Electrocardiographic criteria of left ventricular hypertrophy in the presence of left bundle branch block

When left bundle branch block (LBBB) is present on the electrocardiogram, the diagnosis of left ventricular hypertrophy (LVH) may be difficult. The left ventricular mass in 70 patients with LBBB was estimated by echocardiography, and was compared to the QRS configuration on the electrocardiogram. We found that there was agreement between a monophasic R pattern in lead 1 or V6 (sensitivity 79.3%, 70.7%) and left ventricular hypertrophy. We suggest that a monophasic R pattern in L1 and V6 may provide a useful simple index of left ventricular hypertrophy in the presence of left bundle branch block.     

Primary arteriovenous fistula between common iliac vessels: ultrasound, computer tomographic, and angiographic findings--a case report

A giant aneurysm of the right common iliac artery presenting with an arteriovenous fistula (AVF) between the iliac artery and iliac vein and deep venous thrombosis of the right lower extremity is reported. The clinical signs and the radiologic and surgical management of the condition are discussed. In addition a brief review of the literature is given.     

Functional development of the visual system in normal and protein-deprived rats. IV. Latencies in the specific visual pathway of adult rats

It was recently shown that an increase in latency of the cortical visual evoked response (VER) seen in young malnourished animals persists in adult rats given a low protein diet. In the present paper the VER latencies of the specific visual pathway were measured in order to establish the level at which the latency increase occurs in protein-deprived rats. The VER in the dorsal lateral geniculate nucleus (dLGN) showed no significant differences to onset or peak latencies between control (C) and the protein-deprived (PD) rats. The dLGN activity was higher in C rats than in PD rats. Late components differed in median values between the two groups, but the individual variations were large. Generally, the VER of the dLGN in PD rats was more stereotype compared with the C rats. Intracortical VER at a depth of 0.4-0.5 mm showed a small negative component of short onset latency in both C and PD rats. This component preceded the onset of the initial positivity recorded from the cortical surface by 1-2 ms in C rats and by 3-6 ms in PD rats. Following electrical stimulation of the dLGN, no differences in onset latency of the first cortical activity (monosynaptic response) were recorded between C and PD rats, whereas later activity was significantly delayed in PD compared with C rats. The laminar potential pattern was less distinct in PD compared with C rats, and the late components of the evoked response from deep cortical layers were markedly attenuated or lacking.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fate of micelles and quantum dots in cells.

Micelles and quantum dots have been used as experimental drug delivery systems and imaging tools both in vitro and in vivo. Investigations of their fate at the subcellular level require different surface-core modifications. Among the most common modifications are those with fluorescent probes, dense-core metals or radionucleids. Cellular fate of several fluorescent probes incorporated into poly(caprolactone)-b-copolymer micelles (PCL-b-PEO) was followed by confocal microscopy, and colloidal gold incorporated in poly 4-vinyl pyridine-PEO micelles were developed to explore micelle fate by electron microscopy. More recently, we have examined quantum dots (QDs) as the next-generation-labels for cells and nanoparticulate drug carriers amenable both to confocal and electron microscopic analyses. Effects of QDs at the cellular and subcellular levels and their integrity were studied. Results from different studies suggest that size, charge and surface manipulations of QDs may play a role in their subcellular distribution. Examples of pharmacological agents incorporated into block copolymer micelles, administered or attached to QD surfaces show how the final biological outcome (e.g. cell death, proliferation or differentiation) depends on physical properties of these nanoparticles.     

Evidence of lowest brain penetration of an antiemetic drug, metopimazine, compared to domperidone, metoclopramide and chlorpromazine, using an in vitro model of the blood-brain barrier.

PURPOSE: The objective of the current study was to determine the ability of some antiemetic compounds to cross the blood-brain barrier (BBB) and thereby to determine possible side effects of compounds for the central nervous system (CNS). METHODS: We compared the brain penetration of some antiemetic compounds using an in vitro BBB model consisting in brain capillary endothelial cells co-cultured with primary rat glial cells. RESULTS: This study clearly demonstrated that the metopimazine metabolite, metopimazine acid, has a very low brain penetration, lower than metopimazine and even less than the other antiemetic compounds tested in this study. CONCLUSIONS: The poor brain penetration of metopimazine acid, metopimazine biodisponible form, seems very likely related to the clinically observed difference in therapeutic and safety profile.     

A novel assay for factor XIII based on cross-linking of synthetic peptides: analysis of different substrates.

A novel assay for factor XIII is described that utilizes exclusively small synthetic peptides as substrates for the cross-linking reaction catalyzed by activated factor XIII (FXIIIa). The acyl donor substrate (selection peptide) is immobilized on a microplate via biotin while the acyl acceptor substrate (detection peptide) is labeled with the fluorochrome Oregon green to allow sensitive detection without the need for secondary enzyme systems for signal amplification. Starting with an amino acid sequence from the fibrin gamma-chain (GQQHHLGGAKQAGDV) as a prototype peptide, the influence of amino acid exchanges were investigated with respect to their impact on the FXIIIa-catalyzed reaction. It was found that FXIIIa readily accepts a broad range of substrate peptides, with a proline neighboring the essential lysine having the most detrimental effect. The assay appears to be valuable for the molecular characterization of factor XIII and may be used for a deeper investigation into the substrate requirements of this final enzyme of wound repair, and eventually also for the characterization of other transglutaminases.     

First-pass effects of verapamil on the intestinal absorption and liver disposition of fexofenadine in the porcine model.

The aim of this study in pigs was to investigate the local pharmacokinetics of fexofenadine in the intestine and liver by using the pig as a model for drug transport in the entero-hepatobiliary system. A parallel group design included seven pigs (10-12 weeks, 22.2-29.5 kg) in three groups (G1, G2, G3), and a jejunal single-pass perfusion combined with sampling from the bile duct and the portal, hepatic, and superior caval veins was performed. Fexofenadine was perfused through the jejunal segment alone (G1: 120 mg/l, total dose 24 mg) or with two different verapamil doses (G2: 175 mg/l, total dose 35 mg; and G3: 1000 mg/l, total dose 200 mg). The animals were fully anesthetized and monitored throughout the experiment. Fexofenadine had a low liver extraction (E(H); mean +/- S.E.M.), and the given doses of verapamil did not affect the E(H) (0.13 +/- 0.04, 0.16 +/- 0.03, and 0.12 +/- 0.02 for G1, G2, and G3, respectively) or biliary clearance. The E(H) for verapamil and antipyrine agreed well with human in vivo data. Verapamil did not increase the intestinal absorption of fexofenadine, even though the jejunal permeability of fexofenadine, verapamil, and antipyrine showed a tendency to increase in G2. This combined perfusion and hepatobiliary sampling method showed that verapamil did not affect the transport of fexofenadine in the intestine or liver. In this model the E(H) values for both verapamil and antipyrine were similar to the corresponding values in vivo in humans.     

18F-FDG PET/CT for detecting nodal metastases in patients with oral cancer staged N0 by clinical examination and CT/MRI.

(18)F-FDG PET has a high accuracy in staging head and neck cancer, but its role in patients with clinically and radiographically negative necks (N0) is less clear. In particular, the value of combined PET/CT has not been determined in this group of patients. METHODS: In a prospective study, 31 patients with oral cancer and no evidence of lymph node metastases by clinical examination or CT/MRI underwent (18)F-FDG PET/CT before elective neck dissection. PET/CT findings were recorded by neck side (left or right) and lymph node level. PET/CT findings were compared with histopathology of dissected nodes, which was the standard of reference. RESULTS: Elective neck dissections (26 unilateral, 5 bilateral; a total of 36 neck sides), involving 142 nodal levels, were performed. Only 13 of 765 dissected lymph nodes harbored metastases. Histopathology revealed nodal metastases in 9 of 36 neck sides and 9 of 142 nodal levels. PET was TP in 6 nodal levels (6 neck sides), false-negative in 3 levels (3 neck sides), true-negative in 127 levels (23 neck sides), and false-positive in 6 levels (4 neck sides). The 3 false-negative findings occurred in metastases smaller than 3 mm or because of inability to distinguish between primary tumor and adjacent metastasis. TP and false-positive nodes exhibited similar standardized uptakes (4.8 +/- 1.1 vs. 4.2 +/- 1.0; P = not significant). Sensitivity and specificity were 67% and 85% on the basis of neck sides and 67% and 95% on the basis of number of nodal levels, respectively. If a decision regarding the need for neck dissection had been based solely on PET/CT, 3 false-negative necks would have been undertreated, and 4 false-positive necks would have been overtreated. CONCLUSION: (18)F-FDG PET/CT can identify lymph node metastases in a segment of patients with oral cancer and N0 neck. A negative test can exclude metastatic deposits with high specificity. Despite reasonably high overall accuracy, however, the clinical application of PET/CT in the N0 neck may be limited by the combination of limited sensitivity for small metastatic deposits and a relatively high number of false-positive findings. The surgical management of the N0 neck should therefore not be based on PET/CT findings alone.     

Seasons and other factors affecting the quality of life of asthmatic children.

OBJECTIVE: To study the effect of seasons on the health-related quality of life (HRQL) of asthmatic children. METHODS: Four groups of asthmatic children 7 to 14 years old were recruited by pediatricians during each season of the year. Their HRQL was assessed by means of the Paediatric Asthma Quality of Life Questionnaire (PAQLQ). Other factors surveyed were asthma severity, atopy, medical treatment, immunotherapy, obesity, parental smoking, and anti-allergic measures. RESULTS: The mean (SD) overall PAQLQ score was highest in summer at 6.2 (1.0) and lowest in autumn at 5.5 (1.2). The same trend was found for domains in summer and autumn, respectively: symptoms, 6.2 (1.0) vs 5.4 (1.4); emotions, 6.5 (0.8) vs 6.0 (1.0); and activities, 5.9 (1.4) vs. 5.0 (1.5). Factors such as male gender (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.41-0.87), being on immunotherapy (OR, 0.59; 95% CI, 0.38-0.92), living in an urban environment (OR, 0.56; 0.33-0.93), and residing on the northern coast of Spain along the Bay of Biscay (OR, 0.56; 0.36-0.89) were independent protective factors against having a total PAQLQ score in the lower tertile. Conversely, being recruited in a primary care setting (OR, 1.55; 1.01-2.38) and having more severe asthma were risks for being in the lower tertile. CONCLUSIONS: Irrespective of the severity of the disease, season has a significant influence on the HRQL of asthmatic children.     

Genetics of epilepsy: epilepsy research foundation workshop report.

The Sixth Epilepsy Research Foundation workshop, held in Oxford in March 2006, brought together basic scientists, geneticists, epidemiologists, statisticians, pharmacologists and clinicians to consider progress, issues and strategies for harnessing genetics to improve the understanding and treatment of the epilepsies. General principles were considered, including the fundamental importance of clear study design, adequate patient numbers, defi ned phenotypes, robust statistical data handling, and follow-up of genetic discoveries. Topics where some progress had been made were considered including chromosomal abnormalities, neurodevelopment, hippocampal sclerosis, juvenile myoclonic epilepsy, focal cortical dysplasia and pharmacogenetics. The ethical aspects of epilepsy genetics were reviewed. Principles and limitations of collaboration were discussed. Presentations and their matched discussions are produced here. There was optimism that further genetic research in epilepsy was not only feasible, but might lead to improvements in the lives of people with epilepsy.