Assessment of the acceptability of the Elekta multileaf collimator (MLC) within the Corvus planning system for static and dynamic delivery of intensity modulated beams (IMBs).

The sliding window technique used for static and dynamic segmentation of intensity modulated beams is evaluated. Dynamic delivery is preferred since the resulting distributions correspond better with the calculated distributions, the treatment beam is used more efficiently and the delivery is less sensitive to small variations in the accuracy of the multileaf collimator (MLC).     

Chronic and subacute myelomonocytic leukaemia in the adult: a report of 60 cases with special reference to prognostic factors

We report 60 cases of chronic and subacute myelomonocytic leukaemias (CMML and SMML) in the adult, using the FAB group criteria. The M/F sex ratio was 3.3 and the mean age 67.5 years. Splenomegaly was found in 32% of cases, hyperleucocytosis in 52% of cases and mean blood monocytosis was 4.3 X 10(9)/l. Marrow smears showed an excess of blasts in 57% of patients, a moderate increase in monocytes in most cases and frequent myelodysplastic features. An increase in serum lysozyme and polyclonal hypergammaglobulinaemia were usual and clonal cytogenetic anomalies found in about half of the patients tested. Treatment was usually palliative and the median survival was 28 months, a blastic transformation being responsible for a third of the deaths. Prognostic factors at diagnosis were analysed retrospectively in the 46 patients who had sufficient follow up. Percentage of marrow blasts haemoglobin level and blood monocytosis at diagnosis, were subject to multivariate analysis, resulting in a discriminant 'score'. This allowed assignment of each patient into one of two prognostic subgroups (10.9% probability of error): a poor prognosis one, with a life expectancy of less than 1 year and a high risk of acute transformation (subgroup termed SMML) and a better prognosis subgroup (termed CMML), with some CMML patients surviving over 5 years.     

Automated detection of local normalization areas for ictal-interictal subtraction brain SPECT.

Whole-brain activity is often chosen to quantitatively normalize peri-ictal and interictal SPECT scans before their subtraction. This use is not justified, because significant and extended modification of the cerebral blood flow can occur during a seizure. We validated and compared 2 automatic methods able to determine the optimal reference region, using simulation and clinical data. METHODS: In the first method, the selected reference region is the intersection of peri-ictal-interictal areas with no significantly different z values. The other method relies on a 3-dimensional iterative voxel aggregation. The increase of the selected volume is stopped by using 2 different variance tests (Levene and SE). These algorithms were tested on 39 epileptic patients and were validated using 1 interictal and 10 peri-ictal scans simulated from the mean image of 22 healthy subjects. RESULTS: In the patient studies, the mean relative activity of the selected regions, compared with whole-brain activity (classic normalization), was 122.6%. Their average relative size (compared with the size of the whole brain) was 33.2% for the z map method, 22.8% for the SE test, and 11.8% for the Levene test. After application of our automatic processes, subtraction of the simulated images revealed a recovery of abnormal regions up to 45% larger than the region obtained with classic normalization. CONCLUSION: These results illustrate the role of normalization on the subtracted peri-ictal and interictal images. Our methods are automatic and objective and give good results on various simulated images. The z map construction is worth considering because it is simple, selects large parts of the brain, and requires little computation time.     

Detection of alpha- and beta-human papillomavirus (HPV) in cutaneous melanoma: a matched and controlled study using specific multiplex PCR combined with DNA microarray primer extension

Abstract:  There are few contradictory studies investigating the involvement of HPV in melanoma. We designed a controlled study to evaluate the HPV DNA prevalence in melanoma. One hundred patients with cutaneous malignant melanoma diagnosed between 2002 and 2006 were included. Complementary wide excision (healthy skin) was performed in 85 patients and was used as internal control. After DNA extraction, 68 different HPV types were studied using a multiplex PCR combined with microarray primer extension. We did not observe any statistical significant difference in terms of HPV DNA prevalence in melanoma (38.8%) and in healthy skin from wide excision (42.4%). Twenty-one different HPV types were detected but only one type was present in the majority of our samples (80/85 melanoma vs 59/66 HS). The distribution of HPV genera and types was similar in melanoma and HS, and beta-HPV was predominant (30.6% and 31.8%). Among alpha-HPV (10.6%), high-risk mucosal HPV16 was predominant. Among beta-HPV, melanoma harboured significantly more type 22 than control normal skin from the same patients and significantly less type 21 than paired control normal skin. No correlation between clinical and pathological melanoma characteristics and HPV DNA prevalence was found. Our data do not support a role of HPV infection in melanocarcinogenesis, but confirm the previous data suggesting that HPV DNA is widely distributed among the population and that occult HPV infections are frequent. Furthermore, specific HPV types, such as a-HPV16 and beta-HPV species 2 may be involved in a sub-group of melanoma.     

Neurobarrier coupling in the brain: a partner of neurovascular and neurometabolic coupling?

Neurovascular and neurometabolic coupling help the brain to maintain an appropriate energy flow to the neural tissue under conditions of increased neuronal activity. Both coupling phenomena provide us, in addition, with two macroscopically measurable parameters, blood flow and intermediate metabolite fluxes, that are used to dynamically image the functioning brain. The main energy substrate for the brain is glucose, which is metabolized by glycolysis and oxidative breakdown in both astrocytes and neurons. Neuronal activation triggers increased glucose consumption and glucose demand, with new glucose being brought in by stimulated blood flow and glucose transport over the blood-brain barrier. Glucose is shuttled over the barrier by the GLUT-1 transporter, which, like all transporter proteins, has a ceiling above which no further stimulation of the transport is possible. Blood-brain barrier glucose transport is generally accepted as a nonrate-limiting step but to prevent it from becoming rate-limiting under conditions of neuronal activation, it might be necessary for the transport parameters to be adapted to the increased glucose demand. It is proposed that the blood-brain barrier glucose transport parameters are dynamically adapted to the increased glucose needs of the neural tissue after activation according to a neurobarrier coupling scheme. This review presents neurobarrier coupling within the current knowledge on neurovascular and neurometabolic coupling, and considers arguments and evidence in support of this hypothesis.     

Toll-like receptor 4 (TLR4)-dependent proinflammatory and immunomodulatory properties of the glycoinositolphospholipid (GIPL) from Trypanosoma cruzi

We have demonstrated recently that the glycoinositolphospholipid (GIPL) molecule from the protozoan Trypanosoma cruzi is a TLR4 agonist with proinflammatory effects. Here, we show that GIPL-induced neutrophil recruitment into the peritoneal cavity is mediated by at least two pathways: one, where IL-1beta acts downstream of TNF-alpha, and a second, which is IL-1beta- and TNFRI-independent. Moreover, NKT cells participate in this proinflammatory cascade, as in GIPL-treated CD1d(-/-) mice, TNF-alpha and MIP-2 levels are reduced significantly. As a consequence of this inflammatory response, spleen and lymph nodes of GIPL-treated mice have an increase in the percentage of T and B cells expressing the CD69 activation marker. Cell-transfer experiments demonstrate that T and B cell activation by GIPL is an indirect effect, which relies on the expression of TLR4 by other cell types. Moreover, although signaling through TNFRI contributes to the activation of B and gammadelta+ T cells, it is not required for increasing CD69 expression on alphabeta+ T lymphocytes. It is interesting that T cells are also functionally affected by GIPL treatment, as spleen cells from GIPL-injected mice show enhanced production of IL-4 following in vitro stimulation by anti-CD3. Together, these results contribute to the understanding of the inflammatory properties of the GIPL molecule, pointing to its potential role as a parasite-derived modulator of the immune response during T. cruzi infection.     

El Registro de Gemelos de Murcia. Un recurso para la investigación sobre conductas relacionadas con la salud

Genetically informative designs and, in particular, twin studies, are the most widely used methodology to analyse the relative contribution of genetic and environmental factors to inter-individual variability. These studies basically compare the degree of phenotypical similarity between monozygotic and dizygotic twin pairs. In addition to the traditional estimate of heritability, this kind of registry enables a wide variety of analyses which are unique due to the characteristics of the sample. The Murcia Twin Registry is population-based and focused on the analysis of health-related behaviour. The observed prevalence of health problems is comparable to that of other regional and national reference samples, which guarantees its representativeness. Overall, the characteristics of the Registry facilitate developing various types of research as well as genetically informative designs, and collaboration with different initiatives and consortia.