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Biomedical subjects

P Rodrigues

Publications and source records attributed to P Rodrigues.

At least 19 recordsLinked to original sources

Urogenital papilla feminization in male Pomatoschistus minutus from two estuaries in northwestern Iberian Peninsula.

Recently, male urogenital papilla feminization (UGPF) in the sand goby Pomatoschistus minutus was reported in several UK estuaries with high levels of estrogenic compounds. The fact that this species is also common in southern European estuaries, together with its life-cycle characteristics, prompted us to investigate P. minutus UGPF in the northwestern of Iberian Peninsula. Specimens of P. minutus were periodically sampled during 2004 at several locations in two estuaries (Minho and Lima). Evidence for UGPF was recorded in both estuaries, the highest incidence being observed in the Lima estuary (50%). Estrogen levels (17beta-estradiol and estrone) above 100 pg/l were observed in both estuaries, the higher concentrations being found in the Lima estuary. Overall, the results suggest a relationship between the feminization of male P. minutus urogenital papilla and the presence of estrogenic compounds. In the future, more in-depth studies are required in order to use P. minutus as a sentinel species for estrogenic compound monitoring in estuaries.

Animals↗

Quantification by image analysis of the Gallus gallus lung elastic fibres from embryonic to adult birds.

The organization of the lung's elastic fibres is amazingly uniform in all vertebrates, with the possible exception of birds, whose pulmonary architecture and air movement are unique. The overall goal of this work was to study and quantify elastic fibre distribution patterns and relative amounts in the parabronchi, during the incubation period until the 42nd day after hatching. Chick embryo lungs were examined on the 14th, 16th, 18th and 20th days of incubation and chick lungs on the 1st, 2nd, 7th, 14th, 35th and 42nd days after hatching. Four animals were used daily, and the observations were randomly performed on both lungs. A morphometric study was carried out focusing on the computerized image analysis of histological sections stained according to a modified Gomori technique. The values obtained for each day result from the observation and processing of 20 images. Complementary studies were performed using transmission electron microscopy, as on the 14th embryonic day the fibres were not visible on light microscopy. The results show that the area occupied by the elastic fibres increases gradually from the 16th day of incubation up till the 7th day after hatching and decreases slowly in the following days of the study. A prominent increase takes place before hatching, which points out to the adequate and essential structural roles played by the elastic fibres in the pulmonary maturation process.

Aging↗

A new low-energy bremsstrahlung generator for GEANT4.

The 2BN bremsstrahlung cross section is a well-adapted distribution to describe the radiative processes at low-electron kinetic energy (E(k) < 500 keV). In this work a method to implement this distribution in a Monte Carlo generator is developed.

Computer Simulation↗

Clear-PEM: a dedicated PET camera for improved breast cancer detection.

Positron emission mammography (PEM) can offer a non-invasive method for the diagnosis of breast cancer. Metabolic images from PEM using 18F-fluoro-deoxy-glucose, contain unique information not available from conventional morphologic imaging techniques like X-ray radiography. In this work, the concept of Clear-PEM, the system presently developed in the frame of the Crystal Clear Collaboration at CERN, is described. Clear-PEM will be a dedicated scanner, offering better perspectives in terms of position resolution and detection sensitivity.

Breast Neoplasms↗

The genetics of non-host disease resistance in wheat to barley yellow rust.

Non-host resistance is investigated as a potential source of durable resistance. However, the genetics of non-host resistance between closely related plant species and their corresponding pathogens would indicate that in these interactions, non-host resistance primarily involves major genes that operate on a gene-for-gene principal similar to that seen in host resistance. Wheat is a non-host of the barley-attacking form of the fungus responsible for yellow rust, i.e. Puccinia striiformis f. sp. hordei. While P. striiformis f. sp. hordei is generally unable to infect wheat, a partial susceptibility was exhibited by the wheat variety Chinese 166. Consequently, in the cross Lemhi x Chinese 166 two major QTLs for resistance to P. striiformis f. sp. hordei were identified: one on chromosome 1D and a second on 2B. These two QTLs accounted for 43.5% and 33.2% of the phenotypic variance for resistance to barley yellow rust, respectively. In addition, two QTLs of smaller effect were also identified: one on chromosome 5A, contributing 5.1% of the variance and a second on chromosome 6A, contributing 10.9% to the phenotype. The QTL on 6A was derived from the susceptible variety, Chinese 166. In all cases the resistance towards P. striiformis f. sp. hordei was associated with a visual chlorosis/necrosis response typical of race-specific host resistance.

Basidiomycota↗

Application of GEANT4 radiation transport toolkit to dose calculations in anthropomorphic phantoms.

In this paper, we present a novel implementation of a dose calculation application, based on the GEANT4 Monte Carlo toolkit. Validation studies were performed with an homogeneous water phantom and an Alderson-Rando anthropomorphic phantom both irradiated with high-energy photon beams produced by a clinical linear accelerator. As input, this tool requires computer tomography images for automatic codification of voxel-based geometries and phase-space distributions to characterize the incident radiation field. Simulation results were compared with ionization chamber, thermoluminescent dosimetry data and commercial treatment planning system calculations. In homogeneous water phantom, overall agreement with measurements were within 1-2%. For anthropomorphic simulated setups (thorax and head irradiation) mean differences between GEANT4 and TLD measurements were less than 2%. Significant differences between GEANT4 and a semi-analytical algorithm implemented in the treatment planning system, were found in low-density regions, such as air cavities with strong electronic disequilibrium.

Algorithms↗

Use of bisphosphonates can dramatically improve pain in advanced hormone-refractory prostate cancer patients.

INTRODUCTION: Approximately 85% of patients who die from prostate cancer present the spread of bone metastases. Even though the radiological appearance of such metastases is osteoblastic, it is now known that these lesions coexist in their microenvironment with blastic and lytic lesions. The process always begins with bone lysis by osteoclast proliferation, paralleling nearby bone deposition. The treatment options are palliative and have poor clinical response with short-lived improvement. We have studied the clinical effect of bisphosphonates (clodronate) in the treatment of skeletal complications from prostate cancer. MATERIALS AND METHODS: In an open prospective study, 58 patients with hormone-refractory prostate cancer with bone metastases were assessed from November 2000 to September 2003. The mean age was 70.3 y (range: 51-87 y). Bone scintigraphy, plain X-ray, assaying of prostate-specific antigen (PSA) and biochemical tests were requested before and following treatment. Patients were previously and subsequently assessed using the visual pain scale (0-10) and Karnofsky's index after the first and second intravenous (i.v.) infusions (administration of i.v. clodronate every 28 days) and every 4-6 months thereafter. Student's t-test was used for statistical analysis. RESULTS: A total of 53 patients (91.4%) showed improvement after the first and/or second cycle, which persisted for at least 4 months (average 6.3 months). The averages on the visual pain scale improved from 7.4 (range: 2-8) to 2.4 (0-7) and on Karnofsky's index from 43 (32-58) to 73 (50-82). The radiological appearance of the metastases improved in 27 patients (46.5%) and there were few relapses (six patients; 10.3%). CONCLUSIONS: Clodronate was effective in the treatment of skeletal complications from prostate cancer. There was an objective response in 91.4% of treated patients, with a marked improvement in the subjective visual pain scale evaluation as well as on Karnofsky's index, with low side effects.

Aged↗

Involvement of the major histocompatibility complex region in the genetic regulation of circulating CD8 T-cell numbers in humans.

Variability in T-lymphocyte numbers is partially explained by a genetic regulation. From studies in animal models, it is known that the Major Histocompatibility Complex (MHC) is involved in this regulation. In humans, this has not been shown yet. The objective of the present study was to test the hypothesis that genes in the MHC region influence the regulation of T-lymphocyte numbers. Two approaches were used. Association studies between T-cell counts (CD4(+) and CD8(+)) or total lymphocyte counts and HLA class I alleles (A and B) or mutations in the HFE (C282Y and H63D), the hemochromatosis gene, in an unrelated population (n = 264). A second approach was a sibpair correlation analysis of the same T-cell counts in relation to HLA-HFE haplotypes in subjects belonging to 48 hemochromatosis families (n = 456 sibpairs). In the normal population, results showed a strong statistically significant association of the HLA-A*01 with high numbers of CD8(+) T cells and a less powerful association with the HLA-A*24 with low numbers of CD8(+) T cells. Sibpair correlations revealed the most significant correlation for CD8(+) T-cell numbers for sibpairs with HLA-HFE-identical haplotypes. This was not observed for CD4(+) T cells. These results show that the MHC region is involved in the genetic regulation of CD8(+) T-cell numbers in humans. Identification of genes responsible for this control may have important biological and clinical implications.

Adolescent↗

Management of Portuguese patients with hyperplastic polyposis and screening of at-risk first-degree relatives: a contribution for future guidelines based on a clinical study.

BACKGROUND: Hyperplastic polyposis (HP) is a rare condition characterized by the presence of multiple hyperplastic polyps in the colon, which has been associated to an increased risk of colorectal cancer (CRC). Guidelines for management of this disease remain, so far, undefined. AIMS: To evaluate, in symptomatic patients with HP, phenotypic characteristics as well as results of a screening program in their at-risk first-degree relatives. PATIENTS: Pedigree information and clinical and endoscopic data of 14 patients with HP was studied. SEVENTEEN AND METHODS: at-risk first-degree relatives from six families were also invited to perform screening colonoscopy. RESULTS: Twelve of fourteen (86%) patients had fewer than 100 colorectal polyps. Polyps' sizes ranged from 2 to 25 mm and were uniformly distributed through the whole colon in 43% of the patients. Hyperplastic polyps predominated, but 11/14 (79%) patients also harbored serrated as well as classic adenomatous polyps. CRC was present in 6/14 (43%) of the patients at the time of diagnosis. Familial history of CRC/polyps was positive in 6/12 (50%) of cases. Colonoscopy in at-risk relatives disclosed polyps in 10/17 (59%) of cases with at least one additional patient having criteria for HP. CONCLUSIONS: Although small, this series demonstrates that a high level of suspicion is needed to diagnose the HP syndrome, in which serrated adenomas seem to be the hallmark. Although an elevated percentage of CRC was observed in this series of symptomatic patients with HP, prospective studies in asymptomatic individuals are needed to clearly quantify the risk of CRC in patients with HP. Because familial aggregation of HP was present in 3/12 (25%) of kindreds, screening colonoscopy should be offered to first-degree relatives.

Adenomatous Polyposis Coli↗

A Monte Carlo multiple source model applied to radiosurgery narrow photon beams.

Monte Carlo (MC) methods are nowadays often used in the field of radiotherapy. Through successive steps, radiation fields are simulated, producing source Phase Space Data (PSD) that enable a dose calculation with good accuracy. Narrow photon beams used in radiosurgery can also be simulated by MC codes. However, the poor efficiency in simulating these narrow photon beams produces PSD whose quality prevents calculating dose with the required accuracy. To overcome this difficulty, a multiple source model was developed that enhances the quality of the reconstructed PSD, reducing also the time and storage capacities. This multiple source model was based on the full MC simulation, performed with the MC code MCNP4C, of the Siemens Mevatron KD2 (6 MV mode) linear accelerator head and additional collimators. The full simulation allowed the characterization of the particles coming from the accelerator head and from the additional collimators that shape the narrow photon beams used in radiosurgery treatments. Eight relevant photon virtual sources were identified from the full characterization analysis. Spatial and energy distributions were stored in histograms for the virtual sources representing the accelerator head components and the additional collimators. The photon directions were calculated for virtual sources representing the accelerator head components whereas, for the virtual sources representing the additional collimators, they were recorded into histograms. All these histograms were included in the MC code, DPM code and using a sampling procedure that reconstructed the PSDs, dose distributions were calculated in a water phantom divided in 20000 voxels of 1 x 1 x 5 mm3. The model accurately calculates dose distributions in the water phantom for all the additional collimators; for depth dose curves, associated errors at 2sigma were lower than 2.5% until a depth of 202.5 mm for all the additional collimators and for profiles at various depths, deviations between measured and calculated values were less than 2.5% or 1 mm.

Algorithms↗

Basic dosimetry of radiosurgery narrow beams using Monte Carlo simulations: a detailed study of depth of maximum dose.

In radiosurgery narrow photon beams, the depth of maximum dose d(max), in the beam central axis increases as the size of the additional collimator increases. This behavior is the opposite of what is observed in radiotherapy conventional beams. To understand this effect, experimental depth dose curves of the additional collimators were obtained for a Siemens KD2 linear accelerator in 6 MV photon mode and the shift of d(max) varied from 11.0 +/- 0.6 mm for the 5 mm collimator to 14.5 +/- 0.6 mm for the 23 mm collimator. Monte Carlo simulations showed that the photons that had no interactions in the additional collimators, contributing more than 90% to the total dose in water, were responsible for the shift in d(max). Monte Carlo simulations also showed that electrons originated from these photons and contributing to the dose deposit in water in the beam central axis could be divided in two groups: those that deposit energy far away from their point of origin (the point of the first photon collision in water) and those that deposit energy locally (originated at more than one photon collision in water). Applying a simplified model based on the fact that the photons originating Compton electrons (at the first and subsequent collisions) have similar characteristics in air for all the additional collimators, it was shown that these electrons were also responsible for the shift of d(max) in the beam central axis. Finally, it was shown that the changes in the initial gradients of the depth dose curves of the additional collimators were mainly due to electrons originated from the first photon collision in water.

Algorithms↗

Effect of ascorbic acid on the stability of beta-carotene and capsanthin in paprika (Capsicum annuum) powder.

The effect of ascorbic acid, light, and storage on the stability of the pigments beta-carotene and capsanthin in red pepper (Capsicum annuum) powder has been elucidated by determining the amount of pigment in samples treated by various concentrations of ascorbic acid. Determination of pigment concentration has been performed after different storage times using high-performance liquid chromatography. The dependence of the concentration of pigments on the concentration of ascorbic acid, presence of light and the storage time has been assessed by stepwise regression analysis. The concentration of pigments decreased at longer storage time and increased at higher concentration of ascorbic acid, beta-carotene being more sensitive towards storage time and concentration of ascorbic acid than capsanthin. Interaction between the effects of light and storage time, and light and concentration of ascorbic acid has been established.

Antioxidants↗

Characterization of recombinant Desulfovibrio gigas ferredoxin.

Dg ferredoxin gene was cloned using the polymerase chain reaction (PCR), inserted into vector pT7-7, and overexpressed in Escherichia coli (E. coli) grown in aerobic media. The recombinant protein is a dimer and contains a [3Fe-4S] cluster per monomer. EPR and (1)H NMR data of recombinant and wild-type protein are compared.

Cloning, Molecular↗

T-cell receptor repertoire in hereditary hemochromatosis: a study of 32 hemochromatosis patients and 274 healthy subjects.

Low CD8(+) T lymphocyte numbers have contributed to deciphering the genotype/phenotype discrepancies found in hereditary hemochromatosis (HH) patients genotyped for the Hfe mutations, C282Y and H63D. In this study, we extend the analysis of T lymphocytes in HH to the T cell receptor (TcR) repertoire. Thirty-two HH patients (C282Y homozygous) and 274 Hfe genotyped healthy subjects were studied. The following TcR chains were analyzed: Valpha2.3, Vbeta5.1, Vbeta5.2, Vbeta5.3, Vbeta6.7, Vbeta8, and Vbeta12 among the CD4(+) and CD8(+) populations. Lymphopenias and absence of expansions of the Vbeta5.2 and Vbeta12 chains in the CD8(+) pool were seen in controls heterozygous for the C282Y mutation. Expansions in the control group were seen within the CD8(+) pool and were rare/absent within the CD4(+) pool. TcR expansions were found more frequent in patients with iron overload related pathology than in patients without pathology. 9/16 of the patients with pathology have at least one expansion among the CD8(+) pool a number significantly higher compared with patients without pathology (1/16). These findings suggest that Hfe has an effect in the shaping of T-cell populations either directly, as indicated by the lymphopenia seen in the two chains in C282Y heterozygous without iron overload, or indirectly by contributing to iron overload pathology.

Adolescent↗

Comparative study of the two more frequent HFE mutations (C282Y and H63D): significant different allelic frequencies between the North and South of Portugal.

An earlier study of reference values of iron parameters in Portugal showed significant differences between populations from northern and southern villages. This study addresses the question of the geographical distribution in Portugal of the two main mutations (C282Y and H63D) of the hereditary hemochromatosis gene, HFE. For that purpose, a stratified sample of 640 anonymous dried blood spot samples was randomly selected from the major regions of Portugal: North, Center, Lisbon and the Tagus Valley, Alentejo and Algarve. Differences in the geographical distribution of these two mutations were observed thus confirming the presumed differences between the age of the two mutations which is compatible with the postulated Celtic/Nordic origin of the C282Y mutation. The finding of a significantly higher allelic frequency of the C282Y mutation in the North (0.058) than in the South (0.009) could also point to an effect of differential selective forces acting in the different geographical areas of the country. Data on archaeological, ethnographic and linguistic records and on the North/South distribution of Portuguese cattle breeds of European or African origin have also been reported. In addition to their interest for population genetics, the results represent a reminder of the need to take into account regional differences in the design of strategies for population screening of hereditary hemochromatosis.

DNA↗

A randomised, double-blind, placebo-controlled clinical trial of vitamin A in severe malaria in hospitalised Mozambican children.

This paper reports a randomised, double-blind, placebo-controlled clinical trial of the effect of routine vitamin A supplementation given on admission to children with severe malaria with regard to survival, recovery during hospitalisation and outcome 6 weeks after discharge. Children aged between 6 and 72 months admitted to the paediatric wards of the Central Hospital of Maputo (CHM), Mozambique with a diagnosis of severe malaria were randomly assigned either to a control group (placebo) or an experimental group (vitamin A) and were followed up 6 weeks after discharge. There were 280 children in the experimental and 290 in the placebo group. Seven (2.5%) and 13 (4.5%) children died in the experimental and the placebo groups, respectively, a relative risk of death of 0.56 (95% CI 0.23-1.38, p = 0.201). During the 1st 5 hours of admission, the relative risk of death in the vitamin A-supplemented group was 2.54 (0.50-12.96); after 5 hours of admission it was 0.19 (95% CI 0.04-0.85; p = 0.015). In the supplemented group, 4/82 (4.9%) of the children developed neurological sequelae vs 2/78 (2.6%) in the placebo group (RR = 1.90; 95% CI 0.36-10.09; p = 0.682). Although the overall reduction in the risk of death observed for all children receiving vitamin A is not statistically significant, it might be clinically important. This finding cannot, however, be accepted as a firm conclusion and requires validation by future trials.

Child↗