Significant Tissue Injury Research Articles

Cardiac Dysfunction and Prolonged Hemodynamic Deterioration After Implantable Cardioverter-Defibrillator Shock in Patients With Systolic Heart Failure

We investigated the acute effects of implantable cardioverter-defibrillator shock on myocardium, cardiac function, and hemodynamics in relation to left ventricular systolic function. We studied 50 patients who underwent implantable cardioverter-defibrillator implantation and defibrillation threshold (DFT) testing: 25 patients with left ventricular ejection fraction (LVEF) ≥ 45% and 25 patients with LVEF <45%. We measured cardiac biomarkers (creatine kinase, creatine kinase-MB, myoglobin, cardiac troponin T and I, and N-terminal probrain natriuretic peptide). Left ventricular relaxation was assessed by global longitudinal strain rate during the isovolumetric relaxation period using speckle-tracking echocardiography. Blood sampling and echocardiography were performed before, immediately after, and 5 minutes and 4 hours after DFT testing. Mean arterial pressure was measured directly during DFT testing. Cardiac biomarkers showed no significant changes in either group. LVEF was decreased until 5 minutes after DFT testing and had recovered to the baseline at 4 hours in the group with reduced LVEF (P<0.001), whereas LVEF reduction was not observed in the group with preserved LVEF (P=0.637). Global isovolumetric relaxation period was decreased until 5 minutes after DFT testing and had recovered to the baseline at 4 hours in both groups (preserved LVEF: 0.39 ± 0.14 versus 0.23 ± 0.13* versus 0.23 ± 0.13* versus 0.40 ± 0.13 s(-1), *P<0.001 versus baseline; reduced LVEF: 0.15 ± 0.05 versus 0.08 ± 0.04† versus 0.09 ± 0.04† versus 0.15 ± 0.05 s(-1), †P<0.001 versus baseline, repeated-measures ANOVA). Time to recovery of mean arterial pressure to the baseline was prolonged in the group with reduced LVEF (P<0.001). Implantable cardioverter-defibrillator shock transiently impairs cardiac function and hemodynamics especially in patients with systolic dysfunction, although significant tissue injury is not observed.

Neurobiological responses to stereotactic focal irradiation of the adult rodent hippocampus

Radiation effectively treats brain tumors and other pathologies but dose and treatment plans are limited by normal tissue injury, a major cause of morbidity in survivors. Clinically significant normal tissue injury can occur even with therapies that target pathological tissue and limit out-of-target irradiation. Elucidating the mechanisms underlying normal tissue injury is facilitated by studying the effects of focal irradiation and comparing irradiated and un-irradiated tissue in experimental animals. Young adult rats were irradiated using the Leksell Gamma Knife® with a 10 Gy maximum dose directed at the left hippocampus and shaped to minimize irradiation contralaterally. At least 95% of targeted hippocampus received ≥ 3 Gy, while all points in the contralateral hippocampus received < 0.3 Gy. Neuronal and microglial markers of damage were assessed in the targeted and contralateral hemispheres of Gamma Knife®-treated rats and compared to non-irradiated controls. Acute cell death and sustained changes in neurogenesis and in microglia occurred in the dentate gyrus of the targeted, but not the contralateral, hippocampus, providing experimental evidence that focal irradiation at doses received by peri-target regions during targeted radiation therapy produces robust normal tissue responses. Additional studies using this approach will facilitate assessment of in vivo dose responses and the cellular and molecular mechanisms of radiation-induced brain injury.

Rhinoscleroma: a retrospective study of pathologic and clinical features.

Rhinoscleroma, a chronic granulomatous bacterial disease of the nasal mucosa that often extends through the lower respiratory tract, is caused by infection with the gram-negative bacillus Klebsiella rhinoscleromatis (KR). We report the clinicopathology and histology associated with KR infection-induced rhinoscleroma in patients admitted to the Beijing Tongren Hospital over a 30-year period. The clinical and pathologic features of 40 cases of upper aerodigestive tract infections were retrospectively studied. Histochemical examination of biopsy samples was performed, including periodic acid-Schiff, modified Warthin-Starry, and acid-fast stains. In addition, immunohistochemical staining for CD43, CD20, CD68, and lysozymes was performed in 11 specimens, and 8 specimens were analyzed by transmission electron microscopy. KR infection was confirmed in each of the 40 samples. Twenty-seven patients remained relapse free 1 to 10 years following treatment with antibiotic supplemented in some cases with surgery or radiotherapy, and all 13 cases of relapse were successfully eradicated by the end of treatment. KR infection was localized to phagosomes within Mikulicz cells, as determined by immunohistochemistry and electron microscopy. Significant tissue injury was observed in most cases. Long-term antibiotic therapy successfully eradicated KR infection in all cases. Although late diagnosis was common in this cohort, retrospective examination of biopsy samples suggests that diagnosis can be improved by combining clinical findings with histologic analysis.

Espécies reativas do oxigênio e as doenças respiratórias em grandes animais

As espécies reativas do oxigênio (ERO) são moléculas instáveis e extremamente reativas capazes de transformar outras moléculas com as quais colidem. As ERO são geradas em grande quantidade durante o estresse oxidativo, condição em que são afetadas moléculas como proteínas, carboidratos, lipídeos e ácido nucleicos. Neste trabalho, são discutidos os principais conceitos sobre os radicais livres e as ERO: principais tipos, sua formação e a forma como atuam sobre as estruturas celulares, provocando lesão tecidual significativa. Os principais sistemas de defesa antioxidantes e a influência do aumento na produção dessas ERO no trato respiratório de grandes animais também são discutidos, dando ênfase ao envolvimento das ERO em doenças como a pneumonia em ruminantes e na obstrução recorrente das vias aéreas e a hemorragia pulmonar induzida por exercício em equinos.

INITIAL SURGICAL EXPERIENCE WITH A DENSE CORTICAL MICROARRAY IN EPILEPTIC PATIENTS UNDERGOING CRANIOTOMY FOR SUBDURAL ELECTRODE IMPLANTATION

Detailed investigations of cortical physiology require the ability to record brain electrical activity at a submillimeter scale. Standard intracranial electrodes result in significant averaging of potentials generated by large numbers of neurons. In contrast, microelectrode arrays allow for recording of local field potentials and single-unit activity. We describe our initial surgical experience with the NeuroPort microelectrode array (Cyberkinetics Neurotechnology Systems, Inc., Salt Lake City, UT) in a series of patients undergoing subdural electrode implantation for epilepsy monitoring. Seven patients were implanted with and underwent semichronic recording from the NeuroPort array during standard subdural electrode monitoring for epilepsy. The electrode was placed according to company specifications in putative noneloquent epileptogenic cortex. After the monitoring period, microelectrode arrays were removed during explantation of subdural electrodes and resection of epileptogenic tissue. Successful implantation of the microelectrode array was achieved in all patients, with minor operative difficulties. Robust and durable local field potentials and single-unit recordings were obtained from all implanted individuals. Implantation times ranged from 3 to 28 days; histological analysis of implanted tissue demonstrated no significant tissue injury or inflammatory response. There were no neurological complications or infections associated with electrode implantation or prolonged monitoring. Two patients developed postresection issues with wound healing at the site of scalp egress, with 1 requiring operative wound revision. Our experience demonstrates that semichronic microelectroencephalographic recording can be safely and effectively achieved using the NeuroPort microarray. Although significant tissue injury, infection, or cerebrospinal fluid leak was not encountered, the large profile of the connection pedestal resulted in suboptimal wound closure and healing in several patients. We predict that this problem will be easily addressed in second-generation devices.

Ischemic Preconditioning Prevents Skeletal Muscle Tissue Injury, But Not Nerve Lesion Upon Tourniquet-Induced Ischemia

Prolonged ischemia followed by reperfusion (I/R) of skeletal muscle results in significant tissue injury. Ischemic preconditioning (IPC), achieved by brief periods of ischemia before sustained ischemia, has been shown to ameliorate I/R injury in a variety of tissues. We demonstrate that tourniquet hind limb ischemia-induced injury of the muscle benefits from IPC, whereas the peripheral nerve suffers from prolonged ischemia time and mechanical deterioration on IPC. In anesthetized rats, hind limb ischemia was induced by tourniquet for 3 hours followed by 24 hours of reperfusion. In an additional series of experiments, IPC (three cycles of 10 minutes I/10 minutes R) preceded hind limb ischemia. Sham-operated animals without ischemia served as controls. Skeletal muscle tissue injury was assessed with respect to microcirculation, inflammatory cell response, and cell integrity using intravital fluorescence microscopy, Western blot protein analysis, and tissue histochemistry. Analysis of tactile and thermal allodynia served as indicators for postischemic pain. In addition, motor nerve conduction velocity and transmission electron microscopy allowed assessing postischemic nerve lesion. Tourniquet of the hind limb caused marked perfusion failure, enhanced leukocyte-endothelial cell interaction, and apoptotic cell death. IPC was able to improve microvascular perfusion and to reduce inflammatory cell response. Of interest, apoptotic cell death, assessed by cell nuclear morphology in vivo as well as Western blot and immunohistochemical analysis of caspase-3 cleavage, can be substantially reduced by IPC in tourniquet ischemia of the hind limb. Application of the tourniquet abolished nerve conduction in all animals. Non-IPC-treated animals still showed tactile allodynia, whereas IPC further caused loss of pain sensation and motor function of the postischemic hind limb. High susceptibility of the peripheral nerve to compression-induced ischemic injury disproves IPC in its clinical application for surgical procedures requiring prolonged tourniquet ischemia.

Inter-α-Trypsin Inhibitor Attenuates Complement Activation and Complement-Induced Lung Injury

Complement activation is a central component of inflammation and sepsis and can lead to significant tissue injury. Complement factors are serum proteins that work through a cascade of proteolytic reactions to amplify proinflammatory signals. Inter-alpha-trypsin inhibitor (IaI) is an abundant serum protease inhibitor that contains potential complement-binding domains, and has been shown to improve survival in animal sepsis models. We hypothesized that IaI can bind complement and inhibit complement activation, thus ameliorating complement-dependent inflammation. We evaluated this hypothesis with in vitro complement activation assays and in vivo in a murine model of complement-dependent lung injury. We found that IaI inhibited complement activation through the classical and alternative pathways, inhibited complement-dependent phagocytosis in vitro, and reduced complement-dependent lung injury in vivo. This novel function of IaI provides a mechanistic explanation for its observed salutary effects in sepsis and opens new possibilities for its use as a treatment agent in inflammatory diseases.

The Protective Role of Heme Oxygenase-1 Induction on Testicular Tissues After Testicular Torsion and Detorsion

Testicular torsion-detorsion has been identified as an ischemia-reperfusion type of injury. We elucidated the protective role of heme oxygenase-1 super induction on testicular torsion-detorsion injury. Adult male Sprague-Dawley rats were randomly allocated to undergo testicular torsion-detorsion, immediately followed by injection of normal saline, the heme oxygenase-1 inducer hemin or hemin plus the heme oxygenase-1 inhibitor tin protoporphyrin. Another set of rats that underwent sham operation, immediately followed by injection of normal saline, hemin or hemin plus tin protoporphyrin, served as controls. Testes were harvested 4 and 24 hours after detorsion, respectively, in the experimental groups or at comparable time points in the control groups. Histological evaluation confirmed that torsion-detorsion caused significant testicular tissue injury. Torsion-detorsion also caused significant increases in the testicular levels of nitric oxide, malondialdehyde, myeloperoxidase activity and heme oxygenase-1. The heme oxygenase-1 inducer hemin significantly enhanced the heme oxygenase-1 expression induced by torsion-detorsion and in turn attenuated testicular injury, and increases in nitric oxide, malondialdehyde and myeloperoxidase activity. In addition, the protective effects of hemin were significantly offset by the heme oxygenase-1 inhibitor tin protoporphyrin. Super induction of heme oxygenase-1 protects testes from torsion-detorsion injury.

Does noncomplicated acute appendicitis cause bacterial translocation?

It is unknown whether noncomplicated acute appendicitis cause bacterial translocation. In this study, we aimed to test development of the bacterial translocation in the patients who were operated for acute appendicitis. In this prospective study, 10 control patients who underwent elective operations because of other reasons, and 18 patients with noncomplicated acute appendicitis were evaluated. No patients took prophylactic antibiotic. After laparotomy, samples were obtained from peritoneal leaf just close to wound edge, and peritoneal swab culture from right paracolic region. Before appendectomy, a mesenteric lymph node (MLN) adjacent to the terminal ileum was taken out. Tissue samples were placed in a sterile container for microbiological analysis, and 10% formalin for histopathological analysis. Control samples had no bacterial translocation. Only 3 of 18 (16.6%) patients with appendicitis included bacterial translocation to MLN. There was no significant difference between both groups. No bacterial colonization was detected in the peritoneal tissue and peritoneal swab culture. Peritoneal tissue injury score was 2 +/- 1.4 in controls and 2.8 +/- 1.7 in the patients with appendicitis (P>0.05). MLN injury score was 2.5 +/- 1.3 in controls and 3.2 +/- 1.5 in the patients with appendicitis (P>0.05). No patient developed wound and systemic infection. No significant bacterial translocation frequency and tissue injury score was identified in the children with noncomplicated acute appendicitis. This result suggests that antibiotic prophylaxis may be unnecessary in such patients.

P154: Pathogenic IgM antibody initiates cardiac reperfusion injury

Introduction: The injury sustained by ischemic tissues is largely inflammatory, manifesting only after reperfusion of ischemic cells. A single clone of natural B1 cell-derived IgM has been described as the key component in the initiation of reperfusion injury in other tissues. This injurious inflammation is prevented by blockade of the IgM clone with a peptide mimetope of its tissue ligand, as shown in multiple murine models of end-organ I/R. Here, we demonstrate that this process also applies to one of the most clinically relevant ischemia-prone organs, the heart. Methods: We modified an established model of cardiac ischemia/reperfusion to examine extent of injury in three distinct sets of mice: parental strain C57/ B6, RAG -/- (immunoglobulin deficient) and C57/B6 animals with peptide inhibitor. Mice were anesthetized, intubated, placed on a cardiac monitor and mechanically ventilated. The LAD was reversibly occluded through a left thoracotomy and left ventricle was subjected to 30 minutes of ischemia with 60 minutes of reperfusion, after which the animals were sacrificed. The hearts were analyzed using gross visualization of infarct area (TTC staining), histologic analysis of infarct area, and immunohistochemical analysis for IgM binding. Animals undergoing peptide administration were given intravenous peptide immediately prior to release of the LAD ligature. Results: C57/B6 mice demonstrated significant tissue injury with large areas of gross infarct corresponding to microscopic histologic injury and IgM deposition. In comparison, the immunoglobulin deficient RAG mice appeared to be protected, with little evidence of gross infarct or histologic injury as well as attenuated IgM binding. Wild type mice with peptide were equally protected from injury, exhibiting a pattern similar to that of RAG mice and altogether uninjured tissue. Conclusion: These results support of the presence of a common mechanism for initiation of reperfusion injury with natural IgM as an early, key element. The success of the inhibitory peptide in multiple clinically relevant I/R models may lead to novel therapeutic strategies for treating reperfusion injury.

The mammalian host response to borrelia infection

Tick-borne relapsing fever (RF) and Lyme disease (LD) are spirochetal infections of humans caused by different Borrelia species in endemic areas throughout the world. Our laboratory is studying the response of mammalian hosts to borrelia infection in RF and LD. For this, we use mice and non-human primates infected with B. burgdorferi sensu stricto strain N40 (N40) and the Oz1 strain of Borrelia turicatae (Bt), agents of LD and RF in North America, respectively. Our results have revealed that outbred non-human primates are significantly less susceptible than outbred mice to persistent infection with N40. In contrast, the majority of mice inoculated with the RF agent B. turicatae clear the infection, with the notable exception of residual brain or blood infection in up to 25% of cases. Little if any tissue injury occurs in immunocompetent animals with either LD or RF. In contrast, impairment of specific antibody production results in significant tissue injury, most notably in the heart, in both LD and RF. The inflammatory infiltrate is rich in plasma cells, activated macrophages and T cells, and there is significant deposition of antibody and complement, including membrane attack complex, in inflamed tissues and spirochetes. Significant loss of cardiomyocytes with apoptosis and caspase activation was observed in the heart of immunosuppressed non-human primates infected with N40 and in B cell-deficient mice infected with B. turicatae. Unlike the heart, the brain of B cell-deficient mice infected with B. turicatae showed prominent microglial activation but no detectable tissue injury. Tissues from immunosuppressed non-human primates infected with N40 produce large amounts of immunoglobulin and the B cell chemokine CXCL13, both of which significantly correlate with the spirochetal load. We conclude that the main response of mammalian hosts in LD and RF is the production of specific antibody to clear the infection. Failure of this response leads to persistent infection, which can lead to tissue injury, most notably in the heart.

Cellular Autoimmunity in Myocarditis

To understand how autoimmunity occurs, one first needs to review the basic processes of immune response and immune regulation. Host defense mechanisms can be broadly defined as 2 types: innate and adaptive (or antigen-specific) immunity.1,2 Although adaptive immunity is usually the most effective mechanism for eliminating invading organisms, this response is relatively slow, taking up to 7 to 10 days for effective primary immune responses and 2 to 3 days for anamnestic or memory responses. During this time, rapidly proliferating infectious agents could produce significant tissue injury and possibly death of the organism if left uncontrolled. For this reason, broadly reactive host responses, which are constantly maintained or can be rapidly induced, are essential in containing infections until the adaptive immune response “kicks in.”

Reperfusion strategy after regional ischaemia: comparative study of reperfusion conditions and compositions.

We investigated the effects of pressure, temperature and additives on aortic root reperfusion success. Cardiopulmonary bypass and heart arrest were initiated in mongrel dogs and sudden uncontrolled normothermic (group 1), pressure controlled substrate enriched normothermic (group 2a), pressure controlled unmodified normothermic (group 2b) and pressure controlled unmodified tepid (group 3) reperfusion compared. In group 1, the first cardiac rhythm was ventricular fibrillation, but dogs in the other groups showed spontaneous sinus rhythm. Recovery times were significantly longer and cardiac output levels significantly decreased in group 1 compared with the other groups. Prolonged lactate production and oxygen uptake failure were observed in group 1 compared with the other groups; oxidative stress markers and microscopic studies confirmed significant tissue injury in group 1. All parameters were similar between groups 2a, 2b and 3, indicating that low reperfusion pressure in the first 2 min is the most effective component of reperfusion.

Protective role of heme oxygenase-1 in the intestinal tissue injury in an experimental model of sepsis.

The aim of this study was to examine the role of heme oxygenase-1 induction in the intestinal tissue injury in a rat model of sepsis. Randomized, masked, controlled animal study. University-based animal research facility. Sprague-Dawley male rats, weighing 220-250 g (n = 126). Rats were injected with lipopolysaccharide (10 mg/kg) intraperitoneally. Another group of rats was injected with interleukin-6 (10 microg/kg) intravenously. In some rats, tin mesoporphyrin (1 micromol/kg) was administered intravenously 1 hr before lipopolysaccharide treatment. Following lipopolysaccharide treatment, expression of heme oxygenase-1 and nonspecific delta-aminolevulinate synthase (ALAS-N), the rate-limiting enzymes of heme catabolism and biosynthesis, respectively, was examined in various regions of the intestine. Lipopolysaccharide treatment markedly increased heme oxygenase-1 messenger RNA and protein concentrations in the mucosal epithelial cells in the duodenum and the jejunum, whereas its expression in the ileum and the colon was hardly detectable and was not influenced by the treatment. ALAS-N messenger RNA was also more markedly increased in the duodenum, the jejunum, and the ileum than in the colon following lipopolysaccharide treatment. Interleukin-6 administration also induced heme oxygenase-1 and ALAS-N gene expression in a pattern similar to that following lipopolysaccharide treatment. In contrast to the marked heme oxygenase-1 expression in the upper intestine, lipopolysaccharide-induced mucosal injury and inflammation in the upper intestine were far less than observed in the lower intestine as judged both by tumor necrosis factor-alpha gene expression and by histologic analysis. Of note, inhibition of heme oxygenase activity by tin mesoporphyrin produced a significant tissue injury in the upper intestine of the lipopolysaccharide-treated animals. Intestinal heme oxygenase-1 and ALAS-N gene expression was regulated in a site-specific manner in a rat model of sepsis. Our findings also suggest that heme oxygenase-1 induction may play a fundamental role in protecting mucosal epithelial cells of the intestine from oxidative damages that occur in sepsis.

Role of platelets in the pathophysiology of acute coronary syndrome.

Coronary atherosclerosis is the primary cause of heart diseases in industrialized nations. It has now become clear that coronary atherosclerosis is not simply an inevitable consequence of aging but rather a chronic inflammatory process that can be converted into an acute clinical event by plaque rupture and arterial thrombosis. It is well recognized that platelets play a key role in thrombotic vascular occlusion at the ruptured coronary atherosclerotic plaque, leading to acute ischemic episodes, the acute coronary syndromes (ACSs). In addition, both embolization of platelet aggregates and direct, receptor-mediated platelet adhesion to the postischemic microvascular surface result in obstruction and impairment of coronary microcirculation. Such microvascular disturbance may lead to significant additional tissue injury and aggravate myocardial contractile dysfunction. Novel antiplatelet strategies have contributed substantially to improve the outcome of patients with ACSs. However, the availability of new investigative tools, including genetically modified mouse models of disease, has demonstrated that platelets not only contribute to acute thrombotic vascular occlusion but also participate in the inflammatory and matrix-degrading processes of coronary atherosclerosis itself. Platelet- endothelial cell interactions at lesion-prone sites might trigger an inflammatory response in the vessel wall early in the genesis of atherosclerosis and contribute to destabilization of advanced atherosclerotic lesions. Thus, recent progress in defining the complex multistep process that promotes firm arrest of platelets to the (sub-) endothelium and initiates subsequent platelet activation may lead to the development of new antiplatelet strategies that provide an efficacious prophylactic intervention, in particular, for patients with a high atherosclerotic risk factor profile.

Proinflammatory effects of bacterial lipoprotein on human neutrophil activation status, function and cytotoxic potential in vitro.

Bacterial lipoprotein (BLP) is the most abundant protein in gram-negative bacterial cell walls, heavily outweighing lipopolysaccharide (LPS). Herein we present findings demonstrating the potent in vitro effects of BLP on neutrophil (PMN) activation status, function, and capacity to transmigrate an endothelial monolayer. PMNs are the principal effectors of the initial host response to injury or infection and constitute a significant threat to invading bacterial pathogens. The systemic inflammatory response syndrome (SIRS) is characterised by significant host tissue injury mediated, in part, by uncontrolled regulation of PMN cytotoxic activity. We found that BLP-activated human PMN as evidenced by increased CD11b/CD18 (Mac-1) expression. Up-regulation of PMN Mac-1 in response to BLP occurred independently of membrane-bound CD14 (mCD14). A similar up-regulation of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells was observed whilst E-Selectin expression was unaffected. PMN transmigration across a human umbilical vein endothelial cell (HUVEC) monolayer was markedly increased after treating either PMN's or HUVEC independently with BLP. This increased transmigration did not occur as a result of any direct effect of BLP on HUVEC monolayer permeability, assessed objectively using the passage of FITC-labeled Dextran-70. BLP primed PMN for enhanced respiratory burst and superoxide anion production in response to PMA, but did not influence phagocytosis of opsonized Escherichia coli. BLP far exceeds LPS as a gram-negative bacterial wall component, these findings therefore implicate BLP as an additional putative mediator of SIRS arising from gram-negative infection.

Mean Serum Concentration of Vitamin D-binding Protein (Gc Globulin) Is Related to the Gc Phenotype in Women

Immunonephelometry has been reported (1) to be a suitable method for quantification of vitamin D-binding protein (also known as Gc globulin or Gc). We wished to develop such a method and examine the association between the mean serum concentration of Gc in women of known Gc phenotype and the phenotype of Gc. Gc is a 52- to 58-kDa multifunctional plasma protein, synthesized mainly by hepatocytes. Polymorphisms in the Gc gene (codominant alleles) give rise to three major electrophoretic variants of Gc (Gc2, Gc1s, and Gc1f), which differ by amino acid substitutions as well as glycosylation (2)(3). The physiological significance related to the various phenotypes is yet to be discovered. Gc is the major carrier protein of vitamin D and its metabolites in the circulation and is important for preservation of the vitamin (4)(5). Gc also transports components such as fatty acids and endotoxin (6)(7), and it is an important player in the actin scavenging system (8)(9). Gc binds actin released from cells upon injury, and the Gc-actin complexes are rapidly cleared from the circulation, thereby preventing the harmful effects of actin filaments in blood vessels. The resulting decrease in Gc concentration makes Gc usable as a prognostic indicator of survival of patients with significant tissue injury after trauma (10) and among patients with hepatic failure (11). In addition to being a transporter and an actin scavenger protein, Gc may be of importance for bone formation and in the immune system. After in vitro removal of its galactose and sialic acid residues, Gc is converted to a very potent macrophage-activating factor, Gc-MAF (12). Administration of Gc-MAF to osteopetrotic rodents reversed their bone and immunological defects, probably by activating osteoclasts as well as macrophages (13). Finally, together with complement factors C5a and C5a …

Docetaxel Extravasation Causing Significant Delayed Tissue Injury

Purpose. Docetaxel is a relatively new taxane that has not been associated with significant tissue injury after extravasation. We present a case of a patient who had grade 4 tissue toxicity after extravasation of docetaxel infused through a peripheral intravenous site.Case report. A 71-year-old female was being treated for recurrent ovarian cancer with docetaxel and carboplatin. Shortly after the docetaxel infusion began, she experienced docetaxel extravasation into the dorsum of her left hand. The infusion was halted, and then the administration was continued in a peripheral intravenous site in the other upper extremity. Erythema was noted by the patient on the dorsum of her left hand 6 days after infiltration. The following day, the patient noted severe pain, decreased function, and blistering along with increased erythema. The patient presented to the gynecology oncology clinic 11 days after the extravasation injury occurred. Conservative management was undertaken, and over the next 4 weeks the patient had resolution of the skin changes and full return of function.Conclusion. Docetaxel can cause significant delayed tissue injury if extravasation occurs.

Reactive Oxygen Species and Glutathione: Potential for Parenteral Nutrition Supplementation?

Glutathione has been implicated as an important antioxidant in the body's defense against the accumulation of reactive oxygen species (ROS). In critically ill patients, the balance between the production of ROS and the availability of antioxidants may shift to favor proliferation of ROS. This in turn may lead to significant tissue injury. Parenteral nutrition (PN) is a feeding modality often required by critically ill patients. PN solutions do not contain the components needed for endogenous glutathione synthesis and, thus, may reduce antioxidant availability and accentuate ROS damage. Supplementation of PN with nutrients that promote glutathione synthesis may attenuate ROS‐induced cell destruction.

Endoclip: closing the surgical gap

Endoclip: closing the surgical gap