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Alden H Harken

Publications and source records attributed to Alden H Harken.

At least 19 recordsLinked to original sources
PubMed2006

Da Vinci's problem.

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Education, Medical, Graduate↗
PubMed2006

Admission serum lactate levels do not predict mortality in the acutely injured patient.

INTRODUCTION: The conventional view that admission lactate levels predict outcome in trauma patients stems from simple comparisons of mean blood levels between groups and small sample sizes. To better address this question, we performed more rigorous statistical analyses of lactate in a larger patient sample. METHODS: We prospectively collected data on admission lactate and outcomes in 5,995 patients admitted to an urban, university-based trauma center. The ability of admission lactate to predict mortality was assessed by logistic regression, calculation of positive predictive values (PPV), and measurement of areas under receiver operating characteristic (ROC) curves. RESULTS: Differences between survivors and nonsurvivors in means of most proposed prognosticators was again demonstrated. However, the large overlap in these variables between survivors and nonsurvivors prevented clinically useful predictions. The overall PPV of elevated lactate was only 5.4%. Even in severely injured patients (Injury Severity Score >20; mortality 23%), elevated admission lactate level was a poor predictor of outcome. ROC analyses found no useful sensitivity threshold overall or after stratification by age, sex, Glasgow Coma Scale score, revised trauma score, or mechanism of injury. CONCLUSIONS: This large retrospective examination of admission lactate levels failed to show useful predictive accuracy for hospital death. Serum lactate levels need not be obtained routinely but can be reserved for patients who will be admitted to the intensive care unit and/or require an emergency operation.

Adult↗
PubMed2005

Postinjury serum secretory phospholipase A2 correlates with hypoxemia and clinical status at 72 hours.

BACKGROUND: Although trauma patients often suffer direct lung damage, an equally destructive mechanism of lung injury involves postinjury systemic inflammation. We postulate that secretory phospholipase A(2) (sPLA(2)) release induced by trauma relates to systemic inflammation that compromises both lung function and clinical status after injury. The objectives of this study were: to relate Injury Severity Score to postinjury sPLA(2); to determine whether circulating sPLA(2) relates to pulmonary oxygenation and compliance; and to determine whether early or persistent increases in sPLA(2) are associated with abnormal chest x-ray at 72 hours after injury. STUDY DESIGN: The prospective cohort study comprised 54 consecutive intensive care admissions in patients with traumatic injury admitted over a 6-month period from November 1, 1996, to May 1, 1997. RESULTS: Postinjury peak sPLA(2) values were associated with increased ISS (r = 0.49, r(2) = 0.24, p < 0.001). Patients with elevated sPLA(2) had poor oxygenation compared with those with normal sPLA(2) levels (Pa0(2)/Fi0(2) ratio 164 +/- 16 versus 260 +/- 26 mmHg [mean +/- SEM], p < 0.01) and also required additional PEEP (5.5 +/- 0.9 versus 2.5 +/- 0.4 cm H(2)O, p = 0.01). Secretory PLA(2) levels in patients with abnormal chest x-ray 72 hours after injury were higher (1.08 +/- 0.2 versus 0.34 +/- 0.1 activity units, p < 0.001) than levels seen in patients with normal x-rays. CONCLUSIONS: Increasing injury magnitude is associated with elevated sPLA(2) levels, and increased sPLA(2) is related to postinjury hypoxemia and clinical status.

Adolescent↗
PubMed2005

Melanoma inhibits macrophage activation by suppressing toll-like receptor 4 signaling.

BACKGROUND: Activated macrophages defend against tumors by secreting cytokines to recruit secondary immune cells, presenting antigen to T cells, and by direct tumor cytotoxicity. Peritoneal macrophages harvested from melanoma-bearing mice are less cytotoxic to melanoma cells, and produce less superoxide, nitric oxide, and tumor necrosis factor-alpha (TNF-alpha) than those from nontumor-bearing mice. Similar impairment of macrophage activation occurs in vitro using media harvested from cultured melanoma cells. Stimulation of Toll-like receptor 4 (TLR-4) activates macrophages and results in the release of TNF-alpha. We hypothesized that melanoma inhibits macrophage activation by suppressing TLR-4 signaling. STUDY DESIGN: Melanoma conditioned media (MCM) was generated from B16 melanoma cells. Peritoneal macrophages from TLR-4 competent or TLR-4 incompetent mice were exposed to control or MCM for 24 hours; then stimulated with lipopolysaccharide. TNF-alpha secretion, TNF-alpha mRNA production, nuclear factor-kappaB (NF-kappaB) activation, and TLR-4 surface expression were measured. RESULTS: Peritoneal macrophages exposed to MCM produced considerably less TNF-alpha in response to stimulus than controls (691 pg/mL versus 2,066 pg/mL, p < 0.001). TNF-alpha production by TLR-4 incompetent macrophages was not affected by MCM (454 pg/mL versus 480 pg/mL). Stimulated TNF-alpha mRNA and activated NF-kappaB were decreased in MCM treated C57BL/6 macrophages (by 38% and 33%, respectively). TLR-4 surface expression, however, was not decreased by exposure to MCM. CONCLUSIONS: Melanoma inhibits macrophage activation by suppressing TLR-4 signaling downstream of the TLR-4 receptor.

Animals↗
PubMed2005

Quantification of surgical resident stress "on call".

BACKGROUND: We hypothesized that surgical resident stress involves both psychologic and physiologic components that manifest as changes in heart rate (HR) and circulating white blood cell (WBC) count. The purposes of this series of experiments were to monitor HR as a measure of stress "on call"; to monitor WBC count (1,000 cells/microL) during "on call" periods as a measure of stress; and to relate maximum HR and WBC count "on call" to surgical resident training level. STUDY DESIGN: HR was continuously documented by Holter monitor for 24hours "on call" in interns (n = 6), junior residents (n = 5), and senior residents (n = 5). Interns (n = 4), junior residents (n = 4), and senior residents (n = 4) during periods devoid of clinical responsibilities served as controls. WBC counts were obtained from residents "off" and "on call" for interns (n = 5) and junior residents (n = 5). RESULTS: Mean HR "on call" increased in all resident groups as compared with controls: intern mean HR increased from 71 +/- 3 to 87 +/- 2 beats per minute (bpm) (p = 0.003), junior resident mean HR increased from 74 +/- 3 to 88 +/- 4 bpm (p = 0.03), and senior resident mean HR increased from 69 +/- 2 to 80 +/- 2 bpm (p = 0.004). Intern maximum control HR was 119 +/- 3 and increased to 149 +/- 6 bpm (p = 0.005). The increase in maximum HR (control versus "on call") did not reach significance in junior residents (123 +/- 5 to 136 +/- 6 bpm, p = 0.14) and senior residents (115 +/- 6 to 116 +/- 3 bpm, p = 0.9). WBC count in interns increased from control values of 5.2 +/- 0.6 x 1,000 cells/microL to 7.5 +/- 0.9 x 1,000 cells/microL"on call" (p = 0.005). The WBC change in juniors was not significant (control: 6.8 +/- 0.7 x 1,000 cells/microL, "on call": 7.1 +/- 0.7 x 1,000 cells/microL; p = 0.37). CONCLUSIONS: When heart rate is used as an indicator of combined physiologic and psychologic stress, surgical residents achieve stress levels of tachycardia "on call." Surgical residents also exhibit an increase in circulating WBC count "on call." Both the degree of tachycardia and the increase in WBC count are inversely related to the level of training. Senior residents cope better with stress "on call" than junior residents and interns.

Adult↗
PubMed2004

Signaling for myocardial depression in hemorrhagic shock: roles of Toll-like receptor 4 and p55 TNF-alpha receptor.

Hemorrhagic shock causes myocardial contractile depression. Although this myocardial disorder is associated with increased expression of tumor necrosis factor-alpha (TNF-alpha), the role of TNF-alpha as a myocardial depressant factor in hemorrhagic shock remains to be determined. Moreover, it is unclear which TNF-alpha receptor mediates the myocardial depressive effects of TNF-alpha. Toll-like receptor 4 (TLR4) regulates cellular expression of proinflammatory mediators following lipopolysaccharide stimulation and may be involved in the tissue inflammatory response to injury. The contribution of TLR4 signaling to tissue TNF-alpha response to hemorrhagic shock and TLR4's role in myocardial depression during hemorrhagic shock are presently unknown. We examined the relationship of TNF-alpha production to myocardial depression in a mouse model of nonresuscitated hemorrhagic shock, assessed the influence of TLR4 mutation, resulting in defective signaling, on TNF-alpha production and myocardial depression, and determined the roles of TNF-alpha and TNF-alpha receptors in myocardial depression using a gene knockout (KO) approach. Hemorrhagic shock resulted in increased plasma and myocardial TNF-alpha (4.9- and 4.5-fold, respectively) at 30 min and induced myocardial contractile depression at 4 h. TLR4 mutation abolished the TNF-alpha response and attenuated myocardial depression (left ventricular developed pressure of 43.0 +/- 6.2 mmHg in TLR4 mutant vs. 30.0 +/- 3.6 mmHg in wild type, P < 0.05). TNF-alpha KO also attenuated myocardial depression in hemorrhagic shock, and the p55 receptor KO, but not the p75 receptor KO, mimicked the effect of TNF-alpha KO. The results suggest that TLR4 plays a novel role in signaling to the TNF-alpha response during hemorrhagic shock and that TNF-alpha through the p55 receptor activates a pathway leading to myocardial depression. Thus TLR4 and the p55 TNF-alpha receptor represent therapeutic targets for preservation of cardiac mechanical function during hemorrhagic shock.

Animals↗
PubMed2004

Hemorrhage-induced acute lung injury is TLR-4 dependent.

Toll-like receptor 4 (TLR-4), initially identified as an LPS receptor, is critical to the signaling of a variety of danger signals, including heat shock protein 60, fibrinogen, and fibronectin. Recent data also suggest that TLR-4 plays a role in determining survival in both endotoxemia and hemorrhagic shock. We hypothesized that a functional TLR-4 would be required for hemorrhage and endotoxin-induced acute lung injury. Hemorrhage- and endotoxin-induced lung TNF-alpha mRNA and protein production, neutrophil accumulation, and protein permeability were dependent on a functional TLR-4. Hemorrhage-induced nuclear factor (NF)-kappaB activation was independent of functional TLR-4, whereas endotoxin-induced activation of NF-kappaB requires a functional TLR-4 for full response. Therefore, we conclude that 1) hemorrhage-induced acute lung injury is TLR-4 dependent and 2) hemorrhage has a different and distinct TLR-4-dependent intracellular activation mechanism compared with endotoxemia.

Acute Disease↗