Nuclear magnetic resonance structural investigations of ammonia-doped fullerides.

The dynamic and structural properties of the ammonia-doped superconducting fulleride (NH3)xNaK2C60 (0.5< or =x< or =1), well known for its anomalous decrease of transition temperature with doping, have been investigated using sodium and deuterium solid-state NMR techniques. The independence of 23Na quadrupole splitting from the ammonia content x, which, at the same time, substantially affects Tc, suggests a marginal role of the cation position in the superconducting mechanism. On the other hand, a strong reduction of the deuterium quadrupole coupling with respect to the free ammonia value denotes the presence of weak hydrogen bonds between the deuterium atoms and fullerene pi orbitals. Despite the bond weakness, as evinced by the lively ammonia rotational dynamics even at very low temperatures, the resulting electron localization could explain the observed Tc anomaly. The motion of the ND3-Na group (located in the compound's octahedral voids), as well as the evolution of the ammonia dynamics as a function of temperature, were determined from deuterium NMR line shape analysis and from detailed numerical simulations. While at the lowest measured temperatures only the ammonia rotation around its own C3 axis takes place, above approximately 25 and 70 K, respectively, also the wobbling of the C3 axis and the ND3 relocation become active, successfully modeled by a strongly correlated motion involving two different time scales.

A constitutional complex chromosome rearrangement involving meiotic arrest in an azoospermic male: case report.

Complex chromosome rearrangements are rare aberrations that frequently lead to reproductive failure and that may hinder assisted reproduction. A 25-year-old azoospermic male was studied cytogenetically with synaptonemal complex analysis of spermatocytes from a testicular biopsy and fluorescence in situ hybridization (FISH) of lymphocytes. The spermatocytes showed a pentavalent plus a univalent chromosome. Cell death occurred mainly at advanced pachytene stages. The sex chromosomes were involved in the multiple, as shown by their typical axial excrescences. Two autosomal pairs, including an acrocentric chromosome (15), were also involved in the multiple. FISH allowed the definite identification of all the involved chromosomes. An inverted chromosome 12 is translocated with most of one long arm of chromosome 15, while the centromeric piece of this chromosome 15 is translocated with Yqh, forming a small marker chromosome t(15;Y). The euchromatic part of the Y chromosome is joined to the remaining piece of chromosome 12, forming a neo-Y chromosome. The patient shows azoospermia and a normal phenotype. The disruption of spermatogenesis is hypothetically due to the extent of asynaptic segments and to sex-body association during pachytene. This CCR occurred 'de novo' during paternal spermatogenesis. Meiotic analysis and FISH are valuable diagnostic tools in these cases.

Clinical feasibility of low energy internal atrial cardioversion with a three-electrode configuration in patients with unsuccessful conventional configurations.

Low energy internal cardioversion is a safe and highly effective method for atrial fibrillation termination. We will describe 6 patients in whom the conventional 2-electrode systems with the defibrillation leads positioned in the right atrium and in the coronary sinus or left pulmonary artery failed to terminate the arrhythmia despite the use of maximal available energies. A 3-electrode configuration including right atrium, coronary sinus and left pulmonary artery was used in order to encompass as much atrial mass as possible between the cathode and the anode. The atrial fibrillation was successfully interrupted in 4 out of 6 patients. The creation of a 3-electrode configuration may be a further technical expedient in order to increase the success rate of internal cardioversion when usual manoeuvres like lead repositioning, reversion of polarity, or addition of antiarrhythmic drugs are ineffective.

Long-term reliability of single lead atrial synchronous pacing systems using closely spaced atrial dipoles: five-year experience.

To assess the long-term capability of single atrioventricular (AV) lead VDD pacing systems using close atrial dipoles to assure reliable atrial guided pacing, the safety and efficacy of 86 VDD units implanted in 73 patients at a single center since November 1988 was reviewed. All patients suffered from advanced AV block with normal sinoatrial function. Sixty five patients received a LEM/CCS Twinal 30/30S system, four patients received a Vitatron-Saphir system, and four patients received a Medtronic Thera VDR 8348 system. All patients underwent provocative tests in search of myopotential interference, and Holter recordings; in a group of patients who underwent pacemaker replacement a comparison was made between implant and replacement measurements. The mean follow-up duration was 27.3 months. A high percentage of successfully VDD paced patients and a low incidence of pacemaker malfunction, regularly solved by pacemaker reprogramming, was reported. Atrial signal amplitudes comparable to those measured at implant were found at replacement in all patients. These data support the long-term reliability of single AV lead VDD pacing systems with closely spaced atrial dipoles, as well as stable atrial sensing by floating bipolar atrial electrodes and effective atrial synchronous ventricular pacing over time.

AV delay optimization and management of DDD paced patients with dilated cardiomyopathy.

Ten DDD paced patients, suffering from dilated cardiomyopathy in the NYHA functional classes III or IV were studied by means of Doppler echocardiography at different programmed values of atrioventricular (AV) delay (200, 150, 120, 100, and 80 msec). The following variables were evaluated: LV diameter, ejection fraction, mitral and aortic flow velocity integrals, and stroke volume. During VDD pacing, a resting AV delay associated with the best diastolic filling and systolic function was identified and programmed individually. Shortening of the AV delay to about 100 msec was associated with a gradual and progressive improvement. Further decrease caused an impairment of systolic function. The patients were clinically and hemodynamically reevaluated after 2 months of follow-up. A reduction of NYHA class and an improvement of LV function were consistently found. The reported data suggest that programming of an optimal AV delay may improve myocardial function in DDD paced patients with congestive heart failure. This result may be the consequence of an optimization of left ventricular filling and a better use of the Frank-Starling law.

Single lead atrial synchronous ventricular pacing: a dream come true.

Single lead, atrial synchronous pacing systems were developed in the late 1970s. Clinical experience has demonstrated the need to position the "floating" atrial electrode in the mid-to-high right atrium and the need for a specially designed pulse generator (with very high atrial sensitivity) to provide a high quality and amplitude atrial electrogram for consistent sensing. A 12-year experience with different electrode configurations, from the first unipolar designed in 1980 to the most recent atrial bipolar electrodes, has confirmed the validity of the original concept and the long-term reliability of the single lead atrial synchronous pacing system, which can reliably produce long-term atrial sensing and ventricular stimulation in the presence of normal sinoatrial function.

Long-term effects of theophylline in atrial fibrillation with a slow ventricular response.

In 17 patients (aged 78 +/- 9 years) with symptomatic atrial fibrillation and a slow ventricular response not related to drugs, a resting electrocardiogram and 24-hour Holter recording were obtained before and 5 to 6 days after administration of slow-release theophylline (700 mg/day), and successively every 3 months during the long-term phase. Fourteen patients had organic heart disease, and 13 complained of syncope or presyncope, and 4 of asthenia and easy fatigability. At the steady-state evaluation, theophylline significantly increased resting heart rate (HR) by 42%, mean 24-hour HR by 31% and minimal 24-hour HR by 34%. Cardiac pauses > 2,500 ms disappeared or markedly decreased. The daily number of wide QRS complexes increased. Serum theophylline level was 13 +/- 5 ng/ml. During the follow-up period (20 +/- 18 months), the mean daily theophylline dosage was 450 mg and the mean serum theophylline level 9 ng/ml. Seven patients died: 1 because of heart failure, and 6 because of noncardiac death. One patient complained of a syncopal episode during 1 visit. The drug markedly reduced asthenia and easy fatigability. During the long-term phase, HR increased spontaneously in 3 patients, and the treatment was interrupted. In 2 patients, theophylline had to be discontinued because of gastric intolerance. During long-term therapy, HR was similar to that observed at the steady-state evaluation, despite the reduction in daily dosage. The data suggest that theophylline is an effective therapy in most patients with symptomatic atrial fibrillation and a slow ventricular response.

Direct and autonomically mediated effects of oral quinidine on RR/QT relation after an abrupt increase in heart rate.

OBJECTIVES: This study evaluates the direct and autonomically mediated effects of oral quinidine on ventricular repolarization in humans. BACKGROUND: Interactions between quinidine-related vagolytic properties and autonomic modulation on ventricular repolarization are unknown. The relative role of the two components, if present, might improve our understanding of the therapeutic and proarrhythmic mechanisms of quinidine on the ventricular tissue. METHODS: Rate-related changes in the QT interval were investigated after an abrupt increase in heart rate in 15 patients during atrial pacing. In the control study, the QT interval was measured at six paced cycle lengths (600, 540, 500, 460, 430 and 400 ms) both in the basal state and after autonomic blockade (intravenous propranolol, 0.2 mg/kg, and intravenous atropine, 0.04 mg/kg); oral quinidine was then administered at a daily dosage of 1,200 mg for 3 to 4 days, after which the QT duration was reassessed using the same method in a second study. RESULTS: During the control study, the mean slope of the regression curve estimating the correlation between pacing cycle length and QT duration was significantly lower after autonomic blockade (0.14 +/- 0.05) than in the basal state (0.27 +/- 0.10, p < 0.05). Quinidine exhibited a prominent but opposite effect on the mean slope of the regression curves in basal conditions (from 0.27 +/- 0.10 to 0.20 +/- 0.07, p < 0.05) and after withdrawal of autonomic modulation (from 0.14 +/- 0.05 to 0.19 +/- 0.05, p < 0.05), thus annulling the differences observed between the two states in the control study. CONCLUSIONS: A quinidine-induced increase in QT duration as cycle length is prolonged is consistent with a reverse use dependence effect on ventricular repolarization. This effect is not evident in the basal state owing to interaction of quinidine-related vagolytic effect with the autonomic tone. Reverse use dependence and vagolytic activity on ventricular tissue indicate two potentially undesirable effects that could play a role in the lack of efficacy or proarrhythmic effect of quinidine.

Italian multicenter study on a single lead VDD pacing system using a narrow atrial dipole spacing.

Since November 1988, 514 patients with advanced atrioventricular (AV) block and normal sinoatrial function have received the single lead VDD pacing system Twinal 30 Lem/CCS in 30 Italian centers. At implantation, particular attention was paid to the correct positioning of the atrial dipole in the mid- to mid-high right atrium and to the atrial electrogram characteristics. The follow-up included a chest X ray, to be performed before discharge of the patient from the hospital, telemetric evaluations of the endoatrial potential, provocative tests for interferences by myopotentials, 24-hour ambulatory EGG recordings, and where possible, exercise stress tests. The mean follow-up duration was 15.2 months, ranging from 1 to 42 months. A very low percentage of chronic atrial fibrillation, loss of atrial sensing, and system replacement was reported, most of the patients (93.5%) being paced in VDD mode. All investigations indicated an excellent overall system performance, stable AV synchrony, and infrequent myopotential interference, and a low complication rate throughout the follow-up period.

Clinical effects of oral theophylline in sick sinus syndrome.

In 17 patients with symptomatic sinus bradycardia (age: 66 +/- 11 years), a resting electrocardiogram, a 24-hour Holter recording, and a treadmill test were performed both before and after administration of slow-release theophylline (700 mg daily). The drug increased resting heart rate (46 +/- 7 versus 62 +/- 18 beats/min, p less than 0.01), mean 24-hour rate (51 +/- 6 versus 64 +/- 16 beats/min, p less than 0.01), and minimal 24-hour heart rate (36 +/- 6 versus 43 +/- 10 beats/min, p less than 0.05). Cardiac pauses greater than 2.5 seconds were present in four patients during control recording, and disappeared after theophylline. The daily number of premature supraventricular and ventricular beats increased slightly after the drug. Exercise heart rate was higher after theophylline than during the control test (p less than 0.01). Thirteen patients were followed for a period of 17 +/- 3 months. Suppression of symptoms was achieved in 12 patients. Asthenia and easy fatigue were reduced markedly by the drug. During long-term therapy, the sinus rate was similar to that observed at the steady-state evaluation. In 3 of the 17 patients theophylline had to be discontinued because of gastric intolerance (in two at the end of the steady-state evaluation and in one during long-term therapy). These data suggest that oral theophylline can represent an effective therapy in some patients with symptomatic sinus bradycardia.

Sympathetic and vagal influences on rate-dependent changes of QT interval in healthy subjects.

Dependence of QT interval duration on cardiac heart rate has been well established and is considered to be an intrinsic property of ventricular myocardium. Conclusive results of autonomic influences on such phenomena are lacking. To evaluate whether rate-dependent changes of QT interval are conditioned by the autonomic nervous system, 28 normal subjects with no heart disease and a normal QT interval were electrophysiologically assessed. The QT interval was calculated at 6 paced cycle lengths (600, 540, 500, 460, 430 and 400 ms) during the basal state, and after beta blockade (propranolol 0.2 mg/kg) and autonomic blockade (propranolol plus atropine 0.04 mg/kg). Because of atrioventricular nodal conduction limits, intrapatient cross-comparisons were performed in 10 subjects (aged 42 +/- 15 years). Single regression lines, evaluated in each subject, showing correlation between pacing cycle length and QT duration at each of the 3 states were analyzed. The mean slope observed after autonomic blockade (b = 0.10 +/- 0.04) was significantly lower than that seen during the basal state (b = 0.22 +/- 0.12, p less than 0.05) and after beta blockade (b = 0.23 +/- 0.08, p less than 0.05); nonsignificant differences were found between slopes during the basal state and after beta blockade. Results showed that vagal tone increased intrinsic dependence of QT at increasing cycle length, whereas sympathetic tone did not seem to interfere significantly. Since (in each subject) beta blockade was performed--or achieved--before atropine administration, the vagal influences are likely to be directly exerted on the ventricular electrophysiologic substrate.

Role of sinus node artery disease in sick sinus syndrome in inferior wall acute myocardial infarction.

This study was undertaken to evaluate a possible role of sinus node (SN) artery disease in the pathogenesis of sick sinus syndrome (SSS) in patients with an inferior wall acute myocardial infarction (AMI). Coronary angiography and electrophysiologic studies of the SN, both in the basal state and after pharmacologic autonomic blockade, were performed in 23 study patients (mean age 60 years) with SSS and a previous inferior wall AMI and in another 23 control patients (mean age 57 years) with normal sinus rate and a previous inferior AMI. Stenosis of the SN artery (or that proximal to its origin) greater than 50% was present in 13 study patients (56%) and in 8 control patients (34%) (p less than 0.05). In the study group, the intrinsic heart rate was abnormal in 5 of the 6 patients (83%) with severe SN artery stenosis (greater than or equal to 75% narrowing), in 3 of the 7 (43%) with moderate stenosis (50 to 75% narrowing) and in 3 of the 10 (30%) with insignificant stenosis (less than 50% narrowing). In the study group, the correlation between the SN measures (heart rate, corrected SN recovery time and sinoatrial conduction time) and the severity of SN artery stenosis was good after autonomic blockade (r between 0.59 and 0.64) and poor in the basal state. These data provide evidence for a role of SN artery disease in the pathogenesis of SSS in patients with an inferior wall AMI.

AV delay and exercise stress tests: behavior in normal subjects.

In normal subjects the atrioventricular (AV) conduction is accelerated during exertion. The relationship between heart rate and AV delay is usually described as "linear". Looking at the increasing importance given to an appropriate AV synchrony in permanent dual chamber and P synchronous pacing we present the results of an investigation performed to study the correlation between AV conduction time and heart rate under stress conditions, and disclose some new aspects of this matter, which will possibly be useful for a further improvement of pacemaker technology.

A new single lead VDD pacing system.

In 24 patients with advanced heart block and normal sinus node function, a new single lead VDD pacing system was implanted. At implantation, the endoatrial, bipolar electrogram was recorded in all patients. The lead position was checked by means of chest X-ray. At discharge and after 1, 3, and 6 months, testing for myopotential inhibition, telemetric evaluation of the endoatrial potential, and Holter recordings were made. After discharge, 18 patients performed two cardiopulmonary exercise tests at two different rate-matched AV intervals. All investigations showed good AV synchrony and a lack of interferences by myopotentials. The maximum rate-matched AV interval provided a significantly improved exercise capacity, which was more evident in patients with signs of myocardial failure.

[Sexual aspects of physician-patient relations]. / L'aspetto sessuale nel rapporto medico-paziente.

The emotional aspects of the doctor-patient relationship are often overlooked in clinical training, as are the sexual problems. A questionnaire was drawn up in order to obtain further information about the gynecologist's emotional reactions during pelvic examination. An analysis of the results suggests that the doctor's emotional reaction during pelvic examination is not the same in both sexes, whereas both sexes show equal concern for the patient's sexual activity. This suggests that adequate technical and emotional training is necessary in order to establish a good relationship between the gynecologist and the patient.