Spontaneous superior mesenteric artery (SMA) dissection: an unusual cause of abdominal pain.

A 44-year-old woman presented to our Emergency Department with a 4-day history of severe, sharp left upper quadrant abdominal pain associated with nausea and vomiting. She had been seen 3 days prior at another Emergency Department, and had a negative work-up including a normal non-contrast computed tomography (CT) scan of the abdomen/pelvis for possible kidney stone. Vital signs were: temperature 36.3°C (97.3°F), pulse 100 beats/min, respiratory rate 18 breaths/min, and blood pressure 141/80 mm Hg. Physical examination was remarkable for marked tenderness in the left upper and middle quadrants and voluntary guarding. Bowel sounds were normal. Although laboratory studies were normal, a CT scan of the abdomen/pelvis with intravenous contrast suggested a superior mesenteric artery dissection. This was confirmed with arteriography. The clinical presentation, diagnostic evaluation, and management of superior mesenteric artery dissection are reviewed.

Phosphatidylinositol 3'-kinase is required for growth of mast cells expressing the kit catalytic domain mutant.

The Kit receptor tyrosine kinase is critical for the growth and development of hematopoietic cells, germ cells, and the interstitial cells of Cajal. Gain-of-function mutations in codon 816 of the catalytic domain of human Kit [codon 814 of murine Kit (mKit)] are found in patients with mastocytosis, leukemia, and germ cell tumors. There are no drugs that inhibit the activity of Kit catalytic domain mutants to a greater extent than wild-type Kit. The objective of this study was to understand the biochemical mechanisms mediating mast cell transformation by this Kit mutant to identify molecular targets for pharmacological intervention. To this end, we examined signaling pathways activated in the murine mast cell line IC2 infected with either wild-type (IC2-mKit) or mutant mKit (IC2-mKit(D814Y)). In this study, we show that mKit(D814Y) is constitutively phosphorylated on tyrosine 719, and this likely results in constitutive association with activated phosphatidylinositol 3'-kinase (PI3K). In vitro growth of IC2-mKit(D814Y) cells is more sensitive to inhibition of PI3K than SCF-induced growth of IC2-mKit cells. s.c. injection of IC2-mKit(D814Y) in syngeneic mice results in mast cell tumors. To determine whether inhibition of PI3K could reduce mKit(D814Y)-mediated tumorigenicity, mice were treated with 1.5 mg/kg wortmannin three times a week. Five weeks after injection of tumor cells, a 75% reduction in tumor weight was observed when wortmannin treatments were initiated 2 days after inoculation with tumor cells. A 66% reduction occurred when treatment was initiated 2 weeks after inoculation. Treatment with wortmannin increased necrosis in the tumors, and this was associated with apoptosis. Interestingly, there was no effect on tumor vasculature. Thus, PI3K is required for survival and growth of the IC2-mKit(D814Y) mast cell line both in vitro and in vivo. These findings may provide insight into designing strategies for treatment of mastocytosis and other diseases associated with mutations in the Kit catalytic domain.