Hypertension secondary to renal hypoplasia presenting as acute heart failure in a newborn.

INTRODUCTION: Neonatal hypertension is defined as persistent systolic and/or diastolic blood pressures above the 95th percentile compared to other infants of similar gestational age and size. Neonatal hypertension is a rare condition, occurring in only 0.2-3.0% of neonates. The most common etiology of neonatal hypertension is renal vascular or parenchymal disease, and it is usually detected on routine examination in an asymptomatic child. However, it may present in a variety of manners, including acute heart failure, renal dysfunction, feeding difficulties, failure to thrive, tachypnea, apnea, lethargy, irritability, or seizures. CASE PRESENTATION: A term female was born via repeat caesarean section with vacuum extraction. On day of life (DOL) 3, the baby presented to the emergency department with poor feeding and lethargy. Initial laboratory tests indicated severe metabolic acidosis and the patient was transferred to our neonatal intensive care unit (NICU). During the hospital stay, the patient had intermittently high blood pressures. An echocardiogram was ordered, which demonstrated a severely decreased ejection fraction of 33%, but no signs of coarctation of the aorta. The low ejection fraction and constellation of symptoms were consistent with the diagnosis of acute heart failure, so treatment with milrinone was initiated. Further labs demonstrated elevated renin and aldosterone, and a computed tomography scan showed right kidney hypoplasia with reduced perfusion. This suggested a renovascular etiology of hypertension causing the initial presentation of acute heart failure. The patient was started on enalapril and clonidine for blood pressure control and was discharged with a home blood pressure monitoring system. At 5 months of life, this patient was still on enalapril and amlodipine as well as home blood pressure monitoring. CONCLUSIONS: Acute heart failure is a rare presentation of neonatal hypertension, and prompt recognition and treatment for the underlying systemic hypertension is necessary to provide the best possible outcomes for patients. Due to the lack of sufficient evidence, treatment of hypertension in newborns is often anecdotal in nature. Further awareness of neonatal hypertension and research determining ideal methods of diagnosis and treatment would benefit physicians and their affected patients.

DVL1 and DVL3 differentially localize to CYP19A1 promoters and regulate aromatase mRNA in breast cancer cells.

The CYP19A1 gene encodes aromatase, an enzyme that converts androgens into estrogens and consequently directly contributes to both the depletion of androgens and the synthesis of estrogens in several organs. Aromatase is critical for diverse biological processes such as proliferation, regulation of fat metabolism and hormone signaling. Additionally, it is also overexpressed in diverse cancers and drives hormone-dependent tumor progression and increases 17-ß-estradiol (E2) within tumors and the tumor microenvironment. Although the inhibition of E2 production via aromatase inhibitors represents a major therapeutic paradigm in clinical oncology, fundamental questions regarding how cancer cells gain the capacity to overexpress aromatase remain unanswered. Multiple tissue-specific CYP19A1 promoters are known to be aberrantly active in tumors, yet how this occurs is unclear. Here, for the first time, we report that Dishevelled (DVL) proteins, which are key mediators of Wnt signaling, regulate aromatase expression in multiple breast cancer cell lines. We also report that DVL enters the nucleus and localizes to at least two different CYP19A1 promoters (pII and I.4) previously reported to drive overexpression in breast tumors and to a very distal CYP19A1 placental promoter (I.1) that remains poorly characterized. We go on to demonstrate that DVL-1 and DVL-3 loss of function leads to differential changes in various aromatase transcripts and in E2 production. The report, herein, uncovers a new regulator of CYP19A1 transcription and for the first time demonstrates that DVL, a critical mediator of WNT signaling, contributes to aberrant breast cancer-associated estrogen production.

Rhabdomyolysis secondary to systemic lupus erythematosus.

Systemic lupus erythematous (SLE) is a systemic auto-immune disorder with a variety of presentations and wide spread organ involvement. We present a case report of a patient with an SLE exacerbation as well as concurrent rhabdomyolysis with massively elevated CPK (304,700 U/L). Though a rarely reported effect of SLE, rhabdomyolysis can be severe and potentially lethal secondary or concurrent to an acute SLE episode. This case report demonstrates the association between SLE and rhabdomyolysis, which is not well described in the current literature.