Management of acute hypercortisolism

An occasional patient with Cushing's syndrome may require urgent management primarily because the chronic ravages of hypercortisolism have caused the patient to be in a precarious metabolic condition. The side effects of prolonged excess corticosteroids increase the risk of operations in such patients and must be considered in overall management. Among the many effects of hypercortisolism to be considered are hypertension, diabetes, ocular hypertension, myopathies, dermatologic changes including skin infection, pancreatitis, osteoporosis, pathological fractures, peptic ulcers, renal calculi, coagulopathies, hypokalemia, poor wound healing, and increased susceptibility to infection. The most effective way to avert these complications is by earlier diagnosis and definitive treatment of Cushing's syndrome. The present report includes a review of the etiology and diagnosis of Cushing's syndrome and the management of problems associated with hypercortisolism . Il est possible qu'un malade atteint de maladie de Cushing ait besoin d'être traité sans attente en raisons de troubles métaboliques sévères dus aux effets nocifs de l'hypercortisolisme chronique qui augmentent les risques opératoires et doivent être pris en considération avant tout traitement. Il en est ainsi de l'hypertension, du diabète, de l'hypertension intra-oculaire, des lésions dermiques comprenant l'infection cutanée, la pancréatite, l'ostéoporose, les fractures pathologiques, l'ulcère peptique, les calculs rénaux, les coagulopathies, l'hypokaliémie, la lenteur du processus de cicatrisation et l'augmentation de la suceptibilité à l'infection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41309/1/268_2005_Article_BF01655367.pd

Mechanism involved in trichloroethylene-induced liver cancer: Importance to environmental cleanup. 1998 annual progress report

'The objective of this project is to develop critical data for changing risk-based clean-up standards for trichloroethylene (TCE). The project is organized around two interrelated tasks: Task 1 addresses the tumorigenic and dosimetry issues for the metabolites of TCE that produce liver cancer in mice, dichloroacetate (DCA) and trichloroacetate (TCA). Early work had suggested that TCA was primarily responsible for TCE-induced liver tumors, but several, more mechanistic observations suggest that DCA may play a prominent role. This task is aimed at determining the basis for the selection hypothesis and seeks to prove that this mode of action is responsible for TCE-induced tumors. This project will supply the basic dose-response data from which low-dose extrapolations would be made. Task 2 seeks specific evidence that TCA and DCA are capable of promoting the growth of spontaneously initiated cells from mouse liver, in vitro. The data provide the clearest evidence that both metabolites act by a mechanism of selection rather than mutation. These data are necessary to select between a linear (i.e. no threshold) and non-linear low-dose extrapolation model. As of May of 1998, this research has identified two plausible modes of action by which TCE produces liver tumors in mice. These modes of action do not require the compounds to be mutagenic. The bulk of the experimental evidence suggests that neither TCE nor the two hepatocarcinogenic metabolites of TCE are mutagenic. The results from the colony formation assay clearly establish that both of these metabolites cause colony growth from initiated cells that occur spontaneously in the liver of B 6 C 3 F 1 mice, although the phenotypes of the colonies differ in the same manner as tumors differ, in vivo. In the case of DCA, a second mechanism may occur at a lower dose involving the release of insulin. This observation is timely as it was recently reported that occupational exposures to trichloroethylene results in 2 to 4-fold elevations in serum insulin concentrations, as well. The increases in insulin have not been shown responsible for the induction of liver tumors. Therefore, this problem is a subject of a proposal to the Office of Biological and Environmental Research Low-Dose Initiative. However, even if this is demonstrated to be the most sensitive mechanism for liver tumor induction, it is unlikely to contribute to induction of cancer at lower doses, since this involves modification of normal endocrine function. As doses are decreased to levels that do not induce increase in serum insulin level, there should be no risk from this metabolite either. Therefore, there is clearly a rational basis for considering a margin of exposure for low dose extrapolation of liver cancer risks for TCE.

Report on the Brauer-Thrall conjectures: Rojter's theorem and the theorem of Nazarova and Rojter (on algorithms for solving vectorspace problems. I)

Ringel CM. Report on the Brauer-Thrall conjectures: Rojter's theorem and the theorem of Nazarova and Rojter (on algorithms for solving vectorspace problems. I). In: Dlab V, Gabriel P, eds. Representation Theory I. Proceedings of the Workshop on the Present Trends in Representation Theory, Ottawa, Carleton University, August 13-18, 1979: No. 1. Lecture notes in mathematics. Vol 831. Berlin, Heidelberg: Springer; 1980: 104-136

Evolution of host resistance: looking for coevolutionary hotspots at small spatial scales

Natural plant populations are often found to be extremely diverse in their resistance to pathogens. While the potential of pathogens in driving the evolution of resistance in hosts has been widely recognized, empirical evidence linking disease dynamics to host population genetic structure has remained scarce. Here I show that current coevolutionary selection for resistance can be divergent even on a very fine spatial scale. In a natural plant–pathogen metapopulation, disease occurrence patterns were highly aggregated over space and time within host populations. A laboratory inoculation experiment showed higher resistance within areas of the host populations where encounter rates with the pathogen have been high. Higher resistance to sympatric than to allopatric strains of the pathogen suggests that this change has taken place as a response to local selection. These results constitute evidence of adaptive microevolution of resistance resulting from disease epidemics in natural plant–pathogen associations, and highlight the importance of finding the relevant scale at which to address questions of current coevolutionary selection