Successful treatment of pyoderma gangrenosum with intravenous human immunoglobulin.
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Adult↗
Biomedical subjects
S Behrens
Publications and source records attributed to S Behrens.
Kinetics of photosensitivity in bath-PUVA photochemotherapy.
BACKGROUND: Bath-PUVA is used to treat a variety of dermatoses. However, the kinetics of 8-methoxypsoralen during treatment are not completely clarified. OBJECTIVE: The purpose of this study was to investigate the intensity of the phototoxic response and the persistence of phototoxicity after bath-PUVA. METHODS: Twelve volunteers were exposed to UVA doses ranging from 0.5 to 40 J/cm2 from 10 to 240 minutes after bath-PUVA treatment. The resulting phototoxic response of the skin was determined. RESULTS: Irradiation 10 minutes after the psoralen bath led to the lowest assessed minimal phototoxic dose (MPD) of 1.42 J/cm2 (mean, SD +/- 0.29). Thereafter, the MPD increased significantly and sharply every hour. At 4 hours after the psoralen bath, UVA doses up to 40 J/cm2 failed to induce any phototoxic erythema (MPD). CONCLUSION: For optimal effects, UVA irradiation has to be administered immediately after the psoralen bath; no restrictive behavior is necessary after bath-PUVA treatment.
Adult↗
Disseminated pagetoid reticulosis: response to bath PUVA.
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Adult↗
Causes and consequences of the gender difference in age at onset of schizophrenia.
The ABC (age, beginning, course) schizophrenia study was commenced in 1987 to generate and test hypotheses about pathogenic aspects of schizophrenia. One of the main branches of the study focused on how gender influences the age distribution of onset, symptomatology, illness behavior, and early course in schizophrenia. Proceeding from one of the rare, strikingly deviating, consistent findings--the gender difference in age at first admission--we launched a systematic search for explanations by generating and testing hypotheses in a series of substudies. We moved from the epidemiological to the neurobiological and finally to the clinical level. The present article is an attempt to provide a brief overview of the individual stages of the ABC study and the different levels of investigation involved in formulating and testing the estrogen hypothesis in animal experiments and in demonstrating its applicability to human schizophrenia. From these results, three hypotheses were formulated and tested on data from an ABC study sample of 232 first-episode cases of schizophrenia. The analyses described here represent the latest stages of the ABC study.
Adolescent↗
Dispersion of ventricular repolarization in the voltage domain.
Dispersion of ventricular repolarization, assessed as QT dispersion in the ECG or by multiple monophasic action potential (MAP) recordings, is defined as the difference between the earliest and latest repolarization. It is thus measured in the time domain. However, myocardial refractoriness is primarily a function of the membrane potential during phase 3 repolarization. The purpose of this study, therefore, was to measure dispersion of ventricular repolarization in the voltage domain and to study its relation to VF inducibility. To further validate this concept, the effect of chronic amiodarone treatment on the voltage dispersion were assessed. MAPs were recorded simultaneously at 10 epicardial and endocardial sites in isolated rabbit hearts, both under baseline conditions (n = 8) and after chronic amiodarone treatment (n = 8). Repolarization dispersion in the voltage domain was calculated as the difference between the highest and lowest repolarization level of all 10 MAPs at 10-ms steps, starting from the MAP plateau level to complete repolarization. Plotting these voltage differences along the time axis resulted in a dispersion curve, which rose during early repolarization, reached a peak during phase 3 repolarization, and thereafter declined toward zero. There was a close correlation between VF vulnerability in response to electrical field stimuli and the time during which voltage dispersion was maximal (r = 0.828, P < 0.0001). Amiodarone caused a right-ward shift of both the dispersion curve (P = 0.007) and VF vulnerability (P = 0.025), but did not change the magnitude nor the shape of the voltage dispersion curve and its relation to VF vulnerability. Repolarization dispersion in the voltage domain describes an alternate approach for evaluating the heterogeneity of ventricular repolarization and may help to characterize arrhythmia susceptibility under experimental conditions.
Action Potentials↗
Effects of amiodarone on the circadian pattern of sudden cardiac death (Department of Veterans Affairs Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy).
Some antiarrhythmic drugs have been shown to influence the circadian pattern of sudden cardiac death (SCD). The effect of chronic amiodarone therapy on this pattern is unknown. This study determines the circadian pattern of deaths in the Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy (CHF-STAT) and compares the distribution of SCD between the amiodarone and the placebo arms of the trial. CHF-STAT was a multicenter trial that determined whether amiodarone reduces mortality in patients with heart failure and asymptomatic ventricular arrhythmias. The time of death was retrospectively analyzed in patients who died from pump failure and SCD. In patients who died suddenly, the circadian pattern of deaths was compared between patients receiving amiodarone and those receiving placebo. In CHF-STAT, 274 patients died during follow-up. The time of death was available in 65 of the 74 patients who died from pump failure, and in 96 of the 139 patients who died suddenly. There was a circadian variation of all SCDs compared with other deaths with a distinct peak during the morning (p = 0.04). A similar morning peak of sudden cardiac death was found in both the amiodarone (n = 42) and the placebo (n = 54) groups, and the overall circadian pattern did not differ between them (p = 0.16). In contrast, death from pump failure occurred equally distributed over time. Thus, SCD occurs predominantly during the morning, whereas death from heart failure does not exhibit a morning peak. Amiodarone does not influence the circadian pattern of SCD.
Aged↗
Effects of myocardial ischemia on ventricular fibrillation inducibility and defibrillation efficacy.
OBJECTIVES: This study investigated the effects of acute global ischemia on the vulnerable window, the upper limit of vulnerability and the defibrillation threshold. BACKGROUND: Myocardial ischemia, an important factor for arrhythmogenesis and sudden death, may affect the inducibility of ventricular fibrillation by T wave shocks as well as the defibrillation threshold. However, studies of the effect of ischemia on the defibrillation threshold remain inconclusive, and the effect of ischemia on recently established variables of ventricular fibrillation vulnerability is still unknown. METHODS: Ten isolated, perfused rabbit hearts were immersed in a tissue bath between two shock plate electrodes. Truncated 5-ms biphasic shocks were used to determine the vulnerable window, the upper limit of vulnerability and the defibrillation threshold. Measurements were performed during baseline and at 10 to 15 min of acute ischemia induced by an 80% reduction of coronary flow. The effects of ischemia were monitored by measuring the dispersion of ventricular activation and repolarization using multiple monophasic action potential recordings. RESULTS: Acute ischemia caused an increase in dispersion of activation (baseline vs. ischemia [mean +/- SD]: 22 +/- 6 vs. 34 +/- 10 ms, p < 0.001) and dispersion of repolarization (37 +/- 16 vs. 69 +/- 29 ms, p < 0.01). The width of the vulnerable window increased from 25 +/- 22 ms during baseline to 75 +/- 26 ms during ischemia (p = 0.001). The upper limit of vulnerability (baseline vs. ischemia: 294 +/- 44 vs. 274 +/- 53 V, p = 0.21) and the defibrillation threshold (271 +/- 33 vs. 268 +/- 42 V, p = 0.74) remained unchanged during ischemia. CONCLUSIONS: Acute global ischemia caused a threefold increase in the width of the vulnerable window. This increase was associated with increased heterogeneity of ventricular activation and repolarization. Despite these marked changes, the upper limit of vulnerability and the defibrillation threshold were not affected by acute myocardial ischemia. Thus, the previously reported similarity between both measures was maintained under these adverse conditions.
Action Potentials↗
Modification of the circadian pattern of ventricular tachyarrhythmias by beta-blocker therapy.
BACKGROUND: Sudden cardiac death exhibits a circadian variation and predominantly occurs during morning hours, Beta-adrenergic antagonists have shown to blunt this morning peak. However, previous reports studying the effects of beta blockers on the circadian variation did not analyze the underlying cause of sudden cardiac death. It thus remains unclear whether ventricular tachyarrhythmias are influenced by beta-blocker therapy. HYPOTHESIS: This study tested the hypothesis that beta-blocking agents blunt the morning peak of life-threatening ventricular tachyarrhythmias. METHODS: In 87 patients who were treated and monitored with an implantable cardioverter defibrillator, the circadian distribution of ventricular tachyarrhythmias terminated by appropriate shocks was analyzed and compared in those receiving beta blockers versus those not receiving beta-blocker therapy. RESULTS: Tachyarrhythmic episodes in the absence of beta-blocker therapy (n = 344) exhibited a circadian variation with a distinct morning peak (16, 38, 28, and 18% of episodes at 0-6, 6-12, 12-18, and 18-24 h, respectively, p < 0.001). In contrast, tachyarrhythmic episodes during beta-blocker therapy (n = 104) were equally distributed over time (22, 27, 24, and 27% of episodes at 0-6, 6-12, 12-18, and 18-24 h, respectively, p = 0.95). The circadian distribution of episodes was significantly different in patients with and those without beta blockade (p < 0.05). CONCLUSION: Beta-adrenergic antagonists influence the circadian distribution of malignant ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator. The blunted morning peak of tachyarrhythmic events during beta blockade supports the hypothesis that a sympathetic surge is involved in the circadian pattern of malignant arrhythmias.
Adrenergic beta-Antagonists↗
Induction of ventricular fibrillation by T-wave field-shocks in the isolated perfused rabbit heart: role of nonuniform shock responses.
OBJECTIVES: Single electrical field shocks are able to induce ventricular fibrillation (VF) if applied during the vulnerable period. During this period, a shock can either prolong the action potential duration or induce a new action potential. Whether the occurrence of different shock responses contributes to the induction of VF has not been investigated directly in the intact heart. METHODS: In 12 isolated Langendorff-perfused rabbit hearts seven monophasic action potentials (MAPs) were recorded simultaneously during the application of 838 T-wave shocks. Post-shock repolarization was assessed by classifying the shock-induced response in each MAP recording either as a full action potential or an action potential prolongation. Heterogeneity of post-shock repolarization was defined if both response patterns were present in different MAP recordings at the same time. The heterogeneity of post-shock activation was measured as the dispersion of the post-shock activation time (PS-AT). The arrhythmogeneity of a shock was quantified as the number of rapid shock-induced repetitive responses. RESULTS: Shocks inducing nonuniform repolarization were associated with greater arrhythmogeneity than shocks inducing uniform repolarization (17.6 +/- 30.0 versus 1.6 +/- 1.1 shock-induced repetitive responses, p < 0.001). The severity of the induced arrhythmia increased gradually with increasing nonuniformity of repolarization (p < 0.01 for a 10% increase), being maximal when the shock initiated near equal numbers of both full action potentials and action potential prolongations. The induction of severe arrhythmias by T-wave shocks was also associated with a higher dispersion of PS-AT (29 +/- 14 ms for the induction of VF, 19 +/- 12 ms for non-sustained arrhythmia, and 12 +/- 8 ms for no arrhythmic response, all p < 0.001). For VF inducing shocks, an increase in shock strength towards the upper limit of vulnerability decreased the dispersion of PS-AT from 34 +/- 15 ms to 23 +/- 11 ms (p < 0.001). CONCLUSIONS: Nonuniform post-shock repolarization and dispersed post-shock activation contribute to the induction of VF by T-wave shocks. A decreasing dispersion of PS-AT towards higher shock strengths may contribute to the decreased or abolished inducibility by shocks above the upper limit of vulnerability.
Action Potentials↗
[PUVA-bath photochemotherapy in Hallopeau's acrodermatitis continua suppurativa].
A 73-year-old man presented with severe, relapsing acrodermatitis continua of Hallopeau, which had been resistant to prior local and systemic therapy for eight years. The patient was treated with selective hand PUVA-bath photochemotherapy. The cumulative dose of UVA used over 10 weeks of treatment was 54.6 J/cm2 on the palms and 26.8 J/cm2 on the dorsum of the hands. The single UVA doses ranged from 0.5 to 2.5 J/cm2 on the palms and 0.2 to 1.4 J/cm2 on the dorsum of the hands. After 16 treatment sessions, the acrodermatitis continua started to improve, and after 24 treatments, had cleared completely. In the four months following the PUVA therapy, there was no relapse. PUVA-bath photochemotherapy is an efficient therapeutic alternative in the treatment of acrodermatitis continua due to its clinical effectiveness and lack of any systemic side effects. It also possesses the advantage of allowing selective photosensitization of certain areas of the skin such as the hands.
Acrodermatitis↗
Effects of long-term amiodarone treatment on ventricular-fibrillation vulnerability and defibrillation efficacy in response to monophasic and biphasic shocks.
Antiarrhythmic drugs, most notably amiodarone, are often used to combat life-threatening tachyarrhythmias simultaneous with implantable cardioverter defibrillators. However, the effects of long-term amiodarone treatment on ventricular fibrillation (VF) vulnerability and the defibrillation threshold (DFT) remain incompletely understood. VF vulnerability and the DFF for monophasic and biphasic shocks were studied in 10 isolated perfused hearts of rabbits treated over the long term with amiodarone (50 mg/kg/day orally for 28 days) before the experiment. The results were compared with those of a control group (n = 10). Monophasic action potentials were recorded from 10 sites simultaneously to determine ventricular activation and repolarization. Myocardial tissue concentrations were 17.1 +/- 14.8 microg/g for amiodarone and 4.6 +/- 4.4 microg/g for desethylamiodarone. Amiodarone treatment prolonged action-potential duration by 12.9 ms (p = 0.025) and ventricular repolarization by 16.5 ms (p = 0.03) without changing ventricular activation and dispersion of repolarization. Amiodarone treatment caused a rightward shift of the vulnerable window for monophasic and biphasic shocks by 13-17 ms (p < 0.05). The width of the vulnerable window, the upper (ULV) and lower (LLV) limits of VF vulnerability, and the DFT remained unchanged. The fact that ULV and DFT remained unchanged suggests that the ULV still may be valid surrogate for the DFT during long-term amiodarone therapy.
Amiodarone↗
Timing of the upper limit of vulnerability is different for monophasic and biphasic shocks: implications for the determination of the defibrillation threshold.
The upper limit of vulnerability (ULV) has been used in clinical studies to predict the DFT in patients with ICDs. Despite the ULV-DFT correlation, uncertainties about the optimal timing of the ULV determination remain. Previous studies using monophasic or biphasic shock waveforms reported differences in the ULV timing with respect to the electrocardiographic T wave. The purpose of this study was to directly compare the ULV timing for mono- versus biphasic T wave shocks. In ten isolated rabbit hearts, mono- and biphasic shocks were delivered randomly during the vulnerable window and at varying shock strengths to determine the ULV. The ULV timing was expressed as the coupling interval at the ULV, the myocardial repolarization state at the ULV measured by monophasic action potential recordings, and the relation between the ULV and the peak of the simultaneously recorded volume conducted T wave. The ULV for biphasic shocks occurred at longer coupling intervals than for monophasic shocks (188.0 +/- 9.5 ms vs 173.5 +/- 8.8 ms, P < 0.001). This resulted in a more repolarized myocardial state at the ULV for biphasic than for monophasic shocks (81.1% +/- 7.5% vs 66.9% +/- 9.0%, P = 0.002). The ULV for monophasic shocks occurred predominantly during the upslope of the T wave (8.0 +/- 9.7 ms before the peak of the T wave) whereas the ULV for biphasic shocks occurred at or after the peak of the T wave (5.9 +/- 9.3 ms after the peak of the T wave) (P < 0.001). Biphasic shocks delay the timing of the ULV as compared to monophasic shocks. This is important for the prediction of the DFT by ULV measurements.
Action Potentials↗
Risk of ventricular arrhythmias in survivors of myocardial infarction.
The most recent studies have made it clear that the prognosis of asymptomatic post-MI patients has significantly improved in the last two decades. Holter monitoring as well as a low LVEF still is an important method for the risk stratification in the thrombolytic era of patients with post-MI. Patients with normal noninvasive tests do have a good prognosis. The electrophysiological stimulation seems to be the clinically most valuable single method to predict arrhythmic events. However, as an invasive procedure it is not suitable as a screening test for a large cohort. The stepwise risk stratification technique using first noninvasive followed by invasive procedures seem to be most suitable and effective for identifying asymptomatic infarct survivors which incidence of arrhythmic events is as high as the recurrence rate of patients who had been resuscitated from ventricular fibrillation. Consequently, prophylactic implantation of a defibrillator in asymptomatic MI patients, whose positive predictive value is around 30% becomes more and more interesting.
Arrhythmias, Cardiac↗
Shock-induced dispersion of ventricular repolarization: implications for the induction of ventricular fibrillation and the upper limit of vulnerability.
INTRODUCTION: Shock-induced dispersion of ventricular repolarization (SIDR) caused by an electrical field stimulus has been suggested as a mechanism of ventricular fibrillation (VF) induction; however, this hypothesis has not been studied systematically in the intact heart. Likewise, the mechanism underlying the upper (ULV) and lower (LLV) limit of vulnerability remains unclear. METHODS AND RESULTS: In eight Langendorff-perfused rabbit hearts, monophasic action potentials were recorded simultaneously from ten different sites of both ventricles. Truncated biphasic T wave shocks were randomly delivered at various coupling intervals and strengths, exceeding the vulnerable window, ULV, and LLV, SIDR, defined as the difference between the longest and shortest postshock repolarization times, was 64 +/- 15 msec for shocks inducing VF. SIDR was 41 +/- 17 msec for shocks delivered above the ULV, and 33 +/- 14 and 27 +/- 8 msec for shocks delivered 10 msec before and after the vulnerable window, respectively (all P < 0.01 vs VF-inducing shocks). Although SIDR was larger for shocks delivered below the LLV (93 +/- 24 msec, P < 0.01 vs VF-inducing shocks), the repolarization extension was significantly smaller for shocks below the LLV (10.3% +/- 3.9% vs 16.3% +/- 4.9%, P < 0.01). CONCLUSION: SIDR is influenced by the shock timing and intensity. Large SIDR within the vulnerable window and an SIDR decrease toward its borders suggest that SIDR is essential for VF induction. The decrease in SIDR toward greater shock strengths may explain the ULV. Small repolarization extension for shocks below the LLV may explain why these shocks, despite producing large SIDR, fail to induce VF.
Action Potentials↗
Electrophysiologic features of torsades de pointes: insights from a new isolated rabbit heart model.
INTRODUCTION: The exact electrophysiologic mechanism of torsades de pointes (TdP) is under intense investigation. No isolated animal heart model of this particular arrhythmia exists. METHODS AND RESULTS: In isolated rabbit hearts, TdP was induced by means of bradycardia in the presence of a high concentration of d-sotalol (10(-4) M) and shortly after lowering the concentration of potassium and magnesium in the perfusate. Multiple simultaneous epicardial and endocardial monophasic action potentials (MAPs) and volume-conducted 12-lead ECGs were recorded. d-Sotalol prolonged repolarization and increased dispersion of ventricular repolarization compared to baseline recordings. With the onset of low potassium and magnesium concentrations, repolarization was further prolonged and dispersion of repolarization was further increased followed by the occurrence of early afterdepolarizations (EADs) in the majority of MAP recordings, i.e., at both endocardial and epicardial locations of both ventricles. Upon increase of EAD amplitude, triggered arrhythmias with TdP of up to 42 beats ensued in 10 of 11 hearts studied. MAP duration at 90% repolarization (APD90), dispersion of APD90, and the incidence of EADs as well as dispersion of the QT interval and T wave area were significantly higher in beats triggering bigemini, couplets, or runs of TdP. CONCLUSION: TdP observed in this new isolated heart model was associated with markedly increased dispersion of ventricular repolarization and the occurrence of EADs in multiple locations of the heart. TdP is initiated when the amplitude of an EAD reaches threshold for initiation of the first beat of an episode.
Action Potentials↗
Differential effects of D-sotalol, quinidine, and amiodarone on dispersion of ventricular repolarization in the isolated rabbit heart.
INTRODUCTION: Increased dispersion of ventricular repolarization has been suggested as a cause of proarrhythmic effects of Class IA or III antiarrhythmic drugs, such as d-sotalol, quinidine, and amiodarone. METHODS AND RESULTS: The influence of d-sotalol, quinidine, and amiodarone on the dispersion of monophasic action potential (MAP) durations was studied in 55 isolated Langendorff-perfused rabbit hearts at different pacing cycle lengths (CLs). MAP duration measured at 90% repolarization (APD90) was determined from 6 to 8 endocardial and epicardial MAP recordings with dispersion of ventricular repolarization defined as the range of APD90. The protocol was repeated 60 minutes after initiation of a perfusate containing increasing concentrations of d-sotalol (n = 12, 10[-6] M, 10[-5] M, and 5 x 10[-5] M) and quinidine (n = 8, 10[-6] M and 10[-5] M). Seventeen rabbits were fed with an aqueous solution of amiodarone (50 mg/kg per day over 4 weeks). The data of these experiments (n = 17) were compared with a series of 18 untreated control rabbits. Dispersion of ventricular repolarization was unchanged with the low concentration of d-sotalol (10[-6] M) but was increased-particularly at long CLs-with higher d-sotalol concentrations. With both concentrations of quinidine, dispersion of ventricular repolarization was increased in a rate-independent manner. Amiodarone did not affect dispersion of ventricular repolarization. CONCLUSIONS: Rate-dependent and concentration-dependent increases in dispersion of ventricular repolarization by d-sotalol and quinidine in this isolated rabbit heart model may help explain their proarrhythmic effects while the absence of an increase in dispersion of ventricular repolarization with amiodarone correlates with its clinically observed lower incidence of proarrhythmia.
Action Potentials↗
Reduced arrhythmogenicity of biphasic versus monophasic T-wave shocks. Implications for defibrillation efficacy.
BACKGROUND: Biphasic waveforms defibrillate more effectively than monophasic waveforms; however, the mechanism remains unknown. The "upper-limit-of-vulnerability" hypothesis of defibrillation suggests that unsuccessful defibrillation is due to reinduction of ventricular fibrillation (VF). Thus, VF induction mechanisms may be important for the understanding of defibrillation mechanisms. We therefore compared myocardial VF vulnerability for monophasic versus biphasic shocks. METHODS AND RESULTS: In 10 Langendorff-perfused rabbit hearts, monophasic and biphasic T-wave shocks were randomly administered over a wide range of shock coupling intervals and shock strengths, and the two-dimensional coordinates within which VF was induced were used to calculate the area of vulnerability (AOV) for both shock waveforms. The arrhythmic response to biphasic shocks differed from that to monophasic shocks in three distinct ways: (1) the AOV was smaller (8.9 +/- 4.2 versus 13.9 +/- 6.0 area units, P < .02), (2) the transition zone between VF-inducing and nonarrhythmogenic shocks was narrower (14.7 +/- 4.8 versus 29.9 +/- 6.4 area units, P < .001), and (3) the entire AOV shifted toward longer coupling intervals (by 11.0 +/- 8.8 ms at the left border [P < .005] and 6.0 +/- 5.2 ms at the right border [P = .005] of the AOV). CONCLUSIONS: Biphasic shocks encounter a smaller AOV than monophasic shocks, a narrower transition zone from VF to no arrhythmia induction, and a lesser effectiveness in inducing VF at short coupling intervals. In keeping with the upper-limit-of-vulnerability hypothesis, these waveform-dependent differences in VF inducibility might help explain the lower defibrillation threshold for biphasic shocks.
Animals↗