Congenital abnormalities of the aortic arch: MR imaging

Thirty-four patients, 1 month to 63 years old, with known or suspected congenital abnormalities of the aortic arch underwent magnetic resonance (MR) imaging. Sixteen patients were studied retrospectively, 18 prospectively. In all retrospective studies, the aortic arch abnormality was seen with MR imaging. In the prospective studies, MR imaging enabled diagnosis in 15 of 18 (83%) patients. Twenty-nine of 34 patients underwent two-dimensional echocardiography; nine were studied retrospectively, 20 prospectively. In the prospective studies, echocardiography enabled diagnosis in 13 of 20 (65%) patients. Although two-dimensional echocardiography has a high sensitivity in the detection of aortic arch abnormalities in the neonate, arch abnormalities in the neonate, its sensitivity is lower in older children, adults, and postoperative patients. The authors' experience shows that MR imaging is an important, noninvasive modality in the evaluation of older children, adults, and postoperative patients with congenital aortic arch abnormalities.     

Screening of diabetic patients for microalbuminuria in primary care--The PROSIT-Project. Proteinuria Screening and Intervention.

The PROSIT (Proteinuria Screening and Intervention) Project started in 1993 in order to obtain data on the prevalence of micro- and macroalbuminuria in diabetic patients treated in primary care, to establish an easy screening programme for microalbuminuria, in which also diabetic patients can participate in self-responsibility, and to implement a specific intervention programme for incipient nephropathy. In 58 representative doctor's offices 647 diabetic patients were included, who performed at home self-tests for microalbuminuria on three days within one week using the early morning urine and a newly developed qualitative immunologic test-strip for microalbuminuria. After storage they returned the same urine samples to their doctors' offices for semiquantitative retesting with the immunologic test-strip Micral-Test II. In case of positive results the proteinuria dipstick Combur-9-Test was applied in order to exclude other causes of positive microalbuminuria (e.g. urinary tract infection). Data of 569 patients (6% Type 1, 88% Type 2 and 6% secondary diabetes) could be analysed. Both qualitative self-testing for microalbuminuria at home and semiquantitative retesting in doctors' offices were found to be feasible. Based on semiquantitative retesting the prevalences of microalbuminuria (macroalbuminuria) were 19.6% (0%) in Type 1 diabetes, 17.2% (10.8%) in Type 2 diabetes and 11.7% (7.8%) in secondary diabetes. Type 2 diabetic patients showed a clear correlation between albuminuria and diabetes duration, HbA1c, serum creatinine, triglycerides as well as micro- and macrovascular complications. 227 patients with micro- or macroalbuminuria were included into the ongoing PROSIT intervention programme.     

Iron supplementation in female blood donors deferred by copper sulfate screening

Female blood donors with low hematocrit levels detected by copper sulfate screening were selected randomly to receive either 75 mg of iron per day, as ferrous gluconate, or a calcium phosphate placebo. Their ferritin, serum iron, total iron-binding capacity, zinc protoporphyrin, and hemoglobin values, as well as their suitability to donate blood, were determined initially (Visit 1) and at four follow-up visits (Visits 2-5). By the second visit, the serum ferritin and iron values of donors receiving iron supplementation differed significantly from those of donors receiving placebo. By the fifth visit, a less marked but significant increase in hemoglobin had occurred in the iron group, but not in the placebo group. At no time was there a significant difference between the groups' suitability to donate blood, with each group donating at almost half of their visits. The authors conclude that iron supplementation at this dose level in deferred female blood donors improves their iron status and hemoglobin levels, but does not significantly increase their suitability to donate blood as compared with the suitability of placebo-treated donors.     

Evaluation of the Atrial Evoked Response for Capture Detection with High-Polarization Leads

AutoCapture™ based on the evoked response can be confounded by electrode polarization. In this study, polarization was measured in human subjects who had chronic atrial leads. The aim of the study was to determine whether electrode polarization can be measured using a time integral atrial evoked-response integral (AERI) of the negative portion of the atrial paced ER evoked-response signal and to determine whether high-polarization atrial leads unsuitable for AutoCapture™ can be identified a priori. Atrial intracardiac-electrogram (IEGM) signals from 39 patients with implanted pacemakers were recorded and analyzed. The signals were recorded during conventional atrial-threshold searches. A total of 221 atrial-capture thresholds were recorded, ranging from 0.25 to 2.75 V with a mean of 0.79 V. Each evoked response was evaluated using the AERI in a 36 ms window following the 0.4 ms atrial stimulus. The polarization was estimated as a linear function of stimulus voltage using the evoked-response signal integral of captured beats identified on the IEGM. The 221 threshold-search datasets were obtained using leads with eight different electrode materials. Polarization could be measured using AERI as a function of stimulus voltage. Furthermore, this polarization measure can be used to identify high-polarization leads, which are ill suited for the atrial AutoCapture™ algorithm.     

Optimizing the Geometry of Implantable Leads for Recording the Monophasic Action Potential with Fractally Coated Electrodes

This study investigates the influence of various lead geometry on intracardial signals like the monophasic action potential (MAP) to optimize the geometry of implantable MAP leads. The experimental results were compared with a field theoretical approach to the origin of MAP from the transmembrane potential (TAP). During the experiments several lead geometries (tip surface: 1.3 to 12 mm²; tip-ring distance: 0.8 mm to 25 cm; ring surface: 1.8mm² to 40 mm²) were investigated in endo- and epicardial positions in 12 dogs (17±9 kg). The electrodes were fixed passively (tines) or actively (screws). MAP was recorded during several interventions and correlated with MAP measured using an Ag-AgCl MAP catheter. The experimental results showed that small tips provided high MAP amplitudes with less pressure. No difference was observed using active and passive fixations. A tip-ring distance smaller than 5 mm with a ring surface smaller than the tip (<5 mm²) avoided artifacts in the repolarization course. For the theoretical approach the quasistatic, anisotropic bidomain model was calculated in smalt unity volumes V_i where the TAP φ_m was constant and represented by the current density J. Two solutions for electrode positions at and outside the heart were achieved. By superposition of each solution φ_ei the summed potential at the electrode position was calculated. The theoretical findings show in good correlation with the experimental results that a larger distance than 10 mm leads to distortions in repolarization course by signals proportional to φ_out.     

Dual Chamber Pacing in Hypertrophic Obstructive Cardiomyopathy: Beneficial Effect of Atrioventricular Junction Ablation for Optimal Left Ventricular Capture and Filling

Clinical improvement with dual chamber pacing bas largely been reported in patients suffering from hypertrophic obstructive cardiomyopathy and mainly attributed to the reduction of the subaortic pressure gradient. To be effective, pacing must induce a permanent and complete capture of the LV. In two patients of our collective, symptoms (angina and dyspnea NYHA Class III and/or syncopes) persisted or relapsed despite pacing. This was related to the inability to obtain full LV capture due to a too-short native PR interval. RF ablation of the AV junction was therefore performed in botb patients, resulting in permanent AV block in one and prolonged PR interval up to 310 ms in the second. Pacing was thereafter associated with an immediate and significant clinical improvement related to permanent LV capture, whatever the patient's activity. After RF ablation, the AV delay was set up to induce the best LV filling, as assessed by Doppler analysis of mitral flow. Our observations suggest that RF ablation or modification of the AV junction can be a successful procedure in some patients with residual or recurrent symptoms, when the latter result from a loss of capture or from the inability to program an AV delay tbat does not compromise the active component to LV filling. Doppler echocardiography is a simple and effective mean to assess the hemodynamic effect of AV interval modulation in this setting.     

Intraindividual Reproducibility of Heart Rate Variability

Heart rate variability was determined from three consecutive Holter recordings performed on days 1, 7, and 28 in 17 normal subjects, in 13 patients with angiographically normal coronary arteries, and in 9 patients with remote myocardial infarctions. Group data of several time and frequency domain measures of heart rate variability were highly reproducible (correlation coefficients 0.629–0.894). However, some individuals exhibited considerably larger day-to-day variations in heart rate variability. Single heart rate indices differed by up to 50% between two Holter recordings. Such potential differences must be considered when repeated heart rate variability determinations are used to assess changes in neurocardiac reflex regulation or effects of therapeutic interventions.     

Evidence that opioids may have toll-like receptor 4 and MD-2 effects

Opioid-induced proinflammatory glial activation modulates wide-ranging aspects of opioid pharmacology including: opposition of acute and chronic opioid analgesia, opioid analgesic tolerance, opioid-induced hyperalgesia, development of opioid dependence, opioid reward, and opioid respiratory depression. However, the mechanism(s) contributing to opioid-induced proinflammatory actions remains unresolved. The potential involvement of toll-like receptor 4 (TLR4) was examined using in vitro, in vivo, and in silico techniques. Morphine non-stereoselectively induced TLR4 signaling in vitro, blocked by a classical TLR4 antagonist and non-stereoselectively by naloxone. Pharmacological blockade of TLR4 signaling in vivo potentiated acute intrathecal morphine analgesia, attenuated development of analgesic tolerance, hyperalgesia, and opioid withdrawal behaviors. TLR4 opposition to opioid actions was supported by morphine treatment of TLR4 knockout mice, which revealed a significant threefold leftward shift in the analgesia dose response function, versus wildtype mice. A range of structurally diverse clinically-employed opioid analgesics was found to be capable of activating TLR4 signaling in vitro. Selectivity in the response was identified since morphine-3-glucuronide, a morphine metabolite with no opioid receptor activity, displayed significant TLR4 activity, whilst the opioid receptor active metabolite, morphine-6-glucuronide, was devoid of such properties. In silico docking simulations revealed ligands bound preferentially to the LPS binding pocket of MD-2 rather than TLR4. An in silico to in vitro prediction model was built and tested with substantial accuracy. These data provide evidence that select opioids may non-stereoselectively influence TLR4 signaling and have behavioral consequences resulting, in part, via TLR4 signaling.     

Post-thymic regulation of CD5 levels in human memory T cells is inversely associated with the strength of responsiveness to interleukin-15

Immunologic memory is a critical feature of the adaptive immune system to fight recurrent infections. However, the mechanisms that shape the composition and function of the human memory T-cell pool remain incompletely understood. We here demonstrate that post-thymic human T-cell differentiation was associated with the downregulation, but not loss, of the inhibitory molecule CD5. The sensitivity of human CD8(+) and CD4(+) memory T cells to interleukin (IL)-15 was inversely associated with the level of CD5 expression. CD5 expression was downregulated by IL-15-mediated signaling in vitro and CD5(lo) memory T cells accumulated in the bone marrow. Persistent antigenic stimulation, as in the case of cytomegalovirus infection and rheumatoid arthritis (RA), was also associated with an increased number of CD5(lo) memory T cells. In conclusion, CD5 may be a useful marker to identify memory T-cell subsets with distinct responsiveness to the homeostatic cytokine IL-15.