Scatter Diagram Analysis: A New Technique for Discriminating Ventricular Tachyarrhythmias

With the increasing flexibility allowed by implantable cardioverter defibrillators that use tiered therapy, it is important to match the therapy with the arrhythmia. In this article we present scatter diagram analysis, a new computationally efficient two-channel algorithm for distinguishing monomorphic ventricular tachycardia (VT) from polymorphic ventricular tachycardia and ventricular fibrillation (VF). Scatter diagram analysis plots the amplitude from one channel versus the amplitude from another channel on a graph with a 15 × 15 grid. The fraction (percentage) of the 225 grid blocks occupied by at least one sample point is then determined. We found that monomorphic VT traces nearly the same path in space and occupies a smaller percentage of the graph than a nonregular rhythm such as polymorphic VT or VF. Scatter diagram analysis was tested on 27 patients undergoing intraoperative implantable cardioverter defibrillator testing. Passages of 4.096 seconds were obtained from rate (bipolar epicardial) and morphology (patch) leads, and digitized at 125 Hz. Scatter diagram analysis distinguished 13 episodes of monomorphic VT (28.6%± 4.0%) from 27 episodes of polymorphic VT or VE (48.0%± 8.2%) with P < 0.0005. There was overlap in only one monomorphic VT episode and one polymorphic VT or VF episode.     

Entrapment of a Pacing Lead within a Chiari Network: Utility of Intracardiac Echo and a Laser Sheath

Although rare, Chiari networks are elaborate embryological remnants that can pose distinct challenges for catheter and pacing lead manipulation within the right atrium. Device entrapment may require open thoracotomy for removal, with significant morbidity. We report an unusual case of pacing lead entanglement within this structure, followed by prompt intracardiac echocardiographic identification and laser sheath removal.     

Dexmedetomidine pharmacokinetics in pediatric intensive care – a pooled analysis

Background: Published dexmedetomidine pharmacokinetic studies in children are limited by participant numbers and restricted pathology. Pooling the available studies allows investigation of covariate effects. Methods: Data from four studies investigating dexmedetomidine pharmacokinetics after i.v. administration (n = 95) were combined to undertake a population pharmacokinetic analysis of dexmedetomidine time–concentration profiles (730 observations) using nonlinear mixed effects modeling (NONMEM). Estimates were standardized to a 70‐kg adult using allometric size models. Results: Children had a mean age of 3.8 (median 3 years, range 1 week–14 years) and weight of 16.0 kg (median 13.3 kg, range 3.1–58.9 kg). Population parameter estimates (between subject variability) for a two‐compartment model were clearance (CL) 42.1 (CV 30.9%) l·h^?1·70 kg^?1, central volume of distribution (V1) 56.3 (61.3%) l·70 kg^?1, inter‐compartment clearance (Q) 78.3 (37.0%) l·h^?1·70 kg^?1 and peripheral volume of distribution (V2) 69.0 (47.0%) l·70 kg^?1. Clearance maturation with age was described using the Hill equation. Clearance increases from 18.2 l·h^?1·70 kg^?1 at birth in a term neonate to reach 84.5% of the mature value by 1 year of age. Children given infusion after cardiac surgery had 27% reduced clearance compared to a population given bolus dose. Simulation of published infusion rates that provide adequate sedation for intensive care patients found a target therapeutic concentration of between 0.4 and 0.8 μg·l^?1. Conclusions: The sedation target concentration is similar to that described for adults. Immature clearance in the first year of life and a higher clearance (when expressed as l·h^?1·kg^?1) in small children dictate infusion rates that change with age. Extrapolation of dose from children given infusion in intensive care after cardiac surgery may not be applicable to those sedated for noninvasive procedures out of intensive care.     

Review article: Luminex technology for HLA antibody detection in organ transplantation

Since its inception in the early 1960s, the serologically based complement-dependent cytotoxicity (CDC) assay has been the cornerstone technique for the detection of human leucocyte antigen (HLA) antibodies, not only in pre-transplant renal patients, but also in other forms of organ transplantation. Recently, solid phase assays have been developed and introduced for this purpose, and in particular the Flow-based bead assays such as the Luminex system. This latter assay has proved to be far more sensitive than the CDC assay and has revealed pre-sensitization in potential transplant recipients not detected by other methods of HLA antibody detection. However, the clinical implications of this increased sensitivity have not been convincingly demonstrated until recently. This technology for HLA antibody detection permits the evaluation of the clinical importance of antibodies directed at, for example, HLA-DPB1 and HLA-DQA1, which has not been possible to date. There are Luminex issues, however, requiring resolution such as the ability to distinguish between complement fixing and non-complement fixing antibodies and determination of their relative clinical significance. Luminex technology will permit a re-evaluation of the role of HLA antibodies in both early and late antibody-mediated rejection.     

Early white-matter abnormalities of the ventral frontostriatal pathway in fragile X syndrome

Aim  Fragile X syndrome is associated with cognitive deficits in inhibitory control and with abnormal neuronal morphology and development.
Method  In this study, we used a diffusion tensor imaging (DTI) tractography approach to reconstruct white-matter fibers in the ventral frontostriatal pathway in young males with fragile X syndrome ( n =17; mean age 2y 9mo, SD 7mo, range 1y 7mo–3y 10mo), and two age-matched comparison groups: (1) typically developing ( n =13; mean age 2y 3mo, SD 7mo, range 1y 7mo–3y 6mo) and (2) developmentally delayed ( n =8; mean age 3y, SD 4mo, range 2y 9mo–3y 8mo).
Results  We observed that young males with fragile X syndrome exhibited increased density of DTI reconstructed fibers than those in the typically developing ( p =0.001) and developmentally delayed ( p =0.001) groups. Aberrant white-matter structure was localized in the left ventral frontostriatal pathway. Greater relative fiber density was found to be associated with lower IQ (Mullen composite scores) in the typically developing group ( p =0.008).
Interpretation  These data suggest that diminished or absent fragile X mental retardation 1 protein expression can selectively alter white-matter anatomy during early brain development and, in particular, neural pathways. The results also point to an early neurobiological marker for an important component of cognitive dysfunction associated with fragile X syndrome.     

Potency of a Complex Mixture of Polychlorinated Dibenzo-p-dioxin, Dibenzofuran, and Biphenyl Congeners Compared to 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Causing Fish Early Life Stage Mortality

Use of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity equivalentsconcentration (TEC) assumes that polychlorinated di benzo-p-dioxins(PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) act additivelyand via a common mechanism to cause toxicity. To test theseassumptions, 11 TCDD-like congeners and three non-TCDD-likecongeners were combined at ratios typically found in Lake Michiganlake trout. The potency of the mixture, expressed as TEC basedon fish-specific toxic equivalency factors, was compared toTCDD for producing lake trout and rainbow trout early life stagemortality. Signs of toxicity following exposure of newly fertilizedeggs to the mixture or to TCDD were indistinguishable; sac frymortality associated with blue-sac disease, and slopes of thedose-response curves for percentage sac fry mortality versusegg TEC or versus egg TCDD were parallel. However, the mixturedose-response curves were significantly shifted to the rightof the TCDD dose-response curves by 1.3- to 1.8-fold as illustratedby LD₅₀ values. Following exposure to the mixture or TCDD, LD₅₀sfor lake trout early life stage mortality were 97 (89–110)pg TE/g egg and 74 (70–80) pg TCDD/g (LD₅₀, 95% fiduciallimits) and for rainbow trout were 362 (312–406) pg TE/gegg and 200 (148–237) pg TCDD/g egg. These data suggestthat TCDD-like congeners act via a common mechanism to causetoxicity during trout early development, but may not act strictlyadditively when combined in a mixture of TCDD- and non-TCDD-likecongeners at ratios found in Great Lakes fish. The deviationfrom additivity, however, is less than current safety factorsof 10-fold commonly applied in ecological risk assessments,providing support for the continued use of a TE additivity modelfor assessing risk posed by complex mixtures of PCDDs, PCDFs,and PCBs to fish.     

Data sources, bed supply and performance in hospital systems: An Anglo-Czechoslovak comparison

Background: There were a number of similarities, except fortheir effectiveness, in the health care systems of Czechoslovakiaand England and Wales between the Second World War and the late1980s. In a comparison of Czechoslovakia with England and Wales,the objectives of this study were to examine data sources andto report time trends and regional distributions in hospitalbed supply, hospital doctor supply and hospital utilisation.Methods: For the specialties of general medicine and generalsurgery in both countries from 1960 to 1986, data were collatedon bed supply, hospital doctor supply, discharge rates and lengthof stay. Issues concerning the comparability of the data wereaddressed, for example those of the definitions of specialty,length of stay and casemix. Results: In the period 1960 to 1986,in the specialties of general medicine and general surgery,there was a relative excess in the supply of hospital doctorsand beds in Czechoslovakia compared with England and Wales.Hospital performance in terms of discharge rates, dischargesper bed and length of stay remained relatively static in Czechoslovakiaduring this period compared to marked increases in dischargerates and reduced length of stay in England and Wales. Bothcountries recorded reductions in the regional variation of bedand doctor supply and hospital utilisation. Conclusions: Internationalstudies of hospital utilisation need to be interpreted carefullyin the light of definitions of hospital stay, casemix, the useof day cases and the availability of other services. Subjectto these caveats, discharge rates were high and duration ofstay long In Czechoslovakia compared with England and Wales;however, both countries achieved important improvements in regionalequity.     

Continuous Ventricular Volume Assessment for Diagnosis and Pacemaker Control

La mesure du débit systolique par un catheter dans le ventricule droit, utilisant i'impédance intracardiaque, au repos et pendant l'exercise peut être comparée de façon favorable aux mesures obtenues par ventilation à l'acetylene (r = 0.96, n = 13) et par ventriculographie isotopique (r = 0.96, n = 13). Ceci a étéétudié chez un malade de 46 ans en bloc complet. La fréquence de stimulation à l'effort a été déterminée par l'impédance en prenant un algorythme qui maintient un débit systolique constant. Le résultat a montré une augmentation du debit cardiaque de 23% et une baisse du débit systolique de 70%, mesurée à l'effort à une fréquence de 70 cpm.