Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure

The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65×10⁻⁵) and diastolic BP (P=7.61×10⁻³) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0×10⁻³). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, renin-angiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.     

Primary Sinonasal Mucosal Melanoma with Aberrant Diffuse and Strong Desmin Reactivity: A Potential Diagnostic Pitfall!

The broad morphologic spectrum, inherent immunophenotypic heterogeneity of malignant melanoma and its rarity in the sinonasal tract are major challenges in eliciting the correct diagnosis, which may lead to misclassification and inadequate medical management. Herein, we describe a single case of a 70 year-old male with sinonasal mucosal melanoma, exhibiting varying histologic phenotypes including small round blue cell morphology, epithelioid and focal rhabdoid morphology and strong, diffuse desmin immunoreactivity. These constellation of features initially prompted the diagnosis of rhabdomyosarcoma. The differential diagnosis in this anatomic area includes other malignant small round blue cell tumors of the sinonasal mucosa such as rhabdomyosarcoma, olfactory neuroblastoma, sinonasal undifferentiated carcinoma, and lymphoma. We reviewed precedent literature and further discuss the potential pitfalls to which pathologists may be prone.     

Do Regular Ultrasound Scans Reduce the Incidence of Stillbirth in Women with Apparently Normal Pregnancies?

ObjectiveTo determine the incidence of stillbirth in women who have regular ante-natal ultrasound compared to those that have infrequent scans in a low risk population.ResultsOur study included 23,519 ‘low-risk’ deliveries spanning 2007-2011. This included 2,088 (9%) patients who had frequent ultrasound surveillance and delivery at term and 21,431 (91%) patients who did not. The overall stillbirth rate was 0.34% and 0.20% respectively which was not statistically different (p=0.31).ConclusionThere is no difference in the rate of stillbirth between patients who have more frequent ante-natal ultrasound surveillance compared with those who do not in a low risk population.