A devil of a transmissible cancer

Devil facial tumor disease (DFTD) encompasses two independent transmissible cancers that have killed the majority of Tasmanian devils. The cancer cells are derived from Schwann cells and are spread between devils during biting, a common behavior during the mating season. The Centers for Disease Control and Prevention (CDC) defines a parasite as "An organism that lives on or in a host organism and gets its food from, or at, the expense of its host." Most cancers, including DFTD, live within a host organism and derive resources from its host, and consequently have parasitic-like features. Devil facial tumor disease is a transmissible cancer and, therefore, DFTD shares one additional feature common to most parasites. Through direct contact between devils, DFTD has spread throughout the devil population. However, unlike many parasites, the DFTD cancer cells have a simple lifecycle and do not have either independent, vector-borne, or quiescent phases. To facilitate a description of devil facial tumor disease, this review uses life cycles of parasites as an analogy

RAMESES publication standards: realist syntheses

PMCID: PMC3558331This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Adipose tissue levels of organochlorine pesticides and polychlorinated biphenyls and risk of non-Hodgkin's lymphoma.

In this nested case-control study we examined the relationship between non-Hodgkin's lymphoma (NHL) and organochlorine pesticide exposure. We used a data set originally collected between 1969 and 1983 in the U.S. Environmental Protection Agency National Human Adipose Tissue Survey. Adipose samples were randomly collected from cadavers and surgical patients, and levels of organochlorine pesticide residues were determined. From the original study population, 175 NHL cases were identified and matched to 481 controls; 173 controls were selected from accident victims, and 308 from cases with a diagnosis of myocardial infarction. Cases and controls were mainly from cadavers (> 96%) and were matched on sex, age, region of residence within the United States, and race/ethnicity. Conditional logistic regression showed the organochlorine pesticide residue heptachlor epoxide to be significantly associated with NHL [compared with the lowest quartile: third quartile odds ratio (OR) = 1.82, 95% confidence interval (CI), 1.01-3.28; fourth quartile OR = 3.41, 95% CI, 1.89-6.16]. The highest quartile level of dieldrin was also associated with elevated NHL risk (OR = 2.70; 95% CI, 1.58-4.61), as were higher levels of oxychlordane, p,p'-DDE [p,p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], and ss-benzene hexachloride (ORs = 1.79, 1.99, and 2.47, respectively). The p-values for trends for these associations were significant. In models containing pairs of pesticides, only heptachlor epoxide and dieldrin remained significantly associated with risk of NHL. Limitations of this study include collection of samples after diagnosis and a lack of information on variables affecting organochlorine levels such as diet, occupation, and body mass index. Given the persistence of pesticides in the environment, these findings are still relevant today

Synergistic interaction of hypertension and diabetes in promoting kidney injury and the role of endoplasmic reticulum stress

Diabetes mellitus and hypertension are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed interactions of hypertension and diabetes mellitus in causing kidney dysfunction and injury and the role of endoplasmic reticulum (ER) stress. Hypertension was induced by aorta constriction (AC) between the renal arteries in 6-month-old male Goto-Kakizaki (GK) type 2 diabetic and control Wistar rats. Fasting plasma glucose averaged 162±11 and 87±2 mg/dL in GK and Wistar rats, respectively. AC produced hypertension in the right kidney (above AC) and near normal blood pressure in the left kidney (below AC), with both kidneys exposed to the same levels of glucose, circulating hormones, and neural influences. After 8 weeks of AC, blood pressure above the AC (and in the right kidney) increased from 109±1 to 152±5 mm Hg in GK rats and from 106±4 to 141±5 mm Hg in Wistar rats. The diabetic-hypertensive right kidneys in GK-AC rats had much greater increases in albumin excretion and histological injury compared with left kidneys (diabetes mellitus only) of GK rats or right kidneys (hypertension only) of Wistar-AC rats. Marked increases in ER stress and oxidative stress indicators were observed in diabetic-hypertensive kidneys of GK-AC rats. Inhibition of ER stress with tauroursodeoxycholic acid for 6 weeks reduced blood pressure (135±4 versus 151±4 mm Hg), albumin excretion, ER and oxidative stress, and glomerular injury, while increasing glomerular filtration rate in hypertensive-diabetic kidneys. These results suggest that diabetes mellitus and hypertension interact synergistically to promote kidney dysfunction and injury via ER stress

Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice

Patients with bi-allelic loss of function mutations in the voltage-gated sodium channel Nav1.7 present with congenital insensitivity to pain (CIP), whilst low threshold mechanosensation is reportedly normal. Using psychophysics (n = 6 CIP participants and n = 86 healthy controls) and facial EMG (n = 3 CIP participants and n = 8 healthy controls) we have found that these patients also have abnormalities in the encoding of affective touch which is mediated by the specialised afferents; C-low threshold mechanoreceptors (C-LTMRs). In the mouse we found that C-LTMRs express high levels of Nav1.7. Genetic loss or selective pharmacological inhibition of Nav1.7 in C-LTMRs resulted in a significant reduction in the total sodium current density, an increased mechanical threshold and reduced sensitivity to non-noxious cooling. The behavioural consequence of loss of Nav1.7 in C-LTMRs in mice was an elevation in the von Frey mechanical threshold and less sensitivity to cooling on a thermal gradient. Nav1.7 is therefore not only essential for normal pain perception but also for normal C-LTMR function, cool sensitivity and affective touch

Head CT is of limited diagnostic value in critically ill patients who remain unresponsive after discontinuation of sedation

<p>Abstract</p> <p>Background</p> <p>Prolonged sedation is common in mechanically ventilated patients and is associated with increased morbidity and mortality. We sought to determine the diagnostic value of head computed tomography (CT) in mechanically ventilated patients who remain unresponsive after discontinuation of sedation.</p> <p>Methods</p> <p>A retrospective review of adult (age >18 years of age) patients consecutively admitted to the medical intensive care unit of a tertiary care medical center. Patients requiring mechanical ventilation for management of respiratory failure for longer than 72 hours were included in the study group. A group that did not have difficulty with awakening was included as a control.</p> <p>Results</p> <p>The median time after sedation was discontinued until a head CT was performed was 2 days (interquartile range 1.375–2 days). Majority (80%) of patients underwent head CT evaluation within the first 48 hours after discontinuation of sedation. Head CT was non-diagnostic in all but one patient who had a small subarachnoid hemorrhage. Twenty-five patients (60%) had a normal head CT. Head CT findings did not alter the management of any of the patients. The control group was similar to the experimental group with respect to demographics, etiology of respiratory failure and type of sedation used. However, while 37% of subjects in the control group had daily interruption of sedation, only 19% in the patient group had daily interruption of sedation (p < 0.05).</p> <p>Conclusion</p> <p>In patients on mechanical ventilation for at least 72 hours and who remain unresponsive after sedative discontinuation and with a non-focal neurologic examination, head CT is performed early and is of very limited diagnostic utility. Routine use of daily interruption of sedation is used in a minority of patients outside of a clinical trial setting though it may decrease the frequency of unresponsiveness from prolonged sedation and the need for head CT in patients mechanically ventilated for a prolonged period.</p

Clinical trials update of the European Organization for Research and Treatment of Cancer Breast Cancer Group

The present clinical trial update consists of a review of two of eight current studies (the 10981-22023 AMAROS trial and the 10994 p53 trial) of the European Organization for Research and Treatment of Cancer Breast Cancer Group, as well as a preview of the MIND-ACT trial. The AMAROS trial is designed to prove equivalent local/regional control for patients with proven axillary lymph node metastasis by sentinel node biopsy if treated with axillary radiotherapy instead of axillary lymph node dissection, with reduced morbidity. The p53 trial started to assess the potential predictive value of p53 using a functional assay in yeast in patients with locally advanced/inflammatory or large operable breast cancer prospectively randomised to a taxane regimen versus a nontaxane regimen