Acute Pericarditis Resulting From an Endocardial Active Fixation Screw-In Atrial Lead

We examined the occurrence of acute pericarditis after pacemaker implantation in 123 consecutive patients (61 males, 62 females, ages 17–87 years) in whom a newer atrial active fixation bipolar lead was inserted endocardially in the right atrium for dual chamber pacing. The atrial leads were positioned to obtain the best possible pacing and sensing thresholds, after an initial attempt was made for insertion into the right atrial appendage or medially into the right atrial septum. Six patients (4.9%) developed acute symptomatic pericarditis with effusion within 24 hours of implantation. Of these six patients, four had leads screwed into the lateral waH. and the other two had leads placed in the anterolateral wall. The lead implantation parameters between patients with pericarditis and those without did not show any significant difference in the atrial P wave amplitude (2.3 ± 0.4 vs 2.9 ± 0.9 mV), pacing threshold (1.1 ± 0.2 vs 1.1 ± 0.4 V), or resistance (524 ± 112 vs 480 ± 94 ohms). All symptomatic patients were treated with nonsteroidal anti-inflammatory drugs with symptoms resolving in 1–2 weeks. We condude that: (1) a significant number of patients (4.9%) developed acute symptomatic pericarditis after insertion of this type of atrial fixation lead: (2) because of the lead design, the implantation parameters coud not be taken to predict the occurrence of pericarditis: and (3) caution should be taken for the insertion of this lead into the thin atrial wall.     

Radiofrequency Catheter Ablation of the Atrioventricular Junction by a Supravalvular Noncoronary Aortic Cusp Approach

Radiofrequency catheter ablation of the atrioventricular janction is usually achieved from either the right or left atrioventricular junction. We describe a new approach in which the atrioventricular junction was successfully ablated from the supravalvular region of the noncoronary cusp of the aortic valve in an unusual patient in whom conventional approaches were unsuccessful.     

Risk Factors for Implantable Defibrillator Lead Fracture in a Recalled and a Nonrecalled Lead

Risk Factors for ICD Lead Fracture. Introduction: The Medtronic Sprint Fidelis® implantable cardioverter defibrillator (ICD) lead was “recalled” in October 2007 after 268,000 implants worldwide due to increased failure risk. Manufacturer suggested monitoring has not been shown effective at preventing adverse events. Only limited data exist regarding clinical predictors of Fidelis® lead fracture. We sought to identify risk factors for Fidelis® fracture to guide clinical monitoring and compare its performance with a control lead. Methods: Fractured lead cases were retrospectively reviewed for demographic data, implant technique, radiographic appearance and clinical presentation was analyzed. Lead survival was compared using Kaplan‐Meir curves. Results: Study patients (n = 1314) experienced 18 Fidelis® and 6 Quattro? lead fractures. Patients with failed Fidelis® leads were younger than those with surviving leads (49.5 vs 64.6 years, P = 0.0066). Fidelis® lead fractures often occurred around the time of physical activity. No other measured demographic or technique related factors were associated with lead fracture. Fidelis® leads had significantly decreased survival compared with Quattro? leads (89.3 vs 98.9% at 30 months). Patients less than 50 years old had significantly decreased lead survival compared with those older than 50 in both Fidelis® (79.6% vs 96.5% at 24 months) and Quattro? (93.4 vs 99.8%, P < 0.001 at 24 months) leads. Conclusions: Patients under age 50, with either Fidelis® or Quattro? ICD leads, are at increased risk of lead fracture compared with patients over 50, particularly around the time of intense physical activity. Aggressive monitoring and advisory programming appears warranted in patients with Fidelis® leads as well as especially in younger patients. (J Cardiovasc Electrophysiol, Vol. 21, pp. 671‐677, June 2010)     

Circumvention of P-glycoprotein-mediated drug resistance in human leukaemic cells by non-immunosuppressive cyclosporin D analogue, SDZ PSC 833

Summary. Cyclosporin A (CSA) exhibits greater multidrug resistance (MDR) modulating activity in vitro than other MDR modulators such as verapamil and quinidine. However, the immunosuppressive and nephrotoxic effects of CSA may limit its clinical use. PSC 833, a new cyclosporin D derivative, exerts a higher MDR reversal activity but lacks toxic or immunosuppressive effects. The drug-resistant sublines K/DAV₁₀.,, K/DAU₂₀₀. K/DAU₃₀o. K/DAU₄₀o, K/ DAU500 and K/DAU₆₀o have been derived from the drug-sensitive parental cell line, K562 cl.6 and CEM/VLB₁₀₀ is a drug-resistant derivative of CCRF-CEM. We report a comparison of the effects of PSC 833 and CSA on daunorubicin (DAU) transport kinetics and chemosensitivity in these cell lines. Both CEM/VBL₁₀₀ and KS62 cl.6 DAU-resistant cells displayed high levels of P-glycoprotein (PGP), decreased DAU accumulation and increased DAU efflux when compared to their parental cells. PSC 833 was 1-6-, 3-4-, 4-9- and 4-6-fold more effective than CSA in reversing DAU resistance in higher resistance CEM/VLB₁₀o, K/DAU₄₀o, K/DAU500 and K/DAU₆₀o cells respectively. DAU transport kinetics showed that PSC 833 was more effective than CSA in increasing cellular DAU accumulation and decreasing DAU efflux in higher resistant leukaemia subclones. PSC 833 could restore DAU retention at lower doses and was more active than CSA in all the resistant cells. A 89-100% restoration of intracellular DAU retention were gained by PSC 833 at 1-0ftM in K562 cl.6 DAU-resistant sublines, whereas a 73-100% restoration of DAU retention was obtained by CSA only at 30-0 β, M in the same resistant sublines. PSC 833 at 3-0/XM is sufficient to restore full DAU retention in all resistant cells. CSA, however, even at 30-0 pM, cannot confer full restoration of DAU retention in higher resistance K562 cl.6/DAU sublines. By measuring MDR modulator-mediated short-term inhibition of PGP function, PSC 833 was found to be at least 10-30 times more active than CSA. As no effect on DAU retention and sensitivity has been found in sensitive parental cells with PSC 833, it is suggested that PSC 833 may act by blocking the effluxing function of PGP in the resistant leukaemia cells.     

Clinical Application of PET/CT Fusion Imaging for Three-Dimensional Myocardial Scar and Left Ventricular Anatomy during Ventricular Tachycardia Ablation

Background: Image integration has the potential to display three-dimensional (3D) scar anatomy and facilitate substrate characterization for ventricular tachycardia (VT) ablation. However, the current generation of clinical mapping systems cannot display 3D left ventricle (LV) anatomy with embedded 3D scar reconstructions or allow display of border zone and high-resolution anatomic scar features.
Objective: This study reports the first clinical experience with a mapping system allowing an integrated display of 3D LV anatomy with detailed 2D/3D scar and border zone reconstruction.
Methods: Ten patients scheduled for VT ablation underwent contrast-enhanced computed tomography (CT) and Rubidium-82 perfusion/F-18 Fluorodeoxyglucose metabolic Positron Emission Tomography (PET) imaging to reconstruct 3D LV and scar anatomy. LV and scar models were co-registered using a 3D mapping system and analyzed with a 17-segment model. Metabolic thresholding was used to reconstruct the 3D border zone. Real-time display of CT images was performed during ablation.
Results: Co-registration (error 4.3 ± 0.7 mm) allowed simultaneous visualization of 3D LV anatomy and embedded scar and guided additional voltage mapping. Segments containing homogenous or partial scar correlated in 94.4% and 85.7% between voltage maps and 3D PET scar reconstructions, respectively. Voltage-defined scar and normal myocardium had relative FDG uptakes of 40 ± 13% and 89 ± 30% (P < 0.05). The 3D border zone correlated best with a 46% metabolic threshold. Real-time display of registered high-resolution CT images allowed the simultaneous characterization of scar-related anatomic changes.
Conclusion: Integration of PET/CT reconstruction allows simultaneous 3D display of myocardial scar and border zone embedded into the LV anatomy as well as the display of detailed scar anatomy. Multimodality imaging may enable a new image-guided approach to substrate-guided VT ablation.     

Evaluation of recombinant protein r140, a polypeptide segment of tegumental glycoprotein Sm25, as a defined antigen vaccine against Schistosoma mansoni

To investigate the role of tegumental glycoprotein Sm25 in protective immunity against schistosomiasis, codons 43-182 of its gene (GP22) were amplified by PCR and cloned in the pET 15b bacterial expression system. Recombinant protein r140 was inducibly expressed in the presence of rifampicin and purified by Ni-affinity chromatography. In different vaccination trials, Balb/c mice and Fischer rats repeatedly immunized with r140 in combination with one of several adjuvants (alum, cholera toxin or complexed into proteosomes) produced high titre anti-r140 responses. These antibodies detected an N-glycanase sensitive, 25 kDa antigen in a detergent solubilized worm fraction using Western immunoblotting. The choice of adjuvant affected the isotype distribution of the specific anti-r140 antibodies. Despite the presence of high antibody titres and isotypes which have been shown to correlate with protective immunity, protection against subsequent cercarial challenge was not observed. In addition, no appreciable effects on worm sex ratios or liver egg yields were detected in mice. Studies involving biotin labelling of membrane proteins in live worms showed that the majority of anti-r140 reactive molecules present in adult schistosomes are biotinylated after permeabilization of the parasite surface. Several possibilities to account for the lack of protective immunity are analysed .     

Follow-up of Gambian children recruited to a pilot safety and immunogenicity study of the malaria vaccine SPf66

A pilot safety and immunogenicity trial of the malaria vaccine SPf66 was undertaken in The Gambia in 1993. One hundred and fifty infants aged 6–11 months were immunized with either 0.5 mg or 1.0 mg of SPf66 produced either in Colombia or in the USA or with a control vaccine. Children who received SPf66 experienced more clinical attacks of malaria than did children in the control group during the first period of surveillance and the difference in incidence between children who had received high dose Colombian vaccine and the control children was statistically significant at the 5% level. During the 1995 malaria transmission season, 127 children from the original cohort of 150 were observed. During 18 weeks of intensive surveillance, the incidence of clinical malaria was again higher among children who had received SPf66 than among children who had received inactivated polio vaccine (6.23 vs 4.89 clinical attacks per 1000 days at risk), the effect being most marked among children who were in the high dose groups, but differences between groups were now no longer statistically significant .     

Malignancy: Granulocyte Colony Stimulating Factor Increases the Efficacy of Conventional Amphotericin in the Treatment of Presumed Deep-Seated Fungal Infection in Neutropenic Patients following Intensive Chemotherapy or Bone Marrow Transplantation for Haematological Malignancies

A prospective, comparative study of empiric amphotericin B with, or without, granulocyte colony stimulating factor was carried out to assess whether the addition of granulocyte colony stimulating factor to empiric amphotericin B improves the clinical response in neutropenic patients with suspected or proven fungal infection. Fifty nine neutropenic adults with haematological malignancy and antibiotic-refractory fever or clinical evidence of deep-seated fungal infection were studied. Patients received intravenous colloidal amphotericin B (1 milligram per kilogram body weight) with or without subcutaneous granulocyte colony stimulating factor (three to five micrograms per kilogram body weight). Thirty patients received amphotericin alone and 29 amphotericin plus granulocyte colony stimulating factor. Nearly twice as many patients responded to amphotericin B with concomitant administration of granulocyte colony stimulating factor (62%) as responded to amphotericin alone (33%; difference in proportions 0.29, 95%CI 0.03-0.54). Clinical response in patients receiving granulocyte colony stimulating factor coincided with neutrophil recovery in most cases. Addition of granulocyte colony stimulating factor to empiric amphotericin B significantly reduced the number of patients requiring salvage therapy with lipid-associated or liposomal formulations of amphotericin B addition of granulocyte colony stimulating factor to empiric intravenous amphotericin B improves the response rate and thereby reduces the number of patients requiring salvage therapy with liposomal or lipid-associated preparations of amphotericin B.     

A New Defibrillator Discrimination Algorithm Utilizing Electrogram Morphology Analysis

Inappropriate therapies delivered by implantable cardioverter defibrillators (ICDs) for supraventricular arrhythmias remain a common problem, particularly in the event of rapidly conducted atrial fibrillation or marked sinus tachycardia. The ability to differentiate between ventricular tachycardia and supraventricular arrhythmias is the major goal of discrimination algorithms. Therefore, we developed a new algorithm, SimDis, utilizing morphological features of the shocking electrograms. This algorithm was developed from electrogram data obtained from 36 patients undergoing ICD implantation. An independent test set was evaluated in 25 patients. Recordings were made in sinus rhythm, sinus tachycardia, and following the induction of ventricular tachycardia and atrial fibrillation. The arrhythmia complex is defined as wide if the duration is at least 30% greater than the template in sinus rhythm. For narrow complexes, four maximum and minimum values were measured to form a 4-element feature vector, which was compared with a representative feature vector during normal sinus rhythm. For each rhythm, any wide complex was classified as ventricular tachycardia. For narrow complexes, the second step of the algorithm compared the electrogram with the template, computing similarity and dissimilarity values. These values were then mapped to determine if they fell within a previously established discrimination boundary. On the independent test set, the SimDis algorithm correctly classified 100% of ventricular tachycardias (27/27), 98% of sinus tachycardias (54/55), and 100% of episodes of atrial fibrillation (37/37). We conclude that the SimDis algorithm yields high sensitivity (100%) and specificity (99%) for arrhythmia discrimination, using the computational capabilities of an ICD system.     

Interpretation of in-vitro thyroid function tests during pregnancy

Summary. In-vitro thyroid function tests are difficult to interpret in pregnancy because of, among other things, the effect of oestrogens on thyroid binding globulin (TBG) concentrations. In an attempt to clarify the position, serum concentrations of total thyroxine (T₄), free T₄, TBG, T₄/TBG ratio, tri-iodothyronine (T₃) and thyroid stimulating hormone (TSH) were measured. Total T₄ and TBG concentrations rose to above the non-pregnant reference range by 20 weeks. The T₄/TBG ratio fell to hypo-thyroid values by 20 weeks but although the free T₄ level was lower in the third trimester compared with values in the first and second trimesters, only a few subjects had hypothyroid values. The TSH values remained unchanged throughout pregnancy. The significance of these changes is discussed and reference ranges for these hormones at each trimester are provided.