PREPARATIVE OXIDATIVE CONVERSION OF PROTECTED PEPTIDE Cα-HYDRAZIDES INTO THE CORRESPONDING ACIDS BY N-BROMOSUCCINIMIDE

A procedure for the preparative, oxidative conversion of protected peptide hydrazides into the corresponding acids by N-bromosuccinimide is described. Purification was achieved by high performance liquid chromatography on silica gel in chloroform-alcohol-acetic acid systems. Average recovery of purified protected peptide acids was over 90%.     

PREPARATION AND PROPERTIES OF Nα-9-FLUORENYLMETHYLOXYCARBONYLAMINO ACIDS BEARING TERT.-BUTYL SIDE CHAIN PROTECTION

The preparation is described of several Nα-9-fluorenylmethyloxycarbonylamino acids and derivatives bearing tert.-butyl type side-chain protection of amine, carboxyl, guanido, hydroxyl, imidazol, and sulfhydryl functionalities. Physicochemical properties of these compounds have been determined. Cleavage of the Fmoc group by various amines appears to depend on the base strength and steric hindrance. Premature deblocking of Fmoc group by amine on solid support is very slow and may be negligible under the conditions of solid-phase synthesis.     

Role of Left Ventricular Scar and Purkinje‐Like Potentials During Mapping and Ablation of Ventricular Fibrillation in Dilated Cardiomyopathy

Background: Purkinje‐like potentials (PLPs) have been described as important contributors to initiation of ventricular fibrillation (VF) in patients with normal hearts, ischemic cardiomyopathy, and early after‐myocardial infarction. Methods: Of the 11 consecutive patients with VF storm, nonischemic cardiomyopathy (68 ± 22 years, left ventricular ejection fraction 28 ± 8%) who were given antiarrhythmic drugs and/or heart failure management, five had recurrent VF and underwent electrophysiology study (EPS) and catheter ablation. Results: At EPS, frequent monomorphic premature ventricular contractions (PVC) and/or ventricular tachycardia did not occur. With isoproterenol, VF was induced in three patients, and sustained monomorphic PVCs were induced in one patient. Three‐dimensional electroanatomical mapping using CARTO (Biosense‐Webster Inc., Diamond Bar, CA) revealed posterior wall scar in four of the five patients. PLP in sinus rhythm were recorded around the scar border in these four patients, and radiofrequency ablation targeting PLP was successfully performed at these sites. The patient without PLP did not undergo ablation. During follow‐up (12 ± 5 months), only the patient without PLP had four VF recurrences requiring implantable cardioverter‐defibrillator (ICD) shocks. Conclusion: In patients with VF and dilated cardiomyopathy, left ventricular posterior wall scar in the vicinity of the mitral annulus seems to be a common finding. Targeting PLP along the scar border zone for ablation seems to efficiently prevent VF recurrence in these patients.     

Catheter Ablation versus Standard Conventional Treatment in Patients with Left Ventricular Dysfunction and Atrial Fibrillation (CASTLE-AF) - Study Design

Background: Electrical isolation of the pulmonary veins by catheter ablation is an emerging treatment modality for the treatment of atrial fibrillation (AF) and is increasingly used in patients with heart failure.
Methods: The catheter ablation versus standard conventional treatment in patients with left ventricular dysfunction and atrial fibrillation trial (CASTLE-AF) is a randomized evaluation of ablative treatment of atrial fibrillation in patients with left ventricular dysfunction. The primary endpoint is the composite of all-cause mortality or worsening of heart failure requiring unplanned hospitalization using a time to first event analysis. Secondary endpoints are all-cause mortality, cardiovascular mortality, cerebrovascular accidents, worsening of heart failure requiring unplanned hospitalization, unplanned hospitalization due to cardiovascular reason, all-cause hospitalization, quality of life, number of therapies (shock and antitachycardia pacing) delivered by the implantable cardioverter-defibrillator (ICD), time to first ICD therapy, number of device-detected ventricular tachycardia and ventricular fibrillation episodes, AF burden, AF free interval, left ventricular function, exercise tolerance, and percentage of right ventricular pacing. CASTLE-AF will randomize 420 patients for a minimum of 3 years at 48 sites in the United States, Europe, Australia, and South America.     

Successful Results of a Bipolar Active Fixation Lead for Atrial Application: An Interim Analysis

Adequate atrial lead performance consists of stable sensing and pacing properties. To evaluate whether the CPI 4269 bipolar lead, covered with mannitol (Sweet Tip), in the atrial position encounters these properties, we performed a prospective study of this lead. After complete dissolution of the mannitol helix, mapping of the atrium to obtain the highest electrogram and lowest threshold was followed by screw-in into the endocardium. Intraoperative measurements were performed and long-term follow-up was scheduled every 6 to 12 months to measure threshold and perform an intracardial electro-gram. Between February 1993 and December 1996, a total number of 73 leads in the atrial position in a consecutive series of patients was implanted. Implantation was performed in 28 patients receiving an AAIR and 45 patients a DDDR pacemaker. Reason for pacemaker implantation was a third-degree AV block in 37% of patients, type II second-degree AV block in 25%, sick sinus syndrome in 35%, and drug refractory paroxysmal atrial fibrillation following His-bundle ablation in 3%. The intraoperative bipolar atrial electrogram had a mean voltage of 4.25 ± 2.1 mV. The acute atrial bipolar threshold was 0.63 ± 0.43 V, and current was 1.35 ± 0.81 mA at a 1.0-ms pulse duration. The mean acute resistance of the lead was 572 ± 86 Ohm. After a mean follow-up of 18.3 months, the bipolar intracardial electrogram was 3.37 ± 2.00 mV, the mean atrial threshold measured at the last outpatient clinic visit was 0.99 ± 0.74 V and the mean impedance was 640 ±127 Ohm. A sensing problem due to traction of the atrial lead occurred in only one patient. Acute and late dislodgement did not occur. The CPI 4269 (Sweet Tip) lead is manufactured with a dissolvable capsule covering the helix tip electrode, permitting a safe passage through the venous system. This interim analysis shows that this lead in the atrial position has favorable acute and chronic results.     

Long-term follow-up of leukaemia patients after related cryopreserved allogeneic bone marrow transplantation

We have previously shown that allogeneic bone marrow transplantation (BMT) with cryopreserved donor marrow cells can be used without prolonging the engraftment time or interfering with the reconstitution of haemopoiesis. In this report we extend our initial observations of the first 40 patients who underwent allogeneic bone marrow transplantation from related donors with cryopreserved donor bone marrow for haematological malignancies, including the long-term follow-up data of the previously reported patients. The outcome of these patients was compared with that of 40 related BMT recipients receiving fresh donor bone marrow (historic control group). Time until engraftment of all patients receiving cryopreserved bone marrow was not different from the control group (ANC > 0.5 × 10⁹/l 17 d (range 11–24 d) versus 17.5 d (range 10–28 d); platelets > 20 × 10⁹/l 21 d (range 11–85 d) versus 22 d (range 13–69 d), respectively). There was the same incidence of acute and chronic GvHD in patients receiving either cryopreserved bone marrow or fresh bone marrow (acute GvHD ≥ II 61% v 60% and chronic GvHD 56% v 52%, respectively). Chimaerism studies showed no difference between the patient groups. Furthermore, the two groups did not differ in day 100 survival (82% v 72%). With a median follow-up of 520 d (range 47–1365 d) and 1289 d (range 48–1849 d), 60% of the patients receiving cryopreserved and 53% of the patients receiving fresh allogeneic donor bone marrow, respectively, are alive. We conclude that cryopreservation of allogeneic related donor bone marrow does not adversely affect engraftment, does not decrease the incidence of severe acute GvHD, and does not seem to affect the day 100 survival or long-term haemopoiesis.