bluuebunny/crossref_metadata_2025 huggingface dataset:
Consistency of Multicenter Measurements of Heart Rate Variability in Survivors of Acute Myocardial Infarction
Authors: YI GANG , GALLAGHER MARK M. , YAP YEE GUAM , GUO XIAO‐HUA , HARRISON RIGHARD , MCDONALD JOHN T. , CAMM A. JOHN , MALIK MAREK
Published: June 2006

Heart rate variability (HRV) analysis from 24‐hour ambulatory ECG has been widely used in risk stratification of patients after myocardial infarction (MI), The accuracy of HRV assessment is known to potentially vary when different commercial systems are used. However, the consistency of HRV measurements has never been fully investigated. Twenty‐six post‐Mi patients (mean age 59 ± 8 years, 22 men) were studied, of whom 13 succumbed to sudden cardiac death (SCD) within 1 year and 13 remained alive for at least 3 years (MI survivors). Each patient had a 24‐hour Holler ECG recorded before hospital discharge. HRV analysis was performed four times from the same recordings using three different Holter tape analysis systems (Marquette, Reynolds, and CardioData) by four independent operators (CardioData system was used twice, once in the United Kingdom and once in the United States). Mean normal‐to‐normal RR intervals (mNN) and 3 HRV parameters (SDNN, RMSSD, and HRV triangular index [HRVi]) were derived from each recording. The consistency of mNN and HRV measurements was evaluated by coefficient of variance (CV) and by the Bland‐Altman method. The results demonstrated that (1) all indices measured by different systems were statistically similar (P = NS) except the measurement of RMSSD (P = 0.01), (2) the measurements of mNN were highly reproducible with a maximum mean difference of 1.8 ± 13.8 ms and maximum limits of agreement from − 14.6 to + 15.6ms. The maximum mean differences were − 1.8 ± 1.4 unit and 4.4 ± 9.6 ms for HRVi and SDNN, respectively, and RMSSD was less reproducible with a maximum mean difference of—11.1 ± 11.5 ms. and limits of agreement from—16.2 to + 9.6 ms; and (3) the consistency of mNN (CV 0.9%± 0.9%) was significantly higher than that of HRVi, SDNN, and RMSSD (P < 0.0001). The consistency of HRVi was similar to that of SDNN (4.8%± 2.1% vs 5.7%± 4.8%, P = 0.4), and the consistency of RMSSD (26.6%± 13.3%) was significantly lower than that of the other measurements (P < 0.00001). In conclusion, the measurements of mNN by different analytical systems are the most consistent among the parameters studied. The global 24‐hour measurements of HRV (SDNN and HRVi) are highly reproducible, whereas the measurement of short‐term HRV components (RMSSD) is significantly less reproducible.
Scaling Structure of Electrocardiographic Waveform During Prolonged Ventricular Fibrillation in Swine
Authors: CALLAWAY CLIFTON W. , SHERMAN LAWRENCE D. , SCHEATZLE MARK D. , MENEGAZZI JAMES J.
Published: June 2006

Ventricular fibrillation (VF) is the most common arrhythmia causing sudden cardiac death. However, the likelihood of successful defibrillation declines with increasing duration of VF. Because the morphology of the electrocardiogram (ECG) waveform during VF also changes with time, this study examined a new measure that describes the VF waveform and distinguishes between early and late VF. Surface ECG recordings were digitized at 200 samples/s from nine swine with induced VF. A new measure called the scaling exponent was calculated by examining the power‐law relationship between the summation of amplitudes of a 1,024‐point (5.12 second) waveform segment and the time scale of measurement. The scaling exponent is a local estimate of the fractal dimension of the ECG waveform. A consistent power‐law relationship was observed for measurement time scales of 0.005–0.040 seconds. Calculation of the scaling exponent produced similar results between subjects, and distinguished early VF (<4‐minute duration) from late VF (≥4‐minute duration). The scaling exponent was dependent on the order of the data, supporting the hypothesis that the surface ECG during VF is a deterministic rather than a random signal. The waveform of VF results from the interaction of multiple fronts of depolarization within the heart, and may be described using the tools of nonlinear dynamics. As a quantitative descriptor of waveform structure, the scaling exponent characterizes the time dependent organization of VF.
Effect of Underlying Heart Disease on the Frequency Content of Ventricular Fibrillation in the Dog Heart
Authors: JACOBSON JASON T. , JOHNSON DAVID , HORVATH GEORGE , GOLDBERGER JEFFREY , KADISH ALAN
Published: June 2006

Although prior studies have examined the frequency content of heal electro‐gram characteristics during fibrillation, little is know about the effects of underlying heart disease on these parameters. This study was designed to compare the frequency content of local electrograms during VF in canine models of acute ischemia, subacute infarction, and chronic myocardial infarction (MI) to those in control animals to test the hypothesis that underlying heart disease can alter the basic characteristics of VF. VF was induced using burst pacing in three groups of mongrel dogs. Five dogs were evaluated 8 weeks after LAD occlusion MI, five were evaluated 5 days after experimental MI, and 5 had VF induced before (control) and immediately after LAD occlusion (ischemia). During VF, unipolar electrograms were recorded from 112 sites on the anterior LV and electrograms were evaluated 15 and 30 seconds after VF initiation in each group. Electrograms were analyzed by fast Fourier transform. No significant time dependent changes in VF characteristics were noted. The peak frequency was highest in control animals and 8‐week MI, intermediate in 5‐day MI, and lowest in acute ischemia (P < 0.01 for pairwise comparisons). In contrast, the fractional of energy within a bandwidth of 25% peak amplitude was highest in acute ischemia, (P < 0.001) and similar in the other three groups. Infarction decreased total energy by approximately 50%. In conclusion, the pressure of ischemia or infarction alters the frequency content of VF in a complex fashion. In addition to decreasing the peak frequency, the shape of the power spectral curve is altered in models of structural heart disease. These results suggest that the electrophysiological changes produced by infarction or ischemia alter the structural organization of ventricular fibrillation.
Popping Phenomena in Temperature‐Controlled Radiofrequency Ablation: When and Why Do They Occur?
Authors: EICK OLAF J. , GERRITSE BART , SCHUMACHER BURGHARD
Published: June 2006

During temperature‐controlled radiofrequency (RF) ablation a popping sound sometimes occurs. This popping phenomenon is known to be associated with unwanted effects like blood boiling, endocardial rupture, catheter dislocation, and impedance rise. The present in vitro study determined the influence of cooling, electrode contact, and tip temperature on the occurrence of popping phenomena. Pieces of porcine ventricle were immersed in a bath of saline solution at 37°C, Forty‐two RF ablations were performed with different electrode‐tissue contact forces (i.e., 0.0–0.44N) in a temperature‐controlled mode (70°C setpoint, 30 s, 50 W maximum power output, 4‐mm tip, thermocouple). Half of the 42 ablations were performed with fluid flow (0,1 m/s, group I), the other half without flow (group II). In group I, mean tip temperature and power were 55.6 ± 8.5°C and 36.2 ± 13.8 W, resulting in a lesion volume of 121 ± 57 mm. In group II, the respective values were 67.3 ± 1.5°C and 9.9 ± 5.2 W resulting in a volume of 42 ± 18 mm3. The differences between groups were statistically significant. Overall, ten popping phenomenas occurred in group I and none in group II. Pops occurred significantly more often when the contact force was <0.1 N (8/10) and the tip temperature was <60°C (8/10). Two endocardial ruptures occurred, both were associated with a popping phenomenon. Using temperature control, the probability of pops is significantly higher when the ablation electrode and the endocardial tissue surface are exposed to fluid flow and the electrode‐tissue contact is poor. Under these conditions the tissue temperature can be much higher than the temperature measured at the tip electrode and can potentially reach 100°C causing in‐tramyocardial steam formation and a popping phenomenon.
P Wave and Far‐Field R Wave Detection in Pacemaker Patient Atrial Electrograms
Authors: THERES HEINZ , SUN WEIMIN , COMBS WILLIAM , PANKEN ERIC , MEAD HARDWIN , BAUMANN GERT , STANGL KARL
Published: June 2006

This study was undertaken to develop and test a morphology‐based adaptive algorithm for real‐time detection of P waves and far‐field R waves (FFRWs) in pacemaker patient atrial electrograms. Cardiac event discrimination in right atrial electrograms has been a problem resulting in improper atrial sensing in implantable devices; potentially requiring clinical evaluation and device reprogramming. A morphologybased adaptive algorithm was first evaluated with electrograms recorded from 25 dual chamber pacemaker implant patients. A digital signal processing (DSP) system was designed to implement the algorithm and test real‐time detection. In the second phase, the DSP implementation was evaluated in 13 patients, Atrial and ventricular electrograms were processed in real‐time following algorithm training performed in the first few seconds for each patient. Electrograms were later manually annotated for comparative analysis. The sensitivity for FFRW detection in the atrial electrogram during off‐line analysis was 92.5% (± 10.9)and the positive predictive value was 99.1% (± 1.8). Real‐time P wave detection using a DSP system had a sensitivity of 98,9% (± 1.3) and a positive predictivity of 97.3% (± 3.5). FFRW detection had a sensitivity of 91.0% (± 12.4) and a positive predictivity of 97.1% (± 4.2) in atrial electrograms. DSP algorithm tested can accurately detect both P waves and FFRWs in right atrium real‐time. Advanced signal processing techniques can be applied to arrhythmia detection and may eventually improve detection, reduce clinician interventions, and improve unipolar and bipolar lead sensing.
Permanent Transfemoral Pacemaker Implantation Is the Technique of Choice for Patients in Whom the Superior Vena Cava Is Inaccessible
Authors: BARAKAT KHALID , HILL JONATHAN , KELLY PAUL
Published: June 2006

We describe transfemoral pacemaker implantation in three patients in whom pacing via the superior vena cava was not possible or suboptimal. The first was an 88‐year‐old man with superior vena cava obstruction presenting with fractured spicardial pacing leads. Recent pneumonia increased the risks of a general anesthetic. The second patient was a 57‐year‐old man who was intolerant of a pectorally sited pacemaker because of the thinness of his anterior chest wall. The third patient was a 69‐year‐old woman who presented with an infected eroding pectorally sited pacemaker. Scarring secondary to a previous pacemaker infection rendered the contralateral pectoral site inaccessible. Since the subclavian route was inaccessible (case 1) or suboptimai (case 2 and 3), we implanted transvenous pacemakers via the femoral route, which was safe, and effective, during a 6‐month follow‐up period.
Influence of Acute Exposure to High Altitude and Hypoxemia on Ventricular Stimulation Thresholds in Pacemaker Patients
Authors: WEILENMANN DANIEL , DURU FIRAT , SCHÖNBECK MARIETTE , SCHENK BENNO , ZWICKY PETER , RUSSI ERICH W. , CANDINAS RETO
Published: June 2006

Cardiac stimulation threshold of implanted pacemakers may be influenced by a variety of endogenous and exogenous factors. High altitude provokes hypoxemia, which may change stimulation thresholds, besides causing other important physiological changes. The aim of our study was to investigate the influence of high altitude on ventricular stimulation thresholds in pacemaker patients. Thirteen patients (10 men; aged 65.5 ± 4.8 years) with implanted single chamber pacemakers (nine with Pacesetter Regency SR+ with the Autocapture feature) were exposed to an altitude of 4,000 m above sea level, as simulated in a hypobaric chamber. Stepwise ascension was performed with a speed of 5 m/s starting at 450 m above sea level. A 5‐minute rest was performed every 500 m to measure stimulation threshold at each step. After a stay of 30 minutes at 4,000 m stimulation threshold was measured, followed by a stepwise descent. Pacemaker interrogation and arterial blood gas analysis were performed at 450 and at 4,000 m, and a strength‐duration curve was determined. Blood pressure, heart rate, and oxygen saturation were monitored continuously during the study. Ascent to 4,000 m above sea level induced a significant decrease in arterial pO2 (10.7 ± 1.1 vs 5.5 ± 0.3 kPa), pCO2 (5.3 ± 0.3 vs 4.7 ± 0.4 kPa), oxygen saturation measured by arterial blood gas analysis (95.5%± 1.2% vs 79.1%± 2.5%), and increase in pH (7.39 ± 0.02 vs 7.45 ± 0.04) (P < 0.0001). Stimulation thresholds and the strength‐duration curve remained unchanged in all patients throughout the study. In conclusion, exposure to an altitude of 4,000 m above sea level with resultant hypobaric hypoxemia has no impact on ventricular stimulation thresholds. Therefore, in regard to the safety of pacing, pacemaker patients can safely be exposed to this altitude.
Voltage Dependence of ICD Lead Polarization and the Effect of Iridium Oxide Coating
Authors: NIEBAUER MARK J. , YAMANOUCHI YOSHIO , HILLS DON , MOWREY KENT , WILKOFF BRUCE L. , TCHOU PATRICK J.
Published: June 2006

Nonthoracotomy leads (NTLs) with an iridium oxide (IROX) coating exhibit lower defibrillation thresholds (DFTs) than uncoated NTLs. We tested whether adding an IROX coating to an active pectoral can would influence defibrillation efficacy. However, the primary purpose of this study was to examine the impedance changes that occur at different voltages for uncoated titanium NTLs and identical NTLs with an IROX coating. We studied anesthetized pigs with an NTL placed in the right ventricle and coupled this to an active pectoral can. Biphasic waveform DFTs were obtained for the four NTLs and can combinations: uncoated NTL and uncoated can, uncoated NTL and IROX can, IROX NTL and uncoated can. and IROX NTL and IROX can. The respective energy DFTs were: 23.6 ± 6.9, 24.1 ± 6.7, 21.3 ± 6.0, and 21.4 ± 7.0 J. The IROX NTL DFTs were significantly lower (P < 0.05) than the uncoated NTL DFTs (either can), confirming our previous study. We then used a low tilt monophasic waveform to assess impedance changes. The impedance rise for each NTL/can combination was measured at 50, 100, 300, and 700 V. Comparisons of impedance changes between voltage levels showed that the impedance rise was inversely related to voltage and was greatest with uncoated NTLs. The IROX coating of the NTL reduced the impedance rise at all shock voltages, but was particularly beneficial at the lower voltages. No advantage was seen when the pectoral can was coated with IROX regardless of which NTL was used. Our results suggest that low voltage applications, such as atrial defibrillation, would benefit most from the IROX‐coated NTL, and further studies are warranted in this area.
Sensing of Atrial Fibrillation by a Dual Chamber Pacemaker: How Should Atrial Sensing Be Programmed to Ensure Adequate Mode Shifting?
Authors: WALFRIDSSON HÅKAN , AUNES MARIA , CAPOCCI MARIANN , EDVARDSSON NILS
Published: June 2006

Patients with atrial fibrillation and a DDDR pacemaker were studied to assess mode switching at different atrial sensitivity settings. Thirty‐one patients were investigated 7 ± 9 months after pacemaker implantation and 20 of those patients were rein‐vestigated 23 ± 9 months after implant. Adequate mods switching was evaluated by stepwise programming the atrial sensitivity setting from maximal to minimal in the bipolar mode. Adequate mode switching was observed in all 31 patients during the first evaluation. The lowermost sensitivity average allowing for mode switching was 1.1 ± 0.7 mV (range 0.3–4.0 mV). A total of 22 (71%) patients demonstrated intermittent mode shifting at sensitivity settings above the atrial sensing threshold. In six (19%) patients, the adequate sensitivity threshold ranged from 0.3 to 0.5 mV, which did not allow for a two‐fold sensitivity safety margin. During the second evaluation, adequate mode switching was achieved in all 20 patients, the lowermost sensitivity average allowing for mode switching being 1.1 ± 0.7 mV (range 0.3–2.0 mV). A total of 16 (80%) patients showed intermittent mode shifting at a sensitivity setting above the atrial sensing threshold. In five (25%) patients, the sensitivity threshold ranged from 0.3 to 0.5 mV, which did not allow for a two‐fold sensitivity safety margin. Adequate mode switching was achieved in 31 of 31 patients in response to atrial fibrillation on one occasion and in all 20 patients on two occasions. It was necessary to program the atrial sensitivity to the highest possible level (0.3 mV) to ensured adequate mode switching in all cases.
Three‐Year Follow‐Up of Atrial Sensing Efficacy in Children and Adults with a Single Lead VDD Pacing System
Authors: ROSENHECK SHIMON , LEIBOWITZ DAVID , SHARON ZEHAVA
Published: June 2006

The purpose of this study was to evaluate the efficacy of atrial sensing in children with a single pass lead VDD pacing system and to compare it with the efficacy of atrial sensing in adult patients with the same pacing system. Although the feasibility of single pass lead VDD pacing system implantation in children was recently demonstrated, the efficacy of atrial sensing remains unclear. In addition, the effect of accelerated growth of children on the systems' efficacy has not been addressed. Atrial sensing followed by ventricular sensing and atrial sensing followed by ventricular pacing was prospectively evaluated in 13 children (age 0.5–15 years) and 24 adult patients (age 19–74 years). All had the same endocardial pacing system using a single pass lead. The children and adults had effective atrial sensing at a success rate of 94.00 ± 9.687% and 96.04 ± 4.64%, respectively, during mean follow‐up of 3.5 years. The atrial electrogram amplitude was similar in both groups, 1.8 ± 1.5 mV in children and 1.8 ± 1.1 mV in adults. The adult patients more frequently exhibited ventricular sensing following atrial sensing. The ventricular pacing threshold and impedance were stable in both groups. When necessary, in children, the atrial sensing was corrected by adjusting the pacemaker's lower rate programming. Highly effective atrial sensing was demonstrated in children and adult patients with a single pass lead VDD pacing system. During a mean follow‐up of 3.5 years, not only was the atrial electrogram amplitude stable, but the clinically relevant atrial sensing was highly effective, justifying endocardial pacing with single pass lead VDD pacing in children and adults with preserved sinus node function.
Basket Catheter‐Guided Three‐Dimensional Activation Patterns Construction and Ablation of Common Type Atrial Flutter
Authors: ZRENNER BERNHARD , NDREPEPA GJIN , SCHNEIDER MICHAEL , KARCH MARTIN , DEISENHOFER ISABEL , SCHREIECK JÜRGEN , SCHÓMIG ALBERT , SCHMITT CLAUS
Published: June 2006

Construction of three‐dimensional activation maps and evaluation of ablation‐created bidirectional block in the tricuspid valve‐inferior vena caval (TV‐IVC) isthmus in patients with atrial flutter (AF) are difficult with conventional mapping technique. In 36 patients with type I AF (25 men, 11 women; mean age 62 ± 10.5 years) a multielectrode basket catheter (BC) was deployed in the right atrium (RA). Out of 64 BC electrodes, 56 bipolar electrograms were derived. Three‐dimensional activation patterns were constructed with a software program. Stable electrograms of satisfactory quality were obtained in 49 ± 2 electrode pairs. Capture was possible in 36 ± 3 of bipoles. In counterclockwise AF (CCW‐AF) and clockwise AF (CW‐AF) episodes, cycle lengths and TV‐IVC isthmus conduction times were 248 ± 26 ms and 251 ± 23 ms, (P = 0.74) and 105 ± 28 ms and 106 ± 33 ms (P = 0.92), respectively. Conduction velocity in the TV‐IVC isthmus was lower than in the anterior or septal limbs of the circuit, in counterclockwise or clockwise episodes. Double potentials were recorded in 94% of patients. Three‐dimensional activation patterns were delineated and displayed as isochronal maps. The reentry circuit involved the TV‐IVC isthmus, septal, and anterior walls and a part of the RA roof anterior to superior vena cava. Postablation isthmus conduction was evaluated through the sequence criteria, local electrogram‐based criteria, and the analysis of three‐dimensional activation patterns of the paced rhythms. The complete isthmus block was associated with a significant increase of the low anterior low septal conduction interval (152 ± 29 vs 104 ± 32 ms, P = 0.001) and the low septal‐low anterior conduction interval (150 ±31 vs 107 ± 33 ms, P = 0.001). Radiofrequency ablation was successful in 32 (90%) of 36 patients. In conclusion, the current mapping system enables construction of three‐dimensional activation patterns and facilitates evaluation of the postablation TV‐IVC isthmus block in patients with AF.
Steady‐State versus Non‐Steady‐State QT‐RR Relationships in 24‐hour Holter Recordings
Authors: LANDE GILLES , FUNCK‐BRENTANO CHRISTIAN , GHADANFAR MATHIEU , ESCANDE DENIS
Published: June 2006

The aim of the present study was to investigate the QT‐RR interval relationship in ambulatory ECG recordings with special emphasis on the physiological circumstances under which the QT‐RR intervals follow a linear relation. Continuous ECG recordings make it possible to automatically measure QT duration in individual subjects under various physiological circumstances. However, identification of QT prolongation in Holter recordings is hampered by the rate dependence of QT duration. Comparison of QT duration and QT interval rate dependence between different individuals implies that the nature of the QT‐RR relationship is defined in ambulatory ECG. Holter recordings were performed in healthy volunteers at baseline and after administration of dofetilide, a Class III antiarrhythmic drug. After dofetilide, beat‐to‐beat automated QT measurements on Holter tapes were compared with manually measured QT intervals on standard ECGs matched by time. The QT‐RR relationship was analyzed at baseline in individual and group data during three different periods: 24‐hour, daytime, and nighttime. Data were collected under steady‐state or non‐steady‐state conditions of cycle length and fitted with various correction formulae. Our study demonstrated an excellent agreement between manually and automated measurements. The classic Bazett correction formula did not fit the QT‐RR data points in individual or group data. When heart beats were selected for a steady rhythm during the preceding minute, QT‐RR intervals fit a linear relationship during the day and night periods, but not during the 24‐hour period in both individual and group data. In contrast, in the absence of beat selection, data fit a more complex curvilinear relationship irrespective of the period. Our study provides the basis for comparison of QT interval durations and QT‐RR relationships between individuals and between groups of subjects.
Rapid and Accurate Measurement of Left Ventricular Function with a New Second‐Harmonic Fast‐Rotating Transducer and Semi‐Automated Border Detection
Authors: Krenning Boudewijn J. , Voormolen Marco M. , Van Geuns Robert‐Jan , Vletter W.B. , Lancée Charles T. , De Jong Nico , Ten Cate Folkert J. , Van Der Steen Anton F.W. , Roelandt Jos R.T.C.
Published: June 2006

Measurement of left ventricular (LV) volume and function are the most common clinical referral questions to the echocardiography laboratory. A fast, practical, and accurate method would offer important advantages to obtain this important information. To validate a new practical method for rapid measurement of LV volume and function. We developed a continuous fast‐rotating transducer, with second‐harmonic capabilities, for three‐dimensional echocardiography (3DE). Fifteen cardiac patients underwent both 3DE and magnetic resonance imaging (reference method) on the same day. 3DE image acquisition was performed during a 10‐second breath‐hold with a frame rate of 100 frames/sec and a rotational speed of 6 rotations/sec. The individual images were postprocessed with Matlab software using multibeat data fusion. Subsequently, with these images, 12 datasets per cardiac cycle were reconstructed, each comprising seven equidistant cross‐sectional images for analysis in the new TomTec 4DLV analysis software, which uses a semi‐automated border detection (ABD) algorithm. The ABD requires an average analysis time of 15 minutes per patient. A strong correlation was found between LV end‐diastolic volume (r = 0.99; y = 0.95x – 1.14 ml; SEE = 6.5 ml), LV end‐systolic volume (r = 0.96; y = 0.89x + 7.91 ml; SEE = 7.0 ml), and LV ejection fraction (r = 0.93; y = 0.69x + 13.36; SEE = 2.4%). Inter‐ and intraobserver agreement for all measurements was good. The fast‐rotating transducer with new ABD software is a dedicated tool for rapid and accurate analysis of LV volume and function.
A Head‐to‐Head Comparison of Infusion and Bolus Doses of Adenosine for Stress Myocardial Contrast Echocardiography
Authors: Nesser Hans Joachim , Yao Jiefen , Soman Prem , Tkalec Wolfgang , Ebner Christian , Steringer‐Mascherbauer Regina , Markt Bernhard , Samenuk David , Ng Choi‐Keung , Morcerf Fernando , Udelson James E. , Pandian Natesa G.
Published: June 2006

Background: This study was a head‐to‐head, intraindividual comparison of the diagnostic accuracy and side effect profile of bolus and infusion administration of adenosine for stress myocardial contrast echocardiography (MCE). Methods: Adenosine MCE was performed in 64 subjects, referred for stress thallium‐201 single‐photon emission computed tomography (SPECT) for known or suspected CAD. Each patient received adenosine by multiple boluses (6–12 mg/bolus) and infusion (140 μg/kg per min for 6 min) forms in random order, given at least 20 minutes apart. Results: No prolonged or serious adverse events occurred during either adenosine bolus or infusion. Compared to SPECT imaging, the sensitivity, specificity, and concordance for the diagnosis of CAD were 77%, 87%, and 82% for adenosine infusion MCE and 81%, 90%, and 86% for adenosine bolus MCE, respectively. Conclusions: Both adenosine infusion and adenosine bolus protocols are safe for MCE in humans and can be used for the diagnosis of CAD.
Eukaryotic expression of the broad‐spectrum chemokine receptor antagonist vMIP‐II and its effects on T‐cell function in vitro and in vivo
Authors: Rubant Simone , Ludwig Ralf J. , Pfeffer Jeannette , Schulze‐Johann Petra , Kaufmann Roland , Pfeilschifter Josef M. , Boehncke Wolf‐Henning , Radeke Heinfried H.
Published: June 2006

Abstract:  Pro‐inflammatory chemokines and their receptors exhibit elementary functions in cell migration and in Th1‐driven inflammatory conditions. One therapeutic strategy to prevent accumulation of pro‐inflammatory immune cells is the use of specific chemokine receptor antagonists. An interesting and promising candidate in this context is the viral antagonist MIP‐II (vMIP‐II) that acts on a broad spectrum of chemokine receptors. To study the in vitro and in vivo effects of vMIP‐II on pro‐inflammatory chemokine receptor function, we further characterized an ovalbumin‐specific murine central memory Th1IF12 clone by using RT‐PCR, cDNA array and cytometry. Using in vitro chemotaxis assays we show that eukaryotically generated vMIP‐II strongly inhibited migration of CCL2‐ or CCL5‐stimulated Th1 IF12 cells. Using intravital microscopy, we observed that CCL5 induced rolling of Th1 cells in the ear vasculature of C57Bl/6 mice. Pre‐treatment with vMIP‐II significantly reduced CCL5‐induced rolling of Th1 cells to basal levels, indicating, that vMIP‐II is also active in vivo (proportion of rolling cells: 19.4 ± 3.8%, 39.8 ± 2.9% and 26.1 ± 3.2%). In addition, investigating the anti‐inflammatory action of vMIP‐II in adoptive transfer of immunity and dinitrofluorobenzene‐induced cutaneous hypersensitivity reaction using C57Bl/6 mice, we show a direct inhibitory effect of vMIP‐II on the sensitization phase [Δ ear swelling 62 and 37 cm × 10−3 for controls and vMIP‐II treated mice (2.5 mg/kg), respectively] and effector phase (Δ ear swelling 14.8 and 3.6 cm × 10−3 for controls and vMIP‐II treated mice (2.5 mg/kg), respectively) of cutaneous hypersensitivity. These data indicate that vMIP‐II is a promising agent to interfere with chronic inflammatory (skin) diseases.
Diaphyseal bone formation in murine tibiae in response to knee loading
Authors: Zhang P. , Tanaka S. M. , Jiang H. , Su M. , Yokota H.
Published: June 2006

Mechanical stimulation is critical for bone architecture and bone mass. The aim of this study was to examine the effects of mechanical loads applied to the knee. The specific question was whether loads applied to the tibial epiphysis would enhance bone formation in the tibial diaphysis. In C57/BL/6 mice, loads of 0.5 N were applied for 3 min/day for 3 days at 5, 10, or 15 Hz. Bone samples were harvested 13 days after the last loading. The strains were measured 13±2 mu strains at 5 Hz in the diaphysis. The histomorphometric data in the diaphysis clearly showed enhanced bone formation. First, compared with nonloaded control the cross‐sectional cortical area was increased by 11% at 5 Hz and 8% at 10 Hz (both P<0.05). Second, the cortical thickness was elevated by 12% at 5 Hz (P<0.01) and 8% at 10 Hz (P<0.05). Third, mineralizing surface (MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR/BS) were increased at 5 Hz (P<0.01 for MS/BS; P<0.001 for MAR and BFR/BS) and at 10 Hz (P<0.05 for MS/BS; P<0.01 for MAR and BFR/BS). Bone formation was enhanced more extensively in the medial side than the lateral or the posterior side. The results reveal that knee loading is an effective means to enhance bone formation in the tibial diaphysis in a loading frequency‐dependent manner without inducing significant in situ strain at the site of bone formation.
The αvβ6 integrin plays a role in compromised epidermal wound healing
Authors: AlDahlawi Salwa , Eslami Ameneh , Häkkinen Lari , Larjava Hannu S.
Published: June 2006

The αvβ6 integrin is an exclusively epithelial integrin that is highly expressed during fetal development. In adult tissue, αvβ6 integrin is expressed during inflammation, carcinogenesis, and in wound healing. We previously reported that αvβ6 integrin is highly expressed in poorly healing human wounds and its over‐expression is associated with chronic wounds in a mouse model. The objective of this study was to investigate the role of αvβ6 integrin in compromised wound healing induced by hydrocortisone treatment or aging by using young and old mice deficient in or overexpressing the β6 integrin subunit in the epidermis. Untreated aged β6 integrin‐deficient (β6−/−) animals showed a significant delay in wound healing when compared to their age‐matched controls or younger β6−/− mice. The most significant delay was observed at the stages where granulation tissue deposition was occurring. Hydrocortisone treatment significantly delayed wound healing in wild‐type and β6 integrin‐deficient mice in comparison with the untreated controls. However, hydrocortisone treatment in β6 integrin overexpressing animals did not cause a significant delay in wound healing. The results of this study suggest that αvβ6 integrin plays an important role in wound healing in animals compromised by either age or stress mimicked by hydrocortisone.
The tetrapeptide acetyl‐serine‐aspartyl‐lysine‐proline improves skin flap survival and accelerates wound healing
Authors: Fromes Yves , Liu Jian‐Miao , Kovacevic Milica , Bignon Jérôme , Wdzieczak‐Bakala Joanna
Published: June 2006

The tetrapeptide acetyl‐serine‐aspartyl‐lysine‐proline (AcSDKP) has recently been recognized as a potent angiogenic factor. Given the importance of vascular blood supply in the process of tissue repair we have investigated the ability of AcSDKP to contribute to the repair of cutaneous injuries by using dorsal and abdominal skin flap models. Postoperative subdermal AcSDKP injections (5 μg/kg/injection twice a day for 3 days following flap elevation) prevented marginally perfused areas from undergoing necrosis. Mean skin survival area of abdominal and dorsal flaps ranged, respectively, from 50.9±19.3 and 53.4±4.2% in the control groups to 66.4±7.5 and 74.7±6.6% in AcSDKP‐treated groups. Furthermore, in an ex vivo assay, AcSDKP applied locally to skin explants at doses from 10−8 to 10−5 M improved survival of the explanted skin exposed to UVB irradiation at 10 J/cm2. Increased reepithelialization, as well as higher levels of expression of basal keratin 14 and increased expression of fibronectin was observed after topical application of AcSDKP. These data provide experimental evidence that AcSDKP can improve the viability of ischemic skin flaps in the rat by promoting angiogenesis. Moreover, it enhances wound healing of injured avascular skin explants. Thus, these findings identify AcSDKP as a new tissue‐repair agent and suggest its potential clinical use for the management of skin wounds.
Clinical assessment of infection in nonhealing ulcers analyzed by latent class analysis
Authors: Lorentzen Henrik F. , Gottrup Finn
Published: June 2006

The distinction between bacterial colonization and infection relies on clinical judgement. Determining sensitivity and specificity of this judgement are problematic as no gold standard exists. Six specialists in wound management independently assessed 120 nonhealing chronic wounds. Sixty‐five (54.2%) patients had venous ulcer, 18 (15%) arterial ulcers, 15 (12.5%) ulcerative pyoderma gangraenosum, 12 (10%) neuropathic or pressure ulcers, six (5%) vasculitis ulcers, and four patients had ulcers caused by a primary or metastatic cancer disease. Unrestricted latent class analysis was used for determining sensitivity and specificity in the observer's assessment of hypergranulation, redness, and overall impression of infection. Interrater agreement among observers was determined by restricted latent class analysis. The observers used the diagnoses (redness, hypergranulation, and overall impression of infection with different frequencies (p<0.001, Cochrane's Q test). A two latent class model fitted data. Sensitivity for hypergranulation ranged from 3 to 82%, for redness from 34 to 91% and for overall impression of infection from 37 to 90%. None of the observers were interchangeable. These results indicate that clinical assessment of chronic wounds for the presence of infection are difficult tasks accompanied by great variability and low reliability.
Management of 13 cases of canine respiratory disease using inhaled corticosteroids
Authors: Bexfield N. H. , Foale R. D. , Davison L. J. , Watson P. J. , Skelly B. J. , Herrtage M. E.
Published: June 2006

Objectives:To determine the value of inhaled corticosteroids in the management of chronic inflammatory airway disease in dogs.

Methods:Medical records of dogs that were presented for the investigation of respiratory disease were reviewed retrospectively. Criteria for inclusion were knowledge of previous medical treatment including side effects, diagnosis of the underlying disease, use of inhaled corticosteroids and at least two‐months follow‐up data.

Results:Thirteen dogs that fulfilled the criteria were identified. Ten dogs were diagnosed with chronic bronchitis and three with eosinophilic bronchopneumopathy. Four dogs had not previously received corticosteroid treatment for their respiratory disease, and all these showed a reduction or a resolution of clinical signs without obvious side effects after inhaled corticosteroid therapy. Nine dogs had previously received oral or parenteral corticosteroids for treatment of their respiratory disease, and all had exhibited side effects. Five of these dogs were treated with inhaled corticosteroids alone, and all exhibited an improvement in clinical signs without observable side effects. The remaining four dogs were treated with a combination of inhaled and oral corticosteroids, and all showed improvement in clinical signs and reduction in side effects. Inhaled medication was well tolerated in all dogs.

ClinicalSignificance:Inhaled corticosteroids were used for the management of chronic bronchitis and eosinophilic bronchopneumopathy in 13 dogs, and these may have the advantage of reducing side effects associated with oral corticosteroids.
Retrospective study of fever in dogs: laboratory testing, diagnoses and influence of prior treatment
Authors: Battersby I. A. , Murphy K. F. , Tasker S. , Papasouliotis K.
Published: June 2006

Objectives: To analyse the demographic information of dogs referred for investigation of fever, to determine the usefulness of various diagnostic investigations and to assess the effect of treatment before referral on the presence of fever at referral, the duration of the investigation and the ability to reach a final diagnosis.

Methods: The clinical records of 66 dogs, in which fever was part of the clinical signs documented by the referring veterinary surgeon, were reviewed. The effects of treatment 24 hours before referral on temperature at initial consultation and on time to diagnosis were evaluated. The effect of body temperature at initial consultation on cost and on time to diagnosis was also determined. The effect of insurance on costs incurred was assessed. The utility of different diagnostic investigations was recorded, and cases were classified according to the final diagnosis.

Results: Only 34·8 per cent of dogs were diagnosed with immune‐mediated disease, with most frequent diagnoses being steroid‐responsive meningitis and polyarthritis. Treatment 24 hours before referral significantly increased the time to diagnosis (P=0·004) and affected the presence of fever at referral (P=0·006). Insurance status did not significantly affect cost incurred by the owner.

Clinical Significance: This study documents a high incidence of immune‐mediated disease in dogs referred for investigation of fever. It also documents a higher incidence of inflammatory central nervous system disease in febrile dogs than that reported previously. Of the diagnostic modalities employed in the majority of cases, radiography, cytology and bacteriological and fungal cultures (fluids/tissues) were the most useful. It is suggested that treatment is withdrawn or withheld before commencing diagnostic investigation of fever.
Lymphocytic‐plasmacytic thyroiditis and glomerulonephritis in a boxer
Authors: Mansfield C. S. , Mooney C. T.
Published: June 2006

An 18‐month‐old boxer was presented for investigation of profound lethargy, and primary hypothyroidism was diagnosed. A strong antithyroglobulin antibody titre was also present, indicating lymphocytic (immune‐mediated) thyroiditis as the cause of hypothyroidism. A concurrent protein‐losing glomerulonephropathy was also detected, although the aetiology could not be determined at initial presentation. Thyroid replacement and dietary therapy were prescribed. The dog improved clinically for approximately 12 months when it was re‐presented with poorly controlled hypothyroidism and renal failure. Postmortem examination confirmed the presence of lymphocytic‐plasmacytic thyroiditis, in conjunction with membranoproliferative glomerulonephritis and renal failure.
Tag-Team Recycling
Authors: Leslie Mitch
Published: June 2006

Tidying up might take a bulldozer or a sponge, depending on whether the mess is a wrecked building or a spilled can of Coke. Similarly, cells rely on different mechanisms when they need to remove damaged proteins in bulk or one by one. New work suggests that, contrary to conventional wisdom, if one of these mechanisms fails, the other can take over part of its work. The results support the notion that deterioration of a particular cleanup system promotes aging.
Environmental Movement
Authors: Leslie Mitch
Published: June 2006

"Out of cell, out of mind" once described researchers' attitude toward the extracellular matrix, the molecular mesh that supports cells. But researchers have learned that cells and the matrix interact. Age alters the extracellular matrix, slowing wound healing, hardening the heart, and preventing brain renewal in Parkinson's disease. By reversing these changes, researchers might be able to fend off some of old age's worst afflictions.
SENS and the Polarization of Aging-Related Research
Authors: Gray Douglas A. , Bürkle Alexander
Published: June 2006

The second Strategies for Engineered Negligible Senescence conference (SENS II) featured some very provocative ideas. The explicit objective of extending human life span indefinitely has opened a large rift between the meeting's organizer and those who believe he is acting unscientifically, perhaps recklessly. Two SENS conference participants present their views on the divisive nature of SENS.
Aging in Check
Authors: Dai Wei , Wang Xiaoxing
Published: June 2006

The spindle checkpoint monitors the interaction between spindle microtubules and kinetochores to prevent precocious entry into anaphase, delaying this stage of mitosis until all condensed chromosomes have been attached to the mitotic spindle in a bi-oriented manner (so that the two kinetochores associated with a pair of sister chromatids are oriented toward opposite poles of the spindle). In addition to conserved
Bub
and
Mad
family members, which are known to function in the spindle checkpoint pathway in organisms ranging from yeast to mammals, two mRNA transport genes,
Rae1
and
Nup9
, are also involved in the spindle checkpoint function in mammals. Biochemically, activated spindle checkpoint components have been shown to suppress the activity of the anaphase promoting complex/cyclosome. It is generally thought that decreased activity of the checkpoint components predisposes cells to chromosomal instability, aneuploidy, and malignant transformation. Interestingly, a recent study has shed light on a new function of the spindle checkpoint components Bub3 and Rae1 in the regulation of aging. Mice with haploinsufficiency of
Bub3
and
Rae1
have a short life span that is associated with the early onset of aging-related features. The progeroid phenotypes caused by deficiency of
Bub3
and
Rae1
are tightly linked to precocious activation of cellular senescence, but not apoptotic, programs. Therefore, premature aging, rather than neoplastic transformation, may be the major manifestation of a compromised spindle checkpoint in vivo.
In Praise of Insulin Resistance
Authors: Leslie Mitch
Published: June 2006

Insulin resistance, a condition in which body cells quit heeding the hormone, is a stop on the road to type 2 diabetes and a possible heart attack. But a new study of mice indicates that if particular immune cells become unresponsive to insulin, they help fend off one lethal complication of diabetes: atherosclerosis. The work suggests that insulin resistance in these cells curtails inflammation that promotes arterial obstructions.
What Good Is Growing Old?
Authors: Leslie Mitch
Published: June 2006

Defying evolutionary orthodoxy that aging is a disorderly collapse, some researchers argue that the process is an adaptation. Many of these scientists posit that group selection, a controversial form of natural selection in which the group's interests take precedence over those of the individual, drives the evolution of aging. To support their contention that senescence is genetically programmed, the researchers list evidence such as the existence of mutant organisms that live longer than normal, which suggests that unaltered creatures are "voluntarily" dying. Most evolutionists scoff at programmed aging and group selection, which conflict with the prevailing view that natural selection favors traits that benefit individuals over groups. Other scientists are probing whether aging helps reduce competition between relatives, a less controversial alternative to group selection.
A Shared Splice Site?
Authors: Leslie Mitch
Published: June 2006

Slicing messenger RNA molecules in the wrong position cuts short the lives of children with a disease that resembles speedy aging, and new research suggests that cells from old people make the same mistake. The finding implies that normal aging shares a mechanism with the rare genetic ailment.
Neuropathology in Alzheimer's Disease: Awaking from a Hundred-Year-Old Dream
Authors: Nunomura Akihiko , Castellani Rudy J. , Lee Hyoung–gon , Moreira Paula I. , Zhu Xiongwei , Perry George , Smith Mark A.
Published: June 2006

For one hundred years after Alois Alzheimer's first report of Alzheimer's disease (AD) in 1906, the pathological hallmarks of the disease, senile plaques and neurofibrillary tangles (NFTs), have been attractive targets for researchers. Therefore, not surprisingly, efforts to understand disease mechanisms have concentrated on the cell biology of amyloid-β (Aβ) deposition as senile plaques or on the phosphorylation and aggregation of tau as NFTs. However, it now appears that this focus on pathology as a central contributor to disease may be misguided. Indeed, neurons associated with Aβ and NFTs in AD brain show a decrease in oxidative damage relative to those in vulnerable but morphologically intact areas of the brain, suggesting that neurodegenerative lesions are compensatory phenomena, and thus manifestations of cellular adaptation. That Aβ and tau accumulations indicate an age-related physiological reaction to chronic stress calls into question the rationale of current therapeutic efforts targeted toward lesion removal. Moreover, if this concept holds true for pathology in other neurodegenerative diseases, we may need to restructure our thinking and undergo a paradigm shift before substantial progress can be made in therapeutic intervention.
Toward a Better Understanding of Klotho
Authors: Nabeshima Yo-ichi
Published: June 2006

klotho
mutant mice were originally described as a short-lived mouse model with premature aging-like disorders. The
klotho
gene responsible for these phenotypes encodes a type I membrane protein with a considerable similarity to β-glycosidase.
klotho
is predominantly expressed in tissues functioning in the regulation of calcium homeostasis. Suggested functions of Klotho are (i) a fundamental regulator of calcium homeostasis, namely, a cofactor for the fibroblast growth factor (FGF) receptor 1c in FGF23 signaling and a regulator of parathyroid hormone secretion; (ii) a hormone that interferes with the intracellular signaling of insulin and insulin-like growth factor-1; and (iii) a β-glucuronidase that activates the transient receptor potential ion channel TRPV5 by trimming its sugar moiety. How can we reconcile these pleiotropic functions of Klotho? Is there any common mechanism? Further in vivo studies, and biochemical as well as physiological analyses, are required for a better understanding of the molecular aspects of Klotho.
Pushing the Envelope
Authors: Leslie Mitch
Published: June 2006

Cell biologists once dismissed lamins as the backside of the nuclear membrane, but within the last 10 years, the proteins have hit the big time. Scientists have identified many new functions for lamins: The proteins help repair DNA, control gene activity, and spur precursor fat cells to grow up. Faulty lamins cause at least 12 diseases, and researchers have been discovering new mutations every year. Although lamin-related diseases remain untreatable, recent findings suggest that certain cancer drugs might alleviate symptoms in one type of illness. New work suggests that lamin defects might also underlie aging.
Shortcut to Death
Authors: Leslie Mitch
Published: June 2006

Like shipwrecked sailors, famished cells sometimes turn to cannibalism. Rather than eating their mateys, though, they devour their own contents. A previously overlooked protein boosts cancer cells' appetite, triggering them to commit suicide, according to a new study. The research solidifies the controversial connection between self-consumption and cancer.