An outbreak of legionnaires disease caused by long-distance spread from an industrial air scrubber in Sarpsborg, Norway.

BACKGROUND: On 21 May 2005, the Norwegian health authorities were alerted by officials from a local hospital that several recent patients had received the diagnosis of legionnaires disease; all patients resided in 2 neighboring municipalities. We investigated the outbreak to identify the source and to implement control measures. METHODS: We interviewed all surviving case patients and investigated and harvested samples from 23 businesses with cooling towers and other potential infection sources. The locations of the businesses and the patients' residences and movements were mapped. We calculated attack rates and risk ratios among people living within various radii of each potential source. Isolates of Legionella pneumophila were compared using molecular methods. RESULTS: Among 56 case patients, 10 died. The case patients became ill 12-25 May, resided up to 20 km apart, and had not visited places in common. Those living up to 1 km from a particular air scrubber had the highest risk ratio, and only for this source did the risk ratio decrease as the radius widened. Genetically identical L. pneumophila serogroup 1 isolates were recovered from patients and the air scrubber. The air scrubber is an industrial pollution-control device that cleans air for dust particles by spraying with water. The circulating water had a high organic content, pH of 8-9, and temperature of 40 degrees C. The air was expelled at 20 m/s and contained a high amount of aerosolized water. CONCLUSIONS: The high velocity, large drift, and high humidity in the air scrubber may have contributed to the wide spread of Legionella species, probably for >10 km. The risk of Legionella spread from air scrubbers should be assessed.     

The effects of a hearing education program on recreational noise exposure,attitudes and beliefs toward noise,hearing loss,and hearing protector devices in young adults

Excessive recreational noise exposure in young adults might result in noise-induced hearing loss (NIHL) and tinnitus. Inducing behavioral change in young adults is one of the aims of a hearing conservation program (HCP). The goal of the current study was to evaluate the effect of a hearing education program after 6 months in young adults in relation to knowledge regarding their individual hearing status. The results of a questionnaire regarding the weekly equivalent recreational noise exposure, attitudes and beliefs toward noise, and hearing loss and hearing protector devices (HPDs) were compared between both sessions. Seventy-eight young adults completed the questionnaire concerning recreational noise exposure, youth attitude to noise scale (YANS), and beliefs about hearing protection and hearing loss (BAHPHL). Their hearing status was evaluated based on admittance measures, audiometry, transient-evoked otoacoustic emissions (TEOAEs), and distortion-product otoacoustic emissions (DPOAEs). The main analysis consisted of a mixed model analysis of variance with dependent variables of either the noise exposure or the scores on (subscales of) YANS and BAHPHL. The independent variables were hearing status and session one versus session two. There was a significant decrease in recreational noise exposure and several (sub) scales of YANS and BAHPHL between both the sessions. This behavioral change resulted in a more frequent use of HPDs in 12% of the participants. However, the behavioral change was not completely related to the knowledge of young adults’ individual hearing status. To prevent hearing damage in young people, investing in HCPs is necessary, apart from regulating sound levels and its compliance at various leisure-time activities. Also, the long-term effect of HCPs and their most cost-efficient repetition rates should be further investigated.     

Gastric perception thresholds are low and sensory neuropeptide levels high in helicobacter pylori-positive functional dyspepsia

BACKGROUND AND AIMS: In functional dyspepsia (FD) decreased perception levels can be shown on gastric distension. Substance P (SP) and calcitonin gene-related peptide (CGRP) are involved in the sensitization of afferent neuronal pathways due to chronic inflammation. The role of Helicobacter pylori-induced gastric mucosal inflammation in the pathogenesis of FD is controversial. The aim of this study was to assess whether FD patients have altered mucosal concentrations of CGRP and SP, and to investigate whether this is associated with visceral hypersensitivity or H. pylori infection. METHODS: Gastrointestinal symptoms, H. pylori status, perception thresholds at gastric balloon distension, and gastric mucosal concentrations of CGRP and SP were determined in 13 FD patients and 18 healthy controls (HC). RESULTS: In H. pylori-positive FD patients discomfort and pain thresholds on gastric distension were lower compared to other groups. Antral mucosal levels of CGRP and SP were higher in H. pylori-positive subjects. In FD significantly negative correlations between discomfort and pain thresholds and antral mucosal concentrations of CGRP and SP were observed. CONCLUSIONS: In FD low perception thresholds on gastric distension are associated with high levels of CGRP and SP in the antrum, suggesting that sensory neuropeptides are involved in FD pathophysiology.     

BRAF and NRAS Mutations Are Frequent in Nodular Melanoma but Are not Associated with Tumor Cell Proliferation or Patient Survival

Previous studies have shown frequent mutations in the BRAF (V-raf murine sarcoma viral oncogene homolog B1) or NRAS (neuroblastoma RAS viral [V-ras] oncogene homolog) genes in cutaneous melanoma, but the relationship between these alterations and tumor cell proliferation has not been examined in human melanoma. In our study of 51 primary nodular melanomas and 18 paired metastases, we found mutations in BRAF (codon 600, previously denoted 599) in 15 primary tumors (29%) and eight metastases (44%). The figures for NRAS mutations were 27% and 22%, respectively. Mutations in BRAF and NRAS genes were mutually exclusive in all but one case, and were maintained from primary tumors through their metastases. Mutations, however, were not associated with tumor cell proliferation by Ki-67 expression, tumor thickness, microvessel density, or vascular invasion, and there were no differences in patient survival. Although BRAF and NRAS mutations are likely to be important for the initiation and maintenance of some melanomas, other factors might be more significant for proliferation and prognosis in subgroups of aggressive melanoma.     

Direct acute tubular damage contributes to Shigatoxin‐mediated kidney failure

The pathogenesis and therapy of Shigatoxin 2 (Stx2)‐mediated kidney failure remain controversial. Our aim was to test whether, during an infection with Stx2‐producing E. coli (STEC), Stx2 exerts direct effects on renal tubular epithelium and thereby possibly contributes to acute renal failure. Mice represent a suitable model because they, like humans, express the Stx2‐receptor Gb3 in the tubular epithelium but, in contrast to humans, not in glomerular endothelia, and are thus free of glomerular thrombotic microangiopathy (TMA). In wild‐type mice, Stx2 caused acute tubular dysfunction with consequent electrolyte disturbance, which was most likely the cause of death. Tubule‐specific depletion of Gb3 protected the mice from acute renal failure. In vitro, Stx2 induced secretion of proinflammatory cytokines and apoptosis in human tubular epithelial cells, thus implicating a direct effect of Stx2 on the tubular epithelium. To correlate these results to human disease, kidney biopsies and outcome were analysed in patients with Stx2‐associated kidney failure (n = 11, aged 22–44 years). The majority of kidney biopsies showed different stages of an ongoing TMA; however, no glomerular complement activation could be demonstrated. All biopsies, including those without TMA, showed severe acute tubular damage. Due to these findings, patients were treated with supportive therapy without complement‐inhibiting antibodies (eculizumab) or immunoadsorption. Despite the severity of the initial disease [creatinine 6.34 (1.31–17.60) mg/dl, lactate dehydrogenase 1944 (753–2792) U/l, platelets 33 (19–124)/nl and haemoglobin 6.2 (5.2–7.8) g/dl; median (range)], all patients were discharged after 33 (range 19–43) days with no neurological symptoms and no dialysis requirement [creatinine 1.39 (range 0.84–2.86) mg/dl]. The creatinine decreased further to 0.90 (range 0.66–1.27) mg/dl after 24 months. Based on these data, one may surmise that acute tubular damage represents a separate pathophysiological mechanism, importantly contributing to Stx2‐mediated acute kidney failure. Specifically in young adults, an excellent outcome can be achieved by supportive therapy only. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Cannabis Use and Deliberate Self-Harm in Adolescence: A Comparative Analysis of Associations in England and Norway

The objective of this study was to test hypotheses on causality and selection regarding associations between cannabis use and deliberate self-harm (DSH) among adolescents. School surveys were conducted among 9,800 adolescents in England and Norway applying identical measures on deliberate self-harm, suicidal thoughts, cannabis use, and various potential confounders. Cannabis use was more prevalent in England than in Norway. It was associated with DHS, suicidal thoughts and various risk factors for DSH. However, these associations were stronger in Norway than in England. The adjusted associations between cannabis use and suicidal thoughts were non-significant in both countries. The adjusted cannabis–DSH association was non-significant in England but significant in Norway. Elevated risk of DSH in adolescent cannabis users seems to be mainly due to selection mechanisms. Thus the association is not likely to be direct but due to other shared contributory factors.     

CD34 marks angiogenic tip cells in human vascular endothelial cell cultures

The functional shift of quiescent endothelial cells into tip cells that migrate and stalk cells that proliferate is a key event during sprouting angiogenesis. We previously showed that the sialomucin CD34 is expressed in a small subset of cultured endothelial cells and that these cells extend filopodia: a hallmark of tip cells in vivo. In the present study, we characterized endothelial cells expressing CD34 in endothelial monolayers in vitro. We found that CD34-positive human umbilical vein endothelial cells show low proliferation activity and increased mRNA expression of all known tip cell markers, as compared to CD34-negative cells. Genome-wide mRNA profiling analysis of CD34-positive endothelial cells demonstrated enrichment for biological functions related to angiogenesis and migration, whereas CD34-negative cells were enriched for functions related to proliferation. In addition, we found an increase or decrease of CD34-positive cells in vitro upon exposure to stimuli that enhance or limit the number of tip cells in vivo, respectively. Our findings suggest cells with virtually all known properties of tip cells are present in vascular endothelial cell cultures and that they can be isolated based on expression of CD34. This novel strategy may open alternative avenues for future studies of molecular processes and functions in tip cells in angiogenesis.