Ventricular Tachycardia After Myocardial Infarction: From Arrhythmia Surgery to Catheter Ablation

Ablation of Ventricular Tachycardia. Ventricular tachycardia due to prior myocardial infarction is caused by reentry. Intraoperative mapping at the time of arrhythmia surgery has shown that the reentry circuits arc diverse in size and location. Many circuits are large, extending over several square centimeters. Endocardial excision guided by activation sequence mapping, fractionated sinus rhythm electrograms, or visual identification of scarred subendo-cardium renders 69% to 95% of patients free from inducible ventricular tachycardia, but with an operative mortality that exceeds 8%, at most centers. Catheter ablation is difficult due to limitations of catheter mapping, relatively small size of lesions produced with current techniques, and limited access to intramural and epicardial portions of the reentry circuits. Many problems need to be overcome for catheter ablation to achieve success comparable to that of surgery. At present, only hemodynamically tolerated ventricular tachycardias can he mapped. Progress is being made, and it is likely that catheter ablation will become a viable therapy for subgroups of patients with postmyocardial infarction ventricular tachycardia.     

Zinc deficiency and energy restriction modify immune responses in mice during both primary and challenge infection with Heligmosomoides polygyrus (Nematoda)

This study characterized the consequences of zinc-sufficient (Zn+, 60 mg zinc/kg diet, ad libitum ), zinc-deficient (Zn−, 0.75 mg zinc/kg diet, ad libitum ) and energy-restricted (ER, 60 mg zinc/kg diet which was restricted to match food intake of Zn− mice) diets on the in vivo and in vitro immune response of BALB/c mice during both primary and challenge infection with Heligmosomoides polygyrus . In Zn+ mice, both primary and challenge infection with H. polygyrus induced not only a strong Th2 response (IgE, IgG1, eosinophilia, IL-4, IL-5, IL-10), but also elements of a Th1 response (IgG3, IFN-γ). Zinc deficiency significantly depressed Th2-dependent antibody production during both primary and challenge infection, and reduced mitogen and antigen-induced T cell proliferation during the challenge infection. Th2 cytokine production was reduced by zinc deficiency (IL-4), energy restriction (IL-5) and by zinc deficiency possibly in combination with energy restriction (IL-10) during the primary infection whereas Th1 cytokine production (IFN-γ) was depressed during the challenge infection by zinc deficiency, possibly together with energy restriction. Both zinc deficiency and energy restriction reduced eosinophilia with the more profound effect being exerted by zinc deficiency. Thus, both zinc deficiency and its concurrent energy restriction modify immune responses in the mice during primary and challenge infection with H. polygyrus.     

Electrophysiological Mapping and Radiofrequency Catheter Ablation for Ventricular Tachycardia in a Patient with Peripartum Cardiomyopathy

A 38‐year‐old female with prior failed endocardial ablation for ventricular tachycardia (VT) was referred for further treatment. She had been diagnosed with peripartum cardiomyopathy 7 years before and had persistent left ventricular dysfunction with an ejection fraction of 20%. Epicardial voltage mapping showed extensive epicardial scar despite absence of endocardial scar. Five distinct VT morphologies were induced. Ablation was aided by electrogram characteristics, pace mapping, entrainment mapping, and establishing electrical inexcitability along areas of epicardial scar. After epicardial ablation no sustained VT was induced. She had been doing well without VT occurrence but died 1 year later unexpectedly at home.     

Zinc deficiency impairs T cell function in mice with primary infection of Heligmosomoides polygyrus (Nematoda)

This study was designed to determine whether severe zinc deficiency would prolong the course of a primary Heligmosomoides polygyrus infection in mice, and whether this could be related to impaired T cell function. Female BALB/c mice were fed a zinc-sufficient (Zn+; 60 mg/kg), a zinc-deficient (Zn-; 0.75 mg/kg) or an energy restricted (PF; 60 mg zinc/kg) diet. After four weeks, some mice in each dietary group were given a primary infection with 100 larvae; nutritional, parasitological and immunological parameters were assayed over the following five weeks. Liver zinc concentrations were significantly reduced in Zn- mice compared with Zn+ mice. In certain cases, PF mice also had reduced liver zinc concentrations, showing the negative effects of restricted food intake on zinc status. Zinc deficiency prolonged the course of a primary infection, with the effects being most evident five weeks post-infection when Zn+ mice had only 40% as many worms as Zn- mice. Parasite infection induced strong immunological responses in Zn+ mice in contrast to Zn- mice. The reduced production of IL-4 and IFN-γ, the reduced peripheral eosinophilia and reduced serum levels of IgE and IgG1 in Zn- mice were attributed to the zinc deficiency, whereas the reduced delayed type hypersensitivity response to parasite antigen and reduced production of IL-5 were in certain instances attributed to reduced energy intake rather than zinc deficiency. These results show that zinc deficiency significantly impairs functions normally attributed to both Th1 and Th2 cell populations, and that these alterations are associated with elevated worm numbers in zinc-deficient mice.     

Rapid cytotoxicity of human B lymphocytes induced by VH4-34 (VH4.21) gene-encoded monoclonal antibodies

We have previously described two human cold agglutinin MoAbs 216 and A6(H4C5), that are derived from the VH4-34 (VH4.21) gene that bind specifically to a cell surface ligand on human B lymphocytes. In this study, we report that binding of 216 and A6(H4C5) leads to rapid killing of target B cells. This complement-independent cytotoxicity was measured by three independent assays, cell viability dye uptake on FACS, ³H-thymidine uptake, and the 3(4,5)-dimethylthiazol-2,5-diphenyl tetrazolium bromide (MTT) assay. Cytotoxicity was specific for CD20⁺ mononuclear cells in human spleen and peripheral blood. The MoAbs were also cytotoxic to human B cell lines Nalm-6, OCI-LY8, Arent and SUP-B8, but not to T cell lines HuT 78 and PEER. As observed by scanning electron microscopy, membrane pores were formed within 15 min of exposure to the MoAbs. Cytotoxic activity was dependent on MoAb concentration and temperature of exposure. Killing was greater at 4°C than 37°C. Sodium azide and EDTA did not block the cytotoxic activity. No DNA fragmentation typical of apoptosis was observed. This rapid cytotoxic activity, independent of physiologic cellular processes and independent of complement, suggests a novel mechanism of cell death via membrane perturbations.     

Neonatal brain structure on MRI and diffusion tensor imaging, sex, and neurodevelopment in very-low-birthweight preterm children

The neurological basis of an increased incidence of cerebral palsy (CP) in preterm males is unknown. This study examined neonatal brain structure on magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) at term‐equivalent age, sex, and neurodevelopment at 1 year 6 months on the basis of the Amiel?Tison neurological examination, Gross Motor Function Classification System, and Bayley Scales of Infant Development in 78 very‐low‐birthweight preterm children (41 males, 37 females; mean gestational age 27.6wks, SD 2.5; mean birthweight 1021g, SD 339). Brain abnormalities on MRI and DTI were not different between males and females except in the splenium of the corpus callosum, where males had lower DTI fractional anisotropy (p=0.025) and a higher apparent diffusion coefficient (p=0.013), indicating delayed splenium development. In the 26 infants who were at higher risk on the basis of DTI, males had more abnormalities on MRI (p=0.034) and had lower fractional anisotropy and a higher apparent diffusion coefficient in the splenium (p=0.049; p=0.025) and right posterior limb of the internal capsule (PLIC; p=0.003; p=0.033). Abnormal neurodevelopment was more common in males (n=9) than in females (n=2; p=0.036). Children with abnormal neurodevelopment had more abnormalities on MRI (p=0.014) and reduced splenium and right PLIC fractional anisotropy (p=0.001; p=0.035). In children with abnormal neurodevelopment, right PLIC fractional anisotropy was lower than left (p=0.035), whereas in those with normal neurodevelopment right PLIC fractional anisotropy was higher than left (p=0.001). Right PLIC fractional anisotropy correlated to neurodevelopment (rho=0.371, p=0.002). Logistic regression predicted neurodevelopment with 94% accuracy; only right PLIC fractional anisotropy was a significant logistic coefficient. Results indicate that the higher incidence of abnormal neurodevelopment in preterm males relates to greater incidence and severity of brain abnormalities, including reduced PLIC and splenium development.     

Concordance: what is the relevance for pharmacists?

Non‐adherence (or non‐compliance) to prescribed medicines has long been regarded as problematic. The concept of concordance, rather than seeking ways to persuade people to take their medicines, instead focuses on the need to adopt a different model of the patient‐prescriber relationship. Much of the discussion about concordance thus far has related to the relationship between doctors and patients. In this article, the role of the pharmacist and ways in which pharmacists could usefully engage with the concordance model, both as part of the primary health care team and as independent practitioners, are considered. Concordance was developed as an ideal to which to aspire and needs to make the transition into practice. It is however important to note that if the move towards concordance is to happen and be successful it will require the support, enthusiasm and commitment of patients and health care professionals generally.