No abstract

Macaques provide excellent models for preclinical testing and safety assessment of female reproductive toxicants. Currently, cynomolgus monkeys are the predominant species for (reproductive) toxicity testing. Marmosets and rhesus monkeys are being used occasionally. The authors provide a brief review on physiology and endocrinology of the cynomolgus monkey ovarian cycle, practical guidance on assessment and monitoring of ovarian cyclicity, and new data on effects of social housing on ovarian cyclicity in toxicological studies. In macaques, cycle monitoring is achieved using daily vaginal smears for menstruation combined with cycle-timed frequent sampling for steroid and peptide hormone analysis. Owing to requirements of frequent and timed blood sampling, it is not recommended to incorporate these special evaluations into a general toxicity study design. Marmosets lack external signs of ovarian cyclicity, and cycle monitoring is done by regular determinations of progesterone. Cynomolgus and marmoset monkeys do not exhibit seasonal variations in ovarian activity, whereas such annual rhythm is pronounced in rhesus monkeys. Studies on pair- and group-housed cynomolgus monkeys revealed transient alterations in the duration and endocrinology of the ovarian cycle followed by return to normal cyclicity after approximately six months. This effect is avoided if the animals had contact with each other prior to mingling. These experiments also demonstrated that synchronization of ovarian cycles did not occur.

Appropriate and inappropriate therapies of implantable cardioverter defibrillators have a major impact on morbidity and quality of life in ICD recipients, but have not been systematically studied in children and young adults during long-term follow-up. ICD implantation was performed in 20 patients at the mean age of 16 +/- 6 years, 11 of which had prior surgical repair of a congenital heart defect, 9 patients had other cardiac diseases. Implant indications were aborted sudden cardiac death in six patients, recurrent ventricular tachycardia in 9 patient, and syncope in 5 patients. Epicardial implantation was performed in 6 and transvenous implantation in 14 patients. Incidence, reasons and predictors (age, gender, repaired congenital heart disease, history of supraventricular tachycardia, and epicardial electrode system) of appropriate and inappropriate ICD therapies were analyzed during a mean follow-up period of 51 +/- 31 months range 18-132 months. There were a total 239 ICD therapies in 17 patients (85%) with a therapy rate of 2.8 per patient-years of follow-up. 127 (53%) ICD therapies in 15 (75%) patients were catagorized as appropriate and 112 (47%) therapies in 10 (50%) patients as inappropriate, with a rate of 1.5 appropriate and 1.3 inappropriate ICD therapies per patient-years of follow-up. Time to first appropriate therapy was 16 +/- 18 months. Appropriate therapies were caused by ventricular fibrillation in 29 and ventricular tachycardia in 98 episodes. Termination was successful by antitachycardia pacing in 4 (3%) and by shock therapy in 123 episodes (97%). Time to first inappropriate therapy was 16 +/- 17 months. Inappropriate therapies were caused by supraventricular tachycardia in 77 (69%), T wave oversensing in 19 (17%), and electrode defect in 16 episodes (14%). It caused shocks in 87 (78%) and only antitachycardia pacing in 25 episodes (22%). No clinical variable could be identified as predictor of either appropriate or inappropriate ICD therapies. There is a high rate of ICD therapies in young ICD recipients, the majority of which occur during early follow-up. The rate of inappropriate therapies is as high as 47% and is caused by supraventricular tachycardia and electrode complications in the majority of cases. Prospective trials are required to establish preventative strategies of ICD therapies in this young patient population.

MD; for the ADRIA InvestigatorsBackground-Supraventricular tachyarrhythmias are the main cause for inappropriate therapy by implantable cardioverterdefibrillators (ICDs). For better rhythm discrimination, an atrial electrogram is helpful and usually obtained from an additional atrial lead, even in the absence of sinus node or atrioventricular nodal disease. An Aϩ-ICD system with integrated atrial sensing rings mounted 15 to 18 cm from the tip of an ICD lead may obviate the need to implant a separate atrial lead. The aim of the study was to compare the novel Aϩ-ICD and a conventional dual-chamber (DR)-ICD. Methods and Results-Two hundred forty-nine patients with standard ICD indications but no requirement for antibradycardia pacing were randomized to receive an Aϩ-ICD (nϭ124) or a DR-ICD (nϭ125). Implantation details, need for ICD system revision, long-term sensing, documented arrhythmia episodes, and the respective rhythm discrimination during follow-up were analyzed. The implantation time was significantly shorter in the Aϩ-ICD group (67Ϯ30 vs 79Ϯ30 minutes, Pϭ0.003). Mean P-wave amplitudes were 3.5Ϯ0.8 mV (Aϩ-ICD) and 3.2Ϯ0.6 mV (DR-ICD) and remained stable during the follow-up period of 12 months. Surgical revision was necessary in 13 patients in the DR-ICD and 10 in the Aϩ-ICD group. All 593 ventricular tachyarrhythmia episodes were correctly discriminated. Sensitivity and specificity of supraventricular tachyarrhythmia discrimination were not different between the study groups. Conclusions-The novel Aϩ-ICD system can be implanted faster and is equivalent to a standard DR-ICD with regard to the detection of ventricular tachyarrhythmias and supraventricular tachyarrhythmias. It represents a useful alternative to obtain atrial sensing. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00324662.

A large proportion of patients carry bacteria on their pacemaker or implantable cardioverter defibrillator asymptomatically. The strains found differ from those commonly seen in clinically evident device infections. Common risk factors for device infection did not correlate with the presence of DNA.