Peptide formation in the presence of metal ion protecting groups

A quantitative study of the degree of racemization induced by the [(NH₃)₅Co-(III)-] protecting group when bound to the C-terminal of the amino acids Leu, Phe, and His, as has been carried out. Racemization was determined by forming the diastereomeric cobalt dipeptides [(Leu)(AA)Co(III)(NH3)₅] where AA = L-Leu, L-Phe, and L-His; after cobalt removal (using NaBH₄), the peptide diastereomers were analyzed quantitatively using an amino acid analyzer. No racemization was observed within experimental error (0.3%) as a result of the substitution of the [(NH3)₅Co(III)-] group on the amino acids and peptides studied.     

Temperature-controlled Radiofrequency Catheter Ablation of Accessory Pathways and Atrioventricular Nodal Reentrant Tachycardia: The 5-French Catheter Approach

Ablation with Temperature-Controlled 5-French Catheters. Introduction: In the present study, we assessed the feasibility of radiofrequency (RF) ablation of accessory pathways and AV nodal reentrant tachycardias with novel 5-French catheters with 4-mm tip electrodes using established mapping criteria and temperature-controlled power output control. Methods and Results: In this prospective study, 60 consecutive adult patients (mean age 36 ± 20 years) with accessory pathways (n = 37; 24 left-sided) or AV nodal reentrant tachycardia (n = 23) underwent RF catheter ablation. A 5-French catheter with a 4-mm tip electrode and an embedded thermistor was used for RF application. The surface of the tip electrodes was 26 mm2 compared to 38 mm² of 7-French catheters with 4-mm tip electrodes from the same catheter series. Power output was automatically and continuously adjusted according to the preset catheter tip temperature of 60° to 70°C. Pulse duration was 90 seconds. For left-sided accessory pathways, the retrograde route via the femoral artery was used. After removing the 5-French sheaths, only 4 hours of bed rest were advised. For ablation of AV nodal reentrant tachycardia, the so-called slow pathway was targeted for ablation. Acute success was achieved in 34 (92%) of 37 patients with accessory pathways and 23 (100%) of 23 patients with AV nodal reentrant tachycardia. A mean of 3 ± 4 RF pulses (median 2 pulses; range 1 to 20 pulses) was applied. The mean fluoroscopy time was 26 ± 21 minutes. No complete AV block or other procedure-related complications were observed. Recurrences occurred in 2 patients with accessory pathways and in 2 patients with AV nodal reentrant tachycardia during a follow-up of 9 ± 4 months. Conclusions: Temperature-controlled RF ablation of accessory pathways and AV nodal reentrant tachycardia in adults using 5-French catheters is feasible, effective, and safe. Ablation with 5-French catheters might help to reduce the complication rate of catheter ablation techniques.     

Radiofrequency Catheter Ablation of Idiopathic Left Ventricular Tachycardia:

Idiopathic Left Ventricular Tachycardia. Introduction: Idiopathic left ventricular tachycardia with a QRS pattern of right bundle branch block and left-axis deviation constitutes a rare but electrophysiologically distinct arrhythmia entity. The underlying mechanism of this tachycardia, however, is still a matter of controversy. This report describes findings in a 42-year-old man who underwent successful radiofrequency catheter ablation of idiopathic left ventricular tachycardia.
Methods and Results: On electrophysiologic study, the tachycardia was reproducibly induced and terminated with double ventricular extrastimuli. Intravenous verapamil terminated the tachycardia whereas adenosine did not. Detailed left ventricular catheter mapping during sinus rhythm revealed a fragmented delayed potential at the mid-apical region of the inferior site near the posterior fascicle of the left bundle branch. At the same site, continuous electrical activity throughout the entire cardiac cycle was recorded during ventricular tachycardia. Repeated spontaneous termination of this continuous electrical activity in late diastole was followed immediately by termination of the tachycardia. Single application of radiofrequency current for 20 seconds at this site completely abolished inducibility of the tachycardia. After catheter ablation, at the identical site of preablation recording of the fractionated potential during sinus rhythm, no fragmented delayed activity could be recorded. There was no complication from the ablation procedure.
Conclusion: The preablation recordings of fragmented delayed potentials during sinus rhythm and continuous diastolic electrical activity during tachycardia, together with ablation characteristics and previously reported electrophysiologic properties of this arrhythmia, may further support microreentry as the underlying mechanism in idiopathic left ventricular tachycardia.     

Anaphylactoid reactions to infusions of plasma protein and human serum albumin Role of aggregated proteins and of stabilizers added during production

Six patients suffering from anaphylactoid reactions after infusion of pasteurized plasma (PP) or human serum albumin (HSA) were investigated. Clinical symptoms ranged from urticaria and hypotension to cardiac arrest. Immunoglobulin levels, especially of IgA, were normal, as were concentrations of complement factors C3, C4 and factor B. In skin and lymphocyte transformation tests patients, with the exception of one severely allergic to protein, did not react to the monomeric pure HSA. Five out of six patients reacted against HSA aggregates and three patients to the HSA modified by caprylate added as stabilizer during commercial HSA production. It is concluded that the anaphylactoid reactions developing after PP or HSA infusion result from a non-specific reaction to protein aggregates and in some cases possibly from a specific immune response to the caprylate-modified HSA.     

Atrial Arrhythmias in Long-QT Syndrome under Daily Life Conditions: A Nested Case Control Study

Background: The long-QT syndromes (LQTS) are inherited electrical cardiomyopathies characterized by prolonged ventricular repolarization and ventricular arrhythmias. Several genetic reports have associated defects in LQTS-causing genes with atrial fibrillation (AF). We therefore studied whether atrial arrhythmias occur in patients with LQTS under daily-life conditions.
Methods: We systematically assessed atrial arrhythmias in LQTS patients and matched controls using implanted defibrillators or pacemakers as monitors of atrial rhythm in a nested case-control study. Twenty-one LQTS patients (3 male; 39 ± 18 years old; 18 on β blocker, ICD therapy duration 6.3 ± 2.7 years; 4 LQT1, 6 LQT2, 2 LQT3) were matched to 21 control subjects (13 male; 50 ± 19 years old; 3 on β blocker; pacemaker therapy duration 8.5 ± 5.5 years; 19 higher-degree AV block, 2 others). LQTS patients were identified by a systematic search of the LQTS patient databases in Münster and Munich.
Results: One-third (7 of 21) of the LQTS patients developed self-terminating atrial arrhythmias (atrial cycle lengths <250 ms). Only one control patient developed a single episode of postoperative AF (P < 0.05 vs LQTS).
Conclusions: LQTS patients at high risk for ventricular arrhythmias may develop short-lasting atrial arrhythmias under daily-life conditions, suggesting that prolonged atrial repolarization may contribute to the initiation of AF.     

Modification of Atrioventricular Conduction Using a Combined Laser-Electrode Catheter

Ablation of the AV junction is an accepted technique for the management of selected supraventricular tachyarrhythmias. Radiofrequency ablation appears to be safe and effective for AV junction ablation in most patients, but the need for firm tissue contact may make it less effective for ventricular tachycardia and certain ectopic atrial tachycardias. Laser energy can also be delivered through a catheter, and thus it may be an attractive alternative energy source for ablation. A new laser-electrode catheter was developed for modification of conduction through the AV node as a model for ablation of an arrhythmia substrate. A window for delivery of continuous-wave Nd:YAG laser energy was placed between the two electrodes of a bipolar electrode catheter. In vitro studies using a matrix of power versus time were performed to determine the energy that would create lesions of the appropriate size in vivo. Using this information, advanced AV block was successfully created in 16 of 17 dogs (94%) with the laser-electrode catheter. Advanced AV block was successfully created in all four dogs in the chronic study, and it persisted for 1-24 weeks of follow-up until sacrifice of the animals. Histologic examination demonstrated discrete thermal damage at the AV junction with no instances of septal perforation in the acute studies or progressive necrosis in chronically maintained dogs. Advanced AV block may be produced consistently and safely in dogs using a combined laser-electrode catheter.     

Normalization of enhanced hepatic gluconeogenesis by the antiglucocorticoid RU 38486 in acutely uraemic rats

Hepatic amino acid uptake, urea and glucose production are increased in acute uraemia. It has been shown that this metabolic pattern is mediated by glucocorticoids. Accordingly, the administration of the antiglucocorticoid RU 38486 to acutely uraemic rats resulted in a reduction of serum urea-N and glucose levels. To clarify whether this effect is due to a reduction in hepatic gluconeogenesis we examined the effect of the antiglucocorticoid RU 38486 on urea and glucose formation in isolated hepatocytes from sham-operated (SHAM) and bilaterally nephrectomized (BNX) rats receiving RU 38486 or the vehicle only. Hepatic glucose production in BNX rats was considerably increased from Na-pyruvate (+79%), alanine (+174%), glutamine (+158%), and serine (+87%) compared with SHAM animals. Concomitantly, hepatic urea formation was also enhanced from amino acid substrates in acutely uraemic rats. When uraemic animals were treated with RU 38486, glucose production from amino acids and Na-pyruvate was reduced to the range of SHAM animals or even lower. This effect could not be demonstrated in SHAM-operated controls. A comparable decrement in hepatic urea production was observed in BNX rats treated with the antiglucocorticoid. Thus, glucocorticoids appear to play a key role in the abnormal hepatic urea and glucose production of acutely uraemic rats.     

Clinical Experience with an Activity Sensing Pacemaker

During clinical evaluation of the Medtronic * Activitrax pacemaker in a worldwide multicenter study, implant and follow-up data were provided by 61 investigators on 222 patients. Pacing indications included two- and three-degree AV block in 149 and atrial arrhythmias in 174 patients; 16 patients received atrial pacing. Average and longest documented follow-up periods were 7.5 and 16 months respectively. Paired treadmill tests, one in Activity mode and one in VVI/AAI mode, were performed by 120 patients. At peak exercise, average heart rate was 95 bpm in VVI/AAI mode and 118 bpm in Activity mode (p < 0.0001). Average exercise time was 9.4 minutes in VVI/AAI mode and 10.8 minutes in Activity mode (p < 0.0001). In 54 patients who exclusively had paced rhythm during both treadmill tests, average heart rates and exercise times were 70 ppm and 8.1 minutes in VVI/AAI mode and 111 ppm and 10.3 minutes in Activity mode respectively (p < 0.0001). 24-hour Holter recordings typically demonstrated pacing at or near basic rate during periods of rest and appropriate increase in pacing rate during daily activities. Patients had significantly fewer problems with physical effort in daily life during a week of Activity mode pacing than during a week of VVI/AAI mode pacing (p < 0.05) as assessed from the symptom scores recorded by 62 patients in special diaries.