Ergotism and factitious hypotension associated with interaction of ergotamine with CYP3A4 inhibitors.

BACKGROUND: Although uncommon, severe ergotism continues to occur. The purpose of this study is to describe causes and clinical effects of ergotism in recent years. METHODS: This is an observational case series with data obtained retrospectively from all patients with ergotism referred to Ramathibodi Poison Center in Bangkok, Thailand from January 2006 to August 2013. RESULT: Twelve cases of ergotism were identified. All cases involved ergotamine 1 mg/caffeine 100 mg combination tablets. Nine cases (75%) were precipitated by drug-drug interactions with CYP3A4 inhibitors. The other cases involved suicidal attempt (2 cases) and pediatric unsupervised ingestion (1 case). Ten patients (83%) had signs of peripheral vascular insufficiency. Five of these patients initially had factitiously low or unmeasurable blood pressure using non-invasive technique and had paradoxical increase following intravenous vasodilator administration. Two patients required partial foot amputations due to gangrene. Two patients, including a 15-month-old boy with an unsupervised ingestion, died. DISCUSSION: In this series, most cases of severe ergotism were associated with interaction with CYP3A4 inhibitors, which increase ergotamine bioavailability. Factitious low blood pressure in these cases was likely caused by severe vasospasm. CONCLUSION: Critical ergotism continues to occur in Thailand, most commonly associated with the drug-drug interactions.

Genetic regulation of systemic angiogenesis in the mouse lung.

The work in this study takes advantage of a new experimental model in the mouse that completely isolates the angiogenic process from the direct effects of ischemia. The model also leads to lung angiogenesis that mimics the vascular source of many lung pathologies, and allows investigation of the temporal and spatial factors that can promote or inhibit angiogenesis. This work describes the expression patterns of genes relevant to pro-angiogenic signals and conditions in response to ischemia in the lung. The most notable changes were increases in the expression of genes involved in inflammation and tissue remodeling. In particular, the results confirm a important role of ELR+ CXC chemokines as proangiogenic signals. In addition, the experimental findings in this mouse lung model show that lung ischemia, rather than hypoxia, is the essential trigger for angiogenesis. Results from this model also suggest potential approaches for determining critical pathways and potential therapeutic strategies related to the control of angiogenesis.