The report of a clinical study of 104 electrical accidents which befell 85 men is divided into two parts.Part I enumerates the different types of accidents as flash burn, Joule burn, arc eye, "held on" shock and "not held" shock, physical shock, and death. These are related to the different voltages involved ranging from 240/415 (medium) voltage to 33 kilovolts. There appeared to be no association between voltage and type of injury and no evidence to suggest that any of the voltages are free from hazard. There were 53 cases of flash burn, affecting mostly the face and extensor surface of the hands and arms. The 16 cases of arc eye caused no serious concern. Of the 15 Joule burns all except one occurred at medium voltages in "held on" accidents, the other being associated with an electric shock at 33 kilovolts. The majority of Joule burns affected the flexor surfaces.Part II of the paper deals with the 43 cases of electric shock (passage of current through the body). Thirty of these cases were "held on" to the circuit by the current. It was found that the longer a victim was held on to the circuit the greater appeared to be his chances of developing heart and chest symptoms suggestive of impending asphyxia, and of losing consciousness. Although about half of these men were released by an external agmncy and others struggled off, a number suddenly became free from the circuit without, they claimed, losing consciousness. This is difficult to explain. Artificial respiration was administered in two cases, one of whom was "held on" and was being asphyxiated. The other case received flash burns only and did not in fact receive an electric shock. PART I: GENERAL REVIEW AND NON-SHOCK CASESElectrical accidents receive little attention in British medical literature. In fact, in the electricity supply industry they account for only 1 % of the total number of accidents but they are the commonest cause of accidental death (Hughes and Corney, 1956). In factories, electrical accidents account for less than 0-5 % of all accidents, but more than 5% of these electrical accidents prove fatal (Emerson, 1961). This paper reports a clinical investigation into a series of electrical accidents; detailed consideration of the cases of electric shock (passage of current through the body) is given in Part II of this paper. MethodThe names of all men in an electricity supply undertaking who had sustained an electrical accident during the preceding three years were obtained. Of the total of 114, 107 were still employed by the undertaking. One man was killed; the remainder were contacted and 84 attended for interview. (The majority of those who were not seen worked in one small area and there is no reason to suppose that the nature of their accidents was any different from the whole.) They were all seen by one investigator and were questioned about the electrical and physical circumstances of the accident, about symptoms, and about subsequent medical history.

Non-Hodgkin's malignant lymphomas (NHML) are malignant lymphoid proliferations which may be of B or T cell type. Thirteen observations of an association between peripheral neuropathy and B type NHML are reported. None of the cases had evidence of meningeal propagation or neurotoxicity from chemotherapy. The NHML were classified according to the Working Formulation and Kiel classifications. The various mechanisms of peripheral neuropathy in these cases were split into four broad groups. Group I consisted of four cases in which the peripheral nerve lesions were directly linked to a propagation of malignant cells into the peripheral nervous system; this was revealed by autopsy and/or nerve biopsy. Malignant B cell proliferation was demonstrated in three out of four of these cases by immunolabelling of the infiltrates. Group II included three patients whose serum contained a monoclonal immunoglobulin (IgM) with antimyelin activity, and two who had pathological IgM deposits in endoneurial connective tissue. Group III comprised two cases. The immune dysfunction of the NHML was responsible for a Guillain-Barré syndrome in one, and for a chronic inflammatory demyelinating polyneuropathy in the other. Group IV included two patients in whom the mechanism of the peripheral neuropathy, although almost certainly directly related to the NHML, could not be determined beyond doubt. The peripheral neuropathy might have been a result of a paraneoplasic process or, possibly, an undetected lymphomatous invasion of nervous tissue. All these cases of clinically diverse peripheral neuropathy, which either occurred before the discovery of the haemopathy or arose as complications of it, are discussed along with similar observations reported in the literature. Immunolabelling of lymphomatous proliferations and nerves is now of considerable value for classifying and indicating the exact aetiology of the peripheral neuropathy. It can also detect pathogenic consequences of any associated monoclonal dysglobulinemia. In any event, a direct link between the peripheral neuropathy and NHML represents an indication for intensification of specific chemotherapy, which in some of our patients led to significant regression of the peripheral neuropathy. Nonetheless, in some cases, the link between peripheral neuropathy and NHML could not be established with certainty. Long-term follow-up is essential in such cases. The present results show the importance of a case by case study of patients with NHML and peripheral neuropathy.

BackgroundNeurotrophin receptors were initially identified in neural cells. They were recently detected in some cancers in association with invasiveness, but the function of these tyrosine kinase receptors was not previously investigated in colorectal cancer (CRC) cells.Methods and FindingsWe report herein that human CRC cell lines synthesize the neural growth factor Brain-derived neurotrophic factor (BDNF) under stress conditions (serum starvation). In parallel, CRC cells expressed high- (TrkB) and low-affinity (p75NTR) receptors at the plasma membrane, whereas TrkA and TrkC, two other high affinity receptors for NGF and NT-3, respectively, were undetectable. We demonstrate that BDNF induced cell proliferation and had an anti-apoptotic effect mediated through TrkB, as assessed by K252a, a Trk pharmacologic inhibitor. It suppressed both cell proliferation and survival of CRC cells that do not express TrkA nor TrkC. In parallel to the increase of BDNF secretion, sortilin, a protein acting as a neurotrophin transporter as well as a co-receptor for p75NTR, was increased in the cytoplasm of primary and metastatic CRC cells, which suggests that sortilin could regulate neurotrophin transport in these cells. However, pro-BDNF, also detected in CRC cells, was co-expressed with p75NTR at the cell membrane and co-localized with sortilin. In contrast to BDNF, exogenous pro-BDNF induced CRC apoptosis, which suggests that a counterbalance mechanism is involved in the control of CRC cell survival, through sortilin as the co-receptor for p75NTR, the high affinity receptor for pro-neurotrophins. Likewise, we show that BDNF and TrkB transcripts (and not p75NTR) are overexpressed in the patients' tumors by comparison with their adjacent normal tissues, notably in advanced stages of CRC.ConclusionTaken together, these results highlight that BDNF and TrkB are essential for CRC cell growth and survival in vitro and in tumors. This autocrine loop could be of major importance to define new targeted therapies.

The transfer of exosomes containing both genetic and protein materials is necessary for the control of the cancer cell microenvironment to promote tumor angiogenesis. The nature and function of proteins found in the exosomal cargo, and the mechanism of their action in membrane transport and related signaling events are not clearly understood. In this study, we demonstrate, in human lung cancer A549 cells, that the exosome release mechanism is closely linked to the multifaceted receptor sortilin (also called neurotensin receptor 3). Sortilin is already known to be important for cancer cell function. Here, we report for the first time its role in the assembly of a tyrosine kinase complex and subsequent exosome release. This new complex (termed the TES complex) is found in exosomes and results in the linkage of the two tyrosine kinase receptors TrkB (also known as NTRK2) and EGFR with sortilin. Using in vitro models, we demonstrate that this sortilin-containing complex exhibits a control on endothelial cells and angiogenesis activation through exosome transfer.