ABSTRACT
BACKGROUND: The acute impact of tobacco smoking on the cardiac hemodynamic parameters and its pathological implication in the process of arterial atherosclerosis need further exploration. This investigation was purposed to assess the acute impact of tobacco smoke on blood pressure and cardiac hemodynamic parameters. METHODS: Using an Ultrasonic Cardiac Output Monitor, and DINAMAP Pro 400 Series V2 blood pressure monitor, several cardiac hemodynamic parameters and the blood pressure were assessed in 14 smokers, 11 females and 3 males, at 2 time points, before and after smoking of one cigarette. Data, in terms of ratio of the means and 95% confidence interval were analyzed using ANOVA. RESULTS: Single-subject design in which the subject has served as his/her own control has been used. Tobacco smoking led to statistically significant acute increase in the means of all hemodynamic parameters, except for heart rate in female subjects, as compared to the means obtained before smoking. CONCLUSIONS: Cigarette smoking induces acute non-physiologic alteration in cardiac outflow forces, exposing the aortic valve and arch to mechanical injury that might be implicated in initiating and promoting the process of aortic arch atherosclerosis and associated pathological lesions.
ABSTRACT
BACKGROUND & AIMS: The search for targeted anti-hepatitis C virus (HCV) drugs is driven by the adverse effect profile and limited efficacy of the current standard of care (pegylated interferon-alpha/ribavirin). In a first-in-human trial, we tested the safety, tolerability, and pharmacokinetics of the macrocyclic HCV NS3/4A protease inhibitor TMC435 in healthy volunteers, followed by HCV genotype 1-infected patients to assess antiviral activity. METHODS: The TMC435350-C101 study was a phase I, randomized, double-blind, placebo-controlled trial in 49 healthy volunteers, followed by an open-label, nonplacebo-controlled panel in 6 genotype 1 hepatitis C patients. Healthy volunteers received oral, single, ascending doses (up to 600 mg) or 5-day multiple ascending doses (200 mg twice daily or 100, 200, or 400 mg once daily). Patients received 200 mg once daily for 5 days. Pharmacokinetics and safety were evaluated for all panels, and plasma HCV-RNA levels were determined in patients. RESULTS: There were no serious adverse events, no grade 3 reactions, and no treatment-related discontinuations; pharmacokinetics supported a once daily dosing regimen. Plasma HCV-RNA levels dropped rapidly in all patients, with a median maximal reduction of 3.9-log(10) IU/mL and a median of 6 days to maximal reduction. The initial steep reduction of HCV-RNA (median 3.5-log(10) IU/mL at day 3) was followed by a more gradual decline that was maintained over the dosing period. No viral breakthroughs (>1-log(10) IU/mL HCV-RNA increase from nadir) were observed during treatment nor in the 3 days posttreatment; HCV-RNA returned to pretreatment levels by week 4. CONCLUSIONS: Once daily TMC435 given orally was generally safe and well tolerated and demonstrated potent antiviral activity.
Subject(s)
Antiviral Agents/administration & dosage , Hepacivirus/drug effects , Hepatitis C/drug therapy , Heterocyclic Compounds, 3-Ring/administration & dosage , Protease Inhibitors/administration & dosage , RNA, Viral/blood , Sulfonamides/administration & dosage , Viral Load/drug effects , Viral Nonstructural Proteins/antagonists & inhibitors , Administration, Oral , Adult , Antiviral Agents/adverse effects , Antiviral Agents/pharmacokinetics , DNA, Viral/analysis , Double-Blind Method , Drug Administration Schedule , Female , Genotype , Hepacivirus/enzymology , Hepacivirus/genetics , Hepatitis C/diagnosis , Heterocyclic Compounds, 3-Ring/adverse effects , Heterocyclic Compounds, 3-Ring/pharmacokinetics , Humans , Male , Middle Aged , Protease Inhibitors/adverse effects , Protease Inhibitors/pharmacokinetics , Simeprevir , Sulfonamides/adverse effects , Sulfonamides/pharmacokinetics , Time Factors , Treatment Outcome , Viral Nonstructural Proteins/genetics , Young AdultABSTRACT
INTRODUCTION: Myocardial injury is one of the most notorious complications of a hypertensive crisis. Key electrocardiograph signs used to detect cardiac injury such as ST segment changes and cardiac arrhythmias usually indicate acute ongoing end-organ damage. Lack of early signs to predict end-organ damage might lead to a delay in the initiation of therapy and selection of the incorrect therapeutic strategy. CASE PRESENTATION: We describe five cases of tall, hyper acute symmetrical T-waves alone or accompanied by other electrocardiograph abnormalities in five healthy participants: three women aged 52, 60 and 62-years and two men aged 49 and 66-years, during a tyramine-monoamine oxidase-inhibitor interaction, phase I clinical trial. T-wave changes appeared early during the course of the hypertensive crisis and were attributed to subendocardial ischemia. The changes were transient and reverted to baseline in parallel with a fall in blood pressure. CONCLUSION: Recognition of tall symmetrical T-waves in early phases of hypertensive crisis heralds commencement of myocardial damage. This calls for prompt medical intervention to avoid an impending irreversible myocardial injury. It is our belief that these findings will add new insight into the management of hypertensive crisis and will open avenues of further investigation.
