Heart rate: is it truly a vital sign?

BACKGROUND: Tachycardia, often defined as heart rate >100 bpm, has been utilized as a physical sign of hypovolemic shock among the injured for decades without evidence to support its use as a predictor of injury or significant hypovolemia. We sought to determine whether admission heart rate is a valid predictor of hemodynamically significant injuries. METHODS: Trauma registry data from 1998 to 2004 were analyzed with logistic regression to determine whether heart rate was associated with need for emergent intervention for bleeding (laparotomy, thoracotomy, or angiography), need for packed red blood cell (pRBC) transfusion in the first 24 hours, or severe injury (ISS >25) after blunt or penetrating trauma. RESULTS: Records of 10,825 patients were analyzed. Overall, heart rate was neither sensitive nor specific in determining the need for emergent intervention, pRBCs in the first 24 hours or severe injury. This was not altered by the presence of hypotension (systolic blood pressure <90 mm Hg) or age in the blunt cohort. CONCLUSIONS: Heart rate alone is not sufficient to determine the need for emergent interventions for hemorrhage. Although tachycardia may still indicate need for emergent intervention in the trauma patient, its absence should not allay such concern.     

Mre11 inhibition by oncolytic adenovirus associates with autophagy and underlies synergy with ionizing radiation

New treatment approaches are needed for hormone refractory prostate cancer. Oncolytic adenoviruses are promising anti‐cancer agents, and their efficacy can be improved by combining with conventional therapies such as ionizing radiation. The aim of this study was to determine the timing of oncolytic adenovirus treatment with regard to radiation and study the mechanisms of synergy in combination treatment. Prostate cancer cells were infected with oncolytic adenoviruses, irradiated and synergy mechanisms were assessed. In vivo models of combination treatment were tested. Radiation and oncolytic viruses were synergistic when viral infection was scheduled 24 hr after irradiation. Combination of oncolytic adenovirus with radiotherapy significantly increased antitumor efficacy in vivo compared to either agent alone. Microarray analysis showed dysregulated pathways including cell cycle, mTOR and antigen processing pathways. Functional analysis showed that adenoviral infection was accompanied with degradation of proteins involved in DNA break repair. Mre11 was degraded for subsequent inactivation of Chk2‐Thr68 in combination treated cells, while γH2AX‐Ser139 was elevated implicating the persistence of DNA double strand breaks. Increased autophagocytosis was seen in combination treated cells. Combination treatment did not increase apoptosis or virus replication. The results provide evidence of the antitumor efficacy of combining oncolytic adenoviruses with irradiation as a therapeutic strategy for the treatment of prostate cancer. Further, these findings propose a molecular mechanism that may be important in radiation induced cell death, autophagy and viral cytopathic effect. © 2009 UICC