamics of R-R intervals during non-sustained VF differs from the dynamics during sustained VF. METHODS. A group of 67 patients undergoing routine implantable cardioverter defibrillator (ICD) testing was studied. Forty-three VF events containing mean of 38 local cardiac activation intervals before the termination by ICD shock were analyzed. From intracardiac electrogram recordings, the ratio between the short and long term variability (SD1/SD2) and fractal scaling exponent ( &#102 ) were analyzed. After the initial analyses, data sets were randomized and reanalyzed. Local activation dynamics were then also compared in seven patients with both sustained and spontaneously terminating VF episodes. RESULTS. Randomization caused a change in the VF dynamics from organized toward less organized dynamics ( &#102 ) from 1.08 &#45 0.57 to 0.81 &#45 0.45, P < 0.05 and SD1/SD2 from 0.80 &#45 0.23 to 1.04 &#45 0.20, P < 0.01). Spontaneously terminating VF showed more organized dynamics than sustained VF terminated by shock (P < 0.05). CONCLUSIONS. Local cardiac activation dynamics during initial phase of human VF shows organized dynamics. Spontaneously terminating VF episodes have more structured dynamics than sustained VF. Thus, the dynamic behavior of local cardiac activation intervals may be related to the maintenance of ventricular tachyarrhythmias.     

Muscle sympathetic nerve activity at rest compared to exercise tolerance

Cardiovascular autonomic function is associated with physical performance and exercise training adaptation. The association between physical performance and sympathetic regulation is not well known. We hypothesized that sympathetic nervous system activity is associated with physical performance among male runners. The study population included 26 healthy male club runners [age 33 ± 5 years, body mass index (BMI) 24 ± 1 kg/m², VO_2max 58 ± 5 ml kg⁻¹ min⁻¹; mean ± SD]. Muscle sympathetic nerve activity (MSNA) was assessed from the peroneal nerve by the microneurography technique during 5 min of supine rest. Physical performance was assessed by time to exhaustion during treadmill running. The mean resting MSNA was 20 ± 6 bursts min⁻¹ (range 6–34). The mean time to exhaustion was 1,005 ± 136 s (range 720–1260). When the study group was divided into tertiles according to their running performance (866 ± 69, 994 ± 30 and 1154 ± 71 s in time to exhaustion, P < 0.0001 between the groups), MSNA was lower (P = 0.032) in the group with the best running performance (16 ± 5 bursts min⁻¹) compared to those with the worst running performance (23 ± 7 bursts min⁻¹). In conclusion, baseline sympathetic activity, measured by a microneurography at rest, may be associated with the maximal running performance of healthy subjects.     

Advanced interatrial block predicts ineffective cardioversion of atrial fibrillation: a FinCV2 cohort study

AimsRhythm control using electrical cardioversion (CV) is a common treatment strategy for patients with symptomatic atrial fibrillation (AF). To guide clinical decision making, we sought to assess if electrocardiographic interatrial blocks could predict CV failure or AF recurrence as the phenomenon is strongly associated with atrial arrhythmias.MethodsThis study included 715 patients who underwent a CV for persistent AF lasting >48 h. P-wave duration and morphology were analyzed in post-procedure or the most recent sinus rhythm electrocardiograms and compared with rates of CV failure and AF recurrence within 30 days after CV as well as their combination (ineffective CV).ResultsCV was unsuccessful in 63 out of 715 patients (8.8%) and AF recurred in 209 out of 652 (29.2%) patients within 30 days after CV. Overall, 272 (38.0%) CVs turned out ineffective. Advanced interatrial block (AIAB) defined as P-wave duration ≥120 ms and biphasic morphology in inferior leads (II, III and aVF) was diagnosed in 72 (10.1%) cases. AIAB was an independent predictor for CV failure (OR 4.51, 95%CI 1.76–11.56, p = .002), AF recurrence (OR 2.93, 95%CI 1.43–5.99, p = .003) and ineffective CV (OR 3.87, 95%CI 2.04–7.36, p < .001).ConclusionAIAB predicted CV failure, AF recurrence as well as their composite. This study presents an easy electrocardiographic tool for the identification of patients with persistent AF who might not benefit from an elective CV in the future.

KEY MESSAGES

• Interatrial blocks are very common in patients with atrial fibrillation.
• Advanced interatrial block predicts ineffective cardioversion.

     

Long-term results of arthroscopic Bankart repair: Minimum 10 years of follow-up

Purpose

This study investigated the long-term results of arthroscopic Bankart repair in terms of rates and timelines of recurrence of instability, with special interest in young adult patients aged ≤20 years.

Methods

Between 2000 and 2005, 186 shoulders [182 patients, 50 women, median age 26 (range 15–58) years] were operated on at a university hospital using arthroscopic Bankart repair because of instability after traumatic anteroinferior shoulder dislocation. Medical records were retrospectively reviewed and patients were assessed using postal questionnaires or telephone interview after a minimum of 10 years of follow-up [median 12.2 (range 10–16) years]. The primary outcome measure was recurrence of instability (assessed from 167 shoulders), other outcome measures included Oxford instability score (OIS), subjective shoulder value (SSV), and Western Ontario instability index (WOSI) (assessed from 157 shoulders).

Results

At the end of follow-up, 50/167 shoulders (30%) had recurrence of instability and 30/167 (18%) were subjected to reoperation due to instability symptoms. Twenty-six (52%) failures occurred within ≤2 years, 11 (22%) within 2–5 years, and 13 (26%) >5 years after surgery. Failure rate was 19/35 (54%) for patients aged ≤20 years and 31/132 (24%) for patients aged >20 years; reoperation rates were 11/35 (31%) and 19/132 (14%), respectively. Mean OIS was 20 (SD 9, range 12–50), SSV 83% (SD 21, range 10–100), and WOSI score 80 (SD 22, range 33–100).

Conclusions

Nearly one-third of patients had recurrence of instability after arthroscopic Bankart repair after a minimum of 10-year follow-up. Patients aged ≤20 years did poorly with more than half of the patients having recurrence; alternative stabilization techniques should probably be considered for these patients.

Level of evidence

IV.

     

A new quantitative measure of disc degeneration

Background Context

The ability to adequately measure a phenomenon is critical to studying and understanding it. Since 1957, a variety of subjective visual grading methods have been used to assess disc degeneration, but these have been limited by gross ordinal scales and imprecision, as well as suboptimal reliability. Conceptually sound, objective, precise measurements are needed to advance knowledge of disc degeneration and its causes, progression, and consequences.

Effects of the wood extractives dehydroabietic acid and betulinol on reproductive physiology of zebrafish (Danio rerio)-a two-generation study

Two wood extractives, dehydroabietic acid (DHAA) and betulinol (BET), present in wood industry effluents were evaluated for their potential effects on the reproductive physiology of zebrafish. Adult zebrafish (F0) were exposed in a continuous flow-through system to 50 microg/l DHAA, 5 microg/l BET and 0.27 microg/l (1 nM) 17beta-estradiol (E2) for 3 months. Eggs were collected from F0 fish and the following F1 generation was exposed for 6 months. Biomarkers analyzed in both F0 and F1 fish were plasma vitellogenin (Vtg), testosterone (T), E2 (only females) and gonadal histology. DHAA and BET affected growth in terms of increased condition factor, and spawning was stimulated in BET-exposed fish of the F0 generation. F0 males exposed to DHAA and F0 females exposed to BET showed lower plasma Vtg concentration, but F1 males exposed to BET showed an increase in Vtg. In fish exposed to E2, the positive control for estrogenic effects, a pronounced increase in Vtg concentration was observed. Plasma sex steroids were not significantly affected by the wood extractives. However, although not statistically significant, the T concentration tended to be lower in fish of all BET treatments. The histological study revealed alterations in spermatogenic stages of F0 males exposed to DHAA and BET, which were different from those caused by E2. In F1 females, the percentage of vitellogenic oocytes was decreased in DHAA, BET and E2 exposures. This study shows that DHAA and BET may contribute to growth alterations and reproductive disturbances reported in fish exposed to pulp and paper mill effluents. Further, these wood extractives may have different effects in F0 and F1 generation fish, which highlights the value of two-generation studies in investigations regarding endocrine disrupting compounds.