The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use

Erythropoietin (EPO) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties. More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin. This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications. There is clear evidence that EPO effectively influences all wound‐healing phases in a dose‐dependent manner. This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound. The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide (NO) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor (VEGF) in the wound. The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound‐healing problems and ischemia/reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.     

Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter

Leukocyte adhesion deficiency II (LAD II) is a rare congenital disease caused by defective fucosylation leading to immuno-deficiency and psychomotor retardation. We have previously identified the genetic defect of LAD II in a patient whose Golgi GDP-fucose transporter (GFTP) bears a single amino acid exchange that renders this protein nonfunctional but correctly localized to the Golgi. We now report a novel dual defect by which a truncated GFTP causes the disease in a new LAD II patient. We show that the truncation renders this GFTP unable to localize to the Golgi, the compartment where it is required. Furthermore, the missing part of the GFTP can be dissected into 2 regions, one that is needed for Golgi localization and one that is additionally required for the function of the GFTP. We investigated the subcellular localization of all known defective GFTPs allowing us to divide all genetically analyzed LAD II patients into 2 groups, one in which single amino acid exchanges in the GFTP impair its function but not its subcellular localization, and another group with a dual defect in function and Golgi expression of the GFTP due to the absence of 2 important molecular regions.     

Reinterpretation of cross-sectional images in patients with head and neck cancer in the setting of a multidisciplinary cancer center

BACKGROUND AND PURPOSE: Patients referred to tertiary care centers frequently arrive with images obtained at outside institutions; these images require reinterpretation. We assessed the clinical value of reinterpreting cross-sectional imaging studies of patients with head and neck cancer, in the setting of a multidisciplinary cancer center. METHODS: Outside CT and MR images of 136 patients with known or presumed head and neck cancer were reinterpreted by a neuroradiologist. Clinical history and findings on physical examination were available. Reinterpretation was performed before review of outside reports, which were subsequently compared with those generated at the cancer center. Changes in interpretation were noted, and their effects on TNM staging, patient care, and prognosis were assessed. Reliability and statistical significance of rates of change in diagnosis were analyzed with 95% confidence intervals (CIs) and the sign test, respectively. Verification of change in diagnosis was confirmed by pathologic analysis (75%), characteristic radiologic findings (18%), or clinical and imaging follow-up (7%). RESULTS: Change in interpretation occurred in 56 patients (41%) (95% CI: 33-49%, P <.001). Forty-six patients (34%) had a change in T, N, and/or M staging (26-42%, P <.001). Change in T stage occurred in 27 cases (20%) (13-27%, P <.001) (upstaged in 22, downstaged in five), and a change in N stage in 26 cases (19%) (12-26%, P <.001) (upstaged in 20, downstaged in six). Two patients (1.5%) had missed systemic metastases. Three patients with an initial diagnosis of cancer were found to be cancer-free, and six patients had a diagnosis of new second primary cancers that were missed at original interpretation. One patient had a missed middle cerebral artery aneurysm. Changes in image interpretation altered treatment in 55 (98%) of 56 patients and affected prognosis in 53 patients (95%) (P <.001). CONCLUSION: Reinterpretation of cross-sectional images in the setting of a multidisciplinary cancer center has a significant effect on staging, management, and prognosis in patients with head and neck cancer.     

Relating Body Image to Psychological and Sexual Functioning in Child Sexual Abuse Survivors

Cognitive-affective body image variables and their relation to long-term psychological and sexual functioning were investigated in a community sample of 57 female adult child sexual abuse (CSA) survivors and 47 comparison subjects. The Body-Self Relations Questionnaire and the Body Esteem Scale were administered to assess cognitive-affective body image. Group comparisons indicated that, after controlling for actual weight status, survivors evaluated their health more negatively and reported less body esteem regarding their sexual attractiveness than comparison subjects. Body image variables related to health and sexual attractiveness significantly explained variance on symptom measures that reflect the diverse CSA long-term sequelae. Results suggest the need for careful assessment of body image disturbances and the development of effective interventions targeting body image in the treatment of CSA survivors.     

Adrenomedullin reduces mesangial cell number and glomerular inflammation in experimental mesangioproliferative glomerulonephritis

BACKGROUND: Adrenomedullin (ADM) is a vasodilator peptide that is abundantly expressed in the kidney. ADM has antiproliferative effects on glomerular mesangial cells (MC) in vitro. Whether or not treatment with ADM can reduce MC proliferation in vivo [i.e., in mesangioproliferative glomerulonephritis (GN)] is unknown. We tested the hypothesis that ADM substitution reduces MC proliferation in GN. METHODS: GN in rats was induced by injection of an anti-Thy-1.1 antibody. Rats received osmotic minipumps, which continuously delivered rat ADM (500 ng/hour, N = 11), or vehicle (N = 13) from day 3 to day 6 after GN induction. Rats were sacrificed 6 days after induction of GN. On kidney sections, cells staining positive for proliferating cell nuclear antigen, mesangial cells, monocytes, and apoptotic cells were counted. Parameters of inflammation and fibrosis were measured in renal cortex and sieved glomeruli by real-time polymerase chain reaction (PCR). RESULTS: Systolic blood pressure, diuresis, albuminuria, creatinine clearance, microaneurysm formation, and mesangial matrix expansion were not influenced by ADM infusion. However, ADM treatment significantly reduced the number of MC, showed a tendency to reduce total glomerular cell proliferation, and significantly increased apoptosis. ADM-treated GN animals showed significantly less glomerular monocyte infiltration. ADM treatment normalized transforming growth factor (TGF)-beta1 mRNA expression and reduced monocyte chemoattractant protein-1 (MCP-1), osteopontin, plasminogen activator inhibitor-1 (PAI-1), collagen I, and collagen III mRNA expression significantly. CONCLUSION: Exogenous ADM infusion reduces MC number and glomerular monocyte infiltration in the state of mesangial proliferation during acute experimental mesangioproliferative GN. These findings indicate that ADM can influence the course of mesangioproliferative GN.