Comparison of the radial and femoral approaches in left main PCI: a retrospective study

Transradial percutaneous coronary intervention (PCI) is a safe and effective method of percutaneous revascularization. However, there are no data on the efficacy of the transradial approach in left main (LM) PCI. We studied 80 patients (pts) who underwent LM PCI between February 1994 and January 2002, and compared the radial (27 pts) and femoral (53 pts) approaches. Patients were considered free of restenosis if they were free of angina and had a negative treadmill or nuclear imaging study 6 months post-PCI. Mean follow-up time was 27.4+/-23.0 months. Reason for PCI (stable angina, unstable angina, acute myocardial infarction) and lesion location (ostial, mid, distal) were similar in both groups (p>0.05), whereas mean ejection fraction was higher in the radial group (56.5+/-11.1% versus 49.2+/-14.7%, respectively; p<0.05). Sheath size (7 or 8 French; 44.4% radial versus 77.3% femoral) and amount of heparin used (9,192+/-3,645 IU versus 11,468+/-5,083 IU) were significantly larger in the femoral group (p<0.05), and the use of intra-aortic balloon pump was significantly more frequent (3.7% versus 22.6%). Mean fluoroscopy time (21.3+/-12.8 minutes versus 16.7+/-8.5 minutes), amount of contrast used (227+/-92 ml versus 225+/-85 ml), mean procedural time (67.0+/-27.6 minutes versus 73.4+/-32.7 minutes), procedure success (96.3% versus 98.1%), in-hospital major adverse cardiac events (MACE; 7.4% versus 5.6%) and 6-month MACE (14.8% versus 25.5%) were similar in the 2 groups (p>0.05). However, major vascular complications occurred only in the femoral group (5.7%). Radial LM PCI is as fast and successful as the femoral approach and results in fewer vascular complications.     

Identification of key components in the irreversibility of salmon calcitonin binding to calcitonin receptors

This study investigates the poor reversibility of salmon calcitonin (sCT) binding to rat and human calcitonin receptors. Efficacy of CT and analogue peptides in (125)I-sCT binding competition and cAMP assays was compared with the dissociation kinetics of (125)I-labelled peptides. Assessment was performed on cells stably expressing either rat or human calcitonin receptors. Dissociation kinetics of the antagonists, sCT(8-32) and AC512, revealed that binding was rapidly and completely reversible at the receptors, despite high affinity binding, suggesting that poor reversibility required the active conformation of the receptor. G protein coupling was not essential as the dissociation kinetics of (125)I-sCT binding to cell membranes did not significantly alter in the presence of GTP gamma S. Time course experiments established that the transition to irreversibility was slow, while the reversible component of binding appeared to involve a single population of either receptor states or binding sites. Pre-bound (125)I-human CT dissociated rapidly from the receptors, indicating that not all agonists bound irreversibly. To identify structural features of sCT that contribute to its poor reversibility, dissociation kinetics of sCT analogues with various structural modifications were examined. Increasing truncation of N-terminal residues of sCT analogues led to a corresponding increase in the rate of peptide dissociation. Salmon CT peptides which had been substituted at the N-terminus by 13-21 residues of human CT (hCT) were equipotent with sCT in binding competition and cAMP accumulation assays but exhibited a dissociation rate similar to hCT. In contrast, despite lower affinity and efficacy at the receptors, the chimeric analogue sCT(1-16)-hCT(17-32) displayed poorly reversible binding, similar to sCT. Analysis of the dissociation kinetics of sCT analogues with differing alpha-helix forming potential indicated that the ability to form alpha-helical secondary structure was an important factor in the rate of ligand dissociation. We hypothesise that poor reversibility results from a conformational change in the receptor and/or ligand and that this is dependent, at least in part, on interaction with residues constrained within the alpha-helix of the peptide.     

Intravenous adenosine: continuous infusion and low dose bolus administration for determination of coronary vasodilator reserve in patients with and without coronary artery disease

To assess the use of adenosine as an alternative agent for determination of coronary vasodilator reserve, hemodynamics and coronary blood flow velocity were measured at rest and during peak hyperemic responses to continuous intravenous adenosine infusion (50, 100 and 150 micrograms/kg per min for 3 min) and intracoronary papaverine (10 mg) in 34 patients (17 without [group 1] and 17 with [group 2] significant left coronary artery disease), and in 17 patients (11 without and 6 with left coronary artery disease) after low dose (2.5 mg) intravenous bolus injection of adenosine. The maximal adenosine dose did not change mean arterial pressure (-10 +/- 14% and -6 +/- 12% for groups 1 and 2, respectively) but increased the heart rate (15 +/- 18% and 13 +/- 16, respectively). For continuous adenosine infusions, mean coronary flow velocity increased 64 +/- 104%, 122 +/- 94% and 198 +/- 59% and 15 +/- 51%, 110 +/- 95% and 109 +/- 86% in groups 1 and 2, respectively for each of the three doses. Mean coronary flow velocity increased significantly after 100 and 150 micrograms/kg of adenosine and 10 mg of intracoronary papaverine (48 +/- 25, 52 +/- 19 and 54 +/- 21 cm/s, respectively; all p less than 0.05 vs. baseline) and was significantly higher than in group 2 (37 +/- 24, 32 +/- 16, 41 +/- 23 cm/s; all p less than 0.05 vs. group 1). The coronary vasodilator reserve ratio (calculated as the ratio of hyperemic to basal mean flow velocity) for adenosine and papaverine was 2.94 +/- 1.50 and 2.94 +/- 1.00, respectively, in group 1 and was significantly and similarly reduced in group 2 (2.16 +/- 0.81 and 2.38 +/- 0.78, respectively; both p less than 0.05 vs. group 1). Low dose bolus injection of adenosine increased mean velocity equivalently to that after continuous infusion of 100 micrograms/kg, but less than after papaverine. There was a strong correlation between adenosine infusion and papaverine for both mean coronary flow velocity and coronary vasodilator reserve ratio (r2 = 0.871 and 0.325; SEE = 0.068 and 0.189, respectively; both p less than 0.0005). No patient had significant arrhythmias or prolongation of the corrected QT (QTc) interval with adenosine, but papaverine increased the QT (QTc) interval from 445 +/- 44 to 501 +/- 43 ms (p less than 0.001 vs. both maximal adenosine and baseline) and produced nonsustained ventricular tachycardia in one patient.(ABSTRACT TRUNCATED AT 400 WORDS)     

Diagnostic testing for galactose-alpha-1,3-galactose,United States, 2010 to 2018

BackgroundAlpha-gal syndrome (AGS) is an emerging immunoglobulin E (IgE)–mediated allergy to galactose-alpha-1,3-galactose (alpha-gal). The geographic distribution and burden of AGS in the United States are unknown.ObjectiveTo characterize alpha-gal IgE testing patterns and describe the trends and distribution from 2010 to 2018 in the United States.MethodsThis retrospective analysis included all persons tested for alpha-gal IgE antibodies by Viracor-IBT Laboratories (Lee’s Summit, Missouri), the primary site of testing in the United States. Data included age and sex of person tested, specimen state of origin, collection date, and result value; persons with at least 1 positive test result (≥0.1 kU/L) were compared with negatives. Proportions tested and with positive test results were calculated using the US Census population estimates.ResultsOverall, 122,068 specimens from 105,674 persons were tested for alpha-gal IgE during July 1, 2010, to December 31, 2018. Nearly one-third (34,256, 32.4%) had at least 1 positive result. The number of persons receiving positive test results increased 6-fold from 1110 in 2011 to 7798 in 2018. Of those receiving positive test results, mean [SD] age was 46.9 (19.8) years; men were more likely to test positive than women (43.3% vs 26.0%). Arkansas, Virginia, Kentucky, Oklahoma, and Missouri had the highest number of persons who were tested and had a positive result per 100,000 population.ConclusionMore than 34,000 persons, most presumably symptomatic, have received positive test results for IgE antibodies to alpha-gal, suggesting AGS is an increasingly recognized public health problem. The geographic distribution of persons who tested positive is consistent with exposure to Amblyomma americanum ticks.     

Applying synthetic radiography to intraoral tomosynthesis: a step towards achieving 3D imaging in the dental clinic

Objectives:A practical approach to three-dimensional (3D) intraoral imaging would have many potential applications in clinical dentistry. Stationary intraoral tomosynthesis (sIOT) is an experimental 3D imaging technology that holds promise. The purpose of this study was to explore synthetic radiography as a tool to improve the clinical utility of the images generated by an sIOT scan.Methods:Extracted tooth specimens containing either caries adjacent to restorations (CAR) or vertical root fractures (VRF) were imaged by sIOT and standard dental radiography devices. Qualitative assessments were used to compare the conspicuity of these pathologies in the standard radiographs and in a set of multi-view synthetic radiographs generated from the information collected by sIOT.Results:The sIOT-based synthetic 2D radiographs contained less artefact than the image slices in the reconstructed 3D stack, which is the conventional approach to displaying information from a tomosynthesis scan. As a single sIOT scan can be used to generate synthetic radiographs from multiple viewing angles, the interproximal space was less likely to be obscured in the synthetic images compared to the standard radiograph. Additionally, the multi-view synthetic radiographs can potentially improve the display of CAR and VRFs as compared to a single standard radiograph.Conclusions:This preliminary experience combining synthetic radiography and sIOT in extracted tooth models is encouraging and supports the ongoing study of this promising approach to 3D intraoral imaging with many potential applications.     

A pilot study of the relationship between Doppler‐estimated carotid and brachial artery flow and cardiac index

We measured carotid and brachial artery blood flow by Doppler ultrasound in 11 human volunteers, and related these to cardiac index and to each other. The median (IQR [range]) carotid arterial blood flow was 0.334 (0.223–0.381 [0.052–0.563]) l.min^?1 on the right and 0.315 (0.223–0.369 [0.061–0.690]) l.min^?1 on the left. The brachial arterial blood flow was 0.049 (0.033–0.062 [0.015–0.204]) l.min^?1 on the right and 0.039 (0.027–0.054 [0.011–0.116]) on the left. Cardiac index was 3.2 (2.8–3.5 [1.9–5.4]) l.min^?1.m^?2. There was a moderate to good correlation between right‐and left‐sided flows (brachial: ρ = 0.45; carotid: ρ = 0.567). Brachial and carotid flow had no or a negative correlation with cardiac index (right brachial: ρ = ?0.145, left brachial: ρ = ?0.349; right carotid: ρ = ?0.376, left carotid: ρ = ?0.285). In contrast to some previous studies, we found that Doppler‐estimated peripheral arterial blood flows only show a weak correlation with cardiac index and cannot be used to provide non‐invasive estimates of cardiac index in man.     

Mechanisms of HFE-induced regulation of iron homeostasis: Insights from the W81A HFE mutation

The mechanisms by which the hereditary hemochromatosis protein, HFE, decreases transferrin-mediated iron uptake were examined. Coimmunoprecipitation studies using solubilized cell extracts demonstrated that transferrin (Tf) competed with HFE for binding to the transferrin receptor (TfR) similar to previous in vitro studies using soluble truncated forms of HFE and the TfR. At concentrations of Tf approaching those found in the blood, no differences in Tf binding to cells were detected, which is consistent with the lower binding constant of HFE for TfR versus Tf. However, cells expressing HFE still showed a decrease in Tf-mediated iron uptake at concentrations of Tf sufficient to dissociate HFE from the TfR. These results indicate that the association of HFE with TfR is not essential for its ability to lower intracellular iron stores. To test the effect of HFE on lowering intracellular iron levels independently of its association with TfR, a mutated HFE (fW81AHFE) that shows greatly reduced affinity for the TfR was transfected into tetracycline-controlled transactivator HeLa cells. HeLa cells expressing fW81AHFE behaved in a similar manner to cells expressing wild-type HFE with respect to decreased intracellular iron levels measured by iron regulatory protein gel-shift assays and ferritin levels. The results indicate that HFE can lower intracellular iron levels independently of its interaction with the TfR.