Pediatric malignancies presenting as a possible infectious disease

<p>Abstract</p> <p>Background</p> <p>The clinical, laboratory, and radiological features of malignancy can overlap with those of infection. The purpose of this study was to determine the findings in children who were initially thought to have an infectious disease but ultimately proved to have a malignancy.</p> <p>Methods</p> <p>The database of patients diagnosed with a malignancy in the Northern Alberta Children's Cancer Program (NACCP) January 1, 1993 to December 31, 2003 was merged with the database of inpatients referred to the infectious diseases service at the Stollery Children's Hospital and charts were reviewed on all patients referred to the infectious diseases consult service prior to the diagnosis of malignancy.</p> <p>Results</p> <p>An infectious diseases consultation for diagnosis was requested in 21 of 561 patients prior to the confirmation of malignancy, and 3 of these 21 patients had both infection and malignancy (leukemia (N = 13), lymphoma (N = 3), rhabdomyosarcoma (N = 1), Langerhan's cell histiocytosis (N = 1), fibrous histicocytosis (N = 1), ependymoma (N = 1), and neuroblastoma (N = 1). The most common reason for infectious diseases consultation was suspected muskuloskeletal infection (N = 9). A palpable or radiographically enlarged spleen was noted in 11 patients (52%). All but 2 patients had abnormal hematologic parameters while an elevated lactate dehydrogenase (LDH) occurred in 10 patients (48%). Delay of diagnosis because of investigation or therapy for an infectious disease occurred in only 2 patients.</p> <p>Conclusion</p> <p>It is not common for treatment of pediatric malignancies to be delayed because infection is thought to be the primary diagnosis. However, pediatric infectious diseases physicians should consider malignancy in the differential diagnosis when they see patients with fever and bone pain, unexplained splenomegaly or abnormal complete blood cell counts. Other clues may include hepatomegaly or elevated LDH.</p

Stochastic light concentration from 3D to 2D reveals ultraweak chemi- and bioluminescence

For countless applications in science and technology, light must be concentrated, and concentration is classically achieved with reflective and refractive elements. However, there is so far no efficient way, with a 2D detector, to detect photons produced inside an extended volume with a broad or isotropic angular distribution. Here, with theory and experiment, we propose to stochastically transform and concentrate a volume into a smaller surface, using a high- albedo Ulbricht cavity and a small exit orifice through cavity walls. A 3D gas of photons produced inside the cavity is transformed with a 50% number efficiency into a 2D Lambertian emitting orifice with maximal radiance and a much smaller size. With high-albedo quartz-powder cavity walls ( P = 99.94%), the orifice area is 1/( 1 - P) approximate to 1600 times smaller than the walls&apos; area. When coupled to a detectivity-optimized photon-counter ( D = 0.015 photon- 1 s1/ 2 cm) the detection limit is 110 photon s- 1 L- 1. Thanks to this unprecedented sensitivity, we could detect the luminescence produced by the non-catalytic disproportionation of hydrogen peroxide in pure water, which has not been observed so far. We could also detect the ultraweak bioluminescence produced by yeast cells at the onset of their growth. Our work opens new perspectives for studying ultraweak luminescence, and the concept of stochastic 3D/2D conjugation should help design novel light detection methods for large samples or diluted emitters

Short- and Long-Term Consequences of Corticotropin-Releasing Factor in Early Development

Corticotropin-releasing factor (CRF) mediates various stress-related responses in adult animals. Little is known about the effects of CRF during early development. Young mammals often vocalize when isolated in novel surroundings. Heightened levels of CRF inhibit vocalizing in isolated rat and guinea pig pups. Still lower levels of CRF may facilitate or permit vocalizing in rat pups. In guinea pigs, CRF appears to move pups from an initial active, to a subsequent passive, stage of behavioral responsiveness. CRF activity prior to birth can also affect the young. Exposing pregnant female rats to stressors during the last trimester of pregnancy alters the morphological and behavioral development of the offspring. Effects of gestational stress can be mimicked by injecting pregnant females with CRF during the last trimester. CRF appears to mediate both short- and long-term responses to stressors during development in rodents

Oxidative Stress and Cancer Heterogeneity Orchestrate NRF2 Roles Relevant for Therapy Response

Oxidative stress and its end-products, such as 4-hydroxynonenal (HNE), initiate activation of the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2)/KEAP1 signaling pathway that plays a crucial role in the maintenance of cellular redox homeostasis. However, an involvement of 4-HNE and NRF2 in processes associated with the initiation of cancer, its progression, and response to therapy includes numerous, highly complex events. They occur through interactions between cancer and stromal cells. These events are dependent on many cell-type specific features. They start with the extent of NRF2 binding to its cytoplasmic repressor, KEAP1, and extend to the permissiveness of chromatin for transcription of ARE-containing genes that are NRF2 targets. This review will explore epigenetic molecular mechanisms of NRF2 transcription through the specific molecular anatomy of its promoter. It will explain the role of NRF2 in cancer stem cells, with respect to cancer therapy resistance. Additionally, it also discusses NRF2 involvement at the cross-roads of communication between tumor associated inflammatory and stromal cells, which is also an important factor involved in the response to therapy

Dietary polyunsaturated fatty acids and heme iron induce oxidative stress biomarkers and a cancer promoting environment in the colon of rats

International audienceThe end products of polyunsaturated fatty acid (PUFA) peroxidation, such as malondialdehyde (MDA), 4-hydroxynonenal (HNE), and isoprostanes (8-iso-PGF2alpha), are widely used as systemic lipid oxidation/oxidative stress biomarkers. However, some of these compounds have also a dietary origin. Thus, replacing dietary saturated fat by PUFAs would improve health but could also increase the formation of such compounds, especially in the case of a pro-oxidant/antioxidant imbalanced diet. Hence, the possible impact of dietary fatty acids and pro-oxidant compounds was studied in rats given diets allowing comparison of the effects of heme iron vs. ferric citrate and of omega-6- vs. omega-3-rich oil on the level of lipid peroxidation/oxidative stress biomarkers. Rats given a heme iron-rich diet without PUFA were used as controls. The results obtained have shown that MDA and the major urinary metabolite of HNE (the mercapturic acid of dihydroxynonane, DHN-MA) were highly dependent on the dietary factors tested, while 8-iso-PGF2alpha was modestly but significantly affected. Intestinal inflammation and tissue fatty acid composition were checked in parallel and could only explain the differences we observed to a limited extent. Thus, the differences in biomarkers were attributed to the formation of lipid oxidation compounds in food or during digestion, their intestinal absorption, and their excretion into urine. Moreover, fecal extracts from the rats fed the heme iron or fish oil diets were highly toxic for immortalized mouse colon cells. Such toxicity can eventually lead to promotion of colorectal carcinogenesis, supporting the epidemiological findings between red meat intake and colorectal cancer risk. Therefore, the analysis of these biomarkers of lipid peroxidation/oxidative stress in urine should be used with caution when dietary factors are not well controlled, while control of their possible dietary intake is needed also because of their pro-inflammatory, toxic, and even cocarcinogenic effects