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Biomedical subjects

L Gonzalez

Publications and source records attributed to L Gonzalez.

At least 19 recordsLinked to original sources

Six years experience in intracoronary brachytherapy procedures: patient doses from fluoroscopy.

Typical patient dose levels during intracoronary brachytherapy (ICB) procedures using beta sources were determined across a sample of 221 treatments. Dose-area product values, fluoroscopy time and number of frames per procedure, with median values of 62 Gy cm2, 17.0 min and 1493 images, respectively, resulted in a 20% to 50% increase in the values measured for percutaneous transluminal coronary angioplasty procedures in the same medical centre (median values 41 Gy cm2, 14.3 min and 1078 images). Likely reasons for this increase include the additional complexity of ICB, the need for recording and reporting every step of the treatment, getting the essential parameters for the volume determination of the lesion and therapeutic radiation dose calculation and, finally, the learning curve for this kind of procedure. A high concentration skin dose distribution during ICB procedures was measured and in 12% of the patients peak skin doses higher than 1.5 Gy were confirmed. 10 patients were submitted to clinical follow-up and skin injuries were not identified.

Angioplasty, Balloon, Coronary↗

Microvascular injury and blood-brain barrier leakage in Alzheimer's disease.

Thinning and discontinuities within the vascular basement membrane (VBM) are associated with leakage of the plasma protein prothrombin across the blood-brain barrier (BBB) in Alzheimer's disease (AD). Prothrombin immunohistochemistry and ELISA assays were performed on prefrontal cortex. In severe AD, prothrombin was localized within the wall and neuropil surrounding microvessels. Factor VIII staining in severe AD patients indicated that prothrombin leakage was associated with shrinkage of endothelial cells. ELISA revealed elevated prothrombin levels in prefrontal cortex AD cases that increased with the Braak stage (Control=1.39, I-II=1.76, III-IV=2.28, and V-VI=3.11 ng prothrombin/mg total protein). Comparing these four groups, there was a significant difference between control and Braak V-VI (p=0.0095) and also between Braak stages I-II and V-VI (p=0.0048). There was no significant difference in mean prothrombin levels when cases with versus without cerebral amyloid angiopathy (CAA) were compared (p-value=0.3627). When comparing AD patients by APOE genotype (ApoE3,3=2.00, ApoE3,4=2.49, and ApoE4,4=2.96 ng prothrombin/mg total protein) an analysis of variance indicated a difference between genotypes at the 10% significance level (p=0.0705). Tukey's test indicated a difference between the 3,3 and 4,4 groups (p=0.0607). These studies provide evidence that in advanced AD (Braak stage V-VI), plasma proteins like prothrombin can be found within the microvessel wall and surrounding neuropil, and that leakage of the blood-brain barrier may be more common in patients with at least one APOE4 allele.

Adult↗

Accreditation in radiation protection for cardiologists and interventionalists.

Training in radiation protection is widely recognised as one of the basic components of optimisation programmes for medical exposures. Occupational and patient radiation risks in interventional radiology can be quite high and international bodies have shown concern on this item. Following recommendations of the International Commission on Radiological Protection and in accordance with the European Directive on medical exposures, some initiatives for training in radiation protection took place in Spain and Luxembourg. These provided practitioners of interventional radiology adequate theoretical and practical training in radiation protection. The main outcome of the pilot courses organised to this end is discussed, concluding its suitability to implement the European Directive in practice.

Accreditation↗

Evaluation of risk of deterministic effects in fluoroscopically guided procedures.

A methodology for the evaluation of skin dose distribution and possible skin injuries on patients undergoing interventional procedures has been developed as part of the European DIMOND programme. Relevant dosimetric data from the procedures are recorded and other specific measurements for skin dose evaluation (slow films for therapy, radiochromic films, thermoluminescence dosemeters and optically stimulated luminescence dosemeters) have been carried out. For non-cardiac and for some cardiac procedures, dose-area product values of 200 and 300 Gy cm2 were proposed, respectively, as a trigger level for further detailed skin dose investigation and possible clinical follow-up. Results from a survey of 191 selected complex procedures are reported. Out of all the patients included in the trial, 16% received skin doses > or =1.5 Gy. No skin injuries were found in any of the patients followed.

Dose-Response Relationship, Radiation↗

Patient dosimetry and image quality in digital radiology from online audit of the X-ray system.

The present work describes an online patient dosimetry and an image quality system in digital radiology. For the patient dosimetry audit, current mean values of entrance surface dose (ESD) were compared with local and national reference values (RVs) for the specific examination type evaluated. Mean values exceeding the RV trigger an alarm signal and then an evaluation of the technical parameters, operational practice and image quality was begun, using data available in the DICOM header to derive any abnormal settings or performance to obtain the image. The X-ray tube output for different kVp values is measured periodically, to allow for the automatic calculation of ESD. The system allows also for image audit, linking the dose imparted, the image quality and the alarm condition, if produced. Results and the benefits derived from this online quality control are discussed here.

Humans↗

Influence of patient thickness and operation modes on occupational and patient radiation doses in interventional cardiology.

Patient and staff dose values in an interventional cardiology laboratory for different operational modes and several patient thicknesses (from 16 to 28 cm, simulated using polymethylmethacrylate) are presented. When increasing patient thicknesses and depending on fluoroscopy and cine modes, occupational doses can increase >30 times the baseline level. Scatter dose rates at the cardiologist's position with no radiation protective tools ranged from 1 to 14 mSv h(-1) for fluoroscopy, and from 10 to 47 mSv h(-1) during cine acquisition. Patient entrance surface air kerma rates increased by nearly 3 and staff dose rates by up to 2.6 when fluoroscopy was moved from the low to the high mode, for a typical 20 cm thickness. The respective increase factors were 6 and 4.2 when patient thickness rose from 16 to 28 cm, and by 10 and 8.3, when comparing cine acquisition with the low fluoroscopy mode. The knowledge of typical dose rates for each X-ray system in use in catheterisation laboratories is essential in order to optimise protection of patients and staff.

Body Constitution↗

Occupational radiation doses in interventional cardiology: a 15-year follow-up.

This report describes occupational radiation doses of interventional cardiologists over 15 years and assesses action undertaken to optimize radiation protection. Personal dosimetry records of nine staff cardiologists and eight interventional cardiology fellows were recorded using personal dosemeters worn over and under their lead aprons. The hospital in which this study was conducted currently performs 5000 cardiology procedures per year. The hospital has improved its facilities since 1989, when it had two old-fashioned theatres, to include four rooms with more advanced and safer equipment. Intensive radiation protection training was also implemented since 1989. Initially, some individual dose values in the range of 100-300 mSv month(-1), which risked exceeding some regulatory dose limits, were measured over the lead apron. Several doses in the range of 5-11 mSv month(-1) were recorded under the apron (mean = 10.2 mSv year(-1)). During the last 5 years of the study, after the implementation of the radiation protection actions and a programme of patient-dose optimization, the mean dose under the apron was reduced to 1.2 mSv year(-1). Current mean occupational doses recorded under the lead apron are 14% of those recorded during 1989-1992 and those recorded over the apron are 14-fold less than those recorded during 1989-1992. The regulatory dose limits and the threshold for lens injuries might have been exceeded if radiation protection facilities had not been used systematically. The most effective actions involved in reducing the radiation risk were training in radiation protection, a programme of patient-dose reduction and the systematic use of radiation protection facilities, specifically ceiling-suspended protective screens.

Body Burden↗

An influx of macrophages is the predominant local immune response in ovine pulmonary adenocarcinoma.

Infection with a retrovirus, Jaagsiekte sheep retrovirus (JSRV), causes ovine pulmonary adenocarcinoma (OPA). The excess production of surfactant proteins by alveolar tumour cells results in increased production of pulmonary fluid, which is characteristically expelled through the nostrils of affected sheep. The immune response to JSRV and the tumour is poorly understood: no JSRV-specific circulating antibodies or T cells have been detected to date. The aim of the present study was to obtain phenotypic evidence for a local immune response in OPA lungs. Specific-pathogen free lambs were infected intratracheally with JSRV. When clinical signs of OPA were apparent, the lungs were removed at necropsy and immunohistochemistry (IHC) was performed on lung sections using a panel of mouse anti-sheep mAbs. No influx of dendritic cells, B cells, CD4, CD8 or gammadelta T cells was seen in the neoplastic nodules or in their periphery. MHC Class II-positive cells were found intratumourally, peritumourally and in the surrounding alveolar lumina. In the tumours, many of these cells were shown to be fibroblasts and the remainder were likely to be mature macrophages. In the alveolar lumen, the MHC Class II-positive cells were CD14-positive and expressed high levels of IFN-gamma. They appeared to be immature monocytes or macrophages which then differentiated to become CD14-negative as they reached the periphery of the tumours. A high level of MHC Class I expression was detected on a range of cells in the OPA lungs but the tumour nodules themselves contained no MHC Class I-positive cells. On the basis of these findings, it is proposed that the lack of an effective immune response in OPA could result from a mechanism of peripheral tolerance in which the activity of the invading macrophages is suppressed by the local environment, possibly as a consequence of the inhibitory properties of the surfactant proteins.

Animals↗

Screens using RNAi and cDNA expression as surrogates for genetics in mammalian tissue culture cells.

We have developed methods for the automation of transfection-grade DNA preparation, high-throughput retroviral preparation, and highly parallel phenotypic screens to establish approaches that will allow investigators to examine in an unbiased manner the roles of proteins in mammalian cells. These methods have been used to raise or lower the levels of individual kinases in individual micro-well cultures either by cDNA or short hairpin RNA expression and will allow investigators to treat mammalian cells in culture in manners that are analogous to genetic screens in yeast. Our proof-of-principle experiments have been performed in human cells using repositories that represent over 75% of the protein, nucleotide, carbohydrate, lipid, and amino acid kinases in the human genome. These initial experiments have demonstrated the feasibility of two general types of screens. We have performed phenotypic screens to identify proteins with specific roles in a chosen function and genetic interaction screens to establish epistatic relations between different proteins. The results suggest that any phenotype that can be scored by a robust assay in tissue culture is amenable to these types of screens and that interactions between mammalian proteins can be established. These results point to the near-term goal of establishing comprehensive, unbiased screens that will allow queries on the roles of all human proteins.

Carcinoma, Non-Small-Cell Lung↗

Reference level for patient dose in dental skull lateral teleradiography.

The present work describes an experiment to obtain a local reference dose value in lateral skull teleradiography for dental applications. The reference value was based on patient measurements in seven dental X-ray units, using thermoluminescent chips, and measurements on a rubber globe filled with water at another 78 installations. Dosemeters were located initially in the head and neck of a human phantom to select the most suitable locations, and on the cephalostat of the X-ray unit at two appropriate locations, which did not interfere with the patient or with the usual imaging routine. The skin projection of the Porion point was considered the best position. 523 patients were monitored in the seven units; then patient doses and dose values from measurements on rubber balloons were compared to normalize and combine the data. The provisional reference value proposed is 400 microGy.

Humans↗

B-lymphocytes and co-stimulatory molecules in Mycobacterium tuberculosis infection.

SETTING: The immunological mechanisms that lead to the control of Mycobacterium tuberculosis infection are not well known. OBJECTIVE: To study the role of lymphocyte subsets and co-stimulatory molecules in M. tuberculosis infection. DESIGN: In 35 patients with pulmonary tuberculosis (PTB) and their contacts, 29 persons with tuberculin skin test conversion (TSTC) and 20 healthy individuals with negative tuberculin skin test (NTST), we studied T-lymphocyte subsets (CD3, CD4, CD8, alphabetaTCR and gammadeltaTCR), B-cells, monocytes and co-stimulatory molecules CD28 and CD86 in peripheral blood. The results were analysed at univariate and multivariate level through discriminant analysis. RESULTS: At univariate level, compared with TSTC and NTST, PTB patients presented a decrease in CD4+ T-cells (P = 0.002), and B-cells (P = 0.02 and 0.001, respectively). With regard to NTST subjects, PTB patients also showed a decrease in the percentage of CD86+ monocytes (P = 0.02) and an increase in the percentage of CD86+ B-lymphocytes (P = 0.02). At multivariate level, CD4+ T-lymphocytes showed statistical differences between PTB and TSTC subjects (P = 0.001). B-lymphocytes were discriminant between PTB and NTST (P < 0.001) and between TSTC and NTST individuals (P = 0.01). CONCLUSION: The number of total CD4+ T-cells is the best discriminant parameter for distinguishing between disease and infection, whereas the B-cell count is the best between healthy and infected individuals.

Adult↗

Patient surface radiation doses at two PET imaging facilities.

To develop a practical means of auditing the procedures and to optimize the administered radionuclide activity, patient surface radiation doses following the administration of 18FDG for PET imaging have been measured at breast and gonad locations at two PET facilities. Patient dosimetry was performed using LiF TLD-100 chips placed near the breasts and gonads for 2 h following tracer injection. Standard uptake values from the image-reconstruction algorithms of one PET camera were investigated in regions of interest in tomograms of the myocardium and liver with the aim of validating dosimetry at breasts. Mean doses measured on the patient's skin ranged between 3.3 and 6.1 microGy MBq(-1) at the gonads and between 3.9 and 6.4 microGy MBq(-1) at the breasts, noticeably lower than the calculations reported in the literature. These values show good concordance with the injected activities, although they are not proportional. The proportion of injected activity actually contributing to image production seems to decrease gradually as the injected activity increases. Conversely, for a given injected activity, breast and gonadal doses were found to be lower than the values expected from the numerical calculations reported in the literature, showing increasing discrepancies when the injected activity increased. Doses measured at the right breast were consistently higher than for the left, which is indicative of greater radiotracer absorption by the liver compared to the average absorption in the body.

Adult↗

Hantavirus infection in people inhabiting a highly endemic region of the Gran Chaco territory, Paraguay: association with Trypanosoma cruzi infection, epidemiological features and haematological characteristics.

The seroprevalences of anti-hantavirus antibodies were determined in 712 individuals (551 Indians, 140 Mennonites of German ancestry, and 21 Paraguayans of Spanish ancestry) inhabiting a region of western Paraguay in the Gran Chaco territory of South America. The overall seroprevalence of hantavirus infection among the 712 subjects, who were aged 2-80 years, was 42.7% (45.2% in the Indians and 34.2% in the non-Indians). Of the 672 subjects also checked for antibodies against Trypanosoma cruzi, 226 (33.6%) were seropositive for this protozoan parasite. The results of a multivariate regression analysis indicated that, after adjusting for age, sex, setting of residence (rural/urban) and infection with the human T-cell leukaemia/lymphoma virus type II (HTLV-II), a T. cruzi-seropositive individual was 1.73 times more likely to be hantavirus seropositive than a T. cruzi-seronegative individual. Living in a rural setting increased the risk of being hantavirus seropositive 2.17-fold. In both the Indians and non-Indian subpopulations, hantavirus seroprevalence increased with age in both sexes, but only in the non-Indian supopulation was this increase significantly greater in males than in females. Hantavirus seropositivity was significantly associated with thrombocytosis, even after adjusting for the relevant confounders.

Adolescent↗

Skin dose and dose-area product values in patients undergoing intracoronary brachytherapy.

Entrance skin doses, dose-area product (DAP) values, fluoroscopy times and digital cine acquisition data were measured for 86 patients undergoing intracoronary brachytherapy procedures with beta sources, to estimate risk of skin injuries. Interventions were carried out in three dedicated X-ray interventional cardiology rooms equipped with X-ray systems operating in pulsed modes, with high filtration and edge filter options. Skin dose distribution was analysed in detail in 56 patients using slow films and thermoluminescent dosimetry. Digital recording of Digital Imaging and Communications in Medicine cine images also allowed analysis of the technical parameters used throughout the procedures. A protocol for clinical follow-up of these patients at the cardiology service is also presented, which prescribes special attention when a threshold dose is reached. Median values for DAP, fluoroscopy time and number of frames were 81.2 Gy cm(2), 17.5 min and 1569 frames, respectively, and maximum values were 323.3 Gy cm(2), 46.2 min and 3213 frames, respectively. In two cases, maximum skin doses in a procedure reached 3.5 Gy and 4.6 Gy. Comparing median values in this study, intracoronary brachytherapy involved approximately two-fold the DAP used in percutaneous transluminal coronary angioplasty procedures performed during the same period in the same catheterization laboratories, as a consequence of the need to monitor the radioactive source location used for the treatment of stenoses and the intravascular ultrasound. Special care must be paid in those cases of high dose in relation to potential patient skin injuries and late effects.

Brachytherapy↗

Short communication: Practical aspects for the evaluation of skin doses in interventional cardiology using a new slow film.

Mapping skin doses in complex fluoroscopy interventions is useful to determine the probability of a possible injury, to detect areas of overlapping irradiation fields and to obtain a permanent register of the most exposed patient skin areas. To fulfil this task, large films with slow X-ray response can be used. Recently, Kodak has introduced a new radiotherapy verification film, named EDR2 (Extended Dose Range). The aim of this paper is to analyse the possibilities of using this new film for estimating skin dose distributions in interventions with potentially higher doses, such as complex percutaneous transluminal coronary angioplasty (PTCA), intravascular brachytherapy procedures (IVB) or cardiac ablations. The EDR2 film by Kodak is an improved option to be used in interventional cardiology to obtain maps of patient skin doses and to estimate maximum skin doses up to 1400 mGy. Film kVp dependence is negligible and the processor conditions can be standardized to obtain skin dose estimations. The linear range for accurate dose measurements is from 50 mGy to 500 mGy.

Angioplasty, Balloon, Coronary↗