Therapy Assessment for Sustained Ventricular Tachyarrhythmias: How Many Electropharmacological Tests are Appropriate?

Surgery, implantable devices or catheter ablations offer therapeutic choices for the treatment of malignant ventricular tachyarrhythmias (VT) resistant to antiarrhythmic drugs. The number of electropharmacological (EP) tests that should precede consideration of a nonpharmacological therapy has not been defined. We performed serial EP tests in 94 patients with inducible sustained VT until an effective drug was identified or all available drugs had failed to suppress VT induction. With up to 11 tests in individual patients, suppression of VT inducibility was finally achieved in 66 patients (70%). In 47 of these 66 patients (70%), only one or two tests were necessary to identify an effective regimen. However, in 40%, 28%, 18%, and 9% of the patients still inducible after 2, 3, 4, and 5 drug tests, respectively, an effective agent could be identified during subsequent tests. No critical number of unsuccessful EP tests clearly separated responders and nonresponders to medical therapy. During follow-up (34 +/- 11 months), 14 patients placed on antiarrhythmic drugs predicted to be effective had symptomatic VT recurrence. VT recurrence was unrelated to the type or the number of unsuccessful EP tests preceding identification of the prescribed drug. Extensive EP testing with all available agents might therefore be worthwhile in selected patients. An "appropriate" number of EP studies has to be determined individually for each patient, based on the chance of finding an effective drug during subsequent studies and the risk and benefit of the therapeutic choices.     

Mortality, Morbidity, and Complications in 3,344 Patients with Implantable Cardioverter Defibrillators:

ICDs are the therapy of choice in patients with life-threatening ventricular arrhythmias. Mortality, morbidity, and complication rates including appropriate and inappropriate therapies are unknown when ICDs are used in routine medical care and not in well-defined patients included in multicenter trials. Therefore, the data of 3,344 patients (   61.1 ± 12.1  years   ; 80.2% men; CAD 64.6%, dilated cardiomyopathy 18.9%; NYHA Class I–III: 19.1%, 54.3%, 20.1%, respectively;   LVEF > 0.50   : 0.234, LVEF 0.30–0.50: 0.472,   LVEF < 0.30   : 0.293, respectively) implanted in 62 German hospitals between January 1998 and October 2000 were prospectively collected and analyzed as a part of the European Registry of Implantable Defibrillators (EURID Germany). The 1-year survival rate was 93.5%. Patients in NYHA Class III and a   LVEF < 0.30   had a lower survival rate than patients in NYHA Class I and a preserved LVEF (0.852 vs 0.975,   P = 0.0001   ). Including the 1-year follow-up, 49.5% of patients had an intervention by the ICD, 39.8% had appropriate ICD therapies, 16.2% had inappropriate therapies. Overall, 1,691 hospital readmissions were recorded. The main causes for hospital readmissions were ventricular arrhythmias (61.3%) and congestive heart failure symptoms (12.9%). Thus, demographic data and mortality of patients treated with an ICD in conditions of standard medical care seems to be comparable and based on, or congruent with, the large secondary preventions trials. When ICDs are used in standard medical care, the 1-year survival rate is high, especially in patients with NYHA Class I and preserved LVEF. However, nearly half of all patients suffer from ICD intervention. (PACE 2003; 26[Pt. I]:1511–1518)     

Simultaneous Recording of Atrial and Ventricular Monophasic Action Potentials: Monophasic Action Potential Duration During Atrial Pacing, Ventricular Pacing, and Ventricular Fibrillation

A newly developed transvenous suction electrode was used in dogs to record monophasic action potentials (MAPs) from the right atrium and right ventricle simultaneously. Continuous MAP recordings could be made from the same endocardial site for test periods of 1.5 hours. Left ventricular pacing at increasing heart rates resulted in a statistically significant decrease of right ventricular MAP duration. A high degree of correlation was found between right ventricular MAP duration at 90% of repolarization and the QT interval during both right atrial and left ventricular pacing. At the onset of ventricular fibrillation (VF), right ventricular MAP duration shortened to 25% of the value obtained during left ventricular pacing at a cycle length of 250 ms. A cyclic alternation in amplitude of the right ventricular MAPs was observed during VF. Fast Fourier Transform Analysis of right ventricular MAPs during VF showed a significant dominant frequency at 12 Hz, with no levels of interest beyond this frequency. This observation might prove to be useful in elaborating a new algorithm for the automatic detection of ventricular fibrillation.     

Microglial Dystrophy in the Aged and Alzheimer''''s Disease Brain Is Associated with Ferritin Immunoreactivity

小胶质细胞变性对认识衰老相关的神经退变和神经退行性疾病的发病机制非常重要.本研究通过铁蛋白免疫组织化学方法来分析非痴呆和阿茨海默病患者大脑中的小胶质细胞形态特征.作者的主要假设为,铁储存蛋白-铁蛋白的表达提高小胶质细胞对退化的敏感性,尤其是在老年大脑中,因为衰老的小胶质细胞越来越无力维持铁环境稳定,而游离铁可促进氧化损伤.在24例34-97岁的病例中,小胶质细胞对铁蛋白的免疫反应被发现组成一个较大的HLA-DR抗体标记的小胶质细胞池.在老年尤其是AD大脑中,铁蛋白阳性的大部分小胶质细胞呈现出异常的形态学变化,即营养不良.铁蛋白阳性的营养不良小胶质细胞和AD组织中的老年斑之间并未发现空间相关性.对平均死亡时间(10.94±5.69)h的人脑组织的研究显示,小胶质细胞营养不良的出现不依赖于死亡时间,因而不是组织自溶的产物.这些结果均提示,包含铁储存和新陈代谢的小胶质细胞的变性可能是通过其高暴露于氧化应激.作者推论,铁蛋白免疫组织化学法可能是检测人脑小胶质细胞退行性变的有效方法.     

Orthodromic and Antidromic Pacemaker Circus Movement Tachycardia

Pacemaker circus movement tachycardia (PCMT) during DDD pacing is usually sustained by retrograde natural and antegrade electronic atrioventricular (AV) conduction. As PCMT is often initiated by a ventricular premature beat (VPB) one method of its prevention is the programming of an atrial stimulus synchronously following a ventricular extrasystole. A patient is described with preserved antegrade, but without retrograde, i.e., VA, conduction. The optional pacemaker mode of synchronous atrial stimulation following a VPB caused an unusual PCMT sustained by retrograde electronic and antegrade natural AV conduction. This PCMT is similar to a natural reentry tachycardia, the most common variety of which (based on retrograde conduction) is termed antidromic and that which we describe is orthodromic.     

HLA-DR3 in dermatitis herpetiformis

Twenty-one patients with dermatitis herpetiformis were typed for HLA-ABC and -DR determinants. The incidence of HLA-AI, -B8 and -DR3 antigens was found to be significantly higher (P: = 10^?3, <10^?6 and <10^?6, respectively) among patients with dermatitis herpetiformis than among the normal population. HLA-DR3 was found in 85.7% of patients, HLA-B8 in 66.7% and HLA-Ai in 61.9% only. These results indicate that HLA-DR3 is the antigen primarily associated in dermatitis herpetiformis and the latter antigens (HLA-Ai and -B8) are present in increased incidence, probably due to the known linkage disequilibrium of these antigens with HLA-DR3.     

Plasma concentration following oral and intramuscular atropine in children and their clinical effects

In a paediatric population, we compared i.m. v oral atropine pre-medication to a control group without atropine and determined atropine plasma concentrations (APC). Forty-five children were randomly assigned to one of three groups. Group I received atropine, 20 μg·kg⁻¹ i.m., 15 min prior to induction. Group II received atropine, 30 μg·kg⁻¹ orally, group III received no atropine. APC (expressed as percent of muscarine-2 receptor subtype occupancy), heart rate, rectal temperature, and salivation were determined before atropine, and 15, 25, 45, 60, 90, 120 (no APC), and 150 min following atropine. Only 10–20% of the M2-cholinoceptors were occupied after oral atropine with a peak at 90 min compared to 60–70% occupancy with a peak 25 min after i.m. atropine. The peak in M2-cholinoceptor occupation in group I was paralleled by a peak percentage change in heart rate of 15% from baseline. The peak in receptor occupation in group II did not correspond to the peak increase in heart rate. The percentage change of heart rate over time was not significantly different from baseline values in any of the groups. Bradycardia or temperature changes did not occur in any of the groups. Antisialogogue effects were observed only in group I. We conclude that atropine, 30 μg·kg⁻¹ orally is not an equipotent dosage to atropine, 20 μg·kg⁻¹ i.m.     

Plasmodium falciparum malaria blood stage parasites preferentially inhibit macrophages with high phagocytic activity

Exposure to malaria blood stage antigens results in several defects of macrophages/monocytes one of which is an irreversible reduction of phagocytic activity. In the present study we analysed phagocytic activity of subpopulations of human monocyte-derived-macrophages (MDM) based on the capacity of individual cells to ingest FITC-labelled microbeads. The results demonstrate that malaria infection affected predominantly MDM subpopulations with high level of phagocytosis. This population decreased during parasitaemia, however, during recovery from the infection the highly phagocytic cells replaced the damaged cells. The exposure of MDM cultures to blood stage antigens showed that the highly active macrophages from persons with active malaria infection decreased further, while the population increased during recovery. Furthermore, we observed that while ingestion of a few parasitized RBC (3 schizonts) stimulated phagocytosis, larger amounts or longer exposure periods eventually paralysed the entire phagocytic system. Accordingly, by selectively blocking actively phagocytizing macrophages, the malaria parasite prevents both specific and non-specific immune responses, which are initiated by macrophages as phagocytes and professional antigen presenting cells.     

THE EFFECT OF D- VERSUS L- PROPRANOLOL IN THE TREATMENT OF HYPERTHYROIDISM

The purpose of this study is to determine whether there is a difference in treatment of hyperthyroidism using either the D- or L-isomer of propranolol. Two groups of 20 patients with overt hyperthyroidism received either 120 mg L- or D-propranolol each for a period of 5 days. In the D-propranolol administered group there was a significant decrease in TT3 and fT3 plasma levels and in the ratio of TT3 to TT4; however, a significant increase occurred in rT3 values up to day 5. On the other hand, L-propranolol treatment resulted in a less pronounced decrease in TT4 and TT3 values, while all other thyroid hormone levels remained unchanged as, above all, did the T3/T4 ratio. The well known effect of D,L-propranolol upon peripheral conversion of T4 to T3 is thus not due to the beta-blocking action of L-propranolol but is mainly conditioned by the D-isomer which has no beta-blocking action itself.