Carpal tunnel syndrome in breast cancer survivors with upper extremity lymphedema

Introduction: Lymphedema has long been considered a risk factor for median nerve compression at the wrist and carpal tunnel syndrome (CTS). This association is based on limited and poor quality data. We analyzed the association between lymphedema and CTS. Methods: Breast cancer survivors with upper extremity lymphedema and electrophysiologically confirmed CTS were assessed retrospectively. The severity of lymphedema was graded using the National Institutes of Health Common Terminology Criteria for Adverse Events (CTCAE) v4.03. The severity of CTS was graded in accordance with accepted criteria. Results: Nineteen patients (38 sides) met the criteria for analysis. There was no association between presence of lymphedema and CTS (P = 0.66) or between lymphedema severity and CTS severity (P = 0.79). There were no cases of infection or worsening lymphedema as a result of needle EMG. Conclusions: These findings do not support lymphedema as an etiologic factor in the pathogenesis of CTS. Muscle Nerve 51 : 864–869, 2015     

Granulocyte colony-stimulating factor attenuates delayed tPA-induced hemorrhagic transformation in ischemic stroke rats by enhancing angiogenesis and vasculogenesis

Treatment with tissue plasminogen activator (tPA) beyond the therapeutic time window (>4.5 hours post stroke) may produce hemorrhagic transformation (HT). Strategies that could extend the narrow time window of tPA will benefit a significant number of stroke patients. Male Sprague–Dawley rats underwent middle cerebral artery occlusion (MCAo) and given vehicle, tPA (10 mg/kg), or tPA and granulocyte colony-stimulating factor (G-CSF, 300 μg/kg), at 6 hours after MCAo. Twenty-four hours post treatment, G-CSF+tPA-treated stroke rats displayed 25% improvement in neurological functions and 38.9% reduction of hemorrhage, with Western blots showing 1.9- and 1.2-fold increments in Ang-2 expression in the ischemic cortex and striatum, respectively, and 3-fold increase in phosphorylated endothelial nitric oxide synthase expression in the ipsilateral cortex relative to tPA-treated rats. Immunohistochemistry also showed 2- and 2.8-fold increase in von-Willebrand expression, 3.2- and 2.2-fold increased CD34+ expression, and 4- and 13-fold upregulation of VEGFR-2 expression in the ischemic cortex and striatum, respectively, in G-CSF+tPA-treated stroke rats relative to tPA-treated subjects. Altogether, these findings indicate that G-CSF attenuated delayed tPA-induced HT likely via the enhancement of angiogenesis and vasculogenesis. The use of G-CSF to protect the vasculature may improve the clinical outcome of tPA even outside the currently indicated therapeutic window for ischemic stroke.     

Cancer Immunoediting from Immunosurveillance to Tumor Escape in Microvillus-Formed Niche: A Study of Syngeneic Orthotopic Rat Bladder Cancer Model in Comparison with Human Bladder Cancer

Cancer cells can develop an attenuated immunogenicity and/or create an immunosuppressive microenvironment to prevent tumor eradication by host immune system, the so-called “cancer immunoediting” hypothesis. The aim of the present study was to find evidence for this hypothesis by using a rat orthotopic bladder cancer model. Fisher rats were inoculated with AY-27 cells (a Fisher rat bladder cancer cell line). Cultured cancer cells, rat and human bladder cancer tissues, and publicly available microarray data from human bladder cancer were analyzed by means of bioinformatics and morphology. Results showed that 12 of 24 differentially expressed pathways were concordant in connection to cell cycle and proliferation between rats and humans (both non-muscle-invasive and muscle-invasive tumors) and that 11 of the 24 pathways, including major histocompatibility complex, were related to host immunosurveillance with activations of T cells and natural killer cells in rats. The altered pathways and morphogenesis of this rat model corresponded more closely with those of human muscle-invasive rather than non-muscle-invasive tumors. A unique ultrastructure displaying microvillus-formed niches was found in small areas within the tumor of both rats and humans. These niches were interconnected with desmosomes between cancer cells and without infiltration of lymphocytes. The expression of E-cadherin, selectins, PGP9.5, vascular endothelial growth factor, caspase-3, CD133, Oct-4, nestin, CD3, and CD45RA was lower in the tumor than in the adjacent normal epithelium. We suggest that the microvillus-formed niche that harbors a few implanted cancer cells might be the compartment that prevents the tumor eradication by the host immune system.     

Free insulin growth factor-I and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy

PURPOSE: To investigate the relationship between insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in the vitreous fluid of diabetic patients with proliferative diabetic retinopathy (PDR). DESIGN: Observational case-control study. METHODS: In a prospective study, 37 consecutive diabetic patients with PDR (14 type I and 23 type II diabetes mellitus) in whom a vitrectomy was performed were compared with 21 nondiabetic patients with other conditions requiring vitrectomy (control group). Free IGF-I and VEGF were measured by ELISA. RESULTS: Vitreal levels of both free IGF-1 and VEGF were higher in diabetic patients with PDR than in control subjects (P <.01, and P <.0001, respectively). After adjusting for total intravitreous protein concentration, VEGF (ng/mg of proteins) remained significantly higher in diabetic patients with PDR than in the control group (P <.0001), whereas free IGF-I (ng/mg of proteins) was lower in diabetic patients than in control subjects (P <.0001). The vitreous concentrations of VEGF were higher in patients with active PDR than in patients with quiescent PDR (P <.005), whereas vitreous free IGF-I was not related to PDR activity. Finally, we did not observe a correlation between the vitreal levels of free IGF-I and VEGF. CONCLUSIONS: We conclude that free IGF-I and VEGF are both increased, but not related, within the vitreous fluid of diabetic patients with PDR. In addition, our results support the current concept that VEGF is directly involved in the pathogenesis of PDR, whereas the precise role of free IGF-I remains to be established.