Plasma concentrations of cyclic 3',5'-guanosine monophosphate in patients with cirrhosis: Relationship with atrial natriuretic peptide and haemodynamics

Little is known about the plasma concentrations of cyclic 3',5'-guanosine monophosphate (cGMP) in patients with cirrhosis. However, plasma cGMP concentrations provide information on cellular cGMP production by particulate guanylyl cyclases (which are stimulated by natriuretic peptides, such as atrial natriuretic peptide; ANP). In contrast, because intracellular cGMP elicits vasorelaxant mechanisms, plasma cGMP concentrations may be related to haemodynamic alterations in patients with cirrhosis. The aim of the present study was to measure plasma cGMP concentrations in patients with cirrhosis and controls and to examine the relationship between cGMP levels and plasma ANP concentrations and haemodynamic values. Plasma concentrations of cGMP and ANP and splanchnic and systemic haemodynamics were measured in 23 subjects; 13 subjects had cirrhosis and 10 were controls. All subjects had normal glomerular filtration. Plasma cGMP concentrations were significantly higher in patients (6.5±0.8 pmol/mL) than in controls (2.7±0.4 pmol/mL), while plasma ANP concentrations did not significantly differ between the two groups (127±22 and 123±27 pg/mL, respectively). In patients with cirrhosis, no significant correlation was found between plasma cGMP concentrations and plasma ANP concentrations, hepatic venous pressure gradient, cardiac output or systemic vascular resistance. In conclusion, in patients with cirrhosis, increased plasma cGMP concentrations may be due to an activation of particulate guanylyl cyclases by natriuretic peptides other than ANP. The present study suggests that plasma cGMP concentrations are not related to cirrhosis-induced haemodynamic alterations.     

DOUBLE-BLIND RANDOMIZED MULTICENTRE TRIAL OF ACAMPROSATE IN MAINTAINING ABSTINENCE FROM ALCOHOL

A prospective placebo-controlled, randomized double-blind studyof Acamprosate at two dose levels in alcohol-dependent patientsfollowed up for 12 months was performed. After detoxification,each of the 538 patients included was randomly assigned to oneof three groups: 177 patients received placebo, 188 receivedAcamprosate at 1.3 g/day (low dose group) and 173 received 2.0g/day(high dose group) for 12 months. This was followed by a singleblind 6 month period on placebo. The patients' mean age was43.2 ± 8.6 years. Their mean daily alcohol intake washigh (nearly 200g/day) and of long duration (9.5 ± 7.1years). Abstinence figures followed the order high dose>lowdose>placebo. The difference was significant at 6 months(P     

Learning Disabilities in Children: Significance of Low-Level Lead-Exposure and Confounding Factors

Abstract. The hypothesis that low-level lead absorption is a risk factor for learning disabilities in school children was examined in the municipality of Aarhus, Denmark. During 1982-1983, a total of 1302 children in the first grade (54 % of the eligible population) delivered shed deciduous teeth. The lead concentration in the circumpulpal dentin was used as an indicator of the cumulated lead absorption, and 200 cases (high-lead) and controls (low-lead) were selected, and matched for socioeconomic group and gender. The parents were interviewed regarding the child's development and past medical history. Possible confounders were identified and controlled for in a logistic multivariate model. The influence of lead absorption became statistically signincant only after exclusion of the children with proven medical risk factors, thereby the adjusted odds ratio in the weighted analysis was changed from 2.2 to 4.3. Thus, in a Scandinavian low-level lead-polluted area, lead absorption appears to be a risk factor for learning disabilities.     

Relationship between hepatic blood flow,liver tests,haemodynamic values and clinical characteristics in patients with chronic liver disease*

Although hepatic blood flow (HBF) has been measured in patients with liver disease for many years, the results of these studies have not provided clear information concerning the usefulness of this measurement. Hepatic blood flow was measured in 392 patients with either cirrhosis (n= 356) or hepatic fibrosis (n= 36). The control group included 59 subjects with normal liver architecture. Hepatic clearance of indocyanine green (ICG) was markedly reduced in patients with cirrhosis and hepatic fibrosis compared with controls (182±5, 276±22 and 421±25 mL/min, respectively). In patients with cirrhosis, ICG clearance and extraction were significantly correlated, but were not correlated to HBF. Although HBF did not differ between patients with cirrhosis and controls (1.26±0.04 vs 1.35±0.07 L/min, respectively), patients with hepatic fibrosis had lower HBF (1.04±0.07 L/min; P< 0.05). In patients with cirrhosis, no correlation was observed between HBF and cardiac output, mean arterial pressure, azygos blood flow, the hepatic venous pressure gradient or Pugh's score. However, a significant difference in HBF was observed in patients with and without hepatic encephalopathy (1.00±0.09 vs 1.28±0.03 L/min, respectively; P<0.05). In conclusion, the present study shows that, in patients with cirrhosis, HBF is normal and is not related to other haemodynamic values or liver tests. These results discourage the measurement of HBF in the evaluation of patients with cirrhosis.     

Impact and Prevention of Far-Field Sensing in Fallback Mode Switches

BORDACHAR, P., et al.: Impact and Prevention of Far-Field Sensing in Fallback Mode Switches. Far-field oversensing (FFOS) promoted by high atrial sensitivity and short atrial refractory periods induces false positive mode switches. We evaluated the incidence of ventricular FFOS in a population of DDD paced patients. Methods: One hundred thirty-seven patients (   71 ± 10   years, 76 men) implanted with a Talent DR pacemaker were studied. Before discharge, an analysis of internal data stored in the memories of the PM was performed by the specific software incorporated in the programmer in parallel with a 24-hour Holter recording. Data were validated by a panel of experts. One and 4 months follow-up was based only on the data stored in the PM memories. Results: Pacing indications were atrioventricular block   (n = 75)   , sinus node dysfunction   (n = 57)   , and other   (n = 5)   . Sustained far-field oversensing was observed in 12/137 patients (9%). Out of a total of 3,511 triggered mode switch episodes, FFOS accounted for 20% and 7% of a 311 days cumulative time in mode switch. Inappropriate mode switch episodes induced by far-field were more numerous but shorter than episodes prompted by atrial arrhythmias. Atrial sensitivity was increased in eight patients, successfully in four. Reprogramming of the atrial refractory period   (156 ± 11 ms)   was successful in five of six patients. Conclusions: A 9% rate of ventricular FFOS was observed in an unselected population, easily and automatically diagnosed using the internal memory function and the automatic analysis provided by the programmer. Prolongation of the atrial refractory period was more effective than resetting of the atrial sensitivity in eliminating FFOS. (PACE 2003; 26[Pt. II]:206–209)     

Optimal Stimulation of the Left Ventricle

Optimal Stimulation of the Left Ventricle. Cardiac resynchronization therapy has been proposed to alleviate heart failure symptoms refractory to classic drug treatment. Potential benefits hinge on a number of key components, including judicious selection of patients likely to respond to the therapy and appropriate placement of the leads, particularly the lead responsible for left ventricular pacing. Evidence of ventricular asynchrony is an individual prerequisite for consideration of cardiac resynchronization therapy. Ventricular asynchrony can be diagnosed by recording a QRS duration > 150 msec or during echocardiography, with the goal of investigating the mechanical aspect of asynchrony. The optimal left ventricular pacing site can be defined by the latest segmental contraction, which is mainly the mid‐lateral wall. The first‐choice technique to initiate left ventricular pacing consists of a transvenous approach via the coronary sinus tributaries. In practice, the final left ventricular pacing location also depends on highly variant coronary sinus anatomy, acceptable electrical parameters, and lead stability. Procedure‐related complications, which consist mainly of coronary sinus perforation and phrenic nerve stimulation, remain low (<1%) and should decrease further with the use of new features specific to the procedure.     

Torsades de Pointes

Torsades de Pointes. Torsades de pointes are typically characterized by an ECG pattern of polymorphous but organized electrical activity of ventricular origin that occurs in the setting of a long QT interval, long-coupled bigeminy, and has specific precipitating causes and therapeutic responses. Torsades de pointes can result from congenital (adrenergic dependent) and acquired (pause dependent) factors and may have similar cardiac substrates with different precipitating events. (J Cardiovasc Electrophysiol, Vol. 3, pp. 281–292, June 1992)     

Transseptal Implantation of a Left Ventricular Pacing Lead for an Ectopic Location of the Coronary Sinus Ostium in the Left Atrium

Congenital abnormalities of the coronary sinus (CS) are rare but can be responsible for unsuccessful implantation of a cardiac resynchronization therapy device. We report the case of an ectopic drainage of the CS in the left atrium. A left ventricular lead was implanted by the transseptal route. (PACE 2013; 36:e51–e52)     

Detoxification Mechanism in the Rat Extraorbital Lacrimal Gland: Conjugation of Brefeldin A to Glutathione

In this work the existence of a glutathione based detoxification system in rat lacrimal glands is reported. We showed that brefeldin A, a drug used as a tool for the study of intracellular trafficking mechanisms, was inactivated by metabolization and converted into two derivatives. We purified them by high performance liquid chromatography and determined, by mass spectroscopy, that they correspond to glutathione and cysteine derivatives of BFA. The determination of the respective amounts of these derivatives in the medium and the tissue in different experimental conditions, revealed that glutathione-BFA is formed in the tissue, excreted from the cells, cleaved by γ-glutamyl transpeptidase and finally converted to cysteine-BFA.