Safety of repetitive nerve stimulation in patients with cardiac implantable electronic devices

Introduction: Pacemakers and implantable cardioverter-defibrillators (ICDs) are vulnerable to inappropriate sensing of electromagnetic interference (EMI), such as from nerve conduction studies. We conducted a prospective study to assess the safety of repetitive nerve stimulation (RNS). Methods: Fourteen patients undergoing insertion of 10 ICDs and 4 pacemakers under general anesthesia received RNS of the median, axillary, and spinal accessory nerves at 2 HZ and 50 HZ . We recorded detection of EMI and whether or not this resulted in an arrhythmia diagnosis or change in pacing output. Results: EMI was visible in 2 ICDs, without spurious tachyarrhythmia detection. EMI was observed in 3 of the 4 pacemakers, which led to pacing inhibition and a pause in 2, both of which were programmed to a unipolar sensing configuration. Conclusions: RNS is safe in patients with ICDs. In pacemaker patients, RNS appears safe during bipolar sensing, but caution is recommended in pacemaker patients with unipolar sensing. Muscle Nerve 47: 840–844, 2013     

Chimerism and tetragametic chimerism in humans: implications in autoimmunity, allorecognition and tolerance

The presence of cells or tissues from two individuals, chimeras, or the presence of cells and tissues that include the gonads, tetragametic chimerism can be detected by the analysis of cytogenetics and analysis of polymorphic genetic markers, using patterns of pedigree inheritance. These methodologies include determination of sex chromosomes, major histocompatibility complex (MHC) polymorphisms and panels of short tandem repeats (STRs) that include mitochondrial DNA markers. Studies routinely involve cases of temporal chimerism in blood transfusion, or following allotransplantation to measure the outcome of the organ, lymphopoietic tissues or bone marrow grafts. Demonstration of persistent chimerism is usually discovered in cases of inter-sexuality due to fusion of fraternal twins or in cases of fusion of embryos with demonstrable allogeneic monoclonality of blood which, excluded maternity or paternity when blood alone is used as the source of DNA. In single pregnancies it is possible to produce two kinds of microchimerism: feto-maternal and materno-fetal, but in cases of fraternal twin pregnancies it is possible to identify three different kinds which are related to cases of vanishing twins that can be identified during pregnancy by imaging procedures; (1) hematopoietic, (2) gonadal, and (3) freemartins when the twins have different sex and the individual born is a female with either gonadal or both gonadal and hematopoietic tissues. Fraternal twin pregnancies can also produce fusion of embryos. Such cases could be of different sex presenting with inter-sexuality or in same sex twins. One of such cases, the best studied, showed evidence of chimerism and tetragametism. In this regard, the case was studied because of disputed maternity of two of her three children. All tissues studied, except for the blood, demonstrated four genetic components but only two in her blood of four possible showed allogeneic monoclonality consistent with the interpretation that her blood originated from one hematopoietic stem cell. Also, microchimerism, due to traffic of cells via materno-fetal or feto-maternal has been prompted by reports of their potential association with the development of autoimmune disorders including systemic lupus erythematosus (SLE) and systemic sclerosis, and in allotransplantation. In addition, their relevance of chimerism in the positive and negative selection of T cells in the thymus has not been addressed. T lymphocytes play a central role in controlling the acquired immune response and furthermore serve as crucial effector cells through antigen specific cytotoxic activity and the production of soluble mediators. Central tolerance is established by the repertoire selection of immature T lymphocytes in the thymus, avoiding the generation of autoreactive T cells. Expression of chimeric antigens in the thymus could modify the generation of specific T cell clones in chimeric subjects and these mechanisms could be important in the induction of central tolerance against foreign antigens important in allo-transplantation. In this review, we discuss the genetics of chimerism and tetragametism and its potential role in thymic selection and the relevance in allotransplantation and autoimmune disorders. This review is dedicated to the memory of Robert A. Good, MD, PhD, an outstanding physician and scientist, one discoverer of the functions of the Thymus in immunobiology and the pioneer of human bone marrow allotransplantation. Presented at the First Robert A Good Society Symposium, St. Petersburg, FL 2006.