Clinical Images: Sigmoid Volvulus

Case Presentation: A 72-year-old male with a history of Parkinson\u27s disease, Type 2 diabetes, hypertension, hyperlipidemia, and cerebral vascular accident presented to the emergency room for 10 minutes of unresponsiveness at his nursing home. A workup for the unresponsiveness was unrevealing. His hospital course was complicated by constipation, a condition that resulted in multiple hospitalizations in the prior 6 months. Abdominal exam was notable for mild distension, and an initial x-ray demonstrated an ileus. The severity of his distention acutely worsened two days after it was initially noted, and was associated with borborygmi and high-pitched bowel sounds. A repeat x-ray was consistent with a sigmoid volvulus. The patient underwent endoscopic colonic decompression with resolution of the volvulus, but due to recurrence, ultimately required a sigmoidectomy

Changes in agriculture and food production in NAE since 1945

v2009okMTT Mikkel

Environmental, economic and social impacts of NAE agriculture and AKST

v2009okMTT Mikkel

An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma

Severe asthma patients with low type 2 inflammation derive less clinical benefit from therapies targeting type 2 cytokines and represent an unmet need. We show that mast cell tryptase is elevated in severe asthma patients independent of type 2 biomarker status. Active β-tryptase allele count correlates with blood tryptase levels, and asthma patients carrying more active alleles benefit less from anti-IgE treatment. We generated a noncompetitive inhibitory antibody against human β-tryptase, which dissociates active tetramers into inactive monomers. A 2.15 Å crystal structure of a β-tryptase/antibody complex coupled with biochemical studies reveal the molecular basis for allosteric destabilization of small and large interfaces required for tetramerization. This anti-tryptase antibody potently blocks tryptase enzymatic activity in a humanized mouse model, reducing IgE-mediated systemic anaphylaxis, and inhibits airway tryptase in Ascaris-sensitized cynomolgus monkeys with favorable pharmacokinetics. These data provide a foundation for developing anti-tryptase as a clinical therapy for severe asthma