Is a self-inflicted burn part of a repeated self-harm pattern?

Self-inflicted burns (SIB) consistently account for a small proportion of burn injuries. There is a wide spectrum of SIB, from minor burns through to major life threatening burn injuries in suicidal patients who have committed self-immolation. Non-fatal deliberate self-harm (DSH) is a common reason for presenting to hospital. This occurs in many forms including wounding, burning and poisoning to name a few. Such behaviours are commonly repeated, sometimes with increasing severity. DSH is a major risk factor for subsequent suicide. We had observed patterns of repeated self harm behaviours in patients presenting to our centre with SIB. Patterns of repeated DSH in those presenting with self-inflicted burns have not previously been described in the literature. In a five-year period (2008 to 2012) 84 patients presented to our burns centre with SIB. Within this population, 39 patients (46%) were identified on a national database as having been admitted to an acute National Health Service (NHS) trust somewhere in the UK with sequelae of deliberate self-harm. There had been a total of 128 additional hospital admissions. In the majority of cases (85%) another admission preceded the presentation to our service with SIB. Only four out of the 17 SIB patients (24%) who died of their injuries had previous hospital admissions with DSH. This lends weight to the need for thorough holistic assessment of any patient admitted to hospital with sequelae of deliberate self-harm in order to try and provide appropriate support and interventions for these vulnerable individuals to prevent recurrent self-harm or suicide.

Les brûlures auto-infligées ne représentent qu'une faible proportion de ce traumatisme. Il existe un large éventail de ce type de lésions depuis les blessures mineures jusqu'aux brûlures graves chez les patients suicidaires. L'automutilation survient sous de nombreuses formes. Ces comportements sont souvent récidivants, parfois avec sévérité croissante, et représentent un facteur de risque majeur de suicide ultérieur. Nous avons observé des cas de comportements répétés d'automutilation chez nos patients. Dans une période de cinq ans (2008-2012) 84 patients ont été admis dans notre centre avec des brûlures auto-infligées. Dans cette population, 39 patients (46%) ont été identifiés sur une base de données nationale comme ayant été admis dans une Association du Service National de Santé britannique quelque part dans le Royaume-Uni avec des séquelles d'automutilation. Il y avait eu un total de 128 hospitalisations supplémentaires. Dans la majorité des cas (85%) une autre admission précédait l'arrivée dans notre service. Seulement 4 des 17 patients (24%) morts de leurs blessures avaient eu des hospitalisations précédentes pour automutilation. Cela montre la nécessité d'une évaluation globale approfondie de tout patient admis à l'hôpital avec des séquelles d'automutilation, afin d'intervenir par une prise en charge appropriée de ces personnes vulnérables et prévenir l'automutilation ou la récidive de la tentative de suicide.

Chemokine-mediated migration of melanoma cells towards lymphatics--a mechanism contributing to metastasis.

The mechanisms that cause tumors such as melanomas to metastasize into peripheral lymphatic capillaries are poorly defined. Non-mutually-exclusive mechanisms are lymphatic endothelial cell (LEC) chemotaxis and proliferation in response to tumor cells (chemotaxis-lymphangiogenesis hypothesis) or LECs may secrete chemotactic agents that attract cancer cells (chemotactic metastasis hypothesis). Using migration assays, we found evidence supporting both hypotheses. Conditioned medium (CM) from metastatic malignant melanoma (MMM) cell lines attracted LEC migration, consistent with the lymphangiogenesis hypothesis. Conversely, CM from mixed endothelial cells or LECs, but not blood endothelial cells, attracted MMM cells but not non-metastatic melanoma cells, consistent with the chemotactic metastasis hypothesis. MMM cell lines expressed CCR7 receptors for the lymphatic chemokine CCL21 and CCL21 neutralizing antibodies prevented MMM chemotaxis in vitro. To test for chemotactic metastasis in vivo tumor cells were xenotransplanted into nude mice approximately 1 cm from an injected LEC depot. Two different MMM grew directionally towards the LECs, whereas non-metastatic melanomas did not. These observations support the hypothesis that MMM cells grow towards regions of high LEC density owing to chemotactic LEC secretions, including CCL21. This chemotactic metastasis may contribute to the close association between metastasizing tumor cells and peri-tumor lymphatic density and promote lymphatic invasion.

Vascular endothelial growth factor-C (VEGF-C) expression in normal human tissues.

OBJECTIVE: To characterize vascular endothelial growth factor-C (VEGF-C) protein expression in normal human tissues by immunohistochemistry (IHC). VEGF-C is a growth factor for lymphatic endothelial cells. VEGF-C mRNA and protein are expressed in a variety of cancerous tissues, but the localization of VEGF-C protein in many normal human tissues has not been clearly demonstrated to date. We therefore performed an immunohistochemical survey of the distribution of intracellular VEGF-C protein in a range of normal human tissue types. METHODS: Five microm sections were cut from archived human tissues. Sections were dewaxed, rehydrated, and subjected to microwave pretreatment. They were incubated with VEGF-C antibody before detection with biotinylated secondary antibody using 'Elite' avidin-biotin enzyme complex and diaminobenzidine substrate. The primary antibody recognized the C-terminus of the VEGF-C propeptide that is cleaved before secretion and hence only cellular protein was detected. Negative controls used the same concentration of normal goat IgG. RESULTS: Staining manifested as small punctate cytoplasmic granules. Strong expression was observed in large intestine epithelium, and mammary duct epithelium, skeletal and cardiac muscle, thyroid, ovary, and the prostate. Weaker expression was also detected in the hepatocytes close to the terminal hepatic venules of the liver, vascular smooth muscle, and placenta. No expression was consistently detected in spleen or thymus. CONCLUSIONS: Intracellular VEGF-C protein is widely expressed in many normal human adult tissues. Its expression in cancer is not therefore per se indicative of a prolymphangiogenic change. To demonstrate the latter, a quantitative change in expression level is required.

VEGF-C promotes survival in podocytes.

Vascular endothelial growth factor (VEGF)-A is an autocrine survival factor for podocytes, which express two VEGF receptors, VEGF-R1 and VEGF-R3. As VEGF-A is not a known ligand for VEGF-R3, the aim of this investigation was to examine whether VEGF-C, a known ligand for VEGF-R3, served a function in podocyte biology and whether this was VEGF-R3 dependent. VEGF-C protein expression was localized to podocytes in contrast to VEGF-D, which was expressed in parietal epithelial cells. Intracellular calcium ([Ca2+]i) experiments demonstrated that VEGF-C induced a 0.74+/-0.09-fold reduction in [Ca2+]i compared with baseline in human conditionally immortalized podocytes (hCIPs; P<0.05, one sample t-test, n=8). Cytotoxicity experiments revealed that in hCIPs VEGF-C reduced cytotoxicity to 81.4+/-1.9% of serum-starved conditions (P<0.001, paired t-test, n=16), similar to VEGF-A (82.8+/-4.5% of serum-starved conditions, P<0.05, paired t-test). MAZ51 (a VEGF-R3 kinase inhibitor) inhibited the VEGF-C-induced reduction in cytotoxicity (106.2+/-2.1% of serum-starved conditions), whereas MAZ51 by itself had no cytotoxic effects on hCIPs. VEGF-C was also shown to induce a 0.5+/-0.13-fold reduction in levels of MAPK phosphorylation compared with VEGF-A and VEGF-A-Mab treatment (P<0.05, ANOVA, n=4), yet had no effect on Akt phosphorylation. Surprisingly, immunoprecipitation studies detected no VEGF-C-induced autophosphorylation of VEGF-R3 in hCIPs but did so in HMVECs. Moreover, SU-5416, a tyrosine kinase inhibitor, blocked the VEGF-C-induced reduction in cytotoxicity (106+/-2.8% of serum-starved conditions) at concentrations specific for VEGF-R1. Together, these results suggest for the first time that VEGF-C acts in an autocrine manner in cultured podocytes to promote survival, although the receptor or receptor complex activated has yet to be elucidated.

Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro.

Maternal iron deficiency during pregnancy induces anaemia in the developing fetus; however, the severity tends to be less than in the mother. The mechanism underlying this resistance has not been determined. We have measured placental expression of proteins involved in iron transfer in pregnant rats given diets with decreasing levels of iron and examined the effect of iron deficiency on iron transfer across BeWo cell layers, a model for placental iron transfer. Transferrin receptor expression was increased at both mRNA and protein levels. Similarly, expression of the iron-responsive element (IRE)-regulated form of the divalent metal transporter 1 (DMT1) was also increased. In contrast, the non-IRE regulated isoform showed no change in mRNA levels. Protein levels of DMT1 increased significantly. Iron efflux is thought to be mediated by the metal transporter protein, IREG1/ferroportin1/MTP1, and oxidation of Fe(II) to Fe(III) prior to incorporation into fetal transferrin is carried out by the placental copper oxidase. Expression of IREG1 was not altered by iron deficiency, whereas copper oxidase activity was increased. In BeWo cells made iron deficient by treatment with desferrioxamine ('deferioxamine'), iron accumulation from iron-transferrin increased, in parallel with increased expression of the transferrin receptor. At the same time, iron efflux also increased, showing a higher flux of iron from the apical to the basolateral side. The data show that expression of placental proteins of iron transport are up-regulated in maternal iron deficiency, resulting in an increased efficiency of iron flux and a consequent minimization of the severity of fetal anaemia.