Embolic Implications of Combined Risk Factors in Patients with Patent Foramen Ovale (the CARPE Criteria): Consideration for Primary Prevention Closure?

Background: Large patent foramen ovale (PFO), spontaneous right‐to‐left shunt, large atrial septal aneurysm (ASA), coagulation abnormalities, and prominent eustachian valve (EV) have all been independently suggested as risk factors for recurrent stroke. We sought to retrospectively evaluate risk of stroke and impact of transcatheter PFO closure in patients with concurrent large PFO, spontaneous right‐to‐left shunt, large ASA, coagulation abnormalities, and prominent EV. Methods: Between March 2006 and October 2008, 36 (mean age 44 ± 10.9 years, 28 females) out of 120 consecutive patients referred to our center for transcatheter PFO closure had concomitant diagnosis of (a) large PFO on transcranial Doppler (TCD) and transesophageal echocardiography (TEE), (b) spontaneous right‐to‐left shunt on TCD, (c) large ASA, (d) prominent EV, and (e) coagulation abnormalities. All patients fulfilled the standard current indications for transcatheter closure and underwent preoperative TEE and brain magnetic resonance imaging (MRI), with subsequent intracardiac echocardiographic‐guided transcatheter PFO closure. Results: Compared to the remaining PFO population in the same period, patients with all five concomitant features had more ischemic brain lesions on MRI, previous history of recurrent stroke, more frequently a history of venous thromboembolism, and more severe migraine with aura. The concomitance of all the features confers the highest risk of recurrent stroke (OR 9.9, 3.0–18 [95% CI], P < 0.001). Conclusions: Despite its small sample size and nonrandomized retrospective nature, this is the first study to suggest that patients with concurrence of all the investigated characteristics have potentially a higher risk of stroke compared to controls. We thus propose the CARP criteria as a basis for further larger, longitudinal studies to assess the potential benefits of transcatheter closure in this patient subset in the absence of clinical recurrent stroke.     

Ultra High‐Density Multipolar Mapping With Double Ventricular Access: A Novel Technique for Ablation of Ventricular Tachycardia

Ultra High‐Density Multipolar Mapping With Double Ventricular Access . Background: Analogous to the use of circular loop catheters to guide ablation around the pulmonary veins, it may be advantageous to use a multipolar catheter in the ventricle for rapid mapping and to guide ablation. We describe a technique using double access into the left ventricle for multipolar electroanatomic mapping and ablation of scar‐mediated ventricular tachycardia (VT). Methods: Double access into the left ventricle was obtained via transseptal technique. Endocardial mapping was performed via the first transseptal sheath using a steerable duodecapolar catheter. Higher density mapping was performed in areas of dense scar (<0.5 mV) and border zone (0.5–1.5 mV). All late potentials (LPs) observed on the 20 poles were tagged and pacemapping was performed at these sites for comparison with the clinical or induced VT 12‐lead template. If VT was hemodynamically tolerated, entrainment mapping was attempted at sites demonstrating diastolic activity. Ablation was performed through the second transseptal sheath with an open‐irrigated catheter at target sites identified by LPs, pacemapping, and/or entrainment on the duodecapolar catheter. Results: Seventeen patients (88% ischemic cardiomyopathy) underwent electroanatomic mapping and ablation with double transseptal access. The mean number of endocardial mapping points was 819 ± 357 with an average mapping time of 31 ± 7 minutes. The mean number of VTs induced was 2.8 ± 1.6, mean cycle length 418 ms ± 101. LPs were seen in all patients during endocardial mapping with the duodecapolar catheter. Good (56%) and perfect (44%) pacemaps were seen in all patients when performed. Concealed entrainment, guided by the earliest diastolic activity seen on the duodecapolar catheter, was demonstrated in 4 patients (24%). Acute success was achieved in 94% of patients with complete success in 47% and partial success in 47%. The intermediate success rate (free of VT recurrence) was 69%, with an average follow‐up of 8 ± 3 months. Conclusion: Mapping and ablation of scar‐mediated VT using a multipolar catheter results in ultra high‐density delineation of the left ventricular substrate. A novel double ventricular access strategy has the potential to facilitate identification of LPs, pacemapping, and entrainment mapping. (J Cardiovasc Electrophysiol, Vol. 22, pp. 49‐56, January 2011)     

Impact of anatomical pielocaliceal topography in the treatment of renal lower calyces stones with extracorporeal shock wave lithotripsy

AIM: There is wide consensus that the lowest success rate of extracorporeal shock wave lithotripsy (ESWL) is in the complete clearance of renal stones located in the lower calyces. We assess the effectiveness of extracorporeal shock wave lithotripsy monotherapy for lower pole renal calculi to determine the relationship between the spatial anatomy of lower pole and the outcome of ESWL. METHODS: We evaluated 107 patients who were treated for solitary lower pole renal stones less than 20 mm in diameter with ESWL. The spatial anatomy of the lower pole, as defined by the lower infundibulopelvic angle, infundibular length and infundibular width, was measured by preoperative intravenous pyelography, while the stone location and size were determined by using abdominal plain X-ray. All patients were followed up at 1 and 3 months with abdominal plain X-ray and ultrasonography. RESULTS: Only 62 patients (58%) became stone free, while 45 (42%) retained residual fragments. A small lower infundibulopelvic angle, a long infundibular length and a tight infundibular width are unfavorable for stone clearance after ESWL. CONCLUSIONS: ESWL is the treatment of choice for most renal and ureteral stones. However, stone clearance from the lower pole following ESWL is poor and significantly affected by the inferior pole collecting system anatomy. Therefore, we believe it is important to evaluate these anatomical factors when deciding on the best treatment for lower pole renal calculi.     

Mycobacterium tuberculosis chaperonin 10 and N-truncated fragments Their synthesis and purification by the isoelectric focusing technique carried out in solution

The Mycobacterium tuberculosis chaperonin 10 protein and fragments corresponding to sequences 59-99, 51-99 and 26-99 were synthesised by the solid-phase methodology using a double coupling protocol and without the aid of capping agents. After the final acid cleavage using the low TFMSA-high HF protocol the polypeptides were purified by either the ion exchange chromatography/RP-HPLC combination or the isoelectric separation carried out in solution and followed by semi-preparative RP-HPLC. Comparison of the results obtained through the two approaches indicated that in general the isoeletricfocusing/HPLC combination was superior both in terms of recovery of final material and its purity. The advantages found were as follows: (i) Unlike ion exchange chromatography, no tailoring of the separation conditions is required. (ii) Several consecutive focusings can be carried out in progressively narrower pH gradients. This increases the separation resolution without the need of changing other separation parameters, (iii) Very little manipulation is needed, and each focusing requires 3-5 h. (iv) Full compatibility with non-ionic denaturants such as 8 M urea. This increases solubility so that using the ROTOFOR instrument described here 50-100 mg crude polypeptide can be processed daily. Thus the isoelectric focusing technique carried out in solution is a valid and inexpensive alternative to ion exchange chromatography. © Munksgaard 1997.     

EFFECT OF SHORT COURSE OF 1,25-DIHYDROXYVITAMIN D3ON BIOCHEMICAL MARKERS OF BONE REMODELLING IN POSTMENOPAUSAL WOMEN

This study was designed to test the hypothesis that a short treatment course of 1,25(OH)₂D₃elicits a stimulation of osteoblast activity without any action on the osteoclast. To test this, oral daily doses of 0.5μg or 1μg of 1,25(OH)₂D₃were administered for 7 days to two groups (n=5 andn=7, respectively) of postmenopausal women with low bone mineral density. Markers of osteoblast activity, i.e. osteocalcin (BGP), total alkaline phosphatase activity (ALP) and bone alkaline phosphatase activity (BALP), and markers of osteoclast activity, i.e. hydroxylysyl-pyridinoline (Pyr), lysyl-pyridoline (D-Pyr), and galactosyl-hydroxylysine (GHyl) were measured in plasma and in fasting urinary samples, respectively, at sequential times during and after 1,25(OH)₂D₃administration. It resulted that short term 1μg 1,25(OH)₂D₃oral administration induced a significant (P<0.05) rise of BGP serum level without any associated increase ofD-Pyr and GHyl, the latter also expressed as GHyl to GGHyl ratio. Urinary Pyr increased significantly after 1μg daily doses of 1,25(OH)₂D₃. Thus, a short course of 1μg daily doses of 1,25(OH)₂D₃elicits a stimulation of osteoblast activity without any enhancement ofD-Pyr, the most specific marker of osteoclast activity. The enhancement of Pyr after 1μg daily doses of 1,25(OH)₂D₃might be due to the activation of extraosseous metabolic pathways rather than to the activation of osteoclast.     

Do different physicians' panels reach similar conclusions?: A case study on practice guidelines for limited surgery in breast cancer

This study was aimed at assessing the extent to which differentpanels of physicians produce similar recommendations and whethertheir agreement is greater when members of the panels practicein the same geographical area. A total of 34 physicians, organizedin 3 multispeciality and one monospeciality (all surgeons) panels,working at both specialized and community hospitals, participatedin the study. They were asked to rate the appropriateness ofan indication for limited surgery in breast cancer for 432 hypotheticalpatients described through clinical scenarios. The primary outcomeof the study was the reliability of appropriateness ratingsbetween the pairs of panels, measured as the percent absoluteagreement and kappa statistic. The agreement of the ratingsbetween pairs of panel of the same region was always quantitativelygood - panels I-II kappa = 0.58 (95% Cl: 0.50–0.67) andpanels III-IV kappa = 0.65 (95% Cl: 0.56–0.75) - and higherthan when panels from different regions were compared. We concludethat in our study an acceptable level of agreement was reachedwhen different panels of experts were asked to produce guidelinesusing a structured process which includes exposure to the relevantscientific literature. The fact that local (organizational,cultural, etc.) factors seemed to play a modulating role overscientific evidence has implications that should be consideredwhen deciding on the level (local versus central) where guidelinesare produced.     

Underdetection of Ventricular Tachycardia Using a 40 ms Stability Criterion: Effect of Antiarrhythmic Therapy

Inappropriate shocks can complicate cardioverter defibrillator therapy. Among solutions proposed to avoid oversensing are algorithms to reduce inappropriate detection of atrial fibrillation (AF) or sinus tachycardia. In patients not on antiarrythmic drugs, an interval stability criterion of 40 ms has been validated with the Medtronic PCD to discriminate ventricular tachycardia (VT) from AF. With this algorithm, VT is considered stable if no interval varies from one of the three preceding in tervals by more than 40 ms. If an interval does not fulfill this criterion, the VT event counter is reset to zero. The aim of this study was to investigate the incidence of underdetection when this criterion is ap plied in patients treated with antiarrhythmic drugs. We studied 132 sustained monomorphic VTs induced in 42 patients during 101 electrophysiological studies (EPS). EPS were performed without treatment (group I. 24 patients, 44 VTs); on Class Ia drug (group II, 17 patients, 24 VTs); Class Ic drug (group III, 22 patients, 39 VTs); or sotalol (group IV, 17 patients, 25 VTs). The endocardial electrogram of all VT episodes was digitized and the stability algorithm was applied. The reset arrhythmias were distributed among no delay, small, moderate (<10 s) and important (>15 s) delay in VT detection. The relation be tween drug use and reset was analyzed. Beset was found in 86 (65%) of induced VTs. No difference in heart rate or induction mode was shown between reset and nonreset VTs. There was a significative asso ciation between drag use and reset probability (Chi² significantly different, P < 0.05). In patients treated with Class Ic drugs, the probability of finding an important delay in VT detection was 12.5% versus 0% in nontreated patients or in patients treated with sotalol. We conclude that a stability criterion of 40 ms is probably safe in nontreated patients but should be used with caution in patients treated with antiarrhythmics, especially in the presence of Class Ic drags.