Project description:Because of its powerful genetics, the adult zebrafish has been increasingly used for studying cardiovascular diseases. Considering its heart rate of ~100 beats per minute at ambient temperature, which is very close to human, we assessed the use of this vertebrate animal for modeling heart rhythm disorders such as sinus arrest (SA) and sick sinus syndrome (SSS). We firstly optimized a protocol to measure electrocardiogram in adult zebrafish. We determined the location of the probes, implemented an open-chest microsurgery procedure, measured the effects of temperature, and determined appropriate anesthesia dose and time. We then proposed an PP interval of more than 1.5 seconds as an arbitrary criterion to define an SA episode in an adult fish at ambient temperature, based on comparison between the current definition of an SA episode in humans and our studies of candidate SA episodes in aged wild-type fish and Tg(SCN5A-D1275N) fish (a fish model for inherited SSS). With this criterion, a subpopulation of about 5% wild-type fish can be considered to have SA episodes, and this percentage significantly increases to about 25% in 3-year-old fish. In response to atropine, this subpopulation has both common SSS phenotypic traits that are shared with the Tg(SCN5A-D1275N) model, such as bradycardia; and unique SSS phenotypic traits, such as increased QRS/P ratio and chronotropic incompetence. In summary, this study defined baseline SA and SSS in adult zebrafish and underscored use of the zebrafish as an alternative model to study aging-associated SSS.
Project description:An 80-year-old man was admitted to the hospital because of fever, bloody sputum and exertional dyspnea of 3 days. Laboratory tests showed anemia and increase of the C-reactive protein level. A chest computed tomography scan revealed diffuse bilateral ground-glass opacities. Bronchoalveolar lavage confirmed the clinical diagnosis of diffuse alveolar hemorrhage (DAH). After methylprednisolone pulse therapy, Enterococcus faecalis was detected in the blood cultures. A diagnosis of infective endocarditis was made according to the Modified Duke's criteria. The causes of DAH are certainly diverse; however, we should consider infective endocarditis as one of the etiologies of DAH.
Project description:Approximately 70% of sudden sensorineural hearing loss (SSNHL) cases are idiopathic, but SSNHL may occasionally be related to fatality. Here, we report the case of a 54-year-old Asian female who complained of hearing loss as a primary symptom and was diagnosed with pyogenic ventriculitis (PV) derived from Streptococcus agalactiae endocarditis. Both PV and S. agalactiae endocarditis are rare and very severe infections with a high mortality rate. Rapid intensive treatment and surgery were required for successful clinical outcomes.
Project description:Streptococcus pneumoniae produces pneumolysin toxin as a key virulence factor against host cells. Pneumolysin is a cholesterol-dependent cytolysin (CDC) toxin that forms lytic pores in host membranes and mediates pneumococcal disease pathogenesis by modulating inflammatory responses. Here, we show that pneumolysin, which is released during bacterial lysis, induces DNA double strand breaks (DSBs), as indicated by ataxia telangiectasia mutated (ATM)-mediated H2AX phosphorylation (?H2AX). Pneumolysin-induced ?H2AX foci recruit mediator of DNA damage checkpoint 1 (MDC1) and p53 binding protein 1 (53BP1), to sites of DSBs. Importantly, results show that toxin-induced DNA damage precedes cell cycle arrest and causes apoptosis when DNA-dependent protein kinase (DNA-PK)-mediated non-homologous end joining is inhibited. Further, we observe that cells that were undergoing DNA replication harbored DSBs in greater frequency during pneumolysin treatment. This observation raises the possibility that DSBs might be arising as a result of replication fork breakdown. Additionally, neutralizing the oligomerization domain of pneumolysin with monoclonal antibody suppresses DNA damage and also cell cycle arrest, indicating that pneumolysin oligomerization is important for causing DNA damage. Taken together, this study reveals a previously unidentified ability of pneumolysin to induce cytotoxicity via DNA damage, with implications in the pathophysiology of S. pneumoniae infection.
Project description:Clinically significant myocardial infiltration by leukemic cells is a rare phenomenon. We describe a case of a 47-year-old woman with newly diagnosed acute myeloid leukemia and pleuritic chest pain with rapid cardiopulmonary decompensation. Post-mortem analyses showed fibrinous pericarditis and extensive leukemic infiltration of the myocardium. (Level of Difficulty: Intermediate.).
Project description:Acute coronary syndromes (ACS) usually occur in patients with multiple cardiac risk factors. In young adults, drug use and hypercoagulable states are common causes for ACS presentations. We report a case of a man in his early 30s who was diagnosed with polycythemia vera (PV) and had a cardiac arrest due to an anterolateral ST elevation myocardial infarction. We discuss his unique management and review the evidence on the management of arterial thromboembolism in PV patients.
Project description:This case report describes the unusual presentation of a previously very well woman with Streptococcus agalactiae endocarditis in the emergency department. History, examination and preliminary laboratory and radiological investigations supported a diagnosis of acalculous cholecystitis, for which she was given intravenous broad spectrum antimicrobial therapy. One day following admission, the patient deteriorated and became unresponsive. Subsequent MRI of the brain revealed multiple bihemispheric cerebral emboli and a large, mobile mitral valve thrombus was visualised on her transoesophageal echocardiogram. S agalactiae was cultured from venous blood samples and her antimicrobial cover was adjusted accordingly. Despite her presumed guarded prognosis, this patient made a remarkable recovery. To our knowledge, the association of S agalactiae endocarditis with acalculous cholecystitis has not been previously described.
Project description:Behçet disease (BD) is a form of widespread vasculitis that involves both arteries and veins. Cardiac involvement in BD is exceedingly rare and can present as a form of non-bacterial- thrombotic-endocarditis (NBTE). A 54-year-old man with Behçet disease was admitted to our hospital after presenting with abdominal pain and fever. He had been recently discharged from a hospital in another country with the diagnosis of infective endocarditis of the mitral valve and mycotic embolization to the superior mesenteric artery. At presentation, oral and genital ulcers were present, raising the suspicion of a flare of BD. Transesophageal echocardiography showed a small vegetation on the anterior leaflet of the mitral valve. Blood cultures results were negative. Computed tomography of the abdomen showed extensive inferior vena cava thrombosis. The aneurysm and thrombotic phenomena were interpreted as related to BD: the vegetation on the mitral valve was diagnosed as NBTE of which BD is a recognized cause. With corticosteroid and anticoagulant therapy, the patient's symptoms steadily improved. NBTE is a rare manifestation of BD; differential diagnosis with infective endocarditis can be challenging and should be focused on identifying predisposing conditions. The mainstay of treatment in NBTE is medical therapy with anticoagulation and treatment of the underlying disease. <Learning objective: Cardiac involvement in the setting of Behçet Disease (BD) is rare and several different manifestations are described (intracardiac thrombus, non-infective endocarditis, myocarditis, pericarditis, endomyocardial fibrosis, coronary arteritis). Non-bacterial thrombotic endocarditis (NBTE) is also a rare finding which can happen in the setting of BD. Its prevalence is unknown and evidence is derived only from scarce case reports.The role of BD as a potential cause of NBTE must be acknowledged to avoid potential misdiagnosis.>.