Multimeric composition of plasma von Willebrand factor in chronic myeloproliferative disorders

Summary In chronic myeloproliferative disorders (CMPD) thrombohaemorrhagic complications occur occasionally in association with thrombocytosis. We studied the multimeric composition of plasma von Willebrand factor (vWf) in 15 patients with polycythaemia vera (PV), 12 with essential thrombocythaemia (ET) and eight with primary myelofibrosis (PMF). The relative content of large (multimer band ≥ 11) multimers calculated by densitometer scan following SDS-agarose gel electrophoresis was 18.5 ± 4.4% (mean±SD) in normal controls, 8.3 ± 7.9% in PV, 8.1 ± 4.6% in ET and 19.6 ± 6.7% in PMF. The patients with PV and ET but not PMF had a significantly lower percentage of large multimers than normal controls (P < 0.001). The relative content of large multimers was negatively correlated with WBC and platelet count (P < 0.02 each) in PV. It was negatively correlated with platelet count (P < 0.005) and was positively correlated with a ratio of ristocetin cofactor/vWf antigen (RCof/vWf: Ag)(P < 0.01) in ET. These results indicate that acquired defects of vWf are quite common in PV and ET but not in PMF. In addition, some CMPD patients with high platelet counts completely lacked large multimers. The negative correlation of the relative content of large multimers with platelet count suggests that large multimers may be preferentially consumed during thrombocytosis or degraded by protease(s) from increased blood cells.     

Specific Electrocardiographic Features of Manifest Coronary Vein Posteroseptal Accessory Pathways

Coronary Vein Accessory Pathways. Introduction: Some posteroseptal accessory pathways (APs) can be successfully ablated by radiofrequency current only from inside the coronary sinus (CS) or its branches, because of an absolute or relatively epicardial location. The aim of this study was to identify ECG features of manifest posteroseptal APs requiring ablation in the CS or the middle cardiac veins (MCVs). Methods and Results: One hundred seventeen consecutive patients with manifest posteroseptal APs successfully ablated: (1) ≥ 1 cm deep inside the MCV (group MCV: n = 13); (2) inside the CS, including the area adjacent to the MCV ostium (group CS: n = 10); (3) at the right (group R: n = 60); or (4) the left posteroseptal endocardial region (group L: n = 34) were included. We reviewed delta wave polarity (initial 40 msec) and QRS morphology during sinus rhythm and atrial pacing as well as electrogram characteristics in these patients. The local target site electrogram in groups MCV and CS was characterized by a longer atrial to ventricular electrogram interval, suggesting a longer course of the pathway and more frequent recording of a presumptive AP potential compared to the group ablated at the right or left endocardium. The most sensitive ECG feature for group CS or group MCV was a negative delta wave in lead II in sinus rhythm (87%), but specificity (79%) and positive predictive value (50%) were relatively low. A steep positive delta wave in aVR during maximal preexcitation possessed the highest specificity and positive predictive value (98% and 88%, sensitivity 61%) which increased to 99% and 91%, respectively, when combined with a deep S wave in V₆ (R wave ≤ S wave). Conclusion: These data suggest that posteroseptal APs ablated inside the coronary venous system have highly specific features, including the combination of a steep positive delta wave in lead aVR and a deep S wave in lead V₆ (R wave ≤ S wave) during maximal preexcitation. The highest sensitivity is provided by a negative delta wave in lead II. These findings may be helpful for anticipating and planning an epicardial ablation strategy.     

Nocturia Potentially Influences Maintenance of Sexual Function in Elderly Men with Benign Prostatic Hyperplasia

Objective: This study examined the relationship between bothersome symptoms of nocturia and erectile function. Methods: Subjects comprised patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Patients were prospectively followed on treatment with the alpha‐1 blocker naftopidil for 8 weeks. Patient backgrounds and efficacy of naftopidil associated with LUTS and sexual activity were evaluated. Results: The percentage of patients who identified nocturia as the most bothersome symptom was 30.2% (n = 135), representing the highest percentage among International Prostate Symptom Score (IPSS) items. The number of patients with nocturia as the most bothersome symptom plateaued at an IPSS for nocturia of two or three points. In contrast, the number of patients with slow stream as the most bothersome symptom increased with symptom severity according to IPSS for slow stream. Logistic regression analysis on association between nocturia and erectile function confirmed that the odds ratio was 1.41 (P < 0.05). Naftopidil showed excellent efficacy related to male LUTS, but International Index of Erectile Function 5 (IIEF5) total score was almost unchanged. Among patients with nocturia improved by naftopidil, IIEF5 total score was significantly changed in the group with IPSS nocturia score ≤1 as compared to the group with IPSS nocturia score ≥2 per night (P = 0.038). Conclusion: Nocturia the most bothersome symptom correlated with aging. Nocturia could associate erectile dysfunction, and keeping the frequency of nocturia at ≤1 episode might be meaningful for maintaining quality of life in elderly men.     

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) as a Direct-Acting Teratogen in Micromass in vitro Tests

3-Chloro-4-(dichloromethyl)-5-hydroxy-2( 5H )-furanone (MX) causes complete inhibition of rat embryonic midbrain (CNS) cell differentiation in the micromass in vitro test when applied at a concentration of 5 μ g/ml under conditions where MX is rapidly degraded in culture medium with a half-life of 56 min. This study investigated whether or not degradation products of MX have inhibitory effects on CNS cell differentiation following pre-incubation of MX in culture medium for 0.5, 1 or 2 hr. When MX was pre-incubated for 0.5 hr, the mean number of differentiated foci was 0.2 against 62.5 for the control. However, the number increased to 44.7 when pre-incubation time was extended to 2 hr. These results suggest that MX, but not its degradation products, is a teratogen in vitro. MX manifested almost complete inhibitory effects on CNS cell differentiation by 0.5 hr of exposure.     

High‐dose unfractionated heparin therapy in a pregnant patient with antiphospholipid syndrome: a case report

A case of a 37‐year‐old pregnant patient with antiphospholipid syndrome (APS), who has a medical history of both thrombosis and recurrent fetal loss, is presented. She was treated with predonisolone and fixed‐dose unfractionated heparin (UFH) infusion, followed by plasmaphereses and fixed‐dose low‐molecular‐weight heparin infusion during her fourth pregnancy. Unfortunately, this treatment did not have beneficial effects, resulting in intrauterine growth restriction and finally neonatal death. Continuous intravenous UFH infusion and low‐dose aspirin were administrated under the monitoring of the activated partial thromboplastin time to achieve a target level of 120 s during her fifth pregnancy. A healthy baby weighing 1818 g at birth was delivered by Cesarean section at the 34th week of pregnancy. High‐dose UFH infusion may be considered to be one of the preferable options to manage pregnant patients with refractory APS.     

Catheter Ablation of Atrial Fibrillation in Patients With Valvular Heart Disease: Long‐Term Follow‐Up Results

AF Ablation in Patients With Valvular Heart Disease . Background: The purpose of this study is to evaluate the efficacy of atrial fibrillation (AF) ablation in patients with moderate valvular heart disease (VHD). Methods: In total, 534 consecutive patients who underwent AF ablation were enrolled. Patients with a history of valve surgery or other structural heart disease were excluded. Patients with clinically moderate VHD (group‐1, n = 45) were compared with those without VHD (control group‐2, n = 436). Ipsilateral pulmonary vein antrum isolation (PVAI) was performed with a double Lasso technique in all the patients. Left atrial (LA) linear ablation was undertaken in persistent AF patients, if AF was inducible after PVAI. Results: Patients in group‐1 were significantly older and had a larger LA. PVAI was successfully achieved in all the patients. Patients in group‐1 received LA linear ablation more frequently during the index procedure. After a median of 26 months from the index procedure, the freedom from AF was significantly lower in group‐1 than group‐2 off antiarrhythmic drugs (AADs) (47% vs 69%, P = 0.002). Although there were more number of total procedures in group‐1 than group‐2, the freedom from AF was lower at median 24 months after the last procedure (78% vs 87%, P = 0.038). There was no significant difference in the freedom from AF on AADs (91% vs 95%, P = 0.356) or complication rate between the 2 groups. Atrial tachycardia following the index procedure was observed more frequently in group‐1 (P = 0.001). Conclusion: The patients with VHD undergoing AF ablation are less likely to remain in sinus rhythm at long term without AADs than those without VHD. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1193‐1198, November 2010)     

Idiopathic retroperitoneal fibrosis associated with IgG4-positive-plasmacyte infiltrations and idiopathic chronic pancreatitis

Idiopathic retroperitoneal fibrosis (IRPF) is an inflammatory fibrosclerosing condition, leading to renal failure by obstruction of the ureters. Idiopathic chronic pancreatitis associated with marked inflammatory infiltrates has recently been referred to as autoimmune pancreatitis (AIP), and infiltrating plasmacytes carrying immunoglobulin-gamma type 4 (IgG4) are relevant to its pathogenesis. The case is described herein of IRPF associated with subclinical pancreatitis that was most probably AIP in a 70-year-old man. Biopsy specimens of the retroperitoneal pseudotumor revealed a marked lymphoplasmacytic infiltration with dense fibrosis. Infiltrating plasma cells were immunoreactive for anti-IgG4 antibodies. Subsequent systemic examinations showed an extremely elevated serum IgG4 level and pancreatitis concordant with AIP. Following oral steroid administration, the serum IgG4 level normalized, although the appearance of the pseudotumor did not alter. Some AIP cases have been associated with idiopathic fibrosclerosing disorders including IRPF, but histological evidence of IgG4-related IRPF has rarely been provided.     

High-Density Circumferential Pulmonary Vein Mapping with a 20-Pole Expandable Circular Mapping Catheter

The differentiation of pulmonary vein (PV) electrograms from atrial far-field signals during PV isolation (PVI) for atrial fibrillation (AF) may be difficult. In addition, owing to highly variable PV ostial sizes, current fixed-diameter circular PV mapping catheters may not yield optimal electrograms. We evaluated an expandable, circular 15–25 mm diameter, 20-pole mapping catheter for PV mapping during sustained AF in 25 patients. After selective PV angiography to define the ostial position and size, the catheter was introduced into each PV and withdrawn to the most stable proximal position, with optimal wall contact ensured by progressive loop expansion. At each PV ostium, electrograms recorded at high resolution (HR) were compared with those recorded at a resolution similar to that of a standard 10-pole Lasso catheter. After PVI performed during ongoing AF, the presence of residual far-field potentials (FFP) under both set-ups was compared. We mapped 97 PV, including 4 pairs with common ostia. In the HR recordings, the PV potentials had greater amplitude (0.5 ± 0.1 vs 0.3 ± 0.1 mV, P = 0.001) and fragmentation, whereas left atrial FFP were minimized. After successful isolation of all PV, FFP were observed in 33% of left superior and 28% of left inferior PV on the HR recordings, compared to 66% and 61%, respectively under normal resolution. Catheter stability and optimal wall contact, in combination with HR electrograms can optimize circumferential PV mapping during AF and improve the discrimination of FFP postablation.