Effects of Procainamide on the Excitable Gap Composition in Common Human Atrial Flutter

The composition of the excitable gap (EG) in common atrial flutter (AFI) was determined before and during infusion of procainamide (PA) in 9 patients (6 men and 3 women; age 70 ± 7 years). The EG was determined by introducing a premature stimulus after every 20th AFI complex detected using a quadripolar electrode catheter placed just above the tricuspid valve. Diastole was scanned in 2- to 4-ms decrements to the atrial effective refractory period (ERP). The relationship between the coupling interval and the return cycle length (CL) determined a reset-response curve (RRC), which described the EG. PA (15 mg/kg) was administered during AFl over 30 minutes and RRC was repeated at maximum AFI CL. PA prolonged AF1 CL from 227 ± 29 to 296 ± 62 ms (P < 0.01) but did not terminate AFI. ERP during AFl prolonged from 169 ± 24 to 219 ± 41 ms (P < 0.01). Control EG was 57 ± 16 ms or 25%± 6% of AFl CL and on PA EG was 77 ± 30 ms (P = 0.01), which was still 26%± 7% of the CL. Without drug, RRC was mixed in eight cases demonstrating an EG composed of fully excitable tissue (10 ± 4 ms or 19%± 10% of the EG) and partially refractory tissue (48 ± 18 ms), PA did not change the duration of the fully excitable region (13 ± 10 ms or 19%± 15% of EG). Peak PA plasma concentration was 47 ± 20 μmol/L. PA prolonged AFI CL, ERP, and EG duration but did not change the proportion of AFI CL occupied by the EG. The persistence of fully excitable tissue at the head of the wavefront in the presence of PA may largely explain its inefficacy in the acute termination of common AFl.     

The Long QT Syndrome with Impaired Atrioventricular Conduction: A Malignant Variant in Infants

Distal Conduction Disease in the Long QT Syndrome. Introduction : The long QT syndrome (LQTS) is occasionally complicated by impaired AV conduction, mostly 2:1 AV block. This form of LQTS can manifest before birth or during neonatal life, and it is more sporadic than familial. It is usually an isolated disorder, although it can be accompanied by a variety of cardiovascular and other anomalies. In spite of different treatment modes, mortality is high.
Methods and Results : The reported case presented not only with 2:1 AV conduction, but also with Wenckebach episodes with impaired right and left bundle branch conduction, and decremental conduction in the His-Purkinje axis. We also observed sinus pauses and accelerated AV junctional escape beats.
Conclusion : Our findings, and similar observations by others., suggest involvement of the sinus node and the distal conduction system in this form of the LQTS. Several histologic studies have documented abnormalities within the conduction system, including apoptosis. Because of the rare occurrence and poor prognosis of the LQTS with impaired AV conduction, international guidelines for diagnosis and treatment are needed. Development of an internal cardiac defibrillator for this young age group is necessary.     

Arg-Gly-Asp-dependent occupancy of GPIIb/IIIa by applaggin: evidence for internalization and cycling of a platelet integrin

Using indirect immunofluorescence microscopy we examined the distribution and cycling of GPIIb/IIIa after binding to applaggin, a high-affinity Arg-Gly-Asp (RGD)--containing ligand. Resting, unfixed platelets were incubated with applaggin for 30 minutes at 37 degrees C, and bound applaggin was detected by an affinity-purified rabbit anti- applaggin antibody. Examination of intact cells showed a rim pattern for applaggin, consistent with its binding to the platelet surface. Staining of Triton X-100--permeabilized cells showed an intracellular pool of applaggin. Competition of applaggin binding by either AP-2, an anti-GPIIb/IIIa monoclonal antibody (MoAb) that blocks fibrinogen binding, or the synthetic peptide RGDW eliminated both surface and intracellular staining, indicating that applaggin is binding to GPIIb/IIIa in an RGD-dependent manner. Inhibition of platelet activation by PGE1 and theophylline had no effect on the observed staining patterns, indicating that cellular activation is not required for surface binding and subsequent internalization. To evaluate whether occupancy of functional binding sites on GPIIb/IIIa is required for internalization, we used mAb15, an anti-GPIIIa antibody that neither blocks fibrinogen binding nor induces the expression of ligand-induced binding sites on GPIIb/IIIa. In these studies mAb15 was internalized in a manner analogous to both AP-2 and applaggin, showing that occupancy of the RGD binding site is not required to initiate receptor internalization. To estimate the size of the newly internalized pool of applaggin, 125I-applaggin--binding studies were performed. Displacement of bound 125I-applaggin by excess unlabeled applaggin or EDTA showed that at least 17% of bound applaggin was nondisplaceable when binding was performed under conditions permitting membrane flow and internalization. These data indicate that GPIIb/IIIa is internalized in unstimulated platelets independent of cellular activation or occupancy of the functional binding site(s) of GPIIb/IIIa by RGD-containing ligands. Thus, internalization of GPIIb/IIIa may represent a mechanism by which the surface expression of this adhesion receptor is regulated.     

Transfected leukocyte integrin CD11b/CD18 (Mac-1) mediates phorbol ester-activated, homotypic cell:cell adherence in the K562 cell line

The CD11b/CD18 leukocyte integrin molecule mediates diverse neutrophil adherence-related functions, including cell:cell and cell:extracellular matrix attachments. To study the individual role of this leukocyte integrin in cell adherence in hematopoietic cells, we expressed the CD11b/CD18 complex on the surface of K562 cells, a cell line derived from an individual with chronic myelogenous leukemia in blast crisis. We used an amphotrophic retroviral vector designated LCD18SN, harboring the complete coding sequence for the CD18 subunit, to transfer the CD18 cDNA into K562 cells and select stable cell lines. The CD11b subunit in the expression plasmid pREP4 was transfected into these K562/CD18 cells by electroporation and stable cell clones were selected. These K562 cells possessed RNA and intracellular protein for each subunit, and they expressed the CD11b/CD18 heterodimer on the cell surface. When CD11b/CD18 expressing K562 cells were stimulated with phorbol myristate acetate (50 ng/mL) for 24 to 48 hours, these K562 cells formed dense cell:cell aggregates. This homotypic aggregation required both activation of the CD11b/CD18 complex and the induction of the counter- receptor for CD11b/CD18 on the conjugate cell. This cell line will (1) enable the structure-function relationships between cell activation and homotypic adherence to be assessed, (2) provide the opportunity to identify accessory molecules required for activation of the CD11b/CD18 complex, and (3) facilitate the identification of novel ligands for the CD11b/CD18 complex.     

口服右旋索他洛尔生存研究(SWORD)

标题　ａ）口服左旋－Ｓｏｔａｔｏｌ治疗心肌梗死后左室功能不全患者生存研究（ＳＷＯＲＤ）：试验依据、设计和方法　　　ｂ）右旋－Ｓｏｔａｔｏｌ对亚急性和陈旧性心肌梗死后左室功能不全患者病死率的影响研究作者　ＷａｌｄｏＡＬ,ＣａｍｍＡＪ,ｄｅｒｕｙｔｅｒＨ,等ａ）ＡｍＪＣａｒｄｉｏｌ,１９９５,７５：１０２３～１０２７ｂ）Ｌａｎｃｅｔ,１９９６,３４８：７～１２　　研究疾病：充血性心力衰竭。目的：右旋－Ｓｏｔａｔｏｌ为一种具有专一性钾通道阻滞作用的抗心律失常药物。本研究将对其降低心肌梗死后左室功能不全…     

Obtaining accurate patient‐specific perioperative anaesthetic costs in orthopaedic anaesthesia

□ The aim of the study was to obtain perioperative patient‐specific costs associated with orthopaedic anaesthesia □ A prospective observational study design was used to determine fixed, semi‐fixed, and variable costs □ The preliminary results of the first 60 patients reports a mean total perioperative anaesthetic cost of £291 (SD: £103.9, median: £278.09, IQR: £219.3–£369.5) □ Fixed and semi‐fixed costs are a major cost component of anaesthesia; variable costs account for only 12 per cent of total cost □ The results of this study will be used in an economic evaluation examining the use of different anaesthetic techniques in orthopaedics     

Chronic daily headache with migrainous features due to papilledema-negative idiopathic intracranial hypertension

Patients with the syndrome of chronic daily headache often report migrainous symptoms and consequently are diagnosed as having a primary headache syndrome. We report two cases of idiopathic intracranial hypertension causing chronic daily headache with migrainous features in the absence of associated papilledema.     

Mitomycin-c application in airway stenosis surgery: analysis of safety and costs.

OBJECTIVE: This study describes a large series of patients receiving topical mitomycin-c (MMC) during airway surgery, including complications, and carries out a cost analysis for its use in laryngotracheal stenosis. STUDY DESIGN AND SETTING: Retrospective review, tertiary center. Airway patients receiving MMC are reviewed for demographics, stenosis characteristics, and MMC usage. A basic cost analysis is carried out. RESULTS: Fifty patients underwent 93 MMC applications (mean = 50.8 years, 25 male, 25 female). In 89 of 93 applications (96%), the concentration of MMC was 0.4 mg/ml. One major complication occurred (1.1%). The expense for MMC is $455; the mean cost for airway surgery is $7,840. It is estimated that if 1 of 17 MMC treated patients requires one less operation, the cost ratio is favorable. CONCLUSIONS: This large series contributes to literature that MMC is a safe adjunct to laryngotracheal surgery. The marginal cost for MMC application is favorable based on our basic cost analysis and existing efficacy data. SIGNIFICANCE: Mitomycin-c seems to be safe and cost-effective in endoscopic airway surgery. EBM rating: C-4.