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Background Operative management of parenchymal lung injury can be complicated by persistent hemorrhage and air leak, which might require resection. Techniques that preserve parenchyma are associated with improved survival. High-intensity focused ultrasound (HIFU) has been demonstrated as a useful method for hemostasis in experimental solid organ injuries. We wished to investigate whether this could be applied to lung injuries. Methods An intraoperative HIFU device (frequency of 5.7 MHz, acoustic power of 65 W), equipped with a titanium coupler, was used. Incisions (average length of 2.5 cm, and depth of 5 mm) were made in the lungs of 11 pigs, which created both parenchymal hemorrhage and air leakage. In treatment experiments, 70 incisions were sealed with HIFU. The HIFU application started within 10 seconds of inducing the injury. Hemostasis was assessed by visual observation of sealed incisions. The possible air leakage was determined by submersing the sealed incision under the layer of water and observing for air bubble formation. In control experiments, five incisions were left untreated to monitor air leaks and bleeding for 2 minutes. Results Hemostasis and pneumostasis (sealing of air leaks) of the treated incisions were achieved in 51 +/- 37 seconds (mean +/- SD) (range of 10-210 seconds) of HIFU application time. Over 95% of incisions were hemostatic within 2 minutes of HIFU application. The treatment time was not dependent on the incision length or depth. In control experiments, the air leaking and bleeding were still present at 2 minutes after the injury. Conclusion Intraoperative HIFU might provide an effective method of hemostasis and control of air leaks from lacerations caused by trauma.

Objective: We have shown that High-Intensity Focused Ultrasound (HIFU) can effectively control bleeding from injuries to solid organs such as liver, spleen, and lung. Achievement of hemostasis was augmented when a homogenate of tissue and blood was formed. The objective of this study was to investigate quantitatively the effect of homogenate production on HIFU application time for hemostasis. Possible mechanisms involved in homogenate production were also studied. Methods: Ten anesthetized rabbits had laparotomy and liver exposure. Liver incisions, 15–25 mm long and 3–4 mm deep, were made followed immediately by HIFU application. Two electrical powers of 80 and 100 W corresponding to focal acoustic intensities of 2264 and 2829 W/cm2, respectively were used. Tissue and homogenate temperatures were measured. Smear and histological tissue sample analysis using light microscopy were performed. Results: In treatments with homogenate formation, hemostasis was achieved in 76 ± 1.3 s (Mean ± Standard Error Mean: SEM) at 80 W. In treatments without homogenate formation (at 80 W), hemostasis was achieved in 106 ± 0.87 s. At 100 W, hemostasis was achieved in 46 ± 0.3 s. The time required for homogenate formation, at 80 and 100 W were 60 ± 2.5 and 23 ± 0.3 s, respectively. The homogenate temperature was 83 °C (SEM 0.6 °C), and the non-homogenate tissue temperature at the treatment site was 60 °C (SEM 0.4 °C). The smear and histological analysis showed significant blood components and cellular debris in the homogenate, with some intact cells. Conclusion: The HIFU-induced homogenate of blood and tissue resulted in a statistically significant shorter HIFU application time for hemostasis. The incisions with homogenate had higher temperatures as compared to incisions without homogenate. Further studies of the correlation between homogenate formation and temperature must be done, as well as studies on the long-term effects of homogenate in achieving hemostasis.

OBJECTIVE Previous studies have shown that high-intensity focused ultrasound can effectively control bleeding from injuries of liver, spleen, and blood vessels. This study investigated long-term hemostasis and tissue repair after high-intensity focused ultrasound treatment in liver. METHODS A total of 21 rabbits were randomly assigned to 2 groups: high-intensity focused ultrasound treatment (n = 14) and sham treatment (n = 7). All animals had sterile laparotomy and liver exposure. The high-intensity focused ultrasound-treated animals received liver incisions, 20 to 25 mm long and 4 to 6 mm deep, followed immediately by high-intensity focused ultrasound application until complete hemostasis was achieved. After recovery, sonographic images, blood samples, and histologic samples were collected immediately and on days 1, 3, 7, 14, 28, and 60 after treatment. RESULTS All 14 liver injuries were hemostatic after an average +/- SD of 78 +/- 44 seconds of high-intensity focused ultrasound application, with no rebleeding at any time point after the treatment. Subsequent blood analysis showed no significant difference in serial hematologic or coagulation measures between the high-intensity focused ultrasound and sham groups. Alanine aminotransferase and aspartate aminotransferase levels increased immediately after surgery by as much as 285% up to day 3 and returned to normal values by day 7. Hematocrit and white blood cell counts showed no statistically significant difference from normal values at all time points. Histologic examination up to 60 days after treatment revealed scarring and liver tissue regeneration at the treatment site. CONCLUSIONS High-intensity focused ultrasound appears to provide long-lasting hemostasis of acute liver injury. Healing and repair mechanisms after high-intensity focused ultrasound application appear to be intact.

BACKGROUND: Patients involved in a high-energy trauma (HET) are usually admitted for clinical observation, even when no significant injury is found after standard care in the emergency room (ER). The necessity of this observation period is not evidence based. The goal of this study was to identify patients who revealed an initially undiagnosed injury during the observation period. METHODS: A retrospective study of consecutive HET patients was conducted in two Level I trauma centers. Patients after a HET with two minor injuries or less, diagnosed during the standard ER care, were included. Data were abstracted from patients' medical records. RESULTS: Five hundred three patients were included. None of the patients developed any complications during the clinical observation period or were readmitted to their own hospital within a week after the trauma. CONCLUSION: There is no evidence for the necessity of clinical observation of HET patients with minimal or no injuries diagnosed after standard ER stabilization and evaluation. Language: en

Background Previous studies have shown that high-intensity focused ultrasound (HIFU) can effectively control bleeding of incised livers and spleens and punctured vessels. This current study investigated the long-term safety of HIFU in splenic hemostasis. Methods A total of 21 rabbits were randomly assigned to two groups: HIFU treatment (n = 14), and sham treatment (n = 7). All animals underwent sterile laparotomy and splenic exposure. The HIFU-treated animals received splenic incisions, 8 to 10 mm long and 4 to 5 mm deep, and immediate 9.6-MHz HIFU until hemostasis was achieved. After recovery, ultrasound images, blood samples, and histologic samples were collected on days 0, 1, 3, 7, 14, 28, and 60. Results All 14 splenic injuries were hemostatic after an average of 96 seconds of HIFU application. There was evidence of rebleeding in one animal between days 3 and 7 posttreatment. Subsequent blood analysis showed no significant difference in serial hematologic or coagulation measures between HIFU and sham groups. Histologic examination up to 60 days posttreatment revealed scarring and spleen tissue regeneration at the treatment site. Conclusion HIFU provides an effective and safe method of achieving hemostasis after acute splenic injury.

BackgroundThe management of colon injuries that require resection is an unresolved issue because the existing practices are derived mainly from class III evidence. Because of the inability of any single trauma center to accumulate enough cases for meaningful statistical analysis, a multicenter prosp

High-intensity focused ultrasound (HIFU) has been shown to control bleeding from liver incisions, and blood vessel punctures and incisions. The objective of the current study was to investigate the capability of HIFU to stop bleeding from splenic injuries in a pig model.Surgical incisions, 25 to 50 mm in length and 2 to 8 mm in depth, were made in the spleens of five anesthetized pigs. HIFU with a frequency of 5 MHz was applied within 5 seconds of making the incision. A total of 39 incisions and HIFU treatments were performed.Bleeding from all incisions was stopped completely after HIFU treatment. The average times to control and completely arrest the hemorrhage were 28 and 55 seconds, respectively. The mechanisms of hemostasis appeared to be thermally induced coagulation necrosis of splenic tissue and occlusion of blood vessels by a mechanically induced homogenized splenic tissue.HIFU may provide a useful method of hemostasis for actively bleeding spleen. Because of its ability to induce hemostasis at adjustable depth, HIFU may prove to be a useful cauterization method both in the operating room and for patients who are managed nonoperatively.

Endothelial cell death may contribute to tissue injury from ischemia. Little is known, however, about the characteristics of endothelial cell death in response to hypoxia. Using an in vitro model, we found that human umbilical vein endothelial cells were resistant to hypoxia-induced cell death with only a 2% reduction in viability at 24 h and 45% reduction in viability at 48 h. Overexpression of a mutant, IκBα, via adenoviral vector did not potentiate cell death in hypoxia, indicating that nuclear factor-κB activation was not involved in cytoprotection. Cell death in hypoxia was determined to be apoptotic by 3′ labeling of DNA using terminal deoxynucleotidyl transferase staining and reversibility of cell death with a caspase inhibitor. Exposure of endothelial cells to hypoxia did not alter levels of proapoptotic and antiapoptotic Bcl-2 family members Bax and Bcl-XL by immunoblot analysis. In contrast, changes in p53 protein levels correlated with the induction of apoptosis in hypoxic endothelial cells. Inhibition of the proteasome increased p53 protein levels and accelerated cell death in hypoxia. Overexpression of p53 by adenoviral transduction was sufficient to initiate apoptosis of normoxic endothelial cells. These data provide a framework for the study of factors regulating endothelial cell survival and death in hypoxia.

E-selectin is an activation-dependent, endothelial cell-restricted adhesion molecule that is internalized and degraded rapidly once expressed on the cell surface. Tyrosine-containing structural motifs play an important role in the internalization of a number of integral proteins, and the membrane-proximal E-selectin cytoplasmic tyrosine residue (Tyr582) conforms to the endocytosis motif proposed previously. To determine the endocytosis motif in E-selectin, we selectively introduced truncation, substitution, and deletion mutations to the cytoplasmic tail of E-selectin. We analyzed the internalization kinetics of surface-expressed wild-type and mutant E-selectin constructs in transiently transfected Chinese hamster ovary cells using 125I-labeled E-selectin monoclonal antibody (125I-P6E2) in an acid elution assay. Interestingly, truncation immediately membrane proximal to Tyr582 (DeltaDGS construct) did not alter internalization kinetics significantly (DeltaDGS versus wild-type, mean surface half-life = 42 versus 45 min, respectively). Thus, it appears that the tyrosine residues are not required for internalization of E-selectin. Additional analyses indicated that Ser581 was necessary but alone was insufficient for surface E-selectin endocytosis. Thus, we conclude that there exists a novel non-tyrosine-containing endocytosis signal in the cytoplasmic tail which involves Ser581 and residues membrane-proximal to it.

Myocardial ischemia and reperfusion is a common occurrence in cardiovascular surgery patients. Acute ischemia results in a spectrum of derangements, which range from transient reversible stunning of the myocardium to severe irreversible abnormalities such as infarction. Many of these abnormalities are accentuated upon reperfusion with oxygenated blood. Recently, the endothelium has been shown to play a key role in the injury suffered after ischemia and reperfusion. When rendered hypoxic and then reoxygenated, endothelial cells become activated to express proinflammatory properties that include the induction of leukocyte-adhesion molecules, procoagulant factors and vasoconstrictive agents that increase vasomotor tone. These changes may contribute to the no-reflow phenomenon by promoting endothelial edema, neutrophil and platelet plugging, microthrombosis, and enhanced vasomotor tone. An increased understanding of the role that hypoxic endothelial cell activation plays in myocardial dysfunction after ischemia/reperfusion may allow therapies to be designed to further attenuate this response.

BACKGROUND High-intensity focused ultrasound (HIFU) is effective in producing hemostasis in injuries from organ lacerations and punctures in animals but has not been evaluated in impact injuries. METHOD High-energy blows were applied to 11 heparinized and anesthetized pigs, resulting in solid organ injury. HIFU was applied to injuries via laparotomy. The animals were closed, administered saline, observed under general anesthesia for 3.6 +/- 0.4 hours, reopened, and inspected, and abdominal free fluid was aspirated. RESULTS Organ hemostasis was achieved (mean +/- SD) with 15 +/- 6 minutes of HIFU treatment and 54 +/- 3 minutes of operating time, and 18.8 +/- 13.1 mL/kg of blood was recovered from the abdomen. One animal died from an untreated occult injury to a large vein. HIFU-treated sites were hemostatic at relaparotomy, with 8.6 +/- 6.2 mL/kg abdominal serosanguinous fluid recovered. CONCLUSION HIFU is effective in producing hemostasis by direct treatment of injured parenchyma in blunt trauma.

Leukocyte Adhesion Deficiency Type II (LAD II) is a recently described syndrome and the two patients with this defect lack fucosylated glycoconjugates. These glycoconjugates include the selectin ligand, sialyl LewisX, and various fucosylated blood group antigens. To date, the molecular anomaly in these patients has not been identified. We localized the defect in LAD II to the de novo pathway of GDP-fucose biosynthesis, by inducing cell-surface expression of fucosylated glycoconjugates after exposure of lymphoblastoid cell lines from the LAD II patients to exogenous fucose. This defect is not restricted to hematopoietic cells, since similar findings were elicited in both human umbilical vein endothelial cells (HUVEC) and fibroblasts derived from an affected abortus. We have used these LAD II endothelial cells to examine the consequence of fucosylation of endothelial cells on the rolling of normal neutrophils in an in vitro assay. Neutrophil rolling on LPS-treated normal and LAD II HUVEC was inhibited by an E-selectin monoclonal antibody at both high and low shear rates. LAD II HUVEC lacking fucosylated glycoproteins supported leukocyte rolling to a similar degree as normal HUVEC or LAD II cells that were fucose-fed. At low shear rates, an L-selectin antibody inhibited neutrophil rolling to a similar degree whether the LAD II cells had been fucose-fed or not. These findings suggest that fucosylation of nonlymphoid endothelial cells does not play a major role in neutrophil rolling and that fucose is not a critical moiety on the L-selectin ligand(s) on endothelial cells of the systemic vasculature.

Publisher Summary Leukocytes are an integral component of the host defense system. However, in some disease states their action may instead be deleterious to the host and they may cause a significant amount of tissue damage. For example, in ischemia-reperfusion (I-R) injury an ischemic insult may trigger an inflammatory response during reperfusion that causes more injury than the initial ischemic insult. In other diseases, such as rheumatoid arthritis, leukocytes cause tissue damage without an apparent initial insult. In still other instances, leukocytes may function normally, but it is advantageous to manipulate their function. In order for leukocytes to cause vascular or tissue damage, they must first adhere to the endothelium and then exit the bloodstream to gain access to extravascular tissue. Leukocyte emigration involves adhesion molecules both on the leukocyte and on the endothelial cell surface. These adhesion molecules are vital not only for adherence but participate in several other leukocyte functions such as signal transduction. Therefore, adherence molecules have emerged as important targets for therapy in a broad spectrum of inflammatory and immune disorders. This chapter reviews the current status of “anti-adhesion’’ therapy in a number of in vivo models of disease states and considers some of the safety concerns associated with anti- adhesion therapy. The chapter discusses the relation between leukocyte and endothelial adhesion molecules—selectins, integrins and immunoglobulin superfamily—adhesion cascade and inflammation, strategies to inhibit adhesion, ischemia- reperfusion injury of the various selectins, oligosaccharides and the various integrins. There are details on atherosclerosis—adhesion molecule expression, anti-adhesion therapy—thermal injury, arthritis, asthma, organ transplantation, acute lung injury, multiple sclerosis and other miscellaneous diseases. Blocking either the initial rolling of leukocytes along the endothelium or the firm adherence of leukocytes to the endothelium has been found to be effective in reducing leukocyte-mediated injury and leukocyte accumulation.

Myocardial ischemia and reperfusion is a common occurrence in cardiovascular surgery patients. Acute ischemia results in a spectrum of derangements, which range from transient reversible stunning of the myocardium to severe irreversible abnormalities such as infarction. Many of these abnormalities are accentuated upon reperfusion with oxygenated blood. Recently, the endothelium has been shown to play a key role in the injury suffered after ischemia and reperfusion. When rendered hypoxic and then reoxygenated, endothelial cells become activated to express proinflammatory properties that include the induction of leukocyte-adhesion molecules, procoagulant factors and vasoconstrictive agents that increase vasomotor tone. These changes may contribute to the no-reflow phenomenon by promoting endothelial edema, neutrophil and platelet plugging, microthrombosis, and enhanced vasomotor tone. An increased understanding of the role that hypoxic endothelial cell activation plays in myocardial dysfunction after ischemia/reperfusion may allow therapies to be designed to further attenuate this response.

Objectives In nursing home settings, providers often think that most percutaneous endoscopic gastrostomy (PEG) tubes are placed in older people, some perhaps inappropriately. We sought to describe the relationships between patient age and the indications for, the decision making behind, and the outcomes of gastrostomy and jejunostomy placement in an urban hospital to give perspective to those of us working in long-term care settings. Design Retrospective, observational study. Setting Urban hospital. Participants Two hundred thirty-nine inpatients who underwent gastrostomy or jejunostomy (G/J) placement. Measurements Hospital records were reviewed for patient demographics, disease process, decision making, and short-term outcomes associated with G/J placement. Mortality at 30 days and 1 year was obtained by a search of the National Death Index. The prevalence of these variables in those aged 65 years and older was compared to the prevalence in those younger than 65 with associations calculated both unadjusted and adjusted for gender, place of residence, underlying condition, and Charlson comorbidity index. Results Patients who were aged 65 years and older were more likely to be female with more comorbid illnesses and were more likely to have had a stroke that precipitated their difficulty eating. They were more likely to have been referred by a medical specialist, to have been seen by a speech pathologist, and to have had their procedure without general anesthesia. The older patients had a shorter mean hospital length of stay with fewer complications but had higher mortality rates at 30 days and 1 year. Conclusion Patient age was associated with gender and type of disease process and may have influenced the decisions made during the hospital stay. Despite a higher burden of chronic illness, older patient age was not associated with adverse short-term outcomes but was associated with higher mortality rates after discharge.

In thoracic surgery, bleeding and air leaks from the lungs can be difficult to control. We have investigated the use of high intensity focused ultrasound (HIFU) for control of lung bleeding and air leaks in operative situations. An intraoperative HIFU device, equipped with a Titanium coupler, was used. The HIFU transducer was a PZT‐8 concave element, with a focal length of 5 cm, and a diameter of 2.5 cm. The transducer was operated at 5.7 MHz and intensity of 5000 W/cm2. The coupler length was 4 cm, placing the focal volume, defined by full‐width half‐maximum at approximately 1 cm from the tip of the coupler. A pig animal model was used. Incisions in the lung were made, having lengths of 2–5 cm, and depths of 3–10 mm which created both parenchymal hemorrhage and air leakage from the lung. HIFU was applied within 10 seconds of inducing the injury. The average hemostasis time was approximately 60 seconds. All incisions were completely sealed, and no blood or air leaked from the incisions. Intraoperative HIF...