Clinical effectiveness of an outpatient pathway for low-risk chest pain emergency department visits.

BACKGROUND: Studies suggest that patients who present with atypical chest pain and are low or low-intermediate risk can safely undergo a rapid rule-out for cardiac ischemia with serial ECGs and cardiac biomarkers followed by additional testing as needed. We sought to evaluate a novel Emergency Department (ED) protocol for patients to undergo their additional functional testing as an outpatient. METHODS: Patients presenting to the ED with atypical chest pain, normal ECG, and negative cardiac troponin felt to be low risk were referred for outpatient stress testing within 72 hours of presentation as part of a pilot program. We analyzed test characteristics, length of stay, and 30-day return visits to ED in the pilot group and compared results to a similar cohort assessed in the ED by a traditional chest pain observation protocol. RESULTS: A total of 156 patients were included over a 5-month period with 29.5% not returning for testing. There was a 70% reduction in length of stay for outpatient stress test protocol patients. All-cause and cardiac return visits to the ED were not significantly different between the outpatient cohort and the traditional chest pain unit group and were reduced by 47 and 75%, respectively, in patients who completed their outpatient testing. The provisional injection protocol resulted in a 81% reduction in radiation exposure when compared to traditional MPI stress protocols due to a greater utilization of exercise treadmill tests without imaging. CONCLUSION: Outpatient stress testing is a reliable alternative to traditional chest pain observation with a significantly shorter length of stay, reduced healthcare costs, and improved radiation safety profile for patients when compared to traditional inpatient observation.

Clinical predictors of antitachycardia pacing response in implantable cardioverter defibrillator patients.

BACKGROUND: Antitachycardia pacing (ATP) provides safe and painless termination of reentrant ventricular arrhythmias in patients with implantable cardioverter defibrillator (ICDs), improving their quality of life. Established predictors of ATP responsiveness are not well known; only longer ventricular tachycardia (VT) cycle length and higher ejection fraction have been found to predict ATP success. OBJECTIVE: To investigate clinical and ECG predictors of ATP response in ICD patients with monomorphic VT. METHODS: The ICD clinic database was searched for monomorphic VT events requiring ICD therapy in patients with ischemic or non-ischemic cardiomyopathy. Each patient's first ICD encounter for VT was assessed. Patient demographics, clinical characteristics, VT rate, and ATP responsiveness (always, sometimes, and never successful) were recorded. An ECG was analyzed for QRS morphology and duration. Data was assessed for predictors of ATP responsiveness. RESULTS: In 527 patients, characteristics associated with always successful ATP included ACE-I/ARB therapy and slower VT rate (never successful ATP 197 ± 28 bpm, sometimes successful ATP 190 ± 27 bpm, always successful ATP 183 ± 22 bpm, P < .0001). Secondary prevention indication, amiodarone therapy, and longer QRS duration were associated with ATP failure. After multivariate analysis, only faster VT rate and amiodarone therapy were predictive of ATP failure. CONCLUSIONS: Neither QRS morphology nor duration was predictive of ATP success. Slower VT rate was predictive of repeated ATP responsiveness. Amiodarone therapy, which is known to increase VT cycle length, interestingly was associated with ATP failure for unclear reasons. More individualized and possibly more aggressive ATP programming may be warranted in patients on amiodarone.

Role of plasma exchange in the treatment of myeloma nephropathy: experience of one institution and systematic review.

Plasmapheresis is an efficient method of removing light chains from the circulation. Several studies have shown that it improves renal function in patients with multiple myeloma and renal impairment due to cast nephropathy. The degree of renal failure has been shown to be an important predictor of morbidity and mortality in myeloma. The use of plasmapheresis remains controversial, since it does not affect plasma cells and thus further production of light chains. In addition, existing evidence does not demonstrate a clear benefit from plasmapheresis in these patients. However, data, including some of the new targeted therapies for myeloma, are lacking. Herein, we present our institution's experience in the use of plasmapheresis in patients with myeloma and renal failure, and review the existing literature.

Interesting medical images: the Jaffe-Campanacci syndrome.

Herein we report the clinical presentation and radiographic findings of a patient with a known history of multiple nonossifying fibromas, also known as the Jaffe-Campanacci syndrome, who presented with persistent pleuritic chest pain after a fall and was found to have a small pulmonary embolus. The presentation, pathophysiology and management of the syndrome are briefly discussed.

Neurosarcoidosis presenting with isolated spinal involvement: report of a case and review of the literature.

Spinal sarcoidosis is a rare manifestation of sarcoidosis that can present a major diagnostic challenge. Herein we present a case of a previously healthy 55-year-old man who presented with leg weakness and was found to have diffuse involvement of his spinal cord by neurosarcoidosis. He was treated with steroids and recovered completely. The clinical characteristics, radiographic and laboratory findings of spinal sarcoidosis are discussed. Management strategies, including the use of newer targeted therapies, are also reviewed.

Eosinophilic Myocarditis: Is Endomyocardial Biopsy Essential for Diagnosis in the Era of Advanced Cardiac Imaging?

A 60-year-old female presented with dyspnea and chest pressure. Clinical presentation, laboratory data, echocardiography, and cardiac magnetic resonance (CMR) imaging findings confirmed diagnosis of eosinophilic myocarditis and obviated unnecessary invasive endomyocardial biopsy. She was treated with oral steroid and oral anticoagulation. Follow-up CMR imaging showed resolution of the left ventricle thrombus with improvement in endomyocardial inflammation.

Mercury induces inflammatory mediator release from human mast cells.

BACKGROUND: Mercury is known to be neurotoxic, but its effects on the immune system are less well known. Mast cells are involved in allergic reactions, but also in innate and acquired immunity, as well as in inflammation. Many patients with Autism Spectrum Disorders (ASD) have "allergic" symptoms; moreover, the prevalence of ASD in patients with mastocytosis, characterized by numerous hyperactive mast cells in most tissues, is 10-fold higher than the general population suggesting mast cell involvement. We, therefore, investigated the effect of mercuric chloride (HgCl2) on human mast cell activation. METHODS: Human leukemic cultured LAD2 mast cells and normal human umbilical cord blood-derived cultured mast cells (hCBMCs) were stimulated by HgCl2 (0.1-10 microM) for either 10 min for beta-hexosaminidase release or 24 hr for measuring vascular endothelial growth factor (VEGF) and IL-6 release by ELISA. RESULTS: HgCl2 induced a 2-fold increase in beta-hexosaminidase release, and also significant VEGF release at 0.1 and 1 microM (311 +/- 32 pg/106 cells and 443 +/- 143 pg/106 cells, respectively) from LAD2 mast cells compared to control cells (227 +/- 17 pg/106 cells, n = 5, p < 0.05). Addition of HgCl2 (0.1 microM) to the proinflammatory neuropeptide substance P (SP, 0.1 microM) had synergestic action in inducing VEGF from LAD2 mast cells. HgCl2 also stimulated significant VEGF release (360 +/- 100 pg/106 cells at 1 microM, n = 5, p < 0.05) from hCBMCs compared to control cells (182 +/- 57 pg/106 cells), and IL-6 release (466 +/- 57 pg/106 cells at 0.1 microM) compared to untreated cells (13 +/- 25 pg/106 cells, n = 5, p < 0.05). Addition of HgCl2 (0.1 microM) to SP (5 microM) further increased IL-6 release. CONCLUSIONS: HgCl2 stimulates VEGF and IL-6 release from human mast cells. This phenomenon could disrupt the blood-brain-barrier and permit brain inflammation. As a result, the findings of the present study provide a biological mechanism for how low levels of mercury may contribute to ASD pathogenesis.

Inhibitory effect of aminoimidazole carboxamide ribonucleotide (AICAR) on endotoxin-induced uveitis in rats.

PURPOSE. To investigate the anti-inflammatory effect of aminoimidazole carboxamide ribonucleotide (AICAR), an analog of adenosine monophosphate (AMP), in endotoxin-induced uveitis (EIU). METHODS. EIU was induced by subcutaneous injection of lipopolysaccharide (LPS) (200 µg) in Lewis rats. AICAR (50 mg/kg, intraperitoneally) was given 6 hours prior and at the same time as LPS injection. Clinical uveitis scores, number of anterior chamber (AC) infiltrating cells, anterior chamber protein concentration, retinal vessel leukocyte adhesion, and protein leakage were measured 24 hours later. Protein levels of C-C chemokine ligand-2 (CCL-2)/monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) in aqueous humor and retina and nuclear translocation of nuclear factor-κB (NF-κB) in the retina were determined by enzyme-linked immunosorbent assay (ELISA). Both mRNA and protein levels of CD14 in peripheral blood mononuclear cells were also measured. RESULTS. AICAR treatment significantly reduced EIU clinical severity as well as inflammatory cell infiltration and protein concentration in aqueous humor. Similarly, the number of retinal vessel-adherent leukocytes and protein leakage were decreased by AICAR treatment. Protein levels of TNF-α, CCL-2/MCP-1, and ICAM-1 in aqueous humor and CCL-2/MCP-1 and ICAM-1 levels in retina were suppressed with AICAR treatment. AICAR also reduced NF-κB translocation and CD14 expression. CONCLUSIONS. AICAR reduces systemic LPS susceptibility and attenuates intraocular inflammation in a rat EIU model by limiting infiltration of leukocytes, suppressing inflammatory mediators, and inhibiting the NF-κB pathway.

A novel nonradioactive method to evaluate vascular barrier breakdown and leakage.

PURPOSE: To identify a novel, sensitive, nonradioactive leakage assay that can be used in the assessment of retinal vascular permeability in rats and mice. METHODS: Breakdown of the vascular barrier was induced by vascular endothelial growth factor (VEGF), lipopolysaccharide (LPS), or diabetes. Biotinylated bovine serum albumin (bBSA) was administered as a tracer. After perfusion with lactated Ringer's solution, extravasated bBSA was detected with immunoprecipitation and Western blot analysis or sandwich ELISA. The results were then normalized against the final bBSA plasma concentration, the circulation time, and the protein concentration of the tissue. RESULTS: Six hours after VEGF injection, BRB breakdown was quantified in the injected eye and was 2.5-fold higher than in the contralateral phosphate-buffered saline (PBS)-injected eye (n = 6 rats, P < 0.01). Intravitreal LPS injection induced severe inflammation in the directly injected eye and moderate inflammation in the contralateral untreated eye. Leakage was six- and threefold higher, respectively, compared with that in the untreated control animals (n = 5 rats, P < 0.01). Nine-month diabetic rats had a threefold increase in vascular leakage compared with age-matched control animals (n = 6 retinas, P < 0.05). Twenty-four hours after intraperitoneal administration of LPS in mice, the animals showed increased vascular leakage in all tissue organs examined (retina, 1.7-fold; brain, 1.5-fold; and kidney, 1.3-fold). CONCLUSIONS: bBSA can serve as an effective alternative to the current methods used for quantitating vascular leakage and especially the blood-retinal barrier breakdown. It is reasonably easy to perform, low in cost, and adaptable to experiments in mice.

Urocortin induces interleukin-6 release from rat cardiomyocytes through p38 MAP kinase, ERK and NF-kappaB activation.

CRH and its structurally related peptide urocortin (Ucn) are released under stress. Ucn is a potent agonist for CRH-receptor 2 (CRH-R2), which is strongly expressed in rodent heart. Stress induces Ucn mRNA expression in the heart, where it may be cardioprotective. However, increasing evidence indicates that Ucn may also have pro-inflammatory actions. Here, we show that neonatal rat cardiomyocytes express CRH-R2 by western blot analysis and Ucn induces interleukin-6 (IL-6) release in a time- and dose-dependent fashion. Ucn stimulates activation of ERK and p38 MAP kinases, while both MEK1 and p38 inhibitor block Ucn-induced IL-6 release. Ucn also activates nuclear factor kappa B (NF-kappaB) and a NF-kappaB inhibitor blocks Ucn-induced IL-6 release. Finally, the CRH-R antagonists alpha-helical (9-41) CRH and astressin-2B completely inhibit Ucn-induced IL-6 release, as well as activation of ERK, p38, and NF-kappaB. These findings indicate that Ucn induces IL-6 synthesis and release from neonatal rat cardiomyocytes. Our findings suggest that even though Ucn may confirm some protection on cardiomyocyte survival, it can also release IL-6, which is an independent risk factor for acute coronary syndrome. The precise role of cardiac Ucn in vivo remains to be elucidated.

Human mast cells stimulate activated T cells: implications for multiple sclerosis.

Multiple sclerosis is an autoimmune demyelinating disease of the central nervous system mainly mediated by Th1 and/or Th17 cells, which cross the blood-brain barrier. Recent evidence indicates that Th2 cells and mast cells, typically associated with allergic reactions, are also involved. Brain mast cells are critically located perivascularly and secrete numerous proinflammatory and vasoactive molecules that can disrupt the blood-brain barrier, a finding that precedes clinical or pathologic signs of multiple sclerosis. Brain mast cells in multiple sclerosis are activated by neural factors, including substance P, myelin basic protein, and corticotropin-releasing hormone, caused by acute stress, which induce release of several inflammatory mediators. Mast cells can stimulate activated T cells coming in contact with them at the blood-brain barrier, as well as after stimulation with myelin basic protein or substance P. Pretreatment with the flavone luteolin blocks mast cell stimulation and T cell activation, as well as experimental autoimmune encephalitis. Interactions between mast cells and T cells could constitute a new and unique therapeutic target for multiple sclerosis.