Visualisation of the gastrin receptor within rat mucosa using a biotinylated gastrin antagonist

We have previously demonstrated that the peptide Boc-l -Trp-l -Leu-β-Ala is a potent and specific antagonist of pentagastrin-stimulated acid secretion in both the rat and the dog. Using conventional solution phase methodology, the analogue biotinyl-l -Trp-l -Leu-β-Ala was prepared in reasonable yield and purity and applied to cryostat sections of rat intestinal and other tissues. The sections were exposed to 5–10 μg of peptide and the bound analogue was visualised using streptavidin-fluorescein. The binding of the analogue was demonstrated in sections from fundus, duodenum, ileum, colon, and lung. However, the analogue failed to bind to tissue from the pancreas, heart, kidney, or liver. The binding of the probe was greatly reduced or completely inhibited by preincubation with Boc-l -Trp-l -Leu-β-Ala, pentagastrin, or gastrin 1–17. The distribution of the cells recognised by the probe was consistent with the distribution of histamine-containing enterochromaffin-like cells. The results of this study may have some bearing on current theories of the mechanism of gastrin-stimulated acid release.     

Variability in Implantable Cardioverter Defibrillator Pulse Generator Longevity Between Manufacturers

ELLINOR, P.T., et al .: Variability in Implantable Cardioverter Defibrillator Pulse Generator Longevity Between Manufacturers. ICDs are used frequently to treat malignant ventricular arrhythmias. Despite the expanding role of these devices, little is known about the manufacturer variability in the performance of ICD generators. The purpose of this study is to explore the indications for ICD pulse generator replacement and to examine performance differences between the three major manufacturers of ICDs in the United States. The authors performed a retrospective review of ICD pulse generators that were implanted and replaced at Massachusetts General Hospital between February 1998 and March 2002. During the study period, 50 (7%) of the 707 devices in the study cohort were replaced. The most common indication for pulse generator replacement was related to battery performance followed by device recall, upgrade to a dual chamber device, and pulse generator malfunction. After exclusion of the recalled devices, a significantly higher number of pulse generators manufactured by St. Jude Medical (14/229) required replacement for battery depletion or prolonged charge times during the study period compared with devices from Guidant (2/220) or Medtronic (0/273),  P = 0.003  and  P < 0.0001  , respectively. This difference was attributable to reduced longevity in the Angstrom series of defibrillators. (PACE 2003; 26[Pt. I]:71–75)     

Impact of Programmed Sensitivity Safety Factor on Atrial Sensing in Children

The relationship between the pacemaker sensitivity safety factor (PSSF) and atrial under- or oversensing as documented by 24-hour Holter monitoring was examined. Our study comprised 78 transvenous fixed atrial leads implanted between 1983–1995 in 71 children. Overall, 210 Holter reports identified 143 (68%) Holters with normal atrial sensing function, 31 (15%) with undersensing, 32 (15%) with oversensing, and 4 (2%) with both problems. From 161 Holter reports in which the PSSF was available, the incidence of undersensing at a PSSF of 2.0 (range 1.5–2.4) was 25% (14/57). There was a dramatic decline in undersensing when the PSSF was 3 (3%) compared to a FSSF < 3 (21 %) (P < 0.001). A PSSF cut-off point of 2.0 best predicted occurrence of undersensing with a sensitivity of 79% and a specificity of 67%. Other variable were also examined by multiple logistic regression analysis, but only PSSF remained highly associated with undersensing (odds ratio [OR] = 0.6, P = 0.03). In contrast, PSSF did not have a significant role in predicting oversensing, but presence of sick sinus syndrome (OR = 10.5) or unipolar lead (OR = 5.6) were significantly associated with oversensing (P = 0.0001). The majority of undersensing problems can be avoided by routinely allowing for at least a threefold or more programmed sensitivity margin. Other factors may increase the risk of oversensing, regardless of the PSSF.     

Inadvertent Detection of 60-Hz Alternating Current by an Implantable Cardioverter Defibrillator

LEE, S.W., et al. : Inadvertent Detection of 60-Hz Alternating Current by an Implantable Cardioverter De-fibrillator. A patient with an ICD received therapies from his ICD while exercising in an indoor swimming pool. Interrogation of the ICD revealed inappropriate detection of 60-Hz alternating current artifact and delivery of ICD therapies.     

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.