A Novel Medical Treatment of Cushing's Due to Ectopic ACTH in a Patient With Neurofibromatosis Type 1

A 64-year-old male presented with neurofibromatosis 1 and Cushing's syndrome. Clinically he was over weight, depressed with extensive skin bruising and hypertension. His 24 hours urinary metanephrines, urinary 5HIAA, gut peptides and chromgranin levels were normal. His renal function and renal MRI scan was also normal. His cortisol failed to suppress on overnight dexamethsone suppression test. His low dose dexamethasone suppression with CRH stimulation showed failure of suppression of cortisol to < 50 nmol/L and ACTH was measurable at 10 ng/L on day 3. There was no response of ACTH or cortisol to CRH stimulation. His ACTH precursors were high at 126 pmol/L consistent with defective pro-opiomelanocortin (POMC) processing suggesting an ectopic source of ACTH production. The MRI scan of his pituitary and CT scan of the adrenal glands was normal. His octreotide scan was negative. The source of his ectopic ACTH was most likely a large retroperitoneal plexiform neurofibroma seen on CT abdomen that had undergone malignant peripheral nerve sheath tumour transformation on histology. He was a poor surgical risk for tumour debulking procedure. In view of the available literature and role of c-kit signalling in neurofibromatosis, he was treated with Imitinib. Four months after the treatment his Cushings had resolved on biochemical testing. After a year his plexiform neurofibroma has not increased in size. To our knowledge, this is the first case of NF1 associated with clinical and biochemical features of Cushing's secondary to ectopic ACTH due to MPNST in a plexiform neurofibroma and its resolution on treatment with imatinib

New treatments for advanced cancer: an approach to prioritization

The allocation of funding for new anticancer treatments within the UK has not kept pace with demand. Clinicians find themselves restricted in the use of licensed drugs which they feel are in the best interests of individual patients. Against this, health authorities have a duty to ensure that scarce resources are used equitably to meet the needs of the local population as a whole. Differential levels of funding for new treatments across the country have led to concerns about rationing by postcode. This paper outlines an approach to the prioritization of new treatment for advanced cancer developed jointly by clinicians and health authorities in South London. The approach involves evidence reviews and consensus meetings. Existing and new treatments are rated on a four-point ‘relative effectiveness scale’, which takes account of the impact of the treatment on quality of life and on survival. The strength of evidence supporting each effectiveness rating is also classified. Health Authorities have used these ratings to determine overall funding levels, while leaving decisions on individual patients to the relevant Trusts. © 2000 Cancer Research Campaig

DFM synthesis approach based on product-process interface modelling. Application to the peen forming process.

Engineering design approach are curently CAD-centred design process. Manufacturing information is selected and assessed very late in the design process and above all as a reactive task instead of being proactive to lead the design choices. DFM appraoches are therefore assesment methods that compare several design alternatives and not real design approaches at all. Main added value of this research work concerns the use of a product-process interface model to jointly manage both the product and the manufacturing data in a proactive DFM way. The DFM synthesis approach and the interface model are presented via the description of the DFM software platform

Universal relationship between the penetration depth and the normal-state conductivity in YBaCuO

The absolute values of the conductivity in the normal state sigma_n and of the low temperature penetration depths lambda(0) were measured for a number of different samples of the YBaCuO family. We found a striking correlation between sigma_n and 1/lambda^2, regardless of doping, oxygen reduction or defects, thus providing a simple method to predict the superconducting penetration depth and to have an estimate of the sample quality by measuring the normal-state conductivity.Comment: 7 pages, 1 figure, Europhys. Lett., accepte

DFM synthesis approach based on product-process interface modelling. Application to the peen forming process.

International audienceEngineering design approach are curently CAD-centred design process. Manufacturing information is selected and assessed very late in the design process and above all as a reactive task instead of being proactive to lead the design choices. DFM appraoches are therefore assesment methods that compare several design alternatives and not real design approaches at all. Main added value of this research work concerns the use of a product-process interface model to jointly manage both the product and the manufacturing data in a proactive DFM way. The DFM synthesis approach and the interface model are presented via the description of the DFM software platform

Bound States and Critical Behavior of the Yukawa Potential

We investigate the bound states of the Yukawa potential $V(r)=-\lambda \exp(-\alpha r)/ r$, using different algorithms: solving the Schr\"odinger equation numerically and our Monte Carlo Hamiltonian approach. There is a critical $\alpha=\alpha_C$, above which no bound state exists. We study the relation between $\alpha_C$ and $\lambda$ for various angular momentum quantum number $l$, and find in atomic units, $\alpha_{C}(l)= \lambda [A_{1} \exp(-l/ B_{1})+ A_{2} \exp(-l/ B_{2})]$, with $A_1=1.020(18)$, $B_1=0.443(14)$, $A_2=0.170(17)$, and $B_2=2.490(180)$.Comment: 15 pages, 12 figures, 5 tables. Version to appear in Sciences in China

Dynamic functional contribution of the water channel AQP5 to the water permeability of peripheral lens fiber cells

Although the functionality of the lens water channels aquaporin 1 (AQP1; epithelium) and AQP0 (fiber cells) is well established, less is known about the role of AQP5 in the lens. Since in other tissues AQP5 functions as a regulated water channel with a water permeability (PH2O) some 20 times higher than AQP0, AQP5 could function to modulate PH2O in lens fiber cells. To test this possibility, a fluorescence dye dilution assay was used to calculate the relative PH2O of epithelial cells and fiber membrane vesicles isolated from either the mouse or rat lens, in the absence and presence of HgCl2, an inhibitor of AQP1 and AQP5. Immunolabeling of lens sections and fiber membrane vesicles from mouse and rat lenses revealed differences in the subcellular distributions of AQP5 in the outer cortex between species, with AQP5 being predominantly membranous in the mouse but predominantly cytoplasmic in the rat. In contrast, AQP0 labeling was always membranous in both species. This species-specific heterogeneity in AQP5 membrane localization was mirrored in measurements of PH2O, with only fiber membrane vesicles isolated from the mouse lens, exhibiting a significant Hg2+-sensitive contribution to PH2O. When rat lenses were first organ cultured, immunolabeling revealed an insertion of AQP5 into cortical fiber cells, and a significant increase in Hg2+-sensitive PH2O was detected in membrane vesicles. Our results show that AQP5 forms functional water channels in the rodent lens, and they suggest that dynamic membrane insertion of AQP5 may regulate water fluxes in the lens by modulating PH2O in the outer cortex