Changes in AV Node Conduction Curves Following Slow Pathway Modification

GELLER, J.C., et al. : Changes in AV Node Conduction Curves Following Slow Pathway Modification. Dual AV node physiology often persists after successful slow pathway (SP) ablation, and the mechanism of tachycardia elimination is unresolved. Therefore, AV node conduction curves were analyzed following successful ablation (  4 ± 1  energy applications) in 85 consecutive patients (58 women, age  50 ± 2  years) with typical AVNRT. Twenty-seven patients (32%) had complete elimination (group 1) whereas 58 (68%) patients had persistence (group 2) of dual AV node physiology. A significant increase in the AV node Wenckebach cycle length (WB-CL) was observed in both groups (  310 ± 9 to 351 ± 15 ms  in group 1, and  325 ± 8 to 369 ± 9 ms  in group  2, P < 0.05  ). A decrease in the fast pathway (FP) ERP (  339 ± 15 to 279 ± 12 ms  ) and an increase in the maximum FP AH interval (  141 ± 5 to 171 ± 7  ) were observed only in group 1 (P < 0.05). In group 2, no change in the SP ERP (  267 ± 7 to 280 ± 10 ms  ) was observed, and the change in the maximum SP-AH following ablation showed a significant inverse relation to the maximum SP-AH at baseline in group 2. In conclusion, (1) an increase in the WB-CL is observed independent of the persistence or elimination of dual physiology after successful ablation; (2) when dual physiology is eliminated, significant changes in the FP ERP and the maximum FP-AH occur; (3) when dual physiology persists, FP physiology and the SP ERP remain unchanged, and a significant inverse relation between the change in the maximum SP-AH following ablation and the maximum baseline SP-AH is observed.     

Plasma concentration following oral and intramuscular atropine in children and their clinical effects

In a paediatric population, we compared i.m. v oral atropine pre-medication to a control group without atropine and determined atropine plasma concentrations (APC). Forty-five children were randomly assigned to one of three groups. Group I received atropine, 20 μg·kg⁻¹ i.m., 15 min prior to induction. Group II received atropine, 30 μg·kg⁻¹ orally, group III received no atropine. APC (expressed as percent of muscarine-2 receptor subtype occupancy), heart rate, rectal temperature, and salivation were determined before atropine, and 15, 25, 45, 60, 90, 120 (no APC), and 150 min following atropine. Only 10–20% of the M2-cholinoceptors were occupied after oral atropine with a peak at 90 min compared to 60–70% occupancy with a peak 25 min after i.m. atropine. The peak in M2-cholinoceptor occupation in group I was paralleled by a peak percentage change in heart rate of 15% from baseline. The peak in receptor occupation in group II did not correspond to the peak increase in heart rate. The percentage change of heart rate over time was not significantly different from baseline values in any of the groups. Bradycardia or temperature changes did not occur in any of the groups. Antisialogogue effects were observed only in group I. We conclude that atropine, 30 μg·kg⁻¹ orally is not an equipotent dosage to atropine, 20 μg·kg⁻¹ i.m.     

Inhibition of Feline Immunodeficiency Virus Infectionin Vitroby Envelope Glycoprotein Synthetic Peptides

Sixty-six 20- to 23-amino-acid synthetic peptides, partially overlapping by 10–12 amino acids, spanning the entire sequence of the envelope SU and TM glycoproteins of the Petaluma isolate of FIV, have been used to investigate the Env domains involved in viral infection. Peptides 5 to 7, spanning amino acids²²⁵E–P²⁶⁴located in a conserved region of the SU protein, and peptides 58 to 61, spanning amino acids⁷⁵⁷N–P⁸⁰⁶and encompassing hypervariable region 8 of TM protein, exhibited a remarkable and specific antiviral effect against the homologous and one heterologous isolate, as judged by inhibition of FIV-induced syncytium formation and p25 production in CrFK cells. Peptides 5 and 7, but not peptides 58 and 59, also inhibited viral replication of a fresh FIV isolate on nontransformed lymphoid cells. By flow cytometry, peptides 5, 7, 58, and 59 were shown to bind the surface of FIV permissive cells. The antiviral activity of peptides 5 and 7, however, was time-dependent, as inhibition of FIV replication was seen when the peptides were administered before or within 3 hr after virus inoculation; in contrast, TM peptides 58 and 59 exerted a potent inhibitory effect when added up to 24 hr after virus inoculation. Circular dychroism analysis showed that peptide 5 folds to a helical conformation in the presence of a hydrophobic environment. Although the basis for the antiviral action of the peptides is not understood, our data suggest that the inhibitory peptides may act by interacting with cell-surface molecules involved in viral infection.     

Improving Medical Device Regulation: The United States and Europe in Perspective

Context: Recent debates and events have brought into question the effectiveness of existing regulatory frameworks for medical devices in the United States and Europe to ensure their performance, safety, and quality. This article provides a comparative analysis of medical device regulation in the two jurisdictions, explores current reforms to improve the existing systems, and discusses additional actions that should be considered to fully meet this aim. Medical device regulation must be improved to safeguard public health and ensure that high-quality and effective technologies reach patients.Methods: We explored and analyzed medical device regulatory systems in the United States and Europe in accordance with the available gray and peer-reviewed literature and legislative documents.Findings: The two regulatory systems differ in their mandate and orientation, organization, pre-and postmarket evidence requirements, and transparency of process. Despite these differences, both jurisdictions face similar challenges for ensuring that only safe and effective devices reach the market, monitoring real-world use, and exchanging pertinent information on devices with key users such as clinicians and patients. To address these issues, reforms have recently been introduced or debated in the United States and Europe that are principally focused on strengthening regulatory processes, enhancing postmarket regulation through more robust surveillance systems, and improving the traceability and monitoring of devices. Some changes in premarket requirements for devices are being considered.Conclusions: Although the current reforms address some of the outstanding challenges in device regulation, additional steps are needed to improve existing policy. We examine a number of actions to be considered, such as requiring high-quality evidence of benefit for medium-and high-risk devices; moving toward greater centralization and coordination of regulatory approval in Europe; creating links between device identifier systems and existing data collection tools, such as electronic health records; and fostering increased and more effective use of registries to ensure safe postmarket use of new and existing devices.     

Single Catheter Determination of Local Electrogram Prematurity Using Simultaneous Unipolar and Bipolar Recordings to Replace the Surface ECG as a Timing Reference

DELACRETAZ, E., et al. : Single Catheter Determination of Local Electrogram Prematurity Using Simultaneous Unipolar and Bipolar Recordings to Replace the Surface ECG as a Timing Reference. Bipolar recordings eliminate much of the far-field signal, while minimally filtered unipolar recordings contain substantial far-field signal components. These properties may allow the onset of the unipolar recording to serve as a timing reference for the bipolar recording obtained from the same electrode catheter during mapping of focal atrial or ventricular tachycardias. Mapping and RF ablation were performed in 26 patients with focal ventricular tachycardia and 14 patients with focal atrial tachycardia. At 205 mapping sites, simultaneous recordings of (1) minimally filtered unipolar electrograms (0.5–500 Hz), (2) high pass filtered unipolar electrograms (100 Hz), and (3) filtered bipolar recordings (30–500Hz) were analyzed. The interval between the onset of the minimally filtered unipolar electrogram and the first peak of the bipolar electrogram (Uni_On - Bi_p) correlated closely with the timing of the local electrogram referenced to the surface ECG (  r = 0.85, P < 0.001  ). Of 53 sites where RF ablation was performed, Uni_On - Bi_P was shorter at successful compared to unsuccessful sites (  3.8 ± 3.5 vs 9.2 ± 5.2ms, P < 0.001  ) and was < 15 ms at all successful sites. In conclusion, the comparison of simultaneous unipolar and bipolar electrograms from a single catheter allows assessment of the prematurity of local electrograms from a focal source without the use of the P wave or QRS onset as a timing reference.