E-SELECTIN EXPRESSION IN EXPERIMENTAL MODELS OF INFLAMMATION IN MICE

E-selectin (CD62E, formerly termed ELAM-1) is a cytokine-inducible adhesion molecule which mediates the binding of neutrophils, monocytes, and skin homing T-cells. The murine homologue of E-selectin has been cloned. A monoclonal antibody (21KC10) was used here to study immunohistochemically the expression and regulation of murine E-selectin in vitro and in vivo . As described for the human system, there was no staining of normal endothelium in skin and other tissues. LPS and tumour necrosis factor-alpha (TNF-α ), but not interleukin-4 (IL-4) or interferon-gamma (IFN- γ), induced a transient expression of E-selectin, both when injected in vivo and when added to endothelial cell lines in vitro. To analyse temporal expression of E-selectin under pathophysiological conditions in vivo, we chose two murine models of inflammation: allergic (ACD) and irritant contact dermatitis (ICD). Expression of E-selectin was found to be induced on vascular endothelium of post-capillary venules in both ACD and ICD. In ICD, maximal staining of endothelial cells occurred earlier than in ACD. Expression of E-selectin during ICD and ACD was then compared between strains of mice which differ with regard to the intensity of their inflammatory reaction. BALB/c mice, which in contrast to C57BI/6 mice show a denser infiltrate and prolonged influx of granulocytes and monocytes, revealed a more pronounced and more prolonged expression of E-selectin than C57BI/6 mice. This held true for both ACD and ICD, and in each case, peak expression of E-selectin was associated with the highest density of the leukocytic infiltrate. This study thus reveals regulatory mechanisms involved in the expression of murine E-selectin in vivo and in vitro . It also demonstrates a correlation between endothelial expression of E-selectin and the genetically determined intensity of the inflammatory response.     

Unusual thionation of a cyclic hexapeptide

One carbonyl oxygen of the cyclic hexapeptide cycle(-Gly¹-Pro²-Phe³-Val⁴-Phe⁵-Phe⁶-) (A) can be selectively exchanged with sulphur using Yokoyama's reagent. Surprisingly it was not the C=O of Gly¹ but that of Phe⁵ which was substituted and cyclo(-Gly¹-Pro62-Phe³-Va1⁴-Phe⁵ψ[CS-NH]Phe⁶-) (B)was obtained. Thionation results in a conformational change of the peptide backbone although the C=O of Phe⁵ and the corresponding C=S are not involved in internal hydrogen bonds. Two isomers in slow exchange, containing a CIS Gly¹-Pro² bond in a βVIa-turn (minor) and a trans Gly-Pro bond in a βII′-turn (major), were analyzed by restrained molecular dynamics in vacuo and in DMSO as well as using time dependent distance constraints. It is impossible to fit all experimental data to a static structure of each isomer. Interpreting the conflicting NOES, local segment flexibility is found. MD simulations lead to a dynamic model for each structure with evidence of an equilibrium between a βI- and βII-turn about the Val⁴-Phe⁵ amide bond in both the cis and trans isomers. Additionally proton relaxation rates in the rotating frame (R_1p) were measured to verify the assumption of this fast βI/βII equilibrium within each isomer. Significant contributions to R_1p-rates from intramolecular motions were found for both isomers. Therefore it is possible to distinguish between at least four conformers interconverting on different time scales based on NMR data and MD refinement. This work shows that thionation is a useful modification of peptides for conformation-activity investigations.     

Incidence of ICD Lead Related Complications During Long-Term Follow-Up: Comparison of Epicardial and Endocardial Electrode Systems

The aim of this study was to evaluate the longterm stability of epicardial and endocardial lead systems for third-generation cardioverter defibrillators (ICDs) and to assess the usefulness of diagnostic tools. One hundred forty patients with 61 epicardial (43.6%) and 79 nonthoracotomy systems (56.4%) were followed for 2 5 ± 19 months. A total of 18 (12.9%) lead related complications were documented. Complications of epicardial systems were detected in 10 patients (16.4%) during a follow-up time of 36 ± 8 months: crinkling of patch electrodes in 6 patients (9.8%), insulation breakage of sensing electrodes in 2 patients (3.3%), and adapter defect in 2 patients (3.3%). Eight of the patients (10.1%) with transvenous-subcutaneous systems had lead related complications during a 13 ± 6 months follow-up: fracture of the subcutaneous patch lead in 2 patients (2.5%), dislodgment of the right ventricular lead in 2 patients (2.5%), dislodgment of the superior vena cava lead in 2 patients (2.5%), insulation breakage of sensing electrodes in 1 patient (1.3%), and connector defect in 1 patient (1.3%). There was no significant difference in the incidence of lead related complications between epicardial and endocardial systems (P > 0.05). Fractures, dislodgments, and crinklings were documented within the first 8 ± 5 months by regular chest X ray. Defects of insulation, adapter, or connector were detected 22 ± 10 months after implantation and were associated with delivery of multiple inappropriate ICD therapies. An operative lead revision was indicated for 4 epicardial (6.6%) and 6 endocardial (7.6%) lead systems. Conclusions: Endocardial lead systems offer a similar long-term stability as compared to epicardial had systems. Chest X ray is the most useful tool to detect lead fracture, dislodgment. and patch crinkling. Marker recordings or real-time electrograms have not been helpful in this series to identify patients with suspected lead defects prior to the experience of inappropriate ICD discharges.     

An 80-kDa Syncytiotrophoblast Alloantigen Bound to Maternal Alloantibody in Term Placenta

PROBLEM : We have shown that most of the IgG present on term syncytiotrophoblast, membrane, microvesicles is bound to an 80 kDa protein antigen (R80K). METHODS : Microvesicles were prepared from term human placenta, and the IgG eluted at pH3. RESULTS : When IgG antibody was eluted at pH3 and reacted with acid-treated vesicles of other placentae, the alloantibody always bound to the preparation from which it was obtained, but only to about 10% of acid-treated preparations from other placentae. A similar polymorphic protein found in association with IgG antibody was found in term horse placentae. Cross-reactivity of the antibodies between species was not found. Using binding of labelled antibody, complement dependent cytotoxicity and FACS two-color analysis, the human polymorphic antigen was present on peripheral blood monocytes and B-lympho-cytes. The R80k antigen on intact microvesicles was resistant to trypsin, but after acid elution of IgG, trypsin released a soluble 50 kDa fragment which reacted with the acid-eluted IgG antibody. CONCLUSION : The presence of antibodies to R80K in all term placentae studied, including first pregnancies, suggests that development of this alloantibody may be a normal requirement for successful pregnancy.     

Early Postinterventional Stent Stenosis of a Ductus Stent Implanted for Palliation in a Newborn with Pulmonary Atresia with Intact Ventricular Septum: Successful Management with Bailout Stenting

A newborn with pulmonary atresia with intact ventricular septum (PA-IVS) was treated with radiofrequency current perforation of the atretic pulmonary valve. As the right ventricle was hypoplastic (z-value of the tricuspid valve: —4) the arterial duct was stented with a Gianturco-Roubin GR II stent. Early postinterventionally, the patient became cyunotic and compromised blood flow across the stented ductus arteriosus despite adequate stent position was detected echographically. The newborn was treated successfully with the implantation of a Palmaz stent (Johnson & Johnson Interventional Systems, Warren, NJ, USA) into the obstructed Gianturco-Roubin GR II stent. The Gianturco-Roubin GR II stents might be associated with the risk of early stent stenosis after implantation in actively contracting tissues like the ductus arteriosus. In patients with early stent stenosis after ductal stenting, bailout implantation of a subsequent stent can be performed. Transcatheter procedures can be effective means for therapy of PA-IVS . (J Interven Cardiol 2000;13:39–44)     

Influence of Different Conditioning Methods on Force and Fatigue Resistance in Chronically Stimulated Skeletal Muscles

A study was undertaken to compare different conditioning methods for the transformation of latissimus dorsi muscle into a fatigue resistant one for application in circulatory assist. In ten sheep four electrodes were sutured to the epineurium of the left thoracodorsal nerve for indirect electrical stimulation of the latissimus dorsi muscle. In six sheep a "carousel stimulation, " a special multichannel stimulation, in combination with a recently developed conditioning protocol was used for muscle conditioning ( multichannel method ). In four sheep, a conventional stimulation protocol using single channel stimulation was applied for transformation of the muscle (single channel method). The final experiments were carried out when fatigue resistance was obtained. The maximum tetanic forces at different preloads were determined and fatigue resistance was tested during 20 minutes of continuous stimulation. Both conditioning patterns led to fatigue-free chronic stimulation. Muscles conditioned by multichannel stimulation exhibited between 20% and 33% less force than the contralateral unconditioned muscles, whereas in the single channel group this loss was between 32% and 43%. Thus, the multichannel method revealed relatively superior in preserving muscle force for chronic stimulation.     

Quality of recovery from two types of general anesthesia for ambulatory dental surgery in children: a double-blind, randomized trial

Background:  Pediatric dental procedures are increasingly performed under general anesthesia because of the inability to cooperate, situational anxiety, or other behavioral problems. Volatile anesthetics have been associated with emergence delirium in children, whereas the use of propofol for anesthetic maintenance has been shown to reduce the incidence of emergence delirium after other types of surgeries. The aim of this study is to compare a sevoflurane-based anesthetic with a propofol-based technique as it relates to the incidence of emergence delirium and the quality of recovery after pediatric dental surgery, in patients who present with risk factors for perioperative behavioral issues.
Methods:  We prospectively collected data of 179 pediatric patients scheduled for ambulatory dental surgery using a double-blind and randomized trial design. Subjects were anesthetized following standardized protocols for either a sevoflurane- or a propofol-based technique. The incidence of emergency delirium, as measured by the Pediatric Anesthesia Emergence Delirium score, was the primary outcome. Secondary outcomes included the incidence of postoperative nausea and vomiting (PONV), number of nursing interventions in the recovery room, time to discharge readiness, and parental satisfaction.
Results:  We found no difference in the incidence of emergence delirium after both types of anesthesia. However, use of sevoflurane significantly increased both the risk of PONV and the number of postoperative nursing interventions. Discharge criteria were met about 10 min earlier in patients anesthetized with sevoflurane. Parental satisfaction was equally high with both anesthesia regimens.
Conclusions:  A propofol-based anesthetic technique did not lead to a lower incidence of emergence delirium after dental surgery in children but did result in significantly less PONV and fewer postoperative nursing interventions.     

Management of Patients with Acute Coronary Syndrome: Should We Rely on Cardiac Markers?

Early diagnosis and risk stratification of patients presenting to the emergency room for a suspected acute coronary syndrome is an emerging problem. In general, diagnosis is based on an ECG, clinical presentation, and elevated cardiac markers. In the past decade cardiac troponins and myoglobin have been identified as important markers for the global assessment and treatment of patients with acute coronary syndromes. Recent studies have identified patients with increased troponin I and T levels as a high risk population gaining benefit from the adjunctive treatment with glycoprotein (GP) IIb/IIIa receptor antagonists or low molecular weight heparin. Myoglobin was introduced as a sensitive marker of successful or failed reperfusion following thrombolytic therapy. These studies indicate that cardiac markers are important tools in the risk stratification of patients with acute coronary syndromes allowing adequate treatment decisions. However, certain limitations of cardiac markers have to be considered. These limitations mainly refer to the delay in time from presentation to the emergency room to the availability of the results of the blood sample. Thus, in the individual case, especially if an ECG and clinical presentation are unspecific or there is doubt concerning the success of thrombolytic therapy, early angiography remains the gold standard for diagnosis and establishment of adequate therapy. In this setting, early reperfusion by percutaneous coronary interventions will increase myocardial salvage, and therefore, should be preferred to the delayed confirmation of the diagnosis by repeated determination of cardiac markers.     

Automatic Implantable Cardioverter/ Defibrillator (AICD) and Antitachycardia Pacemaker (Tachylog): Combined use in Ventricular Tachyarrhythmias

Antitachycardia pacing in ventricular tachyarrhythmias (VT) is associated with potential acceleration of VT: frequency of VT and discomfort of the patient (pt) can limit treatment with the AICD. We therefore evaluated the combined use of antitachycardia pacing and AICD in 6 of 14 patients (age 50–70. mean 60 years) with AICD implantation because of VT, which could he terminated by temporary overdrive pacing. With the interactive mode of the Tachylog, termination of VT by the pacemaker as well as by the AICD was assessed after implantation. In the automatic mode, the Tachylog functioned as a bipolar VVI device with antitachycardia burst stimulation: 2–5 stimuli, interval 260–300 ms. 1–2 interventions. During follow-up of 12±5 months, the Tachylog terminated VT reliably 20 to 327 times per patient. In three patients, burst stimulation accelerated VT, which was terminated then by the AICD discharge. Conclusion: Drug resistant ventricular tachyarrhythmias can be terminated by the Tachylog pacemaker avoiding patients' discomfort. In case of acceleration. ventricular tachyarrhythmias can be controlled by the automatic implantable cardioverter/defibrillator. A universal pacemaker should combine antitachycardia pacing with back-up defibrillation mode.