Faculty Bibliography

The long-term complications of acute deep venous thrombosis (DVT) include recurrence, increased mortality, and the development of the postthrombotic syndrome. Rates of recurrent venous thromboembolism (VTE) are elevated in patients with cancer and thrombophilia. Heparin, administered either as unfractionated or low-molecular weight, is indicated for at least five days for acute DVT. Long-term treatment is currently a vitamin K antagonist with a variable duration depending on the etiology of the DVT and risk of bleeding. Novel anticoagulant agents that target factor Xa and directly inhibit thrombin are being studied in clinical trials and may one day replace vitamin K antagonists for the long-term treatment of VTE.Interventional approaches such as percutaneous mechanical thrombectomy have the potential to reduce clot burden in acute DVT with lower bleeding risks and help prevent development of the postthrombotic syndrome, a common and potentially debilitating complication of DVT

The chronic constriction injury model of mononeuropathy is a direct, partial nerve injury yielding thermal hyperalgesia. The inflammation that results from this injury is believed to contribute importantly to both the neuropathological and behavioral sequelae. This study involved administering a single dose (250 ng) of interleukin-10 (IL-10), an endogenous anti-inflammatory peptide, at the site and time of a chronic constriction injury (CCI) lesion to determine if IL-10 administration could attenuate the inflammatory response of the nerve to CCI and resulting thermal hyperalgesia. In IL-10-treated animals, thermal hyperalgesia was significantly reduced following CCI (days 3, 5 and 9). Histological sections from the peripheral nerve injury site of those animals had decreased cell profiles immunoreactive for ED-1, a marker of recruited macrophages, at both times studied (2 and 5 days post-CCI). IL-10 treatment also decreased cell profiles immunoreactive for the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) at day 2, but not day 5. Qualitative light microscopic assessment of neuropathology at the lesion site did not suggest substantial differences between IL-10 and vehicle-treated sections. The authors propose that initial production of TNF-alpha and perhaps other proinflammatory cytokines at the peripheral nerve lesion site importantly influences the long-term behavioral outcome of nerve injury, and that IL-10 therapy may accomplish this by downregulating the inflammatory response of the nerve to injury.