Caseous Calcification of the Mitral Annulus: Calcified Toothpaste of the Heart.

Caseous calcification of the mitral annulus (CCMA) is a rare variant of mitral annular calcification (MAC) usually described as an antemortem finding. We report a case of sudden cardiac arrest in a 39-year-old male with end-stage renal disease undergoing hemodialysis with a history of Fabry disease by kidney biopsy. Autopsy revealed significant circumferential annular calcification in both mitral and aortic valves with a caseous gross appearance.

Error codes at autopsy to study potential biases in diagnostic error.

Objectives: Current autopsy practice guidelines do not provide a mechanism to identify potential causes of diagnostic error (DE). We used our autopsy data registry to ask if gender or race were related to the frequency of diagnostic error found at autopsy.

Methods: Our autopsy reports include International Classification of Diseases (ICD) 9 or ICD 10 diagnostic codes for major diagnoses as well as codes that identify types of error.

Small Molecule Inhibitors of Nuclear Export and the Amelioration of Lupus by Modulation of Plasma Cell Generation and Survival.

Objective: To investigate the hypothesis that selective inhibitors of nuclear export (SINE compounds), recently approved for treatment of refractory plasma cell (PC) malignancy, may have potential in the treatment of lupus.

Methods: Female NZB/NZW mice were treated with the SINE compound KPT-350 or vehicle control. Tissue specimens were harvested and analyzed by flow cytometry, using standard markers.

The spectrum of macrophage-predominant inflammatory myocardial disease presenting as fulminant heart failure.

Background: Endomyocardial biopsy results are integral for diagnosis and management of myocarditis. Current diagnostic classifications of myocarditis are based on the microscopic and immunochemical characterization of inflammation do not include monocyte/macrophage-predominant (i.e.

Prednisone-induced sustained remission in a patient with familial fibronectin glomerulopathy (GFND).

Glomerulopathy with Fibronectin Deposits (GFND) is a rare, autosomal dominant disease characterized by proteinuria, hematuria and progressive renal failure associated with glomerular deposition of fibronectin, frequently resulting in end-stage renal disease (ESRD). There is no established treatment for this condition beyond conservative measures such as blood pressure control and the use of angiotensin-converting enzyme (ACE) inhibitors. We present a case of GFND associated with progressive chronic kidney disease (CKD) and nephrotic range proteinuria showing a sustained response to prednisone treatment.

Potassium conservation is impaired in mice with reduced renal expression of Kir4.1.

To better understand the role of the inward-rectifying K channel Kir4.1 (KCNJ10) in the distal nephron, we initially studied a global Kir4.1 knockout mouse (gKO), which demonstrated the hypokalemia and hypomagnesemia seen in SeSAME/EAST syndrome and was associated with reduced Na/Cl cotransporter (NCC) expression.

Neutrophils Slow Disease Progression in Murine Lupus via Modulation of Autoreactive Germinal Centers.

Neutrophils are well characterized as mediators of peripheral tissue damage in lupus, but it remains unclear whether they influence loss of self-tolerance in the adaptive immune compartment. Lupus neutrophils produce elevated levels of factors known to fuel autoantibody production, including IL-6 and B cell survival factors, but also reactive oxygen intermediates, which can suppress lymphocyte proliferation. To assess whether neutrophils directly influence the progression of autoreactivity in secondary lymphoid organs (SLOs), we characterized the localization and cell-cell contacts of splenic neutrophils at several stages in the progression of disease in the NZB/W murine model of lupus.

Inhibition of G Protein βγ Subunit Signaling Abrogates Nephritis in Lupus-Prone Mice.

Objective: Despite considerable advances in the understanding of systemic lupus erythematosus (SLE), there is still an urgent need for new and more targeted treatment approaches. We previously demonstrated that small-molecule blockade of G protein βγ subunit (Gβγ) signaling inhibits acute inflammation through inhibition of chemokine receptor signal transduction. We undertook this study to determine whether inhibition of Gβγ signaling ameliorates disease in a mouse model of SLE.

Beneficial effect of novel proteasome inhibitors in murine lupus via dual inhibition of type I interferon and autoantibody-secreting cells.

Objective: To investigate the hypothesis that proteasome inhibition may have potential in the treatment of SLE, by targeting plasmacytoid dendritic cells (PDCs) and plasma cells, both of which are critical in disease pathogenesis.

Methods: Lupus-prone mice were treated with the nonselective proteasome inhibitors carfilzomib and bortezomib, the immunoproteasome inhibitor ONX 0914, or vehicle control. Tissue was harvested and analyzed by flow cytometry using standard markers.

Prolonged effects of short-term anti-CD20 B cell depletion therapy in murine systemic lupus erythematosus.

Objective: Although B cells are implicated in the pathogenesis of systemic lupus erythematosus, the role of B cell depletion (BCD) as a treatment is controversial, given the variable benefit in human disease. This study was undertaken to test the effects of BCD therapy in a murine lupus model to better understand the mechanisms, heterogeneity, and effects on disease outcomes.

Methods: (NZB x NZW)F(1) female mice with varying degrees of disease severity were treated with an anti-mouse CD20 (anti-mCD20) antibody (IgG2a), BR3-Fc fusion protein (for BAFF blockade), or control anti-human CD20 monoclonal antibody (approximately 10 mg/kg each).

Unusual features of malignant pleural mesothelioma metastatic to the mediastinal lymph nodes.

Malignant pleural mesothelioma (MPM) is a rare cancer that metastasizes to mediastinal lymph nodes (MLNs). The diagnosis of MPM metastatic to MLNs may not be straightforward. We describe 3 cases to highlight unusual entities of MPM metastatic to MLNs as follows.

Human myocardial cell lines generated with SV40 temperature-sensitive mutant tsA58.

Conditionally transformed human myocardial cell lines would be a valuable resource for studying human cardiac cell biology. We generated clonal human fetal cardiocyte cell lines by transfection of fetal ventricular cardiac cell clones with a plasmid containing a replication-defective mutant of the temperature-sensitive SV40 strain tsA58. Multiple resulting cell lines showed similar features, namely: (1) T antigen (TAg) expression at both permissive (34 degrees C) and restrictive (40.

Regionally heterogeneous tissue mechanics in cardiac amyloidosis.

Objective: The goal of this study was to examine in vitro tissue stiffness and contractile performance in myocardial amyloidosis.

Background: Primary systemic amyloidosis involves the deposition of amyloid protein in mesodermal tissues including the heart. Functional assessment of cardiac amyloidosis is usually performed using echocardiography.

Potential suitability for transplantation of hearts from human non-heart-beating donors: data review from the Gift of Life Donor Program.

Background: Organ availability limits use of heart transplantation for treatment for end-stage heart disease. Hearts are currently obtained from donors declared brain dead (heart-beating donors [HBDs]). Although use of hearts from non-heart-beating donors (NHBDs) could reduce the shortage, they are considered unusable because of possible peri-mortem ischemic injury.

Effects of nutrient and hemoglobin enriched cell free perfusates upon ex vivo isolated rat heart preparation.

We evaluated the effects of nutrient enriched medium and hemoglobin based oxygen carrier (HBOC) upon myocardial functional recovery after 15 minutes of warm ischemia in an isovolumic Langendorff rat heart model. Hearts (n = 8/group) were perfused at constant pressure (90 mm Hg) with Krebs-Henseleit buffer or HEPES modified cell culture medium (M199) in the absence and presence of HBOC. Hearts received 15 minutes of normothermic no flow ischemia followed by 60 minutes reperfusion.

Effect of older donor age on risk for mortality after heart transplantation.

Background: Despite the increasingly common use of donor hearts at least 50 years of age, controversy still remains regarding long-term outcome. Our goal was to determine if older donor age is associated with an increased risk of mortality and specifically if the use of donor hearts at least 50 years of age reduces survival.

Methods: We retrospectively studied records of all primary heart transplants performed between January 1990 and July 2002.

Identical alpha-chain T-cell receptor transcripts are present on T cells infiltrating coronary arteries of human cardiac allografts with chronic rejection.

Chronic cardiac allograft rejection is characterized by graft arteriopathy and is a major obstacle of graft survival. We investigated T-cell receptor (TCR) alpha-chain transcripts of T cells infiltrating human epicardial coronary arteries from cardiac allografts with chronic rejection. The non-palindromic adaptor-polymerase chain reaction (NPA-PCR) was used to specifically amplify TCR alpha-chain transcripts from five explanted cardiac allografts with chronic rejection.

Reduction of atherosclerosis in low-density lipoprotein receptor-deficient mice by passive administration of antiphospholipid antibody.

Objective: Patients with antiphospholipid syndrome (APS) are at a high risk of developing atherosclerotic complications. Conversely, individuals with primary atherosclerosis have an increased prevalence of antiphospholipid antibodies (aPL) and antibodies to oxidized low-density lipoproteins (ox-LDL). Several studies suggest that these two antibody populations may in fact overlap, although it is unclear how aPL contribute to pathogenesis.

Early and late results of left ventricular reshaping by passive cardiac-support device in canine heart failure.

Background: We tested whether the CardioClasp, a passive non-blood-contacting device could decrease excessive geometric burden in dilated cardiomyopathy and improve left ventricular systolic function and contractility by reshaping the left ventricle (LV) and by decreasing LV wall stress (LVWS) without decreasing arterial blood pressure.

Methods: In mongrel dogs (n = 6, the early group; n = 6, the chronic group; 25-27 kg), 4 weeks of rapid right ventricular pacing (210 to 240 bpm) induced dilated cardiomyopathy with heart failure. In the early group, we used hemodynamic data and echocardiography to evaluate LV systolic function immediately after placing the CardioClasp device.

CardioClasp changes left ventricular shape acutely in enlarged canine heart.

Background: In dilated cardiomyopathy (DCM), eliminating or reducing extra-geometric burden to the myocardial cells would directly reduce myocardial wall stress leading to improved LV systolic performance. In acute experiments, we tested whether a passive non-blood contacting CardioClasp device, which employs two indenting bars to reshape the left ventricle (LV), could reduce extra-geometric burden, LV wall stress (LVWS) and improve LV systolic function and contractility without decreasing arterial blood pressure.

Methods: In mongrel dogs (n = 5), 4 weeks of right ventricular pacing (210-220-230-240 ppm) induced DCM with severe heart failure.

Cardiac transplantation across a positive prospective lymphocyte cross-match in sensitized recipients.

Background: Although there is an increasing body of evidence for a deleterious effect of mismatched donor HLA antigens on the outcome of human cardiac transplantation, the role of anti-HLA lymphocytotoxic antibodies remains controversial. Thus, their appearance after cardiac transplantation has been associated with poor outcome by some groups; whereas others have reported them to be of no clinical significance. Furthermore, their presence prior to cardiac transplantation has also been the subject of similarly conflicting reports.