Supportive care including growth factors in myelodysplastic syndromes

In spite of recent advances in the treatment of myelodysplastic syndromes (MDS), supportive care remains a very important part of the therapy. Red blood cells transfusions are the most important component of this supportive care. They transiently relieve anemia symptoms and alleviate their effects on quality of life and daily functioning. Platelet transfusion therapy is less frequently needed, at least in low-risk MDS. Dealing with an increased risk of infections linked to neutropenia, mainly by broad spectrum antibiotics, is also needed, more often in advanced stages of [dict: MDS] or when the MDS evolves to acute myeloid leukemia. Chronic red blood cell transfusions expose patients to various side-effects, including blood components intolerance reactions and alloimmunization risks, but also increased frequency of iron overload, a more significant problem in low-risk heavily transfused MDS patients, who have prolonged life expectancy. The use of growth factors is becoming a more and more important part of current supportive care. High-dose erythropoietin is able to reduce or suppress red blood cell transfusions needs in selected subgroups of MDS. The short-term use of granulocyte colony-stimulating factor is also often proposed in infections, although not formally established by prospective trials. Although trials of growth factors with thrombopoeitic activity have been performed with interleukin 11 and are underway with thrombopoeitin, none of them are available for routine use.     

Transmembrane peptides as inhibitors of ErbB receptor signaling

Receptor tyrosine kinases have a single transmembrane (TM) segment that is usually assumed to play a passive role in ligand-induced dimerization and activation of the receptor. However, mutations within some of these receptors, and recent studies with the epidermal growth factor (EGF) and ErbB2 receptors have indicated that interactions between TM domains do contribute to stabilization of ligand-independent and/or ligand-induced receptor dimerization and activation. One consequence of the importance of these interactions is that short hydrophobic peptides corresponding to these domains should act as specific inhibitors. To test this hypothesis, we constructed expression vectors encoding short fusion peptides encompassing native or mutated TM domains of the EGF, ErbB2, and insulin receptors. In human cell lines overexpressing the wild-type EGF receptor or ErbB2, we observed that the peptides are expressed at the cell surface and that they inhibit specifically the autophosphorylation and signaling pathway of their cognate receptor. Identical results were obtained with peptides chemically synthesized. Mechanism of action involves inhibition of dimerization of the receptors as shown by the lack of effects of mutant nondimerizing sequences, completed by density centrifugation and covalent cross-linking experiments. Our findings stress the role of TM domain interactions in ErbB receptor function, and possibly for other single-spanning membrane proteins.     

Apport du TDM en imagerie multimodalité : le point de vue du physicien médical

The recent introduction of hybrid systems SPECT/CT and PET/CT in nuclear medicine, greatly improved the diagnostic accuracy for particular clinical indications, due to the possible attenuation correction of functional images and the availability of helpful anatomic information. The introduction of CT in the nuclear diagnostic process results in a significant increase of the patient dose. This increase should be justified and optimized considering both the clinical question and the CT settings available on these systems. The choice of CT settings directly affects the effective dose. It varies basically as the square of the tube voltage, linearly with the length of the scan and the product of the current by the rotation time of the tube. It is also inversely proportional to the pitch. For attenuation correction, the literature shows that it is possible to use a low CT tube current without significant effect on tumor FDG uptake or lesion size. Conversely low CT voltage must be used with caution, depending on the algorithm implemented in the CT hybrid device to transform CT Hounsfield units to the attenuation map at the appropriate energy. The radiation dose for anatomic correlation can be substantially lower than for diagnostic-quality CT. It is possible to reduce the patient's radiation dose by a factor of 2 or 3 by acquiring a low-dose PET/CT scan for anatomic correlation of adequate image quality if compared with diagnostic ¹⁸FDG PET/CT. Using specific CT settings, the effective dose can range 7.3–11.3 mSv depending on the patient weight and age.     

The late Maastrichtian nannofossil record of climate change in the South Atlantic DSDP Hole 525A

The phytoplankton response (calcareous nannofossils) to the Late Maastrichtian climate evolution is investigated in the South Atlantic DSDP Hole 525A and compared to published geochemical and micropaleontological data. The results point to a succession of dramatic climatic fluctuations. “Cool-water indicators” (Ahmuellerella octoradiata, Kamptnerius magnificus and Nephrolithus frequens) suggest cool surface water conditions prevailed during Chron C30n. At the top of C30n, their sudden drop in abundance, the last occurrence of B. constans and the concomitant increase in the tropical species Micula murus suggest warming and lower surface water productivity. An M. murus acme within Chron C29r reflects maximum warming. During the last 100 kyr of the Maastrichtian, the decrease in M. murus and increase in cool-water indicators reflect rapid cooling with the cool climate persisting over. The calcareous nannoplankton response to climate change correlate with similar findings in the Equatorial Atlantic Hole 1258A and parallels the stable isotope record of planktic and benthic foraminifera of DSDP Hole 525A as well as the decline in ¹⁸⁷Os/¹⁸⁸Os. Comparison of this marine record and the continental climate record in North America suggests a link between Deccan volcanism and the late Maastrichtian warm event.     

The Role of Ceramide Synthases in the Pathogenicity of Cryptococcus neoformans

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Occurrence of Tuber melanosporum in relation to soil surface layer properties and soil differentiation

An intensive survey was carried out on a 12-year-old experimental truffle bed of Tuber melanosporum Vitt. located in the central Apennines. The aim of the investigation was to relate the presence and carpophore production of T. melanosporum to changes in soil structure, aeration and fertility — expressed in terms of 0.25–2.00 mm aggregate fraction, total organic carbon, DTPA-extractable Mn and host plant height — and to determine if these modifications, whenever present, could be ascribed to soil differentiation within the truffle bed. The occurrence of pianelli — i.e. areas with little herbaceous ground cover created by T. melanosporum — showed a close relationship with host plant height and aeration of soil surface layers. Where pianelli occurred, the height of symbiont trees increased and the content of reduced Mn, indicating the presence of a well-aerated soil environment, decreased. The variation of host plant height was attributable not only to the increased absorption of nutrients related to the ectomycorrhizal partnership, but also to soil differentiation. The soils of the investigated area were characterized by a relatively low slope gradient, a rigid framework of gravel and a homogeneous physico-chemical behaviour, due to the predominance of Ca among exchangeable bases. In these environmental conditions, T. melanosporum was present in the rather thick soil belonging to Typic Rendolls, whereas it was absent in the area characterized by thin Lithic Rendolls. In the latter case, the plant cover was probably too scarce to protect T. melanosporum from summer dryness, and consequently the more resistant T. aestivum species prevailed. This revised version was published online in June 2006 with corrections to the Cover Date.     

Selective Augmentation of Stem Cell Populations in Structural Fat Grafts for Maxillofacial Surgery

Structural fat grafting utilizes the centrifugation of liposuction aspirates to create a graded density of adipose tissue. This study was performed to qualitatively investigate the effects of centrifugation on stem cells present in adipose tissue. Liposuction aspirates were obtained from healthy donors and either not centrifuged or centrifuged at 1,800 rpm for 3 minutes. The obtained fat volumes were divided into three layers and then analyzed. The results demonstrate that centrifugation induces a different distribution of stem cells in the three layers. The high-density layer displays the highest expression of mesenchymal stem cell and endothelial markers. The low-density layer exhibits an enrichment of multipotent stem cells. We conclude that appropriate centrifugation concentrates stem cells. This finding may influence the clinical practice of liposuction aspirate centrifugation and enhance graft uptake.     

Degradation of 2,4,6-trichlorophenol (2,4,6-TCP) by co-immobilization of anaerobic and aerobic microbial communities in an upflow reactor under air-limited conditions

The co-immobilization and the culture of anaerobic and aerobic communities was tested for the mineralization of 2,4,6-trichlorophenol (2,4,6-TCP). At first, the anaerobic microorganisms (aggregated into granules) were cultivated in an upflow anaerobic sludge blanket (UASB) reactor, in a continuous mode, with glucose, propionate, acetate (COD loading rate = 0.5-2.0 g COD/l per day, ratio 1:1:1) and 2,4,6-TCP (2,4,6-TCP loading rate = 25-278 micromol/l per day) as substrates. 2,4,6-TCP was degraded into 2,4-DCP and 4-CP, but it was not mineralized because of the low degradation rates of 4-CP. Furthermore, the highest loading rates of 2,4,6-TCP (>126 micromol/l per day) caused the inhibition of the strains degrading the propionate. The granules were therefore tested in association with the aerobic community. They were immobilized in kappa-carrageenan/gelatin [2% (w/w) of each polymer] gel beads and cultivated in a reactor, on their own (to test the influence of the gel), and then with the aerobic community, under anaerobic and air-limited conditions, respectively. The results showed that (1) the gel did not influence the activity of the granules, (2) the anaerobic and aerobic communities could be easily co-immobilized in gel beads and cultivated in a reactor, (3) the mineralization of 2,4,6-TCP (2,4,6-TCP loading rate = 10-506 micromol/l per day), its intermediates of degradation and the other substrates [glucose + acetate + propionate (ratio 1:1:1) = COD loading rate = 500 mg COD/l per day] could be obtained under air-limited conditions if the culture parameters were strictly controlled [airflow = 36-48 vvd (volume of air/volume of liquid in the reactor per day), pH value at around 7.5]. Finally, the gel did not retain its structure during the whole culture (263 days) in the air-limited reactor, but the anaerobic and aerobic communities retained their activities and worked together for the mineralization.     

Imagerie hybride : principe,dosimétrie et contrôle de qualité

The recent introduction of hybrid systems combining a SPECT and a CT in nuclear medicine, greatly improved the diagnostic accuracy for particular clinical indications, due to the possible attenuation and/or scatter correction of the SPECT functional images and the availability of helpful anatomic information. Although the gamma cameras performances are noticeably comparable, the associated CT furnished by the manufacturer are relatively different from each other. Whatever the system is, the introduction of CT in the nuclear diagnostic process results in a significant increase of the patient dose. This dose increase should be justified and optimized considering both the clinical question and the CT settings available on these systems. The installation of a hybrid system must be accompanied by the management of a documentary quality insurance program, jointly developed by the technologists, physicists and physicians, both covering its clinical use and the associated dosimetry issues as monitoring its performances. Particular quality control procedures have to be defined because of the coupling between the two devices.