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J Santos

Publications and source records attributed to J Santos.

At least 19 recordsLinked to original sources
PubMed2006

Dosimetry at the Portuguese research reactor using thermoluminescence measurements and Monte Carlo calculations.

This work presents an extensive study on Monte Carlo radiation transport simulation and thermoluminescent (TL) dosimetry for characterising mixed radiation fields (neutrons and photons) occurring in nuclear reactors. The feasibility of these methods is investigated for radiation fields at various locations of the Portuguese Research Reactor (RPI). The performance of the approaches developed in this work is compared with dosimetric techniques already existing at RPI. The Monte Carlo MCNP-4C code was used for a detailed modelling of the reactor core, the fast neutron beam and the thermal column of RPI. Simulations using these models allow to reproduce the energy and spatial distributions of the neutron field very well (agreement better than 80%). In the case of the photon field, the agreement improves with decreasing intensity of the component related to fission and activation products. (7)LiF:Mg,Ti, (7)LiF:Mg,Cu,P and Al(2)O(3):Mg,Y TL detectors (TLDs) with low neutron sensitivity are able to determine photon dose and dose profiles with high spatial resolution. On the other hand, (nat)LiF:Mg,Ti TLDs with increased neutron sensitivity show a remarkable loss of sensitivity and a high supralinearity in high-intensity fields hampering their application at nuclear reactors.

Algorithms↗
PubMed2006

Functional Fas (Cd95/Apo-1) promoter polymorphisms in inbred mouse strains exhibiting different susceptibility to gamma-radiation-induced thymic lymphoma.

The Fas death receptor is a cell surface molecule involved in apoptosis as well as in proliferative or activating signals of many cells types, including T lymphocytes. Using quantitative real-time reverse transcription-PCR analysis, we confirm that expression of this gene is scarcely perceptible in thymic lymphomas induced by gamma-irradiation in C57BL/6J mice. Notably, we also demonstrate for the first time that Fas expression is significantly upregulated in vivo both after single high dose of radiation and in thymic lymphoma-free mice. In addition, we determined its levels of expression in five mouse strains exhibiting different degrees of susceptibility (SPRET/Ei, SEG/Pas, BALB/cJ, C57BL/6J and RF/J). Interestingly, we found the highest levels of expression in SPRET/Ei and SEG/Pas strains (both derived from the Mus spretus species), which are known to have the most resistant phenotype, and the lowest levels in the most susceptible strains C57BL/6J and RF/J. DNA sequencing of the Fas promoter in all five strains showed many polymorphisms that can be classified into three functional haplotypes by using luciferase assays: (1) C57BL/6J and RF/J, (2) BALB/cJ and (3) SPRET/Ei and SEG/Pas. Promoter activities in response to single high doses of radiation correlated well with the levels of Fas expression and are consistent with the degree of strain susceptibility.

Animals↗
PubMed2006

Efficacy and safety of twice-daily pharmacokinetically enhanced amoxicillin/clavulanate (2000/125 mg) in the treatment of adults with community-acquired pneumonia in a country with a high prevalence of penicillin-resistant Streptococcus pneumoniae.

OBJECTIVES: This randomized, double-blind, non-inferiority trial evaluated the efficacy and safety of pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg twice daily versus amoxicillin/clavulanate 875/125 mg three times daily, both given orally for 7 or 10 days, in the treatment of adults with community-acquired pneumonia in Spain, a country with a high prevalence of penicillin-resistant Streptococcus pneumoniae. PATIENTS AND METHODS: Following 2:1 randomization, 566 patients (intent-to-treat population) received either amoxicillin/clavulanate 2000/125 mg (n = 374) or amoxicillin/clavulanate 875/125 mg (n = 192). RESULTS: Among the patients who did not deviate from the protocol (clinical per-protocol population), clinical success at day 21-28 post-therapy (test of cure; primary efficacy endpoint) was 92.4% (266/288) for amoxicillin/clavulanate 2000/125 mg and 91.2% (135/148) for amoxicillin/clavulanate 875/125 mg (treatment difference, 1.1; 95% confidence interval, -4.4, 6.6). Bacteriological success at test of cure in the bacteriology per-protocol population was 90.8% (79/87) with amoxicillin/clavulanate 2000/125 mg and 86.0% (43/50) with amoxicillin/clavulanate 875/125 mg (treatment difference 4.8; 95% confidence interval, -6.6, 16.2). At test of cure, amoxicillin/clavulanate 2000/125 mg was clinically and bacteriologically effective against 7/7 penicillin-resistant Streptococcus pneumoniae (MIC > or = 2 mg/L) isolates (including three amoxicillin non-susceptible strains) and amoxicillin/clavulanate 875/125 mg against 5/5 isolates (including one amoxicillin non-susceptible strain). CONCLUSIONS: Both treatment regimens were well tolerated. Amoxicillin/clavulanate 2000/125 mg was at least as effective clinically and as safe as amoxicillin/clavulanate 875/125 mg in the treatment of community-acquired pneumonia in adults in a country with a high prevalence of penicillin-resistant S. pneumoniae and has a more convenient twice daily posology.

Adult↗
PubMed2006

Lack of correlation between DNA copy number and mRNA expression levels of c-myc in gamma-radiation-induced mouse thymic lymphomas by using quantitative real-time PCR.

BACKGROUND: It is well documented that over-expression of the c-myc proto-oncogene occurs in the vast majority of mouse thymic lymphomas induced by gamma-irradiation, evidencing the importance of this gene in T-cell lymphomagenesis. However, it remains unknown whether elevated levels of c-myc expression are driven by extra c-myc copy numbers. MATERIALS AND METHODS: Here we use a quantitative test on the basis of real-time PCR to determine the cellular copy number of c-myc in a set of 14 g-radiation- induced thymic lymphomas obtained from (C57BL/6J x BALB/cJ) F1 hybrid mice with increased mRNA c-myc expression. RESULTS: Since 5 out of 14 (35.7%) cases had no extra copy numbers of c-myc, gene amplification was obviously not the cause of c-myc over-expression in these tumours. In the remaining 9 tumours, c-myc over-expression was also accompanied with extra DNA copy numbers. Therefore, c-myc amplification might be a consequence of the genomic instability subsequent to the up-regulation of c-myc. However, linear regression analysis showed a lack of correlation between increasing DNA copy numbers and mRNA over expression of c-myc in these tumours (r = 0.029, p = 0.94). CONCLUSION: De-regulation of c-myc does not necessarily imply amplification of this gene in these tumours. This report is, to our knowledge, the first one comparing c-myc amplification with expression in lymphomas of the T-cell lineage.

Animals↗
PubMed2006

Impact of highly active antiretroviral therapy on blood pressure in HIV-infected patients. A prospective study in a cohort of naive patients.

OBJECTIVES: To assess the impact of highly active antiretroviral therapy (HAART) on the blood pressure (BP) of naive patients after 1 year of treatment. METHODS: A prospective, observational study of 95 HIV-positive patients in our Unit starting HAART between January 2001 and October 2002 and maintaining the same regimen for 48 weeks of follow-up was carried out. Data on blood pressure (BP) and demographic, epidemiological, clinical, immunovirological and therapeutic characteristics related to HIV infection were collected prior to HAART and at week 48. High blood pressure (HBP) [systolic BP (SBP) > or =140 mm Hg and/or diastolic BP (DBP) > or =90 mm Hg] was defined according to international criteria. RESULTS: Of the 95 patients, 78 were men, 44% had AIDS and 68% were smokers, and their mean age was 40 years. At week 48 the prevalence of HBP was 26% and SBP, DBP and pulse pressure (PP) increased (121.8 versus 116.6 mm Hg, P=0.0001; 76.3 versus 69.7 mm Hg, P=0.004; 46.9 versus 43.8 mm Hg, P=0.001, respectively). Univariate analysis showed that HBP was associated with older age, higher body mass index (BMI), higher baseline lipids, and higher baseline BP. A linear regression model adjusting for age and sex suggested a significant impact of older age, higher baseline SBP, higher baseline hypercholesterolaemia and lower baseline CD4-cell count on SBP increase. CONCLUSIONS: Blood pressure increased after 48 weeks of HAART, leading to an important prevalence of hypertension. The increase in SBP depended on age and baseline lipid profile and immunological status. BP should be periodically measured and treated when necessary in HIV-infected patients on HAART.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Effect of antiretroviral therapy on admissions of HIV-infected patients to an intensive care unit.

OBJECTIVES: To analyse the characteristics of HIV-infected patients admitted to an Intensive Care Unit (ICU) and to compare them in the pre-highly active antiretroviral therapy (HAART) and HAART eras. METHODS: All HIV-infected patients who were admitted to the ICU of our hospital between January 1990 and December 2003 were reviewed. Patients were divided into two groups based on whether they were admitted before or after the advent of HAART, the cut-off date being 31 December 1996. RESULTS: Data were collected on 66 patients, 17 in the pre-HAART and 49 in the HAART era. The proportion of HIV-infected patients admitted to the ICU in our HIV-infected population increased after the introduction of HAART (3.8 vs 0.5%; P=0.001), and the largest diagnostic group was respiratory pathology in both periods. More than a third of patients were diagnosed with HIV infection during the ICU income, and only 31.2% were on antiretroviral therapy. The in-hospital mortality was 53.0%, and later survival was high. There were no significant differences between the pre-HAART and HAART eras. CONCLUSIONS: Our results suggest that the characteristics of HIV-infected patients admitted to ICU have not changed: respiratory diseases are still the most frequent cause of admission, in-hospital mortality is high, and later survival rates are good.

AIDS-Related Opportunistic Infections↗
PubMed2006

Long-term peritoneal dialysis experience in Portugal.

Peritoneal dialysis (PD) penetration varies widely. Since the beginning of this therapy, indications have changed and outcomes have improved. In Portugal, PD still remains clearly underutilized. The results of a 20 year PD programme were evaluated: 312 cumulative patients, 48+/-16 years, 27%>60 years old, 27% diabetic, 59% with prior hemodialysis (HD). The main reason for admission was vascular access failure (48.7%). Admission due to patient preference has increased significantly between first and second decades of the programme (33% vs 47% (P<0.001)); 98 patients (31.4%) were treated with automated PD but this prescription increased to 43% of the active patients.A total of 376 Tenckhoff catheters were surgically implanted, recently by the Popovich-Moncrief technique (77 catheters): the cumulative survival was 82%, 64% and 50% at 1, 3 and 5 years,respectively. A better catheter survival was found in the last decade (85.7%, 69.6%, 54.8% versus 77.3%, 55.5%, 40.2%, at 1, 3 and 5 years, respectively (P=0.007). The patient and technique cumulative survivals were 91, 74, 55% and 85, 67, 41%, at 1, 3, and 5 years, respectively. The main drop-out was to hemodialysis (35.8%), followed by death (23.7%), and transplantation (21.5%). Peritonitis and access-related infections caused 35% of the transfer to HD. Cardiovascular events caused 58% of deaths. The median PD retention was 35.5 months. The rate of peritonitis has decreased to one episode /30 patient months. Hospital admission has also decreased to 4.8 days/patient year. This is a first report on long-term PD experience in Portugal. It has been an effective modality of renal replacement therapy, reflected by the growing patient preference in our PD programme.Experience, knowledge and new technical solutions have improved the outcomes.

Adolescent↗
PubMed2005

Colonization by high-level aminoglycoside-resistant enterococci in intensive care unit patients: epidemiology and clinical relevance.

A cohort study was performed to investigate the risk factors for colonization with high-level aminoglycoside-resistant enterococci (HLARE) in intensive care unit (ICU) patients. Colonization was investigated by performing surveillance samples during ICU stay. Clonal relatedness of the isolates was assessed by pulsed-field gel electrophoresis. Eighty-six patients with an ICU stay of >48 h were included; two were colonized with HLARE at admission, and 24 (28.5%) acquired HLARE during their stay in the ICU. HLARE were initially isolated from rectal swabs alone. Thirty-five percent of Enterococcus faecalis and 57% of E. faecium showed high-level resistance to gentamicin or streptomycin. Most isolates were clonally unrelated. Using multi-variate analysis, the only variable associated with HLARE colonization was previous antimicrobial use. Five patients had HLARE isolated from clinical samples, three of them with infection; in all of these, colonization with the same clone had been detected previously by surveillance samples. We conclude that most infections due to HLARE in the ICU are preceded by previous colonization, and that antimicrobial use is the main risk factor for colonization.

Aminoglycosides↗
PubMed2005

CA-125 AUC as a new prognostic factor for patients with ovarian cancer.

OBJECTIVE: The aim of the present study was to investigate the usefulness of the CA-125 area under the curve (AUC) as a new kinetic parameter for predicting overall survival in patients with ovarian cancer. In addition, the relationship of CA-125 AUC with other prognostic factors of ovarian cancer was evaluated. METHODS: Ninety-two patients that underwent primary line chemotherapy within 4 months after submission to cytoreductive surgery were included. For each patient, CA-125 AUC was calculated and a statistical analysis was conducted to compare CA-125 AUC behavior among patients according to several covariates. RESULTS: The mean age at diagnostic time was found to be 55.5 (16.1-82.4) years with a mean survival of 39.2 (3.5-100.1; SE = 2.6) months. Across FIGO stage I, II, III, and IV patients had a mean CA-125 AUC of 18.2, 24.6, 147.8, and 574.6 IU/ml*days, respectively (P < 0.05). At the evaluation date, living patients had a mean CA-125 AUC of 40.1 in contrast to 234.1 IU/ml*days (P < 0.05) for deceased ones. Patients with a complete response to primary chemotherapy had a mean CA-125 AUC of 48.8, while patients with a partial response had a mean of 251.7 IU/ml*days, and patients with no response or disease progression had a mean of 316.5 IU/ml*days (P < 0.05). The best CA-125 AUC performance is in predicting patient complete response to chemotherapy with a cut-off of 100 IU/ml*days and an accuracy of 82%. CONCLUSIONS: Despite CA-125 AUC high correlation with the FIGO stage, residual disease, and patient final outcome, the main interest of CA-125 AUC calculation is to evaluate the treatment efficacy and to foresee a full chemotherapy response. Further studies should be carried out before extrapolating these results to other data sets.

Adolescent↗
PubMed2005

Salt sensitivity of blood pressure in patients with psoriasis on ciclosporin therapy.

BACKGROUND: Hypertension is one of the main side-effects of long-term therapy with ciclosporin. However, the influence of salt intake on the 24-h mean blood pressure of patients with psoriasis treated with ciclosporin is not known. OBJECTIVES: To evaluate, in patients with psoriasis, the sodium sensitivity of the ciclosporin-induced rise in blood pressure. METHODS: The 24-h ambulatory blood pressure was evaluated in 13 patients with psoriasis (age range 20-57 years) in two phases, before (phase I) and after the completion of 4 months of therapy with ciclosporin 3 mg kg(-1) daily (phase II). In both phases, the patients were studied in conditions of low sodium (LS) intake followed by a high sodium (HS) diet. RESULTS: Twenty-four-hour mean +/- SD blood pressure during LS and HS intake was, respectively, 86.3 +/- 1.6 mmHg and 85.5 +/- 1.8 mmHg during phase I, and 88.5 +/- 1.5 mmHg and 91.8 +/- 2.2 mmHg (P < 0.001 vs. phase I, HS; P < 0.05 vs. phase II, LS) during phase II. The median (interquartile range) sodium sensitivity index was greater during phase II than during phase I: - 0.0028 (- 0.0071 to 0.0009) vs. 0.0065 (- 0.0055 to 0.0258) (P < 0.02). The plasma levels and the daily urinary excretion of noradrenaline did not differ between phases I and II. CONCLUSIONS: The ciclosporin-induced rise in blood pressure is sodium sensitive. It is also suggested that sympathetic activation is not involved in the pathogenesis of ciclosporin-induced rise in blood pressure.

Adult↗
PubMed2005

Study of patients diagnosed with advanced HIV in the HAART era--OMEGA Cohort.

Our objective is to analyse patients diagnosed with late-stage HIV infection in the highly active antiretroviral therapy (HAART) area. A prospective, observational study of all patients with an initial CD4 < 50 x 10(6)/L was carried out. Epidemiological, clinical and HAART-associated data were analysed. Survival rates were estimated and pairs of survival curves were compared. The statistical program used was SPSS (version 10). In all, 349 HIV-infected patients were diagnosed, 117 (33.5%) had late-stage disease, mean CD4 23.9 x 10(6)/L and mean viral load (VL) 5.38 log10. In 98 men, mean age 39.5 years, percentage of AIDS cases at their first attendance was 83.8%. The median follow-up period was 28 months and 27 died. Pneumocystis carinii was the most frequent cause of AIDS (24.4%) and death (18.5%). Survival rates at 12, 24 and 36 months were 95.6%, 85.8% and 72.4%. HAART was started in 82.1%. VLs < 50 copies/mL at one, two and three years of treatment were 55.2%, 55.7% and 58.0%. Resource utilization included 0.58 hospitalization/patient/year and 0.07 events/patient/year. HAART-related complications were as follows: 50% lipodystrophy, 9.7% hypertension, 22.2% hyperglycaemia, 26.4% hypercholesterolaemia, 31.9% hypertrygliceridaemia and 18.1% mixed hyperlipaemia. Over one-third of our patients have advanced HIV infection at diagnosis. However, the outcome is favourable, with a good immunovirological response and few new opportunistic events. HAART-related complications were frequent.

AIDS-Related Opportunistic Infections↗
PubMed2005

Atherogenic lipid profile and cardiovascular risk factors in HIV-infected patients (Nétar Study).

We undertook a transverse study of 603 HIV outpatients to determine their atherogenic lipid profile (ALP) and cardiovascular risk (CVR) factors. CVR was estimated from the Framingham score. ALP was defined as a total cholesterol to high density lipoprotein (HDL)-cholesterol ratio > or =5 plus triglycerides > or =150 mg/dL and a CVR >10% at 10 years was considered high. The most frequent CVR factor was smoking. ALP was diagnosed in 26.9% and was related to sex (odds ratio [OR] 2.6; 95% confidence interval [CI], 1.3-5.0; P = 0.0047), protease inhibitor use (OR 3.8; 95% CI, 1.8-7.8; P = 0.0002) and sexual HIV risk (OR 2.4; 95% CI, 1.4-4.0; P = 0.0004). The mean 10-year CVR was 6.2%, was high in 20.4% and was related to sexual HIV-risk (OR 3.8; 95% CI, 2.1-6.8; P < 0.00001) and nadir cell differentiation factor (CD4) (OR 1.0; 95% CI, 1.0-1.003; P = 0.0026). Although the current CVR of our patients is not high, the contribution to the lipid profile of highly active antiretroviral therapy (HAART)-associated factors and the high prevalence of some risk factors may lead to an increased future CVR.

Adult↗
PubMed2004

Defective expression of Notch1 and Notch2 in connection to alterations of c-Myc and Ikaros in gamma-radiation-induced mouse thymic lymphomas.

Gamma-radiation-induced thymic lymphomas constitute a heterogeneous group of T-cell lymphomas. Some tumour suppressor genes and oncogenes have been shown to be defective in a fraction of such lymphomas, yet a considerable number of these remain elusive in terms of gene alterations. In the present work we present evidence that gamma-radiation-induced thymic lymphomas in (C57BL/6 J x BALB/c) F1 hybrid mice often exhibit increased levels of Notch1 expression, but, contrary to what was expected, they also exhibit a clearly reduced Notch2 mRNA expression, suggesting a cooperative antagonism of these genes. These results represent the first reported instance for the involvement of Notch2 inactivation in the development of thymic primary tumours while confirming the role of Notch1 as an activated oncogene. Additional analyses revealed that c-Myc over-expression and partial inactivation of Znfn1a1/Ikaros appear to be relevant events some how coupled to alterations in Notch genes inducing these kinds of tumours.

Animals↗
PubMed2004

VOLUS--a visualization system for 3D ultrasound data.

The main goal of this paper is the description of a computer based system for medical applications to estimate the half-ellipsoid model that fits the left ventricle on its two phases of cardiac cycle: diastole and systole. Techniques for registration and rendering of ultrasound images will be presented using 2D freehand spatial calibrated echocardiography images in order to represent the 3D reconstructed data equivalent to the scanned volume. The 3D reconstruction will be used to estimate and measure parameters of the half-ellipsoid model fitted to the left ventricle.

Echocardiography, Three-Dimensional↗
PubMed2004

[Genotype and phenotypic expression of hereditary hemochromatosis in Spain].

INTRODUCTION: The prevalence of C282Y homozygosity in patients with hereditary hemochromatosis (HH) has been reported to be markedly lower in the Mediterranean Basin than in northern Europe. In Spain, the available data are contradictory and limited to small series in specific regions. The objective of this study is to determine the prevalence of the 2 main HFE gene mutations in a large series of unrelated Spanish patients with HH from different geographical origins. PATIENTS AND METHOD: The criteria for HH diagnosis were: repeat serum transferrin saturation index (> 45% plus C282Y homozygosity and/or hepatic iron index (> 1.9 of dry liver weight in non-cirrhotic patients or (> 4.1 in patients with liver cirrhosis. Cases in related individuals were excluded. Demographic data, clinical expression, iron parameters and HFE gene mutations (C282Y and H63D) were assessed in 222 patients. RESULTS: A total of 83.3% of patients were C282Y homozygous and 5% were compound heterozygous (C282Y/H63D). No significant differences in phenotypic expression or in the frequency of C282Y homozygosity were observed between patients born in the North and South of Spain. CONCLUSION: The genotypic and phenotypic expression of HH in Spain is very similar to that reported in Northern Europe. Thus, the genetic heterogeneity described in some Southern European regions cannot be considered a common feature to all countries of the Mediterranean Basin.

Female↗
PubMed2004

Replicase-binding sites on plus- and minus-strand brome mosaic virus RNAs and their roles in RNA replication in plant cells.

The cis-acting elements for Brome mosaic virus (BMV) RNA synthesis have been characterized primarily for RNA3. To identify additional replicase-binding elements, nested fragments of all three of the BMV RNAs, both plus- and minus-sense fragments, were constructed and tested for binding enriched BMV replicase in a template competition assay. Ten RNA fragments containing replicase-binding sites were identified; eight were characterized further because they were more effective competitors. All eight mapped to noncoding regions of BMV RNAs, and the positions of seven localized to sequences containing previously characterized core promoter elements (C. C. Kao, Mol. Plant Pathol. 3:55-62, 2001), thus suggesting the identities of the replicase-binding sites. Three contained the tRNA-like structures that direct minus-strand RNA synthesis, three were within the 3' region of each minus-strand RNA that contained the core promoter for genomic plus-strand initiation, and one was in the core subgenomic promoter. Single-nucleotide mutations known previously to abolish RNA synthesis in vitro prevented replicase binding. When tested in the context of the respective full-length RNAs, the same mutations abolished BMV RNA synthesis in transfected barley protoplasts. The eighth site was within the intercistronic region (ICR) of plus-strand RNA3. Further mapping showed that a sequence of 22 consecutive adenylates was responsible for binding the replicase, with 16 being the minimal required length. Deletion of the poly(A) sequence was previously shown to severely debilitate BMV RNA replication in plants (E. Smirnyagina, Y. H. Hsu, N. Chua, and P. Ahlquist, Virology 198:427-436, 1994). Interestingly, the B box motif in the ICR of RNA3, which has previously been determined to bind the 1a protein, does not bind the replicase. These results identify the replicase-binding sites in all of the BMV RNAs and suggest that the recognition of RNA3 is different from that of RNA1 and RNA2.

Base Sequence↗