Nkx2.5‐negative myocardium of the posterior heart field and its correlation with podoplanin expression in cells from the developing cardiac pacemaking and conduction system

Recent advances in the study of cardiac development have shown the relevance of addition of myocardium to the primary myocardial heart tube. In wild‐type mouse embryos (E9.5–15.5), we have studied the myocardium at the venous pole of the heart using immunohistochemistry and 3D reconstructions of expression patterns of MLC‐2a, Nkx2.5, and podoplanin, a novel coelomic and myocardial marker. Podoplanin‐positive coelomic epithelium was continuous with adjacent podoplanin‐ and MLC‐2a‐positive myocardium that formed a conspicuous band along the left cardinal vein extending through the base of the atrial septum to the posterior myocardium of the atrioventricular canal, the atrioventricular nodal region, and the His‐Purkinje system. Later on, podoplanin expression was also found in the myocardium surrounding the pulmonary vein. On the right side, podoplanin‐positive cells were seen along the right cardinal vein, which during development persisted in the sinoatrial node and part of the venous valves. In the MLC‐2a‐ and podoplanin‐positive myocardium, Nkx2.5 expression was absent in the sinoatrial node and the wall of the cardinal veins. There was a mosaic positivity in the wall of the common pulmonary vein and the atrioventricular conduction system as opposed to the overall Nkx2.5 expression seen in the chamber myocardium. We conclude that we have found podoplanin as a marker that links a novel Nkx2.5‐negative sinus venosus myocardial area, which we refer to as the posterior heart field, with the cardiac conduction system. Anat Rec, 290:115–122, 2007. © 2006 Wiley‐Liss, Inc.     

CADASIL in Arabs: clinical and genetic findings

Background  

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is increasingly recognized as an inherited arterial disease leading to a step-wise decline and eventually to dementia. CADASIL is caused by mutations in NOTCH3 epidermal growth factor-like repeat that maps to chromosome 19. CADASIL cases have been identified in most countries of Western and Central Europe, the Americas, Japan, Australia, the Caribbean, South America, Tanzania, Turkey, South Africa and Southeast Asia, but not in Arabs.     

The possible antianginal effect of allopurinol in vasopressin-induced ischemic model in rats

The anti-anginal effects of allopurinol were assessed in experimental model rats of angina and their effects were evaluated with amlodipine. In the vasopressin-induced angina model, oral administration of allopurinol in dose of 10 mg/kg revealed remarkably analogous effects in comparison with amlodipine such as dose-dependent suppression of vasopressin-triggered time, duration and severity of ST depression. In addition, allopurinol produced dose dependent suppression of plasma Malondialdehyde (MDA) level, systolic blood pressure, cardiac contractility and cardiac oxygen consumption; while in contrast, amlodipine minimally suppressed the elevation of plasma MDA level. Endothelial NO synthase (eNOS) expression, serum nitrate were strikingly increased, however lipid profile was significantly reduced. Seemingly, allopurinol was found to be more potent than amlodipine – a calcium channel antagonist. To conclude, it was explicitly observed and verified that on the ischemic electrocardiography (ECG) changes in angina pectoris model in rats, allopurinol exerts a significant protective effects, reminiscent of enhancement of vascular oxidative stress, function of endothelial cells, improved coronary blood flow in addition to the potential enhancement in myocardial stress. Moreover, our findings were in conformity with several human studies.     

The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.     

Anatomic predictors of recurrence after cryoablation for atrial fibrillation: a computed tomography based composite score

Journal of Interventional Cardiac Electrophysiology - Effective pulmonary vein isolation (PVI) with cryoablation depends on adequate occlusion of pulmonary veins (PV) by the cryoballoon and is...     

The Neglected Lead on Electrocardiogram: T Wave Inversion in Lead aVL,Nonspecific Finding or a Sign for Left Anterior Descending Artery Lesion?

Background

The electrocardiogram (ECG) is the most important diagnostic tool for acute myocardial infarction (AMI). T wave inversion (TWI) in lead aVL has not been emphasized or well recognized.

Objective

This study examined the relationship between the presence of TWI before the event and mid-segment left anterior descending (MLAD) artery lesion in patients with AMI.

Methods

Retrospective charts of patients with acute coronary syndrome between the months of January 2009 and December 2011 were reviewed. All patients with MLAD lesion were identified and their ECG reviewed for TWI in lead aVL.

Results

Coronary angiography was done on 431 patients. Of these, 125 (29%) had an MLAD lesion. One hundred and six patients (84.8%) had a lesion > 50% and 19 patients (15.2%) had a lesion < 50%. Of the 106 patients who had a MLAD lesion > 50%, 90 patients (84.9%) had TWI in lead aVL and one additional lead. Of the 19 patients who had an MLAD lesion < 50%, 8 patients (42.1%) had TWI in lead aVL and one additional lead. Isolated TWI in lead aVL had an overall sensitivity of 76.7% (95% confidence interval [CI] 0.65–0.86), a specificity of 71.4% (95% CI 0.45–0.88), a positive predictive value of 92%, a negative predictive value of 41.7%, a positive likelihood ratio of 2.7 (95% CI 1.16–6.22), and negative likelihood ratio of 0.32 (95% CI 0.19–0.58) for predicting a MLAD lesion of > 50% (p = 0.0011).

Conclusions

TWI in lead aVL might signify a mid-segment LAD lesion. Recognition of this finding and early appropriate referral to a cardiologist might be beneficial. Additional studies are needed to validate this finding.     

Measurements of laser light attenuation following cryogen spray cooling spurt termination

BACKGROUND AND OBJECTIVES: Cryogen spray cooling (CSC) is used to minimize the risk of epidermal damage during laser dermatological surgery. However, while CSC can protect the epidermis from non-specific thermal damage, the cryogen film on the skin surface may pose a potential problem of laser light attenuation due to optical scattering. STUDY DESIGN/MATERIALS AND METHODS: This study is focused on measuring the light transmittance changes that occur following cryogen spurt termination. The wavelengths studied were chosen for their clinical relevance to treatment of hypervascular skin lesions (594 nm) and laser-assisted hair removal (785 nm). Following delivery of cryogen spurts to the surface of an epoxy skin phantom, continuous records of light transmittance for 594 and 785 nm were obtained using an integrating sphere-based light collection apparatus. RESULTS: Shortly after spurt termination, there was negligible light attenuation by the cryogen film at the two wavelengths studied. CONCLUSIONS: For the typical clinical use of a 30 milliseconds spurt duration and 30 milliseconds delay between spurt termination and delivery of the laser pulse, a minimum average transmittance value of approximately 97% was measured.     

Promoting breast health among women in the U.S. Virgin Islands: a focused study of the needs of Caribbean women.

Breast cancer is the number one cause of cancer death among women in the United States Virgin Islands. Consequently, the Bureau of Health has identified breast cancer as a priority health concern. Within the medical community, increasing emphasis is being placed on the importance of hereditary, familial, environmental, and behavioral risk factors to breast cancer control. Little research has been conducted regarding these factors, however, to explore their influence on breast cancer detection and breast cancer risk management. This report highlights the outcomes of a study undertaken to explore the associations between breast cancer risk, risk assessment, risk communication, screening, and receptivity to the management of breast cancer risk among women from the United States Virgin Islands. Results of this study suggest a need within the territory to expand the systems that are responsible for monitoring and reporting breast cancer trends; forums to discuss concerns of women relative to breast health; forums to discuss communication with health-care providers; and, research efforts that address breast cancer detection and control among women in the United States Virgin Islands.