A new enkephalin analogue: trans-4-hydroxycinnamoyl-glycyl-glycyl-phenylalanyl-leucine. Synthesis and biological properties

A new analogue of the leucine-enkephalin in which the N -terminal tyrosine has been replaced by trans -4-hydroxycinnamic acid, has been synthetized by liquid-phase coupling methods. The central cardiovascular effects of this analogue were investigated and the results discussed.     

DOWN THE ROAD TO DEREGULATION

A recent preliminary ruling by the European Court of Justice,that would have ended the Swedish state retail alcohol monopolyon grounds of European law on free movement of goods, highlightsthe international pressure on countries to deregulate furthertheir alcohol markets. However, those countries that have recentlytaken the road to deregulation have not been able to preventthe alcohol industry encouraging people to drink more and theyare experiencing increased alcohol-related problems. The internationaldebates about tradable commodities rarely take account of theconsequences for public health. Alcohol is one such commoditythat is also an important cause of premature death. It is essentialthat this is not overlooked in the race to promote free trade.     

Prevention of Atrial Arrhythmias during DDD Pacing by Atrial Overdrive

We evaluated the effect of atrial overdrive on the incidence of atrial arrhythmias (AA) in 22 patients (67 ± 9 years. 7 women, 15 men) with Chorus 6234 DDD pacemakers. Atrial overdrive was defined as a programmed paced rate 10 ppm faster than the mean ventricular rate stored for the last 24-hour period in the pacemaker memory. The protocol consisted of three phases of 1 month each. Phase I: observation after discontinuation of antiarrhythmic therapy. Phase II: arrhythmia analysis using the pacemaker memory after programming the lower rate to 55 ppm. The fallback function and histogram data were used to document the number and maximal duration of AA episodes as well as the total AA time in a month. Phase III: atrial overdrive. The mean ventricular heart rate was 65 ± 4 beats/min before atrial overdrive versus 75 ± 5 with atrial overdrive (P = 0.02). At the end of phase II, all patients presented with AA episodes (mean number per patient: 42 ± 78 in one month). In phase III (with atrial overdrive), 14 (64.6%) patients had no recorded AA (group A). In the other eight patients with persistent AA episodes in phase III (group B), there was a significant reduction in the number of AA episodes (90 ± 106 in phase II vs 38 ± 87 in phase III; P = 0.01), their total duration (166 ± 115 in phase II vs 92 ± 134 hours in phase HI; P = 0.03) and their maximal duration (121 ± 103 in phase II vs 85 ± 89 min; P = 0.04). Our short-term data suggest tliat atrial overdrive prevents or reduces A A episodes and demonstrate the feasibility and need of long-term studies to determine whether this benefit is sustained.     

Abnormal Nocturnal Heart Rate Variability and QT Dynamics in Patients with Brugada Syndrome

Background: In Brugada syndrome (BSY), most of the ventricular arrhythmic events are nocturnal, suggesting an influence of the autonomic nervous system.
Methods: In 46 patients (mean age = 41 ± 14 years, 43 men) with electrocardiograms (ECG) consistent with BSY and structurally normal hearts, we measured heart rate variability (HRV) and QT dynamics (QT/RR slopes) on 24-hour ambulatory ECG. Type 1 BSY-ECG was spontaneous in 23 (50%) and induced in 23 patients.
Results: History of syncope was present in 23 patients (50%). Programmed ventricular stimulation induced ventricular tachyarrhythmias (VTA) in 13 patients (28%). A single patient developed ventricular tachycardia during a mean follow-up of 34 months. Compared to a control group matched for age and sex, HRV was decreased over 24 hours and during nighttime in patients with BSY (SDNN 122 ± 44 vs 93 ± 36 ms, P = 0.0008 and SDANN 88 ± 39 vs 54 ± 24 ms, P < 0.0001). QTend /RR slopes were decreased over 24 hours in patients with BSY (0.159 ± 0.05 vs 0.127 ± 0.05, P = 0.003) and particularly at night (0.123 ± 0.04 vs 0.089 ± 0.04, P = 0.0001). QTend /RR slopes were significantly decreased during nighttime in patients with spontaneous versus provoked BSY-ECG patterns. By contrast, HRV and QT/RR slopes were similar in symptomatic and asymptomatic patients, whether VTA were induced or not.
Conclusions: Patients with a BSY-ECG pattern had lower HRV and QT/RR slopes than control subjects during nighttime. High-risk patients with spontaneous BSY-ECG patterns had the lowest nocturnal QTend/RR slopes. These unique repolarization dynamics might be related to the frequent nocturnal occurrence of VTA in BSY.     

EXTRAPERITONEAL LAPAROSCOPIC PYELOPLASTY: A MULTICENTER STUDY OF 55 PROCEDURES

PURPOSE: We assessed the feasibility, reproducibility and morbidity of retroperitoneal laparoscopic pyeloplasty for ureteropelvic junction obstruction. MATERIALS AND METHODS: A total of 55 retroperitoneal laparoscopic pyeloplasties were performed at 3 institutions between September 1996 and May 2000 in 33 women and 21 men. Results were analyzed in regard to radiological assessment by excretory urography at 3 months, complications and hospital stay. RESULTS: We performed dismembered pyeloplasty in 48 cases and Fenger plasty in 7 cases. Crossing vessels were noted in 23 patients. The conversion rate was 5.4%. Mean operative time was 185 minutes (range 100 to 260), mean hospital stay was 4.5 days (range 1 to 14) and mean followup was 14.4 months (range 6 to 43.6). The overall complication rate was 12.7%. Complications in 7 patients included hematoma in 3, urinoma in 1, severe pyelonephritis in 1 and anastomotic stricture in 2 requiring open pyeloplasty at 3 weeks and delayed balloon incision at 13 months, respectively. Excretory urography in 50 patients and ultrasound in 4 showed decreased hydronephrosis in 88.9% at 3 months. Normal physical activity and absent pain were reported by 47 patients (87%) 1 month after surgery. CONCLUSIONS: Retroperitoneal laparoscopic pyeloplasty seems to be a valuable alternative to open pyeloplasty for ureteropelvic junction obstruction. The long-term outcome must be assessed before this procedure may be definitively validated.     

Addition of morphine to intra-articular bupivacaine does not improve analgesia after day-case arthroscopy

We conducted a randomized, double-blind, controlled study inpatients undergoing day-case knee arthroscopy to evaluate theanalgesic effect, for 36 h after operation, of the additionof either 2 mg or 5 mg of morphine to intra-articular bupivacaine.Patients in group BM5 (n = 20) received 0.25% bupivacaine 40ml with morphine 5 mg; patients in group BM2 (n = 20) received0.25% bupivacaine 40 ml with morphine 2 mg and patients in groupB0 (n = 18) received 0.25% bupivacaine 40 ml only. The drugswere given by intra-articular injection by the surgeon at theend of the operation and the tourniquet released 70 min later.Preoperative and postoperative pain was assessed over the ensuing36 h, at rest and with movement, using a 100-mm visual analoguescale. There were no significant differences in pain scores,consumption of additional analgesia, or time to first requestfor analgesia between any of the groups. We conclude that, afterday-case knee arthroscopy, no additional analgesic effect wasafforded by the addition of morphine to intra-articular bupivacaine. Present addresses: Department of Anaesthesia, Leicester RoyalInfirmary, Leicester LE1 5WW     

Ventricular Proarrhythmic Effects of Atrial Fibrillation are Modulated by Depolarization and Repolarization Anomalies in Patients with Left Ventricular Dysfunction

Background: Atrial fibrillation (AF) may have a ventricular proarrhythmic effect, particularly in the setting of heart failure. We assessed whether AF predicts appropriate implantable cardioverter-defibrillator (ICD) shocks in patients with left ventricular dysfunction and explored modulators of risk.
Methods and Results: A retrospective cohort study was conducted on 215 consecutive patients with ICDs for primary prevention having a left ventricular ejection fraction ≤ 35%. Mean age at ICD implantation was 61.0 ± 9.7 years and 17% were women. Overall, 22 patients (10.2%) experienced appropriate ICD shocks over a follow-up of 1.3 ± 0.7 years, corresponding to an actuarial event-rate of 5.8% per year. In univariate analysis, AF was associated with a 3.6-fold increased risk of appropriate shocks (P = 0.0037). Annual rates of appropriate ICD shocks in patients with and without AF were 12.9% and 3.5%, respectively (P = 0.0200). In multivariate stepwise Cox regression analyses controlling for baseline imbalances, demographic parameters, underlying heart disease, and therapy, history of AF independently predicted appropriate shocks (hazard ratio 2.7, P = 0.0278). Prolonged QRS duration (>130 ms) and QTc (>440 ms) modulated the effect of AF on appropriate shocks. Patients with both AF and QRS > 130 ms were more than five times more likely to receive an appropriate ICD shock (hazard ratio 5.4, P = 0.0396). Patients with AF and QTc > 440 ms experienced a greater than 12-fold increased risk of appropriate shocks (hazard ratio 12.7, P = 0.0177).
Conclusion: In prophylactic ICD recipients with left ventricular dysfunction, AF is associated with increased risk for ventricular tachyarrhythmias, particularly when combined with conduction and/or repolarization abnormalities.     

Transesophageal Echocardiography for the Prevention of Embolic Complications After Catheter Ablation for Atrial Fibrillation

Background: Thromboembolic complications during left-sided ablations range between 1.5 and 5.4%. Preprocedural TEE has been used to exclude the presence of left atrial thrombi in order to minimize risk. The use of TEE is empiric and it has not been evaluated in contemporary practice.
Methods and Results: A multicenter national survey describing the practice at 11 Canadian teaching hospitals. A total of 2,225 patients underwent elective catheter ablation for symptomatic AF. Transesophageal echocardiography (TEE) was used either routinely or selectively as a preablative strategy in patients. There were 996 patients in a routine preprocedure TEE strategy and 1,190 in a selected TEE strategy; 1 center (n = 39 patients) did not perform TEE. Twelve of 996 (1.2%) in the routine unselected cohort had thrombi identified. TEEs were performed in 200 of 1,190 in the selected cohort; 4 (2.0%) left atrial thrombi were observed; there was no significant difference in the prevalence of thrombi (P = 0.34). A total of 11 embolic events occurred inclusive of all groups. There was no difference in event rates between the 2 strategies (0.6% and 0.4%, P = 0.54). Events were unrelated to AF duration (persistent vs paroxysmal, r = 0.03, N = 2,225, P = 0.9).
Conclusion: The selection criteria employed to perform TEEs did not increase the chance of identifying LA thrombi in a patient cohort with primarily nondilated left atria and paroxysmal AF. The overall thromboembolic event rate was low (0.49%) and was not significantly different between the 2 TEE strategies.     

SERUM TYPE III PROCOLLAGEN PEPTIDE CONCENTRATIONS IN SYSTEMIC SCLEROSIS AND RAYNAUD'S PHENOMENON: RELATIONSHIP TO DISEASE ACTIVITY AND DURATION

Serum levels of the amino-terminal type III procollagen peptide(P-3-NP) have been used as an index of collagen synthesis. Systemicsclerosis (SS) is characterized by uncontrolled production ofcollagen of several types. This study aimed to explore the profileof P-3-NP in patients with SS and Raynaud's phenomenon, a commonforerunner of the disease. Using a radioimmunoassay, the mean level for P-3-NP was foundto be raised in SS compared with both the control (p>0.001)and Raynaud's groups (p>0.001). Analysis of serial samplesfrom the patients with SS suggested that the P-3-NP level reflectedchanging clinical activity. Three groups emerged: a group withstable disease which showed a less than 20%change in P-3-NPlevel (mean 5.7%); a group with increasing activity which showedan increase of >20%(mean 35.8%) and a group of decreasingactivity which showed a decrease of >20%(mean 33.6%). Thesedata suggest that there is an increase in collagen metabolismin SS and that changes in P-3-NP levels may reflect the clinicalcourse of the disease. KEY WORDS: Systemic sclerosis, Raynaud's, Type III procollagen peptide, Disease activity