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Background: Fluoroquinolone (FQ) agents have been speculated to influence the risk of Torsades de pointes (Tdp). Methods of evaluating this risk are varied and not systematic. QTc interval (QTc) prolongation is the most commonly used marker of Tdp, but has questionable utility. QT dispersion (QTd) may be a more selective marker of Tdp. No assessment of QTd for FQs has been reported. The current study evaluates the effects of three commonly prescribed FQs by comprehensive QT analysis.Methods: In an open-label crossover study, 13 healthy participants received 3 treatments in random order: ciprofloxacin 500 mg twice daily, levofloxacin 500 mg once daily, and moxifloxacin 400 mg once daily. Each treatment was given for 7 days with a 1-week washout period. Twelve-lead electrocardiographic measurements were performed prior to the first dose, 2 hours after the first dose, and following the 7-day medication course. QTc prolongation was determined by measurement of lead II, and QTd from the difference between the maximum and minimum QTc intervals among the 12 leads. The data were analyzed using Friedman ANOVA, with the Wilcoxon signed rank test post hoc analysis, with P < 0.05 significance.Results and Conclusions: No difference was seen in baseline QTc (P = 0.48) or QTd (P = 0.92). Following 7 days of moxifloxacin, the QTc was prolonged by 6 ms relative to baseline (408 ms, P = 0.022), and 11 ms from the 2-hour measurement (403 ms, P = 0.003). Ciprofloxacin and levofloxacin had no effect on QTc, and no FQ changed the QTd. Within our study population, ciprofloxacin and levofloxacin did not display an increased risk for Tdp. Moxifloxacin, while showing QTc prolongation, did not affect QTd, and an increased Tdp risk is questionable. [ABSTRACT FROM AUTHOR]

There is a common belief in a class effect among angiotensin-converting enzyme (ACE) inhibitors. This is unsubstantiated for acute myocardial infarction (AMI). Because vascular tissue is a source of the endogenous fibrinolytic markers, and ACE inhibition in vascular tissue favorably influences the fibrinolytic system, the authors hypothesized that a high-tissue-penetrating ACE inhibitor would provide a more favorable reduction in plasminogen activator inhibitor-1 (PAI-1) and an increase in tissue plasminogen activator (t-PA) after AMI compared to a low-tissue-penetrating ACE inhibitor. In a randomized open-label trial, patients received the high-tissue-penetrating quinapril (n = 15) or low-tissue-penetrating enalapril (n = 15) immediately following an AMI. PAI-1 and t-PA antigen (ng/mL) were measured at baseline and through 14 days of treatment. There was no difference in baseline PAI-1 or t-PA antigen between treatments. PAI-1 antigen trended toward being lower with quinapril versus enalapril on day 1 (24.44 +/- 14.96 vs. 36.94 +/- 19.49, respectively, p = 0.059) and was significantly lower on day 3 (17.32 +/- 9.57 vs. 27.49 +/- 9.61, respectively, p = 0.009). Analysis of PAI-1 antigen over time by two-factor ANOVA with replication found significantly lower concentrations of PAI-1 antigen over the entire treatment period with quinapril versus enalapril (p < 0.003). This investigation of ACE inhibitor tissue-penetrating influence on markers of reinfarction risk suggests there may be a greater early reduction in PAI-1 with a more highly tissue-penetrating ACE inhibitor. [ABSTRACT FROM AUTHOR]

Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of endogenous thrombolysis, thereby promoting thrombosis. PAI-1 is also a primary contributor to the development and recurrence of acute myocardial infarction. The renin angiotensin system, hypertriglyceridemia, hyperglycemia and hyperinsulinemia, and estrogen all influence the fibrinolytic system and PAI-1 in particular. Available data strongly suggest that angiotensin-converting enzyme (ACE) inhibitors and hormone replacement therapy with estrogen beneficially reduce PAI-1 production. Metformin, an agent commonly used for non-insulin-dependent diabetes mellitus (NIDDM), appears to favorably decrease PAI-1 production in NIDDM patients but not nondiabetic patients. Among the cholesterol-lowering statins, clinical literature evaluating pravastatin provides the most compelling data to support this agent's favorable effect on PAI-1. Other available statins either have not displayed an effect on PAI-1 or do not have clear data to conclusively define their effects on the fibrinolytic system. [ABSTRACT FROM AUTHOR]

Two major treatment strategies have emerged for the management of chronic atrial fibrillation (AF). The first is to allow the patient to remain in AF and to pharmacologically control the ventricular rate to minimize symptoms while administering antithrombotic therapy to prevent stroke. The second strategy, which is more appropriate for patients who are highly symptomatic or are not candidates for chronic anticoagulation, is to maintain sinus rhythm with antiarrhythmic drugs. The class III antiarrhythmic agents sotalol, amiodarone, and dofetilide have become the mainstay in managing chronic AF Each of the two treatment strategies carries significant benefits and risks, and the optimal approach has not yet been determined. Until it is, symptomatology and the likelihood of maintaining sinus rhythm are the chief guides for selecting which strategy is best for individual patients, along with duration of AF, left atrial size, contraindications to anticoagulation, and proarrhythmic risk with class III agents. [ABSTRACT FROM AUTHOR]

Current approaches to the diagnosis and therapy of atherosclerosis cannot target lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing inflammatory responses. The presence of these cells is positively associated with lesion progression, severity and destabilization. Hence, they are an important diagnostic and therapeutic target. The objective of this study was to noninvasively assess the distribution and accumulation of intimal macrophages using CD36-targeted nanovesicles. Soy phosphatidylcholine was used to synthesize liposome-like nanovesicles. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine was incorporated on their surface to target the CD36 receptor. All in vitro data demonstrate that these targeted nanovesicles had a high binding affinity for the oxLDL binding site of the CD36 receptor and participated in CD36-mediated recognition and uptake of nanovesicles by macrophages. Intravenous administration into LDL receptor null mice of targeted compared to non-targeted nanovesicles resulted in higher uptake in aortic lesions. The nanovesicles co-localized with macrophages and their CD36 receptors in aortic lesions. This molecular target approach may facilitate the in vivo noninvasive imaging of atherosclerotic lesions in terms of intimal macrophage accumulation and distribution and disclose lesion features related to inflammation and possibly vulnerability thereby facilitate early lesion detection and targeted delivery of therapeutic compounds to intimal macrophages., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: To evaluate whether the direct renin inhibitor, aliskiren, has a more favorable effect compared to amlodipine on atherosclerotic biomarkers in patients with stable coronary artery disease and diabetes currently receiving standard secondary prevention therapy., Methods: A total of 38 patients were randomly assigned initially to either aliskiren (150 mg daily) or amlodipine (5 mg daily) for 2 weeks after which the dose of either medication was increased to its maximum daily dose for 4 additional weeks. Baseline and 6-week blood samples were analyzed for changes from baseline and between treatment groups for vascular and intracellular cell adhesion molecule, C-reactive protein, nitric oxide, plasminogen activator inhibitor 1, 8-isoprostane, and thiobarbituric acid reactive substances., Results: Thirty-one patients completed the study. More of the dropouts occurred in patients receiving aliskiren. Systolic blood pressure decreased in both treatment arms with no differences between the groups being noted. Plasminogen activator inhibitor 1, nitric oxide, and C-reactive protein concentrations increased in both groups from baseline but changes from baseline or between groups were not significant. Vascular and intracellular cell adhesion molecule, thiobarbituric acid reactive substances, and isoprostane concentrations decreased in each treatment arm from baseline, but these changes were not significant and no differences were noted between the groups., Conclusions: Treatment with either aliskiren or amlodipine did not significantly alter surrogate biomarkers of atherosclerosis in patients with both diabetes and established cardiovascular disease already receiving appropriate secondary cardiovascular prevention therapy. The study is limited in its size and duration to see an effect.

An 81-year-old man was incidentally found to have a large pericardial cyst on a chest computed tomography. Before surgical removal, an echocardiogram demonstrated that the cyst was more likely a large (7.5 cm) right coronary arterial aneurysm. A cardiac blood-pool study demonstrated a blood-filled structure adjacent to the heart, roughly the same size as the combined size of both the right and left ventricles. Coronary angiography confirmed the presence of a large right coronary artery aneurysm. A coronary aneurysm should be considered when a blood-filled structure is seen adjacent to the heart on a multigated acquisition scan.

This study evaluated gender variability in platelet aggregation in response to common agonists. Platelet aggregation was measured in 36 healthy men and women free of any antiplatelet medication, aged 22-36 years, of Caucasian (White not of Hispanic origin), Hispanic, and African-American not of Hispanic origin. In this ex-vivo study, we investigated platelet aggregation in response to adenosine-5'-diphosphate (ADP), epinephrine (EPI), arachidonic acid (AA) and collagen (COL), using a platelet ionized calcium aggregometer (Chrono-Log Co.). Platelet aggregation response to all tested agonists was higher in females than in males regardless of ethnicity. The most significant differences were observed with collagen (P < 0.01). Among the ethnic groups, Caucasian women were most prone to platelet aggregation. Gender is a determinant of agonist effects on platelet aggregability in healthy subjects.

Background: Diastolic dysfunction is common in the elderly. Increased myocardial fibrosis, a major determinant of diastolic function, has been observed with advancing age. Spironolactone prevents age-related increases in myocardial fibrosis in old normotensive rats., Hypothesis: Spironolactone, via its antifibrotic activity, can improve diastolic function in the elderly with isolated diastolic dysfunction., Methods: The study was a prospective, double-blind, randomized, placebo-controlled trial. Thirty elderly subjects between 60 and 85 years of age with isolated diastolic dysfunction and no contraindications for spironolactone were randomized to 25 mg/day of spironolactone or placebo for 4 months. Mitral E/A and deceleration time, plasma levels of carboxy-terminal of procollagen type I (PICP), and brain natriuretic peptide (BNP) were measured at baseline and at the end of 4 months. Plasma level of potassium was also monitored to prevent clinically significant hyperkalemia., Results: There was no serious adverse event or clinically significant hyperkalemia in the spironolactone group. Compared with baseline values, spironolactone significantly improved mitral E/A ratio (0.71 +/- 0.08 vs. 0.84 +/- 0.19, p = 0.025) and deceleration time (285.5 +/- 73.1 vs. 230.0 +/- 54.7, p = 0.035). There were no significant differences in the magnitude of change in the levels of PICP and BNP between the two treatment groups., Conclusion: Spironolactone may improve diastolic function in the elderly.

Study Objective: To explore the potential of a direct drug interaction between unfractionated heparin (UFH) and tenecteplase that lowers the pharmacologic propensity of UFH to prolong the activated partial thromboplastin time (aPTT)., Design: In vitro experiment., Setting: Texas Tech University School of Pharmacy, with sample analysis performed at an independent, contract laboratory. Samples. Blood samples collected from healthy volunteers., Intervention: Three separate in vitro experiments were conducted to explore the relative influence of various thrombolytic agents with and without UFH on aPTT prolongation. In each experiment, blood from healthy volunteers (12 for each experiment) was treated with different concentrations and combinations of tenecteplase and UFH., Measurements and Main Results: When the effects of tenecteplase plus UFH versus UFH alone on aPTT prolongation were compared, each experiment demonstrated attenuation of aPTT with the combination versus UFH alone. In contrast, findings for other thrombolytic agents combined with UFH demonstrate elevation of the aPTT compared with UFH alone., Conclusion: The results indicate a possible drug interaction between tenecteplase and UFH, with tenecteplase attenuating the intensity of anticoagulation of UFH in vitro. Further investigation into this possible interaction is warranted in the clinical setting.

The authors report a rare case of renal failure secondary to abdominal cyst in a newborn girl. The clinical presentation was one of a largely distended abdomen coupled with anuria. The histopathologic and clinical findings suggest mesenteric cyst causing renal failure by mass effect.

The true existence of a class effect in angiotensin-converting enzyme (ACE) inhibitors remains controversial. The present trial explored the effects of 2 ACE inhibitors after acute myocardial infarction and found no difference in endothelin-1 production but a greater increase in the production of total nitric oxide with quinapril than with enalapril., (Copyright 2004 Excerpta Medica, Inc.)

Acute massive pulmonary embolism (PE) is a frequently fatal event that causes significant compromise of hemodynamic stability. Unfortunately, mortality rates for PE have remained relatively constant despite advances in prophylactic and treatment measures. In addition to embolus size, symptom recognition for diagnosis and emergent treatment are two distinct factors that dictate survival. Treatment generally includes thrombolytic agents; however, not all patients are candidates for aggressive thrombolytic management. Development of catheter thrombectomy devices provides an alternative treatment modality for severe cases when thrombolytics are contraindicated. Catheter thrombectomy devices have undergone major advances over the last decade, but literature support of their success is limited., (Copyright 2004 S. Karger AG, Basel)

A 74-year-old hypertensive woman presented with abdominal discomfort and a pulsatile abdominal mass. Anterior abdominal angiography during cardiac blood pool, and renal scintigraphic imaging demonstrated a large abdominal aortic aneurysm. 1, 2 Before endovascular repair with an aortoiliac endograft, the abdominal aneurysm measured 7.5 x 7.0 cm on abdominal computed tomography. This study demonstrates that a suspected abdominal aortic aneurysm can be confirmed using the addition of anterior abdominal imaging with normal posterior imaging at the time of renal scintigraphy.

Despite limited comparative data, guidelines suggest the same concomitant unfractionated heparin (UFH) dose for all fibrin-specific thrombolytic agents in acute myocardial infarction. Since a supratherapeutic activated partial thromboplastin time (aPTT) correlates with adverse outcomes, clarifying effects of various agents on aPTT are needed. The present in vitro study evaluated the influence of alteplase (rt-PA), reteplase (r-PA), and tenecteplase (TNK) on aPTT prolongation. Blood samples from healthy volunteers (n = 12) were treated with equipotent concentrations of rt-PA, r-PA, and TNK, with and without UFH. Samples of each treatment group were incubated at 37 degrees C; aPTT and fibrinogen activity were measured after 4 h. Mean aPTT values for rt-PA alone and r-PA alone were prolonged versus those of TNK alone (P = 0.001 for both). Combined with UFH, rt-PA and r-PA increased the aPTT versus UFH alone (P < 0.05 for both). Interestingly, TNK + UFH reduced the aPTT versus UFH alone (P < 0.001). A negative correlation existed between fibrinogen activity and aPTT for all treatments, except TNK alone. The present investigation illustrates that an agent with maximal fibrin specificity (TNK) has minimal effect on the aPTT, while agents with less fibrin specificity are more likely to prolong the aPTT, with and without UFH present.

We report a case of diffuse large cell non-Hodgkin's lymphoma with concomitant lupus anticoagulant at initial diagnosis. Progressive thrombosis occurred despite radiologically proven response of the lymphoma after chemotherapy treatment. Extraordinary bone scintigraphy with multiple "cold" lesions probably due to bone ischemia is described.

Thirty consecutive patients with intact gallbladders and biliary pain were evaluated to determine whether gallbladder ejection fraction could identify sphincter of Oddi dysfunction. The mean gallbladder ejection fraction was 45% in patients with abdominal pain and 72% in normal controls. Gallbladder ejection fractions were then correlated with endoscopically measured sphincter of Oddi pressures in patients with abdominal pain. The mean gallbladder ejection fraction was 41% in 7 patients with elevated sphincter pressures and 46% in 23 patients with normal pressures (P = NS). Thirty-six percent of patients with elevated pressures and 33% of patients with normal pressures had abnormal gallbladder ejection fractions. Gallbladder ejection fraction had a sensitivity of 33%, a specificity of 63%, and a positive predictive value of 25% for detection of elevated pressures. Regression analysis revealed a poor correlation between sphincter pressure and gallbladder ejection fraction (r2 = 0.02). These findings suggest that gallbladder ejection fraction cannot be used to diagnose sphincter of Oddi dysfunction in patients before they undergo cholecystectomy.

Cerebral atrophy often coexists with other brain disorders and by itself may alter the pattern of cerebral perfusion. If unrecognized, it may confound diagnoses based on brain single-photon emission tomography (SPET). In this retrospective study, we describe and evaluate criteria for the diagnosis of cerebral atrophy on technetium-99m hexamethylpropylene amine oxime brain SPET studies. The SPET scans of 11 patients with cerebral atrophy and ten controls were evaluated for the presence of a prominent interhemispheric fissure, presence of prominent cerebral sulci, separation of thalamic nuclei, and pronounced separation of caudate nuclei. The SPET studies were interpreted by two independent observers blind to the findings of magnetic resonance imaging, which provided the final diagnosis of cerebral atrophy. The combination of the four scintigraphic signs was accurate in the diagnosis of cerebral atrophy in 95% of the cases and had a sensitivity of 91% and a specificity of 100%.

Background: Published reports on patients with cortical blindness describe bilateral brain hemispheric lesions visualized in radiological and functional imaging studies., Case Description: We present a case with a unilateral lesion on radiological studies and bilateral abnormalities on single-photon emission-computed tomographic (SPECT) scanning., Conclusions: SPECT images correlated much more closely than radiological studies with the patient's clinical status. We suggest that SPECT scanning can be a useful indicator of focal brain dysfunction in brain injury in spite of normal radiological studies. We also hypothesize that our patient's clinical and functional imaging findings could be attributed in part to the process of diaschisis.