Human monoclonal antibodies against Plasmodium falciparum: production, stabilization and characterization

Nine human monoclonal antibodies (MoAbs) recognizing 7 different antigenic structures of blood-stages of the human malarial parasite P. falciparum (Pf) were produced by Epstein-Barr virus transformed B-cell lines (EBV-TCL) with or without fusion to the lymphoblastoid cell line KR4. The peripheral blood B-lymphocytes were obtained from 8 Gambian donors immune to Pf malaria. Two of the EBV-TCL could be expanded and maintained for more than 6 months but neither one could be cloned. Six additional EBV-TCL were stabilized after fusion with the KR4 lymphoblastoid cell line. All resulting hybridomas permitted easy cloning. Some of the MoAbs produced distinct fluorescent staining patterns of asexual Pf blood-stage parasites when using high-resolution digitized video-intensified fluorescence microscopy. Antigens on 195 kD and 155 kD proteins were recognized by 3 and 1 MoAb, respectively, using Western blotting and immunoprecipitation techniques.     

Intermittent Capture of the Left Bundle With Permanent His Bundle Pacing: Mechanistic Insights and Implications for an Emerging Field

We present a case of a patient with elevated His lead capture thresholds and intermittent recruitment of the left bundle. The patient underwent a noninvasive electrophysiology study and was determined to have a left bundle branch block due to postrepolarization refractoriness. The nature of bundle branch block can have important implications for optimal patient selection and device programming in the emerging field of His bundle pacing.     

Neuroimaging in childhood arterial ischaemic stroke: evaluation of imaging modalities and aetiologies

Aim The aim of this study was to describe neuroimaging patterns associated with arterial ischaemic stroke (AIS) in childhood and to differentiate them according to stroke aetiology. Method Clinical and neuroimaging (acute and follow‐up) findings were analysed prospectively in 79 children (48 males, 31 females) aged 2 months to 15 years 8 months (median 5y 3mo) at the time of stroke by the Swiss Neuropaediatric Stroke Registry from 2000 to 2006. Results Stroke was confirmed in the acute period in 36 out of 41 children who underwent computed tomography, in 53 of 57 who underwent T2‐weighted magnetic resonance imaging (MRI) and in all 48 children who underwent diffusion‐weighted MRI. AIS occurred in the anterior cerebral artery (ACA) in 63 participants and in all cases was associated with lesions of the middle cerebral artery (MCA). The lesion was cortical–subcortical in 30 out of 63 children, cortical in 25 out of 63, and subcortical in 8 of 63 children. Among participants with AIS in the posterior circulation territory, the stroke was cortical–subcortical in 8 out of 16, cortical in 5 of 16, and thalamic in 3 out of 16 children. Interpretation AIS mainly involves the anterior circulation territory, with both the ACA and the MCA being affected. The classification of Ganesan is an appropriate population‐based classification for our Swiss cohort, but the neuroimaging pattern alone is insufficient to determine the aetiology of stroke in a paediatric population. The results show a poor correlation between lesion pattern and aetiology.     

The Basis for Activity Controlled Rate Variable Cardiac Pacemakers: An Analysis of Mechanical Forces on the Human Body Induced by Exercise and Environment

We conducted tests on six healthy volunteers and six pacemaker patients. With the aid of three straight line frequency acceleration pickups attached to the body, the mechanical signals were recorded on the three axes during different activities. Along with standardized exercise on bicycle and treadmill ergometers, we tested the influence of household activities and interference influences. The results were analyzed in terms of the amplitude and frequency content of the signals. For walking activities, we found a signal amplitude increasing in a largely linear fashion with the walking speed, the signal amplitudes being approximately twice as high on the vertical axis as on the other two axes. Exercise on the bicycle ergometer produced mechanical signals of clearly lower amplitude than comparable walking activities. The Fast-Fourier analysis showed amplitude peaks in the low frequency range of 1 to 4 Hz for all forms of physiological exercise, while interference influences showed amplitude peaks mainly in the range above 8 Hz. The use of a straight line-frequency acceleration pickup and a corresponding low pass filter might be a way of reducing the effect of unphysiological interference influences on an activity controlled pacemaker system. A sensor measuring on the horizontal axis appears to be the most favorable compromise for the various types of exercise. However, due to the considerable difference in signal amplitude for different types of exercise of the same intensity, an activity controlled pacemaker system cannot entirely meet metabolic conditions and requirements.     

The Feasibility of Fully Automated Pacemaker Advise in Treating Atrial Tachyarrhythmias

Background: Modern pacemakers continuously store significant cardiac‐related events. Interpreting these data and reprogramming the pacemaker can be time‐consuming and demands expert knowledge. A software‐based expert system, the therapy advisor (TA), was developed, which analyzes stored data and provides reprogramming recommendations. This study addresses whether pacemaker experts consider the messages that are automatically generated appropriate in the management of atrial tachyarrhythmias/atrial fibrillation (AT/AF). Methods: This observational, international, multicenter study follows 150 patients with suspected or documented atrial arrhythmias who received a dual‐chamber pacemaker (model Vitatron T‐70, Medtronic Inc., Minneapolis, MN, USA) incorporating the TA. The TA summarizes technical and clinical data stored in the pacemaker into key messages and may suggest programming changes. Twenty‐five cardiologists examined their patients per normal practice during two follow‐up visits. They reported the therapy changes they deemed necessary without initially reviewing the TA messages. Next, they rated their satisfaction with and the clinical relevance of the TA messages and recorded the final therapy changes. Results: The TA generated (mostly AT/AF‐related) main observations in 49% and programming advice in 33% of the patients. The experts rated 95% of the TA messages as satisfactory and deemed therapy changes necessary in roughly half the patients. Pacemaker changes in AT/AF therapy or general settings were prompted primarily by the diagnostic information stored in the device. Medication changes were mostly led by the symptoms reported by the patient. Conclusion: This study demonstrates that experienced cardiologists agree with 95% of the observations and programming suggestions that the TA automatically generates. (PACE 2010; 605–614)