Nguyen

Potentiation of neuromuscular blockade by verapamil.

The effects of intravenous (iv) verapamil (0.01 to 1.0 mg/kg) on the constant neuromuscular block produced by an iv infusion of either pancuronium or succinylcholine were studied on the indirectly stimulated gastrocnemius and tibialis-anterior muscles of the rabbit anesthetized with halothane in oxygen. Verapamil alone (n = 6) had no significant effect. However, the drug did significantly potentiate the 50% twitch depression of the gastrocnemius muscle produced by a constant iv infusion of either pancuronium (n = 5) or succinylcholine (n = 5) to 36 ± 6% and 45 ± 1% of control, respectively. This effect of verapamil occurred with doses of 0.1 mg/kg for pancuronium and 0.01 mg/kg for succinylcholine; these doses of verapamil were the lowest which produced a significant effect. In contrast, verapamil had no significant effect on the progression of the neuromuscular blockade of either the gastrocnemius or tibialis-anterior muscles produced by alpha-bungarotoxin (n = 5). Verapamil also significantly prolonged the P-R interval of the ECG from a control value of 71 ± 2 ms to 78 ± 3 ms at a dose of 0.1 mg/kg and to 93 ± 6 ms at a dose of 0.3 mg/kg. The possible mechanisms of the neuromuscular actions of verapamil are discussed and it is concluded that verapamil can produce potentiation of either pancuronium- or succinylcholine-induced neuromuscular block at doses within the therapeutic range.

HIV-1 Quasispecies Delineation by Tag Linkage Deep Sequencing

Trade-offs between throughput, read length, and error rates in high-throughput sequencing limit certain applications such as monitoring viral quasispecies. Here, we describe a molecular-based tag linkage method that allows assemblage of short sequence reads into long DNA fragments. It enables haplotype phasing with high accuracy and sensitivity to interrogate individual viral sequences in a quasispecies. This approach is demonstrated to deduce ∼2000 unique 1.3 kb viral sequences from HIV-1 quasispecies in vivo and after passaging ex vivo with a detection limit of ∼0.005% to ∼0.001%. Reproducibility of the method is validated quantitatively and qualitatively by a technical replicate. This approach can improve monitoring of the genetic architecture and evolution dynamics in any quasispecies population.

Sex Differences in Clinical Characteristics, Hospital Management Practices, and In-Hospital Outcomes in Patients Hospitalized in a Vietnamese Hospital with a First Acute Myocardial Infarction

Background Cardiovascular disease is one of the leading causes of morbidity and mortality in Vietnam. We conducted a pilot study of Hanoi residents hospitalized with acute myocardial infarction (AMI) at the Vietnam National Heart Institute in Hanoi. The objectives of this observational study were to examine sex differences in clinical characteristics, hospital management, in-hospital clinical complications, and mortality in patients hospitalized with an initial AMI. Methods The study population consisted of 302 Hanoi residents hospitalized with a first AMI at the largest tertiary care medical center in Hanoi in 2010. Results The average age of study patients was 66 years and one third were women. Women were older (70 vs. 64 years) and were more likely than men to have had hyperlipidemia previously diagnosed (10% vs. 2%). During hospitalization, women were less likely to have undergone percutaneous coronary intervention (PCI) compared with men (57% vs. 74%), and women were more likely to have developed heart failure compared with men (19% vs. 10%). Women experienced higher in-hospital case-fatality rates (CFRs) than men (13% vs. 4%) and these differences were attenuated after adjustment for age and history of hyperlipidemia (OR: 2.64; 95% CI: 1.01, 6.89), and receipt of PCI during hospitalization (OR: 2.09; 95% CI: 0.77, 5.09). Conclusions Our pilot data suggest that among patients hospitalized with a first AMI in Hanoi, women experienced higher in-hospital CFRs than men. Full-scale surveillance of all Hanoi residents hospitalized with AMI at all Hanoi medical centers is needed to confirm these findings. More targeted and timely educational and treatment approaches for women appear warranted.

Prevalence of comorbidities and their impact on hospital management and short-term outcomes in Vietnamese patients hospitalized with a first acute myocardial infarction.

Background Cardiovascular disease is one of the leading causes of morbidity and mortality in Vietnam. We conducted a pilot study of Hanoi residents hospitalized with a first acute myocardial infarction (AMI) at the Vietnam National Heart Institute in Hanoi for purposes of describing the prevalence of cardiovascular (CVD) and non-CVD comorbidities and their impact on hospital management, in-hospital clinical complications, and short-term mortality in these patients. Methods The study population consisted of 302 Hanoi residents hospitalized with a first AMI at the largest tertiary care medical center in Hanoi in 2010. Results The average age of study patients was 66 years and one third were women. The proportions of patients with none, any 1, and ≥ 2 CVD comorbidities were 34%, 42%, and 24%, respectively. Among the CVD comorbidities, hypertension was the most commonly reported (59%). There were decreasing trends in the proportion of patients who were treated with effective cardiac medications and coronary interventions as the number of CVD comorbidities increased. Patients with multiple CVD comorbidities tended to develop acute clinical complications and die at higher rates during hospitalization compared with patients with no CVD comorbidities (Odds Ratio: 1.40; 95% Confidence Interval: 0.40–4.84). Conclusions Our data suggest that patients with multiple cardiac comorbidities tended to experience high in-hospital death rates in the setting of AMI. Full-scale surveillance of Hanoi residents hospitalized with AMI at all Hanoi hospitals is needed to confirm these findings. Effective strategies to manage Vietnamese patients hospitalized with AMI who have multiple comorbidities are warranted to improve their short-term prognosis.

A comparison of 3,4-diaminopyridine and 4-aminopyridine in the anaesthetized cat.

3,4-Diaminopyridine and 4-aminopyridine were compared in the anaesthetized cat and found to be equiactive in their anti-curare activity. This in vivo similarity is at variance with previous in vitro studies which demonstrate 3,4-diaminopyridine to be more active than 4-aminopyridine at the neuromuscular junction. Possible reasons for the similarity between the two aminopyridines at the in vivo neuromuscular junction are discussed and it is concluded that 3,4-diaminopyridine has only marginal advantages over 4-aminopyridine as a potential anti-curare agent.

High-throughput functional annotation of influenza A virus genome at single-nucleotide resolution

A novel genome-wide genetics platform is presented in this study, which permits functional interrogation of all point mutations across a viral genome in parallel. Here we generated the first fitness profile of individual point mutations across the influenza virus genome. Critical residues on the viral genome were systematically identified, which provided a collection of subdomain data informative for structure-function studies and for effective rational drug and vaccine design. Our data was consistent with known, well-characterized structural features. In addition, we have achieved a validation rate of 68% for severely attenuated mutations and 94% for neutral mutations. The approach described in this study is applicable to other viral or microbial genomes where a means of genetic manipulation is available.