Functional Competence of Dendritic Cells of Ageing C57BL/6 Mice

Highly polymorphic age-dependent differences in progression of T and B cells have been found in various strains of inbred mice. In the immune system of C57BL/6 mice these occur first in B cells and, later in life, in T cells. In this paper, we have examined the progression in the functional capacity of C57BL/6 dendritic cells (DC). Age-dependent changes were found in the syngeneic mixed leucocyte reaction, in which the stimulatory capacity of DC increased with age. This increase was independent of the age of the donor of the serum that was added to the culture, and occurred when young donors provided the T cells. Age-dependent changes in DC properties were not detected in terms of direct plaque-forming response, response to concanavalin A, or in the allogeneic mixed leucocyte reaction.     

Characterization and Modification of Brain Activity with Deep Brain Stimulation in Patients in a Persistent Vegetative State: Pain-Related Late Positive Component of Cerebral Evoked Potential

A series of eight patients in a persistent vegetative state (PVS) were subjected to chronic deep brain stimulation (DBS) for the purpose of promoting recovery from the PVS. The characteristics of the brain activity in these patients were evaluated from the late positive component of the cerebral evoked potential in response to painful stimuli (pain-related P250). While any neurological scoring system for the comatose state includes evaluations of motor reactions to painful stimuli, the pain-related P250 is unique in terms of its ability to assess the cortical responsiveness to painful stimuli directly and quantitatively without involving functions of the motor system. It was found that the pain-related P250 was more or less depressed in patients in a PVS. It was repeatedly demonstrated in four patients, however, that the pain-related P250 could be transiently increased by preceding stimulation of the mesencephalic reticular formation. Furthermore, a persistent increase in the pain-related P250 was produced in these four patients following chronic DBS of the mesencephalic reticular formation or nonspecific thalamic nuclei for more than 6 months, and this was correlated with the clinical improvements. These results imply that responsiveness at the cortical level to pain is depressed in the PVS. It also appears that some fraction of the depression may, however, be functionally produced and potentially reversible.     

Electrophysiological Findings in Idiopathic Recurrent Ventricular Fibrillation: Special Reference to Mode of Induction, Drug Testing, and Long-Term Outcomes

Electrophysiological studies can be useful in the presence of idiopathic ventricular fibrillation (VF) and may be used when selecting antiarrhythmic drugs. However, the yield, the mode, and the long-term reproducibility of the induction of VF have not yet been fully elucidated. Eight patients with idiopathic VF underwent electrophysiological study. The mean age (± SD) was 45 ± 17 years. Six were males and two were females. Diagnosis was done by exclusion. VF was induced in 6 (75%) of 8 patients using double extra stimuli at coupling intervals of 233 ± 39 and 191 ± 20 ms for the first and second extra stimuli, respectively. Of note, VF was induced by stimulation exclusively at the origin of the premature ventricular beat, which was the first complex of VF in two patients. In another patient, VF was initiated by two premature stimuli and also by a pause produced by rapid pacing. The inducibility of VF was reproduced 9–18 months after the first induction in all of the four patients studied. When the ability of antiarrhythmic drugs to suppress VF inducibility was confirmed, no recurrence was observed during the follow-up period of 40–160 months, but a recurrence of VF was observed in one of two nonresponders. In one patient, amiodarone administration failed in preventing VF induction 9 months after initiation of therapy, and reassessment of long-term drug-efficacy might be indicated in some patients. In conclusion, idiopathic VF was highly inducible (75%) with double extra stimuli. In this study, it was induced from a specific site (2/8) or by a pause (1/8). Induction of VF seemed to be reproduced 9–18 months after the first study. The outcome was considered favorable when the inducibility of VF was suppressed by antiarrhythmic drugs.     

VDD Pacing with a Previously Implanted Single Lead System

Three patients who had undergone implantation of a rate modulated, afrial sensitive RS4 pacemaker, with a single orthogonal lead underwent replacement of a depleted unit with a DDD pulse generator, reusing the original lead with an adapter that allowed conversion of the bipolar atrial electrode into unipolar configuration. The mean atrial electrogram amplitude was 1,8 mV and no significant atrial sensing defects were found during Holler monitoring. As the RS4 pulse generator is no longer available, continued VDD pacing is possible by replacing it with a DDD pulse generator using the previously implanted single lead system.     

Radiofrequency Catheter Ablation of Concealed Atrioventricular Accessory Pathways Using a "Simultaneous Pacing Method"

The retrograde atrial potential at a successful ablation site is usually obscured by the wide and large ventricular potential during atrioventricular reentrant tachycardia or ventricular pacing, which makes it difficult to determine the appropriate ablation site for concealed accessory pathway. A pacing maneuver named the “simultaneous pacing method” is proposed herein to differentiate the retrograde atrial potential from the ventricular potential for a successful ablation of the concealed accessory pathway. Catheter ablation was performed in 12 patients with a single left free-wall concealed accessory pathway. The atrial insertion site was determined by the simultaneous pacing method in six patients (group I) and by ventricular pacing in six patients (group II), In the simultaneous pacing method, electrograms recorded during ventricular pacing in the earliest retrograde atrial activation site are a fusion of the ventricular potential and the following retrograde atrial potential. When atrial and ventricular pacings are performed simultaneously (simultaneous pacing), the end portion of the electrograms recorded at the same site is solely the ventricular component, because atrial is activated earlier. The atrial potential can be confirmed during ventricular pacing in comparison with the electrograms during the “simultaneous pacing.” Radiofrequency catheter ablation was successful in eliminating conduction through the accessory pathway in all 12 patients. The radiofrequency applications in group I were significantly fewer than those in group II (1.7 ± 1.0 in group I, 5.3 ± 3.2 in group II, P < 0.05). The total procedure time in group I was significantly shorter than in group II (57.8± 15.7 vs 106.7 ± 41.6 mins in group II. respectively, P < 0.05). The fluoroscopy time in group I was significantly shorter than in group II (54.0 ± 7.9 vs 81.3± 26.3 mins, respectively, P < O.05). We were able to determine the atrial insertion site of accessory pathways by the simultaneous pacing method. The simultaneous pacing method was useful in eliminating concealed left free-wall accessory pathways.     

Significance of Ventricular Pacing Site in Manifest Entrainment During Orthodromic Atrioventricular Reentrant Tachycardia with Left-Sided Accessory Pathway

We examined entrainment by ventricular pacing in six patients during orthodromic atrioventricular reentrant tachycardia (AVRT) utilizing a left-sided lateral accessory pathway. Constant fusion and progressive fusion were demonstrated in all patients by left ventricular pacing during tachycardia, but in none of the patients by right ventricular pacing. When left ventricular pacing was performed during AVRT, the antidromic wave front from the pacing impulse (n) collided with the orthodromic wave front of the previous pacing beat (n - 1) within the ventricle, therefore, constant fusion and progressive fusion were demonstrated in the surface electrocardiographic QRS complexes. On the other hand, when right ventricular pacing was performed during orthodromic AVRT, the antidromic wave front from the pacing impulse (n) collided with the orthodromic wave front of the previous paced beat (n - 1) within the normal atrioventricular pathway, and constant fusion and progressive fusion were therefore not demonstrated. These phenomena were explained by the relationship of the ventricular pacing site and the reentrant circuit. This study demonstrates the importance of the pacing site in manifest entrainment of orthodromic AVRT during ventricular pacing.     

Clinical and Electrophysiological Difference Between Idiopathic Right Ventricular Outflow Tract Arrhythmias and Pulmonary Artery Arrhythmias

Characteristics of Pulmonary Artery Arrhythmias. Introduction: The precise incidence and characteristics of ventricular arrhythmias originating from the pulmonary artery have not been fully described. The purpose of this prospective study was to clarify these points. Methods: Thirty‐three consecutive patients with an idiopathic left bundle branch block and inferior‐axis deviation type ventricular arrhythmia were included. All patients underwent detailed electroanatomical mapping (CARTO, Biosense‐Webster, Diamond Bar, CA, USA) during sinus rhythm prior to the catheter ablation. The precise location of the catheter tip at the successful ablation site was confirmed by both electroanatomical mapping and contrast radiography. The clinical and electrophysiological data were compared between the right ventricular outflow tract (RVOT) arrhythmia patients (RVOT group) and PA arrhythmia patients (PA group). Results: Eight patients (8/33 patients: 24.2%) had their ventricular arrhythmias successfully ablated within the PA. The local bipolar electrogram at the successful ablation sites in the PA group exhibited a significantly greater duration (P < 0.05) and lower amplitude (P < 0.05) than did those in the RVOT group (n = 19). In the PA group, all patients exhibited a multicomponent electrograms composed of a spiky potential and a dull potential, which might have consisted of near‐field PA activation and a far‐field ventricular activation, respectively, at the successful ablation site. Direct ablation to the spiky electrogram was able to eliminate the arrhythmias in all the PA group patients. Conclusions: PA arrhythmias may be more common than previously recognized. Careful mapping and interpretation of low amplitude and multicomponent electrograms are important for recognizing ventricular arrhythmias originating from the PA. (J Cardiovasc Electrophysiol, Vol. 21, pp. 163‐169, February 2010)     

Very high doses of valsartan provide renoprotection independently of blood pressure in a type 2 diabetic nephropathy rat model

Aim:   Angiotensin II type 1 receptor blockers (ARB) retard the progression of hypertensive diabetic kidney disease. Clinical evidence suggests that the dose of ARB required to correct hypertension is suboptimal for renoprotection evaluated by proteinuria. No systematic, prospective study has yet evaluated separately the effect of increasing doses of ARB on blood pressure and proteinuria.
Methods:   Over a period of 8 weeks, the effect of seven constant doses of an ARB, valsartan (4–160 mg/kg per day), on blood pressure and proteinuria taken as a surrogate marker of nephropathy in a hypertensive, type 2 diabetic rat model, the spontaneously hypertensive/NIH-corpulent rat (SHR/NDmcr-cp), was assessed. In this spontaneously hypertensive rat strain, a genetic mutation in the leptin receptor gene is associated with hyperphagia leading to obesity with metabolic syndrome and eventually to nephropathy.
Results:   No additional blood pressure lowering was observed above 120 mg/kg per day of valsartan, suggesting that a dose of 80–120 mg/kg per day had a maximal effect. Nevertheless, higher doses of valsartan further reduced proteinuria in a dose-dependent fashion suggesting the absence of a maximal dose. Obesity, hyperglycaemia and hypercholesterolaemia were unaffected but hypertriglyceridaemia was partially corrected at various ARB doses.
Conclusion:   ARB improve renoprotection at doses above those required for a maximal effect on blood pressure. The mechanism of the renoprotection obtained at high doses of ARB is yet to be elucidated.     

Epidermolysis bullosa acquisita with oesophageal stenosis

Epidermolysis bullosa acquisita (EBA) is a rare acquired subepidermal blistering disorder associated with autoimmunity to type VII collagen. Although the full clinical spectrum of EBA is still being defined, it is now known that EBA has greater clinical heterogeneity than previously suggested. We describe a patient with EBA which closely approximated the severity of the recessive form of dystrophic epidermolysis bullosa.