THE PHARMACOLOGICAL ROLE OF P-GLYCOPROTEIN IN THE INTESTINAL EPITHELIUM

P-glycoprotein, a membrane-associated transport protein, has recently been recognised as an important element of the intestinal epithelium. This paper summarises thein vivodata on the pharmacological role of intestinal P-glycoprotein. These data show that P-glycoprotein contributes to the elimination of many drugs by mediating their direct secretion from the blood into the intestinal lumen. In addition, there is also evidence that this protein can limit oral drug absorption. Hence, inhibition of intestinal P-glycoprotein, e.g. by a reversal agent like cyclosporin A, may be a promising strategy for improving the oral bioavailability of P-glycoprotein substrate drugs. Indeed, several preclinical and clinical studies have shown that coadministration of drugs with a reversal agent can substantially increase oral drug absorption.     

Role of the Atrial Rate as a Factor Modulating Ventricular Response during Atrial Fibrillation

Background: During atrial fibrillation (AF), RR interval histograms show different populations of predominant RR (pRR) intervals. These pRR intervals have been suggested to be multiples of the refractory period of the atrioventricular (AV) node or caused by the existence of a dual AV node physiology. In this study, the hypothesis that pRR intervals are related to the dominant atrial fibrillatory rate is tested. Methods: In this study, Holter electrocardiogram signals from 55 patients with persistent AF were analyzed. Number and position of pRR intervals were detected and compared with mean and standard deviation of the dominant atrial cycle length (DACL). In addition, effects of an enhancement of vagal activity and rate‐control treatments (β‐blockers and verapamil) were evaluated. Results: In all patients with more than one pRR interval and in 47% with one pRR interval, RR interval populations were statistically related with multiples of the DACL. During night activities and during β‐blockers treatment, mean ventricular rate was decreased (P < 0.01). This change was associated with a variation in the percentage of occurrences of each pRR (P < 0.01), whereas no statistical differences were present in the mean DACL or in the position of pRR intervals. A variation of the DACL due to verapamil was associated with a consistent modification in the position of the pRR intervals. Conclusion: The relation between pRR and multiples of the DACL during AF suggests that more probable RR intervals are caused by different conduction ratios of the atrial rate. (PACE 2010; 33:1510–1517)     

Primary Immunodeficiency Diseases in Latin America: The Second Report of the LAGID Registry

This is the second report on the continuing efforts of LAGID to increase the recognition and registration of patients with primary immunodeficiency diseases in 12 Latin American countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Honduras, Mexico, Panama, Paraguay, Peru, Uruguay, and Venezuela. This report reveals that from a total of 3321 patients registered, the most common form of primary immunodeficiency disease was predominantly antibody deficiency (53.2%) with IgA deficiency reported as the most frequent phenotype. This category was followed by 22.6% other well-defined ID syndromes, 9.5% combined T- and B-cell inmunodeficiency, 8.6% phagocytic disorders, 3.3% diseases of immune dysregulation, and 2.8% complement deficiencies. All countries that participated in the first publication in 1998 reported an increase in registered primary immunodeficiency cases, ranging between 10 and 80%. A comparison of the estimated minimal incidence of X-linked agammaglobulinemia, chronic granulomatous disease, and severe combined immunodeficiency between the first report and the present one shows an increase in the reporting of these diseases in all countries. In this report, the estimated minimal incidence of chronic granulomatous disease was between 0.72 and 1.26 cases per 100,000 births in Argentina, Chile, Costa Rica, and Uruguay and the incidence of severe combined immunodeficiency was 1.28 and 3.79 per 100,000 births in Chile and Costa Rica, respectively. However, these diseases are underreported in other participating countries. In addition to a better diagnosis of primary immunodeficiency diseases, more work on improving the registration of patients by each participating country and by countries that have not yet joined LAGID is still needed. Latin American Group for Primary Immunodeficiency Diseases     

Bacteraemia as Predictor of HIV Infection in African Children

ABSTRACT. In Rwanda, both HIV infection and bacteraemia represent major health problems among paediatric populations. We carried out a prospective study to determine if bacteraemia is a marker of HIV infection among ambulatory and hospitalized Rwandese children. All children presenting at the Department of Paediatrics of the Centre Hospitalier de Kigali and who had their blood cultured during a two-month period were eligible for the study. One hundred and thirty-five children were included in the study. A pathogen was isolated from 36 children (26.7 %): S. typhimurium (10 cases), S. enteritidis (6), S. typhi (4), Str. pneumoniae (9). H. influenzae (6) and S. aureus (1). No association was found between bacteraemia and HIV seropositivity when all the children were considered. However, among patients less than 2 years old, bacteraemic subjects were more frequently ( p ≤0.05) HIV seropositive (44 %) than those with negative blood cultures (19 %). Our study shows that in young children in Central Africa, the presence of bacteraemia may be an important marker of HIV seropositivity.     

Clinical Observations with a Dual Sensor Rate Adaptive Single Chamber Pacemaker

The Topaz model 515 (Vitatron B.V.) is a dual sensor rate responsive pacemaker for single chamber stimulation. It can be driven by activity counts (ACT) and QT interval measurements. Inappropriate rate modulation due to one sensor can be corrected by "sensor cross-checking." It was implanted in ten patients (20-86 years) of whom seven had complete heart block and atrial arrhythmias. After implantation T-wave amplitude ranged from 0.9mV-3.5 mV. T-wave sensing ranged from 88%–99% in 9/10 patients at the follow-up of 3 weeks. Eight patients remained in default setting of the activity threshold, after evaluation with a short walking test. An exercise test was performed on all patients. In one test, QT sensing was marginal because of lead implantation in the right ventricular outflow tract. Therefore, this pacing rate was only modulated by ACT sensing. All others were tested with equal contribution of information from both sensors (ACT = QT). In 7/9, rate response was satisfactory. When the treadmill was repeated with ACT in five of these seven patients, rate generally accelerated too fast. In one patient the setting was adjusted to "QT > ACT," because of inappropriate acceleration due to activity sensing, in another it was adjusted to "QT < ACT" because of delayed response to activity. The pacing rate and the ACT during treadmill tests in "QT = ACT" mode were more closely correlated in the first 3 minutes, compared with the last 3 minutes. We feel that rate modulation with this new pacemaker is adequate. Sensor blending and sensor cross-checking are of clinical importance.     

Usual sleep duration and cognitive function in older adults in Spain

The few studies that have examined the association between usual sleep duration and cognitive function have shown conflicting results. This cross‐sectional study examined the association between sleep duration and cognitive function among 3212 people, representative of the non‐institutionalized population aged 60 years and over in Spain. Sleep duration was self‐reported, and cognitive function was measured with the Mini‐Examen Cognoscitivo (MEC), a version of the Mini‐Mental State Examination that has been validated in Spain. Linear regression, with adjustment for the main confounders, was used to obtain mean differences in the MEC between the categories of sleep duration (≤5, 6, 7, 8, 9, 10, ≥11 h day^?1). The MEC score decreased progressively (became worse) across sleep categories from 7 to ≥11 h (P for linear trend <0.001). People who slept for ≥11 h had a significantly lower MEC score than those who slept for 7 h (mean difference ?1.48; 95% confidence interval ?2.12 to ?0.85). This difference in the MEC was similar to that observed for a 10‐year increase in age. The results did not vary significantly by sex (P for interaction >0.05). No association was observed between short sleep duration (<7 h) and cognitive function. We conclude that long sleep duration is associated with poorer cognitive function in older adults from the general population.     

Coronary Sinus Aneurysm and Left Ventricular‐Coronary Sinus Fistula. Implantation of CRT Device

We describe a 72‐year‐old man referred for implantation of a cardiac resynchronization therapy device who had previously undergone repeated operations to replace the mitral valve. Retrograde venography of the coronary sinus (CS) to implant the left ventricular (LV) pacing lead revealed aneurysmal dilatation of the CS with LV‐CS fistula that hindered—but did not prevent—complete implantation of the system. (PACE 2013; 36:e38–e40)