ORTHOTOPIC BLADDER SUBSTITUTION AFTER RADICAL CYSTECTOMY: 5 YEARS OF EXPERIENCE WITH A NOVEL PERSONAL MODIFICATION OF THE ILEAL S POUCH

PURPOSE: We report a 5-year experience with 52 patients who underwent radical cystoprostatectomy for bladder cancer and orthotopic bladder substitution using a novel personal modification of the S pouch. MATERIALS AND METHODS: From September 1995 to December 1999, 52 men 36 to 72 years old (mean age 63) underwent bladder substitution with an S pouch. They were followed until September 2000. The pouch was constructed with a 36 cm. segment of ileum with the whole length used for the reservoir. The ureters were directly anastomosed with one above the other in the mid segment of the pouch without any antireflux procedure. Complications were documented and classified as early or up to 3 months postoperatively and late, and further subdivided by the relationship to neobladder construction. Continence and voiding pattern were evaluated by personal interview and neobladder function was urodynamically assessed. Mean followup in our patients was 30 months. RESULTS: The most common of the 5 early and 9 late neobladder related complications were persistent urine leakage and reflux, respectively. There was no reflux greater than grade III in the 4 patients with reflux (5 refluxing ureters) and no functional disorders. We observed 12 early and 5 late complications unrelated to the neobladder. Open reoperation was required in 5 cases. Good or satisfactory daytime and nighttime continence was reported by 95% and 88% of our patients, respectively. By year 1 postoperatively 91% of our patients voided at an interval of 3 to 5 hours during the day. Mean maximum neobladder capacity was 672 ml. and mean post-void residual was 30 ml. by year 3 postoperatively. Two patients required self-catheterization once daily and mild hyperchloremia without acidosis developed in 2. CONCLUSIONS: The advantages of our modified S pouch are technical simplicity, substantially shorter operative time and decreased bowel length required. It is associated with an acceptable complication rate and functional parameters with subsequent patient satisfaction and good quality of life.     

Time Dependent Changes in Duration of Ventricular Repolarization After AV Node Ablation: Insights into the Possible Mechanism of Postprocedural Sudden Death

DIZON, J., et al. : Time Dependent Changes in Duration of Ventricular Repolarization After AV Node Ablation: Insights into the Possible Mechanism of Postprocedural Sudden Death. Although effective, there is a disturbing incidence of sudden death after AV node ablation. The mechanism may be related to proarrhythmia associated with prolongation in ventricular repolarization from the sudden decrease in heart rate. To examine this issue, we studied 15 patients undergoing complete radiofrequency ablation of the AV node for rapid atrial arrhythmias. Twelve‐lead ECGs of paced rhythms at rates of 60, 80, 100, and 120 beats/min were recorded at time points of 30 minutes, 24 hours, 1 week, and 1 month after ablation. The QT interval was measured in the limb and precordial leads with the best T wave offset. The change in the QT interval (ΔQT) relative to the measurement at 30‐minute postablation was calculated. For comparison, a similar procedure was performed on patients receiving pacemakers for primary bradycardia (n = 5 ). The mean QT interval at 60 beats/min, 30‐minutes postablation was significantly longer than at time points thereafter (482 ± 39 vs 446 ± 28 ms at 1 month, limb leads, for example, P < 0.05 ). Analysis of ΔQT revealed a significant shortening of the QT interval at nearly every paced rate at every time point relative to the value at 30‐minute postablation. The QT intervals shortened and stabilized after 24 hours. Neither the QT interval nor ΔQT changed significantly in patients paced for primary bradycardia. We conclude that there is a relative increase in the duration of ventricular repolarization after AV node ablation, which then decreases and stabilizes after 24 hours. Such changes are not seen in patients being paced for primary bradycardia. This data is consistent with the hypothesis that sudden death after AV node ablation may be related to proarrhythmia from prolonged ventricular repolarization.     

Transcoronary Ethanol Ablation of the Atrioventricular Node in a Young Patient with Tricuspid Atresia

Catheter ablation of AV conduction with radiofrequency energy can be challenging in the presence of structural abnormalities of the AV junction, either congenitally or after reconstructive surgery. We used transcoronary ethanol to ablate the AV node in a patient with classic tricuspid atresia and refractory intraatrial reentry tachycardia. This approach provides an alternative means of creating complete heart block with catheter-based techniques, when radiofrequency catheter ablation is technically impossible or ineffective.     

COMPARATIVE EVALUATION OF THE DIAGNOSTIC PERFORMANCE OF THE BTA STAT TEST, NMP22 AND URINARY BLADDER CANCER ANTIGEN FOR PRIMARY AND RECURRENT BLADDER TUMORS

PURPOSE: We compared overall sensitivity and specificity of the urinary bladder cancer antigen enzyme-linked immunosorbent assay (UBC, IDL Biotech, Sollentuna, Sweden), BTA stat test (Bion Diagnostic Sciences, Inc., Redmond, Washington) and NMP22 test kit (Matritech, Newton, Massachusetts), and the differential sensitivity regarding the histological pattern of tumors. MATERIALS AND METHODS: A total of 213 patients with clinical and/or imaging signs of bladder cancer provided a single voided urine sample for the bladder cancer antigen, BTA stat test and NMP22 before cystoscopy. Of these patients 95 were monitored for superficial bladder cancer, while the remaining 118 had no history of bladder cancer. All detected bladder tumors or suspicious lesions were resected transurethrally. A group of 21 age and sex matched healthy volunteers were also evaluated with the same tests. RESULTS: Bladder cancer was confirmed histologically in 118 patients, of whom primary and recurrent tumors were in 68 and 50, respectively. The optimal cutoffs calculated with receiver operating characteristics curves were 8 units per ml. for NMP22 and 12 microg./l. for bladder cancer antigen. Overall sensitivity and specificity were 72.9% and 64.6% for the BTA stat test, 63.5% and 75.0% for NMP22, and 80.5% and 80.2%, respectively, for bladder cancer antigen. Bladder cancer antigen proved significantly more sensitive than NMP22 for detecting bladder cancer (p = 0.001) but not more than the BTA stat test, while the specificity of it was significantly higher than that of the BTA stat test (p = 0.009). Bladder cancer antigen had a sensitivity of 80.7% for stage Ta tumors, which was significantly higher than NMP22 (52.6%, p = 0.001) and the BTA stat test (57.9%, p = 0.01). In grade I tumors the sensitivity of bladder cancer antigen (70%) did not differ significantly than that of the BTA stat test (50%) and NMP22 (50%, p = 0.14). Bladder cancer antigen had the least false-positive results in patients with a history of bladder cancer and negative cystoscopy, and those with urological disease other than bladder cancer. CONCLUSIONS: Our data indicate that bladder cancer antigen may be a more potent diagnostic marker for bladder cancer than NMP22 and the BTA stat test based on the higher sensitivity for detecting low stage and low grade tumors, and the higher specificity. The contribution of these tests for detection of bladder cancer should still be considered adjunctive to cystoscopy.     

Immunoreactivity and conformation of the P-P-G-M-R-P-P repetitive epitope of the Sm autoantigen

Anti-Sm antibodies are usually considered highly specific for systemic lupus erythematosus (SLE), while anti-UI RNP antibodies are found in high titers in patients with mixed connective tissue disease (MCTD). The sequence P¹-P-G-M-R-P-P⁷, present in three copies in the Sm (Ul-U6 RNA-protein complex) autoantigen, is an important functional domain of the antigenic determinants. The immunoreactivity of this proline-rich repetitive epitope was investigated by testing sera with various autoantibody specificities for reactivity against this epitope, as well as its conformational properties by means of ID and 2D ¹HNMR spectroscopy. It was found that the P-P-G-M-R-P-P epitope is recognized mainly by anti-UlRNP and/or anti-Sm positive sera, but also by anti-Ro(SSA) (hY1RNA-protein complex) and anti-La(SSB) (hY1RNA-protein complex) positive sera, although these sera are negative for anti-UlRNP and anti-Sm. Conformational analysis of the proline-rich epitope in DMSO-d₆ solution obtained from lyophilized aqueous solution at pH 5 showed the presence of at least three conformers. The main conformer A (62%) is stabilized by an ionic interaction between the guanidinium and the C-terminal carboxylate groups, and the Pro⁶-Pro⁷ peptide bond adopts the cis form. A type II β-turn is also present in the N-terminal sequence (Pro¹-Pro-Gly-Met⁴-) of this conformer. Conformer B (21%) is also stabilized by a similar ionic interaction, as in conformer A, while the NMR data indicate the absence of a folded structure in the N-terminal tetrapeptide of this conformer. Conformer C (17%) adopts a completely extended structure. The multiple conformers of the P-P-G-M-R-P-P may offer some explanation for the reactivity of sera with various autoantibody specificities against this epitope. © Munksgaard 1996.     

Predictors of Atrial Tachyarrhythmias in Subjects with Type 1 ECG Pattern of Brugada Syndrome

Background: Previous studies have demonstrated a high incidence of atrial tachyarrhythmias (ATs) in patients with Brugada syndrome (BS). The present study aimed to investigate whether various 12-lead electrocardiogram (ECG) and electrophysiological parameters may help to differentiate subjects with a high probability to develop ATs.
Methods and Results: The clinical records of 38 individuals (31 males, age 44.4 ± 13.9) with spontaneous (n = 15) or ajmaline-induced (n = 23) type 1 ECG pattern of BS were analyzed. During a mean follow-up period of 4.6 ± 2.2 years, nine subjects suffered ATs (24%). Six subjects displayed paroxysmal atrial fibrillation and three typical atrial flutter. Among the studied 12-lead ECG parameters, subjects with ATs exhibited increased values of P-wave duration in lead II, P-wave dispersion, PR interval in leads II, QRS duration in leads II and V₂, Tpeak-end interval in lead II, and Tpeak-end dispersion of the 12 leads in relation to those without ATs (P < 0.05). Among the assessed electrophysiological parameters, atrial-His (AH) and His-ventricular (HV) intervals were significantly prolonged in subjects with ATs (P < 0.05). Multiple Cox proportional hazards analysis revealed that P-wave duration in lead II, P-wave dispersion, Tpeak-end in lead II, Tpeak-end dispersion of the 12 leads, as well as AH and HV intervals are independent predictors of ATs in subjects with BS (P < 0.05). Cut-off point analysis showed that an HV interval ≥ 56 ms displayed the highest predictive ability (P < 0.01).
Conclusion: Our findings demonstrate that simple 12-lead ECG and electrophysiological parameters may easily be applied to identify high-risk subjects with BS ECG phenotype to develop ATs .     

8-hydroxy-2′ -deoxyguanosine (8-OHdG): A Critical Biomarker of Oxidative Stress and Carcinogenesis

There is extensive experimental evidence that oxidative damage permanently occurs to lipids of cellular membranes, proteins, and DNA. In nuclear and mitochondrial DNA, 8-hydroxy-2′ -deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2′ -deoxyguanosine (8-oxodG) is one of the predominant forms of free radical-induced oxidative lesions, and has therefore been widely used as a biomarker for oxidative stress and carcinogenesis. Studies showed that urinary 8-OHdG is a good biomarker for risk assessment of various cancers and degenerative diseases. The most widely used method of quantitative analysis is high-performance liquid chromatography (HPLC) with electrochemical detection (EC), gas chromatography-mass spectrometry (GC-MS), and HPLC tandem mass spectrometry. In order to resolve the methodological problems encountered in measuring quantitatively 8-OHdG, the European Standards Committee for Oxidative DNA Damage was set up in 1997 to resolve the artifactual oxidation problems during the procedures of isolation and purification of oxidative DNA products. The biomarker 8-OHdG or 8-oxodG has been a pivotal marker for measuring the effect of endogenous oxidative damage to DNA and as a factor of initiation and promotion of carcinogenesis. The biomarker has been used to estimate the DNA damage in humans after exposure to cancer-causing agents, such as tobacco smoke, asbestos fibers, heavy metals, and polycyclic aromatic hydrocarbons. In recent years, 8-OHdG has been used widely in many studies not only as a biomarker for the measurement of endogenous oxidative DNA damage but also as a risk factor for many diseases including cancer.