AlphaV beta3 (αvβ3) integrin inhibition reduces leukocyte–endothelium interaction in a pressure-induced reperfusion model

The leukocyte-endothelium interaction is known to contribute to reperfusion injury, which is considered to participate in the pathophysiology of pressure ulcers, and integrin alphaV beta3 (alphavbeta3) has been shown to mediate the processes of cellular adhesion in various types of cells. This study aims to clarify leukocyte behavior in our original microcirculatory pressure-induced reperfusion model, which can visualize the microcirculation in vivo. We also estimated the effect of alphavbeta3 integrin inhibition on the reduction of the leukocyte-endothelium interaction. Mice with dorsal skinfold chambers were divided into three groups: the baseline group (n=6), in which animals received no compression; the compression-reperfusion group (n=6), in which animals underwent 2-hour compression of the dorsal skin, followed by release, and the inhibitor-treated group (n=7), in which an alphavbeta3 inhibitor, CP4715, was administered in addition to the compression-release procedure. Staining with rhodamine 6G quantitatively visualized leukocyte behavior under the intravital fluorescent microscope. Compression-reperfusion induced a significant increase in rolling, sticking, and extravasation of the leukocytes. Treatment with the inhibitor strikingly reduced leukocyte sticking and extravasation. The present experiment has provided evidence that alphavbeta3 inhibition reduces leukocyte-endothelium interaction in our original pressure-induced reperfusion model.     

A skin abscess model for teaching incision and drainage procedures

Background  

Skin and soft tissue infections are increasingly prevalent clinical problems, and it is important for health care practitioners to be well trained in how to treat skin abscesses. A realistic model of abscess incision and drainage will allow trainees to learn and practice this basic physician procedure.     

Raf-1 kinase,epidermal growth factor receptors,and mutant ras proteins in colonic carcinomas

Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr).     

Analysis of ischemia-reperfusion injury in a microcirculatory model of pressure ulcers

The aim of this study was to establish a pressure ulcer model that visualizes the microcirculation, and to examine the participation of ischemia-reperfusion injury in the pathophysiology of pressure ulcers. An original system composed of a new skin fold chamber and compression device allowed loading quantitative vertical stress to the skin. An intravital microscopic technique enabled direct visualization of the microcirculation in the physiological condition and in response to pressure application. To estimate the effect of ischemia-reperfusion injury, animals were divided into two groups: the compression-release group (n = 8), in which the animals received four cycles of compression-release which consisted of 2 hours of compression followed by 1 hour of pressure release; and the compression alone group (n = 8) in which the animals underwent continuous compression for 8 hours. Functional capillary density was quantified before the compression procedure and on day 1 (35 hours) after the first evaluation. The cyclic compression-release procedure significantly decreased functional capillary density as compared to continuous compression, indicating that in our experimental setting repetition of ischemia-reperfusion cycle more severely damaged the microcirculation than single prolonged ischemic insult. This finding supports the significant contribution of ischemia-reperfusion injury to the pathophysiology of pressure ulcers at the level of dynamic in vivo microcirculation.     

Corpus callosum: interactive effects of infantile handling and testosterone in the rat

Previous research found that the corpus callosum of male rats is larger than that of females; handling rats in infancy enhances this sex difference; and female rat pups, when handled in infancy and given 1 injection of testosterone propionate (TP) on Day 4 of life, will have callosa as large as those of males. In 2 experiments, male pups were castrated on Day 1 or received sham surgery; female pups were injected with TP on Day 4 or received an oil injection. Litters were handled or nonhandled. The previous finding that females, when handled and given TP in infancy, have a larger callosum was confirmed; however, a TP effect when administered to nonhandled females was not found. Because handling is known to cause a corticosterone release, these findings were interpreted as evidence of a developmental interaction between adrenal and gonadal hormones at the cortical level.     

Bilateral transpedicular decompression and Harrington rod stabilization in the management of severe thoracolumbar burst fractures.

Fifty-eight patients with severe thoracolumbar burst fractures were treated with bilateral transpedicular decompression, Harrington rod instrumentation, and spine fusion. Spinal realignment and stabilization was achieved by contoured dual Harrington distraction rods supplemented by segmental sublaminal wiring. Posterior element fractures were noted in 25 patients, 9 of whom had associated dural tears. Computed tomography was performed to assess the cross-sectional area of the spinal canal before surgery and after decompression. Patients at initial evaluation averaged greater than 67% spinal canal compromise. After surgery, successful decompression was accomplished in 57 patients. One patient required staged, anterior thoracoabdominal decompression and fibula strut grafting. At follow-up (average, 43 months; range, 25-70 months), neurologic improvement was found in 77% of the patients who initially presented with neurologic deficits. Thirty-four of 40 patients with incomplete paraplegia improved one or more subgroups on the Frankel scale. A solid fusion was attained in all 58 patients. No patient had a significant residual kyphotic deformity. Single-stage bilateral transpedicular decompression and dual Harrington rod instrumentation reliably provides decompression of the spinal canal and restores spinal alignment. The procedure allows early mobilization and provides an environment for solid fusion and maximum neurologic return.     

Responsiveness of the cerebral circulation to acute alterations in mean arterial pressure during the administration of propofol

The responsiveness of the cerebral circulation to acute increases in mean arterial pressure was studied before and during the administration of propofol 3, 6, or 12 mg/kg/h in the anaesthetised baboon. Although mean arterial pressure increased significantly on each occasion, there were no significant changes in cerebral blood flow. This indicates that the physiological responsiveness of the cerebral circulation to alterations in mean arterial pressure was preserved during the administration of propofol in the concentrations studied.     

Immunotopographic assessment of lymphoid and plasma cell malignancies in the bone marrow

To determine the utility of tissue section immunochemistry in the evaluation of bone marrow involved by lymphoid and plasma cell malignancies, snap-frozen, undecalcified bone marrow core and aspirate samples from 23 patients with these disorders were studied with a battery of monoclonal antibodies. With techniques that preserve architecture, difficult diagnostic cases characterized by core but not aspirate involvement, or the reverse, were resolved. By means of an extensive battery of monoclonal antibodies applied to serial sections, complex tumor cell phenotypes were established in all 23 cases. In addition to the identification of straightforward monoclonal surface immunoglobulin expression in small cleaved cell lymphomas (four cases), the battery approach added immunologic certainty in malignancies with unusual or difficult phenotypes: peripheral T-cell lymphomas with idiosyncratic antigen expression, and chronic lymphocytic leukemias and small cell lymphomas with faint surface immunoglobulin expression (four cases). For the chronic lymphocytic leukemias and the small cell lymphomas, the combined IgD+, B2+, B1+, Ia+, Leu-1+ phenotype taken as a whole had greater utility than any isolated marker. The acute lymphocytic leukemias and the myelomas studied demonstrate the wide range of B-cell antigens that must be detected to account for the variety of B-cell neoplasms encountered. Additionally, the previously undescribed phenotypic subset of CALLA+ myelomas, which is of prognostic relevance, was identified. Marrow frozen section immunotyping is a major asset in the evaluation of patients with lymphoma, leukemia, and myeloma when special care is accorded to tissue handling and to treatment of endogenous peroxidase/pseudoperoxidase and interstitial immunoglobulin.