DOUBLE-BLIND STUDY OF THE REVERSAL OF MIDAZOLAM-SUPPLEMENTED GENERAL ANAESTHESIA WITH RO 15-1788

The actions and side effects of the benzodiaze-pine antagonistRo 15–1788 were evaluated in a randomized double-blindclinical study in which midazolam was used as an anaestheticagent. Sixty women who underwent laparoscopy were treated withRo 15–1788 or with placebo after the surgical procedure.Ro 15–1788 reversed the hypnotic effect of midazolam withina few minutes. The patients were alert, co-operative, orientedand had good recall of events after awakening. The effects werestatistically better than placebo for up to 30 min after administration.Arterial pressure and heart rate remained stable and there wereno significant side effects. The availability of Ro 15–1788allows effective reversal of midazolam when this is used duringgeneral anaesthesia. Presented at the 18th Congress of the Scandinavian Society ofAnaesthesiologists, Reykjavik, Iceland, June 25–29, 1985and at the 19th Central European Congress of Anaesthesiology,Graz, Austria, September 10–14, 1985.     

QRS Fragmentation and the Risk of Sudden Cardiac Death in MADIT II

QRS Fragmentation and the Risk of Sudden Cardiac Death in MADIT II. Background: QRS fragmentation (fQRS) has been reported as a useful ECG parameter in predicting mortality in high‐risk postinfarction patients. Its prognostic value for sudden cardiac death (SCD) and ventricular arrhythmias in ischemic cardiomyopathy (ICM) remains unknown. Methods: MADIT II enrollment 12‐lead ECGs were analyzed for fQRS defined as RSR’ patterns (≥1 R’ or notching of S or R wave) in patients with a normal QRS duration and >2 notches on the R or S wave in patients with abnormal QRS duration, present in 2 contiguous leads. Exclusion criteria included a paced rhythm and an uninterpretable or incomplete ECG. Study endpoints included SCD, SCD or appropriate implantable cardioverter defibrillator (ICD) shock, and total mortality (TM). Results: Of the 1,232 ECGs reviewed, 1,040 were of suitable quality for fQRS analysis. QRS fragmentation was found in 33% of patients in any leads, in 10% of patients in anterior leads, in 8% of patients in lateral leads and in 21% of patients in inferior leads. Anterior and lateral location of QRS fragmentation was not associated with follow‐up events. Inferior location of fQRS was found to be predictive of SCD/ICD shock (hazard ratio [HR] 1.46, P = 0.032), SCD (HR 2.05, P = 0.007), and TM (HR 1.44, P = 0.036). This association was driven primarily by the increase in events found in LBBB patients: SCD/ICD shock (HR 2.05, P = 0.046), SCD (HR 4.24, P = 0.002), and TM (HR 2.82, P = 0.001). Conclusions: Fragmented QRS, especially identified in inferior leads, is predictive of SCD, SCD or appropriate ICD shock, and all‐cause mortality in patients with ICM. Identifying inferior fQRS in patients with LBBB is of particular prognostic significance and should reinforce the use of ICD therapy in this high‐risk group. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1343‐1348, December 2012)     

Risk Factors for Recurrent Heart Failure Events in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT‐II)

Risk Factors for Recurrent Heart Failure . Background: This study was designed to identify risk factors for recurrent heart failure (HF) events in patients with ischemic left ventricular dysfunction enrolled in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT‐II). Methods and Results: The Prentice, Williams, and Peterson (PWP) statistical model was utilized to identify and compare risk factors for 1 or ≥2 HF hospitalizations among 1,218 patients with ischemic left ventricular dysfunction enrolled in the MADIT‐II trial. Risk factors for a first HF hospitalization included treatment with an ICD (HR = 1.31; P = 0.05), New York Heart Association class >II (HR = 1.95; P < 0.001), female gender (HR = 1.38; P = 0.05), atrial fibrillation (HR = 1.90; P = 0.001), QRS >120 ms (HR = 1.41; P = 0.01), diabetes mellitus (HR = 1.51; P = 0.003), heart rate ≥80 (HR = 1.35; P = 0.04), diuretic therapy (HR = 1.82; P < 0.001), and the presence of prerenal azotemia (defined as blood urea nitrogen:creatinine >20; HR = 1.45; P = 0.01). In contrast, prerenal azotemia was the only risk factor that was independently associated with a significant increase in the risk of ≥2 HF hospitalizations (HR = 1.52; P = 0.027). The occurrence of 1 HF event after enrolment was associated with a 2.8‐fold (P < 0.001) increase in the risk of death, whereas after the occurrence of a second event there was a 6.7‐fold (P < 0.001) increase in the risk of subsequent mortality. Conclusions: In MADIT‐II, prerenal azotemia was the only significant and independent risk factor for HF progression after a first event, and recurrent HF was the most powerful predictor of mortality. These findings stress the importance of identifying risk factors for HF progression among patients who receive an ICD for primary prevention. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1217‐1223, November 2010)     

Nonmelanocytic Lesions Defying the Two-Step Dermoscopy Algorithm

The first step of the two-step algorithm of dermoscopy aims at differentiating melanocytic from nonmelanocytic pigmented lesions, using a stepwise evaluation for the presence of specific dermoscopic criteria. The purpose of this article is to heighten awareness of clinicians to nonmelanocytic lesions that defy the two-step algorithm, thus simulating melanocytic lesions dermoscopically. Seborrheic keratosis, solar lentigo, dermatofibroma, and supernumerary accessory nipple may present with network-like structures. Seborrheic keratosis, dermatofibroma, subcorneal hemorrhage, basal cell carcinoma (BCC), and cutaneous metastases of breast and other cancers may contain pigmented globules. Peripheral streaks can also be seen in seborrheic keratosis and BCC. Homogenous bluish pigmentation, simulating a blue nevus, can also be seen in benign vascular lesions, Kaposi sarcoma, radiation tattoo, and BCC. This overlap of features between melanocytic and nonmelanocytic lesions suggests that integration of all dermoscopic features in the lesion, rather than a stepwise evaluation, may facilitate reaching the correct diagnosis in select cases as outlined in this article.     

Leukotriene C4 decreases the activity of respiratory cilia in vitro

In the present study we assessed the effect of leukotriene C4 on ciliary beat frequency in vitro. Chicken tracheas were sliced into thin rings and ciliary activity was viewed microscopically. Ciliary beat frequency was measured through an optical fibre by a fast Fourier transformer analyser and recorded on an oscilloscope. Ciliary beat frequency was measured at one fixed point during 30 min at room temperature in RPMI-HEPES medium alone and in medium containing leukotriene C4 at a range of concentrations (10(-6)-10(-9) M). Our results demonstrate that leukotriene C4 (10(-7) and 10(-8) M) caused a significant decrease in ciliary beat frequency in all tracheal rings tested (mean decrease of 24%). The specificity and Ca2(+)-dependency of leukotriene C4 activity was elucidated by the ability of FPL 55712 (SRS-A specific antagonist), Ca2(+)-free medium, calcium channel blockers (nifedipine and verapamil) and the calmodulin inhibitor trifluroperazine to abrogate its effect on ciliary beating.     

Ion Channel Mechanisms Related to Sudden Cardiac Death in Phenotype‐Negative Long‐QT Syndrome Genotype–Phenotype Correlations of the KCNQ1(S349W) Mutation

Phenotype‐Negative LQTS. Background: Data regarding possible ion channel mechanisms that predispose to ventricular tachyarrhythmias in patients with phenotype‐negative long‐QT syndrome (LQTS) are limited. Methods and Results: We carried out cellular expression studies for the S349W mutation in the KCNQ1 channel, which was identified in 15 patients from the International LQTS Registry who experienced a high rate of cardiac events despite lack of significant QTc prolongation. The clinical outcome of S349W mutation carriers was compared with that of QTc‐matched carriers of haploinsufficient missense (n = 30) and nonsense (n = 45) KCNQ1 mutations. The channels containing the mutant S349W subunit showed a mild reduction in current (<50%), in the haploinsuficient range, with an increase in maximal conductance compared with wild‐type channels. In contrast, expression of the S349W mutant subunit produced a pronounced effect on both the voltage dependence of activation and the time constant of activation, while haploinsuficient channels showed no effect on either parameter. The cumulative probability of cardiac events from birth through age 20 years was significantly higher among S349W mutation carriers (58%) as compared with carriers of QTc‐matched haploinsufficent missense (21%, P = 0.004) and nonsense (25%, P = 0.01) mutations. Conclusions: The S349W mutation in the KCNQ1 potassium channel exerts a relatively mild effect on the ion channel current, whereas an increase in conductance compensates for impaired voltage activation of the channel. The changes observed in voltage activation of the channel may underlie the mechanisms predisposing to arrhythmic risk among LQTS patients with a normal‐range QTc. (J Cardiovasc Electrophysiol, Vol. 22, pp. 193‐200, February 2011)