Oral cisapride increases gallbladder volume in volunteers

It has been previously reported that intravenous application of cisapride leads to a contraction of the gallbladder. To evaluate this potential prokinetic effect cisapride was given to healthy subjects in the clinically relevant oral form. In a randomized double-blinded placebo controlled design gallbladder volumes were monitored by ultrasound. Orally given single doses above 5 mg cisapride resulted in a significant increase of gallbladder volume reaching a maximum of 176.7 ± 10.0% at 90 min after ingestion of the 40 mg dose. This effect was observed over more than 3 h. Contraction after a standard meal was significantly impaired by 20 mg cisapride (minimal residual volumes 8.4 ± 2.3% vs. 18.7 ± 3.7%; P < 0.05). Refilling of the gallbladder started significantly earlier after cisapride ingestion. The underlying mechanisms of these observations being in contrast to the prokinetic effects cisapride generally exerts on the gastrointestinal tract are still unknown.     

Ventricular Oversensing:

WERETKA, S., et al. : Ventricular Oversensing: A Study of 101 Patients Implanted with Dual Chamber Defibrillators and Two Different Lead Systems . Modern dual chamber ICD systems are able to overcome various sensing problems. However, improvement of their performance is still required. The aim of this study was to assess the sensing function in 101 consecutive patients (84 men, 17 women; mean age 63 ± 12 years; mean follow-up 24 ± 4 months) implanted with dual chamber defibrillators and integrated (IB) or dedicated bipolar (DB) lead systems. Follow-up data were analyzed for the presence of ventricular oversensing. Oversensing occurred in 25 (25%) patients, significantly more frequent in patients implanted with IB compared to DB lead systems (21/52 vs 4/49, P = 0.0002). Patients with cardiomyopathies (CMs) were more prone to sensing malfunctions than patients with no CM (12/30 vs 13/71, P = 0.04). T wave oversensing (n = 14), respirophasic ventricular oversensing (n = 4), and P wave oversensing (n = 6) were the most common pitfalls of ventricular sensing. P wave oversensing was unique to the IB lead system. CT scans performed in these patients disclosed the position of the RV coil to be proximal to the tricuspid area. Four patients received inappropriate ICD shocks due to oversensing. In all but two patients who received lead revision, oversensing was resolved by noninvasive means. In conclusion: (1) ventricular oversensing is a common problem occurring in up to 25% of patients with dual chamber ICDs; (2) P wave oversensing is a ventricular sensing problem affecting function of 11% of dual chamber devices with IB lead systems; (3) IB leads are significantly more susceptible to T wave and P wave oversensing than DB leads; and (4) patients with cardiomyopathies are more prone to oversensing than patients with other heart diseases. (PACE 2003; 26[Pt. I]:65–70)     

α-Amylases from Thermoactinomyces vulgaris: characteristics,primary structure and structure prediction

Two amylolytic active protein fractions (named α-amylase 1 and α-amylase 2) were isolated from the bacterium Thermoactinomyces vulgaris strain 94-2A. α-Amylase 1 had a molecular mass of 51.6 kDa, whereas α-amylase 2 consists of two fragments which have molecular masses of 17.0 and 34.6 kDa, respectively. These two fragments are products from a proteolytic cleavage of a-amylase 1 at amino acid position 303 (tryptophan) by a serine protease (thermitase) which is also produced by T. vulgaris. The purified α-amylase 1 and 2 follow the Michaelis-Menten kinetics in the presence of starch as substrate with K_m values of 1.37 ± 0.07 and 1.29 ± 0.18 mg/mL, respectively. In effect they differ in their stability characteristics. The amino acid sequence of α-amylase from T. vulgaris derived from DNA sequence (1) was compared with those of other α-amylases. It reveals high homologies to α-amylases from other microorganisms (e.g. B. polymyxa, A. oryzae, S. occidentalis and S.fibuligera). A three-dimensional structure model for α-amylase 1 on the basis of the 3 Å X-ray structure of Taka-amylase was constructed.     

High Resolution ECG and Left Ventricular Volume After Acute Myocardial Infarction

The presence of ventricular late potentials (LPs) early after acute myocardial infarction (AMI) was recently reported to correlate with left ventricular dilatation subsequent to AMI. We assessed prospectively the relationship between LP (time domain) in the late phase of AMI and left ventricular end-diastolic volume (EDV) measured by equilibrium radionuclide angiocardiography 4 weeks and 12 months after AMI. In 80 consecutive patients 4 weeks and 12 months after thrombolytic therapy for AMI, LP and EDV were deter mined (EDV1, EDV2). There was no significant correlation between QRS duration (r = 0.18), RMS40 (r = 0.08), or LAS40 (r = 0.1) and EDV1 or EDV2 in patients with or without LP at baseline. In both groups (patients with [n = 15] and without LP [n = 65]), EDVl and EDV2 were comparable (128 ± 32 mL vs 126 ± 35 mL; 114 ± 40 mL vs 117 ± 36 mL; P = NS). In addition, there was no significant difference between EDVl and EDV2 in patients who developed new LP (n = 6) or lost LP (n = 9) 12 months after AMI. In contrast to LP in the very early phase after AMI, there seems to be no significant correlation between the high resolution ECG in the late phase after thrombolytic therapy for AMI and left ventricular EDV.     

Far-Field R Wave Oversensing in a Dual Chamber Arrhythmia Management Device: Predisposing Factors and Practical Implications

WERETKA, S., et al. : Far-Field R Wave Oversensing in a Dual Chamber Arrhythmia Management Device: Predisposing Factors and Practical Implications. Initial experience with the Medtronic Jewel 7250, the ICD designed to detect and treat ventricular and supraventricular tachyarrhythmias, is very promising. Its effectiveness, however, depends on sensing performance, which has not yet been systematically examined. The aim of the study was to determine the incidence of, predisposing factors for, and practical implications of far-field R wave oversensing (FFRWOS) in this dual chamber ICD. During a total follow-up of 797 months in 48 patients who had the Jewel 7250, follow-up strip charts, 12-channel Holter recordings and, in particular cases, Holter recordings with intracardiac markers were analyzed for the presence of FFRWOS. FFRWOS was documented in ten (21.3%) patients. Compared to other lead locations, the right atrial appendage lead position was most frequently associated with FFRWOS (  7/27 vs 3/21, P < 0.05  ). Patients with FFRWOS had significantly more treated and nontreated atrial episodes, many of which were judged to have been detected inappropriately. In one case, inappropriate atrial antitachycardia pacing due to R wave oversensing triggered sustained ventricular tachycardia, terminated eventually with a high energy shock. In dual chamber ICDs, FFRWOS may represent a frequent phenomenon possibly leading to serious consequences. For atrial leads, a lateral atrial wall position seems to be preferable. In most cases, FFRWOS can be eliminated by optimization of atrial sensing parameters. Given the possibility of ventricular proarrhythmia with atrial pacing therapy, the capability of ventricular backup defibrillation in respective devices is at least reassuring.     

Trisomy 3 in marginal zone B-cell lymphoma: a study based on cytogenetic analysis and fluorescence in situ hybridization

Trisomy 3 represents the most frequent and consistent chromosomal abnormality characterizing the recently defined entity marginal zone B-cell lymphoma (MZBCL). By cytogenetic analysis and/or fluorescence in situ hybridization (FISH) on interphase nuclei we found an increased copy number of chromosome 3 in 22/36 (61%) successfully analysed cases, including 8/12 cases with extranodal MZBCL, 8/13 cases with nodal MZBCL, and 6/11 patients with splenic MZBCL. Sensitivity of interphase cytogenetics was somewhat higher than that of conventional cytogenetic investigation. Structural chromosomal changes involving at least one chromosome 3 were seen in 11/20 cases with an increased copy number of chromosome 3: +del(3)(p13) was demonstrated in three cases, and was the sole chromosomal abnormality in one of them; +i(3)(q10) was seen in two other patients; and rearrangements involving various breakpoints on the long arm of chromosome 3 were found in the remaining cases. FISH on metaphase spreads confirmed these structural abnormalities and additionally showed two unexpected translocations involving chromosome 3. We conclude that: (1) trisomy 3 occurs in a high proportion of extranodal, nodal and splenic MZBCL; (2) FISH on interphase nuclei is an additional and sensitive tool in detecting an increased copy number of chromosome 3 in MZBCL; (3) additional structural abnormalities involving the long arm of chromosome 3 are frequent but non-recurrent and are perhaps secondary changes; and (4) abnormalities such as +del(3)(p13) and +i(3)(q10) suggest that genes located on the long arm of chromosome 3 are of particular importance in the pathogenesis of MZBCL.     

Acute Efficacy and Chronic Follow-Up of Patients with Non-Thoracotomy Third Generation Implantahle Defibrillators

Non-thoracotomy implantation of implantable cardioverter defibrillators (ICDs) has simplified the process of device inserfion, promising to decrease associated procedural coniplications while providing sudden death protection at least equal to epicardial systems. This study presents the acute and chronic results of 110 patients who underwent attempted non-thoracotomy ICD impiuntation wiih the Medtronic Transvene lead system and PCD model 7217 or 7219. Of the 110 patients attempted, 100 (91%) had the system successfully implanted without the need for an epicar-dial patch. One patient died 1 week postoperatively of septic shock related to the implantation (0.9% perioperative mortality). During folloiv-up of 16 ± 11 months, 45% of the patients had an event detected as ventricular tachycardia; 26% of these detections were felt clinically to be due to supraventricular rhythms. Of the remainder, 87% were successfully treated with the first VT therapy, and 98% were terminated by the final therapy; 66% of the patients had at least one episode of ventricular fibrillation, of which 5% were felt to be inappropriate detections; 65% of the appropriate episodes were successfully treated with the first VF therapy, and all were converted by the final therapy. Total mortality at 6, 12, and 24 months was 3%, 11%, and 19% respectively. Only one patient had sudden cardiac death, occurring at 13 months postimplant. Overall, the non-thoracotomy lead system for this ICD displayed infrequent implant complications and proved to be reliable ai terminating arrhythmias and maintaining a low rate of sudden cardiac death in this high risk popuiation.     

Cortical correlates of semantic classical conditioning

Event-related potentials to visually displayed pseudowords were registered from 13 individuals. In a differential conditioning paradigm, half of the pseudowords had previously been paired with a painful electric shock (shock words) and the other half had been presented without shock (nonshock words). Participants were asked to decide if the words had been presented during the conditioning phase or not. Larger N100 amplitudes and a more negativegoing slow wave 400–800 ms after word presentation were found for shock as compared with nonshock words. This effect was stronger over the left than over the right hemisphere. This left-lateralized negativity might reflect the activation of a cell assembly representing the memory of the learned word-shock contingency. Furthermore, the increased N100 amplitude elicited by shock as compared with nonshock words may be interpreted as an increased attentive facilitation for aversive pain-related information as a consequence of conditioning.