BackgroundStudies in multiple organ systems have shown cross-talk between signaling through the bone morphogenetic protein receptor type 2 (BMPR2) and estrogen pathways. In humans, pulmonary arterial hypertension (PAH) has a female predominance, and is associated with decreased BMPR2 expression. The goal of this study was to determine if estrogens suppress BMPR2 expression.MethodsA variety of techniques were utilized across several model platforms to evaluate the relationship between estrogens and BMPR2 gene expression. We used quantitative RT-PCR, gel mobility shift, and luciferase activity assays in human samples, live mice, and cell culture.ResultsBMPR2 expression is reduced in lymphocytes from female patients compared with male patients, and in whole lungs from female mice compared with male mice. There is an evolutionarily conserved estrogen receptor binding site in the BMPR2 promoter, which binds estrogen receptor by gel-shift assay. Increased exogenous estrogen decreases BMPR2 expression in cell culture, particularly when induced to proliferate. Transfection of increasing quantities of estrogen receptor alpha correlates strongly with decreasing expression of BMPR2.ConclusionsBMPR2 gene expression is reduced in females compared to males in live humans and in mice, likely through direct estrogen receptor alpha binding to the BMPR2 promoter. This reduced BMPR2 expression may contribute to the increased prevalence of PAH in females.

In the absence of increasing size, persistent central arterial hyperenhancement and wash-out can occur within the first 12 months after SBRT in successfully treated HCCs and may not represent residual viable tumor. Liver parenchyma adjacent to the treated lesion showed inflammation followed by fibrosis, without significant change in hepatic function. Until a radiologic signature of tumor control is determined, freedom from local progression seems to be the best measure of HCC control after SBRT.

We are currently in the midst of a worldwide obesity epidemic, including in patients with end-stage kidney disease. Placing hemodialysis catheters is a particular challenge in patients with extreme obesity. Here we describe the merging of two technologies to place catheters in patients who are too heavy (over 225 kg) to be placed safely on a procedure table for fluoroscopic guidance. The first technology is ECG-guided placement of catheters, well established for guidance of peripherally inserted central catheters (PICCs) and tunneled and nontunneled central venous catheters. The second is reverse-tunneling dialysis catheters, which allow precise placement of the tip of the catheter before creating the tunnel. We successfully placed catheters in three morbidly obese patients with acute kidney injury and followed them until their kidneys recovered and the catheters were removed. The catheters were placed in the patient's bed in a procedure room with subsequent confirmatory chest radiographs. Catheter performance based on blood flow rates was excellent and there were no complications. We suggest placement of ECG-guided tunneled hemodialysis catheters using a reversed-tunneling technique in those patients with extreme obesity who are too heavy to place on a fluoroscopy procedure table.

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